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Weigand K, Peschel G, Grimm J, Höring M, Krautbauer S, Liebisch G, Müller M, Buechler C. Serum Phosphatidylcholine Species 32:0 as a Biomarker for Liver Cirrhosis Pre- and Post-Hepatitis C Virus Clearance. Int J Mol Sci 2024; 25:8161. [PMID: 39125730 PMCID: PMC11311844 DOI: 10.3390/ijms25158161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 07/23/2024] [Accepted: 07/25/2024] [Indexed: 08/12/2024] Open
Abstract
Phosphatidylcholine (PC) is an essential lipid for liver health and lipoprotein metabolism, but its circulating levels have rarely been studied in patients with cirrhosis. Chronic hepatitis C virus (HCV) infection causes lipid abnormalities and is a major cause of cirrhosis. Effective HCV elimination with direct-acting antivirals (DAAs) is associated with the normalization of serum low-density lipoprotein cholesterol levels. Since PC is abundant in all lipoprotein particles, this study analyzed the association between serum PC species levels and liver cirrhosis before and after HCV eradication. Therefore, 27 PC species were measured by Fourier Transform Mass Spectrometry in the serum of 178 patients with chronic HCV infection at baseline and in 176 of these patients at the end of therapy. The PC species did not correlate with viral load, and the levels of 13 PC species were reduced in patients infected with genotype 3a compared to those affected with genotype 1. Four PC species were slightly elevated 12 weeks after DAA initiation, and genotype-related changes were largely normalized. Patients with HCV and cirrhosis had higher serum levels of PC 30:0 and 32:0 before and at the end of therapy. PC species containing polyunsaturated fatty acids were mostly decreased in cirrhosis. The levels of polyunsaturated, but not saturated, PC species were inversely correlated with the model of the end-stage liver disease score. A receiver operating characteristic curve analysis showed area under the curve values of 0.814 and 0.826 for PC 32:0 and 0.917 and 0.914 for % PC 32:0 (relative to the total PC levels) for the classification of cirrhosis at baseline and at the end of therapy, respectively. In conclusion, the specific upregulation of PC 32:0 in cirrhosis before and after therapy may be of diagnostic value in HCV-related cirrhosis.
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Affiliation(s)
- Kilian Weigand
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (K.W.); (G.P.); (J.G.); (M.M.)
- Department of Gastroenterology, Gemeinschaftsklinikum Mittelrhein, 56073 Koblenz, Germany
| | - Georg Peschel
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (K.W.); (G.P.); (J.G.); (M.M.)
- Department of Internal Medicine, Klinikum Fürstenfeldbruck, 82256 Fürstenfeldbruck, Germany
| | - Jonathan Grimm
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (K.W.); (G.P.); (J.G.); (M.M.)
| | - Marcus Höring
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany; (M.H.); (S.K.); (G.L.)
| | - Sabrina Krautbauer
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany; (M.H.); (S.K.); (G.L.)
| | - Gerhard Liebisch
- Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany; (M.H.); (S.K.); (G.L.)
| | - Martina Müller
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (K.W.); (G.P.); (J.G.); (M.M.)
| | - Christa Buechler
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany; (K.W.); (G.P.); (J.G.); (M.M.)
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Tao XM, Zeng MH, Zhao YF, Han JX, Mi YQ, Xu L. Direct-acting antivirals failed to reduce the incidence of hepatocellular carcinoma occurrence in hepatitis C virus associated cirrhosis: A real-world study. World J Hepatol 2024; 16:41-53. [PMID: 38313240 PMCID: PMC10835484 DOI: 10.4254/wjh.v16.i1.41] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 12/18/2023] [Accepted: 01/09/2024] [Indexed: 01/23/2024] Open
Abstract
BACKGROUND Direct-acting antivirals (DAAs) revolutionized the treatment of chronic hepatitis C virus (HCV)-associated disease achieving high rates of sustained virological response (SVR). However, whether DAAs can reduce the occurrence of hepatocellular carcinoma (HCC) in patients with HCV-associated cirrhosis who are at high risk have not been concluded. AIM To investigate the effect of DAAs on the occurrence of HCC in patients with HCV-associated cirrhosis after achieving SVR. METHODS Of 427 inpatients with HCV-associated cirrhosis were enrolled in Tianjin Second People's Hospital from January 2014 to April 2020. 118 patients weren't received antiviral treatment with any reasons named non-antiviral treatment group, and 236 patients obtained from the 309 DAAs treatment patients according to the propensity score matching named DAAs treatment group. Demographic information and laboratory data were collected from baseline and the following up. Kaplan-Meier curve and Log-Rank test were used to compare the incidence and cumulative incidence of HCC between the two groups. Cox proportional risk regression was used to re-evaluate the risk factors for HCC. RESULTS HCC incidence was 4.68/100PY (95%CI, 3.09-6.81) in the DAAs treatment group, while it was 3.00/100PY (95%CI, 1.50-5.37) in the non-antiviral treatment group, and the relative risk was 1.82 (95%CI, 0.93-3.53, P > 0.05). The incidence of HCC at 12, 24, 36 and 48 months was 3.39%, 6.36%, 8.47% and 10.17% in the DAAs treatment group, and it was 0%, 0%, 3.39% and 9.32% in the non-antiviral treatment group, respectively. Age > 58 [hazard ratio (HR) = 1.089; 95%CI, 1.033-1.147; P = 0.002] and liver stiffness measurement > 27.85 kPa (HR = 1.043; 95%CI, 1.022-1.065; P = 0.000) were risk factors for HCC in all patients (n = 427), and DAAs treatment didn't show protective efficacy. CONCLUSION DAAs treatment seems failed to reduce the incidence of HCC occurrence in HCV-associated cirrhosis in 48 months, and even increased the incidence of HCC in 36 months.
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Affiliation(s)
- Xue-Mei Tao
- 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
| | - Ming-Hui Zeng
- 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
| | - You-Fei Zhao
- 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
| | - Jia-Xin Han
- 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
| | - Yu-Qiang Mi
- 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
| | - Liang Xu
- 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
- Department of Hepatology, Tianjin Research Institute of Liver Diseases, Tianjin 300192, China.
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Pugliese N, Polverini D, Arcari I, De Nicola S, Colapietro F, Masetti C, Ormas M, Ceriani R, Lleo A, Aghemo A. Hepatitis C Virus Infection in the Elderly in the Era of Direct-Acting Antivirals: Evidence from Clinical Trials and Real Life. Trop Med Infect Dis 2023; 8:502. [PMID: 37999621 PMCID: PMC10674442 DOI: 10.3390/tropicalmed8110502] [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: 09/19/2023] [Revised: 11/09/2023] [Accepted: 11/16/2023] [Indexed: 11/25/2023] Open
Abstract
The introduction of direct-acting antiviral agents (DAAs) into clinical practice has revolutionized the therapeutic approach to patients with chronic hepatitis C virus (HCV) infection. According to the most recent guidelines, the first line of treatment for HCV infection involves the use of one of three pan-genotypic DAA combinations, sofosbuvir/velpatasvir (SOF/VEL), glecaprevir/pibrentasvir (GLE/PIB), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). These drugs have been shown to be effective and safe in numerous clinical trials and real-world studies, but special populations have been neglected. Among the special populations to be treated are elderly patients, whose numbers are increasing in clinical practice. The management of these patients can be challenging, in particular due to multiple comorbidities, polypharmacotherapy, and potential drug-drug interactions. This narrative review aims to summarize the current scientific evidence on the efficacy and safety of DAAs in the elderly population, both in clinical trials and in real-life settings. Although there is still a paucity of real-world data and no clinical trials have yet been conducted in the population aged ≥ 75 years old, some considerations about the efficacy and safety of DAAs in the elderly can be made based on the results of these studies. The pan-genotypic associations of DAAs appear to be as efficacious and safe in the elderly population as in the general population; this is both in terms of similar sustained virologic response (SVR) rates and similar frequencies of adverse events (AEs). However, further studies specifically involving this patient population would be necessary to confirm this evidence.
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Affiliation(s)
- Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy; (N.P.); (D.P.); (I.A.); (F.C.); (A.L.)
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| | - Davide Polverini
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy; (N.P.); (D.P.); (I.A.); (F.C.); (A.L.)
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| | - Ivan Arcari
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy; (N.P.); (D.P.); (I.A.); (F.C.); (A.L.)
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| | - Stella De Nicola
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| | - Francesca Colapietro
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy; (N.P.); (D.P.); (I.A.); (F.C.); (A.L.)
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| | - Chiara Masetti
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| | - Monica Ormas
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| | - Roberto Ceriani
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| | - Ana Lleo
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy; (N.P.); (D.P.); (I.A.); (F.C.); (A.L.)
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, MI, Italy; (N.P.); (D.P.); (I.A.); (F.C.); (A.L.)
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy; (S.D.N.); (C.M.); (M.O.); (R.C.)
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Abdulla M, Al Ghareeb AM, Husain HAHY, Mohammed N, Al Qamish J. Effectiveness and safety of generic and brand direct acting antivirals for treatment of chronic hepatitis C. World J Clin Cases 2022; 10:12566-12577. [PMID: 36579085 PMCID: PMC9791528 DOI: 10.12998/wjcc.v10.i34.12566] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 09/28/2022] [Accepted: 11/08/2022] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND Direct acting antivirals (DAAs) are a very effective treatment for hepatitis C virus (HCV). However, brand DAAs are expensive. The licensing of cheaper generic DAAs may address this issue, but there is a lack of clinical studies comparing the efficacy of generic vs brand DAA formulations.
AIM To compare the efficacy and safety of generic against brand DAAs for chronic hepatitis C treatment in Bahrain.
METHODS This was a retrospective observational study involving 289 patients with chronic HCV infection during 2016 to 2018. There were 149 patients who were treated with brand DAAs, while 140 patients were treated with generic DAAs. Commonly used DAAs were Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir ± Ribavirin, and Sofosbuvir/Daclatasvir ± Ribavirin. SVR at 12 wk post treatment was the main outcome variable.
RESULTS Overall, 87 patients (30.1%) had cirrhosis and 68.2% had genotype 1 HCV infection. At 12 wk post treatment, SVR was achieved by 271 (93.8%) of the patients. In patients who were treated with generic medications, 134 (95.7%) achieved SVR at 12 wk post treatment, compared to 137 (91.9%) among those treated with brand medications (P = 0.19). Having cirrhosis [odds ratio (OR): 9.41, 95% confidence interval (CI): 2.47–35.84] and having HCV genotype 3 (OR: 3.56, 95%CI: 1.03–12.38) were significant independent predictors of not achieving SVR. Alanine transaminase, gamma-glutamyl transpeptidase, and total bilirubin levels decreased significantly following therapy with both generic and brand DAAs.
CONCLUSION Generic and brand DAAs demonstrate comparable effectiveness in the treatment of chronic hepatitis C patients. Both are safe and equally effective in improving biochemical markers of hepatic inflammation.
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Affiliation(s)
- Maheeba Abdulla
- Department of Internal Medicine, Salmaniya Medical Complex, Arabian Gulf University, Manama 2904, Bahrain
| | | | | | - Nafeesa Mohammed
- Department of Internal Medicine, Salmaniya Medical Complex, Manama 2904, Bahrain
| | - Jehad Al Qamish
- Internal Medicine Department, Ibn AlNafees Hospital, Manama 3302, Bahrain
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Lee SW, Chen LS, Yang SS, Huang YH, Lee TY. Direct-Acting Antiviral Therapy for Hepatitis C Virus in Patients with BCLC Stage B/C Hepatocellular Carcinoma. Viruses 2022; 14:v14112316. [PMID: 36366415 PMCID: PMC9695594 DOI: 10.3390/v14112316] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 10/07/2022] [Accepted: 10/20/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND The benefits of hepatitis C virus (HCV)eradication for hepatocellular carcinoma (HCC) patients in Barcelona Clinic Liver Cancer (BCLC) stage B/C remain uncertain. METHODS In this hospital-based cohort study, all HCV-infected patients with BCLC stage B/C HCC during the period January 2017 to March 2021 were retrospectively screened, with 97 patients who had completed direct-acting antiviral (DAA) therapy being enrolled for final analysis. RESULTS In total, the sustained virological response (SVR) rate was 90.7%. In logistic regression analysis, progressive disease (PD) to prior tumor treatments was significantly associated with SVR failure (odds ratio 5.59, 95% CI 1.30-24.06, p = 0.021). Furthermore, the overall survival (OS) rate was significantly higher in the SVR group than that in the non-SVR group (1-year OS: 87.5% vs. 57.1%, p = 0.001). SVR was found to be an independent factor related to OS (hazard ratio 8.42, 95% CI 2.93-24.19, p = 0.001). However, even upon achieving SVR, the OS rates in BCLC stage C or Child-Pugh stage B patients remained poor. CONCLUSIONS In BCLC stage B/C HCC, DAA could achieve a high SVR rate except in those patients with PD to prior HCC treatments. SVR was related to improvements in OS; therefore, DAA therapy should be encouraged for patients diagnosed without a short life expectancy.
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Affiliation(s)
- Shou-Wu Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, Chung Hsing University, Taichung 40227, Taiwan
| | - Li-Shu Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
- Ph.D. Program in Translational Medicine, Chung Hsing University, Taichung 40227, Taiwan
- Institute of Biomedical Sciences, Chung Hsing University, Taichung 40227, Taiwan
| | - Yi-Hsiang Huang
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
| | - Teng-Yu Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
- Correspondence: ; Tel.: +886-4-23592525
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Direct-Acting Antivirals for HCV Treatment in Decompensated Liver Cirrhosis Patients: A Systematic Review and Meta-Analysis. J Pers Med 2022; 12:jpm12091517. [PMID: 36143302 PMCID: PMC9506163 DOI: 10.3390/jpm12091517] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 09/03/2022] [Accepted: 09/05/2022] [Indexed: 11/30/2022] Open
Abstract
DAA therapy is known to clear hepatitis C virus infection in patients with decompensated cirrhosis (DC). However, the safety and benefits of DAA in DC remain unclear, especially with the use of protease inhibitors (PI). Therefore, we evaluated the efficacy and clinical safety of DAA in DC patients and observed whether there was a discrepancy between PI-based and non-PI-based treatment. We searched Ovid-Medline, Ovid-EMBASE, Cochrane Library, and three local medical databases through October 2021 to identify relevant studies on the clinical safety and effectiveness of DAA in DC patients. The outcomes were sustained virologic response (SVR), overall mortality, the incidence rate of hepatocellular carcinoma (HCC), adverse events, improvement or deterioration of liver function, and delisting from liver transplantation (LT). Two independent reviewers extracted the data from each study using a standardized form. The pooled event rate in DC patients and relative effect (odds ratio (OR)) of PI-treated versus non-PI-based DAA in DC patients were calculated using a random-effects model. In patients with DC, the SVR rate was 86% (95% CI 83–88%), the development of HCC 7% (95% CI 5–9%), and mortality 6% (95% CI 4–8%). Improvement in liver function was observed in 51% (95% CI 44–58%) of patients, and 16% (95% CI 5–40%) were delisted from LT. PI-based treatment showed a similar rate of serious adverse events (23% vs. 18%), HCC occurrence (5% vs. 7%), and mortality (5% vs. 6%) to that of non-PI-based DAA treatment in DC patients. HCC occurrence and mortality rates were low in patients with DC following DAA treatment. PI-based treatment in DC patients was relatively safe when compared to non-PI-based treatment. Overall, DAA improved liver function, which may have allowed for delisting from LT.
