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Truscello E, Wang S, Young J, Sebastiani G, Walmsley SL, Hull M, Cooper C, Klein MB. Changes in Hepatic Steatosis Before and After Direct-Acting Antiviral Treatment in People With HIV and Hepatitis C Coinfection. J Infect Dis 2025; 231:e101-e112. [PMID: 39417816 PMCID: PMC11793071 DOI: 10.1093/infdis/jiae487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 09/09/2024] [Accepted: 10/04/2024] [Indexed: 10/19/2024] Open
Abstract
BACKGROUND Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections increase the risk of hepatic steatosis (HS), which in turn contribute to the severity and progression of liver disease. Direct-acting antivirals (DAAs) can cure HCV but whether they reduce HS is unclear. METHODS HS was assessed using the controlled attenuation parameter (CAP) and the Hepatic Steatosis Index (HSI) in participants coinfected with HIV and HCV from the Canadian Coinfection Cohort. Changes in HS, before, during, and after successful DAA treatment were estimated using generalized additive mixed models, adjusted for covariates measured prior to treatment (age, sex, duration of HCV infection, body mass index, diabetes, prior exposure to dideoxynucleosides, and hazardous drinking). RESULTS In total, 431 participants with at least 1 measure of CAP or HSI before treatment were included. CAP steadily increased over time: adjusted annual slope 3.3 dB/m (95% credible interval [CrI], 1.6-4.9) before, and 3.9 dB/m (95% CrI, 1.9-5.9) after DAA treatment, irrespective of pretreatment CAP. In contrast, HSI changed little over time: annual slope 0.2 (95% CrI, -0.1 to 0.5) before and 0.2 (95% CrI, -0.1 to 0.5) after, but demonstrated a marked reduction during treatment -4.5 (95% CrI, -5.9 to -3.1). CONCLUSIONS When assessed by CAP, HS was unaffected by DAA treatment and steadily increased over time. In contrast, HSI did not appear to reflect changes in HS, with the decrease during treatment likely related to resolution of hepatic inflammation. Ongoing HS may pose a risk for liver disease in coinfected people cured of HCV.
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Affiliation(s)
- Esther Truscello
- Faculty of Health, Medicine, and Life Sciences, Maastricht University, Maastricht, The Netherlands
| | - Shouao Wang
- Department of Medicine, Division of Infectious Diseases, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
| | - Jim Young
- Department of Medicine, Division of Infectious Diseases, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
| | - Giada Sebastiani
- Department of Medicine, Division of Infectious Diseases, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
- Division of Experimental Medicine, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
| | - Sharon L Walmsley
- University Health Network, University of Toronto, Toronto, Ontario, Canada
- Canadian Institutes of Health Research Canadian HIV Trials Network, Vancouver, British Columbia, Canada
| | - Mark Hull
- Department of Medicine, British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada
| | - Curtis Cooper
- Department of Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Marina B Klein
- Department of Medicine, Division of Infectious Diseases, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
- Canadian Institutes of Health Research Canadian HIV Trials Network, Vancouver, British Columbia, Canada
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Iwamoto T, Nozaki Y, Inoue T, Suda T, Mizumoto R, Arimoto Y, Ohta T, Yamaguchi S, Ito Y, Sudo Y, Yoshimura M, Kai M, Sasaki Y, Tahata Y, Hikita H, Takehara T, Hagiwara H. Histological improvement of fibrosis in patients with hepatitis C who achieved a 5-year sustained virological response to treatment with direct-acting antivirals. J Gastroenterol 2025; 60:197-209. [PMID: 39585387 PMCID: PMC11794422 DOI: 10.1007/s00535-024-02165-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 10/25/2024] [Indexed: 11/26/2024]
Abstract
BACKGROUND The histological improvement in liver fibrosis in patients with hepatitis C who achieved a sustained virological response (SVR) to direct-acting antiviral (DAA) treatment has not been comprehensively investigated. Therefore, we assessed the histological changes in liver fibrosis among patients with hepatitis C who underwent long-term follow-up after achieving SVR to treatment with DAA. METHODS This retrospective study enrolled 71 patients with hepatitis C who achieved SVR to treatment with DAA. Changes in histological liver fibrosis and fibrosis biomarkers (hyaluronic acid, type 4 collagen 7S, Mac-2 binding protein glycosylation isomer, autotaxin, and Fibrosis-4 index) were assessed before and 5 years after treatment. Transient elastography using the FibroScan® device was performed 5 years after treatment. Advanced fibrosis and cirrhosis were defined as Ishak fibrosis scores of ≥ 4 and ≥ 5, respectively. RESULTS Histological liver fibrosis significantly regressed after SVR. Fibrosis biomarkers were significantly reduced after SVR. Transient elastography was the most helpful after evaluating the predictive performance of advanced fibrosis and cirrhosis after SVR, with an area under the receiver operating characteristic curve of 0.965 and a cut-off value of 6.75 kPa. The cut-off values of serum fibrosis biomarkers for identifying advanced fibrosis and cirrhosis after SVR were lower than those before treatment. CONCLUSIONS Long-term SVR to treatment with DAA ameliorated histological liver fibrosis. Noninvasive tests helped predict the degree of liver fibrosis after SVR, but their cut-off values should be redefined to avoid underestimation of liver fibrosis.
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Affiliation(s)
- Takayuki Iwamoto
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Yasutoshi Nozaki
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Takanori Inoue
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Takahiro Suda
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Rui Mizumoto
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Yuki Arimoto
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Takashi Ohta
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Shinjiro Yamaguchi
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Yoshiki Ito
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Yoshiko Sudo
- Department of Diagnostic Pathology, Kansai Rosai Hospital, Hyogo, Japan
| | - Michiko Yoshimura
- Department of Diagnostic Pathology, Kansai Rosai Hospital, Hyogo, Japan
| | - Machiko Kai
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yoichi Sasaki
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yuki Tahata
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hayato Hikita
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hideki Hagiwara
- Department of Gastroenterology and Hepatology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki, Hyogo, 660-8511, Japan.
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Zhang Y, Xia H, Fan L, Jiang L, Yang B, Wang F. Five-Year Prospective Follow-Up of Patients with Hepatitis C Virus Infection Treated with Direct-Acting Antiviral Agents. Infect Drug Resist 2025; 18:455-471. [PMID: 39877380 PMCID: PMC11774102 DOI: 10.2147/idr.s487414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 01/11/2025] [Indexed: 01/31/2025] Open
Abstract
Purpose The research intended to present prospective data on the long-term prognosis of individuals with hepatitis C virus (HCV) infection who received direct-acting antiviral agent (DAA) treatment. Patients and Methods Patients who received DAA treatment at Tianjin Third Central Hospital and Tianjin Second People's Hospital were prospectively enrolled and subsequently underwent a longitudinal follow-up. This research monitored occurrences of virological relapse, hepatocellular carcinoma (HCC), mortality, and liver disease progression. The annualized incidence rates (AIRs), cumulative incidence rates of adverse events and risk factors were investigated. Changes in liver stiffness measurement (LSM), aspartate aminotransferase-to-platelet ratio index (APRI) score, fibrosis-4 (FIB-4) index, as well as the albumin-bilirubin (ALBI) scores were also documented. Results A total of 862 individuals were followed up for 4.86 (P25, P75; 4.48, 5.48) years. The proportion of all participants with undetectable HCV-RNA exceeded 98% at all follow-up time points. Patients experienced virological relapse, HCC, death and disease progression with a cumulative AIRs of 1.03% (95% confidence interval [CI] 0.6-1.5), 1.76% (95% CI 1.2-2.3), 1.51% (95% CI 1.0-2.0), and 5.81% (95% CI 4.8-6.8), respectively. Cirrhotic patients were at a heightened risk of virological relapse (adjusted hazard ratio [aHR] 3.20, 95% CI 1.59-9.75; p = 0.016), HCC (aHR 6.57, 95% CI 2.66-16.28; p < 0.0001), and unfavorable prognosis (aHR 6.93, 95% CI 2.56-18.74; p < 0.0001). Additionally, patients with diabetes faced an elevated risk of HCC (aHR 2.33, 95% CI 1.05-5.15; p = 0.038) and poor prognosis (aHR 2.72, 95% CI 1.13-6.55; p = 0.026). Furthermore, liver stiffness measurement (LSM) exhibited a significant decrease compared to baseline. Additionally, patients in the cirrhosis group showed reductions in APRI score, FIB-4 index and ALBI score to different degrees. Conclusion Cirrhotic patients exhibited increased susceptibility to virological relapse, HCC, unfavorable prognosis, and liver disease progression following DAA treatment. Consequently, it is imperative to implement a rigorous monitoring protocol for all cirrhotic patients after DAA treatment.
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Affiliation(s)
- Yaping Zhang
- The Third Central Clinical College of Tianjin Medical University, Tianjin Medical University, Tianjin, 300170, People’s Republic of China
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Nankai University Affiliated Third Central Hospital, Tianjin, 300072, People’s Republic of China
| | - Huan Xia
- Department of Infectious Diseases, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China
| | - Luchang Fan
- The Third Central Clinical College of Tianjin Medical University, Tianjin Medical University, Tianjin, 300170, People’s Republic of China
| | - Lu Jiang
- Department of Hepatology and Gastroenterology, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of China
| | - Bin Yang
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Institute of Hepatobiliary Disease, Nankai University Affiliated Third Central Hospital, Tianjin, 300072, People’s Republic of China
| | - Fengmei Wang
- Department of Hepatology and Gastroenterology, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of China
- Tianjin Key Laboratory of Molecular Diagnosis and Treatment of Liver Cancer, Tianjin First Central Hospitial, Tianjin, 300192, People’s Republic of China
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Hsieh MH, Kao TY, Hsieh TH, Kao CC, Peng CY, Lai HC, Cheng HH, Ho MW, Chi CY, Kao JT. Predictors of liver fibrosis changes assessed by paired liver biopsies in chronic hepatitis C patients treated with direct-acting antivirals. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2024; 57:840-853. [PMID: 39216998 DOI: 10.1016/j.jmii.2024.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 07/15/2024] [Accepted: 08/12/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND/PURPOSE There are limited studies performing paired liver biopsies in chronic hepatitis C (CHC) patients treated with direct-acting antivirals (DAA). We aimed to investigate the predictors of liver fibrosis changes assessed by paired liver biopsies in these patients. METHODS From March 2017 to March 2020, 113 CHC patients were prospectively enrolled to receive DAA therapy at our hospital. Paired liver biopsies were performed at baseline and 12 weeks after the end of treatment. RESULTS Among the entire cohort, the rate of sustained virological response (SVR) was 100%. Four baseline variables independently predicted fibrosis regression, including age <65 years [odds ratio (OR) = 2.725, p = 0.036], fibrosis stages (METAVIR scores) < 3 (OR = 4.874, p = 0.040), hemoglobin levels ≥12.5 g/dL (OR = 3.538, p = 0.029), and platelet counts ≥160 103/μL (OR = 2.958, p = 0.023). Besides, five independent predictors of fibrosis progression included baseline age ≥66 years (OR = 16.351, p = 0.024), body mass index (BMI) ≥26.5 kg/m2 (OR = 21.666, p = 0.009), sofosbuvir/ribavirin use (OR = 29.465, p = 0.031), platelet counts <119 103/μL (OR = 33.739, p = 0.026), and the absence of alanine aminotransferase (ALT) levels declining from >35 U/L at baseline to ≤35 U/L at 4 weeks after baseline (OR = 284.534, p = 0.026). CONCLUSION For DAA-treated CHC patients, those with baseline age <65 years, fibrosis stages <3, hemoglobin levels ≥12.5 g/dL, or platelet counts ≥160 103/μL are more likely to attain fibrosis regression. There is a higher risk of fibrosis progression in those with baseline age ≥66 years, BMI ≥26.5 kg/m2, sofosbuvir/ribavirin use, platelet counts <119 103/μL, or the absence of early ALT normalization at 4 weeks after baseline.
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Affiliation(s)
- Ming-Han Hsieh
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Tzu-Yu Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Ting-Hui Hsieh
- Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Chi Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Yuan Peng
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Hsueh-Chou Lai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Hsing-Hung Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Mao-Wang Ho
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chih-Yu Chi
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Jung-Ta Kao
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
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Cespiati A, Coelho Rodrigues I, Santos I, Policarpo S, Carvalhana S, Fracanzani AL, Cortez-Pinto H. Effect of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, and associated metabolic comorbidities: A systematic review. Liver Int 2024; 44:1075-1092. [PMID: 38385567 DOI: 10.1111/liv.15876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 12/11/2023] [Accepted: 02/08/2024] [Indexed: 02/23/2024]
Abstract
BACKGROUND AND AIMS The beneficial effect of Hepatitis C virus (HCV) eradication by direct antiviral agents (DAAs) on liver fibrosis is well defined. Despite this, the impact of viral eradication in both hepatic and extra-hepatic metabolic features is underreached. This systematic review aimed to synthesize the evidence on the impact of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, glucidic impairment, dyslipidaemia, and weight gain. METHODS A systematic search of the existing literature (up to December 2022) identified 97 original studies that fulfilled the inclusion criteria. RESULTS Whereas total cholesterol and low-density lipoprotein (LDL) seem to increase after viral eradication, the cardiovascular damage expressed as carotid plaques and intima-media thickness seems to improve. Otherwise, the effect on liver steatosis, glucidic homeostasis, and weight seems to be strictly dependent on the presence of baseline metabolic disorders. CONCLUSION Despite high heterogeneity and relatively short follow-up of included studies, we can conclude that the presence of metabolic risk factors should be strictly evaluated due to their impact on liver steatosis, glucidic and lipid homeostasis, and on weight gain to better identify patients at risk of liver disease progression despite the virus eradication.
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Affiliation(s)
- Annalisa Cespiati
- Unit of Medicine and Metabolic Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Inês Coelho Rodrigues
- Departamento de Gastrenterologia, Centro Hospitalar Universitário Lisboa Norte, Departamento de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
| | - Inês Santos
- Laboratório de Nutrição, Faculdade de Medicina, Centro Académico de Medicina de Lisboa, Universidade de Lisboa, Lisbon, Portugal
- Faculdade de Medicina, Instituto de Saúde Ambiental (ISAMB), Universidade de Lisboa, Lisbon, Portugal
| | - Sara Policarpo
- Laboratório de Nutrição, Faculdade de Medicina, Centro Académico de Medicina de Lisboa, Universidade de Lisboa, Lisbon, Portugal
- Serviço de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, E.P.E., Lisbon, Portugal
| | - Sofia Carvalhana
- Departamento de Gastrenterologia, Centro Hospitalar Universitário Lisboa Norte, Departamento de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
- Clínica Universitária de Gastrenterologia, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Anna Ludovica Fracanzani
- Unit of Medicine and Metabolic Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Helena Cortez-Pinto
- Departamento de Gastrenterologia, Centro Hospitalar Universitário Lisboa Norte, Departamento de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
- Clínica Universitária de Gastrenterologia, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
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Celsa C, Veneziano M, Di Giorgio FM, Cannova S, Lombardo A, Errigo E, Landro G, Simone F, Sinagra E, Calvaruso V. Non-Invasive Diagnostic Tests for Portal Hypertension in Patients with HBV- and HCV-Related Cirrhosis: A Comprehensive Review. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:690. [PMID: 38792873 PMCID: PMC11123262 DOI: 10.3390/medicina60050690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 04/10/2024] [Accepted: 04/17/2024] [Indexed: 05/26/2024]
Abstract
Clinically significant portal hypertension (CSPH) in patients with compensated advanced chronic liver disease indicates an increased risk of decompensation and death. While invasive methods like hepatic venous-portal gradient measurement is considered the gold standard, non-invasive tests (NITs) have emerged as valuable tools for diagnosing and monitoring CSPH. This review comprehensively explores non-invasive diagnostic modalities for portal hypertension, focusing on NITs in the setting of hepatitis B and hepatitis C virus-related cirrhosis. Biochemical-based NITs can be represented by single serum biomarkers (e.g., platelet count) or by composite scores that combine different serum biomarkers with each other or with demographic characteristics (e.g., FIB-4). On the other hand, liver stiffness measurement and spleen stiffness measurement can be assessed using a variety of elastography techniques, and they can be used alone, in combination with, or as a second step after biochemical-based NITs. The incorporation of liver and spleen stiffness measurements, alone or combined with platelet count, into established and validated criteria, such as Baveno VI or Baveno VII criteria, provides useful tools for the prediction of CSPH and for ruling out high-risk varices, potentially avoiding invasive tests like upper endoscopy. Moreover, they have also been shown to be able to predict liver-related events (e.g., the occurrence of hepatic decompensation). When transient elastography is not available or not feasible, biochemical-based NITs (e.g., RESIST criteria, that are based on the combination of platelet count and albumin levels) are valid alternatives for predicting high-risk varices both in patients with untreated viral aetiology and after sustained virological response. Ongoing research should explore novel biomarkers and novel elastography techniques, but current evidence supports the utility of routine blood tests, LSM, and SSM as effective surrogates in diagnosing and staging portal hypertension and predicting patient outcomes.
