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Al-Naamani KM, Omar H, Al Busafi SA, Al Shuaili HH, Al-Naamani Z, Al-Khabori M, Said EA, AlKalbani AH, Kamath BR, Emad B, Daar S, Alhajri L, AlKalbani A, AlFarsi Z, Alzuhaibi H. Real-World Experience, Effectiveness, and Safety of Direct-Acting Antivirals for the Treatment of Hepatitis C in Oman: A Cross-Sectional, Multicenter Study. J Clin Med 2024; 13:7411. [PMID: 39685869 DOI: 10.3390/jcm13237411] [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: 09/28/2024] [Revised: 11/20/2024] [Accepted: 11/30/2024] [Indexed: 12/18/2024] Open
Abstract
Background: The advent of direct-acting antiviral (DAA) therapy has revolutionized the treatment landscape of the hepatitis C virus (HCV) infection. This study aimed to provide a comprehensive research study of the real-world effectiveness and safety of DAA treatment, representing the first study conducted in the Omani population. Methods: A cross-sectional study was conducted including 375 HCV patients with different genotypes, treated using different DAA regimens, with or without ribavirin, between January 2012 and December 2020 at the Sultan Qaboos University Hospital and the medical city for military and security services, two tertiary hospitals in Muscat, Oman. The rate of sustained virologic response 12 weeks after completing the regimen (SVR-12) was analyzed as the primary outcome. Secondary outcomes included treatment safety and adverse events related to DAA therapy, as reported by patients and treating physicians. Results: A total of 375 patients were included in the study, with a mean age of 47.3 ± 15.4 years. Most were male (59.2%) and treatment-naïve (71.7%). The prevalence of liver cirrhosis was 19.7%, while 4.0% had hepatocellular carcinoma (HCC). The SVR-12 rate among treatment-naïve and treatment-experienced patients was 95.0% and 93.4%, respectively. Several parameters were associated with DAA treatment failure, including liver cirrhosis (p = 0.004) and active HCC (p = 0.009). Following SVR-12, significant improvements were observed in alanine transaminase, bilirubin, and albumin levels, Fibrosis-4 Index, and liver stiffness measurements compared to baseline (p <0.001 each). No significant adverse effects were reported. Conclusions: Based on our real-world experience, DAAs are highly effective in treating patients with HCV infection in Oman, with an excellent tolerability and safety profile.
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Affiliation(s)
- Khalid M Al-Naamani
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, The Medical City of Military and Security Services, Muscat 111, Oman
| | - Heba Omar
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, The Medical City of Military and Security Services, Muscat 111, Oman
- Endemic Medicine and Hepatology Department, Faculty of Medicine, Cairo University, Cairo 11652, Egypt
| | - Said A Al Busafi
- Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
| | - Halima H Al Shuaili
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, The Medical City of Military and Security Services, Muscat 111, Oman
| | - Zakariya Al-Naamani
- Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
| | - Murtadha Al-Khabori
- Department of Hematology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
| | - Elias A Said
- Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
| | - Abdullah H AlKalbani
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, The Medical City of Military and Security Services, Muscat 111, Oman
| | - B R Kamath
- Department of Internal Medicine, Division of Gastroenterology & Hepatology, The Medical City of Military and Security Services, Muscat 111, Oman
| | - Bashar Emad
- Department of Medicine, Jordan University of Science and Technology, Ar-Ramtha 22110, Jordan
| | - Shahina Daar
- Department of Hematology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
| | - Lolo Alhajri
- Department of Nursing, The Medical City of Military and Security Services, Muscat 111, Oman
| | - Alya AlKalbani
- Department of Nursing, The Medical City of Military and Security Services, Muscat 111, Oman
| | - Zainab AlFarsi
- Department of Nursing, Sultan Qaboos University Hospital, University Medical City, Muscat 123, Oman
| | - Haifa Alzuhaibi
- Department of Nursing, Sultan Qaboos University Hospital, University Medical City, Muscat 123, Oman
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Hsieh MH, Kao TY, Hsieh TH, Kao CC, Peng CY, Lai HC, Cheng HH, Ho MW, Chi CY, Kao JT. Predictors of liver fibrosis changes assessed by paired liver biopsies in chronic hepatitis C patients treated with direct-acting antivirals. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2024; 57:840-853. [PMID: 39216998 DOI: 10.1016/j.jmii.2024.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 07/15/2024] [Accepted: 08/12/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND/PURPOSE There are limited studies performing paired liver biopsies in chronic hepatitis C (CHC) patients treated with direct-acting antivirals (DAA). We aimed to investigate the predictors of liver fibrosis changes assessed by paired liver biopsies in these patients. METHODS From March 2017 to March 2020, 113 CHC patients were prospectively enrolled to receive DAA therapy at our hospital. Paired liver biopsies were performed at baseline and 12 weeks after the end of treatment. RESULTS Among the entire cohort, the rate of sustained virological response (SVR) was 100%. Four baseline variables independently predicted fibrosis regression, including age <65 years [odds ratio (OR) = 2.725, p = 0.036], fibrosis stages (METAVIR scores) < 3 (OR = 4.874, p = 0.040), hemoglobin levels ≥12.5 g/dL (OR = 3.538, p = 0.029), and platelet counts ≥160 103/μL (OR = 2.958, p = 0.023). Besides, five independent predictors of fibrosis progression included baseline age ≥66 years (OR = 16.351, p = 0.024), body mass index (BMI) ≥26.5 kg/m2 (OR = 21.666, p = 0.009), sofosbuvir/ribavirin use (OR = 29.465, p = 0.031), platelet counts <119 103/μL (OR = 33.739, p = 0.026), and the absence of alanine aminotransferase (ALT) levels declining from >35 U/L at baseline to ≤35 U/L at 4 weeks after baseline (OR = 284.534, p = 0.026). CONCLUSION For DAA-treated CHC patients, those with baseline age <65 years, fibrosis stages <3, hemoglobin levels ≥12.5 g/dL, or platelet counts ≥160 103/μL are more likely to attain fibrosis regression. There is a higher risk of fibrosis progression in those with baseline age ≥66 years, BMI ≥26.5 kg/m2, sofosbuvir/ribavirin use, platelet counts <119 103/μL, or the absence of early ALT normalization at 4 weeks after baseline.
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Affiliation(s)
- Ming-Han Hsieh
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Tzu-Yu Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Ting-Hui Hsieh
- Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Chi Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Yuan Peng
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Hsueh-Chou Lai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Hsing-Hung Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Mao-Wang Ho
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chih-Yu Chi
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Jung-Ta Kao
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
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Kim MN, Han JW, An J, Kim BK, Jin YJ, Kim SS, Lee M, Lee HA, Cho Y, Kim HY, Shin YR, Yu JH, Kim MY, Choi Y, Chon YE, Cho EJ, Lee EJ, Kim SG, Kim W, Jun DW, Kim SU. KASL clinical practice guidelines for noninvasive tests to assess liver fibrosis in chronic liver disease. Clin Mol Hepatol 2024; 30:S5-S105. [PMID: 39159947 PMCID: PMC11493350 DOI: 10.3350/cmh.2024.0506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 08/12/2024] [Accepted: 08/16/2024] [Indexed: 08/21/2024] Open
Affiliation(s)
- Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Ji Won Han
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Young-Joo Jin
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Seung-seob Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Hee Yeon Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yu Rim Shin
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jung Hwan Yu
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Young Eun Chon
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Eun Joo Lee
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - on behalf of The Korean Association for the Study of the Liver (KASL)
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Korea
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Nakano M, Kuromatsu R, Kawaguchi T. Ultrasonographic Assessment of Tissue Stiffness: Recent Progress in Transient Elastography and Shear Wave Elastography in the Liver and Various Organs. Kurume Med J 2024; 70:1-10. [PMID: 38763738 DOI: 10.2739/kurumemedj.ms7012010] [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] [Indexed: 05/21/2024]
Abstract
Ultrasonography is a noninvasive and widely accessible modality in clinical practice. Recently, ultrasonography has been used to evaluate tissue stiffness; the two representative techniques are transient elastography (FibroScan®) and shear wave elastography. These modalities are now generally used for the assessment of liver fibrosis, the prediction of hepatocarcinogenesis, and determining prognosis. In addition, shear wave elastography is available, not only for the liver but also for various other organs, including the breast and brain. In the breast and brain, shear wave elastography distinguishes malignant lesions from benign ones. Moreover, shear wave elastography can be useful for differentiating between ischemic and hemorrhagic strokes. This review summarizes the recent progress in transient elastography and shear wave elastography of the liver and introduces the advantages of ultrasonographic assessment of tissue stiffness in various organs, including the breast, brain, kidney, heart, thyroid, pancreas, muscle, and bone.
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Affiliation(s)
- Masahito Nakano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
| | - Ryoko Kuromatsu
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
- Ultrasound Diagnostic Center, Kurume University Hospital
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine
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Sirinawasatien A, Supawan P. Sustained virological response in chronic hepatitis C patients by direct-acting antiviral treatment significantly reduces liver stiffness over 24 weeks posttreatment. Medicine (Baltimore) 2024; 103:e38096. [PMID: 38728473 PMCID: PMC11081621 DOI: 10.1097/md.0000000000038096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 04/11/2024] [Indexed: 05/12/2024] Open
Abstract
To investigate whether direct-acting antiviral (DAA) treatment affected liver fibrosis testing, including transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and Fibrosis-4 (FIB-4) index, after establishing a sustained virological response for 24 weeks. This prospective cohort study was conducted between October 1, 2019, and September 30, 2020, at Rajavithi Hospital, Bangkok, Thailand. All the patients had significant liver fibrosis (TE ≥ 7.0 kPa) at baseline and completed 12 weeks of DAA therapy. After achieving SVR, liver stiffness measurements were repeated for at least 24 weeks. The primary outcome was a > 30% improvement in TE score at the end of the study compared to baseline. A multivariate logistic regression model was used to identify the parameters associated with the primary outcome. Temporal changes in APRI and FIB-4 indices from baseline to 24 weeks posttreatment were also examined. A total of 110 chronic HCV patients were included in our cohort, of which 57 (52.3%) achieved the primary outcome. The median TE decreased from 15.05 (8.76-23.68) kPa at pretreatment to 9.60 (6.50-14.40) kPa at 24 weeks posttreatment (P < .001). Those who had a baseline TE ≥ 9.5 kPa had higher odds of meeting the primary outcome, and this remained significant after adjusting for age, sex, baseline body mass index, underlying diabetes mellitus, HCV genotype 3, baseline laboratory levels, and treatment regimens (OR 3.04; 95% CI 1.22-7.60, P = .017). Similar to TE, the median APRI and FIB-4 index displayed a considerable reduction from baseline to 24 weeks after successful therapy. Modern DAA treatment has been associated with considerable improvement in liver stiffness measured by TE in chronic HCV patients who achieve SVR, with roughly 52% of patients experiencing a reduction of > 30% in TE over 24 weeks posttreatment compared to baseline. This probably indicates early fibrosis regression, although the effect of resolution of inflammation after treatment completion cannot be ruled out.