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Switching from Tenofovir-Based Combination Therapy to Tenofovir Monotherapy in Multidrug-Experienced Chronic Hepatitis B Patients: a 5-Year Experience at Two Centers. Antimicrob Agents Chemother 2022; 66:e0027522. [PMID: 35867571 PMCID: PMC9380523 DOI: 10.1128/aac.00275-22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Patients with chronic hepatitis B (CHB) who were administered tenofovir disoproxil fumarate (TDF)-based combination therapy after receiving multiple drugs are frequently switched to TDF monotherapy in South Korea. We evaluated the efficacy and safety of switching to TDF monotherapy from TDF-based combination therapy over 5 years. This was a retrospective study of multidrug-experienced CHB patients who switched from TDF-based combination therapy to TDF monotherapy after achieving a virologic response (VR; <20 IU/mL) at Konkuk University Hospital and Sanggye Paik Hospital. The biochemical response was defined as a normalized serum ALT level during follow-up. Each patient was assessed from the date of switching to TDF monotherapy to the date of the last follow-up over 5 years. A total of 39 patients who received at least one antiviral therapy before TDF-based combination therapy were analyzed. The median duration of VR before switching to TDF monotherapy was 18 months and the median duration of TDF monotherapy was 55 months. In this study, except for one patient who had poor compliance, all patients maintained a VR. Three patients had a temporarily increased HBV DNA level and 91.2% of the patients showed a biochemical response. Switching multidrug-experienced patients to TDF monotherapy is generally safe and effective.
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Viral eradication by direct-acting antivirals does not decrease the serum myostatin level in hepatitis C virus-infected patients. Nutrition 2022; 101:111699. [DOI: 10.1016/j.nut.2022.111699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 03/07/2022] [Accepted: 04/10/2022] [Indexed: 11/18/2022]
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Hypoalbuminemia Is a Hepatocellular Carcinoma Independent Risk Factor for Tumor Progression in Low-Risk Bridge to Transplant Candidates. Cancers (Basel) 2022; 14:cancers14071684. [PMID: 35406456 PMCID: PMC8996921 DOI: 10.3390/cancers14071684] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 03/13/2022] [Accepted: 03/24/2022] [Indexed: 02/06/2023] Open
Abstract
Due to active hepatocellular carcinoma (HCC) surveillance, many patients are diagnosed with early-stage disease and are usually amendable to curative treatments. These patients lack poor prognostic factors associated with Milan Criteria and alpha fetoprotein (AFP) biomarker levels. There are currently limited strategies to assess prognosis in the patients who remain at risk of post-treatment HCC progression. In a cohort of liver transplant (LT) candidates with HCC, this study seeks to identify factors prior to liver-directed therapy (LDT) associated with time to progression (TTP). This is a retrospective analysis of prospectively collected data from LT candidates with recently diagnosed HCC and receiving LDT as a bridge to LT at three interventional oncology programs within a single system (n = 373). Demographics, clinical hepatology and serology, and factors related to HCC burden were extracted and analyzed for associations with TTP risk. Albumin level below the cohort median (3.4 g/dL) emerged as an independent risk factor for TTP controlling for AFP > 20 ng/mL as well as Milan, T-stage, and Barcelona Clinic Liver Cancer (BCLC) stage individually. In modality-specific subgroup survival analysis, albumin-based TTP stratification was restricted to patients receiving first cycle microwave ablation (p = 0.007). In n = 162 patients matching all low-risk criteria for Milan, T-stage, BCLC stage, and AFP, the effect of albumin < 3.4 g/dL remained significant for TTP (p = 0.004) with 2-year TTP rates of 68% (<3.4 g/dL) compared to 95% (≥3.4 g/dL). In optimal bridge to LT candidates with small HCC and low AFP biomarker levels, albumin level at treatment baseline provides an HCC-independent positive prognostic factor for risk of HCC progression prior to LT.
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Atsukawa M, Tsubota A, Kondo C, Toyoda H, Nakamuta M, Takaguchi K, Watanabe T, Hiraoka A, Uojima H, Ishikawa T, Iwasa M, Tada T, Nozaki A, Chuma M, Fukunishi S, Asano T, Ogawa C, Abe H, Kato K, Hotta N, Shima T, Matsuura K, Mikami S, Tachi Y, Fujioka S, Okubo H, Shimada N, Tani J, Morishita A, Hidaka I, Moriya A, Tsuji K, Akahane T, Okubo T, Arai T, Kitamura M, Morita K, Kawata K, Tanaka Y, Kumada T, Iwakiri K. Time-course changes in liver functional reserve after successful sofosbuvir/velpatasvir treatment in patients with decompensated cirrhosis. Hepatol Res 2022; 52:235-246. [PMID: 34861090 DOI: 10.1111/hepr.13739] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 11/15/2021] [Accepted: 11/30/2021] [Indexed: 12/24/2022]
Abstract
AIM Direct-acting antivirals (DAAs) are currently available even for patients with decompensated cirrhosis. Reportedly, hepatic functional reserve improved in the short term after achievement of sustained virologic response (SVR). We aimed to clarify the outcomes after achievement of SVR in patients with decompensated cirrhosis who were treated by DAAs in real-world clinical practice. METHODS A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted in 86 patients with decompensated cirrhosis, who were evaluated for 48 weeks post-treatment. RESULTS The cohort included 8 patients with Child-Pugh class A, 56 with B, and 22 with C. The proportion of Child-Pugh class A patients increased from 9.1% at baseline to 44.1% at 48 weeks post-treatment, while that of class B and C patients decreased from 66.2% to 35.1% and from 24.7% to 14.3%, respectively. Among the patients with Child-Pugh class B and C, univariate analysis identified low total bilirubin, Child-Pugh score, Child-Pugh class B, ALBI score, and high serum albumin as factors associated with improvement to Child-Pugh class A. The optimal cut-off value of the factors for predicting improvement to Child-Pugh class A were 1.4 mg/dl for total bilirubin, 2.9 g/dl for serum albumin, 8 points for Child-Pugh score, and -1.88 for ALBI score. CONCLUSION Achievement of SVR with sofosbuvir/velpatasvir improved the liver functional reserve at 12 weeks post-treatment and maintained the stable effects until 48 weeks post-treatment in patients with decompensated cirrhosis. Specifically, the patients with less advanced conditions had the likelihood of improving to Child-Pugh class A at 48 weeks post-treatment.
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Affiliation(s)
- Masanori Atsukawa
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Akihito Tsubota
- Core Research Facilities for Basic Science, The Jikei University School of Medicine, Tokyo, Japan
| | - Chisa Kondo
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Makoto Nakamuta
- Department of Gastroenterology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, Japan
| | - Tsunamasa Watanabe
- Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan
| | - Haruki Uojima
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Kanagawa, Japan
| | - Toru Ishikawa
- Department of Hepatology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Motoh Iwasa
- Department of Gastroenterology and Hepatology, Mie University School of Medicine, Mie, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Himeji Red Cross Hospital, Hyogo, Japan
| | - Akito Nozaki
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Shinya Fukunishi
- Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan
| | - Toru Asano
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Hiroshi Abe
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Keizo Kato
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Naoki Hotta
- Department of Internal Medicine, Division of Hepatology, Masuko Memorial Hospital, Nagoya, Japan
| | - Toshihide Shima
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan
| | - Kentaro Matsuura
- Department of Virology & Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Aichi, Japan
| | - Shigeru Mikami
- Department of Internal Medicine, Division of Gastroenterology, Kikkoman General Hospital, Noda, Japan
| | - Yoshihiko Tachi
- Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan
| | - Shinichi Fujioka
- Department of Gastroenterology, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Hironao Okubo
- Department of Gastroenterology, Juntendo Nerima University Hospital, Tokyo, Japan
| | - Noritomo Shimada
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan
| | - Joji Tani
- Department of Gastroenterology, Kagawa University Graduate School of Medicine, Kagawa, Japan
| | - Asahiro Morishita
- Department of Gastroenterology, Kagawa University Graduate School of Medicine, Kagawa, Japan
| | - Isao Hidaka
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Akio Moriya
- Department of Gastroenterology, Mitoyo General Hospital, Kannonji, Japan
| | - Kunihiko Tsuji
- Gastroenterology Center, Teine Keijinkai Hospital, Sapporo, Japan
| | - Takehiro Akahane
- Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Japan
| | - Tomomi Okubo
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Taeang Arai
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Michika Kitamura
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | | | - Kazuhito Kawata
- Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yasuhito Tanaka
- Department of Virology & Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Aichi, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Katsuhiko Iwakiri
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
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11
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Abstract
The development of direct-acting antivirals (DAA) has revolutionized the treatment of chronic hepatitis C, enabling cure of hepatitis C virus (HCV) infection in more than 95% of cases. There are essentially no contraindications, so almost any patient can now be successfully treated. The result is the prevention or amelioration of cirrhosis, hepatocellular carcinoma (HCC), and extrahepatic manifestations. Consequently, the 2020 Nobel Prize in Medicine and Physiology was awarded for the discovery of HCV. Due to the high efficacy of therapy, even global HCV elimination is conceivable even without a vaccine. Here, we would like to venture a SWOT analysis of current HCV therapies aimed at HCV elimination.
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Affiliation(s)
- Markus Cornberg
- Department of Gastroenterology, Hepatology, and Endocrinology, 9177Hannover Medical School Hannover, Hannover, Germany.,Centre for Individualised Infection Medicine (CiiM), a joint venture of Helmholtz Centre for Infection Research and Hannover Medical School, Hannover, Germany.,German Center for Infection Research (DZIF), Partner-Site Hannover-Braunschweig, Hannover, Germany
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12
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Hamura R, Onda S, Shirai Y, Yasuda J, Haruki K, Furukawa K, Sakamoto T, Gocho T, Ikegami T. Safe perioperative management of major hepatectomy in a patient with portal hypertension after elimination of hepatitis C: a case report. Surg Case Rep 2022; 8:3. [PMID: 34982291 PMCID: PMC8727663 DOI: 10.1186/s40792-021-01357-7] [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: 08/30/2021] [Accepted: 12/22/2021] [Indexed: 11/30/2022] Open
Abstract
Background The administration of direct-acting antiviral agents in patients with liver cirrhosis and hepatitis C has been shown to improve liver function and long-term prognosis after sustained virological response (SVR) is achieved. However, in patients with portal hypertension (PH) at the time of SVR, PH may persist despite improvement in liver function. Case presentation An 82-year-old woman with liver cirrhosis due to hepatitis C was treated with direct-acting antiviral agents and achieved SVR. During follow-up, computed tomography revealed a low-density tumor in the left lateral region of the liver with dilation of the left intrahepatic bile duct. Considering the patient’s advanced age and PH persistence with a mild decrease in liver reserve function after SVR, preoperative percutaneous transhepatic portal embolization (PTPE) and partial splenic embolization (PSE) were performed concomitantly. Laparoscopic left hemihepatectomy was performed 8 days after the PTPE and PSE. The patient was discharged 8 days after surgery without any postoperative complications. Conclusions Laparoscopic left hemihepatectomy after preoperative management of PH was performed safely in a patient after the elimination of hepatitis C.
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Affiliation(s)
- Ryoga Hamura
- Division of Hepatobiliary and Pancreas Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
| | - Shinji Onda
- Division of Hepatobiliary and Pancreas Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Yoshihiro Shirai
- Division of Hepatobiliary and Pancreas Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Jungo Yasuda
- Division of Hepatobiliary and Pancreas Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Koichiro Haruki
- Division of Hepatobiliary and Pancreas Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Kenei Furukawa
- Division of Hepatobiliary and Pancreas Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Taro Sakamoto
- Division of Hepatobiliary and Pancreas Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Takeshi Gocho
- Division of Hepatobiliary and Pancreas Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Toru Ikegami
- Division of Hepatobiliary and Pancreas Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan
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13
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Rosato V, Ascione A, Nevola R, Fracanzani AL, Piai G, Messina V, Claar E, Coppola C, Fontanella L, Lombardi R, Staiano L, Valente G, Fascione MC, Giorgione C, Mazzocca A, Galiero R, Perillo P, Marrone A, Sasso FC, Adinolfi LE, Rinaldi L. Factors affecting long-term changes of liver stiffness in direct-acting anti-hepatitis C virus therapy: A multicentre prospective study. J Viral Hepat 2022; 29:26-34. [PMID: 34582610 DOI: 10.1111/jvh.13617] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Revised: 09/07/2021] [Accepted: 09/23/2021] [Indexed: 12/11/2022]
Abstract
The long-term changes of liver stiffness (LS) in patients who achieve viral clearance after direct-acting anti-HCV therapy remain undefined. We conducted a multicentre prospective study to investigate this aspect. Patients with HCV infection treated with DAAs were enrolled from six Italian centres; they underwent clinical, biochemical, ultrasound and transient elastography evaluations before treatment (T0), 12 weeks (SVR12) and 24 months (T24) after the end of therapy. Among the 516 consecutive patients enrolled, 301 had cirrhosis. LS significantly decreased from T0 to SVR (14.3 vs 11.1 kPa, p = .002), with a progressive reduction until T24 (8.7 kPa, p < .001). However, only patients with steatosis and those who developed HCC did not experience a late improvement in LS. Multivariate analysis of baseline and follow-up variables identified steatosis as the only independent predictor of failure of LS improvement (OR 1.802, p = .013). ROC curve analysis of the association of LS with the risk of developing HCC showed that SVR12 ≥14.0 kPa had the highest accuracy (sensitivity 82%, specificity 99%; AUC: 0.774). Multivariate analysis revealed that LS was the only variable independently associated with an increased risk of developing HCC (OR 6.470, p = .035). Achieving an SVR was associated with a progressive, long-term decline of LS, suggesting a late improvement in liver fibrosis, besides the resolution of inflammation. Fatty liver and the development of HCC interfered with late reduction of LS. Patients with an LS ≥14 kPa at 12 weeks after the end of treatment were at higher risk for developing HCC.
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Affiliation(s)
| | - Antonio Ascione
- Center for Liver Disease, Ospedale Buon Consiglio - Fatebenefratelli, Napoli, Italy
| | - Riccardo Nevola
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Napoli, Italy
| | - Anna Ludovica Fracanzani
- Department of Pathophysiology and Transplantation, Fondazione Cà Granda IRCCS, Ospedale Maggiore Policlinico Hospital, University of Milan, Milan, Italy
| | - Guido Piai
- Liver Unit for Transplant Management (SATTE), AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | - Vincenzo Messina
- Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | - Ernesto Claar
- Liver Unit, Ospedale Evangelico Betania, Napoli, Italy
| | - Carmine Coppola
- Internal Medicine and Hepatology Unit, Gragnano Hospital, Gragnano, Italy
| | - Luca Fontanella
- Center for Liver Disease, Ospedale Buon Consiglio - Fatebenefratelli, Napoli, Italy
| | - Rosa Lombardi
- Department of Pathophysiology and Transplantation, Fondazione Cà Granda IRCCS, Ospedale Maggiore Policlinico Hospital, University of Milan, Milan, Italy
| | - Laura Staiano
- Internal Medicine and Hepatology Unit, Gragnano Hospital, Gragnano, Italy
| | - Giovanna Valente
- Liver Unit for Transplant Management (SATTE), AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | - Maria Chiara Fascione
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Napoli, Italy
| | - Chiara Giorgione
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Napoli, Italy
| | - Annalisa Mazzocca
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Napoli, Italy
| | - Raffaele Galiero
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Napoli, Italy
| | | | - Aldo Marrone
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Napoli, Italy
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Napoli, Italy
| | - Luigi Elio Adinolfi
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Napoli, Italy
| | - Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Napoli, Italy
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14
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Abstract
In the 1970s, an unknown virus was suspected for documented cases of transfusion-associated hepatitis, a phenomenon called non-A, non-B hepatitis. In 1989, the infectious transmissible agent was identified and named hepatitis C virus (HCV) and, soon enough, the first diagnostic HCV antibody test was developed, which led to a dramatic decrease in new infections. Today, HCV infection remains a global health burden and a major cause of liver cirrhosis, hepatocellular carcinoma and liver transplantation. However, tremendous advances have been made over the decades, and HCV became the first curable, chronic viral infection. The introduction of direct antiviral agents revolutionized antiviral treatment, leading to viral eradication in more than 98% of all patients infected with HCV. This Perspective discusses the history of HCV research, which reads like a role model for successful translational research: starting from a clinical observation, specific therapeutic agents were developed, which finally were implemented in national and global elimination programmes.