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Affiliation(s)
- Ciro Celsa
- Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, 90127 Palermo, Italy; (M.V.); (F.M.D.G.); (S.C.); (A.L.); (E.E.); (G.L.); (F.S.); (V.C.)
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London W12 0NN, UK
| | - Marzia Veneziano
- Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, 90127 Palermo, Italy; (M.V.); (F.M.D.G.); (S.C.); (A.L.); (E.E.); (G.L.); (F.S.); (V.C.)
| | - Francesca Maria Di Giorgio
- Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, 90127 Palermo, Italy; (M.V.); (F.M.D.G.); (S.C.); (A.L.); (E.E.); (G.L.); (F.S.); (V.C.)
| | - Simona Cannova
- Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, 90127 Palermo, Italy; (M.V.); (F.M.D.G.); (S.C.); (A.L.); (E.E.); (G.L.); (F.S.); (V.C.)
| | - Antonino Lombardo
- Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, 90127 Palermo, Italy; (M.V.); (F.M.D.G.); (S.C.); (A.L.); (E.E.); (G.L.); (F.S.); (V.C.)
| | - Emanuele Errigo
- Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, 90127 Palermo, Italy; (M.V.); (F.M.D.G.); (S.C.); (A.L.); (E.E.); (G.L.); (F.S.); (V.C.)
| | - Giuseppe Landro
- Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, 90127 Palermo, Italy; (M.V.); (F.M.D.G.); (S.C.); (A.L.); (E.E.); (G.L.); (F.S.); (V.C.)
| | - Fabio Simone
- Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, 90127 Palermo, Italy; (M.V.); (F.M.D.G.); (S.C.); (A.L.); (E.E.); (G.L.); (F.S.); (V.C.)
| | - Emanuele Sinagra
- Gastroenterology and Endoscopy Unit, Fondazione Istituto G. Giglio, 90015 Cefalù, Italy;
| | - Vincenza Calvaruso
- Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, 90127 Palermo, Italy; (M.V.); (F.M.D.G.); (S.C.); (A.L.); (E.E.); (G.L.); (F.S.); (V.C.)
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Rinaldi L, Giorgione C, Mormone A, Esposito F, Rinaldi M, Berretta M, Marfella R, Romano C. Non-Invasive Measurement of Hepatic Fibrosis by Transient Elastography: A Narrative Review. Viruses 2023; 15:1730. [PMID: 37632072 PMCID: PMC10459581 DOI: 10.3390/v15081730] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/04/2023] [Accepted: 08/11/2023] [Indexed: 08/27/2023] Open
Abstract
Transient elastography by FibroScan® (Echosens, Paris, France) is a non-invasive method that can provide a reliable measurement of liver fibrosis through the evaluation of liver stiffness. Despite its limitations and risks, liver biopsy has thus far been the only procedure able to provide data to quantify fibrosis. Scientific evidence and clinical practice have made it possible to use FibroScan® in the diagnostic work-up of several liver diseases to monitor patients' long-term treatment response and for complication prevention. For these reasons, this procedure is widely used in clinical practice and is still being investigated for further applications. The aim of this narrative review is to provide a comprehensive overview of the main applications of transient elastography in the current clinical practice.
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Affiliation(s)
- Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Chiara Giorgione
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Andrea Mormone
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Francesca Esposito
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Michele Rinaldi
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, “Federico II” University of Naples, 80131 Naples, Italy;
| | - Massimiliano Berretta
- Department of Clinical and Experimental Medicine, University of Messina, 98121 Messina, Italy;
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
| | - Ciro Romano
- Department of Advanced Medical and Surgical Sciences, “Luigi Vanvitelli” University of Campania, 80131 Naples, Italy; (L.R.); (R.M.)
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Du Y, Khera T, Liu Z, Tudrujek-Zdunek M, Dworzanska A, Cornberg M, Xu CJ, Tomasiewicz K, Wedemeyer H. Controlled Attenuation Parameter Is Associated with a Distinct Systemic Inflammatory Milieu after Clearance of HCV Infection. Biomedicines 2023; 11:1529. [PMID: 37371624 DOI: 10.3390/biomedicines11061529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 05/15/2023] [Accepted: 05/17/2023] [Indexed: 06/29/2023] Open
Abstract
Hepatitis C virus (HCV) infection is closely associated with lipid metabolism defects along with a high prevalence of hepatic steatosis. After HCV clearance, steatosis persists in many patients. However, the reasons behind this phenomenon are not completely clear. To investigate the association between 92 soluble inflammatory mediators (SIMs) and the steatosis grade, we made use of a cohort of 94 patients with chronic HCV infection who cleared HCV after direct-acting antiviral agent (DAA) treatment. Patients were classified into three groups according to their controlled attenuation parameter (CAP). CAP is associated with ALT, γ-GT and liver stiffness after HCV clearance. While stem cell factor (SCF) and tumor necrosis factor ligand superfamily member 12 (TWEAK) levels were significantly reduced in patients with CAP > 299 dB/m, the levels of fibroblast growth factor (FGF)-21 and interleukin-18 receptor 1 (IL-18R1) were higher in those patients at week 96 after virus clearance. These four markers also showed a linear correlation with CAP values. FGF-21 levels correlated with CAP only after HCV clearance. Taken together, these four biomarkers, namely SCF, TWEAK, FGF-21 and IL-18R1, are associated with CAP status after virus clearance. A potential role of these proteins in the pathogenesis of post-sustained viral response (SVR) nonalcoholic steatohepatitis requires further investigation.
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Affiliation(s)
- Yanqin Du
- Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
- Department of Infectious Diseases, Union Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Tanvi Khera
- Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, 30625 Hannover, Germany
- International AIDS Vaccine Initiative (IAVI), 122002 Gurugram, Haryana, India
| | - Zhaoli Liu
- Centre for Individualized Infection Medicine (CiiM), a Joint Venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), 30625 Hannover, Germany
- TWINCORE Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), 30625 Hannover, Germany
| | | | - Anna Dworzanska
- Department of Infectious Diseases, Medical University of Lublin, 20-081 Lublin, Poland
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, 30625 Hannover, Germany
- TWINCORE Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), 30625 Hannover, Germany
| | - Cheng-Jian Xu
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, 30625 Hannover, Germany
- Centre for Individualized Infection Medicine (CiiM), a Joint Venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), 30625 Hannover, Germany
- TWINCORE Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), 30625 Hannover, Germany
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
| | - Krzysztof Tomasiewicz
- Department of Infectious Diseases, Medical University of Lublin, 20-081 Lublin, Poland
| | - Heiner Wedemeyer
- Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, 30625 Hannover, Germany
- Excellence Cluster Resist, Hannover Medical School, 30625 Hannover, Germany
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9
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Niu B, Zang W, Zhou H, Mi Y, Lu C, Li P. Regression in hepatic fibrosis in elderly Chinese patients with hepatitis C receiving direct-acting antiviral treatment. BMC Gastroenterol 2023; 23:102. [PMID: 37013471 PMCID: PMC10069046 DOI: 10.1186/s12876-023-02732-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 03/20/2023] [Indexed: 04/05/2023] Open
Abstract
BACKGROUND Patients infected with Hepatitis C virus (HCV) are recommended to receive treatment with direct-acting antiviral agents (DAAs), which have been certified to obtain a high sustained virological response (SVR). However, little is known about the benefits of successful anti-viral treatment to elderly patients with hepatic fibrosis. In this study, we aimed to assess degree of fibrosis in elderly patients with chronic hepatitis C (CHC) treated with DAAs, and to evaluate the correlations between identified factors associated with these changes. METHODS This study retrospectively enrolled elderly patients with CHC who received DAAs in Tianjin Second People's Hospital from April 2018 to April 2021. The degree of liver fibrosis was assessed using serum biomarkers and transient elastography (TE) expressed as the liver stiffness (LSM), while the hepatic steatosis was evaluated by controlled attenuated parameter (CAP). Changes in factors related to hepatic fibrosis were examined following treatment with DAAs, and associated prognostic factors were further evaluated. RESULTS We included 347 CHC patients in our analysis, where 127 of these were elderly patients. For the elderly group, the median LSM was 11.6 (7.9-19.9) kPa, and this value was significantly reduced to 9.7 (6.2-16.6) kPa following DAA treatment. Similarly, GPR, FIB-4 and APRI indices were significantly reduced from 0.445 (0.275-1.022), 3.072 (2.047-5.129) and 0.833 (0.430-1.540) to 0.231 (0.155-0.412), 2.100 (1.540-3.034) and 0.336 (0.235-0.528), respectively. While in younger patients, the median LSM reduced from 8.8 (6.1-16.8) kPa to 7.2 (5.3-12.4) kPa, and the trends of GPR, FIB-4 and APRI were also consistent. The CAP in younger patients increased with statistical significance, but we did not observe any significant change in CAP for the elderly group. Based on multivariate analysis, age, LSM, and CAP before baseline were identified as determinants for LSM improvement in the elderly. CONCLUSION In this study, we found that elderly CHC patients treated with DAA had significantly lower LSM, GPR, FIB-4, and APRI values. DAA treatment did not significantly change CAP. Furthermore, we observed correlations between three noninvasive serological evaluation markers and LSM. Finally, age, LSM, and CAP were identified as independent predictors of fibrosis regression in elderly patients with CHC.
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Affiliation(s)
- Bin Niu
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, 300192, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China
| | - Wenqian Zang
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China
| | - Hui Zhou
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, 300192, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China
| | - Yuqiang Mi
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, China
| | - Chengzhen Lu
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, China
| | - Ping Li
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China.
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, China.
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Cheng PN, Sun HY, Feng IC, Wang ST, Chiu YC, Chiu HC, Chien SC, Young KC. Post-therapeutic reversibility of oxidative-stress markers in chronic hepatitis C patients receiving direct-acting antiviral agents. J Virus Erad 2023; 9:100318. [PMID: 37065432 PMCID: PMC10091014 DOI: 10.1016/j.jve.2023.100318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 12/08/2022] [Accepted: 02/19/2023] [Indexed: 02/27/2023] Open
Abstract
Introduction Hepatitis C (HCV) is associated with extra-hepatic involvment, morbidity as well as metabolic changes. Whether these might be reversible if sustained virologic response (SVR) is achieved by direct-acting antiviral (DAA) therapy remains unknown. Methods Chronic hepatitis C (CHC) individuals receiving DAA treatment with SVR were compared to those who underwent spontaneous clearance (SC) of HCV infection at the 2-year follow-up. Plasma oxidative stress markers (oxidized low-density lipoprotein (oxLDL), 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA) and ischemia-modified albumin (IMA)) as well as progression of liver fibrosis were evaluated. Results Compared to SC individuals, those in the CHC group exhibited at baseline higher levels of oxLDL, 8-OHdG and IMA but not of MDA. In the SC group, 8-OHdG levels were elevated at 2-year post-SVR (p = 0.0409), while the DAA-treated CHC group showed decrease in oxLDL (p < 0.0001) and 8-OHdG (p = 0.0255) levels, approaching those of the SC group, but increased MDA (p = 0.0055) levels. Additionally, oxLDL levels were positively correlated with liver stiffness measurements at SVR (p = 0.017) and at 1 year post- SVR (p = 0.002). Conclusions Plasma oxLDL showed post-SVR normalization after clearance of HCV viremia with DAAs and was associated with levels of hepatic fibrosis.
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Affiliation(s)
- Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hung-Yu Sun
- Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - I-Che Feng
- Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
| | - Sin-Tian Wang
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yen-Cheng Chiu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hung-Chih Chiu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Shih-Chieh Chien
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Kung-Chia Young
- Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Corresponding author. Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, No. 1 University Rd, Tainan, 70101, Taiwan.
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Cai D, Zhang D, Hu P, Ren H. A Comprehensive Hepatitis B Surface Antigen-Positive Patient-Centered Screening and Linkage to Care Strategies Targeting Microelimination of Hepatitis C Virus Infection in Chongqing, China. Can J Gastroenterol Hepatol 2022; 2022:9644576. [PMID: 36606100 PMCID: PMC9810400 DOI: 10.1155/2022/9644576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 10/18/2022] [Accepted: 12/13/2022] [Indexed: 12/28/2022] Open
Abstract
Background and Aims The likelihood of coinfection increases in regions where HBV is endemic because of the similar transmission route. China is another endemic nation, with 5.9% of the population being HBsAg-positive. This study aimed to evaluate the prevalence of HCV antibody positivity in HBsAg-positive subjects, HCV RNA positivity in anti-HCV positive subjects, and HBV/HCV coinfection with the hope of exploring hepatitis C microelimination using currently available therapies. Method 12,500 HBsAg-positive serum samples were collected. All samples were screened for anti-HCV. Furthermore, positive samples were screened for HCV RNA. All patients with positive HCV RNA were followed up for suspicious transmission routes of HCV and linkage to care. Results 44 out of 10,560 (0.4%) patients with positive HBsAg had detectable anti-HCV. There were 32 males and 12 females, with a statistical difference. 17 out of 44 were HCV RNA positive. Among them, 15 out of 38 patients were HCV RNA positive; 8 patients had started anti-HCV treatment with the DAA regimen, while the other 7 patients had not. After patient education, one patient had begun treatment and reached SVR12, while three patients still refused anti-HCV treatment. Conclusion The HCV/HBV coinfection prevalence was found to be lower in this study. Even though HBV and HCV share a somewhat similar transmission route, HBsAg-positive subjects may not be at high risk for HCV infection. The process of hepatitis C's microelimination could be accelerated by increasing patient awareness and education. This trail is registered with NCT03794791.
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Affiliation(s)
- Dachuan Cai
- Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
- Institute for Viral Hepatitis, Chongqing Medical University, Chongqing, China
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Chongqing, China
| | - Dazhi Zhang
- Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
- Institute for Viral Hepatitis, Chongqing Medical University, Chongqing, China
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Chongqing, China
| | - Peng Hu
- Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
- Institute for Viral Hepatitis, Chongqing Medical University, Chongqing, China
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Chongqing, China
| | - Hong Ren
- Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
- Institute for Viral Hepatitis, Chongqing Medical University, Chongqing, China
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Chongqing, China
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12
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Chuaypen N, Siripongsakun S, Hiranrat P, Tanpowpong N, Avihingsanon A, Tangkijvanich P. Improvement of liver fibrosis, but not steatosis, after HCV eradication as assessment by MR-based imaging: Role of metabolic derangement and host genetic variants. PLoS One 2022; 17:e0269641. [PMID: 35696400 PMCID: PMC9191717 DOI: 10.1371/journal.pone.0269641] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 05/22/2022] [Indexed: 12/05/2022] Open
Abstract
Significant liver fibrosis regression occurs after hepatitis C virus (HCV) therapy. However, the impact of direct-acting antivirals (DAAs) on steatosis is less clear. This study was aimed at evaluating serial fibrosis and steatosis alterations in patients with HCV genotype 1, who achieved sustained virological response (SVR). We enrolled 55 HCV mono-infected and 28 HCV/HIV co-infected patients receiving elbasvir/grazoprevir from a clinical trial. Fibrosis and steatosis were assessed at baseline, follow-up week-24 (FUw24) and week-72 (FUw72) by magnetic resonance elastography (MRE) and proton density fat fraction (PDFF), respectively. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409, transmembrane six superfamily member 2 (TM6SF2) rs58542926 and membrane bound O-acyltransferase domain-containing 7 (MBOAT7) rs641738 polymorphisms were determined by allelic discrimination. Overall, mean MRE decreased significantly from baseline to FUw24 and FUw72. At FUw72, patients with baseline F2-F4 had higher rate of ≥30% MRE decline compared with individuals with baseline F0-F1 (30.2%vs.3.3%, P = 0.004). In multivariate analysis, significant fibrosis was associated with MRE reduction. The prevalence of steatosis (PDFF≥5.2%) at baseline was 21.7%. Compared to baseline, there were 17 (20.5%) patients with decreased PDFF values at FUw72 (<30%), while 23 (27.7%) patients had increased PDFF values (≥30%). Regarding the overall cohort, mean PDFF significantly increased from baseline to FUw72, and displayed positive correlation with body mass index (BMI) alteration. In multivariate analysis, the presence of diabetes, PNPLA3 CG+GG genotypes and increased BMI at FUw72 were significantly associated with progressive steatosis after SVR. Other genetic variants were not related to fibrosis and steatosis alteration. This study concluded that HCV eradication was associated with fibrosis improvement. However, progressive steatosis was observed in a proportion of patients, particularly among individuals with metabolic derangement and PNPLA3 variants. The combined clinical parameters and host genetic factors might allow a better individualized strategy in this sub-group of patients to alleviate progressive steatosis after HCV cure.