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Affiliation(s)
- Apichet Sirinawasatien
- Division of Gastroenterology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand
| | - Paweenuch Supawan
- Division of Gastroenterology, Department of Medicine, Buriram hospital, Medical Education Center, Suranaree University, Buriram, Thailand
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Cespiati A, Coelho Rodrigues I, Santos I, Policarpo S, Carvalhana S, Fracanzani AL, Cortez-Pinto H. Effect of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, and associated metabolic comorbidities: A systematic review. Liver Int 2024; 44:1075-1092. [PMID: 38385567 DOI: 10.1111/liv.15876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 12/11/2023] [Accepted: 02/08/2024] [Indexed: 02/23/2024]
Abstract
BACKGROUND AND AIMS The beneficial effect of Hepatitis C virus (HCV) eradication by direct antiviral agents (DAAs) on liver fibrosis is well defined. Despite this, the impact of viral eradication in both hepatic and extra-hepatic metabolic features is underreached. This systematic review aimed to synthesize the evidence on the impact of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, glucidic impairment, dyslipidaemia, and weight gain. METHODS A systematic search of the existing literature (up to December 2022) identified 97 original studies that fulfilled the inclusion criteria. RESULTS Whereas total cholesterol and low-density lipoprotein (LDL) seem to increase after viral eradication, the cardiovascular damage expressed as carotid plaques and intima-media thickness seems to improve. Otherwise, the effect on liver steatosis, glucidic homeostasis, and weight seems to be strictly dependent on the presence of baseline metabolic disorders. CONCLUSION Despite high heterogeneity and relatively short follow-up of included studies, we can conclude that the presence of metabolic risk factors should be strictly evaluated due to their impact on liver steatosis, glucidic and lipid homeostasis, and on weight gain to better identify patients at risk of liver disease progression despite the virus eradication.
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Affiliation(s)
- Annalisa Cespiati
- Unit of Medicine and Metabolic Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Inês Coelho Rodrigues
- Departamento de Gastrenterologia, Centro Hospitalar Universitário Lisboa Norte, Departamento de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
| | - Inês Santos
- Laboratório de Nutrição, Faculdade de Medicina, Centro Académico de Medicina de Lisboa, Universidade de Lisboa, Lisbon, Portugal
- Faculdade de Medicina, Instituto de Saúde Ambiental (ISAMB), Universidade de Lisboa, Lisbon, Portugal
| | - Sara Policarpo
- Laboratório de Nutrição, Faculdade de Medicina, Centro Académico de Medicina de Lisboa, Universidade de Lisboa, Lisbon, Portugal
- Serviço de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, E.P.E., Lisbon, Portugal
| | - Sofia Carvalhana
- Departamento de Gastrenterologia, Centro Hospitalar Universitário Lisboa Norte, Departamento de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
- Clínica Universitária de Gastrenterologia, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Anna Ludovica Fracanzani
- Unit of Medicine and Metabolic Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Helena Cortez-Pinto
- Departamento de Gastrenterologia, Centro Hospitalar Universitário Lisboa Norte, Departamento de Dietética e Nutrição, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
- Clínica Universitária de Gastrenterologia, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
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Matsuzaki S, Hase E, Takanari H, Hayashi Y, Hayashi Y, Oshikata H, Minamikawa T, Kimura S, Ichimura-Shimizu M, Yasui T, Harada M, Tsuneyama K. Quantification of collagen fiber properties in alcoholic liver fibrosis using polarization-resolved second harmonic generation microscopy. Sci Rep 2023; 13:22100. [PMID: 38092851 PMCID: PMC10719293 DOI: 10.1038/s41598-023-48887-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 11/30/2023] [Indexed: 12/17/2023] Open
Abstract
Liver fibrosis is assessed mainly by conventional staining or second harmonic generation (SHG) microscopy, which can only provide collagen content in fibrotic area. We propose to use polarization-resolved SHG (PR-SHG) microscopy to quantify liver fibrosis in terms of collagen fiber orientation and crystallization. Liver samples obtained from autopsy cases with fibrosis stage of F0-F4 were evaluated with an SHG microscope, and 12 consecutive PR-SHG images were acquired while changing the polarization azimuth angle of the irradiated laser from 0° to 165° in 15° increments using polarizer. The fiber orientation angle (φ) and degree (ρ) of collagen were estimated from the images. The SHG-positive area increased as the fibrosis stage progressed, which was well consistent with Sirius Red staining. The value of φ was random regardless of fibrosis stage. The mean value of ρ (ρ-mean), which represents collagen fiber crystallinity, varied more as fibrosis progressed to stage F3, and converged to a significantly higher value in F4 than in other stages. Spatial dispersion of ρ (ρ-entropy) also showed increased variation in the stage F3 and decreased variation in the stage F4. It was shown that PR-SHG could provide new information on the properties of collagen fibers in human liver fibrosis.
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Affiliation(s)
- Saya Matsuzaki
- Department of Radiology, Institute of Biomedical Sciences, Tokushima University Graduate School of Medicine, Tokushima, Japan
| | - Eiji Hase
- Division of Interdisciplinary Research for Medicine and Photonics, Institute of Post-LED Photonics, Tokushima University, Tokushima, Japan
| | - Hiroki Takanari
- Division of Interdisciplinary Research for Medicine and Photonics, Institute of Post-LED Photonics, Tokushima University, Tokushima, Japan
- Department of Legal Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Yuri Hayashi
- Division of Interdisciplinary Research for Medicine and Photonics, Institute of Post-LED Photonics, Tokushima University, Tokushima, Japan
- Tokushima University Faculty of Medicine, Tokushima, Japan
| | - Yusaku Hayashi
- Division of Interdisciplinary Research for Medicine and Photonics, Institute of Post-LED Photonics, Tokushima University, Tokushima, Japan
- Tokushima University Faculty of Medicine, Tokushima, Japan
| | - Haruto Oshikata
- Division of Interdisciplinary Research for Medicine and Photonics, Institute of Post-LED Photonics, Tokushima University, Tokushima, Japan
- Tokushima University Faculty of Medicine, Tokushima, Japan
| | - Takeo Minamikawa
- Division of Interdisciplinary Research for Medicine and Photonics, Institute of Post-LED Photonics, Tokushima University, Tokushima, Japan
| | | | - Mayuko Ichimura-Shimizu
- Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School of Medicine, 3-18-15, Kuramoto, Tokushima, 770-8503, Japan
| | - Takeshi Yasui
- Division of Next-Generation Photonics, Institute of Post-LED Photonics, Tokushima University, Tokushima, Japan
| | - Masafumi Harada
- Department of Radiology, Institute of Biomedical Sciences, Tokushima University Graduate School of Medicine, Tokushima, Japan
| | - Koichi Tsuneyama
- Division of Interdisciplinary Research for Medicine and Photonics, Institute of Post-LED Photonics, Tokushima University, Tokushima, Japan.
- Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School of Medicine, 3-18-15, Kuramoto, Tokushima, 770-8503, Japan.
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Almutawakel S, Halleck F, Dürr M, Grittner U, Schrezenmeier E, Budde K, Althoff CE, Hamm B, Sack I, Fischer T, Marticorena Garcia SR. Shear Wave Elastography for Assessing Liver Stiffness in HCV-Infected Kidney Transplant Recipients after Direct-Acting Antiviral Treatment: A Comparative Study with Magnetic Resonance Elastography. J Clin Med 2023; 12:7547. [PMID: 38137615 PMCID: PMC10743898 DOI: 10.3390/jcm12247547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 11/22/2023] [Accepted: 12/04/2023] [Indexed: 12/24/2023] Open
Abstract
Hepatitis C virus (HCV) infection can lead to hepatic fibrosis. The advent of direct-acting antivirals (DAAs) has substantially improved sustained virological response (SVR) rates. In this context, kidney transplant recipients (KTRs) are of particular interest due to their higher HCV infection rates and uncertain renal excretion and bioavailability of DAAs. We investigated liver stiffness after DAA treatment in 15 HCV-infected KTRs using ultrasound shear wave elastography (SWE) in comparison with magnetic resonance elastography (MRE). KTRs were treated with DAAs (daclatasvir and sofosbuvir) for three months and underwent SWE at baseline, end of therapy (EOT), and 3 (EOT+3) and 12 months (EOT+12) after EOT. Fourteen patients achieved SVR12. Shear wave speed (SWS)-as a surrogate parameter for tissue stiffness-was substantially lower at all three post-therapeutic timepoints compared with baseline (EOT: -0.42 m/s, p < 0.01; CI = -0.75--0.09, EOT+3: -0.43 m/s, p < 0.01; CI = -0.75--0.11, and EOT+12: -0.52 m/s, p < 0.001; CI = -0.84--0.19), suggesting liver regeneration after viral eradication and end of inflammation. Baseline SWS correlated positively with histopathological fibrosis scores (r = 0.48; CI = -0.11-0.85). Longitudinal results correlated moderately with APRI (r = 0.41; CI = 0.12-0.64) but not with FIB-4 scores (r = 0.12; CI = -0.19-0.41). Although higher on average, SWE-derived measurements correlated strongly with MRE (r = 0.64). In conclusion, SWE is suitable for non-invasive therapy monitoring in KTRs with HCV infection.
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Affiliation(s)
- Salma Almutawakel
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (S.A.)
| | - Fabian Halleck
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
| | - Michael Dürr
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
| | - Ulrike Grittner
- Institute of Biometry and Clinical Epidemiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
| | - Eva Schrezenmeier
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
| | - Klemens Budde
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
| | - Christian E. Althoff
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (S.A.)
| | - Bernd Hamm
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (S.A.)
| | - Ingolf Sack
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (S.A.)
| | - Thomas Fischer
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (S.A.)
| | - Stephan R. Marticorena Garcia
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (S.A.)