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Affiliation(s)
- Michael P. Manns
- grid.10423.340000 0000 9529 9877Hannover Medical School, Hannover, Germany
| | - Benjamin Maasoumy
- grid.10423.340000 0000 9529 9877Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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15
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El Kassas M, Abdeen N, Omran D, Alboraie M, Salaheldin M, Eltabbakh M, Farghaly R, Emadeldeen M, Afify S, Sweedy A, Ghalwash A, Abbass A, Ezzat S, Tahoon M, ELshazly HM, Hamdy H, Omar H. Safety and efficacy of sofosbuvir/ledipasvir and sofosbuvir/daclatasvir in the treatment of hepatitis C in patients with decompensated cirrhosis. Eur J Gastroenterol Hepatol 2021; 33:e877-e882. [PMID: 34560693 DOI: 10.1097/meg.0000000000002287] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV)-related decompensated cirrhosis is a severe life-threatening illness. The safety of direct-acting antivirals (DAAs) has opened a gate of hope for that subgroup of patients who were previously contraindicated for interferon therapy. OBJECTIVE We aimed at the investigation of the safety and efficacy of different DAAs regimens in the treatment of HCV-related decompensated cirrhosis patients, to determine sustained virological response (SVR)12 rates and to analyze the factors associated with response. METHODS A retrospective, single-center study including HCV-related decompensated cirrhosis patients who received DAAs. Demographic, laboratory and clinical data were analyzed. The SVR12 rate was the primary outcome measure. Secondary outcomes included the predictors of response, changes in the baseline model for end-stage liver disease and child-turcotte-pugh (CTP) scores, and fibroindices (APRI and fibrosis-4 index) at 12 weeks after treatment. RESULTS In total, 145 eligible patients (141 with CTP class B and 4 with class C) were enrolled in this study. SVR12 was achieved by 88.06% (118/134) of efficacy population on different DAAs regimens, Treatment was discontinued in 11 patients because of severe side effects without any deaths. Younger age showed a significant positive association with SVR12. CONCLUSIONS DAAs can be used for the treatment of HCV-related decompensated liver disease, with acceptable SVR12 rates and safety profiles.
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Affiliation(s)
- Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo
| | - Nermeen Abdeen
- Tropical medicine, Faculty of Medicine, Alexandria University, Alexandria
| | - Dalia Omran
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University
| | | | - Mohamed Salaheldin
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo
| | - Mohamed Eltabbakh
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo
| | - Rasha Farghaly
- Department of community medicine, Faculty of Medicine, Suez Canal University
| | - Mohammed Emadeldeen
- Hepatogastroenterology Department, National Hepatology & Tropical Medicine Research Institute, Cairo
| | - Shimaa Afify
- Hepatogastroenterology Department, National Hepatology & Tropical Medicine Research Institute, Cairo
| | - Ahmad Sweedy
- Gastroenterology Department, Damietta Cardiology and Gastroenterology Center, Damietta
| | - Ahmed Ghalwash
- Hepatology and Gastroenterology Department, AGOZA Police Hospital, Cairo
| | - Amr Abbass
- Hepatology and Gastroenterology Department, AGOZA Police Hospital, Cairo
| | - Sameera Ezzat
- Epidemiology and Preventive Medicine Department, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Marwa Tahoon
- Epidemiology and Preventive Medicine Department, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Helmy M ELshazly
- Hepatology and gastroenterology department, national liver institute.Menoufia University, Egypt
| | - Hassan Hamdy
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo
| | - Heba Omar
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University
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16
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Long-term clinical outcomes in sustained responders with chronic hepatitis C after treatment with direct-acting antivirals. Eur J Gastroenterol Hepatol 2021; 33:e746-e752. [PMID: 34231522 DOI: 10.1097/meg.0000000000002240] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Little is known about how the achievement of sustained virological response (SVR) after treatment with direct-antiviral agents (DAAs) affects fibrosis and clinical outcomes in the long term. Our study aimed to evaluate the impact of achieving SVR on long-term changes in fibrosis and clinical outcomes in CHC patients treated with different DAAs-based regimens. METHODS a prospective, 3-year follow-up study of 113 CHC patients who had achieved SVR after treatment with different DAAs-based regimens between January and June 2015 was conducted. The clinical outcomes of SVR on the biochemical profile, changes in fibrosis, ALBI score and grade and occurrence of liver-related events were analyzed. RESULTS Overall, liver function parameters and serum alpha-fetoprotein level showed improvement from baseline to SVR12 and remained steady thereafter. Moreover, the ALBI score showed nonsignificant change at baseline to SVR12 (P = 0.2) but it was significantly better at 3-years follow-up than at SVR12 (P = 0.001). Regarding liver stiffness (LS) by transient elastography, a significant decrease in TE values was observed between baseline to SVR12 (P ≤ 0.0001) as well as between SVR12 to 3-years follow-up (P = 0.0005). Stratified by fibrosis stage, patients with advanced fibrosis and cirrhosis showed a more pronounced and significant improvement of LS during follow-up after SVR compared to patients with less advanced fibrosis stage. During the follow-up period, 3 (5.2%) cirrhotic patients developed liver-related events, including 2 (3.4%) patients with de novo HCC and one (1.7%) patient experienced ascites for the first time. CONCLUSION This 3-year follow-up study provides evidence for the durability of SVR, improvement of liver function parameters and ALBI score and grade in patients with an advanced stage of fibrosis, in particular, and reduction of the clinical events after successful treatment with DAAs.
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17
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El Kassas M, Alboraie M, El-Sayed M, Elbehiry S, Sherief A, Youssef M, Moaz I, El Tahan A, Abdeen N, Eysa B, Aziz AA, Tawheed A, Ezzat S, Hassany M. Effect of disease stage and treatment outcomes on the dynamics of liver functions during and after treatment of hepatitis C with directly acting antivirals. Eur J Gastroenterol Hepatol 2021; 33:e302-e307. [PMID: 34080825 DOI: 10.1097/meg.0000000000002043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Virus C infection is recently treated successfully with plenty of direct antiviral agents (DAAs). We aimed to evaluate the effect of disease stage and treatment outcome on the dynamics of liver functions during treatment of hepatitis C with DAAs. METHODS We reported the liver function in 2354 subjects diagnosed as chronic hepatitis C before, during and after treatment with different DAAs regimens. Patients were classified into two groups according to treatment response with further subclassification according to the presence or absence of cirrhosis, and changes in liver functions were compared in each group and subgroup. RESULTS Totally 2213 (94%) achieved sustained virological response (SVR) to DAAs therapy with significant improvement in all liver biochemistry. Also, there was an improvement in the non-SVR group's liver enzymes in relapsers during and after treatment; however, there was no improvement in serum albumin. We noticed a slight increase in serum bilirubin at weeks 4 and 8 for both groups. CONCLUSION DAAs therapy is associated with improvement of the liver biochemical profile and improved outcome in the majority of chronic hepatitis C virus patients due to suppression of viral replication. However, the long-term impact of DAAs therapy needs to be further evaluated.
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Affiliation(s)
| | | | | | | | - Ahmed Sherief
- Tropical Medicine Department, Faculty of Medicine Ain Shams University, Cairo
| | | | - Inas Moaz
- Epidemiology and Preventive Medicine Department, National Liver Institute, Menoufia University, Menoufia
| | - Adel El Tahan
- New Cairo Viral Hepatitis, Treatment Unit, New Cairo Hospital, Cairo
| | - Nermeen Abdeen
- Tropical Medicine, Faculty of Medicine, Alexandria University, Alexandria
| | - Basem Eysa
- Tropical Medicine Department, National Hepatology and Tropical Medicine Research Institute
| | - Ayman A Aziz
- Gastroenterology and Hepatology Department, Theodor Bilharz Research Institute, Cairo, Egypt
| | - Ahmed Tawheed
- Endemic Medicine Department, Faculty of Medicine, Helwan University
| | - Sameera Ezzat
- Epidemiology and Preventive Medicine Department, National Liver Institute, Menoufia University, Menoufia
| | - Mohamed Hassany
- Tropical Medicine Department, National Hepatology and Tropical Medicine Research Institute
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18
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Ali ME, Halby HM, Ali MY, Hassan EA, El-Mokhtar MA, Sayed IM, Thabet MM, Fouad M, El-Ashmawy AM, Mahran ZG. Role of Serum Vitamin D, Interleukin 13, and microRNA-135a in Hepatocellular Carcinoma and Treatment Failure in Egyptian HCV-Infected Patients Receiving Direct Antiviral Agents. Viruses 2021; 13:2008. [PMID: 34696438 PMCID: PMC8539757 DOI: 10.3390/v13102008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 09/17/2021] [Accepted: 09/25/2021] [Indexed: 12/12/2022] Open
Abstract
Direct-acting antivirals (DAAs) are used for hepatitis C virus (HCV) treatment. However, treatment failure and hepatocellular carcinoma (HCC) development following treatment was reported. In this study, we assessed the role of serum vitamin D, interleukin 13 (IL-13), and microRNA-135a in the prediction of treatment failure with DAA and HCC development among Egyptian HCV-infected patients. A total of 950 patients with HCV-related chronic liver disease underwent DAA treatment. Before DAAs, serum vitamin D and IL-13 were determined by ELISA, and gene expression of miRNA-135a was assessed in serum by real-time PCR. The predictive abilities of these markers were determined using the receiver operating characteristic (ROC) curve. Sustained virological response (SVR) was achieved in 92.6% of HCV-infected patients (responders). High viral load, IL-13, miRNA-135a, and low vitamin D levels were associated with treatment failure and HCC development. HCC development was recorded in non-responders, but not in the responders (35.7% vs. 0% p < 0.001). In conclusion: serum IL-13, Vitamin D, and miRNA-135a could be potential biomarkers in monitoring DAA treatment and HCC prediction. DAAs-induced SVR may decrease the incidence of HCC.
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Affiliation(s)
- Mohamed E. Ali
- Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt; (M.E.A.); (H.M.H.); (M.Y.A.)
| | - Hamada M. Halby
- Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt; (M.E.A.); (H.M.H.); (M.Y.A.)
| | - Mamdouh Yones Ali
- Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt; (M.E.A.); (H.M.H.); (M.Y.A.)
| | - Elham Ahmed Hassan
- Department of Gastroenterology and Tropical Medicine, Faculty of Medicine, Assiut University, Assiut 71515, Egypt;
| | - Mohamed A. El-Mokhtar
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt; (M.A.E.-M.); (I.M.S.)
| | - Ibrahim M. Sayed
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt; (M.A.E.-M.); (I.M.S.)
| | - Marwa M. Thabet
- Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt;
| | - Magdy Fouad
- Hepato-Gastroenterology Unit, Tropical Medicine Department, Faculty of Medicine, El-Minia University, Minya 61519, Egypt;
| | - Ahmed M. El-Ashmawy
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Assiut University, Assiut 71515, Egypt;
| | - Zainab Gaber Mahran
- Department of Gastroenterology and Tropical Medicine, Faculty of Medicine, Assiut University, Assiut 71515, Egypt;
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19
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Effectiveness of Direct-Acting Antivirals in Treatment of Elderly Egyptian Chronic Hepatitis C Patients. GASTROENTEROLOGY INSIGHTS 2021. [DOI: 10.3390/gastroent12030031] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Background: Hepatitis C virus treatment has dramatically improved by direct-acting antiviral (DAA) therapy. The aim of this study was to assess the efficacy and safety of DAA in elderly Egyptian chronic hepatitis C (CHC) patients. Methods: The study was carried out on 327 CHC elderly patients >60 years; patients were divided into 3 age subgroups (<65, 65–75 and >75 years) on DAA therapy for 12 weeks. Ninety-one patients (27.8%) were treated with dual therapy, 234 patients (71.6%) with triple therapy and 2 patients (0.6%) with quadrable therapy. Results: All patients achieved end-of-treatment virological response (100%). ALT levels normalized during therapy. The follow-up rate of sustained virological response at 12 weeks after the end of treatment (SVR12) was 100%. One hundred and two patients had missed SVR12 data due to being lost tofollow-up. Two hundred twenty-two adverse events were reported (67.8%), including anemia in 30 patients (9.1%), leucopenia in 129 patients (39.4%) and thrombocytopenia in 63 patients (19.2%). No serious side effects led to discontinuation of therapy. No hepatic decompensation was observed, and no patients died. Conclusion: Age does not influence the success of DAA treatment and all DAA regimens are well tolerated, safe and highly efficacious, even in those aged 75 years or older.
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20
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Wellhöner F, Döscher N, Woelfl F, Vital M, Plumeier I, Kahl S, Potthoff A, Manns MP, Pieper DH, Cornberg M, Wedemeyer H, Heidrich B. Eradication of Chronic HCV Infection: Improvement of Dysbiosis Only in Patients Without Liver Cirrhosis. Hepatology 2021; 74:72-82. [PMID: 33411981 DOI: 10.1002/hep.31700] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 11/14/2020] [Accepted: 12/13/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS It is well accepted that liver diseases and their outcomes are associated with intestinal microbiota, but causality is difficult to establish. The intestinal microbiota are altered in patients with hepatitis C. As chronic HCV infection can now be cured in almost all patients, it is an ideal model to study the influence of liver disease on the microbiota. APPROACH AND RESULTS We aimed to prospectively analyze the changes in the gut microbiome in patients who received direct-acting antivirals (DAA) and achieved sustained virological response (SVR). Amplicon sequencing of the V1-V2 region in the 16S ribosomal RNA gene was performed in stool samples of patients with chronic hepatitis C. Patients in the treatment group received DAA (n = 65), whereas in the control group, no DAA were given (n = 33). Only patients achieving SVR were included. The alpha diversity increased numerically but not significantly from baseline to SVR at week 24 or 48 (SVR24/48; 2.784 ± 0.248 vs. 2.846 ± 0.224; P = 0.057). When stratifying for the presence of liver cirrhosis, a significant increase in diversity was only seen in patients without cirrhosis. Differences in the microbial community structure induced by the achievement of SVR were only observed in patients without liver cirrhosis. In patients with liver cirrhosis and in the control group, no significant differences were observed. CONCLUSIONS In conclusion, the achievement of SVR24/48 in patients with chronic HCV was associated with changes in the intestinal microbiota. However, these changes were only seen in patients without liver cirrhosis. A major role of liver remodeling on the intestinal microbiota is indicated by the dynamics of the intestinal microbial community structure depending on the stage of fibrosis in patients resolving chronic hepatitis C.