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Affiliation(s)
- Natthaya Chuaypen
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Surachate Siripongsakun
- Sonographer School, Faculty of Health Science Technology, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Pantajaree Hiranrat
- Sonographer School, Faculty of Health Science Technology, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Natthaporn Tanpowpong
- Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Anchalee Avihingsanon
- The HIV Netherlands Australia Thailand Research Collaboration (HIV NAT), Bangkok, Thailand
| | - Pisit Tangkijvanich
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- * E-mail:
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13
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Trifan A, Stratina E, Rotaru A, Stafie R, Zenovia S, Nastasa R, Huiban L, Sfarti C, Cojocariu C, Cuciureanu T, Muzica C, Chiriac S, Girleanu I, Singeap AM, Stanciu C. Changes in Liver Steatosis Using Controlled Attenuation Parameter among Patients with Chronic Hepatitis C Infection Treated with Direct-Acting Antivirals Therapy Who Achieved Sustained Virological Response. Diagnostics (Basel) 2022; 12:702. [PMID: 35328255 PMCID: PMC8947513 DOI: 10.3390/diagnostics12030702] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection induces hepatic steatosis due to viral and host factors. However, information regarding the effects of direct-acting antivirals (DAAs) therapy on liver steatosis and fibrosis is limited. Vibration-controlled transient elastography (VCTE) with a controlled attenuation parameter (CAP) represents a non-invasive method, which has been used in the last few years for the detection of hepatic steatosis and fibrosis before and at a sustained virological response at 12 weeks (SVR12). The aim of this study was to assess the modifications of liver steatosis and fibrosis in HCV-infected patients who achieved SVR12. Consecutive patients with chronic HCV infection that were treated with DAAs in a tertiary gastroenterology center from Romania were included. Demographics, laboratory data, and VCTE evaluation were recorded in all patients. Patients with previous hepatic decompensation and those who did not achieve SVR were excluded. Two hundred and eighty patients (67.1% females) who achieved SVR12 were included. Regarding the changes in biological parameters, including liver enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), reduced to normal levels at SVR12 compared to the baseline (28.72 ± 24.71 U/L vs. 40.72 ± 27.34 U/L for ALT, p < 0.013 and 27.21 ± 11.15 U/L vs. 33.35 ± 23.37 U/L for AST, p = 0.029). On the contrary, the levels of triglycerides increased significantly from the baseline to SVR12 (124.03 ± 113.49 mg/dL to 153.78 ± 94.53, p = 0.004). Regarding hepatic steatosis by CAP evaluation, at SVR12, 186 (66.4%) of the individuals had a CAP score of ≥248 dB/m, an increase of 4.6% from the baseline. After viral eradication with DAAs, we observed an increase in hepatic steatosis. Hence, a long-term follow-up is mandatory to identify HCV-infected patients with hepatic steatosis post-SVR and the risk factors for more severe outcomes.
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Affiliation(s)
- Anca Trifan
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Ermina Stratina
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Adrian Rotaru
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Remus Stafie
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Sebastian Zenovia
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Robert Nastasa
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Laura Huiban
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Catalin Sfarti
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Tudor Cuciureanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Cristina Muzica
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Stefan Chiriac
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Irina Girleanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Ana-Maria Singeap
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Carol Stanciu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
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Tahtasakal CA, Oncul A, Sevgi DY, Demirbas D, Gunduz A, Dokmetas I. Fibrosis scores that can be used in follow-up of after direct-acting antiviral treatment: APRI, FIB-4, King score and GUCI. Eur J Gastroenterol Hepatol 2022; 34:308-315. [PMID: 34091480 DOI: 10.1097/meg.0000000000002204] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
INTRODUCTION Sustained virologic response in the treatment of chronic hepatitis C can be achieved with direct-acting antivirals (DAA) in recent years. Monitoring virologic and histologic response to treatment is essential and noninvasive methods are preferred. In our study, we aimed to determine the regression of fibrosis following DAA treatment with serum fibrosis indices constituting a noninvasive method. METHOD Patients with chronic hepatitis C to whom DAA treatment is started between January 2016 and January 2018 in our clinic are evaluated retrospectively. The fibrosis scores [fibrosis 4 index (FIB-4), aminotransferase platelet ratio (APRI), Fibro QKing score, age platelet index, Goteburg University Cirrhosis Index (GUCI), aspartate transaminase/alanine transaminase ratio (AAR)] are calculated with routine biochemical and hematologic tests of DAA-treated patients before treatment, at the end of treatment, and in the 12th and 24th weeks of treatment. In total, the course of seven scores calculated at four separate times including baseline was recorded and compared. RESULTS In total 91 patients are included in the study. The average age was 51.16 ± 13.78 and 59.3% (n = 54) of patients were women. According to the baseline FIB-4 values, the patients were grouped as cirrhotic or noncirrhotic, and 11 of them were cirrhotic (12.1%). Statistically significant regression in APRI, FIB-4, GUCI and King scores is seen in all groups regardless of their cirrhotic status, treatment experience or genotype (P < 0.001). Specified scores had a positive, significant correlation with pretreatment biopsy results [area under curve (AUC): 0.800, 0.782, 0.749 and 0.746]. CONCLUSION APRI, FIB-4, GUCI and King scores that have a positive correlation with biopsy can also be used for fibrosis recovery follow-up after treatment with DAAs.
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Affiliation(s)
- Ceren Atasoy Tahtasakal
- University of Health Sciences Sisli Hamidiye Etfal Training and Research Hospital, İnfectious Diseases and Clinical Microbiology, Istanbul, Turkey
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15
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Role of liver stiffness measurements in patients who develop hepatocellular carcinoma after clearance of the hepatitis C virus. J Med Ultrason (2001) 2022; 49:253-259. [PMID: 35129720 PMCID: PMC9038899 DOI: 10.1007/s10396-021-01188-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 11/28/2021] [Indexed: 11/02/2022]
Abstract
PURPOSE To measure changes in liver stiffness over time due to direct-acting antiviral (DAA) therapy in hepatitis C patients using shear wave elastography (SWE). METHODS Patients with hepatitis C treated with DAA therapy in a university medical center between July 2015 and April 2020 were evaluated. Shear wave velocity (Vs) of the liver was measured using SWE. Alanine aminotransferase (ALT), platelet count, and α-fetoprotein (AFP) were measured at the same time, and the FIB-4 index was estimated. Absence of hepatocellular carcinoma was confirmed at baseline and end of therapy. Imaging was then performed every 6 months. Patient characteristics were compared between patients who did and did not develop carcinoma. RESULTS The mean age of the 229 patients (93 men) was 65.6 years. Eight patients developed carcinoma during follow-up (mean 32.6 ± 19.5 months). Significant differences were found between the groups in terms of AFP, platelet count, and Fib-4 index at baseline; the pre-treatment data had the best relationship with hepatocarcinogenesis. Mean Vs decreased significantly during DAA therapy, and then decreased further. Liver stiffness 6 months after treatment ended had the best relationship with hepatocarcinogenesis. CONCLUSION In patients with a sustained virological response, risk of developing cancer can be predicted by measuring Vs approximately 6 months after treatment.
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16
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Gatzios A, Rombaut M, Buyl K, De Kock J, Rodrigues RM, Rogiers V, Vanhaecke T, Boeckmans J. From NAFLD to MAFLD: Aligning Translational In Vitro Research to Clinical Insights. Biomedicines 2022; 10:biomedicines10010161. [PMID: 35052840 PMCID: PMC8773802 DOI: 10.3390/biomedicines10010161] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/09/2022] [Accepted: 01/10/2022] [Indexed: 11/16/2022] Open
Abstract
Although most same-stage non-alcoholic fatty liver disease (NAFLD) patients exhibit similar histologic sequelae, the underlying mechanisms appear to be highly heterogeneous. Therefore, it was recently proposed to redefine NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) in which other known causes of liver disease such as alcohol consumption or viral hepatitis do not need to be excluded. Revised nomenclature envisions speeding up and facilitating anti-MAFLD drug development by means of patient stratification whereby each subgroup would benefit from distinct pharmacological interventions. As human-based in vitro research fulfils an irrefutable step in drug development, action should be taken as well in this stadium of the translational path. Indeed, most established in vitro NAFLD models rely on short-term exposure to fatty acids and use lipid accumulation as a phenotypic benchmark. This general approach to a seemingly ambiguous disease such as NAFLD therefore no longer seems applicable. Human-based in vitro models that accurately reflect distinct disease subgroups of MAFLD should thus be adopted in early preclinical disease modeling and drug testing. In this review article, we outline considerations for setting up translational in vitro experiments in the MAFLD era and allude to potential strategies to implement MAFLD heterogeneity into an in vitro setting so as to better align early drug development with future clinical trial designs.
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Affiliation(s)
| | | | | | | | | | | | | | - Joost Boeckmans
- Correspondence: (A.G.); (J.B.); Tel.: +32-(0)-2-477-45-94 (A.G.)
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17
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Matsumoto K, Miyaaki H, Fukushima M, Sasaki R, Haraguchi M, Miuma S, Nakao K. The impact of single-nucleotide polymorphisms on liver stiffness and controlled attenuation parameter in patients treated with direct-acting antiviral drugs for hepatitis C infection. Biomed Rep 2022; 16:9. [PMID: 34987793 PMCID: PMC8719319 DOI: 10.3892/br.2021.1492] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Accepted: 11/18/2021] [Indexed: 11/18/2022] Open
Abstract
Single-nucleotide polymorphisms (SNPs) of patatin-like phospholipase domain-containing 3 (PNPLA3), tolloid-like protein 1 (TLL1) and interleukin-28 (IL28) have been identified as susceptibility factors for liver steatosis, inflammation and fibrosis in patients with hepatitis C virus (HCV) infection. Here, whether these polymorphisms affected predispositions to changes in liver stiffness (LS) and controlled attenuation parameter (CAP) following direct-acting antiviral (DAA) therapy was assessed. The changes in LS and steatosis in 77 HCV-infected patients receiving DAA therapy were compared with PNPLA3, TLL1 and IL28 genotypes, using CAP, FibroScan and Virtual Touch tissue quantification (VTTQ) before treatment and 12 weeks after the end of the treatment. VTTQ results showed that LS significantly decreased in PNPLA3 CC (P=0.035), TLL1 AA (P=0.011) and IL28B TT (P=0.005) genotypes; no significant differences were observed in PNPLA3 CG/GG, TLL1 AT/TT and IL28B TG/GG. FibroScan results showed that LS significantly decreased in TLL1 AA (P=0.028) and IL28B TT (P=0.032), with no significant difference in PNPLA3 CC. No significant differences were observed in PNPLA3 CG/GG, TLL1 AT/TT and IL28B TG/GG groups. CAP was significantly increased in PNPLA3 CG/GG (P=0.039 and P<0.05) and IL28B TT (P=0.014); no significant difference was observed in PNPLA3 CC and all genotypes of TLL1 and IL28B TG/GG. Therefore, these results indicated that SNPs could predict changes in LS and steatosis after DAA therapy.
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Affiliation(s)
- Kosuke Matsumoto
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
| | - Hisamitsu Miyaaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
| | - Masanori Fukushima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
| | - Ryu Sasaki
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
| | - Masafumi Haraguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
| | - Satoshi Miuma
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan
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Cerrito L, Ainora ME, Nicoletti A, Garcovich M, Riccardi L, Pompili M, Gasbarrini A, Zocco MA. Elastography as a predictor of liver cirrhosis complications after hepatitis C virus eradication in the era of direct-acting antivirals. World J Hepatol 2021; 13:1663-1676. [PMID: 34904036 PMCID: PMC8637667 DOI: 10.4254/wjh.v13.i11.1663] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 07/08/2021] [Accepted: 08/17/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic inflammation due to hepatitis C virus (HCV) infection leads to liver fibrosis and rearrangement of liver tissue, which is responsible for the development of portal hypertension (PH) and hepatocellular carcinoma (HCC). The advent of direct-acting antiviral drugs has revolutionized the natural history of HCV infection, providing an overall eradication rate of over 90%. Despite a significant decrease after sustained virological response (SVR), the rate of HCC and liver-related complications is not completely eliminated in patients with advanced liver disease. Although the reasons are still unclear, cirrhosis itself has a residual risk for the development of HCC and other PH-related complications. Ultrasound elastography is a recently developed non-invasive technique for the assessment of liver fibrosis. Following the achievement of SVR, liver stiffness (LS) usually decreases, as a consequence of reduced inflammation and, possibly, fibrosis. Recent studies emphasized the application of LS assessment in the management of patients with SVR in order to define the risk for developing the complications of chronic liver disease (functional decompensation, gastrointestinal bleeding, HCC) and to optimize long-term prognostic outcomes in clinical practice.
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Affiliation(s)
- Lucia Cerrito
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Maria Elena Ainora
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Alberto Nicoletti
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Matteo Garcovich
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Laura Riccardi
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Maurizio Pompili
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Antonio Gasbarrini
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Maria Assunta Zocco
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168,
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Siphepho PY, Liu YT, Shabangu CS, Huang JF, Huang CF, Yeh ML, Yu ML, Wang SC. The Impact of Steatosis on Chronic Hepatitis C Progression and Response to Antiviral Treatments. Biomedicines 2021; 9:1491. [PMID: 34680608 PMCID: PMC8533513 DOI: 10.3390/biomedicines9101491] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 10/12/2021] [Accepted: 10/13/2021] [Indexed: 02/07/2023] Open
Abstract
Metabolic derangement is characteristic in patients with hepatitis C virus (HCV) infection. Aside from established liver injury, various extrahepatic metabolic disorders impact the natural history of the disease, clinical outcomes, and the efficacy of antiviral therapy. The presence of steatosis, recently redefined as metabolic-associated fatty liver disease (MAFLD), is a common feature in HCV-infected patients, induced by host and/or viral factors. Most chronic HCV-infected (CHC) patients have mild steatosis within the periportal region of the liver with an estimated prevalence of 40% to 86%. Indeed, this is higher than the 19% to 50% prevalence observed in patients with other chronic liver diseases such as chronic hepatitis B (CHB). The histological manifestations of HCV infection are frequently observed in genotype 3 (G-3), where relative to other genotypes, the prevalence and severity of steatosis is also increased. Steatosis may independently influence the treatment efficacy of either interferon-based or interferon-free antiviral regimens. This review aimed to provide updated evidence of the prevalence and risk factors behind HCV-associated steatosis, as well as explore the impact of steatosis on HCV-related outcomes.
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Affiliation(s)
- Phumelele Yvonne Siphepho
- Program in Tropical Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (P.Y.S.); (M.-L.Y.)
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
| | - Yi-Ting Liu
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
| | - Ciniso Sylvester Shabangu
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Jee-Fu Huang
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ming-Lung Yu
- Program in Tropical Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (P.Y.S.); (M.-L.Y.)