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9
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Kim SH, Park SH, Lee H. Machine learning for predicting hepatitis B or C virus infection in diabetic patients. Sci Rep 2023; 13:21518. [PMID: 38057379 PMCID: PMC10700585 DOI: 10.1038/s41598-023-49046-9] [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: 04/03/2023] [Accepted: 12/04/2023] [Indexed: 12/08/2023] Open
Abstract
Highly prevalent hepatitis B and hepatitis C virus (HBV and HCV) infections have been reported among individuals with diabetes. Given the frequently asymptomatic nature of hepatitis and the challenges associated with screening in some vulnerable populations such as diabetes patients, we conducted an investigation into the performance of various machine learning models for the identification of hepatitis in diabetic patients while also evaluating the significance of features. Analyzing NHANES data from 2013 to 2018, machine learning models were evaluated; random forest (RF), support vector machine (SVM), eXtreme Gradient Boosting (XGBoost), and least absolute shrinkage and selection operator (LASSO) along with stacked ensemble model. We performed hyperparameter tuning to improve the performance of the model, and selected important predictors using the best performance model. LASSO showed the highest predictive performance (AUC-ROC = 0.810) rather than other models. Illicit drug use, poverty, and race were highly ranked as predictive factors for developing hepatitis in diabetes patients. Our study demonstrated that a machine-learning-based model performed optimally in the detection of hepatitis among diabetes patients, achieving high performance. Furthermore, models and predictors evaluated from the current study, we expect, could be supportive information for developing screening or treatment methods for hepatitis care in diabetes patients.
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Affiliation(s)
- Sun-Hwa Kim
- Department of Clinical Medicinal Sciences, Konyang University, Nonsan, Republic of Korea
| | - So-Hyeon Park
- Department of Clinical Medicinal Sciences, Konyang University, Nonsan, Republic of Korea
| | - Heeyoung Lee
- College of Pharmacy, Inje University, Gimhae, Republic of Korea.
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10
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Bojanic K, Bogojevic MS, Vukadin S, Sikora R, Ivanac G, Lucic NR, Smolic M, Tabll AA, Wu GY, Smolic R. Noninvasive Fibrosis Assessment in Chronic Hepatitis C Infection: An Update. J Clin Transl Hepatol 2023; 11:1228-1238. [PMID: 37577224 PMCID: PMC10412701 DOI: 10.14218/jcth.2022.00365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 11/04/2022] [Accepted: 02/27/2023] [Indexed: 07/03/2023] Open
Abstract
Liver biopsy is historically the gold standard for liver fibrosis assessment of chronic hepatitis C patients. However, with the introduction and validation of noninvasive tests (NITs) to evaluate advanced fibrosis, and the direct-acting antiviral agents for treatment of chronic hepatitis C virus (HCV), the role of NITs have become even more complex. There is now need for longitudinal monitoring and elucidation of cutoff values for prediction of liver-related complication after sustained virological response. The aim of this report is to provide a critical overview of the various NITs available for the assessment of liver fibrosis in HCV patients.
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Affiliation(s)
- Kristina Bojanic
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Health Center Osijek-Baranja County, Osijek, Croatia
| | | | - Sonja Vukadin
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Renata Sikora
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Health Center Osijek-Baranja County, Osijek, Croatia
| | - Gordana Ivanac
- University Hospital Dubrava, Zagreb, Croatia
- School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Nikola Raguz Lucic
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Martina Smolic
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Ashraf A. Tabll
- Microbial Biotechnology Department, Biotechnology Research Institute, National Research Center, Giza, Egypt
- Egypt Center for Research and Regenerative Medicine (ECRRM), Cairo, Egypt
| | - George Y. Wu
- University of Connecticut Health Center, Farmington, CT, USA
| | - Robert Smolic
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
- Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
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11
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Niu B, Zang W, Zhou H, Mi Y, Lu C, Li P. Regression in hepatic fibrosis in elderly Chinese patients with hepatitis C receiving direct-acting antiviral treatment. BMC Gastroenterol 2023; 23:102. [PMID: 37013471 PMCID: PMC10069046 DOI: 10.1186/s12876-023-02732-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 03/20/2023] [Indexed: 04/05/2023] Open
Abstract
BACKGROUND Patients infected with Hepatitis C virus (HCV) are recommended to receive treatment with direct-acting antiviral agents (DAAs), which have been certified to obtain a high sustained virological response (SVR). However, little is known about the benefits of successful anti-viral treatment to elderly patients with hepatic fibrosis. In this study, we aimed to assess degree of fibrosis in elderly patients with chronic hepatitis C (CHC) treated with DAAs, and to evaluate the correlations between identified factors associated with these changes. METHODS This study retrospectively enrolled elderly patients with CHC who received DAAs in Tianjin Second People's Hospital from April 2018 to April 2021. The degree of liver fibrosis was assessed using serum biomarkers and transient elastography (TE) expressed as the liver stiffness (LSM), while the hepatic steatosis was evaluated by controlled attenuated parameter (CAP). Changes in factors related to hepatic fibrosis were examined following treatment with DAAs, and associated prognostic factors were further evaluated. RESULTS We included 347 CHC patients in our analysis, where 127 of these were elderly patients. For the elderly group, the median LSM was 11.6 (7.9-19.9) kPa, and this value was significantly reduced to 9.7 (6.2-16.6) kPa following DAA treatment. Similarly, GPR, FIB-4 and APRI indices were significantly reduced from 0.445 (0.275-1.022), 3.072 (2.047-5.129) and 0.833 (0.430-1.540) to 0.231 (0.155-0.412), 2.100 (1.540-3.034) and 0.336 (0.235-0.528), respectively. While in younger patients, the median LSM reduced from 8.8 (6.1-16.8) kPa to 7.2 (5.3-12.4) kPa, and the trends of GPR, FIB-4 and APRI were also consistent. The CAP in younger patients increased with statistical significance, but we did not observe any significant change in CAP for the elderly group. Based on multivariate analysis, age, LSM, and CAP before baseline were identified as determinants for LSM improvement in the elderly. CONCLUSION In this study, we found that elderly CHC patients treated with DAA had significantly lower LSM, GPR, FIB-4, and APRI values. DAA treatment did not significantly change CAP. Furthermore, we observed correlations between three noninvasive serological evaluation markers and LSM. Finally, age, LSM, and CAP were identified as independent predictors of fibrosis regression in elderly patients with CHC.
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Affiliation(s)
- Bin Niu
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, 300192, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China
| | - Wenqian Zang
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China
| | - Hui Zhou
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, 300192, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China
| | - Yuqiang Mi
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, China
| | - Chengzhen Lu
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, China
| | - Ping Li
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, 300192, China.
- Tianjin Research Institute of Liver Diseases, Tianjin, 300192, China.
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12
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Buckholz AP, Brown RS. Noninvasive Fibrosis Testing in Chronic Liver Disease Including Caveats. Clin Liver Dis 2023; 27:117-131. [PMID: 36400461 DOI: 10.1016/j.cld.2022.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Assessment of liver fibrosis is important as the range of liver disease management has expanded, rendering biopsy both imperfect and impractical in many situations. Noninvasive tests of fibrosis leverage laboratory, imaging and elastography techniques to estimate disease extent, often with the goal of identifying advanced fibrosis. This review attempts to summarize their utility across a broad range of possible clinical scenarios while considering the central tenets of health care quality: access, quality, and cost. For each test, it also discusses the caveats whereby each test may have reduced effectiveness and how to consider each in a typical clinical setting.
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Affiliation(s)
- Adam P Buckholz
- Division of Gastroenterology and Hepatology, NewYork-Presbyterian/Weill Cornell Medical Center, 1305 York Avenue 4th Floor, New York, NY 10021, USA
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, NewYork-Presbyterian/Weill Cornell Medical Center, 1305 York Avenue 4th Floor, New York, NY 10021, USA.
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13
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Huang PY, Chen CH, Tsai MJ, Yao CC, Wang HM, Kuo YH, Chang KC, Hung CH, Chuah SK, Tsai MC. Effects of direct anti-viral agents on the gut microbiota in patients with chronic hepatitis C. J Formos Med Assoc 2023; 122:157-163. [PMID: 36155707 DOI: 10.1016/j.jfma.2022.08.022] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 08/21/2022] [Accepted: 08/30/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND/PURPOSE Gut microbiology is associated with liver disease due to gut-liver circulation via the gut microbial-liver axis. There is a paucity of data regarding the effects of treatment to cure hepatitis C virus (HCV) infection on the gut microbiota. The aim of this study was to evaluate the fecal microbiota before and after treatment with direct antiviral agents (DAA) in patients with HCV infection. METHODS This prospective study was conducted at Kaohsiung Chung-Gung Memorial Hospital, Taiwan, between December 2019 and November 2020. We recruited patients with chronic hepatitis C (CHC) receiving DAA treatment. Fecal samples were collected twice: at baseline (before DAA treatment; CHC group) and 24 weeks after the end of treatment (EOT; SVR24 group), and once from healthy controls at baseline (control group). The taxonomic composition of the gut microbiota was determined using 16 S ribosomal RNA gene sequencing of stool samples. RESULTS A total of 60 patients with CHC and 60 healthy controls matched by age and gender were enrolled. All patients achieved a sustained virologic response (SVR). Alpha diversity was not significantly difference between any groups. Analysis of similarities (ANOSIM) revealed minor differences in the microbial community structure between the control group and CHC group (R = 0.0146, P = 0.098) and less significant differences between the CHC group and SVR24 group (R = -0.0139; P = 0.94). Three phyla and eight genera were differentially abundant between the control group and CHC group. CONCLUSION Individuals with CHC do not exhibit significant gut microbiota alterations and eradication of HCV by DAA is not associated with significant modification of the gut microbiota.
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Affiliation(s)
- Pao-Yuan Huang
- Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Mu-Jung Tsai
- Kaohsiung Municipal Kaohsiung Senior High School, Kaohsiung 807, Taiwan
| | - Chih-Chien Yao
- Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Hsin-Ming Wang
- Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Yuan-Hung Kuo
- Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Kuo-Chin Chang
- Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Seng-Kee Chuah
- Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Ming-Chao Tsai
- Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung 804, Taiwan.