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Affiliation(s)
- Freya Wellhöner
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Nico Döscher
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Franziska Woelfl
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Marius Vital
- Microbial Interactions and Processes Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany
| | - Iris Plumeier
- Microbial Interactions and Processes Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany
| | - Silke Kahl
- Microbial Interactions and Processes Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany
| | - Andrej Potthoff
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Michael Peter Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany
| | - Dietmar Helmut Pieper
- Microbial Interactions and Processes Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany.,German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany
| | - Benjamin Heidrich
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,Microbial Interactions and Processes Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany.,German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany
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21
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Kikukawa K, Uchida-Kobayashi S, Tamori A, Yoshida K, Kotani K, Motoyama H, Kozuka R, Hagihara A, Fujii H, Morikawa H, Enomoto M, Murakami Y, Kawada N. Serum Mac-2-binding protein glycosylation isomer predicts esophagogastric varices in cirrhotic patients with chronic hepatitis C virus infection treated with IFN-free direct-acting antiviral agent: M2BPGi levels predict varices in SVR patients. Ann Hepatol 2021; 19:367-372. [PMID: 32444247 DOI: 10.1016/j.aohep.2020.04.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Revised: 04/22/2020] [Accepted: 04/23/2020] [Indexed: 02/06/2023]
Abstract
INTRODUCTION AND OBJECTIVES We examined whether Mac-2-binding protein glycosylation isomer (M2BPGi) levels could be a predictive marker for the presence of esophagogastric varices (EGV) in cirrhotic patients after hepatitis C virus (HCV) eradication with direct-acting antivirals (DAAs). PATIENTS AND METHODS A total of 102 cirrhotic patients with HCV infection treated with DAAs were enrolled. Esophagogastroduodenoscopy was performed in 84 of the patients before treatment (Cohort A), in 66 after treatment (Cohort B), and in 48 at both time points (Cohort C). We examined factors associated with EGV before and after DAA treatment. RESULTS In Cohort A, M2BPGi levels and liver stiffness were significantly higher in the EGV-positive group than the EGV-negative group (p=0.034, and p=0.042, respectively). The proportion of EGV-positive patients with before-treatment levels of M2BPGi ≧ 7.3 C.O.I. was significantly higher than in patients with M2BPGi levels<7.3 C.O.I. (p=0.015). In Cohort B, M2BPGi levels were significantly higher in the EGV-positive group than EGV-negative group (p=0.003). The proportion of EGV-positive patients with after-treatment levels of M2BPGi ≧ 3.4 C.O.I. was significantly higher than in patients with M2BPGi levels<3.4C.O.I. (p=0.001). In Cohort C, M2BPGi levels decreased during DAA treatment regardless of EGV development, but there was no significant difference in the reduction of M2BPGi among the EGV-improvement, EGV-invariant, and EGV-exacerbation groups (p=0.659). CONCLUSIONS M2BPGi levels may be a novel serum marker for the presence of EGV before and after DAA treatment.
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Affiliation(s)
- Kanako Kikukawa
- Department of Hepatology, Endowed Department of Liver Cirrhosis Therapeutics, Japan
| | | | - Akihiro Tamori
- Department of Hepatology, Endowed Department of Liver Cirrhosis Therapeutics, Japan; Department of Bool Transfusion, Osaka City University Hospital, Japan.
| | - Kanako Yoshida
- Department of Hepatology, Endowed Department of Liver Cirrhosis Therapeutics, Japan
| | - Kohei Kotani
- Department of Hepatology, Endowed Department of Liver Cirrhosis Therapeutics, Japan
| | - Hiroyuki Motoyama
- Department of Hepatology, Endowed Department of Liver Cirrhosis Therapeutics, Japan
| | - Ritsuzo Kozuka
- Department of Hepatology, Endowed Department of Liver Cirrhosis Therapeutics, Japan
| | - Atsushi Hagihara
- Department of Hepatology, Endowed Department of Liver Cirrhosis Therapeutics, Japan
| | - Hideki Fujii
- Department of Premier Preventive Medicine, Japan; Osaka City University Graduate School of Medicine, Japan
| | - Hiroyasu Morikawa
- Department of Hepatology, Endowed Department of Liver Cirrhosis Therapeutics, Japan
| | - Masaru Enomoto
- Department of Hepatology, Endowed Department of Liver Cirrhosis Therapeutics, Japan
| | - Yoshiki Murakami
- Department of Hepatology, Endowed Department of Liver Cirrhosis Therapeutics, Japan
| | - Norifumi Kawada
- Department of Hepatology, Endowed Department of Liver Cirrhosis Therapeutics, Japan; Department of Premier Preventive Medicine, Japan
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22
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Krassenburg LAP, Zanjir WR, Georgie F, Stotland E, Janssen HLA, Hansen BE, Feld JJ. Evaluation of Sustained Virologic Response as a Relevant Surrogate Endpoint for Long-term Outcomes of Hepatitis C Virus Infection. Clin Infect Dis 2021; 72:780-786. [PMID: 32052014 PMCID: PMC7935378 DOI: 10.1093/cid/ciaa144] [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: 10/16/2019] [Accepted: 02/11/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The causal link of sustained virologic response (SVR) with outcome has been challenged. With improved SVR rates with direct-acting antivirals (DAAs), the benefit of SVR would be expected to diminish if the association with outcome is not causal. METHODS Data were collected for patients starting treatment with interferon (IFN) or DAAs between June 2006 and December 2016. To control for disease severity, criteria for the IDEAL (Individualized Dosing Efficacy vs. Flat Dosing to Assess Optimal Pegylated Interferon Therapy) trial determined IFN-eligibility. Clinical events were decompensation, hepatocellular carcinoma, liver transplantation, and all-cause mortality. RESULTS In 1078 IDEAL-eligible patients, 1306 treatments occurred (52% IFN, 49% DAAs). Cirrhosis was present in 30% DAAs vs 21% IFN (P < .001). SVR was 97% with DAAs vs 52% with IFN (P < .0001). The 24-month cumulative event-free survival was 99% for IFN and 97% for DAAs with SVR (P = .08) and 96% and 75%, respectively, for non-SVR (P = .01). SVR was associated with improved event-free survival with an adjusted hazard ratio of 0.21 (95% confidence interval, .06-.71; P = .01). Using inverse probability of treatment weighting to match IFN nonresponders with DAA-treated patients, the 24-month event-rate was 1.1% with DAAs compared to 3.4% in IFN nonresponders (P = .005), highlighting the clinical benefit of maximizing SVR. CONCLUSIONS In IFN-eligible patients, SVR is more commonly achieved with DAAs and confers a similar clinical benefit as in those treated with IFN. The reduced event-rate with DAAs compared to IFN, despite similar disease severity, confirm that SVR alters prognosis leading to improved clinical outcomes.
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Affiliation(s)
- Lisette A P Krassenburg
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.,Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Wayel R Zanjir
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Firas Georgie
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Emily Stotland
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Harry L A Janssen
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Bettina E Hansen
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.,Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | - Jordan J Feld
- Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
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23
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Fahmy DM, Shokeir M, El Zeiny SM, Jonas MM, Abdallah A. Changes in Liver Stiffness and Noninvasive Fibrosis Scores in Egyptian Adolescents Successfully Treated with Ledipasvir-Sofosbuvir for Chronic Hepatitis C Virus Infection. J Pediatr 2021; 231:110-116. [PMID: 33347957 DOI: 10.1016/j.jpeds.2020.12.031] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 11/22/2020] [Accepted: 12/14/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To assess changes in noninvasive liver fibrosis measurements after chronic hepatitis C eradication by direct-acting antivirals in Egyptian adolescents. STUDY DESIGN Liver stiffness measurement (LSM), by vibration-controlled transient elastography and noninvasive fibrosis scores (Firbosis-4, aspartate aminotransferase-platelet ratio index), was obtained before and 12 months after eradication with ledipasvir-sofosbuvir. The primary outcome was a more than 30% decrease in LSM with resulting fibrosis stage regression for initial fibrosis of F2 or higher and nonprogression of F0-F1, using the Ishak score (F0-F6). The secondary outcome was change in noninvasive fibrosis scores after treatment. RESULTS Analyzing 85 patients, the median baseline LSM was 5.8 (IQR, 4.2-6.5) and at follow-up 5.1 kPa (IQR, 4-6 kPa) (P = .045); 62 (73%) met the primary outcome, 16 patients (19%) experienced regression, and 46 (54%) nonprogression of LSM. Of 18 with initial fibrosis of F2 0r higher, 13 regressed to F0-F1 and 2 from F6 to F5, 1 unchanged at F3, and 1 increased to F3 and 1 to F4. Among 67 patients with a baseline fibrosis of F0-F1, 62 were unchanged and 5 increased-4 to F2 and 1 to F3. Although 23 (27%) had a more than 30% LSM increase, only 7 (8%), with associated comorbidities (4 β-thalassemia, 3 hepatic steatosis), had increased fibrosis stage. The median baseline FIB-4 and aspartate aminotransferase-platelet ratio index scores were 0.34 (IQR, 0.22-0.47) and 0.35 (0.24-0.57), and at follow-up 0.3 (IQR, 0.22-0.34) and 0.2 (0.18-2.8) (P < .001, <.001), respectively. CONCLUSIONS Chronic hepatitis C eradication by direct-acting antiviral agents in Egyptian adolescents was associated with nonprogression or regression of liver fibrosis, by noninvasive fibrosis measurements, at 12 months after treatment in the majority of cases.
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Affiliation(s)
- Doaa M Fahmy
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA.
| | - Mohamed Shokeir
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Sherine M El Zeiny
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Maureen M Jonas
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA
| | - Ahmed Abdallah
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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24
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Ibrahim ES, Abdel-Samiee M, Youssef MI, El-Shazly H, A El-Gendy AE, Sakr AA, Elwazzan D, Nassar MR, Aly Elshormilisy A, Madkour A, Kamal M, Amrousy YM, Elkhadry SW, Abdelsameea E. Variceal recurrence 4 years post endoscopic band ligation in hepatitis C patients who achieved sustained virological response with oral direct-acting antiviral therapy. J Viral Hepat 2021; 28:279-287. [PMID: 33098209 DOI: 10.1111/jvh.13426] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Revised: 09/14/2020] [Accepted: 09/15/2020] [Indexed: 01/06/2023]
Abstract
Oral Direct-acting antivirals (DAAs) are safe, highly effective altering disease burden and prognosis in hepatitis C patients. Sustained virologic response (SVR) is achieved nowadays in more than 90% of the treated patients and related to the improvements in functions of the liver, fibrosis plus survival. Furthermore, portal hypertension is thought to be improved with achievement of virological response, parallel to the improvements in hepatic inflammation and fibrosis. We aimed to assess the recurrence rate of oesophageal varices by long-term follow-up in patients treated with different DAAs regimens who had achieved SVR. We studied 176 Child A cirrhotic HCV patients who achieved SVR after DAAs treatment and had a history of endoscopic oesophageal varices obliteration and were on maximum tolerated propranolol dose. They were subjected to follow-up upper gastrointestinal endoscopy repeated every 6 months for 4 years. Fifty-two patients (29.5%) had recurrence of oesophageal varices observed during the 4-years follow-up upper GIT endoscopy. On multivariate analysis, platelet count was the only significant variable, P-value = .007*. HbA1C, HOMA IR, BMI 1 and BMI 2 showed non-significant differences between the studied groups. By ROC analysis, we identified baseline platelet count of 96 000/µL with 100% sensitivity (95% confidence interval [CI] [91%-100%]) and 74% specificity (95% CI [65%-81%]). Spearman correlation showed a positive correlation between AFP, age, AST, Bilirubin, creatinine, INR. Patients who achieved SVR post DAAs showed a significant decrease in oesophageal varices recurrence post endoscopic obliteration. Baseline platelet count was found to be a strong independent predictor for oesophageal varices recurrence.
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Affiliation(s)
- El-Sayed Ibrahim
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Mohamed Abdel-Samiee
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Mohamed I Youssef
- Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Helmy El-Shazly
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Menoufia, Egypt
| | | | - Ayman Ahmed Sakr
- Department of Tropical Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Doaa Elwazzan
- Department of Tropical Medicine, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Mervat Ragab Nassar
- Department of Tropical Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Amr Aly Elshormilisy
- Department of Internal Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Ahmad Madkour
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Mostafa Kamal
- Department of Clinical and Chemical Pathology, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Yasmine M Amrousy
- Department of Clinical and Chemical Pathology, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Sally Waheed Elkhadry
- Department of Epidemiology and Preventive Medicine, National Liver Institute, Menoufia University, Menoufia, Egypt
| | - Eman Abdelsameea
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Menoufia, Egypt
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25
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Endo K, Sato T, Suzuki A, Yoshida Y, Kakisaka K, Miyasaka A, Takikawa Y. Sustained virologic response by direct-acting antivirals suppresses skeletal muscle loss in hepatitis C virus infection. J Gastroenterol Hepatol 2020; 35:1602-1609. [PMID: 31975438 DOI: 10.1111/jgh.14991] [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: 06/22/2019] [Revised: 12/17/2019] [Accepted: 01/22/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Although chronic liver disease is associated with secondary sarcopenia, the effect of primary disease treatment (hepatitis C virus elimination) on the skeletal muscle is unclear. This study aimed to determine the effect of a sustained virologic response at 24 weeks following direct-acting antiviral therapy on the skeletal muscle in hepatitis C virus-infected patients. METHODS Hepatitis C virus-infected patients treated with direct-acting antivirals between 2014 and 2017 in our hospital were included. We evaluated the skeletal muscle index and intramuscular adipose tissue content at the third lumbar vertebra on abdominal computed tomography and compared the rate of change in the skeletal muscle index per year and intramuscular adipose tissue content per year before and after direct-acting antiviral treatment. RESULTS Ninety-two patients participated. At sustained virologic response at 24 weeks, liver test results, including fibrosis marker levels, were significantly improved compared to those before direct-acting antiviral treatment. Skeletal muscle index measured before direct-acting antiviral treatment initiation was significantly lower than that at the first computed tomography scan. However, no significant change was found between the skeletal muscle index at the second computed tomography scan and final follow up. The rate of change in skeletal muscle index measured after direct-acting antiviral treatment was significantly higher than that before direct-acting antiviral treatment (-0.07 vs -0.99% per year). There was no significant difference between the change in intramuscular adipose tissue content before and after direct-acting antiviral treatment. CONCLUSIONS Viral eradication by direct-acting antiviral treatment improved the liver function and suppressed skeletal muscle loss in hepatitis C virus-infected patients.
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Affiliation(s)
- Kei Endo
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Takuro Sato
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Akiko Suzuki
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Yuichi Yoshida
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Keisuke Kakisaka
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Akio Miyasaka
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
| | - Yasuhiro Takikawa
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan
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26
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Domínguez Domínguez L, Matarranz M, Lagarde M, Bisbal O, Hernando A, Lumbreras C, Rubio R, Pulido F. HCV eradication with all-oral therapy in cirrhotic HIV-coinfected patients: an observational study of early changes in liver function and fibrosis tests. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2020; 111:626-632. [PMID: 31240941 DOI: 10.17235/reed.2019.6086/2018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
INTRODUCTION liver laboratory tests improve in hepatitis C virus (HCV)-monoinfected and cirrhotic patients who achieve HCV cure after interferon-free treatment. OBJECTIVE AND METHODS this study evaluates the changes in those tests in human immunodeficiency virus (HIV)-positive subjects with an eradicated HCV-coinfection using direct-acting antivirals and with a pre-therapy liver stiffness ≥ 14.6 kPa or clinical data of cirrhosis. Serum albumin, bilirubin, creatinine, platelet count and international normalized ratio (INR) values were collected at baseline, week 4, at the end of treatment and 24 weeks after the end-of-treatment. Fibrosis-4 score (FIB4) and Model for End-stage Liver Disease (MELD) score values were calculated and liver stiffness was estimated by transient elastography at baseline and 24 weeks after the end-of-treatment. The means were compared with the Student's t test or the repeated measures ANOVA test. RESULTS direct-acting antivirals were prescribed to 131 HIV/HCV-coinfected cirrhotic patients. A sustained virological response was confirmed in 120 cases. Albumin, bilirubin and platelet count values improved in the entire population 24 weeks after the end-of-treatment. INR and MELD score values decreased when patients with atazanavir and/or acenocoumarol were excluded and liver fibrosis tests significantly diminished. Nine patients developed liver decompensation and there were three deaths. CONCLUSION in conclusion, HCV eradication was associated with a short-term improvement in biochemical liver function and fibrosis tests in HIV-coinfected patients with cirrhosis, although clinical events still occur.