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Shu-Chi Wang
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
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20
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Ferraioli G. Quantitative assessment of liver steatosis using ultrasound controlled attenuation parameter (Echosens). J Med Ultrason (2001) 2021; 48:489-495. [PMID: 34132934 PMCID: PMC8578057 DOI: 10.1007/s10396-021-01106-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 05/27/2021] [Indexed: 01/01/2023]
Abstract
Controlled attenuation parameter (CAP) is the algorithm available on the FibroScan system (Echosens, France) for quantification of liver steatosis. It assesses the ultrasound beam attenuation, which is directly related to liver fat content. The inter-observer reproducibility of the technique is high, with a reported concordance correlation coefficient of 0.82. Specific quality criteria for CAP measurements are not clearly defined yet, and there are conflicting results in the literature. Using liver biopsy as the reference standard, several studies have assessed the CAP performance in grading liver steatosis, and have reported that values are not affected by liver fibrosis. The cutoff for detection of liver steatosis reported in the literature ranges from 222 decibels per meter (dB/m) in a cohort of patients with chronic hepatitis C to 294 dB/m in a meta-analysis of nonalcoholic fatty liver disease (NAFLD) patients. CAP has been used as a tool to noninvasively evaluate the prevalence of NAFLD in groups at risk or in the general population; however, it should be underscored that different CAP cutoffs for steatosis detection (S > 0) were used in different studies, and this limits the robustness of the findings. CAP, alone or combined with other noninvasive indices or biomarkers, has been proposed as a tool for assessing nonalcoholic steatohepatitis or as a noninvasive predictor of prognosis in patients with chronic liver disease. CAP is easy to perform and has become a point-of-care technique. However, there is a large overlap of values between consecutive grades of liver steatosis, and cutoffs are not clearly defined.
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Affiliation(s)
- Giovanna Ferraioli
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, Medical School University of Pavia, Viale Brambilla 74, 27100, Pavia, Italy.
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21
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Su PY, Su WW, Wu LS, Hsu PK, Huang SP, Hsu YC. Reduction of Shear Wave Elastography but Not Shear Wave Dispersion After Successful Hepatitis C Treatment With Direct-Acting Antiviral Agents. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2021; 40:1919-1926. [PMID: 33400288 DOI: 10.1002/jum.15576] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 10/27/2020] [Accepted: 10/30/2020] [Indexed: 06/12/2023]
Abstract
OBJECTIVES Successful antiviral treatment in patients with hepatitis C can lead to reduced liver stiffness. In this study, we attempted to compare 2-dimensional (2D) shear wave elastography (SWE), shear wave dispersion (SWD), and attenuation imaging (ATI) with transient elastography (TE) and the controlled attenuation parameter (CAP) in patients under direct-acting antiviral (DAA) therapy. METHODS Patients with chronic hepatitis C infection undergoing DAA therapy from January 2017 to June 2020 were retrospectively examined. The results of 2D SWE, SWD, ATI, TE, and CAP were recorded before and 12 weeks after the completion of DAA therapy. RESULTS A total of 122 patients with a median age of 61 years were investigated; among them, 121 (99.2%) achieved a sustained virologic response at 12 weeks after DAA therapy. Fibrosis 4, the aspartate aminotransferase-to-platelet ratio index, 2D SWE, and TE were reduced after DAA therapy. The CAP was increased; however, SWD and ATI showed no statistically significant changes after DAA therapy. Two-dimensional SWE and TE were strongly correlated (r = 0.885-0.897; P < .001). Albumin and the baseline liver stiffness measurement were independent factors of liver stiffness measurement changes after DAA therapy. CONCLUSIONS Direct-acting antiviral therapy can significantly decrease liver stiffness (using both 2D SWE and TE) but not SWD and ATI values in patients with hepatitis C. An increased CAP is also observed after DAA therapy.
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Affiliation(s)
- Pei-Yuan Su
- Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
| | - Wei-Wen Su
- Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
| | - Li-Sha Wu
- Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
| | - Po-Ke Hsu
- Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
| | - Siou-Ping Huang
- Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
| | - Yu-Chun Hsu
- Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
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Spaziante M, Taliani G, Marchetti G, Tavelli A, Lichtner M, Cingolani A, Cicalini S, Biliotti E, Girardi E, Antinori A, Puoti M, d’Arminio Monforte A, Cozzi-Lepri A. Impact of HCV Eradication on Lipid Metabolism in HIV/HCV Coinfected Patients: Data from ICONA and HepaICONA Foundation Cohort Study. Viruses 2021; 13:v13071402. [PMID: 34372608 PMCID: PMC8310285 DOI: 10.3390/v13071402] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 07/13/2021] [Accepted: 07/13/2021] [Indexed: 12/23/2022] Open
Abstract
OBJECTIVES HCV shows complex interactions with lipid metabolism. Our aim was to examine total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) changes in HIV/HCV coinfected patients, after achieving sustained virological response (SVR), according to different HCV genotypes and specific antiretroviral use. METHODS HIV/HCV coinfected patients, enrolled in the ICONA and HepaICONA cohorts, who achieved DAA-driven SVR were included. Paired t-tests were used to examine whether the pre- and post-SVR laboratory value variations were significantly different from zero. ANCOVA regression models were employed to estimate the causal effect of SVR and of PI/r use on lipid changes. The interaction between the effect of eradication and HCV genotype was formally tested. RESULTS six hundred and ninety-nine HIV/HCV coinfected patients were enrolled. After HCV eradication, a significant improvement in liver function occurred, with a significant decrease in AST, ALT, GGT, and total plasmatic bilirubin. TC and LDL-C significantly increased by 21.4 mg/dL and 22.4 mg/dL, respectively (p < 0.001), after SVR, whereas there was no evidence for a change in HDL-C (p = 0.45) and triglycerides (p = 0.49). Notably, the TC and LDL-C increase was higher for participants who were receiving darunavir/ritonavir, and the TC showed a more pronounced increase among HCV genotype 3 patients (interaction-p value = 0.002). CONCLUSIONS complex and rapid changes in TC and LDL-C levels, modulated by HCV genotype and PI/r-based ART combinations, occurred in HIV/HCV coinfected patients after SVR. Further studies are needed to evaluate the clinical impact of these changes on the long-term risk of cardiovascular disease.
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Affiliation(s)
- Martina Spaziante
- Clinical Epidemiology Unit, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy; (M.S.); (E.G.)
| | - Gloria Taliani
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy;
- Task Force Anti-COVID, AORN San Giuseppe Moscati, 83100 Avellino, Italy
- Correspondence:
| | - Giulia Marchetti
- ASST Santi Paolo e Carlo, Clinic of Infectious and Tropical Diseases, Department of Health Sciences, University of Milan, 20122 Milan, Italy; (G.M.); (A.d.M.)
| | | | - Miriam Lichtner
- Department of Infectious Diseases, La Sapienza University, Polo Pontino, 04100 Latina, Italy;
| | - Antonella Cingolani
- Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Policlinico Agostino Gemelli IRCCS, 00168 Rome, Italy;
| | - Stefania Cicalini
- HIV/AIDS Clinical Unit, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy; (S.C.); (A.A.)
| | - Elisa Biliotti
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy;
| | - Enrico Girardi
- Clinical Epidemiology Unit, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy; (M.S.); (E.G.)
| | - Andrea Antinori
- HIV/AIDS Clinical Unit, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy; (S.C.); (A.A.)
| | - Massimo Puoti
- Division of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy;
| | - Antonella d’Arminio Monforte
- ASST Santi Paolo e Carlo, Clinic of Infectious and Tropical Diseases, Department of Health Sciences, University of Milan, 20122 Milan, Italy; (G.M.); (A.d.M.)
| | - Alessandro Cozzi-Lepri
- Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, London WC1N 1EH, UK;
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23
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Florea M, Serban T, Tirpe GR, Tirpe A, Lupsor-Platon M. Noninvasive Assessment of Hepatitis C Virus Infected Patients Using Vibration-Controlled Transient Elastography. J Clin Med 2021; 10:jcm10122575. [PMID: 34200885 PMCID: PMC8230562 DOI: 10.3390/jcm10122575] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 06/06/2021] [Accepted: 06/08/2021] [Indexed: 02/08/2023] Open
Abstract
Chronic infection with hepatitis C virus (HCV) is one of the leading causes of cirrhosis and hepatocellular carcinoma (HCC). Surveillance of these patients is an essential strategy in the prevention chain, including in the pre/post-antiviral treatment states. Ultrasound elastography techniques are emerging as key methods in the assessment of liver diseases, with a number of advantages such as their rapid, noninvasive, and cost-effective characters. The present paper critically reviews the performance of vibration-controlled transient elastography (VCTE) in the assessment of HCV patients. VCTE measures liver stiffness (LS) and the ultrasonic attenuation through the embedded controlled attenuation parameter (CAP), providing the clinician with a tool for assessing fibrosis, cirrhosis, and steatosis in a noninvasive manner. Moreover, standardized LS values enable proper staging of the underlying fibrosis, leading to an accurate identification of a subset of HCV patients that present a high risk for complications. In addition, VCTE is a valuable technique in evaluating liver fibrosis prior to HCV therapy. However, its applicability in monitoring fibrosis regression after HCV eradication is currently limited and further studies should focus on extending the boundaries of VCTE in this context. From a different perspective, VCTE may be effective in identifying clinically significant portal hypertension (CSPH). An emerging prospect of clinical significance that warrants further study is the identification of esophageal varices. Our opinion is that the advantages of VCTE currently outweigh those of other surveillance methods.
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Affiliation(s)
- Mira Florea
- Community Medicine Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Teodora Serban
- Medical Imaging Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - George Razvan Tirpe
- Department of Radiology and Medical Imaging, County Emergency Hospital Cluj-Napoca, 3-5 Clinicilor Street, 400000 Cluj-Napoca, Romania;
| | - Alexandru Tirpe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania;
| | - Monica Lupsor-Platon
- Medical Imaging Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
- Medical Imaging Department, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
- Correspondence:
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Sadeghi A, Amiri R, Akbarpour E, Mirminachi B, Sharifi AH, Merat S. Changes in liver fibrosis in patients with chronic hepatitis C after successful direct-acting antiviral therapy. Int J Clin Pract 2021; 75:e14145. [PMID: 33709413 DOI: 10.1111/ijcp.14145] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 03/09/2021] [Indexed: 12/28/2022] Open
Abstract
INTRODUCTION AND OBJECTIVES After successful treatment of hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs), the stage of liver fibrosis decreases over time. Here, we aimed to assess the changes in the liver fibrosis stage using transient elastography (TE) after successful DAA therapy in HCV-infected cirrhotic patients who were referred to Shariati hospital from 2016 to 2017. MATERIAL AND METHODS In this observational cohort, all HCV-infected cirrhotic patients who were treated with a combination of sofosbuvir/daclatasvir, had sustained virologic response (SVR), and had undergone pre- and post-treatment TE, were enrolled. The primary outcome was the changes in TE parameters six months after the end of treatment compared with baseline. RESULTS A total of 442 eligible subjects received DAA therapy. Overall, the SVR rate was 96.6%. Of these, 149 patients had completed the protocol and were enrolled. The mean age of patients was 56.1 ± 10.3 years and the predominant sex was male (77.9%). The median (Q1 -Q3 ) liver stiffness (LS) value at baseline was 26.3 kPa (18.1-38 kPa), which significantly decreased to 20.9 kPa (12-29.7 kPa) [z = -8.45, P-value < .001]. Also, the liver steatosis of patients with baseline CAP ≥ 220 dB/m had a significant response to treatment [z = -2.3, P-value = .023]. Based on multivariate analysis, a higher baseline liver fibrosis stage was the only determinant of LS values improvement in our study. CONCLUSION Successful HCV eradication in patients with liver fibrosis results in significant improvement in LS, even in cirrhotic patients.
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Affiliation(s)
- Anahita Sadeghi
- Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Roya Amiri
- Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Elham Akbarpour
- Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Babak Mirminachi
- Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir-Houshang Sharifi
- Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Shahin Merat
- Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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Fouad Y, Lazarus JV, Negro F, Peck-Radosavljevic M, Sarin SK, Ferenci P, Esmat G, Ghazinian H, Nakajima A, Silva M, Lee S, Colombo M. MAFLD considerations as a part of the global hepatitis C elimination effort: an international perspective. Aliment Pharmacol Ther 2021; 53:1080-1089. [PMID: 33751604 DOI: 10.1111/apt.16346] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 02/17/2021] [Accepted: 03/09/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND The World Health Organization (WHO) set a goal to eliminate hepatitis C (HCV) infection globally by 2030, with specific targets to reduce new viral hepatitis infections by 80% and reduce related deaths by 65%. However, an overlooked aspect that may hinder these efforts is the impact other liver diseases could have by continuing to drive liver disease progression and offset the beneficial impact of DAAs on end-stage liver disease and hepatocellular carcinoma (HCC). In particular, the decrease in HCV prevalence has been countered by a marked increase in the prevalence of metabolic-associated fatty liver disease (MAFLD). AIMS To review the potential interaction of HCV and MAFLD. METHODS We have reviewed the literature relating to an arrange of interaction of HCV, metabolic dysfunction and MAFLD. RESULTS In this viewpoint, international experts suggest a holistic and multidisciplinary approach for the management of the growing number of treated HCV patients who achieved SVR, taking into consideration the overlooked impact of MAFLD for reducing morbidity and mortality in people who have had HCV. CONCLUSIONS This will strengthen and improve the continuum of care cascade for patients with liver disease(s) and holds the potential to alleviate the cost burden of disease; and increase quality of life for patients following DAAs treatment.
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Kumada T, Toyoda H, Yasuda S, Sone Y, Ogawa S, Takeshima K, Tada T, Ito T, Sumida Y, Tanaka J. Prediction of Hepatocellular Carcinoma by Liver Stiffness Measurements Using Magnetic Resonance Elastography After Eradicating Hepatitis C Virus. Clin Transl Gastroenterol 2021; 12:e00337. [PMID: 33888672 PMCID: PMC8078363 DOI: 10.14309/ctg.0000000000000337] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 03/05/2021] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Liver fibrosis stage is one of the most important factors in stratifying the risk of developing hepatocellular carcinoma (HCC). We evaluated the usefulness of liver stiffness measured by magnetic resonance elastography (MRE) to stratify the risk of developing HCC in patients who underwent MRE before receiving direct-acting antivirals (DAAs) and subsequently achieved sustained virological response (SVR). METHODS A total of 537 consecutive patients with persistent hepatitis C virus who underwent initial MRE before DAA therapy and achieved SVR were enrolled. Factors associated with HCC development were analyzed by univariate and multivariate Cox proportional hazards models. RESULTS Albumin-bilirubin score ≥ -2.60 (adjusted hazard ratio [aHR] 6.303), fibrosis-4 (FIB-4) score >3.25 (aHR 7.676), and MRE value ≥4.5 kPa (aHR 13.190) were associated with HCC development according to a univariate Cox proportional hazards model. A multivariate Cox proportional hazards model showed that an MRE value ≥4.5 kPa (aHR 7.301) was the only factor independently associated with HCC development. Even in patients with an FIB-4 score >3.25, the cumulative incidence rate of HCC development in those with an MRE value <4.5 kPa was significantly lower than that in patients with an MRE value ≥4.5 kPa. DISCUSSION Liver stiffness measured by MRE before DAA therapy was an excellent marker for predicting subsequent HCC development in patients with hepatitis C virus infection who achieved SVR. The same results were observed in patients with high FIB-4 scores.