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14
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Effect of Direct-Acting Antiviral Agents on Gastroesophageal Varices in Patients with Hepatitis C Virus-Related Cirrhosis. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58081077. [PMID: 36013545 PMCID: PMC9415929 DOI: 10.3390/medicina58081077] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Revised: 08/06/2022] [Accepted: 08/09/2022] [Indexed: 11/16/2022]
Abstract
Aim: In patients with hepatitis C virus-related liver cirrhosis (LC) who achieve sustained virological responses (SVRs) through treatment with direct-acting antiviral agents (DAAs), it remains unclear whether there are improvements in gastroesophageal varices (GEVs) and portal hypertension. We investigated changes in liver function and GEVs that occurred after DAA therapy. Materials and Methods: We evaluated the medical records of 195 patients with hepatitis C virus-related LC who received DAAs. A total of 171 patients achieved SVRs, among whom 36 had GEVs before or after receiving DAA therapy. The liver function, fibrosis, and GEVs were re-evaluated every 6 months after receiving DAA therapy. The risk factors for progressive GEVs were investigated. Results: DAA therapy resulted in improvements in liver function (indicated by aspartate transaminase, alanine transaminase, and serum albumin levels) and fibrosis (indicated by type IV collagen levels and the Fibrosis-4 index). After receiving DAA therapy, 27 patients had stable GEVs and 9 had progressive GEVs. With respect to GEV grades before DAA therapy, there was a significant difference between patients with stable and progressive GEVs (p = 0.027). Presence of grade-2 GEVs before starting DAA therapy was a risk factor for GEV progression (odds ratio: 5.83; p = 0.04). Patients with grade-2 GEVs had significantly shorter progression-free periods than those with grade < 2 GEVs (p = 0.025). Conclusions: DAA therapy does not ameliorate GEVs. Furthermore, grade-2 GEVs can worsen after DAA therapy. Therefore, patients with GEVs of grades ≥ 2 should undergo endoscopic surveillance after receiving DAAs.
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15
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Aydın NN, Köksal İ. An Evaluation of Chronic Hepatitis C Patients’ Responses to Direct-Acting Antivirals According to Transient Elastography and Serum Biomarkers. Egypt J Immunol 2022. [DOI: 10.4274/vhd.galenos.2022.2021-8-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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16
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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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Thanapirom K, Suksawatamnuay S, Tanpowpong N, Chaopathomkul B, Sriphoosanaphan S, Thaimai P, Srisoonthorn N, Treeprasertsuk S, Komolmit P. Non-invasive tests for liver fibrosis assessment in patients with chronic liver diseases: a prospective study. Sci Rep 2022; 12:4913. [PMID: 35318425 PMCID: PMC8941081 DOI: 10.1038/s41598-022-08955-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 03/15/2022] [Indexed: 12/11/2022] Open
Abstract
There is an urgent need of non-invasive tests (NITs) for monitoring treatment response and disease progression in chronic liver disease. Liver stiffness (LS) evaluated by transient elastography (TE), shear wave elastography (SWE), and magnetic resonance elastography (MRE) and serum markers e.g. APRI and FIB-4 scores were assessed at baseline and the 1-year follow-up. In all, 89 chronic hepatitis C virus (HCV) patients with sustained virological response and 93 non-alcoholic fatty liver disease (NAFLD) patients were included. There was a significantly strong correlation among imaging techniques. Using MRE as the reference standard, the area under the receiver operating characteristics curves for TE, SWE, APRI, and FIB-4 in detecting stage1-4 fibrosis were 0.88-0.95, 0.87-0.96, 0.83-0.89, and 0.79-0.92, respectively. In chronic HCV patients, the values of TE, SWE, MRE, APRI and FIB-4 significantly decreased from baseline to the 1-year follow-up. Liver steatosis did not significantly change over time. In NAFLD, compared to obese patients, non-obese patients had less LS and steatosis at baseline, and these values did not show significant changes at the 1-year follow-up. Our study suggests that the current NITs have a good correlation and accuracy in monitoring the treatment outcomes in patients with chronic liver diseases.
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Affiliation(s)
- Kessarin Thanapirom
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.,Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.,Research Unit of Liver Fibrosis and Cirrhosis, Chulalongkorn University, Bangkok, Thailand
| | - Sirinporn Suksawatamnuay
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.,Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.,Research Unit of Liver Fibrosis and Cirrhosis, Chulalongkorn University, Bangkok, Thailand
| | - Natthaporn Tanpowpong
- Department of Radiology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Bundit Chaopathomkul
- Department of Radiology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Supachaya Sriphoosanaphan
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.,Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Panarat Thaimai
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.,Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Nunthiya Srisoonthorn
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Piyawat Komolmit
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. .,Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. .,Research Unit of Liver Fibrosis and Cirrhosis, Chulalongkorn University, Bangkok, Thailand.
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18
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Role of liver stiffness measurements in patients who develop hepatocellular carcinoma after clearance of the hepatitis C virus. J Med Ultrason (2001) 2022; 49:253-259. [PMID: 35129720 PMCID: PMC9038899 DOI: 10.1007/s10396-021-01188-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 11/28/2021] [Indexed: 11/02/2022]
Abstract
PURPOSE To measure changes in liver stiffness over time due to direct-acting antiviral (DAA) therapy in hepatitis C patients using shear wave elastography (SWE). METHODS Patients with hepatitis C treated with DAA therapy in a university medical center between July 2015 and April 2020 were evaluated. Shear wave velocity (Vs) of the liver was measured using SWE. Alanine aminotransferase (ALT), platelet count, and α-fetoprotein (AFP) were measured at the same time, and the FIB-4 index was estimated. Absence of hepatocellular carcinoma was confirmed at baseline and end of therapy. Imaging was then performed every 6 months. Patient characteristics were compared between patients who did and did not develop carcinoma. RESULTS The mean age of the 229 patients (93 men) was 65.6 years. Eight patients developed carcinoma during follow-up (mean 32.6 ± 19.5 months). Significant differences were found between the groups in terms of AFP, platelet count, and Fib-4 index at baseline; the pre-treatment data had the best relationship with hepatocarcinogenesis. Mean Vs decreased significantly during DAA therapy, and then decreased further. Liver stiffness 6 months after treatment ended had the best relationship with hepatocarcinogenesis. CONCLUSION In patients with a sustained virological response, risk of developing cancer can be predicted by measuring Vs approximately 6 months after treatment.
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Nada A, Sabry A, Elabd NS, Abdu Allah AM, Elnaidany N, Abbasy M. B-type natriuretic peptide (BNP) in HCV-positive Egyptian patients: the impact of HCV eradication on plasma BNP levels. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00133-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Chronic hepatitis C virus (HCV) infection represents a major health-related burden in Egypt. HCV is considered as a major cardiovascular risk factor. BNP (B-type natriuretic peptide) has been determined as a credible diagnostic and prognostic cardiac biomarker. We aimed to assess plasma BNP in HCV-positive Egyptian patients prior and after HCV eradication by direct-acting antiviral agents (DAAs) therapy. Eighty-nine chronic HCV-positive patients were enrolled in our prospective research. They were provided with DAAs therapy in the form of sofosbuvir and daclatasvir without or with ribavirin for 12 weeks. History, clinical evaluation, and laboratory assessment: CBC, liver and kidney function tests, viral markers (HCVAb, HBVsAg, and HIVAb) by ELISA, HCV RNA by real-time PCR, and BNP by ELISA were assessed. FIB-4 and aspartate aminotransferase-to-platelet ratio index (APRI) scores were ranked.
Results
Plasma BNP displayed a non-significant (p = 0.124) increase of its serum mean values in post eradication of HCV than its baseline values. Baseline BNP exhibited a significant positive correlation with FIB4 (r = 0.411, P < 0.001) and APRI score (r = 0.418, p < 0.001) with a considerably negative correlation with platelets (r = − 0.274, p = 0.009), in addition to higher pretreatment BNP values in cirrhotic than in non-cirrhotic patients (p < 0.001), while non-significant relations were found regarding sex, BMI, and drug regimen (with or without ribavirin) (p = 0.950, 0.845, and 0.738, respectively). Additionally, plasma BNP values considerably decreased post-treatment in patients presented with higher baseline BNP values and more advanced liver disease (higher FIB4, APRI, and the presence of liver cirrhosis).
Conclusion
Our findings propose on the one side, the necessity of cardiac monitoring during chronic HCV infection and, on the other, the valuable impacts of HCV eradication on HCV-associated cardiac morbidities.
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Cerrito L, Ainora ME, Nicoletti A, Garcovich M, Riccardi L, Pompili M, Gasbarrini A, Zocco MA. Elastography as a predictor of liver cirrhosis complications after hepatitis C virus eradication in the era of direct-acting antivirals. World J Hepatol 2021; 13:1663-1676. [PMID: 34904036 PMCID: PMC8637667 DOI: 10.4254/wjh.v13.i11.1663] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 07/08/2021] [Accepted: 08/17/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic inflammation due to hepatitis C virus (HCV) infection leads to liver fibrosis and rearrangement of liver tissue, which is responsible for the development of portal hypertension (PH) and hepatocellular carcinoma (HCC). The advent of direct-acting antiviral drugs has revolutionized the natural history of HCV infection, providing an overall eradication rate of over 90%. Despite a significant decrease after sustained virological response (SVR), the rate of HCC and liver-related complications is not completely eliminated in patients with advanced liver disease. Although the reasons are still unclear, cirrhosis itself has a residual risk for the development of HCC and other PH-related complications. Ultrasound elastography is a recently developed non-invasive technique for the assessment of liver fibrosis. Following the achievement of SVR, liver stiffness (LS) usually decreases, as a consequence of reduced inflammation and, possibly, fibrosis. Recent studies emphasized the application of LS assessment in the management of patients with SVR in order to define the risk for developing the complications of chronic liver disease (functional decompensation, gastrointestinal bleeding, HCC) and to optimize long-term prognostic outcomes in clinical practice.
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Affiliation(s)
- Lucia Cerrito
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Maria Elena Ainora
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Alberto Nicoletti
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Matteo Garcovich
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Laura Riccardi
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Maurizio Pompili
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Antonio Gasbarrini
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
| | - Maria Assunta Zocco
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome (Italy), Rome 00168, Italy
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21
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Freekh DA, Helmy MW, Said M, El-Khodary NM. The effect of direct acting antiviral agents on vascular endothelial function in Egyptian patients with chronic hepatitis C virus infection. Saudi Pharm J 2021; 29:1120-1128. [PMID: 34703365 PMCID: PMC8523355 DOI: 10.1016/j.jsps.2021.08.006] [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: 03/11/2021] [Accepted: 08/01/2021] [Indexed: 02/07/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection is correlated with cerebrovascular and cardiovascular disease (CVD). This study aimed to assess the effect of treatment with DAAs on vascular endothelial function in cirrhotic and non-cirrhotic HCV infected patients without any CVD risk factors. Fifty chronic HCV genotype 4 infected patients, without cardiovascular risks who have been listed to receive sofosbuvir/daclatasvir with ribavirin combination as triple therapy for 3 months were prospectively recruited. Endothelial dysfunction markers as soluble vascular cell adhesion molecule-1 (sVCAM-1) and Von willebrand factor (vWf) and inflammation marker (IL6) were estimated at baseline and 3 months post the end of therapy (SVR). All patients achieved SVR. VCAM1 level was significantly improved after HCV clearance with DAA in cirrhotic HCV patients (P = 0.002) compared to patients with mild liver fibrosis (P = 0.006). Levels of vWF also decreased significantly in cirrhosis and non-cirrhosis groups after SVR (P < 0.001 and P = 0.011, respectively). Systemic inflammatory marker (IL6) showed significant decrease in cirrhotic patients (P = 0.001). While, IL6 level did not change significantly in non-cirrhotic group (P = 0.061). Also at SVR, noninvasive liver fibrosis indices have been reduced significantly in the two groups (P < 0.001). HCV clearance by new DAA treatment improves the vascular endothelial dysfunction in Egyptian HCV infected patients with different levels of liver fibrosis and with no risk factors for endothelial dysfunction or CVD.