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Affiliation(s)
| | - Mariano Matarranz
- Unidad VIH, Servicio de Medicina Interna, Hospital Universitario 12 de Octubre
| | - María Lagarde
- Unidad VIH, Servicio de Medicina Interna, Hospital Universitario 12 de Octubre
| | - Otilia Bisbal
- Unidad VIH, Servicio de Medicina Interna, Hospital Universitario 12 de Octubre
| | | | - Carlos Lumbreras
- Unidad VIH, Servicio de Medicina Interna, Hospital Universitario 12 de Octubre
| | - Rafael Rubio
- Unidad VIH, Servicio de Medicina Interna, Hospital Universitario 12 de Octubre
| | - Federico Pulido
- Unidad VIH, Servicio de Medicina Interna, Hospital Universitario 12 de Octubre
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27
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Lin MT, Chang KC, Yen YH, Tsai MC, Chen CH, Wang JH, Hsiao CC, Chiu YH, Hu TH. Chronic hepatitis B exhibited higher rate of hepatocellular carcinoma occurrence than hepatitis C in cirrhotic patients after effective antiviral treatment. J Formos Med Assoc 2020; 120:621-628. [PMID: 32718890 DOI: 10.1016/j.jfma.2020.07.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Revised: 06/07/2020] [Accepted: 07/15/2020] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND/PURPOSE Effective antiviral-therapy can reduce the risk of liver cirrhosis related hepatocellular carcinoma in patients with chronic hepatitis B and hepatitis C. Yet, the difference of hepatocellular carcinoma development in chronic hepatitis B and hepatitis C patients with cirrhosis after effective antiviral therapy treatment is unknown. In this study, We comprehensive explored the difference among them. METHODS 1363 patients with cirrhosis and hepatitis B virus treated with nucleos(t)ide analogues (NUCs) with completely suppressed virus, and patients with cirrhosis and hepatitis C virus treated with pegylated interferon (peg-IFN)/ribavirin (RBV) combination therapy who achieved sustained virologic response were enrolled. RESULTS Total 261 developed hepatocellular carcinoma within a median follow-up of 4.25 years. Univariate analysis, patients developed hepatocellular carcinoma tended to be of older age, and had lower platelet counts, were chronic hepatitis B carriers, and had higher serum alfa-fetoprotein (AFP) (≥20 ng/mL), FIB-4 index and APRI scores. Subsequent multivariate analysis revealed older age, lower platelet counts, high AFP levels and chronic hepatitis B carriers were independent risk factors of hepatocellular carcinoma. CONCLUSION Our findings identify that chronic hepatitis B patients were with a higher risk of hepatocellular carcinoma compared to chronic hepatitis C patients after achieving virological response. Special attention should be paid to those patients.
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Affiliation(s)
- Ming-Tsung Lin
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taiwan
| | - Kuo-Chin Chang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan
| | - Yi-Hao Yen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan
| | - Ming-Chao Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan
| | - Jing-Houng Wang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan
| | - Chang-Chun Hsiao
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taiwan; Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan
| | - Yueh-Hsia Chiu
- Department of Health Care Management, College of Management, Chang Gung University, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan.
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Saleh SA, Salama MM, Alhusseini MM, Mohamed GA. M2BPGi for assessing liver fibrosis in patients with hepatitis C treated with direct-acting antivirals. World J Gastroenterol 2020; 26:2864-2876. [PMID: 32550761 PMCID: PMC7284180 DOI: 10.3748/wjg.v26.i21.2864] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Revised: 03/27/2020] [Accepted: 05/28/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Assessing liver fibrosis is important for predicting the efficacy of direct-acting antivirals (DAAs) and patient prognosis. Non-invasive techniques to assess liver fibrosis are becoming important. Recently, serum Mac-2 binding protein glycosylation isomer (M2BPGi) was identified as a non-invasive marker of liver fibrosis.
AIM To investigate the diagnostic accuracy of M2BPGi in assessing liver fibrosis in patients with chronic hepatitis C (CHC) treated with DAAs.
METHODS From December 2017 to August 2018, 80 treatment-naïve adult patients with CHC who were eligible for DAAs therapy were consecutively enrolled in this observational cohort study. For 12 weeks, 65 patients were treated with sofosbuvir/daclatasvir, and 15 patients were treated with sofosbuvir/daclatasvir and a weight-based dose of ribavirin at knowledge and technology association for hepatitis C management clinic, Cairo, Egypt. We measured serum M2BPGi levels, PAPAS index, fibrosis-4 (FIB-4) score and liver stiffness measurements (LSM) at baseline and 12 weeks after the end of treatment. Serum M2BPGi levels were measured using enzyme-linked immunosorbent assay.
RESULTS All patients achieved sustained virologic response (SVR12) (100%). Serum M2BPGi levels, LSM, FIB-4 score and PAPAS index decreased significantly at SVR12 (P < 0.05). Serum M2BPGi levels correlated positively with LSM at baseline and SVR12 (P < 0.001). At baseline, compared with the FIB-4 score and PAPAS index, M2BPGi was the best marker to distinguish patients with grade F4 fibrosis (AUC = 0.801, P < 0.001), patients with grade F2 from grade F0-1 fibrosis (AUC = 0.713, P = 0.012), patients with grade F3-4 from grade F0-2 fibrosis (AUC = 0.730, P < 0.001), and patients with grade F2-4 from grade F0-1 fibrosis (AUC = 0.763, P < 0.001). At SVR12, M2BPGi had the greatest AUCs for differentiating patients with grade F4 fibrosis (AUC = 0.844, P < 0.001), patients with grade F3 from grade F0-2 fibrosis (AUC = 0.893, P = 0.002), patients with grade F3-4 from grade F0-2 fibrosis (AUC = 0.891, P < 0.001), and patients with grade F2-4 from grade F0-1 fibrosis (AUC = 0.750, P < 0.001).
CONCLUSION M2BPGi is a reliable marker for the non-invasive assessment and prediction of liver fibrosis regression in patients with CHC who achieved an SVR with DAAs therapy.
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Affiliation(s)
- Shereen A Saleh
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11341, Egypt
| | - Mohamed M Salama
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11341, Egypt
| | - Marwan M Alhusseini
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11341, Egypt
| | - Ghada A Mohamed
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11341, Egypt
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Wake T, Tateishi R, Fukumoto T, Nakagomi R, Kinoshita MN, Nakatsuka T, Sato M, Minami T, Uchino K, Enooku K, Nakagawa H, Fujinaga H, Asaoka Y, Tanaka Y, Otsuka M, Koike K. Improved liver function in patients with cirrhosis due to chronic hepatitis C virus who achieve sustained virologic response is not accompanied by increased liver volume. PLoS One 2020; 15:e0231836. [PMID: 32310974 PMCID: PMC7170262 DOI: 10.1371/journal.pone.0231836] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Accepted: 04/01/2020] [Indexed: 12/14/2022] Open
Abstract
Background Serum albumin level improves in patients with chronic hepatitis C virus (HCV) infection who achieve sustained virologic response (SVR) with antiviral therapy. However, it remains controversial whether liver volume increases along with SVR. Methods Patients with chronic HCV infection with a history of hepatocellular carcinoma (HCC) who achieved SVR with anti-HCV treatment from March 2003 to November 2017 were enrolled. Patients were followed up with periodic computed tomography (CT) scans to detect HCC recurrence. Patients who underwent treatment for HCC recurrence within 1 year after initiation of anti-HCV treatment were excluded. Laboratory data, including alanine aminotransferase (ALT) level, serum albumin level, and platelet count, were collected at baseline and timepoints after treatment initiation. Liver volume was evaluated at baseline and 24 and 48 weeks after treatment initiation using a CT volume analyzer. A linear mixed-effects model was applied to analyze the chronologic change in liver volume. The correlations between changes in ALT level, albumin level, and liver volume were also evaluated. Results Of 108 enrolled patients, 78 had cirrhosis. Serum albumin level continued to increase through 48 weeks after treatment initiation. A significant increase in liver volume was observed only in patients without cirrhosis (P = 0.005). There was a significant correlation between ALT level decrease and albumin level increase (P = 0.018). Conclusions Improved liver albumin production with SVR was contributed by improved liver cell function rather than increased liver volume in patients with cirrhosis.
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Affiliation(s)
- Taijiro Wake
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- * E-mail:
| | - Tsuyoshi Fukumoto
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryo Nakagomi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | | | - Takuma Nakatsuka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masaya Sato
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tatsuya Minami
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Koji Uchino
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kenichiro Enooku
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hayato Nakagawa
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hidetaka Fujinaga
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yoshinari Asaoka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Gastroenterology, Teikyo University, Tokyo, Japan
| | - Yasuo Tanaka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Motoyuki Otsuka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Ozeki I, Nakajima T, Suii H, Tatsumi R, Yamaguchi M, Arakawa T, Kuwata Y. Predictors of hepatocellular carcinoma after hepatitis C virus eradication following direct-acting antiviral treatment: relationship with serum zinc. J Clin Biochem Nutr 2020; 66:245-252. [PMID: 32523252 DOI: 10.3164/jcbn.19-98] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Accepted: 12/04/2019] [Indexed: 12/20/2022] Open
Abstract
The recently approved direct-acting antivirals (DAA) agents are effective in terms of sustained virologic response (SVR) rates and are well tolerated in most hepatitis C virus (HCV) patients. This study aimed to analyze the association between serum zinc levels in patients who developed hepatocellular carcinoma (HCC) following HCV eradication after DAA treatment. The retrospective study included 769 HCV-infected patients who achieved SVR after DAA treatment. We calculated the annual incidence rate of HCC and identified risk factors associated with HCC development. We also assessed serum zinc and clinical factors at both baseline and end of treatment (EOT). During follow-up (median duration 35 months), HCC occurred in 18/769 (2.3%) patients. From the multivariate analysis, serum zinc <60 µg/dl [hazard ratio (HR) 5.936] and AFP ≥6.0 ng/dl (HR 5.862) at baseline, baseline-zinc <60 µg/dl (HR 6.283), EOT-serum zinc <63 µg/dl (HR 6.011), baseline-AFP ≥6.0 ng/dl (HR 8.163), and EOT-M2BPGi ≥2.5 (HR 12.194) at baseline and EOT were independently associated with increased HCC risk. In patients who achieved HCV eradication following DAA treatment, serum zinc levels before and at EOT could be a risk factor for developing HCC.
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Affiliation(s)
- Itaru Ozeki
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Tomoaki Nakajima
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Hirokazu Suii
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Ryoji Tatsumi
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Masakatsu Yamaguchi
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Tomohiro Arakawa
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Yasuaki Kuwata
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
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Imai K, Takai K, Hanai T, Suetsugu A, Shiraki M, Shimizu M. Sustained virological response by direct-acting antivirals reduces the recurrence risk of hepatitis C-related hepatocellular carcinoma after curative treatment. Mol Clin Oncol 2019; 12:111-116. [PMID: 31929880 PMCID: PMC6951252 DOI: 10.3892/mco.2019.1956] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Accepted: 08/09/2019] [Indexed: 02/06/2023] Open
Abstract
The present study aimed to assess the suppressive effect of direct-acting antivirals (DAAs) on hepatocellular carcinoma (HCC) recurrence following curative treatment, particularly compared with interferon (IFN)-based therapy. Among 117 curative cases of HCV-related initial HCC between 2006 and 2017 at Gifu University Hospital, 13 and 14 cases achieved a sustained virological response (SVR) by DAA- (DAA group) or IFN-based therapies (IFN group), and 64 cases were not treated with any antiviral therapy (non-treatment group). Recurrence-free survival (RFS) following curative treatment in each group was analyzed using the Kaplan-Meier method and log-rank test. A Cox proportional hazards model was used to analyze the factors that affected RFS. Age was significantly lower and serum alanine aminotransferase level was significantly higher in the IFN group than in both the DAA and non-treatment groups. There was a significant difference in RFS between the non-treatment group and antiviral therapy groups, including the DAA (P=0.014) and IFN groups (P=0.009); however, no significant difference was identified in RFS between the DAA and IFN groups (P=0.564). SVR achieved by DAA [P=0.011; hazard ratio (HR), 0.222; 95% CI, 0.069-0.758] or IFN therapy (P=0.007; HR, 0.327; 95% CI, 0.145-0.742) was an independent factor for the prevention of HCC recurrence. SVR by DAA therapy exhibited an anti-liver tumorigenesis effect equal to that of IFN-based therapy and reduced the risk of HCC recurrence.
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Affiliation(s)
- Kenji Imai
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
| | - Koji Takai
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
| | - Tatsunori Hanai
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
| | - Atsushi Suetsugu
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
| | - Makoto Shiraki
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
| | - Masahito Shimizu
- Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
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Hanafy AS, Seleem WM, Basha MAA, Marei AM. Residual hepatitis C virus in peripheral blood mononuclear cell as a risk factor for hepatocellular carcinoma after achieving a sustained virological response: a dogma or fiction. Eur J Gastroenterol Hepatol 2019; 31:1275-1282. [PMID: 31149912 DOI: 10.1097/meg.0000000000001459] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
BACKGROUND Clinical worsening after achieving a sustained virological response (SVR) needs to be clarified and explained. Persistence of hepatitis C virus (HCV) core antigen interacts with the host proteins to interfere with signaling pathways and increases the susceptibility to hepatic carcinogenesis. OBJECTIVE This study aimed to investigate the risk factors that increase the progression of liver disease and hepatocellular carcinoma in a subgroup of HCV patients who achieved a SVR. PATIENTS AND METHODS Eighty-nine HCV patients with hepatic decompensation were selected 8.2 ± 1.8 months after achieving SVR24. HCV core antigen and HCV RNA were detected in peripheral blood mononuclear cells. Matched control (n = 100) and training (n = 200) groups were recruited. RESULTS Eighty-five patients showed a progression of Child-Turcotte-Pugh and model for end-stage liver disease scores, with positive RNA in peripheral blood mononuclear cell (357.4 ± 42.1 IU/million cell) and positive hepatitis C virus core antigen (n = 73); four patients were excluded. Susceptibility to decompensation and hepatocellular carcinoma after direct-acting antiviral drugs increased with age [odds ratio (OD) = 1.87], and was associated with male sex (OD = 1.65), diabetes (OD = 3.68), thrombocytopenia (OD = 2.44), pretreatment Alfa-fetoprotein (OD = 3.41), and occult HCV (OD = 4.1). CONCLUSION Clinical deterioration after SVR could be explained by occult HCV mainly in older male patients with diabetes and thrombocytopenia.