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Affiliation(s)
- Takashi Kumada
- Department of Nursing, Faculty of Nursing, Gifu Kyoritsu University, Ogaki, Gifu, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Yasuhiro Sone
- Department of Radiology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Sadanobu Ogawa
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Kenji Takeshima
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Toshifumi Tada
- Department of Internal Medicine, Himeji Red Cross Hospital, Himeji, Hyougo, Japan
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
| | - Yoshio Sumida
- Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
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Nakazawa A, Fujioka S, Notsumata K, Shima T, Yangita K, Kawaguchi M, Tahara T, Oomoto M, Ishikawa T, Kawana I, Tsukada N, Funakoshi S, Itoh H, Nagano T, Horie Y, Tatemichi M, Yamamoto K, Okanoue T. Absence of differences in the recurrence rates of hepatitis C virus‑associated hepatocellular carcinoma between direct‑acting antivirals and interferon‑based treatments: A multicenter study. WORLD ACADEMY OF SCIENCES JOURNAL 2021; 3:27. [DOI: 10.3892/wasj.2021.98] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/28/2023]
Affiliation(s)
- Atsushi Nakazawa
- Department of Internal Medicine, Saiseikai Central Hospital, Tokyo 108‑0073, Japan
| | - Shinichi Fujioka
- Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama 700‑8511, Japan
| | - Kazuo Notsumata
- Department of Internal Medicine, Fukui‑ken Saiseikai Hospital, Fukui 918‑8503, Japan
| | - Toshihide Shima
- Department of Gastroenterology and Hepatology, Osaka Saiseikai Suita Hospital, Osaka 564‑0013, Japan
| | - Kimihiko Yangita
- Department of Internal Medicine, Saiseikai Karatsu Hospital, Karatsu, Saga 847‑0852, Japan
| | - Masanori Kawaguchi
- Department of Gastroenterology, Saiseikai Wakayama Hospital, Wakayama 640‑8158, Japan
| | - Toshiyuki Tahara
- Department of Internal Medicine, Saiseikai Utsunomiya Hospital, Utsunomiya, Tochigi 321‑0974, Japan
| | - Masaki Oomoto
- Department of Internal Medicine and Gastroenterology, Saiseikai Imabari Hospital, Imabari, Ehime 799‑1502, Japan
| | - Toru Ishikawa
- Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata 950‑1104, Japan
| | - Ichiro Kawana
- Department of Gastroenterology, Saiseikai Yokohamashi Nanbu Hospital, Yokohama, Kanagawa 234‑0054, Japan
| | - Nobuhiro Tsukada
- Department of Internal Medicine, Saiseikai Central Hospital, Tokyo 108‑0073, Japan
| | - Shinsuke Funakoshi
- Department of Internal Medicine, Saiseikai Central Hospital, Tokyo 108‑0073, Japan
| | - Hiroyuki Itoh
- Department of Internal Medicine, Saiseikai Kure Hospital, Kure, Hiroshima 737‑0821, Japan
| | - Tomoo Nagano
- Department of Internal Medicine, Kamisu Saisekai Hospital, Kamisu, Ibaraki 314‑0112, Japan
| | - Yutaka Horie
- Department of Gastroenterology, Shimaneken Saiseikai Gotsu General Hospital, Gotsu, Shimane 695‑0011, Japan
| | - Masayuki Tatemichi
- Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Kanagawa, 259‑1193, Japan
| | - Kazuhide Yamamoto
- Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama 700‑8511, Japan
| | - Takeshi Okanoue
- Department of Gastroenterology and Hepatology, Osaka Saiseikai Suita Hospital, Osaka 564‑0013, Japan
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Risk of hepatocellular carcinoma and fibrosis evolution in hepatitis C patients with severe fibrosis or cirrhosis treated with direct acting antiviral agents. Acta Gastroenterol Belg 2021; 84:25-32. [PMID: 33639690 DOI: 10.51821/84.1.420] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background and study aims Cirrhosis associated to chronic hepatitis C virus (HCV) is one of the leading cause of hepatocellular carcinoma (HCC). The goal of our study was to evaluate first the risk and determinants of HCC and second the evolution of fibrosis in patients treated for HCV with advanced fibrosis stages who achieved sustained virological response (SVR) after direct-acting antivirals (DAA) treatment. Patients and methods We conducted a prospective study on HCV patients with F3 or F4 Metavir fibrosis scores treated with DAA between October 2014 and February 2017. The annual incidence rate for HCC was calculated. We used Cox regression model in order to identify factors associated with HCC. Transient elastography (TE) was performed 12 and 24 months after the end of DAA treatment and non-invasive liver fibrosis biomarkers were performed twice a year during follow-up. Results 143 patients with severe fibrosis or cirrhosis were enrolled in the study. 6 patients developed HCC. The annual incidence rate of HCC in our cohort was 2.7 per 100 patients. Risk factors associated with HCC after DAA were genotype 2 and steatosis. Overall TE values significantly decreased after DAA treatment with a median value prior to treatment of 16.9 kPa to a median of 10.8 kPa 24 months after the end of the treatment. Biological fibrosis scores also significantly decreased following viral eradication. Conclusions DAA treatment does not seem to be associated with HCC promotion after HCV eradication in patients with severe fibrosis stages. DAA-induced SVR is associated with a reduced estimation of fibrosis.
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Fraquelli M, Fanetti I, Costantino A. Elastography After Treatment and During Follow-Up. ELASTOGRAPHY OF THE LIVER AND BEYOND 2021:119-141. [DOI: 10.1007/978-3-030-74132-7_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Chayanupatkul M, Chittmittraprap S, Pratedrat P, Chuaypen N, Avihingsanon A, Tangkijvanich P. Efficacy of elbasvir/grazoprevir therapy in HCV genotype-1 with or without HIV infection: role of HCV core antigen monitoring and improvement of liver stiffness and steatosis. Antivir Ther 2020; 25:305-314. [PMID: 32910788 DOI: 10.3851/imp3370] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/20/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND The combination of elbasvir and grazoprevir (EBR/GZR) has been approved for treating HCV infection. This study aimed to evaluate the efficacy of EBR/GZR in terms of sustained virological response (SVR) and improvement of liver fibrosis in Thai patients with HCV genotype-1 (GT1). The utility of serum HCV core antigen (HCVcAg) as an alternative to HCV RNA in assessing SVR was also investigated. METHODS A total of 101 HCV GT1-infected patients (65 monoinfection and 36 HIV coinfection) who received EBR/GZR for 12-16 weeks were included. Liver stiffness (LS) and controlled attenuation parameter (CAP) were measured by transient elastography. Serum HCVcAg was measured in parallel with HCV RNA. RESULTS The overall SVR12 and SVR24 rates in the cohort were 98.0% and 95.0%, respectively. SVR24 rates were consistently high (90.0% to 100%) across all subgroups of patients. A significant LS decline ³30% was observed more frequently in cirrhotic than non-cirrhotic individuals who achieved SVR (63.3% versus 30.3%; P=0.003). The magnitude of LS decline following HCV eradication was comparable between HCV monoinfection and HCV-HIV coinfection. The reduction of CAP was also observed in responders who had significant steatosis at baseline. Compared with HCV RNA, HCVcAg testing displayed high sensitivity (100%) and specificity (99.0-100%) in determining SVR12 and SVR24. CONCLUSIONS This study confirms that EBR/GZR is effective for HCV GT1-infected Thai patients with or without HIV infection. HCV eradication is associated with LS and CAP improvement regardless of HIV status. HCVcAg testing could be a potential replacement for HCV RNA for assessing SVR in resource-limited settings.
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Affiliation(s)
- Maneerat Chayanupatkul
- Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Salyavit Chittmittraprap
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Pornpitra Pratedrat
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Natthaya Chuaypen
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Anchalee Avihingsanon
- The HIV Netherlands Australia Thailand Research Collaboration (HIV NAT), Bangkok, Thailand
| | - Pisit Tangkijvanich
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Wang JH, Ou HY, Yen YH, Chen CH, Lu SN. Usefulness of Controlled Attenuation Parameter in Detecting and Monitoring Hepatic Steatosis with MRI-PDFF as Reference. Dig Dis Sci 2020; 65:1512-1519. [PMID: 31617130 DOI: 10.1007/s10620-019-05883-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 10/09/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Controlled attenuation parameter (CAP) has been developed to estimate the extent of hepatic steatosis. AIMS The purpose was to evaluate the usefulness of CAP in assessing hepatic steatosis and its change using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as reference standard. METHODS Consecutive patients with liver steatosis were enrolled prospectively. We assessed hepatic steatosis with CAP and MRI-PDFF at enrollment and 12-month follow-up. The correlations between the two methods were analyzed. With MRI-PDFF as reference, the performance of CAP in diagnosis of steatosis severity and its changes was assessed. RESULTS A total of 50 patients were enrolled, and 45 of them had follow-up MRI-PDFF and CAP at a median interval of 399 days. The mean hepatic steatosis was 13.4% by MRI-PDFF and 291.6 dB/m by CAP. There were positive correlations between CAP and MRI-PDFF in steatosis severity and its change. The median value of CAP was 254, 301.5, and 329.5 dB/m for steatosis < 10%, 10-20%, and > 20%, respectively. For CAP in detecting steatosis ≥ 10% and > 20%, the diagnostic performance was 0.821 and 0.814. With the cutoff of 275 dB/m for ≥ 10% steatosis, the positive predictive value was 84.8%. With the cutoff of 325 dB/m for > 20% steatosis, the negative predictive value was 91.9%. In multiple linear regression, one dB/m change by CAP was associated with 0.039% change by MRI-PDFF. CONCLUSIONS In assessing liver fat content, CAP correlated with MRI-PDFF and was useful for detection and monitoring of hepatic steatosis.
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Affiliation(s)
- Jing-Houng Wang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123, Ta Pei Road, Niao Sung 833, Kaohsiung City, Taiwan
| | - Hsin-You Ou
- Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City, Taiwan
| | - Yi-Hao Yen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123, Ta Pei Road, Niao Sung 833, Kaohsiung City, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123, Ta Pei Road, Niao Sung 833, Kaohsiung City, Taiwan
| | - Sheng-Nan Lu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123, Ta Pei Road, Niao Sung 833, Kaohsiung City, Taiwan.
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi County, Taiwan.
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Dash S, Aydin Y, Wu T. Integrated stress response in hepatitis C promotes Nrf2-related chaperone-mediated autophagy: A novel mechanism for host-microbe survival and HCC development in liver cirrhosis. Semin Cell Dev Biol 2020; 101:20-35. [PMID: 31386899 PMCID: PMC7007355 DOI: 10.1016/j.semcdb.2019.07.015] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 06/26/2019] [Accepted: 07/30/2019] [Indexed: 02/06/2023]
Abstract
The molecular mechanism(s) how liver damage during the chronic hepatitis C virus (HCV) infection evolve into cirrhosis and hepatocellular carcinoma (HCC) is unclear. HCV infects hepatocyte, the major cell types in the liver. During infection, large amounts of viral proteins and RNA replication intermediates accumulate in the endoplasmic reticulum (ER) of the infected hepatocyte, which creates a substantial amount of stress response. Infected hepatocyte activates a different type of stress adaptive mechanisms such as unfolded protein response (UPR), antioxidant response (AR), and the integrated stress response (ISR) to promote virus-host cell survival. The hepatic stress is also amplified by another layer of innate and inflammatory response associated with cellular sensing of virus infection through the production of interferon (IFN) and inflammatory cytokines. The interplay between various types of cellular stress signal leads to different forms of cell death such as apoptosis, necrosis, and autophagy depending on the intensity of the stress and nature of the adaptive cellular response. How do the adaptive cellular responses decode such death programs that promote host-microbe survival leading to the establishment of chronic liver disease? In this review, we discuss how the adaptive cellular response through the Nrf2 pathway that promotes virus and cell survival. Furthermore, we provide a glimpse of novel stress-induced Nrf2 mediated compensatory autophagy mechanisms in virus-cell survival that degrade tumor suppressor gene and activation of oncogenic signaling during HCV infection. Based on these facts, we hypothesize that the balance between hepatic stress, inflammation and different types of cell death determines liver disease progression outcomes. We propose that a more nuanced understanding of virus-host interactions under excessive cellular stress may provide an answer to the fundamental questions why some individuals with chronic HCV infection remain at risk of developing cirrhosis, cancer and some do not.
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Affiliation(s)
- Srikanta Dash
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA.
| | - Yucel Aydin
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA
| | - Tong Wu
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA
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Paternostro R, Pfeiffenberger J, Ferenci P, Stättermayer AF, Stauber RE, Wrba F, Longerich T, Lackner K, Trauner M, Ferlitsch A, Reiberger T, Weiss KH. Non-invasive diagnosis of cirrhosis and long-term disease monitoring by transient elastography in patients with Wilson disease. Liver Int 2020; 40:894-904. [PMID: 31898387 PMCID: PMC7187206 DOI: 10.1111/liv.14368] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Revised: 12/05/2019] [Accepted: 12/30/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS The value of liver stiffness measurement (LSM) by transient elastography (TE) for non-invasive fibrosis staging and disease monitoring has not been established in patients with Wilson disease (WD). METHODS Liver stiffness measurement by TE and non-invasive fibrosis scores (APRI, FIB-4) were analysed from 188 WD patients with liver biopsy (LBX). Longitudinal LSM was performed in 128 (68.1%) patients. RESULTS One hundred and eighty-eight patients (mean age: 35 ± 14 years, 54.8% women; 27.1% with histological cirrhosis) were studied. Forty-four[23.4%] patients were recently diagnosed with WD, while 144[76.6%] were previously diagnosed (>1 year between LBX and LSM). Overall, LSM (11.3 vs 6.1 kPa, P < .001), APRI (0.72 vs 0.38, P < .001) and FIB-4 (1.54 vs 0.89, P < .001) were higher in cirrhotic than in non-cirrhotic patients. This was even more pronounced in recently diagnosed patients (35.2 kPa vs 6.4 kPa, P < .001). Accuracy for diagnosing cirrhosis at an LSM cut-off ≥9.9 kPa was better in recently diagnosed (PPV: 74%, NPV: 100%) vs previously diagnosed (PPV: 53%, NPV: 82%) patients. Recently diagnosed patients had higher Area Under the Curve (AUC) for APRI (0.79 vs 0.61) and FIB-4 (0.84 vs 0.65) than previously diagnosed patients. At APRI <1.5 and FIB-4 <3.25 cirrhosis was ruled out with a specificity of 93% and 95% respectively. During a median follow-up of 46 (24-66) months, only 5.9% (5/85) of non-cirrhotic WD patients showed progression to cirrhotic LSM values, while 30.8% (4/13) of cirrhotic WD patients showed LSM suggestive of cirrhosis regression. CONCLUSION TE-based LSM ≥9.9 kPa accurately identifies cirrhosis in WD patients. Next to TE-LSM <9.9 kPa, APRI <1.5 and FIB-4 <3.25 values assist to non-invasively rule out cirrhosis. LSM remains stable in most non-cirrhotic patients on WD therapy, while one-third of cirrhotic patients present clinically relevant decreases in LSM.
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Affiliation(s)
- Rafael Paternostro
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Jan Pfeiffenberger
- Department of Internal Medicine IVUniversity Hospital HeidelbergHeidelbergGermany
| | - Peter Ferenci
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Albert F. Stättermayer
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Rudolf E. Stauber
- Division of Gastroenterology and HepatologyDepartment of Internal MedicineMedical University of GrazGrazAustria
| | - Fritz Wrba
- Department of PathologyMedical University of ViennaViennaAustria
| | - Thomas Longerich
- Institute of PathologyUniversity Hospital HeidelbergHeidelbergGermany
| | | | - Michael Trauner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Arnulf Ferlitsch
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Thomas Reiberger
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
- Ludwig Boltzmann Institute for Rare and Undiagnosed DiseasesViennaAustria
- CeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesViennaAustria
| | - Karl Heinz Weiss
- Department of Internal Medicine IVUniversity Hospital HeidelbergHeidelbergGermany
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Ogasawara N, Saitoh S, Akuta N, Sezaki H, Suzuki F, Fujiyama S, Kawamura Y, Hosaka T, Kobayashi M, Suzuki Y, Arase Y, Ikeda K, Kumada H. Advantage of liver stiffness measurement before and after direct-acting antiviral therapy to predict hepatocellular carcinoma and exacerbation of esophageal varices in chronic hepatitis C. Hepatol Res 2020; 50:426-438. [PMID: 31785120 DOI: 10.1111/hepr.13467] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 11/26/2019] [Accepted: 11/28/2019] [Indexed: 02/08/2023]
Abstract
AIM The risk of development of hepatocellular carcinoma (HCC) persisted in patients with advanced fibrosis, even after achieving sustained virologic response (SVR). This study aimed to show the advantage of liver stiffness measurement (LSM) at baseline and after SVR to predict HCC occurrence and esophageal varices (EV) exacerbation. METHODS These risks were evaluated in 398 chronic hepatitis C patients without a history of HCC who achieved SVR after direct-acting antiviral agent and evaluated LSM at least twice during follow up. We defined liver cirrhosis and chronic hepatitis as LSM of ≥12 kPa and <12 kPa, respectively. RESULTS LSM was significantly correlated with serum fibrosis markers, such as Fib-4 index and Wisteria floribunda agglutinin-positive Mac-2 binding protein, at baseline and SVR at 24 weeks after treatment (SVR24). Five patients received preventive treatment of EV, but no EV bleeding occurred after SVR, and their LSM at baseline and SVR24 was significantly higher than that of other cirrhosis patients. The annual rate of HCC during the first 4 years was 1.5%. LSM in HCC patients tended to decrease after direct-acting antiviral agent therapies, but significantly higher than that of cirrhosis patients without HCC before and after treatment. Multivariate analysis identified LSM and alpha-fetoprotein at baseline and LSM at SVR24 as significant independent predictors of HCC. CONCLUSIONS Evaluating LSM not only at baseline, but also SVR24, was found to be useful for the detection of advanced fibrosis patients at high risk of HCC occurrence and EV exacerbation. We recommend focused surveillance of HCC and EV for these patients.