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Affiliation(s)
- Dalia A Freekh
- Clinical Pharmacy & Pharmacy Practice Department, Faculty of Pharmacy, Damanhour University, Damanhour City, Egypt
| | - Maged W Helmy
- Professor of Pharmacology & Toxicology, Pharmacology & Toxicology Department, Faculty of Pharmacy, Damanhour University, Damanhour City, Egypt
| | - Mohamed Said
- Professor of Endemic Medicine & Hepatology, Endemic Medicine & Hepatology Department, Cairo University, Cairo City, Egypt
| | - Noha M El-Khodary
- Lecturer of Clinical Pharmacy, Clinical Pharmacy & Pharmacy Practice Department, Faculty of Pharmacy, Damanhour University, Damanhour City, Egypt
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22
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Yaraş S, Sezgin O, Üçbilek E, Özdoğan O, Altıntaş E. Significant decrease in liver stiffness detected by two dimensional shear-wave elastography after treatment with direct-acting antiviral agents in patients with chronic Hepatitis C. TURKISH JOURNAL OF GASTROENTEROLOGY 2021; 31:142-147. [PMID: 32141823 DOI: 10.5152/tjg.2020.19418] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIMS Two-dimensional shear-wave (2D-SWE) elastography is one of the noninvasive methods for the evaluation of liver fibrosis. The purpose of this study is to investigate the changes in liver stiffness (LS) by employing 2D-SWE as well as its correlation with noninvasive fibrosis markers in patients with chronic hepatitis C (CHC), who are undergoing direct-acting antiviral (DAA) therapy. MATERIALS AND METHODS The researchers included all the patients with CHC who are scheduled for DAA treatment in this study. 2D-SWE measurements were performed at baseline, end of treatment (EOT), and 12 weeks after the treatment. According to the latest EFSUMB guidelines, elastography measurements were performed during the ultrasonographic evaluation and recorded in kilopascals (unit). The correlation between biochemical and viral responses, and noninvasive fibrosis scores (FIB-4, AST-to-platelet ratio index (APRI)) was also evaluated. RESULTS This study employed 230 patients who underwent treatment with DAAs between September 2016 and September 2017. However, 131 patients were able to complete the study, of which 48 (36.6%) were male and 83 (63.4%) were female. The mean age was 65.0 (±11.18) years. Both EOT and sustained viral response (SVR) had the same rate of 99.2% (130/131). The SWE measurement (mean) values at pretreatment, EOT, and 12 weeks after treatment was 12.92, 10.45, and 9.07 kPa, respectively (p<0.05), whereas the APRI scores were 0.76, 0.39, and 0.30, respectively (p<0.05). Additionally, the FIB-4 scores at pretreatment, EOT, and 12 weeks after treatment were 2.98, 2.43, and 2.03, respectively (p<0.05). The results of liver stiffness measurements (LSM) were similar in all the groups of cirrhotic, noncirrhotic, treatment-experienced, and treatment-naive patients. CONCLUSION DAA treatments in the patients with CHC led to almost a complete SVR and a considerable decrease in LS in a short time.
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Affiliation(s)
- Serkan Yaraş
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
| | - Orhan Sezgin
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
| | - Enver Üçbilek
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
| | - Osman Özdoğan
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
| | - Engin Altıntaş
- Department of Gastroenterology, Mersin University School of Medicine, Mersin, Turkey
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23
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Long-Term Impact of Hepatitis C Virus Eradication on Liver Stiffness in Egyptian Patients. Can J Gastroenterol Hepatol 2021; 2021:4961919. [PMID: 34589447 PMCID: PMC8476245 DOI: 10.1155/2021/4961919] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 08/25/2021] [Accepted: 08/26/2021] [Indexed: 12/11/2022] Open
Abstract
METHODS Liver stiffness measurements (LSM) have been serially assessed 1, 3, and 5 years after HCV clearance in 655 patients who have been treated with DAAs. RESULTS The mean age was 51.44 ± 10 years. 73% of patients were males. 48% were cirrhotics. In noncirrhotics, the mean LSM was significantly decreased from 8.29 ± 2.3 kPa to 4.03 ± 1.0 kPa (p < 0.0001) at the end of the follow-up. Likewise, LSM decreased in cirrhotics from 29.66 ± 14.25 kPa to 22.50 ± 11.16 kPa (p < 0.0001). The proportions of F1, F2, F3, and F4 patients at the baseline were 17.7%, 17.9%, 16.6%, and 47.8%, which became 56.5%, 4.1%, 4.9%, and 34.5%, respectively, with a substantial reversal of cirrhosis in 87 patients (27.7%) at the end of follow-up. CONCLUSIONS There was an overall significant regression of liver stiffness in all patients after sustained HCV eradication. Liver stiffness reflecting mild fibrosis (F0-F2) usually improves shortly after treatment, while measurements reflecting advanced fibrosis (F3-F4) take a longer time to regress to lower fibrosis stages.
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Kang Q, Xu J, Luo H, Tan N, Chen H, Cheng R, Pan J, Han Y, Yang Y, Liu D, Xi H, Yu M, Xu X. Direct antiviral agent treatment leads to rapid and significant fibrosis regression after HCV eradication. J Viral Hepat 2021; 28:1284-1292. [PMID: 34105867 DOI: 10.1111/jvh.13558] [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: 01/05/2021] [Revised: 04/22/2021] [Accepted: 05/21/2021] [Indexed: 12/14/2022]
Abstract
Limited data are currently available regarding fibrosis progression after hepatitis C virus (HCV) eradication. The goal of the present study was to evaluate the effects of HCV eradication on liver stiffness measurements (LSMs), aspartate aminotransferase/platelet ratio index (APRI) scores, fibrosis-4(FIB-4) scores, chitinase-3-like protein 1 (CHI3L1) levels and Golgi protein 73 (GP73) levels in patients with chronic hepatitis C (CHC). One hundred and two patients who received direct antiviral agents (DAAs) therapy at Peking University First Hospital participated in the present study. Clinical information and serum samples were collected at baseline, at the end of treatment (EOT), and at the weeks 12, 24 and 48 after treatment (W12, W24 and W48, respectively). Of the 102 patients, 51 had mild-to-moderate fibrosis (F1/F2), and 51 had advanced fibrosis (F3/F4). The LSMs improved for all patients at the EOT, with observed changes of 2.85 kPa, and the decrease continued to W12. However, a more pronounced improvement was noted for the advanced fibrosis (F3/F4) patients, with a change of 3.6 kPa from baseline to the EOT. Significant decreases between the baseline and EOT measurements were observed in the APRI and FIB-4 scores [0.64 (0.39-1.21) vs. 0.35 (0.26-0.52), p<0.001; 2.53 (1.30-3.91) vs. 1.87 (0.89-2.5), p<0.001], after which the values decreased until W12, with no significant difference observed. Serum CHI3L1 and GP73 levels were profoundly decreased at the EOT compared with those at baseline [134.07 (154.49) vs. 103.75 (98.04), p=0.025; 98.24 (64.76) vs. 88.91 (50.89), p=0.002]. DAA treatments could significantly improve liver fibrosis of CHC patients as evidenced by decreased liver stiffness, APRI scores and FIB-4 scores. Improvements in liver fibrosis markers (especially serum CHI3L1 and GP73) were prominent in patients with advanced fibrosis, indicating that serum CHI3L1 and GP73 could be noninvasive markers for monitoring fibrosis in CHC patients. Significance Statement The prospective cohort evaluated the effect of direct antiviral agents (DAAs) on fibrosis regression after hepatitis C virus (HCV) eradication of Chinese people in the real-world study. This study highlighted that rapid and significant fibrosis regression rather than reduction in inflammation was achieved with DAA treatment, and this regression could be detected as early as the end of treatment. We found the serum CHI3L1 and GP73 levels can be used to monitor changes in fibrosis in CHC patients.
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Affiliation(s)
- Qian Kang
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Jinghang Xu
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Hao Luo
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Ning Tan
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Hongyu Chen
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Ran Cheng
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Jiali Pan
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Yifan Han
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Yuqing Yang
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Dan Liu
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Hongli Xi
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Min Yu
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
| | - Xiaoyuan Xu
- Departments of Infectious Diseases, Peking University First Hospital, Beijing, People's Republic of China
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25
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Kronfli N, Young J, Wang S, Cox J, Walmsley S, Hull M, Cooper C, Martel-Laferriere V, Wong A, Pick N, Klein MB. Liver Fibrosis in Human Immunodeficiency Virus (HIV)-Hepatitis C Virus (HCV) Coinfection Before and After Sustained Virologic Response: What Is the Best Noninvasive Marker for Monitoring Regression? Clin Infect Dis 2021; 73:468-477. [PMID: 32504083 DOI: 10.1093/cid/ciaa702] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Accepted: 06/01/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Noninvasive markers of liver fibrosis such as aspartate aminotransferase-to-platelet ratio (APRI) and transient elastography (TE) have largely replaced liver biopsy for staging hepatitis C virus (HCV). As there is little longitudinal data, we compared changes in these markers before and after sustained virologic response (SVR) in human immunodeficiency virus (HIV)-HCV coinfected patients. METHODS Participants from the Canadian Coinfection Cohort study who achieved SVR after a first treatment with either interferon/ribavirin or direct acting antivirals (DAAs), with at least 1 pre- and posttreatment fibrosis measure were selected. Changes in APRI or TE (DAA era only) were modeled using a generalized additive mixed model, assuming a gamma distribution and adjusting for sex, age at HCV acquisition, duration of HCV infection, and time-dependent body mass index, binge drinking, and detectable HIV RNA. RESULTS Of 1981 patients, 151 achieved SVR with interferon and 553 with DAAs; 94 and 382 met inclusion criteria, respectively. In the DAA era, APRI increased (0.03 units/year; 95% credible interval (CrI): -.05, .12) before, declined dramatically during, and then changed minimally (-0.03 units/year; 95% CrI: -.06, .01) after treatment. TE values, however, increased (0.74 kPa/year; 95% CrI: .36, 1.14) before treatment, changed little by the end of treatment, and then declined (-0.55 kPa/year; 95% CrI: -.80, -.31) after SVR. CONCLUSIONS TE should be the preferred noninvasive tool for monitoring fibrosis regression following cure. Future studies should assess the risk of liver-related outcomes such as hepatocellular carcinoma according to trajectories of fibrosis regression measured using TE to determine if and when it will become safe to discontinue screening.