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Affiliation(s)
- Amr S Hanafy
- Internal Medicine Department, Hepatology Division
| | | | | | - Ayman M Marei
- Immunology Department, Faculty of Medicine, Zagazig University, Zagazig
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Lymphovascular invasion on explant is associated with presenting tumor characteristics and not direct acting antiviral utilization in hepatitis C candidates undergoing liver transplantation. Clin Exp Hepatol 2019; 5:279-284. [PMID: 31893238 PMCID: PMC6935850 DOI: 10.5114/ceh.2019.88105] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 06/16/2019] [Indexed: 12/11/2022] Open
Abstract
Aim of the study Utilization of direct acting antiviral (DAA) therapy in candidates with well-compensated hepatitis C virus (HCV) cirrhosis and hepatocellular carcinoma (HCC) accruing end stage liver disease (MELD) exception points is highly variable among transplant centers based on center location, local organ procurement dynamics, HCV(+) organ availability, and patient preference. The association between DAA utilization prior to transplant and incidence of lymphovascular invasion on explant is unknown. Material and methods Retrospective evaluation from 2013-2017 of patients on a liver transplant (LT) waitlist with HCV-related cirrhosis, MELD-Na < 15, and HCC (within T2/Milan criteria). The cohort was divided into the pre-LT DAA treated group and untreated group with clinical/viral demographics collected. Tumor presenting characteristics, locoregional treatments, wait time to LT, dropout rates and explant pathology were compared. Results DAAs were used in 44 patients prior to LT (SVR12 of 37/44 [84%]) and 19 left untreated with LT performed in 81% (51/63) of the waitlisted cohort. No significant differences were found between groups with regards to clinical/viral demographics, local-regional therapy (LRT) sessions, or frequency of lymphovascular invasion on explant. The untreated cohort had a higher rate of dropout (6.3% vs. 3.2%) (p = 0.041). On subgroup analysis of 51 subjects undergoing LT, AFP > 250 ng/ml (p = 0.003) and multifocal HCC (> 1 lesion) (p = 0.006) were associated with lymphovascular invasion on explant while DAA therapy was not (p = 0.578). Conclusions DAA therapy for waitlist active HCV candidates accruing MELD exception points has no deleterious effects on bridging LRT, nor is it associated with increased frequency of lymphovascular invasion on explant. The latter appears driven by tumor related characteristics (AFP and number of lesions) irrespective of DAA utilization prior to LT.
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Is Transient Elastography Needed for Noninvasive Assessment of High-Risk Varices? The REAL Experience. Am J Gastroenterol 2019; 114:1275-1282. [PMID: 31135449 DOI: 10.14309/ajg.0000000000000266] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The Baveno VI consensus guidelines and an expanded algorithm suggest that transient elastography (TE) and platelet (PLT) count can be used to identify patients with cirrhosis who can avoid esophagogastroduodenoscopy (EGD). The primary aims of this study were to assess the ability of a simple algorithm, which uses only laboratory parameters, to predict medium/large esophageal varices (EV) in patients with hepatitis C virus (HCV) and cirrhosis from the Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) cohort and to compare the performance of the algorithm with Baveno VI and Expanded Baveno VI criteria. The secondary aim was to assess the role of TE in ruling out large EV. METHODS In total, 1,381 patients with HCV-associated cirrhosis who had EGD and TE within 1 year of starting treatment with direct-acting antivirals were evaluated. Using multivariate logistic analysis, laboratory variables were selected to determine which were independently associated with medium/large EV to create the RESIST-HCV criteria. These criteria were tested in a training cohort with patients from a single center (Palermo) and validated with patients from the 21 other centers of the RESIST-HCV program (validation cohort). RESULTS In the entire cohort, medium/large EV were identified in 5 of 216 patients (2.3%) using the Baveno VI criteria and 13 of 497 patients (2.6%) using the Expanded Baveno VI criteria. PLT count and albumin level were independently associated with medium/large EV. The best cut-off values were a PLT count greater than 120 × 10 cells/μL and serum albumin level greater than 3.6 g/dL; negative predictive values (NPVs) were 97.2% and 94.7%, respectively. In the training cohort of 326 patients, 119 (36.5%) met the RESIST-HCV criteria and the NPV was 99.2%. Among 1,055 patients in the validation cohort, 315 (30%) met the RESIST-HCV criteria and the NPV was 98.1%. Adding TE to the RESIST-HCV criteria reduced the avoided EGDs for approximately 25% of patients and the NPV was 98.2%. DISCUSSION The "easy-to-use" RESIST-HCV algorithm avoids EGD for high-risk EV screening for more than 30% of patients and has the same performance criteria as TE. Using these criteria simplifies the diagnosis of portal hypertension.
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Deterding K, Manns MP, Wedemeyer H. [Current drug treatment of hepatitis C : Useful therapy algorithms taking into consideration economical aspects]. Internist (Berl) 2019; 59:401-409. [PMID: 29497776 DOI: 10.1007/s00108-018-0390-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Treatment of chronic hepatitis C (HCV) has changed dramatically since the approval of the direct-acting antivirals (DAA). Depending on the HCV genotype and the stage of liver disease, sustained HCV clearance can be achieved in more than 95% of patients with a treatment duration of 8-12 weeks in most of the cases. The selection and combination of the drugs depends on previous antivirals therapies, the stage of liver fibrosis, HCV genotype and subtype, viral load at baseline, and renal function. Nowadays, potent antiviral therapy with minimal side effects can be offered to almost every patient. In the real-world setting, a high quality of HCV therapy considering economic aspects has been documented in the German Hepatitis C Registry. A reduction of clinical complications of chronic liver disease by clearance of HCV has already been documented.
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Affiliation(s)
- K Deterding
- Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland. .,Universitätsklinikum Essen, Hufelandstr. 55, 45147, Essen, Deutschland.
| | - M P Manns
- Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland
| | - H Wedemeyer
- Universitätsklinikum Essen, Hufelandstr. 55, 45147, Essen, Deutschland
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Bach TA, Zaiken K. Outcomes of treatment with direct-acting antivirals for infection with hepatitis C virus genotypes 1-4 in an ambulatory care setting. Am J Health Syst Pharm 2019; 74:S1-S9. [PMID: 28213381 DOI: 10.2146/ajhp160567] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
PURPOSE Outcomes with direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) genotypes 1-4 were determined. METHODS A total of 360 patients at 36 clinical sites in Massachusetts with HCV genotypes 1-4 and a prescription for at least one DAA medication between May 2011 and October 2015 were included. The primary investigator completed a retrospective and concurrent chart review, and data were collected through April 2016. RESULTS A total of 446 patients were assessed for eligibility into the study, with 86 patients excluded. The majority of patients were white males with genotype 1 infection. About half of the patients were treatment naive (TN), and 40% of patients had documented cirrhosis. TN patients without cirrhosis had the highest overall sustained virologic response (SVR) rate at 107 of 109 (98.2%), followed by treatment-experienced (TE) patients without cirrhosis at 59 of 63 (93.7%), TN patients with cirrhosis at 40 of 46 (87.0%), and TE patients with cirrhosis at 64 of 79 (81.0%) when boceprevir- and telaprevir-containing regimens were excluded. A total of 7 of 360 (1.9%) patients reported missing at least one dose of medication. Adverse drug reactions reported in the electronic medical record (EMR) were collected for analysis and included patients who received at least one dose of medication and had adequate EMR documentation. CONCLUSION In patients treated with DAAs for infection with HCV genotypes 1-4, variables favoring achievement of SVR included an age of <45 years, a body mass index of <25 kg/m2, absence of cirrhosis, a fibrosis score of 0-2, and being TN.
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Hsu WF, Lai HC, Su WP, Lin CH, Chuang PH, Chen SH, Chen HY, Wang HW, Huang GT, Peng CY. Rapid decline of noninvasive fibrosis index values in patients with hepatitis C receiving treatment with direct-acting antiviral agents. BMC Gastroenterol 2019; 19:63. [PMID: 31029101 PMCID: PMC6486982 DOI: 10.1186/s12876-019-0973-5] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Accepted: 03/31/2019] [Indexed: 12/23/2022] Open
Abstract
Background Studies on temporal changes in noninvasive fibrosis indices and liver stiffness measurement (LSM) in patients with chronic hepatitis C (CHC) treated with direct-acting antiviral agents (DAAs) are limited. Methods We retrospectively enrolled consecutive patients with CHC who had received DAAs. Results In total, we recruited 395 consecutive patients, of which 388 (98.2%) achieved a sustained virologic response (SVR) at 12 weeks after therapy. In patients who received DAA therapy and achieved SVR 12 weeks after therapy (n = 388), the median aspartate aminotransferase/platelet ratio index (APRI) value decreased from 1.19 (0.62–2.44) at baseline to 0.50 (0.32–0.95), 0.51 (0.31–0.92), 0.48 (0.31–0.88), and 0.52 (0.33–0.92) at week 2, week 4, end of therapy, and PW12, respectively (all P < 0.001). The median FIB-4 value decreased from 2.88 (1.56–5.60) at baseline to 2.10 (1.30–3.65), 2.15 (1.30–3.65), 2.11 (1.37–3.76), and 2.22 (1.45–3.82) at week 2, week 4, end of therapy, and PW12, respectively (all P < 0.001). The median alanine aminotransferase level significantly decreased from week 2 until PW12 (all P < 0.001). The platelet count significantly increased from 2 weeks after DAA therapy initiation until PW12 (all P < 0.001); however, the magnitude of changes in the platelet count was low. In patients with paired LSMs obtained using acoustic radiation force impulse elastography at baseline and PW12 (n = 199), the median LSM decreased from 1.78 (1.25–2.30) m/s at baseline to 1.38 (1.14–1.88) m/s at PW12 (P < 0.001). Conclusions Noninvasive fibrosis indices, namely APRI and FIB-4, exhibited a rapid and sustained decline from week 2 until PW12 in patients with CHC who achieved SVR to DAA therapy. The rapid decline in APRI and FIB-4 values might mainly result from improvement in necroinflammation. Electronic supplementary material The online version of this article (10.1186/s12876-019-0973-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Wei-Fan Hsu
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, 40447, Taichung, Taiwan.,Graduate Institute of Biomedical Science, China Medical University, 40442, Taichung, Taiwan
| | - Hsueh-Chou Lai
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, 40447, Taichung, Taiwan.,School of Chinese Medicine, China Medical University, 40442, Taichung, Taiwan
| | - Wen-Pang Su
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, 40447, Taichung, Taiwan.
| | - Chia-Hsin Lin
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, 40447, Taichung, Taiwan
| | - Po-Heng Chuang
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, 40447, Taichung, Taiwan
| | - Sheng-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, 40447, Taichung, Taiwan.,Graduate Institute of Biomedical Science, China Medical University, 40442, Taichung, Taiwan.,School of Medicine, China Medical University, 40442, Taichung, Taiwan
| | - Hung-Yao Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, 40447, Taichung, Taiwan
| | - Hung-Wei Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, 40447, Taichung, Taiwan
| | - Guan-Tarn Huang
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, 40447, Taichung, Taiwan.,School of Medicine, China Medical University, 40442, Taichung, Taiwan
| | - Cheng-Yuan Peng
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, 40447, Taichung, Taiwan. .,School of Medicine, China Medical University, 40442, Taichung, Taiwan.
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Akahane T, Kurosaki M, Itakura J, Tsuji K, Joko K, Kimura H, Nasu A, Ogawa C, Kojima Y, Hasebe C, Wada S, Uchida Y, Sohda T, Suzuki H, Yoshida H, Kusakabe A, Tamada T, Kobashi H, Mitsuda A, Kondo M, Shigeno M, Ide Y, Morita A, Kitamura T, Abe T, Izumi N. Real-world efficacy and safety of sofosbuvir + ribavirin for hepatitis C genotype 2: A nationwide multicenter study by the Japanese Red Cross Liver Study Group. Hepatol Res 2019; 49:264-270. [PMID: 30171740 DOI: 10.1111/hepr.13246] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Revised: 08/15/2018] [Accepted: 08/27/2018] [Indexed: 12/15/2022]
Abstract
AIM This study aimed to describe the real-world efficacy and safety of sofosbuvir (SOF) + ribavirin (RBV) for chronic hepatitis C, genotype 2. METHODS This was a retrospective analysis of a nationwide, multicenter registry including 914 hepatitis C genotype 2 Japanese patients treated with SOF + RBV for 12 weeks. The rate of sustained virologic response at 12 weeks after treatment (SVR12), incidence of adverse events, and changes in serological parameters were analyzed. RESULTS Treatment was completed in 98.9% of patients. Ribavirin dose reduction was required in 29.7% of patients. The SVR12 rate was 96.8% in the intention-to-treat population and 97.6% in the per-protocol population. Factors associated with SVR12 were absence of advanced fibrosis (odds ratio, 5.76, P = 0.003) and interferon-treatment-naïve status (odds ratio, 4.79, P = 0.017). Dose reduction or total adherence of RBV was not associated with SVR. The resistance-associated substitution S282 T in NS5B was not detected in any patient at virologic failure. Serum albumin levels significantly increased, and the degree of increase was greater in patients with advanced fibrosis than in those without (0.21 ± 0.32 vs. 0.05 ± 0.29, P < 0.0001). Alpha-fetoprotein decreased significantly at end of treatment (P < 0.0001), and the degree of decrease was greater in patients with advanced fibrosis than in those without (21.7 ± 60.8 vs. 2.5 ± 15.5, P < 0.001). The most commonly reported adverse event was anemia (13.7%). CONCLUSIONS Treatment with SOF + RBV was highly effective and safe in Japanese patients with HCV genotype 2 infection.
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Affiliation(s)
- Takehiro Akahane
- Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Jun Itakura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Keiji Tsuji
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Kouji Joko
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - Hiroyuki Kimura
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Akihiro Nasu
- Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan
| | - Chikara Ogawa
- Department of Gastroenterology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Yuji Kojima
- Department of Hepatology, Japanese Red Cross Ise Hospital, Ise, Japan
| | - Chitomi Hasebe
- Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Asahikawa, Japan
| | - Shuichi Wada
- Department of Gastroenterology, Nagano Red Cross Hospital, Nagano, Japan
| | - Yasushi Uchida
- Department of Gastroenterology, Matsue Red Cross Hospital, Matsue, Japan
| | - Tetsuro Sohda
- Department of Hepatology, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan
| | - Hideyuki Suzuki
- Department of Internal Medicine, Japanese Red Cross Haramachi Hospital, Haramachi, Japan
| | - Hideo Yoshida
- Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Atsunori Kusakabe
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan
| | - Takashi Tamada
- Department of Gastroenterology, Takatsuki Red Cross Hospital, Takatsuki, Osaka, Japan
| | - Haruhiko Kobashi
- Department of Hepatology, Japanese Red Cross Okayama Hospital, Okayama, Japan
| | - Akeri Mitsuda
- Department of Internal Medicine, Tottori Red Cross Hospital, Tottori, Japan
| | - Masahiko Kondo
- Department of Gastroenterology, Japanese Red Cross Otsu Hospital, Otsu, Japan
| | - Masaya Shigeno
- Department of Gastroenterology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan
| | - Yasushi Ide
- Department of Internal Medicine, Karatsu Red Cross Hospital, Karatsu, Japan
| | - Atsuhiro Morita
- Department of Gastroenterology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan
| | - Tadashi Kitamura
- Department of Gastroenterology, Shizuoka Red Cross Hospital, Shizuoka, Japan
| | - Takehiko Abe
- Department of Gastroenterology, Japanese Red Cross Maebashi Hospital, Maebashi, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
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Different kinetics of liver stiffness using shear wave elastography in patients with chronic hepatitis C infection treated with interferon-free regimens. Eur J Gastroenterol Hepatol 2019; 31:67-74. [PMID: 30239347 DOI: 10.1097/meg.0000000000001259] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Direct-acting antivirals (DAAs) lead to a high rate of sustained virologic response (SVR) in chronic hepatitis C infection. The aim was to evaluate liver stiffness kinetics, using acoustic radiation force impulse (ARFI) imaging elastography, during and after DAAs in patients who had reached SVR. PATIENTS AND METHODS A total of 275 consecutive chronic hepatitis C virus-infected patients were included in this longitudinal prospective single-centre study. All patients received DAAs for 8 to 24 weeks, and liver stiffness measurements (LSMs) by ARFI at baseline, at week 4, week 12, week 24, and 24 weeks (SVR24) and 48 weeks (FU48) after the end of treatment were recorded. Transient elastography was performed at baseline and at SVR24. RESULTS A decrease in LSM was detected at SVR24 by ARFI and transient elastography (P<0.001 and <0.001, respectively). A continuous gradual decrease in ARFI was observed in patients with cirrhosis versus a nonsignificant change in patients without cirrhosis until FU48 (P<0.001 vs. 0.877, respectively). At SVR24, higher baseline ARFI values (P=0.038) were associated with a decrease in LSM in patients with cirrhosis versus normal international normalization ratio (P=0.003), lower bilirubin (P=0.003), and higher albumin (P=0.007) in patients without cirrhosis. The incidence of liver stiffness decrease from baseline was higher in patients with cirrhosis than in those without cirrhosis (P<0.001), whereas the incidence of liver stiffness progression was more pronounced in advanced than in compensated cirrhosis (P<0.001). CONCLUSION After DAAs in patients with SVR, liver stiffness improves in patients with cirrhosis, whereas non-cirrhotic patients show no true change in liver stiffness. Liver stiffness worsens in patients with advanced liver disease.