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Affiliation(s)
| | - Satoshi Saitoh
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Norio Akuta
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Hitomi Sezaki
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | | | | | | | - Tetsuya Hosaka
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | | | | | - Yasuji Arase
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Kenji Ikeda
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
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Liver stiffness in chronic hepatitis C virus infection. ACTA ACUST UNITED AC 2020; 57:85-98. [PMID: 30447147 DOI: 10.2478/rjim-2018-0034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Indexed: 11/20/2022]
Abstract
INTRODUCTION The severity of liver fibrosis can be assessed noninvasively today by liver stiffness measurements. Vibration-controlled transient elastography, shear wave elastography or magnetic resonance elastography are techniques increasingly used for this purpose. METHODS This article presents the recent advances in the use of new techniques for liver fibrosis assessment in chronic hepatitis C: the correlation between liver stiffness values and liver fibrosis estimated by liver biopsies, the prognosis role of liver stiffness values, their usefulness in monitoring the treatment response, in assessing the severity of portal hypertension and in estimating the presence of esophageal varices. Scientific articles from January 2017 to January 2018 were searched in PubMed and PubMed Central databases, using the terms "liver stiffness" and "hepatitis C". RESULTS The median liver stiffness values measured with different techniques are not identical, so that FibroScan thresholds cannot be used on any other elastographic machine. The higher the liver's stiffness measurement, the higher the liver-related events in patients with chronic hepatitis C. A liver stiffness measurement over 17 kPa could be an independent predictor for the presence of esophageal varices as well as a spleen with a longitudinal span ≥ 15 cm for patients with a value of liver stiffness < 17 kPa. A progressive and persistent decrease in liver stiffness is dependent on sustained virological response achievement. The lack of liver stiffness decrease has been associated with relapsers and a low value of liver stiffness at baseline. CONCLUSION Liver stiffness provides clues about the severity and evolution of liver disease.
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Kanwal F, Kramer JR, Asch SM, Cao Y, Li L, El-Serag HB. Long-Term Risk of Hepatocellular Carcinoma in HCV Patients Treated With Direct Acting Antiviral Agents. Hepatology 2020; 71:44-55. [PMID: 31222774 DOI: 10.1002/hep.30823] [Citation(s) in RCA: 190] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Accepted: 06/10/2019] [Indexed: 02/03/2023]
Abstract
Sustained virologic response (SVR) after direct acting antiviral agents (DAAs) holds promise for reducing hepatocellular cancer (HCC). DAAs have recently been available long enough to estimate the long-term risk. We conducted a retrospective cohort study of hepatitis C virus (HCV) patients who achieved SVR with DAAs from 129 Veterans Health Administration hospitals between January 1, 2015, and December 31, 2015, with follow-up through September 30, 2018. We calculated the overall and quarterly HCC incidence rates. We examined the effect of demographic, clinical, and behavioral factors and the decline or increase of FIB-4 and aspartate aminotransferase to platelet ratio index (APRI) on HCC risk. Among the 18,076 patients with SVR, 544 incident cases of HCC were diagnosed during the mean 2.9 years of follow-up. The cumulative 1, 2, and 3-year risks of HCC were 1.1%, 1.9% and 2.8%, respectively. Cirrhosis was strongly associated with HCC risk (adjusted hazard ratio = 4.13, 95% confidence interval = 3.34-5.11). The quarterly incidence rate of HCC remained stable between 1.00 and 1.23/100 person-years (PY) and 1.5 to 2.3/100 PY in patients with cirrhosis. The risk of HCC was the highest in patients who had persistently high FIB-4/APRI and both with and without cirrhosis. HCC risk fell in patients with cirrhosis who experienced a decrease of FIB-4/APRI scores yet remained higher than the accepted threshold for HCC surveillance. HCC risk was also higher in patients with alcohol use, older age, and infection with HCV genotype 3. Most patients treated at an early stage of liver fibrosis had a stable low risk. Conclusion: Patients successfully treated with DAAs and at risk of HCC did not regress after 3.6 years of follow-up. HCC risk remained above the accepted thresholds for surveillance in patients with cirrhosis. These data have important implications for HCC surveillance in cured HCV patients.
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Affiliation(s)
- Fasiha Kanwal
- Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX.,Section of Gastroenterology and Hepatology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX
| | - Jennifer R Kramer
- Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX.,Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Steven M Asch
- Center for Innovation to Implementation (Ci2i), Palo Alto Veterans Affairs Medical Center, Palo Alto, CA.,Division of Primary Care and Population Health, Stanford University, Palo Alto, CA
| | - Yumei Cao
- Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX.,Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX
| | - Liang Li
- Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Hashem B El-Serag
- Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX.,Section of Gastroenterology and Hepatology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX
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Fernandes FF, Piedade J, Guimaraes L, Nunes EP, Chaves U, Goldenzon RV, Cardoso SW, Duarte J, Grinsztejn B, Veloso VG, Pereira G, Perazzo H. Effectiveness of direct-acting agents for hepatitis C and liver stiffness changing after sustained virological response. J Gastroenterol Hepatol 2019; 34:2187-2195. [PMID: 31062880 DOI: 10.1111/jgh.14707] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 04/16/2019] [Accepted: 05/03/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM Few studies have evaluated sustained virological response (SVR) rates by direct-acting agents (DAAs) and liver stiffness measurement (LSM) changing post-SVR in limited-resource settings. We aimed to describe the effectiveness of DAAs for hepatitis C virus treatment and to assess the changing of LSM post-SVR. METHODS This retrospective study analyzed data of consecutive hepatitis C virus-infected patients treated by DAAs from 2015 to 2017 in two tertiary centers in Brazil. SVR rates were reported by intention-to-treat and per-protocol analyses. LSM by transient elastography performed before treatment and post-SVR was compared, and logistic regression models were performed. RESULTS Six hundred seventy-one patients (63% female, 62 years [55-68], 89% genotype 1, 8% HIV co-infected, and 64% with cirrhosis) were included. Most patients were treated by sofosbuvir/daclatasvir ± ribavirin (74%) and sofosbuvir/simeprevir ± ribavirin (21%). SVR rates (95% confidence interval [CI]) were 94.6% (92.7-96.1) and 97.8% (96.4-98.7) for intention-to-treat and per-protocol analyses, respectively. The leading adverse event was anemia (9.6% [95% CI 7.6-12.1]). Pretreatment and post-SVR12 LSM were available in 400 patients. LSM had significantly decreased after SVR (13.6 kPa [interquartile range, 10.0-21.6] vs 10.2 kPa [7.0-17.6], P < 0.001). A total of 167 patients (42%) decreased at least 30% of LSM post-SVR. The absence of type 2 diabetes (odds ratio = 1.52 [95% CI 1.05-2.21], P = 0.028) and presence of platelet count ≥ 150 × 109 /mm3 (odds ratio = 1.75 [1.23-2.50], P = 0.002) were independently associated with a significant LSM regression (≥ 30%) post-SVR. CONCLUSION DAAs were highly effective and safe, and LSM significantly decreased after SVR in a real-life cohort in Brazil. The absence of type 2 diabetes and presence of high platelet count were independently associated with LSM decrease post-SVR.
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Affiliation(s)
- Flavia F Fernandes
- Gastroenterology and Hepatology Department, Bonsucesso Federal Hospital, Rio de Janeiro, Brazil
| | - Juliana Piedade
- Gastroenterology and Hepatology Department, Bonsucesso Federal Hospital, Rio de Janeiro, Brazil.,Laboratory of Clinical Research on STD/AIDS, Evandro Chagas National Institute of Infectious Disease (INI)-Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
| | - Livia Guimaraes
- Gastroenterology and Hepatology Department, Bonsucesso Federal Hospital, Rio de Janeiro, Brazil
| | - Estevao P Nunes
- Laboratory of Clinical Research on STD/AIDS, Evandro Chagas National Institute of Infectious Disease (INI)-Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
| | - Ursula Chaves
- Laboratory of Clinical Research on STD/AIDS, Evandro Chagas National Institute of Infectious Disease (INI)-Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
| | - Rafaela V Goldenzon
- Laboratory of Clinical Research on STD/AIDS, Evandro Chagas National Institute of Infectious Disease (INI)-Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
| | - Sandra W Cardoso
- Laboratory of Clinical Research on STD/AIDS, Evandro Chagas National Institute of Infectious Disease (INI)-Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
| | - Joana Duarte
- Gastroenterology and Hepatology Department, Bonsucesso Federal Hospital, Rio de Janeiro, Brazil
| | - Beatriz Grinsztejn
- Laboratory of Clinical Research on STD/AIDS, Evandro Chagas National Institute of Infectious Disease (INI)-Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
| | - Valdilea G Veloso
- Laboratory of Clinical Research on STD/AIDS, Evandro Chagas National Institute of Infectious Disease (INI)-Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
| | - Gustavo Pereira
- Gastroenterology and Hepatology Department, Bonsucesso Federal Hospital, Rio de Janeiro, Brazil.,School of Medicine, Estácio de Sá University, Rio de Janeiro, Brazil
| | - Hugo Perazzo
- Laboratory of Clinical Research on STD/AIDS, Evandro Chagas National Institute of Infectious Disease (INI)-Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
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Ioannou GN, Beste LA, Green PK, Singal AG, Tapper EB, Waljee AK, Sterling RK, Feld JJ, Kaplan DE, Taddei TH, Berry K. Increased Risk for Hepatocellular Carcinoma Persists Up to 10 Years After HCV Eradication in Patients With Baseline Cirrhosis or High FIB-4 Scores. Gastroenterology 2019; 157:1264-1278.e4. [PMID: 31356807 PMCID: PMC6815714 DOI: 10.1053/j.gastro.2019.07.033] [Citation(s) in RCA: 285] [Impact Index Per Article: 47.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Revised: 07/03/2019] [Accepted: 07/22/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS It is unclear if hepatocellular carcinoma (HCC) risk declines over time after hepatitis C virus (HCV) eradication. We analyzed changes in HCC annual incidence over time following HCV eradication and identified dynamic markers of HCC risk. METHODS We identified 48,135 patients who initiated HCV antiviral treatment from 2000 through 2015 and achieved a sustained virologic response (SVR) in the Veterans Health Administration (29,033 treated with direct-acting antiviral [DAA] agents and 19,102 treated with interferon-based regimens). Patients were followed after treatment until February 14, 2019 (average 5.4 years), during which 1509 incident HCCs were identified. RESULTS Among patients with cirrhosis before treatment with DAAs (n = 9784), those with pre-SVR fibrosis-4 (FIB-4) scores ≥3.25 had a higher annual incidence of HCC (3.66%/year) than those with FIB-4 scores <3.25 (1.16%/year) (adjusted hazard ratio 2.14; 95% confidence interval 1.66-2.75). In DAA-treated patients with cirrhosis and FIB-4 scores ≥3.25, annual HCC risk decreased from 3.8%/year in the first year after SVR to 2.4%/year by the fourth year (P=.01). In interferon-treated patients with FIB-4 scores ≥3.25, annual HCC risk remained above 2%/year, even 10 years after SVR. A decrease in FIB-4 scores from ≥3.25 pre-SVR to <3.25 post-SVR was associated with an approximately 50% lower risk of HCC, but the absolute annual risk remained above 2%/year. Patients without cirrhosis before treatment (n = 38,351) had a low risk of HCC, except for those with pre-SVR FIB-4 scores ≥3.25 (HCC risk 1.22%/year) and post-SVR FIB-4 scores ≥3.25 (HCC risk 2.39%/year); risk remained high for many years after SVR. CONCLUSIONS Patients with cirrhosis before an SVR to treatment for HCV infection continue to have a high risk for HCC (>2%/year) for many years, even if their FIB-4 score decreases, and should continue surveillance. Patients without cirrhosis but with FIB-4 scores ≥3.25 have a high enough risk to merit HCC surveillance, especially if FIB-4 remains ≥3.25 post-SVR.
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Affiliation(s)
- George N. Ioannou
- Division of Gastroenterology, Department of Medicine, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle, WA.,Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle, WA
| | - Lauren A Beste
- Division of General Internal Medicine, Department of Medicine, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle, WA
| | - Pamela K. Green
- Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle, WA
| | - Amit G. Singal
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas TX
| | - Elliot B. Tapper
- Division of Gastroenterology and Hepatology, VA Ann Arbor Healthcare System and University of Michigan, Ann Arbor MI
| | - Akbar K. Waljee
- Division of Gastroenterology and Hepatology, VA Ann Arbor Healthcare System and University of Michigan, Ann Arbor MI
| | - Richard K. Sterling
- Division of Gastroenterology, Department of Medicine, Virginia Commonwealth University, Richmond, VA
| | - Jordan J. Feld
- Toronto Centre for Liver Disease, University Health Network, Sandra Rotman Centre for Global Health, University of Toronto
| | - David E. Kaplan
- Division of Gastroenterology, Department of Medicine, Corporal Michael J. Crescenz Veterans Affairs Medical Center and Perelman University of Pennsylvania School of Medicine, Philadelphia, PA
| | - Tamar H. Taddei
- Section of Digestive Diseases, Yale School of Medicine, New Haven, CT and VA Connecticut Healthcare System, West Haven, CT
| | - Kristin Berry
- Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle, WA
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Sezaki H, Suzuki F, Hosaka T, Fujiyama S, Kawamura Y, Akuta N, Kobayashi M, Suzuki Y, Saitoh S, Arase Y, Ikeda K, Kobayashi M, Kumada H. Initial- and re-treatment effectiveness of glecaprevir and pibrentasvir for Japanese patients with chronic hepatitis C virus-genotype 1/2/3 infections. J Gastroenterol 2019; 54:916-927. [PMID: 30903385 DOI: 10.1007/s00535-019-01575-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Accepted: 03/17/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND Glecaprevir and pibrentasvir (GLE/PIB) are potent antiviral agents for hepatitis C virus (HCV) pan-genotypic infections; however, their clinical effectiveness and safety remain limited in the real-world. This study aimed to evaluate viral responses and the safety of GLE/PIB for patients with chronic HCV-1/2/3 infections during both initial- (Arm A) and re-treatment (Arm B) with all-oral direct-acting antiviral agents (DAAs). METHODS This prospective-observational cohort study included Japanese patients with chronic HCV-1/2/3 infections (n = 271: 183 in Arm A and 83 in Arm B), who had started receiving GLE/PIB. Primary end point was a sustained virological response (SVR) rate at week 12 (SVR12) after the end of GLE/PIB treatment (EOT). RESULTS SVR12 was achieved by 99.4% of patients (180/181: modified intention-to-treat (mITT) analysis excluding 2 patients lost to follow-up) in Arm A. One patient with an HCV-3b infection who discontinued at week 8 failed to achieve SVR12. SVR12 was achieved by 97.7% of patients (85/87: mITT excluding 1 patient lost to follow-up) in Arm B. Virological relapse occurred in 2 patients with HCV-1b, presenting common 5 loci of resistance-associated substitutions (RASs) including A92 RASs in the NS5A lesion at baseline. Any adverse events (AEs) (grade ≥ 3) occurred in 8 patients (3.0%). 8 patients (3.0%) discontinued due to AEs, however, all of them achieved SVR12. CONCLUSIONS Initial and re-treatment with GLE/PIB are effective and safe for Japanese patients with HCV-1/2/3 in real-life settings. Further studies are required to elucidate the mechanism underlying treatment failures of GLE/PIB to completely eradicate HCV worldwide.