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Affiliation(s)
- Nadine Kronfli
- Department of Medicine, Division of Infectious Diseases and Chronic Viral Illness Service, McGill University, Montreal, Quebec, Canada
| | - Jim Young
- Department of Medicine, Division of Infectious Diseases and Chronic Viral Illness Service, McGill University, Montreal, Quebec, Canada.,Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.,Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Canada
| | - Shouao Wang
- Department of Medicine, Division of Infectious Diseases and Chronic Viral Illness Service, McGill University, Montreal, Quebec, Canada
| | - Joseph Cox
- Department of Medicine, Division of Infectious Diseases and Chronic Viral Illness Service, McGill University, Montreal, Quebec, Canada.,Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Canada
| | - Sharon Walmsley
- University Health Network, University of Toronto, Toronto, Canada.,CIHR Canadian HIV Trials Network, Vancouver, Canada
| | - Mark Hull
- BC Centre of Excellence, St. Paul's Hospital, Vancouver, Canada
| | | | - Valerie Martel-Laferriere
- Departement de Microbiologie et Infectiologie, Centre Hospitalier de l'Université de Montréal, Montreal, Canada
| | | | - Neora Pick
- Department of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, Canada
| | - Marina B Klein
- Department of Medicine, Division of Infectious Diseases and Chronic Viral Illness Service, McGill University, Montreal, Quebec, Canada.,CIHR Canadian HIV Trials Network, Vancouver, Canada
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26
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Hepatitis C Virus Clearance by Direct-Acting Antivirals Agents Improves Endothelial Dysfunction and Subclinical Atherosclerosis: HEPCAR Study. Clin Transl Gastroenterol 2021; 11:e00203. [PMID: 32955194 PMCID: PMC7431267 DOI: 10.14309/ctg.0000000000000203] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection has been related to increased cardiovascular (CV) risk. The aim of this study was to analyze the impact of sustained virological response (SVR) on endothelial dysfunction and subclinical atherosclerosis in patients with hepatitis C virus treated with direct-acting antiviral agents. METHODS A total of 114 patients were prospectively recruited and underwent CV risk assessment including (i) endothelial dysfunction determined through laser Doppler flowmetry and (ii) subclinical atherosclerosis, elucidated by the ankle-brachial index (ABI). Atherogenic lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides); markers of oxidative stress (oxidized low-density lipoprotein antibodies [OLAbs]), soluble markers of adhesion (vascular cell adhesion molecule [VCAM], e-selectin, and soluble markers of angiogenesis; and vascular endothelial growth factor, endothelial [EMPs] and platelet [PMPs] apoptotic microparticles, and cell-free DNA [cfDNA]) were measured. All determinations were performed at baseline, 12 weeks (SVR time), and 1 year after treatment. RESULTS In patients with endothelial dysfunction, area of hyperemia improved after virus clearance (P = 0.013) and was related to significant decrease in VCAM, e-selectin (P < 0.001), and cfDNA (P = 0.017) and to increased OLAb levels (P = 0.001). In patients with subclinical atherosclerosis at baseline, a significantly improved ABI was seen after HCV clearance (P < 0.001). Levels of both EMPs and PMPs also decreased after SVR and at follow-up (P = 0.006 and P = 0.002, respectively). DISCUSSION HCV clearance improved not only liver function but also endothelial dysfunction and subclinical atherosclerosis promoted by decrease in levels of VCAM, e-selectin, cfDNA, and PMPs and EMPs.
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27
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Florea M, Serban T, Tirpe GR, Tirpe A, Lupsor-Platon M. Noninvasive Assessment of Hepatitis C Virus Infected Patients Using Vibration-Controlled Transient Elastography. J Clin Med 2021; 10:jcm10122575. [PMID: 34200885 PMCID: PMC8230562 DOI: 10.3390/jcm10122575] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 06/06/2021] [Accepted: 06/08/2021] [Indexed: 02/08/2023] Open
Abstract
Chronic infection with hepatitis C virus (HCV) is one of the leading causes of cirrhosis and hepatocellular carcinoma (HCC). Surveillance of these patients is an essential strategy in the prevention chain, including in the pre/post-antiviral treatment states. Ultrasound elastography techniques are emerging as key methods in the assessment of liver diseases, with a number of advantages such as their rapid, noninvasive, and cost-effective characters. The present paper critically reviews the performance of vibration-controlled transient elastography (VCTE) in the assessment of HCV patients. VCTE measures liver stiffness (LS) and the ultrasonic attenuation through the embedded controlled attenuation parameter (CAP), providing the clinician with a tool for assessing fibrosis, cirrhosis, and steatosis in a noninvasive manner. Moreover, standardized LS values enable proper staging of the underlying fibrosis, leading to an accurate identification of a subset of HCV patients that present a high risk for complications. In addition, VCTE is a valuable technique in evaluating liver fibrosis prior to HCV therapy. However, its applicability in monitoring fibrosis regression after HCV eradication is currently limited and further studies should focus on extending the boundaries of VCTE in this context. From a different perspective, VCTE may be effective in identifying clinically significant portal hypertension (CSPH). An emerging prospect of clinical significance that warrants further study is the identification of esophageal varices. Our opinion is that the advantages of VCTE currently outweigh those of other surveillance methods.
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Affiliation(s)
- Mira Florea
- Community Medicine Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Teodora Serban
- Medical Imaging Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - George Razvan Tirpe
- Department of Radiology and Medical Imaging, County Emergency Hospital Cluj-Napoca, 3-5 Clinicilor Street, 400000 Cluj-Napoca, Romania;
| | - Alexandru Tirpe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania;
| | - Monica Lupsor-Platon
- Medical Imaging Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
- Medical Imaging Department, Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
- Correspondence:
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28
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Peschel G, Grimm J, Buechler C, Gunckel M, Pollinger K, Aschenbrenner E, Kammerer S, Jung EM, Haimerl M, Werner J, Müller M, Weigand K. Liver stiffness assessed by shear-wave elastography declines in parallel with immunoregulatory proteins in patients with chronic HCV infection during DAA therapy. Clin Hemorheol Microcirc 2021; 79:541-555. [PMID: 34120896 DOI: 10.3233/ch-211193] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND A rapid decline of liver stiffness (LS) was detected by non-invasive methods in patients with chronic hepatitis C (HCV) infection during treatment with direct-acting antivirals (DAA). OBJECTIVE To investigate the influence of inflammation on LS. METHODS We prospectively examined LS by sonographic shear-wave elastography in 217 patients during DAA therapy from treatment initiation (BL) to 12 weeks after end of therapy (SVR12). Demographic data, laboratory findings and serum levels of cytokines were determined. RESULTS Values of LS decreased from 1.86 m/s to 1.68 m/s (p = 0.01) which was most pronounced in patients who had F4 fibrosis at BL (3.27 m/s to 2.37 m/s; p < 0.001). Initially elevated values of aminotransferases, ferritin, IgG (p < 0.001 each) and international normalized ratio (p < 0.003) declined, thrombocyte count (p = 0.007) increased. Correlations of these laboratory parameters with BL levels of LS measurement (LSM) were most apparent in patients with F1-F3 fibrosis. Tumor necrosis factor (TNF)-α (p = 0.031), interleukin (IL)-10 (p = 0.005) and interferon y inducible protein (IP)-10 (p < 0.001) decreased in parallel with LSM under DAA therapy and corelated with BL values. CONCLUSION Decrease of systemic inflammatory parameters correlated with LSM under DAA therapy. We conclude that regression of LSM is attributable to the decline of inflammation rather than reflecting fibrosis.
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Affiliation(s)
- G Peschel
- Department of Gastroenterology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany
| | - J Grimm
- Department of Gastroenterology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany
| | - C Buechler
- Department of Gastroenterology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany
| | - M Gunckel
- Department of Gastroenterology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany
| | - K Pollinger
- Department of Gastroenterology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany
| | - E Aschenbrenner
- Department of Gastroenterology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany
| | - S Kammerer
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
| | - E M Jung
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
| | - M Haimerl
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
| | - J Werner
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - M Müller
- Department of Gastroenterology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany
| | - K Weigand
- Department of Gastroenterology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany
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29
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Sadeghi A, Amiri R, Akbarpour E, Mirminachi B, Sharifi AH, Merat S. Changes in liver fibrosis in patients with chronic hepatitis C after successful direct-acting antiviral therapy. Int J Clin Pract 2021; 75:e14145. [PMID: 33709413 DOI: 10.1111/ijcp.14145] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 03/09/2021] [Indexed: 12/28/2022] Open
Abstract
INTRODUCTION AND OBJECTIVES After successful treatment of hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs), the stage of liver fibrosis decreases over time. Here, we aimed to assess the changes in the liver fibrosis stage using transient elastography (TE) after successful DAA therapy in HCV-infected cirrhotic patients who were referred to Shariati hospital from 2016 to 2017. MATERIAL AND METHODS In this observational cohort, all HCV-infected cirrhotic patients who were treated with a combination of sofosbuvir/daclatasvir, had sustained virologic response (SVR), and had undergone pre- and post-treatment TE, were enrolled. The primary outcome was the changes in TE parameters six months after the end of treatment compared with baseline. RESULTS A total of 442 eligible subjects received DAA therapy. Overall, the SVR rate was 96.6%. Of these, 149 patients had completed the protocol and were enrolled. The mean age of patients was 56.1 ± 10.3 years and the predominant sex was male (77.9%). The median (Q1 -Q3 ) liver stiffness (LS) value at baseline was 26.3 kPa (18.1-38 kPa), which significantly decreased to 20.9 kPa (12-29.7 kPa) [z = -8.45, P-value < .001]. Also, the liver steatosis of patients with baseline CAP ≥ 220 dB/m had a significant response to treatment [z = -2.3, P-value = .023]. Based on multivariate analysis, a higher baseline liver fibrosis stage was the only determinant of LS values improvement in our study. CONCLUSION Successful HCV eradication in patients with liver fibrosis results in significant improvement in LS, even in cirrhotic patients.