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Impact of new direct-acting antiviral drugs on hepatitis C virus-related decompensated liver cirrhosis. Eur J Gastroenterol Hepatol 2019; 31:53-58. [PMID: 30247174 DOI: 10.1097/meg.0000000000001250] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND The benefits of treatment of hepatitis C virus with direct-acting antiviral drugs in patients with decompensated liver cirrhosis (DLC) are still unclear. AIM To evaluate the degree of improvement in hepatic decompensation events and quality of life (QOL) in treated patients with DLC. PATIENTS AND METHODS One hundred and fifty patients with hepatitis C virus-related DLC were included; 75 of these patients received treatment (group I) [sofosbuvir (SOF) with either daclatasvir or ledipasvir for 24 weeks without ribavirin (RBV) or for 12 weeks with RBV] and 75 patients did not receive treatment as a comparable group (group II). Patients who achieved a sustained virological response at 12 weeks were assessed in terms of decompensation events, model for end-stage liver disease score, Child-Turcotte-Pugh score, biochemical changes, and QOL (applied on Mcguill QOL questionnaire) before starting treatment and 6 months after end of treatment, and were compared with untreated patients. RESULTS Forty-two (56%) patients received SOF/daclatasvir for 24 weeks without RBV and 19 (25.3%) patients received SOF/ledipasvir for 24 weeks without RBV. The model for end-stage liver disease score improved in treated patients (mean change -1.73), but worsened in untreated patients (mean change +11.8) before and after 6 months. Also, the Child-Turcotte-Pugh score improved significantly (P<0.001). Serum albumin, prothrombin time, bilirubin, α-fetoprotein, and alanine aminotransferase improved in treated patients (P<0.001). Health-related QOL improved in treated patients (mean change +17.65) and worsened in untreated ones (mean change -18.68; P<0.001). CONCLUSION Treated patients with DLC showed an improvement in liver tests and health-related QOL. Longer durations of follow-up for decompensation events are needed.
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Ravaioli F, Colecchia A, Dajti E, Marasco G, Alemanni LV, Tamè M, Azzaroli F, Brillanti S, Mazzella G, Festi D. Spleen stiffness mirrors changes in portal hypertension after successful interferon-free therapy in chronic-hepatitis C virus patients. World J Hepatol 2018; 10:731-742. [PMID: 30386466 PMCID: PMC6206152 DOI: 10.4254/wjh.v10.i10.731] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Revised: 07/27/2018] [Accepted: 08/13/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate changes in spleen stiffness measurements (SSMs) and other non-invasive tests (NITs) after treatment with direct-acting antivirals (DAAs) and identify predictors of SSM change after sustained virological response (SVR).
METHODS We retrospectively analysed 146 advanced-chronic liver disease (ACLD) patients treated with DAA with available paired SSM at baseline and SVR24. Liver stiffness (LSM), spleen diameter (SD), platelet count (PLT) and liver stiffness-spleen diameter to platelet ratio score(LSPS) were also investigated. LSM ≥ 21 kPa was used as a cut-off to rule-in clinically significant portal hypertension (CSPH). SSM reduction > 20% from baseline was defined as significant.
RESULTS SSM significantly decreased at SVR24, in both patients with and without CSPH; in 44.8% of cases, SSM reduction was > 20%. LSPS significantly improved in the entire cohort at SVR24; SD and PLT changed significantly only in patients without CSPH. LSM significantly decreased in 65.7% of patients and also in 2/3 patients in whom SSM did not decrease. The independent predictor of decreased SSM was median relative change of LSM. CSPH persisted in 54.4% patients after SVR. Delta LSM and baseline SSM were independent factors associated with CSPH persistence.
CONCLUSION SSM and other NITs significantly decrease after SVR, although differently according to the patient’s clinical condition. SSM faithfully reflects changes in portal hypertension and could represent a useful NIT for the follow-up of these patients.
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Affiliation(s)
- Federico Ravaioli
- Gastroenterology Unit, Sant’Orsola-Malpighi University Hospital, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Antonio Colecchia
- Gastroenterology Unit, Sant’Orsola-Malpighi University Hospital, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
- Unit of Gastroenterology, Borgo Trento University Hospital, Verona 37100, Italy
| | - Elton Dajti
- Gastroenterology Unit, Sant’Orsola-Malpighi University Hospital, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Giovanni Marasco
- Gastroenterology Unit, Sant’Orsola-Malpighi University Hospital, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Luigina Vanessa Alemanni
- Gastroenterology Unit, Sant’Orsola-Malpighi University Hospital, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Mariarosa Tamè
- Gastroenterology Unit, Sant’Orsola-Malpighi University Hospital, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Francesco Azzaroli
- Gastroenterology Unit, Sant’Orsola-Malpighi University Hospital, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Stefano Brillanti
- Gastroenterology Unit, Sant’Orsola-Malpighi University Hospital, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Giuseppe Mazzella
- Gastroenterology Unit, Sant’Orsola-Malpighi University Hospital, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
| | - Davide Festi
- Gastroenterology Unit, Sant’Orsola-Malpighi University Hospital, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna 40138, Italy
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Abozeid M, Alsebaey A, Abdelsameea E, Othman W, Elhelbawy M, Rgab A, Elfayomy M, Abdel-Ghafar TS, Abdelkareem M, Sabry A, Fekry M, Shebl N, Rewisha E, Waked I. High efficacy of generic and brand direct acting antivirals in treatment of chronic hepatitis C. Int J Infect Dis 2018; 75:109-114. [PMID: 30077791 DOI: 10.1016/j.ijid.2018.07.025] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Revised: 07/26/2018] [Accepted: 07/27/2018] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Direct acting antivirals (DAAs) are highly effective for treatment of hepatitis C (HCV) but brand products are priced beyond the means of most low and middle income countries (LMICs). Although a few DAAs are offered at reduced prices in access programs, they are still beyond affordability in limited resource settings with a large HCV infected population. Cheap generics might fill this economic need, but studies comparing their clinical efficacy to that of original products are limited. AIM To compare efficacy of brand and generic DAAs used in the national treatment program in Egypt. METHODS HCV treatment eligible patients (n=971) were enrolled. They were treated with 12 weeks of either sofosbuvir-daclatasvir (SOF-DCV) or SOF-ledipasvir (SOF-LDV). Ribavirin (RBV) was added to patients with cirrhosis and to SOF experienced patients. Patients with cirrhosis who were RBV intolerant were treated for 24 weeks without RBV. RESULTS Most patients were males (61.4%), treatment naïve (88.6%), without cirrhosis (61.7%), and the mean age was 51.3±11.31 years. Baseline characteristics were not different in patients treated with brand or generic medications regarding age, liver tests, creatinine, platelets, MELD score, baseline HCV-RNA and transient elastography. Overall sustained virologic response (SVR) rate was 98.1%, which was similar for generic and brand drugs (98.2% vs. 98.1%; p=1), and similar with both regimens used (SOF-DCV±RBV: brand: 98.1%, generic 97.8%; p=0.729, SOF-LDV±RBV: brand 98.2%, generic 100%; p=0.729). AST and ALT decreased significantly with initiation of therapy with both generic and original drugs. CONCLUSION Generic and brand DAAs are equally effective for achieving SVR and improving aminotransferases.
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Affiliation(s)
- Mai Abozeid
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Ayman Alsebaey
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt.
| | - Eman Abdelsameea
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Warda Othman
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Mostafa Elhelbawy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Amr Rgab
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Marwa Elfayomy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Tamer Samir Abdel-Ghafar
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Mervat Abdelkareem
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Alyaa Sabry
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Marwa Fekry
- Department of Public Health, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Nashwa Shebl
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Eman Rewisha
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Imam Waked
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
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Abozeid M, Alsebaey A, Abdelsameea E, Othman W, Elhelbawy M, Rgab A, Elfayomy M, Abdel-Ghafar TS, Abdelkareem M, Sabry A, Fekry M, Shebl N, Rewisha E, Waked I. High efficacy of generic and brand direct acting antivirals in treatment of chronic hepatitis C. Int J Infect Dis 2018. [DOI: https:/doi.org/10.1016/j.ijid.2018.07.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
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Abozeid M, Alsebaey A, Abdelsameea E, Othman W, Elhelbawy M, Rgab A, Elfayomy M, Abdel-Ghafar TS, Abdelkareem M, Sabry A, Fekry M, Shebl N, Rewisha E, Waked I. High efficacy of generic and brand direct acting antivirals in treatment of chronic hepatitis C. Int J Infect Dis 2018. [DOI: https://doi.org/10.1016/j.ijid.2018.07.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
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Kostadinova L, Shive CL, Zebrowski E, Fuller B, Rife K, Hirsch A, Compan A, Moreland A, Falck-Ytter Y, Popkin DL, Anthony DD. Soluble Markers of Immune Activation Differentially Normalize and Selectively Associate with Improvement in AST, ALT, Albumin, and Transient Elastography During IFN-Free HCV Therapy. Pathog Immun 2018; 3:149-163. [PMID: 30370392 PMCID: PMC6201254 DOI: 10.20411/pai.v3i1.242] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background During chronic hepatitis C virus (HCV) infection, Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels mark active liver inflammation and tissue damage, while albumin reflects synthetic liver function and nutritional status. Transient Elastography (TE) is a clinical measure of liver stiffness that facilitates evaluation of liver damage stage. While a portion of the TE score is attributable to liver fibrosis and relatively irreversible damage, another component of the TE score is attributable to liver inflammation or edema. Markers of inflammation during chronic HCV infection include soluble markers of immune activation, which are also associated with morbid outcome (including cardiovascular disease and liver-disease progression). Whether soluble markers of immune activation or changes in their level during HCV therapy relate to normalization of AST, ALT, Albumin, or TE score, is not clear. Methods We evaluated soluble markers of immune activation (plasma sCD14, IL-6, sCD163, autotaxin [ATX], and Mac2BP) and TE score, and their relationship in 20 HCV-infected patients before, during, and after HCV-directed IFN-free direct-acting antiviral (DAA) therapy. We evaluated normalization of parameters and the relationship between each over a 6-month window. Results Before therapy, serum AST levels positively correlated with plasma levels of sCD14, sCD163, and Mac2BP, while ALT levels positively correlated with Mac2BP. Serum albumin level negatively correlated with plasma IL-6 and ATX levels. IFN-free therapy uniformly resulted in sustained virological response at 12 and 24 weeks after therapy completion. After initiation of therapy AST and ALT normalized, while levels of ATX, Mac2BP, sCD163, and TE score partially normalized over 6 months. Additionally, change in AST level and APRI score correlated with change in sCD163, IL-6, and Mac2BP levels, and change in ALT correlated with change in IL-6 and Mac2BP levels. Improvement in TE score correlated with a decrease in the level of sCD14 at week 4, and almost statistically significant with decrease in sCD14 at weeks 20-24 after initiation of IFN-free HCV therapy. Conclusions Soluble markers of immune activation normalize or partially normalize at different rates after initiation of curative HCV DAA therapy, and TE scores improve, with wide variability in the degree of absolute improvement in liver stiffness from patient to patient. Decline magnitude of sCD14 was associated with improvement in TE score, while magnitude of improvement in AST correlated with reduction in sCD163 levels. These data provide support for a model where monocyte/Kupffer cell activation may account for a portion of the liver inflammation and edema, which is at least partially reversible following initiation of HCV DAA therapy.
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Affiliation(s)
- Lenche Kostadinova
- The Louis Stokes VA Medical Center, Cleveland, Ohio.,Department of Medicine, University Hospitals Medical Center, and the Center for AIDS Research, Case Western Reserve University, Cleveland, Ohio
| | - Carey L Shive
- The Louis Stokes VA Medical Center, Cleveland, Ohio.,Department of Medicine, University Hospitals Medical Center, and the Center for AIDS Research, Case Western Reserve University, Cleveland, Ohio
| | - Elizabeth Zebrowski
- The Louis Stokes VA Medical Center, Cleveland, Ohio.,Department of Medicine, University Hospitals Medical Center, and the Center for AIDS Research, Case Western Reserve University, Cleveland, Ohio
| | - Brianna Fuller
- The Louis Stokes VA Medical Center, Cleveland, Ohio.,Department of Medicine, University Hospitals Medical Center, and the Center for AIDS Research, Case Western Reserve University, Cleveland, Ohio
| | - Kelsey Rife
- The Louis Stokes VA Medical Center, Cleveland, Ohio
| | - Amy Hirsch
- The Louis Stokes VA Medical Center, Cleveland, Ohio
| | - Anita Compan
- The Louis Stokes VA Medical Center, Cleveland, Ohio
| | | | - Yngve Falck-Ytter
- The Louis Stokes VA Medical Center, Cleveland, Ohio.,Department of Medicine, University Hospitals Medical Center, and the Center for AIDS Research, Case Western Reserve University, Cleveland, Ohio
| | - Daniel L Popkin
- The Louis Stokes VA Medical Center, Cleveland, Ohio.,Department of Dermatology, University Hospitals Medical Center, Case Western Reserve University, Cleveland, Ohio
| | - Donald D Anthony
- The Louis Stokes VA Medical Center, Cleveland, Ohio.,Department of Medicine, University Hospitals Medical Center, and the Center for AIDS Research, Case Western Reserve University, Cleveland, Ohio
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Kranidioti H, Chatzievagelinou C, Protopapas A, Papatheodoridi M, Zisimopoulos K, Evangelidou E, Antonakaki P, Vlachogiannakos J, Triantos C, Elefsiniotis I, Goulis J, Mela M, Anagnostou O, Tsoulas C, Deutsch M, Papatheodoridis G, Manolakopoulos S. Clinical and epidemiological characteristics of hepatitis C virus-infected people who inject drugs: a Greek descriptive analysis. Ann Gastroenterol 2018; 31:598-603. [PMID: 30174397 PMCID: PMC6102460 DOI: 10.20524/aog.2018.0293] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Accepted: 06/26/2018] [Indexed: 02/07/2023] Open
Abstract
Background It is estimated that 17,000 people who inject drugs (PWID) in Greece have hepatitis C virus (HCV) viremia. The aim of our study was to explore the characteristics of the HCV-infected, direct acting antiviral (DAA)-naïve PWID. Methods This is a retrospective analysis of PWID with HCV infection. We selected data from six liver clinics during the period from 1st May 2014 to 31st May 2017 in order to record the characteristics of infected PWID. Results We included 800 PWID with HCV infection (78.5% male, mean age 42±10 years) who had not received DAAs before 1st June 2017. One third of the patients had comorbidities (diabetes mellitus, arterial hypertension and psychological disorders); 70% were smokers, 27% alcohol users, 67% unemployed, 29% married, and 34% had education >12 years; 65% were attending addiction programs; 57% were receiving methadone and 36% buprenorphine. Sporadic or systemic drug use was reported by 37% while 1.4% and 2.9% had HIV and HBV coinfection, respectively. The genotype distribution was 20.5%, 4.6%, 3.3%, 61% and 10% for genotypes 1a, 1b, 2, 3 and 4, respectively. Mean (±SD) liver stiffness was 9±7 kPa and 21% of the patients had cirrhosis. Half of the patients were in the F0-F1 stage of liver disease, defined as stiffness ≤7 kPa. Conclusions Our real-life data suggest that HCV genotype 3 remains the predominant genotype among PWID. One third of PWID had comorbidities and one-fifth cirrhosis. Half of PWID had early-stage liver disease and remained without access to DAAs according to the Greek prioritization criteria.