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Affiliation(s)
- Hitomi Sezaki
- Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
| | - Fumitaka Suzuki
- Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Tetsuya Hosaka
- Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Shunichirou Fujiyama
- Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Yusuke Kawamura
- Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Norio Akuta
- Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Masahiro Kobayashi
- Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Yoshiyuki Suzuki
- Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Satoshi Saitoh
- Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Yasuji Arase
- Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Kenji Ikeda
- Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Mariko Kobayashi
- Research Institute for Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Hiromitsu Kumada
- Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
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Farhang Zangneh H, Wong WWL, Sander B, Bell CM, Mumtaz K, Kowgier M, van der Meer AJ, Cleary SP, Janssen HLA, Chan KKW, Feld JJ. Cost Effectiveness of Hepatocellular Carcinoma Surveillance After a Sustained Virologic Response to Therapy in Patients With Hepatitis C Virus Infection and Advanced Fibrosis. Clin Gastroenterol Hepatol 2019; 17:1840-1849.e16. [PMID: 30580095 DOI: 10.1016/j.cgh.2018.12.018] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Revised: 11/20/2018] [Accepted: 12/10/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Hepatitis C virus (HCV)-related cirrhosis increases the risk for hepatocellular carcinoma (HCC). After a sustained virologic response (SVR) to anti-HCV therapy, the risk of HCC is reduced but not eliminated. Recent developments in antiviral therapy have increased rates of SVR markedly. Guidelines recommend indefinite biannual ultrasound surveillance after SVR for patients with advanced fibrosis before treatment. Surveillance for HCC is cost effective before anti-HCV treatment; we investigated whether it remains so after SVR. METHODS We developed a Markov model to evaluate the cost effectiveness of biannual or annual HCC ultrasound surveillance vs no surveillance in 50-year-old patients with advanced fibrosis after an SVR to anti-HCV therapy. Parameter values were obtained from publications and expert opinions. Primary outcomes were quality-adjusted life-years (QALYs), costs, and the incremental cost-effectiveness ratios (ICERs). RESULTS With a constant 0.5% annual incidence of HCC, biannual and annual surveillance resulted in ICERs of $106,792 and $72,105 per QALY, respectively, with high false-positive rates. When surveillance was limited to patients with cirrhosis, but not F3 fibrosis, biannual surveillance likely was cost effective, with ICERs of $48,729 and $43,229 per QALY after treatment with interferon and direct-acting antiviral agents, respectively. In patients with F3 fibrosis, the incidence of HCC was 0.3% to 0.4% per year, leading to an ICER of $188,157 per QALY for biannual surveillance. If HCC incidence increases with age, surveillance becomes more cost effective but remains below willingness-to-pay thresholds only for patients with cirrhosis or with pretreatment aspartate aminotransferase to platelet ratio index greater than 2.0 or FIB-4 measurements greater than 3.25. Sensitivity analyses identified HCC incidence and transition rate to symptomatic disease without surveillance as factors that affect cost effectiveness. CONCLUSIONS In a Markov model, we found HCC surveillance after an SVR to HCV treatment to be cost effective for patients with cirrhosis, but not for patients with F3 fibrosis.
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Affiliation(s)
- Hooman Farhang Zangneh
- Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | | | - Beate Sander
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; Public Health Ontario, Ontario, Canada
| | - Chaim M Bell
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Khalid Mumtaz
- Wexner Medical Center, Ohio State University, Columbus, Ohio
| | - Matthew Kowgier
- Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | | | - Sean P Cleary
- Department of General Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada; Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Kelvin K W Chan
- Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada; Canadian Centre for Applied Research in Cancer Control, Vancouver, Canada
| | - Jordan J Feld
- Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
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Chromy D, Mandorfer M, Bucsics T, Schwabl P, Bauer D, Scheiner B, Schmidbauer C, Lang GF, Szekeres T, Ferenci P, Trauner M, Reiberger T. Prevalence and Predictors of Hepatic Steatosis in Patients with HIV/HCV Coinfection and the Impact of HCV Eradication. AIDS Patient Care STDS 2019; 33:197-206. [PMID: 31067123 DOI: 10.1089/apc.2018.0333] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Human immunodeficiency virus (HIV)-induced metabolic abnormalities and antiretroviral therapy (ART), genetic factors, most importantly the rs738409 C > G p.I148M variant in the patatin-like phospholipase domain containing 3 (PNPLA3)-gene, as well as hepatitis C virus (HCV) coinfection may all cause hepatic steatosis (HS). However, recent studies suggest a protective effect of HCV infection on HS. Thus, we evaluated HS prior and after HCV eradication in an HIV/HCV-coinfected cohort at the Medical University of Vienna between January 2014 and June 2017. Two hundred forty-seven patients underwent liver stiffness measurement and controlled attenuation parameter (CAP)-based steatosis assessment. A subcohort of 138 patients also had follow-up CAP measurement after HCV eradication by direct-acting antivirals (DAAs). A CAP value ≥248 dB/m defined HS and all CAP values were adapted to compensate for body mass index (BMI) and diabetes mellitus. Among all 247 HIV/HCV-coinfected patients, HS was prevalent in 31%, mean age was 43.3 years, 75% were male, the main ethnicity was Caucasian (96%), and mean BMI was 23.33 kg/m2. Independent risk factors for HS were BMI, years exposed to HIV, PNPLA3 G-alleles, and protease inhibitor (PI) intake. Notably, a significant increase in CAP (from 225 ± 52.9 to 235 ± 50.7 dB/m; p = 0.047) was observed after HCV eradication, whereas patients on PI-containing ART experienced a significant decrease in CAP. Overall, one-third of HIV/HCV-coinfected patients are affected by HS with PI-based ART and PNPLA3 impacting on HS prevalence. While HCV eradication by DAAs increased HS, as assessed by CAP, future studies should account for metabolic syndrome and evaluate whether changes in CAP-based steatosis assessments correspond to a clinically relevant outcome.
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Affiliation(s)
- David Chromy
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- 2 Vienna HIV & Liver Study Group, Vienna, Austria
| | - Mattias Mandorfer
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- 2 Vienna HIV & Liver Study Group, Vienna, Austria
| | - Theresa Bucsics
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- 2 Vienna HIV & Liver Study Group, Vienna, Austria
| | - Philipp Schwabl
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- 2 Vienna HIV & Liver Study Group, Vienna, Austria
| | - David Bauer
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- 2 Vienna HIV & Liver Study Group, Vienna, Austria
| | - Bernhard Scheiner
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- 2 Vienna HIV & Liver Study Group, Vienna, Austria
| | - Caroline Schmidbauer
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- 2 Vienna HIV & Liver Study Group, Vienna, Austria
| | - Gerold Felician Lang
- 2 Vienna HIV & Liver Study Group, Vienna, Austria
- 3 Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Thomas Szekeres
- 4 Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Peter Ferenci
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
- 2 Vienna HIV & Liver Study Group, Vienna, Austria
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Wei L, Huang YH. Long-term outcomes in patients with chronic hepatitis C in the current era of direct-acting antiviral agents. Expert Rev Anti Infect Ther 2019; 17:311-325. [PMID: 30856022 DOI: 10.1080/14787210.2019.1588112] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Introduction: Within the past decade, antiviral treatment for chronic hepatitis C virus (HCV) infection has evolved from interferon (IFN)-based regimens to IFN-free oral direct-acting antiviral agents (DAAs). However, data on long-term outcomes in HCV patients treated by DAAs are limited and complex. Areas covered: Original studies and meta-analyses reporting data on the impacts of IFN - and DAA-based treatments on late relapse, liver fibrosis/cirrhosis, decompensation progression, hepatocellular carcinoma (HCC) occurrence and recurrence, need for liver transplantation, mortality, and other topics of interest for long-term observation of HCV patients treated with DAAs. Articles published up to June 2018, and proceedings from annual meetings of major international liver diseases associations (from 2015 to June 2018) were reviewed. Relevant references from selected papers were also reviewed. Expert opinion: In HCV patients treated with DAAs or IFN-based regimens, late relapse beyond 12 weeks after completion of treatment is uncommon. Results from long-term follow-up studies suggest responders to antiviral treatment achieve benefits on regression of fibrosis/cirrhosis, decreasing risk of progression to liver decompensation, reductions in the need for liver transplantation and mortality. Well-designed studies with robust comparisons are needed to determine the effect of DAAs on the recurrence of HCC in the future.
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Affiliation(s)
- Lai Wei
- a Center for Hepatology Pancrease Disease, Beijing Tsinghua Changgung Hospital , Tsinghua University , Beijing.,b Peking University Hepatology Institute, Beijing Key Laboratory for Hepatitis C and Immunotherapy for Liver Disease , Peking University People's Hospital , Beijing
| | - Yi-Hsiang Huang
- c Division of Gastroenterology and Hepatology , Taipei Veterans General Hospital , Taipei
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Lee YC, Hu TH, Hung CH, Lu SN, Chen CH, Wang JH. The change in liver stiffness, controlled attenuation parameter and fibrosis-4 index for chronic hepatitis C patients with direct-acting antivirals. PLoS One 2019; 14:e0214323. [PMID: 30939158 PMCID: PMC6445421 DOI: 10.1371/journal.pone.0214323] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 03/10/2019] [Indexed: 12/17/2022] Open
Abstract
Background and aim Transient elastography and fibrosis-4 index (FIB-4) have been proposed to access hepatic fibrosis and steatosis for patients with chronic liver disease. This study was to determine the changes of liver stiffness (LS), controlled attenuation parameter (CAP) value and FIB-4 and their associated factors for chronic hepatitis C (CHC) patients who underwent direct-acting antivirals (DAAs). Patients and methods Consecutive patients with CHC in advanced fibrosis or compensated cirrhosis undergoing paritaprevir/ritonavir/ombitasvir plus dasabuvir therapy and with LS and CAP before and 12 weeks after treatment were enrolled. The demographics, clinical characteristics and treatment outcomes were reviewed. The changes of LS, FIB-4, CAP and their associated factors were analyzed. Results A total of 213 patients (mean age: 63.7 years) with complete recommended treatment were enrolled. All patients achieved sustained virological response at 12 weeks (SVR12) of follow-up. The mean values of LS, CAP and FIB-4 index before treatment were 18.5kPa, 283dB/m and 5.05 respectively. While there was no significant change in CAP, LS and FIB-4 decreased significantly at the time of SVR12 (p<0.001). Compared with follow-up period, LS and FIB-4 decreased rapidly during DDAs. Multivariate analysis showed that higher baseline LS and FIB-4 were associated with greater reductions at the time of SVR12. Conclusion For CHC patients in advanced fibrosis or compensated cirrhosis, DAAs improved LS and FIB-4 index at SVR12. Higher baseline LS and FIB-4 contributed to greater reductions. However, there was no significant change in CAP value.
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Affiliation(s)
- Yu-Chi Lee
- Division of Hepato-Gastroenterology, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung City, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung City, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung City, Taiwan
- Division of Hepato-Gastroenterology, Department of Medicine, Chia-Yi Chang Gung Memorial Hospital, Chia-Yi City, Taiwan
| | - Sheng-Nan Lu
- Division of Hepato-Gastroenterology, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung City, Taiwan
- Division of Hepato-Gastroenterology, Department of Medicine, Chia-Yi Chang Gung Memorial Hospital, Chia-Yi City, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung City, Taiwan
| | - Jing-Houng Wang
- Division of Hepato-Gastroenterology, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung City, Taiwan
- * E-mail:
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Seko Y, Moriguchi M, Hara T, Kataoka S, Okuda K, Furuta M, Takemura M, Taketani H, Umemura A, Nishikawa T, Yamaguchi K, Yasui K, Minami M, Itoh Y. Presence of varices in patients after hepatitis C virus eradication predicts deterioration in the FIB-4 index. Hepatol Res 2019; 49:473-478. [PMID: 30549372 DOI: 10.1111/hepr.13296] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Revised: 11/27/2018] [Accepted: 12/11/2018] [Indexed: 02/08/2023]
Abstract
AIMS The liver function of patients with hepatitis C virus (HCV) infection who obtained sustained virologic response (SVR) has been known to improve after HCV eradication. However, a predictor of liver function after SVR has not been definitively identified. The aim of this retrospective study was to identify a predictor of deteriorated liver function and Fibrosis-4 (FIB-4) index after SVR was achieved by direct-acting antiviral (DAA) treatment. METHODS This study retrospectively enrolled 248 patients who obtained SVR by DAA treatment. None of the patients developed hepatocellular carcinoma during this study. Liver function was assessed at the end of treatment (EOT) and at 24, 48, 72, and 96 weeks after EOT. RESULTS At 96 weeks after EOT, the serum aspartate aminotransferase and alanine aminotransferase levels were significantly decreased from those at EOT. The platelet count was significantly increased from 14.9 × 104 /μL at EOT to 17.1 × 104 /μL at 96 weeks after EOT. Ten patients showed an increased FIB-4 (>1.00) index. Multivariate analysis with 171 patients who underwent endoscopic assessment revealed that the presence of varices was an independent predictor of deterioration in the FIB-4 index (odds ratio, 5.56; P = 0.041). CONCLUSION Most of the study patients who obtained SVR showed improved liver function after EOT. Patients without increasing platelet counts after SVR due to DAA therapy should be evaluated for complications induced by portal hypertension.
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Affiliation(s)
- Yuya Seko
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Michihisa Moriguchi
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tasuku Hara
- Department of Gastroenterology, Fukuchiyama City Hospital, Fukuchiyama, Japan
| | - Seita Kataoka
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Keiichiroh Okuda
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Mitsuhiro Furuta
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Masashi Takemura
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hiroyoshi Taketani
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Atsushi Umemura
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Taichiro Nishikawa
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kanji Yamaguchi
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kohichiroh Yasui
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Masahito Minami
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yoshito Itoh
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Giannini EG, Crespi M, Demarzo M, Bodini G, Furnari M, Marabotto E, Torre F, Zentilin P, Savarino V. Improvement in hepatitis C virus patients with advanced, compensated liver disease after sustained virological response to direct acting antivirals. Eur J Clin Invest 2019; 49:e13056. [PMID: 30474209 DOI: 10.1111/eci.13056] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Revised: 10/18/2018] [Accepted: 11/20/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND The outcome of patients with chronic hepatitis C virus infection (HCV) and advanced, compensated liver disease after sustained virological response (SVR) to direct-acting antivirals (DAAs) has not yet been completely depicted. We aimed to assess the clinical, biochemical and instrumental outcome of patients with advanced, compensated chronic HCV-related liver disease with DAA-induced SVR to DAAs and who had at least 1-year follow-up. MATERIALS AND METHODS Fifty-two patients with cirrhosis (n = 27) and fibrosis stage F3 (n = 25) followed up for a median of 60 weeks after successful DAA treatment were included. Laboratory work-up, including APRI and FIB-4 scores, liver transient elastography and measurement of the spleen bi-polar diameter were carried out before treatment and at the end of follow-up. RESULTS Liver stiffness decreased (P < 0.0001) from a median baseline of 15.2 kPa (12.0-20.0) to 9.3 kPa (7.5-12.0) at follow-up. A liver stiffness value suggestive of the presence (ie, ≥21.0 kPa) of clinically significant portal hypertension was found in 13 patients (25.0%) at baseline and in seven patients (13.5%) at follow-up (P = 0.037). Both APRI (P < 0.0001) and FIB-4 score (P = 0.025) progressively decreased, while platelet count increased (143 × 109 /L [117-176] to 153 × 109 /L [139-186], P = 0.003), and spleen bi-polar diameter decreased (120 mm [112-123] to 110 mm [102-116], P = 0.0009) from baseline to the end of follow-up. CONCLUSIONS In patients advanced, compensated chronic liver disease, liver stiffness significantly improves in the long-term after SVR, and this improvement is accompanied by an amelioration of indirect indices of liver fibrosis and function, and by a decrease in parameters of portal hypertension.