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Affiliation(s)
- Anahita Sadeghi
- Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Roya Amiri
- Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Elham Akbarpour
- Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Babak Mirminachi
- Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir-Houshang Sharifi
- Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Shahin Merat
- Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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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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Nozaki A, Chuma M, Hara K, Moriya S, Fukuda H, Numata K, Tanaka K, Morimoto M, Sakamaki K, Yamanaka T, Kondo M, Maeda S. Sofosbuvir-based therapies associated with regression of liver fibrosis in patients with hepatitis C virus infection: A prospective observational study. Medicine (Baltimore) 2021; 100:e25110. [PMID: 33761674 PMCID: PMC9281984 DOI: 10.1097/md.0000000000025110] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 02/19/2021] [Indexed: 01/05/2023] Open
Abstract
Oral direct-acting antiviral (DAA) treatment leads to >95% sustained virological response (SVR) and could be clinically useful in regression of liver fibrosis in chronic hepatitis C virus (HCV) infection. We evaluated if ledipasvir/sofosbuvir or sofosbuvir + ribavirin is associated with regression of fibrosis in HCV patients who achieved SVR.In this prospective cohort study performed at 3 sites in Japan, patients with genotype 1 and genotype 2 were given standard treatment of ledipasvir 90 mg/sofosbuvir 400 mg and sofosbuvir 400 mg + 200-1000 mg/day ribavirin, respectively, for 12 weeks. Liver fibrosis was assessed using Mac-2-binding protein glycosylation isomer (M2BPGi) and other fibrosis markers (platelet count, Fib-4 index, liver stiffness measurement [LSM]) in patients who achieved SVR.A total of 98.1% of (n = 101/103) patients in genotype 1 cohort and 100% (n = 16/16) in the genotype 2 cohort achieved SVR12. Based on per-protocol analysis, M2BPGi levels showed a significant decrease (-2.2 cut-off index [COI], P < .0001) at week 48 after treatment initiation. Forty-three patients showed a significant decrease in Fib-4 index (-1.2, P < .0001), and 44 patients showed improvement in LSM (-5.9 kPa, P < .0001).Achievement of SVR after antiviral therapy was associated with fibrosis regression. M2BPGi correlated well with LSM at week 48 after treatment initiation, supporting the sustainable benefit of HCV therapy.
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Affiliation(s)
- Akito Nozaki
- Gastroenterological Center, Yokohama City University Medical Center
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center
| | - Koji Hara
- Gastroenterological Center, Yokohama City University Medical Center
| | - Satoshi Moriya
- Gastroenterological Center, Yokohama City University Medical Center
| | - Hiroyuki Fukuda
- Gastroenterological Center, Yokohama City University Medical Center
| | - Kazushi Numata
- Gastroenterological Center, Yokohama City University Medical Center
| | - Katsuaki Tanaka
- Gastroenterological Center, Yokohama City University Medical Center
| | - Manabu Morimoto
- Department of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center
| | | | - Takeharu Yamanaka
- Department of Biostatistics, School of Medicine, Yokohama City University
| | - Masaaki Kondo
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine
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Elabd NS, Tayel SI, Elhamouly MS, Hassanein SA, Kamaleldeen SM, Ahmed FE, Rizk M, Gadallah AA, Ajlan SE, Sief AS. Evaluation of MicroRNA-122 as a Biomarker for Chronic Hepatitis C Infection and as a Predictor for Treatment Response to Direct-Acting Antivirals. Hepat Med 2021; 13:9-23. [PMID: 33758557 PMCID: PMC7979684 DOI: 10.2147/hmer.s292251] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Accepted: 02/05/2021] [Indexed: 11/23/2022] Open
Abstract
Background Treatment response to antiviral drugs is a challenging issue in patients with chronic hepatitis C virus (HCV) infection. Although microRNA-122 represents the majority of the microRNA content in hepatic tissues, few studies have evaluated its role in the treatment response, so we aimed to study its role in chronic HCV patients and in predicting the treatment response to direct-acting antivirals (DAAs). Methods The study included 125 chronic HCV patients (89 naïve and 36 with a prior failed peginterferon/ribavirin response) and 50 apparently healthy subjects. Complete blood count, liver function, α-fetoprotein, lipid profiles, serum creatinine, abdominal ultrasound, and FibroScan® were assessed. Viral markers, HCV antibodies, and hepatitis B surface antigen were measured by enzyme-linked fluorescent immunoassay, with quantitative estimation of HCV RNA and microRNA-122 levels by real-time PCR. Results The microRNA-122 level in HCV patients (those with a sustained virologic response 12 weeks after finishing therapy [SVR12] and non-responders) was significantly increased compared with controls and expressed more in non-responders versus SVR12 (p=0.042). ROC curve analysis of microRNA-122 for differentiating HCV patients from healthy controls revealed that a cut-off point of >1.45 had a sensitivity of 67.20%, specificity of 94.0%, AUC=0.861, and p<0.001; and for predicting response to treatment a cut-off point ≤5.66 could significantly (p=0.022) predict the occurrence of SVR, with a sensitivity of 60.34%, specificity of 66.67%, and AUC=0.729. Logistic regression analysis showed significant values for microRNA-122 in multivariate and univariate analysis for the prediction of response to DAAs. Conclusion The results demonstrated the possible function of microRNA-122 as an indicative tool for distinguishing chronic HCV patients from controls and in the assessment of the therapeutic reaction to DAAs.
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Affiliation(s)
- Naglaa S Elabd
- Tropical Medicine Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Safaa I Tayel
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Moamena S Elhamouly
- Tropical Medicine Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Shaimaa A Hassanein
- Diagnostic Radiology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Samar M Kamaleldeen
- Clinical Pathology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Fatma E Ahmed
- Clinical Pharmacology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Mahmoud Rizk
- Internal Medicine Department, Faculty of Medicine, Banha University, Banha, Egypt
| | - Abdelnaser A Gadallah
- Internal Medicine Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Soma E Ajlan
- Microbiology and Immunology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Ahmed S Sief
- Hepatology and Gastroenterology Department, Shebin Elkom Teaching Hospital, Menoufia, Egypt
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Ridziauskas M, Zablockienė B, Jančorienė L, Samuilis A, Zablockis R, Jackevičiūtė A. Assessment of Liver Stiffness Regression and Hepatocellular Carcinoma Risk in Chronic Hepatitis C Patients after Treatment with Direct-Acting Antiviral Drugs. ACTA ACUST UNITED AC 2021; 57:medicina57030210. [PMID: 33652777 PMCID: PMC7996730 DOI: 10.3390/medicina57030210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 02/20/2021] [Accepted: 02/22/2021] [Indexed: 11/23/2022]
Abstract
Background and Objectives: Chronic hepatitis C virus infection affects about 71 million people worldwide. It is one of the most common chronic liver conditions associated with an increased risk of developing liver cirrhosis and cancer. The aim of this study was to evaluate changes in liver fibrosis and the risk of developing hepatocellular carcinoma after direct-acting antiviral drug therapy, and to assess factors, linked with these outcomes. Materials and Methods: 70 chronic hepatitis C patients were evaluated for factors linked to increased risk of de novo liver cancer and ≥ 20% decrease of ultrasound transient elastography values 12 weeks after the end of treatment. Results: The primary outcome was an improvement of liver stiffness at the end of treatment (p = 0.004), except for patients with diabetes mellitus type 2 (p = 0.49). Logistic regression analysis revealed factors associated with ≥ 20% decrease of liver stiffness values: lower degree of steatosis in liver tissue biopsy (p = 0.053); no history of interferon-based therapy (p = 0.045); elevated liver enzymes (p = 0.023–0.036); higher baseline liver stiffness value (p = 0.045) and absence of splenomegaly (p = 0.035). Hepatocellular carcinoma developed in 4 (5.7%) patients, all with high alpha-fetoprotein values (p = 0.0043) and hypoechoic liver mass (p = 0.0001), three of these patients had diabetes mellitus type 2. Conclusions: Liver stiffness decrease was significant as early as 12 weeks after the end of treatment. Patients with diabetes and advanced liver disease are at higher risk of developing non-regressive fibrosis and hepatocellular carcinoma even after successful treatment.
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Affiliation(s)
- Martynas Ridziauskas
- Vilnius University Faculty of Medicine, M.K. Ciurlionio 21, LT-03101 Vilnius, Lithuania;
- Correspondence: ; Tel.: +370-606-98744
| | - Birutė Zablockienė
- Center of Infectious Diseases, Vilnius University Hospital Santaros Klinikos, LT-08406 Vilnius, Lithuania; (B.Z.); (L.J.)
- Clinic of Infectious Diseases and Dermatovenerology, Institute of Clinical Medicine, Vilnius University Faculty of Medicine, M.K. Ciurlionio 21, LT-03101 Vilnius, Lithuania
| | - Ligita Jančorienė
- Center of Infectious Diseases, Vilnius University Hospital Santaros Klinikos, LT-08406 Vilnius, Lithuania; (B.Z.); (L.J.)
- Clinic of Infectious Diseases and Dermatovenerology, Institute of Clinical Medicine, Vilnius University Faculty of Medicine, M.K. Ciurlionio 21, LT-03101 Vilnius, Lithuania
| | - Artūras Samuilis
- Center of Radiology and Nuclear Medicine, Vilnius University Hospital Santaros Klinikos, LT-08661 Vilnius, Lithuania;
- Department of Radiology, Nuclear Medicine and Medical Physics, Faculty of Medicine, Vilnius University, M.K. Ciurlionio 21, LT-03101 Vilnius, Lithuania
| | - Rolandas Zablockis
- Center of Pulmonology and Allergology, Vilnius University Hospital Santaros Klinikos, Santariskiu 2, LT-08661 Vilnius, Lithuania;
- Clinic of Chest Diseases, Immunology and Allergology, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, M.K. Ciurlionio 21, LT-03101 Vilnius, Lithuania
| | - Aušrinė Jackevičiūtė
- Vilnius University Faculty of Medicine, M.K. Ciurlionio 21, LT-03101 Vilnius, Lithuania;
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Marticorena Garcia SR, Althoff CE, Dürr M, Halleck F, Budde K, Grittner U, Burkhardt C, Jöhrens K, Braun J, Fischer T, Hamm B, Sack I, Guo J. Tomoelastography for Longitudinal Monitoring of Viscoelasticity Changes in the Liver and in Renal Allografts after Direct-Acting Antiviral Treatment in 15 Kidney Transplant Recipients with Chronic HCV Infection. J Clin Med 2021; 10:jcm10030510. [PMID: 33535495 PMCID: PMC7867050 DOI: 10.3390/jcm10030510] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 01/21/2021] [Accepted: 01/23/2021] [Indexed: 01/07/2023] Open
Abstract
Besides the liver, hepatitis C virus (HCV) infection also affects kidney allografts. The aim of this study was to longitudinally evaluate viscoelasticity changes in the liver and in kidney allografts in kidney transplant recipients (KTRs) with HCV infection after treatment with direct-acting antiviral agents (DAAs). Fifteen KTRs with HCV infection were treated with DAAs (daclatasvir and sofosbuvir) for 3 months and monitored at baseline, end of treatment (EOT), and 3 (FU1) and 12 (FU2) months after EOT. Shear-wave speed (SWS) and loss angle of the complex shear modulus (φ), reflecting stiffness and fluidity, respectively, were reconstructed from multifrequency magnetic resonance elastography data with tomoelastography post-processing. After virus elimination by DAAs, hepatic stiffness and fluidity decreased, while kidney allograft stiffness and fluidity increased compared with baseline (hepatic stiffness change at FU1: -0.14 m/s, p < 0.01, and at FU2: -0.11 m/s, p < 0.05; fluidity at FU1: -0.05 rad, p = 0.04 and unchanged at FU2: p = 0.20; kidney allograft stiffness change at FU1: +0.27 m/s, p = 0.01, and at FU2: +0.30 m/s, p < 0.01; fluidity at FU1 and FU2: +0.06 rad, p = 0.02). These results suggest the restoration of mechanically sensitive structures and functions in both organs. Tomoelastography can be used to monitor the therapeutic results of HCV treatment non-invasively on the basis of hepatic and renal viscoelastic parameters.