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Affiliation(s)
- Hariklia Kranidioti
- 2 Academic Department of Internal Medicine, Hippokration General Hospital, Athens (Hariklia Kranidioti, Pinelopi Antonakaki, Olga Anagnostou, Melanie Deutsch, Spilios Manolakopoulos), Greece
| | - Christina Chatzievagelinou
- Department of Gastroenterology, Evangelismos-Opthalmiatrion Athinon-Polykliniki Hospitals, Athens (Christina Chatzievagelinou, Maria Mela), Greece
| | - Adonis Protopapas
- 4 Academic Department of Internal Medicine, Hippokration General Hospital, Thessaloniki (Adonis Protopapas, John Goulis), Greece
| | - Margarita Papatheodoridi
- Academic Department of Gastroenterology, Laiko General Hospital, Athens (Margarita Papatheodoridi, John Vlachogiannakos, George Papatheodoridis, Spilios Manolakopoulos), Greece
| | - Konstantinos Zisimopoulos
- Department of Gastroenterology, University of Patras (Konstantinos Zisimopoulos, Christos Triantos), Greece
| | - Eftychia Evangelidou
- "Agioi Anargyroi" General and Oncology Hospital of Kifissia, Athens (Eftychia Evangelidou, Ioannis Elefsiniotis), Greece
| | - Pinelopi Antonakaki
- 2 Academic Department of Internal Medicine, Hippokration General Hospital, Athens (Hariklia Kranidioti, Pinelopi Antonakaki, Olga Anagnostou, Melanie Deutsch, Spilios Manolakopoulos), Greece
| | - John Vlachogiannakos
- Academic Department of Gastroenterology, Laiko General Hospital, Athens (Margarita Papatheodoridi, John Vlachogiannakos, George Papatheodoridis, Spilios Manolakopoulos), Greece
| | - Christos Triantos
- Department of Gastroenterology, University of Patras (Konstantinos Zisimopoulos, Christos Triantos), Greece
| | - Ioannis Elefsiniotis
- "Agioi Anargyroi" General and Oncology Hospital of Kifissia, Athens (Eftychia Evangelidou, Ioannis Elefsiniotis), Greece
| | - John Goulis
- 4 Academic Department of Internal Medicine, Hippokration General Hospital, Thessaloniki (Adonis Protopapas, John Goulis), Greece
| | - Maria Mela
- Department of Gastroenterology, Evangelismos-Opthalmiatrion Athinon-Polykliniki Hospitals, Athens (Christina Chatzievagelinou, Maria Mela), Greece
| | - Olga Anagnostou
- 2 Academic Department of Internal Medicine, Hippokration General Hospital, Athens (Hariklia Kranidioti, Pinelopi Antonakaki, Olga Anagnostou, Melanie Deutsch, Spilios Manolakopoulos), Greece
| | | | - Melanie Deutsch
- 2 Academic Department of Internal Medicine, Hippokration General Hospital, Athens (Hariklia Kranidioti, Pinelopi Antonakaki, Olga Anagnostou, Melanie Deutsch, Spilios Manolakopoulos), Greece
| | - George Papatheodoridis
- Academic Department of Gastroenterology, Laiko General Hospital, Athens (Margarita Papatheodoridi, John Vlachogiannakos, George Papatheodoridis, Spilios Manolakopoulos), Greece
| | - Spilios Manolakopoulos
- 2 Academic Department of Internal Medicine, Hippokration General Hospital, Athens (Hariklia Kranidioti, Pinelopi Antonakaki, Olga Anagnostou, Melanie Deutsch, Spilios Manolakopoulos), Greece.,Academic Department of Gastroenterology, Laiko General Hospital, Athens (Margarita Papatheodoridi, John Vlachogiannakos, George Papatheodoridis, Spilios Manolakopoulos), Greece
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Sagnelli E, Starace M, Minichini C, Pisaturo M, Macera M, Sagnelli C, Coppola N. Resistance detection and re-treatment options in hepatitis C virus-related chronic liver diseases after DAA-treatment failure. Infection 2018; 46:761-783. [PMID: 30084057 DOI: 10.1007/s15010-018-1188-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2018] [Accepted: 07/30/2018] [Indexed: 12/12/2022]
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48
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Lund Laursen T, Brøckner Siggard C, Kazankov K, Damgaard Sandahl T, Møller HJ, Ong A, Douglas MW, George J, Tarp B, Hagelskjaer Kristensen L, Lund Laursen A, Hiramatsu A, Nakahara T, Chayama K, Grønbaek H. Rapid and persistent decline in soluble CD163 with successful direct-acting antiviral therapy and associations with chronic hepatitis C histology. Scand J Gastroenterol 2018; 53:986-993. [PMID: 29987961 DOI: 10.1080/00365521.2018.1481996] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIM Soluble CD 163 (sCD163) is released from activated liver macrophages in chronic viral hepatitis C (HCV) and serum levels reflect liver disease severity. The impact of direct-acting antiviral (DAA)-therapy on sCD163-levels and the ability of sCD163 to predict the presence of liver fibrosis remain unclear. In a combined observational and prospective study, we aimed to investigate changes in sCD163 with DAA-treatment, to investigate associations between sCD163 and histopathological activity and fibrosis and to validate the sCD163-based fibrosis score in HCV-patients. METHODS We examined three groups of patients: an Australian (n = 28) treated with pegylated-interferon and a first-generation DAA, a Danish (n = 38) treated with sofosbuvir-based DAA-regimens and a Japanese (n = 562) assessed for activity and fibrosis (Metavir scoring system) in liver biopsies. Serum sCD163-levels were quantified by ELISA. RESULTS Thirteen (46%) of the Australian patients achieved sustained virological response (SVR) and only these patients had significant decreases in sCD163-levels (2.7 (95%CI:1.9-3.6) vs. 4.1(2.9-5.7) mg L - 1, p = .008). In the Danish group, 37 (97%) patients achieved SVR at 12-weeks post-treatment with 32% reduction in sCD163-levels (5.0 (4.3-5.8) vs. 7.4 (6.3-8.7), p < .001). The decline was rapid and persisted 12 months after treatment cessation (p < .007). sCD163 levels increased in parallel with inflammatory activity and fibrosis (p < .001). The sCD163-based fibrosis score outperformed established fibrosis scores for significant fibrosis (areas under the receiver operating characteristics curves (AUROCs): 0.79 (0.75-0.83) vs. aspartate aminotransferase to platelet ratio index (APRI) 0.73 (0.69-0.77), Fibrosis-4 (FIB-4) 0.74 (0.70-0.78), p < .001). CONCLUSION sCD163-levels decline rapidly with successful DAA therapy and are associated with histological inflammatory activity and fibrosis, confirming a key role for macrophages in HCV inflammation and fibrosis and supporting sCD163 as a biomarker of treatment response.
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Affiliation(s)
- Tea Lund Laursen
- a Department of Hepatology & Gastroenterology , Aarhus University Hospital , Aarhus , Denmark
| | | | - Konstantin Kazankov
- a Department of Hepatology & Gastroenterology , Aarhus University Hospital , Aarhus , Denmark
| | - Thomas Damgaard Sandahl
- a Department of Hepatology & Gastroenterology , Aarhus University Hospital , Aarhus , Denmark
| | - Holger Jon Møller
- b Department of Clinical Biochemistry , Aarhus University Hospital , Aarhus , Denmark
| | - Adrian Ong
- c Storr Liver Centre , Westmead Institute for Medical Research, Westmead Hospital and University of Sydney , Sydney , Australia
| | - Mark W Douglas
- c Storr Liver Centre , Westmead Institute for Medical Research, Westmead Hospital and University of Sydney , Sydney , Australia
| | - Jacob George
- c Storr Liver Centre , Westmead Institute for Medical Research, Westmead Hospital and University of Sydney , Sydney , Australia
| | - Britta Tarp
- d Diagnostic Centre , Silkeborg Regional Hospital , Silkeborg , Denmark
| | | | - Alex Lund Laursen
- f Department of Infectious Diseases , Aarhus University Hospital , Aarhus , Denmark
| | - Akira Hiramatsu
- g Department of Gastroenterology and Metabolism , Institute of Biomedical and Health Sciences, Hiroshima University , Hiroshima , Japan
| | - Takashi Nakahara
- g Department of Gastroenterology and Metabolism , Institute of Biomedical and Health Sciences, Hiroshima University , Hiroshima , Japan
| | - Kazuaki Chayama
- g Department of Gastroenterology and Metabolism , Institute of Biomedical and Health Sciences, Hiroshima University , Hiroshima , Japan.,h Laboratory for Digestive Diseases , RIKEN Center for Integrative Medical Sciences , Hiroshima , Japan
| | - Henning Grønbaek
- a Department of Hepatology & Gastroenterology , Aarhus University Hospital , Aarhus , Denmark
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49
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Saraiya N, Yopp AC, Rich NE, Odewole M, Parikh ND, Singal AG. Systematic review with meta-analysis: recurrence of hepatocellular carcinoma following direct-acting antiviral therapy. Aliment Pharmacol Ther 2018; 48:127-137. [PMID: 29851093 PMCID: PMC6019180 DOI: 10.1111/apt.14823] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2018] [Revised: 03/22/2018] [Accepted: 05/06/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Although studies suggest decreased incident hepatocellular carcinoma (HCC) after direct-acting antivirals (DAA), data are conflicting regarding HCC recurrence and aggressiveness in patients who have a history of HCC with complete response. AIM Characterize HCC recurrence patterns after DAA therapy. METHODS Two reviewers searched MEDLINE and SCOPUS from January 2015 to December 2017 and identified studies evaluating HCC recurrence patterns following DAA therapy. A pooled estimate was calculated using the DerSimonian and Laird method for a random effects model. The study was conducted in accordance with PRISMA guidelines. RESULTS Among 24 studies (n = 1820 patients), the proportion of patients with HCC recurrence following DAA therapy ranged from 0% to 59% (pooled estimate 24.4%; 95% CI: 18.4%-30.4%). Among 11 full text manuscripts, pooled HCC recurrence was 21.9% (95% CI: 16.2%-28.3%). Factors associated with recurrence included history of prior HCC recurrence and a shorter interval between HCC complete response and DAA initiation. Nine studies comparing DAA-treated and interferon-treated or untreated patients found similar recurrence among DAA-treated patients. Most (77.8%) patients with HCC recurrence were detected at an early tumour stage, of whom 64.7% received curative treatment. Study limitations included heterogeneous cohorts, potential misclassification of HCC absence prior to DAA, ascertainment bias for recurrence, and short durations of follow-up. CONCLUSIONS Current data suggest acceptable HCC recurrence rates after DAA therapy, particularly if DAA therapy is delayed at least 6 months after HCC complete response. However, data characterising HCC recurrence after DAA therapy are of limited quality, highlighting the need for high quality prospective studies.
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Affiliation(s)
- Neema Saraiya
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
| | - Adam C. Yopp
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX
| | - Nicole E. Rich
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
| | - Mobolaji Odewole
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
| | - Neehar D. Parikh
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | - Amit G. Singal
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX,Department of Clinical Sciences, University of Texas Southwestern, Dallas, TX
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50
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Cacciola I, Filomia R, Alibrandi A, Franzè MS, Caccamo G, Maimone S, Saitta C, Saffioti F, Squadrito G, Raimondo G. Hypergammaglobulinemia is a strong predictor of disease progression, hepatocellular carcinoma, and death in patients with compensated cirrhosis. Liver Int 2018; 38:1220-1229. [PMID: 29194934 DOI: 10.1111/liv.13649] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2017] [Accepted: 11/19/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS The outcome of compensated cirrhosis may vary considerably and cannot be predicted by routinely performed tests at present. The aim of this study was to evaluate possible predictors of clinical evolution in patients with Child-Pugh (C-P) class A cirrhosis because of untreatable causes by analysing clinical/biochemical/instrumental parameters evaluated at the time of diagnosis and during the subsequent long-lasting follow-up. METHODS Two hundred and seventy-two consecutive C-P class A cirrhotic patients (155 males; median age 63 years, range 34-81) were analysed. All patients were followed up for a median time of 96 months (range 21-144) through periodically performed clinical/biochemical/ultrasonographic and esophagogastroduodenoscopic examinations. RESULTS During the follow-up, 97 individuals (36%) were clinically stable, 104 (38%) developed hepatocellular carcinoma (HCC) and 71 (26%) progressed towards C-P class B/C without developing cancer. One hundred and thirty-one patients (48%) died or underwent liver transplantation. Multivariate regression analysis showed that clinical stability was significantly associated with older age (P < .001), the absence of diabetes (P = .04) and of oesophageal varices (P < .001), serum albumin >3.5 gr/dL (P = .01) and gamma globulin <1.8 gr/dL (P = .01). HCC development was significantly associated with younger age (P = .01) and serum gamma globulin values ≥1.8 gr/dL (P < .001). C-P score progression was associated with oesophageal varices (P < .001), lower serum albumin (P = .03) and cholesterol (P = .01) values, and hypergammaglobulinemia (P = .02). Death was associated with younger age (P < .001) and hypergammaglobulinemia (P = .01). Multivariate Cox regression analysis and Kaplan-Meier's survival test confirmed that gammaglobulinemia ≥1.8 g/dL was a significant predictor of death (P < .02, and P < .01 respectively). CONCLUSIONS Hypergammaglobulinemia identifies C-P class A cirrhotic patients at higher risk of disease progression, HCC development and death.
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Affiliation(s)
- Irene Cacciola
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy.,Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Roberto Filomia
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy.,Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Angela Alibrandi
- Department of Economics, Unit of Statistical and Mathematical Sciences, University of Messina, Messina, Italy
| | - Maria Stella Franzè
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy.,Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Gaia Caccamo
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Sergio Maimone
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Carlo Saitta
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
| | - Francesca Saffioti
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Giovanni Squadrito
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy.,Department of Human Pathology, University of Messina, Messina, Italy
| | - Giovanni Raimondo
- Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy.,Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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