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Affiliation(s)
- Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, Ospedale Policlinico San Martino-IRCCS per l'Oncologia, University of Genoa, Genoa, Italy
| | - Mattia Crespi
- Gastroenterology Unit, Department of Internal Medicine, Ospedale Policlinico San Martino-IRCCS per l'Oncologia, University of Genoa, Genoa, Italy
| | - Mariagiulia Demarzo
- Gastroenterology Unit, Department of Internal Medicine, Ospedale Policlinico San Martino-IRCCS per l'Oncologia, University of Genoa, Genoa, Italy
| | - Giorgia Bodini
- Gastroenterology Unit, Department of Internal Medicine, Ospedale Policlinico San Martino-IRCCS per l'Oncologia, University of Genoa, Genoa, Italy
| | - Manuele Furnari
- Gastroenterology Unit, Department of Internal Medicine, Ospedale Policlinico San Martino-IRCCS per l'Oncologia, University of Genoa, Genoa, Italy
| | - Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, Ospedale Policlinico San Martino-IRCCS per l'Oncologia, University of Genoa, Genoa, Italy
| | - Francesco Torre
- Gastroenterology Unit, Department of Internal Medicine, Ospedale Policlinico San Martino-IRCCS per l'Oncologia, University of Genoa, Genoa, Italy
| | - Patrizia Zentilin
- Gastroenterology Unit, Department of Internal Medicine, Ospedale Policlinico San Martino-IRCCS per l'Oncologia, University of Genoa, Genoa, Italy
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine, Ospedale Policlinico San Martino-IRCCS per l'Oncologia, University of Genoa, Genoa, Italy
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Rout G, Nayak B, Patel AH, Gunjan D, Singh V, Kedia S, Shalimar. Therapy with Oral Directly Acting Agents in Hepatitis C Infection Is Associated with Reduction in Fibrosis and Increase in Hepatic Steatosis on Transient Elastography. J Clin Exp Hepatol 2019; 9:207-214. [PMID: 31024203 PMCID: PMC6477071 DOI: 10.1016/j.jceh.2018.06.009] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2018] [Accepted: 06/10/2018] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND/AIMS Direct-Acting Antivirals (DAAs) are now the standard of care for management of Chronic Hepatitis C (CHC) infection. The aim of this study was to evaluate change in Liver Stiffness Measurement (LSM) and Controlled Attenuation Parameter (CAP) by transient elastography (FibroScan®) after completion of DAA therapy. METHODS LSM and CAP were measured serially (baseline pre-treatment, at 12 weeks post therapy, and one year after completion of therapy) in a prospective cohort of 372 CHC patients treated with DAAs. Patients with at least two FibroScan measurements were included. RESULTS The mean age was 38.1 ± 12.6 years; 58.3% males. Cirrhosis as defined by biopsy or fibroscan measurement (≥12.5) kPa was found in 25.5%. On paired analysis (n = 317), LSM (IQR) decreased from a baseline value 7.1 (5.3-13.8) kPa to 6.2 (4.8-11.2) kPa 12 weeks post therapy with a median decline 0.7 (-0.6-2.6) kPa, P < 0.001. Similarly, on paired analysis (n = 160), LSM decreased from baseline 6.9 (5.1-12.7) kPa to 6.1 (4.8-9.4) kPa after one year of treatment with median decline 0.9 (-0.6-3.2) kPa, P < 0.001. In contrast, on paired analysis (n = 317), CAP increased from baseline of 213.0 (180.0-254.5) dB/m to 225.0 (190.0-269.0) dB/m at 12 weeks post therapy with median increase 7.0 (-23.5-45.5), P = 0.001. Similarly, on paired analysis (n = 160), CAP increased from baseline of 210.0 (180.3-260.8) dB/m to 234.0 (204.0-282.0) dB/m at one year post therapy with median increase 25.0 (-12.5-61.5) dB/m, P < 0.001. On multivariate linear regression analysis, low baseline CAP value and low albumin were significantly associated with increase in CAP values. CONCLUSION Treatment with DAAs reduces liver stiffness, but is associated with increase in hepatic steatosis.
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Key Words
- AASLD, American Association for the Study of Liver Diseases
- ALT, Alanine Aminotransferase
- AST, Aspartate Aminotransferase
- BMI, Body Mass Index
- CAP, Controlled Attenuation Parameter
- CHC, Chronic Hepatitis C
- DAAs, Directly-Acting Antivirals
- F0-4, METAVIR Fibrosis Stage 0 to 4
- Fibroscan
- HCV, Hepatitis C Virus
- HIV, Human Immunodeficiency Virus
- IFN, Interferon
- IQR, Interquartile Range
- LSM, Liver Stiffness Measurement
- NAFLD, Non-alcoholic Fatty Liver Disease
- SD, Standard Deviation
- SVR12
- SVR12, Sustained Viral Response at 12 Weeks
- TE, Transient Elastography
- controlled attenuation parameter
- liver stiffness measurement
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Affiliation(s)
- Gyanranjan Rout
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Baibaswata Nayak
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Arpan H. Patel
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Deepak Gunjan
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Vishwajeet Singh
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India,Address for correspondence: Shalimar, Associate Professor, Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi 110029, India. Tel.: +91 11 26596643.
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47
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Kawagishi N, Suda G, Nakamura A, Kimura M, Maehara O, Suzuki K, Nakamura A, Ohara M, Izumi T, Umemura M, Nakai M, Sho T, Natsuizaka M, Morikawa K, Ogawa K, Kudo Y, Nishida M, Miyoshi H, Sakamoto N. Liver steatosis and dyslipidemia after HCV eradication by direct acting antiviral agents are synergistic risks of atherosclerosis. PLoS One 2018; 13:e0209615. [PMID: 30576386 PMCID: PMC6303061 DOI: 10.1371/journal.pone.0209615] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Accepted: 11/28/2018] [Indexed: 12/11/2022] Open
Abstract
Aim We comprehensively analyzed how hepatitis C virus (HCV) eradication by interferon (IFN)-free direct-acting-antiviral-agents (DAAs) affects liver steatosis and atherogenic risk. Methods Patients treated with IFN-free-DAAs who underwent transient elastography before and at 24-weeks post-treatment, including controlled attenuation parameter (CAP), and achieved sustained viral response (SVR) were enrolled. The association between changes in liver steatosis, lipid-metabolism, and genetic and clinical factors was analyzed. Results A total of 117 patients were included. The mean CAP and low-density lipoprotein cholesterol (LDL-C) levels were significantly elevated at SVR24. However, baseline LDL-C and CAP values were significantly negatively correlated with changes in these values after HCV eradication, indicating that in patients with high baseline values, the values generally decreased after HCV eradication. Mean small-dense LDL-C (sdLDL-C), which has greater atherogenic potential, was significantly elevated only in patients with both dyslipidemia (LDL-C >140 mg/dL) and liver steatosis (CAP >248 dB/m) at SVR24. Those patients had significant higher baseline BMI, LDL-C, and total-cholesterol levels. Conclusions Generally, successful HCV eradication by IFN-free-DAAs decreases CAP and LDL-C in patients with high baseline values. However, elevated LDL-C was accompanied with elevated sdLDL-C only in patients with liver steatosis and dyslipidemia at SVR24; therefore, those patients may require closer monitoring.
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Affiliation(s)
- Naoki Kawagishi
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Akinobu Nakamura
- Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Megumi Kimura
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Osamu Maehara
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Kazuharu Suzuki
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Akihisa Nakamura
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Masatsugu Ohara
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Takaaki Izumi
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Machiko Umemura
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Masato Nakai
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Takuya Sho
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Mitsuteru Natsuizaka
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Yusuke Kudo
- Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Hokkaido, Japan
| | - Mutsumi Nishida
- Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Hokkaido, Japan
| | - Hideaki Miyoshi
- Division of Diabetes and Obesity, Faculty of Medicine and Graduate School of Medicine Hokkaido University, Sapporo, Hokkaido, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
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Ferraioli G, Wong VWS, Castera L, Berzigotti A, Sporea I, Dietrich CF, Choi BI, Wilson SR, Kudo M, Barr RG. Liver Ultrasound Elastography: An Update to the World Federation for Ultrasound in Medicine and Biology Guidelines and Recommendations. ULTRASOUND IN MEDICINE & BIOLOGY 2018; 44:2419-2440. [PMID: 30209008 DOI: 10.1016/j.ultrasmedbio.2018.07.008] [Citation(s) in RCA: 358] [Impact Index Per Article: 51.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 07/02/2018] [Accepted: 07/13/2018] [Indexed: 06/08/2023]
Abstract
The World Federation for Ultrasound in Medicine and Biology has produced these guidelines for the use of elastography techniques in liver diseases. For each available technique, the reproducibility, results and limitations are analyzed, and recommendations are given. This set of guidelines updates the first version, published in 2015. Since the prior guidelines, there have been several advances in technology. The recommendations are based on the international published literature, and the strength of each recommendation is judged according to the Oxford Centre for Evidence-Based Medicine. The document has a clinical perspective and is aimed at assessing the usefulness of elastography in the management of liver diseases.
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Affiliation(s)
- Giovanna Ferraioli
- Ultrasound Unit, Department of Clinical Sciences and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, School of Medicine, University of Pavia, Pavia, Italy
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong
| | - Laurent Castera
- Service d'Hepatologie, Hopital Beaujon, Clichy, Assistance Publique-Hopitaux de Paris, INSERM UMR 1149 CRI, Universite Denis Diderot Paris-VII, Paris, France
| | - Annalisa Berzigotti
- Swiss Liver Center, Hepatology, University Clinic for Visceral Surgery and Medicine, Inselspital, University of Bern, Switzerland
| | - Ioan Sporea
- Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy, Timisoara, Romania
| | | | - Byung Ihn Choi
- Department of Radiology, Seoul National University Hospital, Seoul, South Korea
| | - Stephanie R Wilson
- Department of Diagnostic Imaging, Foothills Medical Centre, University of Calgary, Calgary, Alberta, Canada
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University School of Medicine, Osaka Sayama, Japan
| | - Richard G Barr
- Department of Radiology, Northeastern Ohio Medical University and Southwoods Imaging, Youngstown, Ohio, USA.
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Enomoto M, Ikura Y, Tamori A, Kozuka R, Motoyama H, Kawamura E, Hagihara A, Fujii H, Uchida-Kobayashi S, Morikawa H, Murakami Y, Kawada N. Short-term histological evaluations after achieving a sustained virologic response to direct-acting antiviral treatment for chronic hepatitis C. United European Gastroenterol J 2018; 6:1391-1400. [PMID: 30386612 PMCID: PMC6206535 DOI: 10.1177/2050640618791053] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2018] [Accepted: 06/25/2018] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Interferon-free, direct-acting antiviral treatments can result in a sustained virologic response in nearly 100% of patients with chronic hepatitis C virus infection. AIMS The purpose of this study was to evaluate histological improvement after achieving a sustained virologic response to direct-acting antiviral treatments in patients with chronic hepatitis C. METHODS Among 691 patients with chronic hepatitis C who achieved a sustained virologic response to direct-acting antivirals, 51 underwent liver biopsy 41 ± 20 weeks after the end of treatment despite normal transaminase levels. In 20 patients, liver biopsy specimens obtained a median of 1.2 years before the start of treatment were available. RESULTS Among the 51 patients who underwent post-sustained virologic response biopsies, the grade of inflammation was A0 in 18 patients, A1 in 24, A2 in eight, and A3 in one; the stage of fibrosis was F0 in three patients, F1 in 20, F2 in 15, F3 in nine, and F4 in four. Among the nine post-sustained virologic response biopsy specimens with moderate-to-severe inflammation (≥A2), four showed S1-to-S3 steatosis (>5% of hepatocytes affected). In the 20 paired biopsy specimens, the inflammation grade significantly regressed (p = 0.0043), but the fibrosis stage did not (p = 0.45). Histological improvement, defined as a ≥ 2-point decrease in the Knodell inflammatory score and no worsening of the fibrosis, was found in 11 (55%) patients. The iron accumulation had significantly regressed (p = 0.0093), but the steatosis had not (p = 0.10). CONCLUSIONS Even if transaminases become normal after obtaining a sustained virologic response, significant histological inflammation of unknown cause was found in some patients. Additionally, improvement in liver fibrosis was not evident in the short term.
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Affiliation(s)
- Masaru Enomoto
- Department of Hepatology,
Osaka
City University Medical School, Osaka,
Japan
| | - Yoshihiro Ikura
- Department of Pathology, Takatsuki
General Hospital, Takatsuki, Japan
| | - Akihiro Tamori
- Department of Hepatology,
Osaka
City University Medical School, Osaka,
Japan
| | - Ritsuzo Kozuka
- Department of Hepatology,
Osaka
City University Medical School, Osaka,
Japan
| | - Hiroyuki Motoyama
- Department of Hepatology,
Osaka
City University Medical School, Osaka,
Japan
| | - Etsushi Kawamura
- Department of Gastroenterology and
Hepatology, Osaka City Juso Hospital, Osaka, Japan
| | - Atsushi Hagihara
- Department of Hepatology,
Osaka
City University Medical School, Osaka,
Japan
| | - Hideki Fujii
- Department of Hepatology,
Osaka
City University Medical School, Osaka,
Japan
| | | | - Hiroyasu Morikawa
- Department of Hepatology,
Osaka
City University Medical School, Osaka,
Japan
| | - Yoshiki Murakami
- Department of Hepatology,
Osaka
City University Medical School, Osaka,
Japan
| | - Norifumi Kawada
- Department of Hepatology,
Osaka
City University Medical School, Osaka,
Japan
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Potent viral suppression and improvements in alpha-fetoprotein and measures of fibrosis in Japanese patients receiving a daclatasvir/asunaprevir/beclabuvir fixed-dose combination for the treatment of HCV genotype-1 infection. J Gastroenterol 2018; 53:1089-1097. [PMID: 29500489 DOI: 10.1007/s00535-018-1445-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Accepted: 02/22/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND In the UNITY-3 study, 96% sustained virologic response (SVR12) rate was observed in Japanese patients with hepatitis C virus (HCV) genotype (GT)-1 infection treated for 12 weeks with fixed-dose daclatasvir, asunaprevir, and beclabuvir (DCV-TRIO). As HCV clearance may improve liver outcomes, we assessed hepatic fibrosis and alpha-fetoprotein (AFP), a hepatocellular carcinoma risk marker, pre- and post-treatment in UNITY-3. METHODS Treatment-naive or interferon-experienced UNITY-3 patients with HCV GT-1 who received twice-daily DCV-TRIO were assessed for fibrosis [FibroTest; FibroScan; fibrosis-4 index (FIB-4), aspartate-aminotransferase-to-platelet-ratio index] and AFP at baseline and Weeks 4 (FIB-4 only), 12 or 24 post-treatment. RESULTS Of 217 patients, 99% had GT-1b infection, 46% were aged > 65 years, 21% had compensated cirrhosis, and 26% baseline HCV-RNA > 107 IU/mL. All GT-1b patients treated ≥ 4 weeks achieved SVR12 with (n = 54) or without (n = 144) baseline NS5A polymorphisms associated with DCV resistance (positions 28/30/31/93). Statistically significant post-treatment reductions from baseline were observed for all fibrosis measures and AFP, with numerically greater reductions in cirrhotic patients. FibroTest category improved in 44%, remained stable in 50%, and worsened in 6% of patients; 98% with baseline AFP < 6 μg/L remained < 6 μg/L and 51% with baseline AFP ≥ 6 μg/L were < 6 μg/L post-treatment. CONCLUSIONS DCV-TRIO administered for 12 weeks to Japanese patients with primarily GT-1b infection achieved a high SVR12 rate and resulted in improved measures of hepatic fibrosis and serum AFP that may reduce the risk of future liver disease progression and hepatocellular carcinoma, particularly in those with compensated cirrhosis.
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