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Affiliation(s)
- Stephan R. Marticorena Garcia
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (C.E.A.); (C.B.); (T.F.); (B.H.); (I.S.); (J.G.)
- Correspondence: ; Tel.: +49-30-450-527082; Fax: +49-30-450-7527911
| | - Christian E. Althoff
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (C.E.A.); (C.B.); (T.F.); (B.H.); (I.S.); (J.G.)
| | - Michael Dürr
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (M.D.); (F.H.); (K.B.)
| | - Fabian Halleck
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (M.D.); (F.H.); (K.B.)
| | - Klemens Budde
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (M.D.); (F.H.); (K.B.)
| | - Ulrike Grittner
- Institute of Biometry and Clinical Epidemiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany;
- Berlin Institute of Health (BIH), Anna-Louisa-Karsch 2, 10178 Berlin, Germany
| | - Christian Burkhardt
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (C.E.A.); (C.B.); (T.F.); (B.H.); (I.S.); (J.G.)
| | - Korinna Jöhrens
- Department of Pathology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany;
| | - Jürgen Braun
- Institute for Medical Informatics, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany;
| | - Thomas Fischer
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (C.E.A.); (C.B.); (T.F.); (B.H.); (I.S.); (J.G.)
| | - Bernd Hamm
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (C.E.A.); (C.B.); (T.F.); (B.H.); (I.S.); (J.G.)
| | - Ingolf Sack
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (C.E.A.); (C.B.); (T.F.); (B.H.); (I.S.); (J.G.)
| | - Jing Guo
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (C.E.A.); (C.B.); (T.F.); (B.H.); (I.S.); (J.G.)
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Shear wave elastography and transient elastography in HCV patients after direct-acting antivirals. Radiol Med 2021; 126:894-899. [PMID: 33492651 DOI: 10.1007/s11547-020-01326-4] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 12/14/2020] [Indexed: 02/06/2023]
Abstract
PURPOSE To compare the ultrasound (US) and pulse shear wave elastography (pSWE, Elast PQ®) methods with transient elastography (TE), clinical scores and laboratory tests, during the follow-up of HCV patients receiving direct-acting antiviral drugs (DAA). METHODS Our prospective study from June 2016 to December 2017 included 22 consecutively enrolled HCV-positive patients (59.7 ± 12.3 years, 11 male) which were subjected to antiviral therapy. All patients underwent B-mode ultrasound, color-Doppler, pSWE and TE five times: before therapy (T0), at the end of therapy (post-Tx), and at 12, 24, 48 weeks post-therapy. The liver stiffness (LS) values obtained with pSWE and TE and the data coming from US assessment and clinical evaluation were compared. RESULTS We obtained a statistically significant reduction of LS values (kPa) measured by pSWE, between T0 (14.3 ± 9.3), post-Tx (11.8 ± 10.5), 12 weeks (7.5 ± 3.3), 24 weeks (8 ± 3.8) and 48 weeks (8.5 ± 4.6) (p = 0.02). The reduction of kPa measured by TE was not significant between T0 (14.7 ± 9.3), post-Tx (12 ± 9.5), 12 weeks (11.6 ± 7.7), 24 weeks (10.3 ± 6) and 48 weeks (10.8 ± 7.5) (p > 0.05). Multivariate baseline analysis showed significant independent association among measurement of TE stiffness with cirrhosis, type of vein hepatic flow and showed significant independent association between delta-pSWE measurement (difference between stiffness measurements at the baseline and 12 months after treatment) with staging of fibrosis (p = 0.006) and sustained virologic response after 12 weeks of treatment (SVR12, p = 0.017). CONCLUSION The pSWE method has shown better ability than TE to identify a reduction in LS. Therefore, pSWE allow to evaluate stiffness reduction in HCV patient during DAA treatment follow-up, which is related to SVR12.
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Abstract
Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and the second leading cause of cancer-related death worldwide.
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Fraquelli M, Fanetti I, Costantino A. Elastography After Treatment and During Follow-Up. ELASTOGRAPHY OF THE LIVER AND BEYOND 2021:119-141. [DOI: 10.1007/978-3-030-74132-7_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Wei H, Song B. Elastography for Longitudinal Assessment of Liver Fibrosis after Antiviral Therapy: A Review. J Clin Transl Hepatol 2020; 8:445-453. [PMID: 33447528 PMCID: PMC7782123 DOI: 10.14218/jcth.2020.00033] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 07/23/2020] [Accepted: 08/10/2020] [Indexed: 02/05/2023] Open
Abstract
Chronic hepatitis B or C viral infection is a common cause of liver cirrhosis and hepatocellular carcinoma. Fibrosis regression can be achieved after long-term antiviral therapy (AVT). Monitoring of dynamic changes in liver fibrosis after treatment is essential for establishing prognosis and formulation of a follow-up surveillance program. Routine surveillance of fibrosis after AVT by liver biopsy, the gold standard for fibrosis assessment, is hindered by its invasive nature, sampling error and observer variability. Elastography is a noninvasive quantitative alternative that has been widely used and validated for the staging of liver fibrosis prior to treatment. Recently, increasing research interest has been focused on the role of elastography in longitudinal assessment of liver fibrosis after AVT. In this review, the basic principles, acquisition techniques, diagnostic performances, and strengths and limitations of ultrasound elastography and magnetic resonance elastography are presented. Emerging evidence regarding the use of elastography techniques for the monitoring of liver fibrosis after AVT is summarized. Current challenges and future directions are also discussed, designed to optimize the application of these techniques in clinical practice.
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Affiliation(s)
- Hong Wei
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Bin Song
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China
- Correspondence to: Bin Song, Department of Radiology, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, Sichuan 610041, China. Tel: +86-28-85423680, Fax: +86-28-85582499, E-mail:
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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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Analysis of hepatic stiffness after viral eradication in a population with chronic hepatitis C treated with DAAs. Med Clin (Barc) 2020; 156:317-323. [PMID: 32788043 DOI: 10.1016/j.medcli.2020.04.050] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 04/07/2020] [Accepted: 04/15/2020] [Indexed: 12/16/2022]
Abstract
INTRODUCTION AND OBJECTIVES Despite chronic hepatitis C (CHC) is still a global burden as the high morbidity and mortality, the recently approved direct-acting antivirals (DAAs) permit a very high rate of sustained virologic response (SVR) in these patients. The clinical improvement due to viral eradication is being documented, however it is not clear why a subset of patients does not benefit in terms of fibrosis regression or hepatocellular carcinoma (HCC) development. Aim of the study was to assess the hepatic stiffness regression at SVR24 and detect factors impacting stiffness course. PATIENTS AND METHODS Hepatic stiffness assessed by acoustic radiation force impulse (ARFI) and anthropometric- and biochemical parameters were retrospectively collected by 166 CHC patients treated with DAAs, form baseline and SVR24. RESULTS Viral eradication significantly improved overall hepatic stiffness and other related hepatitis hallmarks such as ALT, AST, γGT, platelets count, AST to Platelets ratio Index (APRI), total- and LDL cholesterol. The multiple regression analysis showed that patients with baseline glucose > 110mg/dl presented a stiffness regression significantly lower when compared to low glucose patients (<110mg/dl), moreover baseline HbA1c strongly correlated with DeltaStiffness. 7 patients (4.2%) developed HCC and importantly, presented hyperglycaemia and no stiffness regression nor platelets count recover. CONCLUSIONS Although viral eradication with DAAs entails overall benefits, glycaemic decompensation negatively affects fibrosis regression and probably facilitates HCC development.
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Ito T. Editorial: impact of the introduction of direct-acting anti-viral drugs on hepatocarcinogenesis-a prospective serial follow-up MRI study. Aliment Pharmacol Ther 2020; 52:735-736. [PMID: 32886380 DOI: 10.1111/apt.15911] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Knop V, Mauss S, Goeser T, Geier A, Zimmermann T, Herzer K, Postel N, Friedrich-Rust M, Hofmann WP. Dynamics of liver stiffness by transient elastography in patients with chronic hepatitis C virus infection receiving direct-acting antiviral therapy-Results from the German Hepatitis C-Registry. J Viral Hepat 2020; 27:690-698. [PMID: 32096310 DOI: 10.1111/jvh.13280] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 01/20/2020] [Accepted: 02/09/2020] [Indexed: 12/13/2022]
Abstract
The impact of direct-acting antiviral (DAA) therapies on fibrosis regression remains uncertain. In the current study, we prospectively evaluated dynamics of liver stiffness by transient elastography (TE) in patients with chronic HCV infection receiving DAA-based treatment. Patients (260) were enrolled in the German Hepatitis C-Registry (DHC-R), a national multicentre real-world cohort. Liver stiffness (LS) was assessed at baseline, end of treatment (EOT) and 24 weeks after EOT (FU24) by TE. Biochemical, virological and clinical data were obtained in parallel. In patients with SVR, there was a significant improvement of LS between baseline (median [range], 8.6 [1.7-73.5] kPa) and FU24 (7.9 [1.7-75 kPa]; P < .0001) as well as between EOT (8.4 [1.7-73.5 kPa]) and FU24 [P < .0001]. Stratified by fibrosis stage, patients classified into F4 had higher magnitude of LS reduction between BL (median [range], 25.1 [13.5-73.5] kPa) and FU24 (21.5 [3.1-75] kPa; P = .002) compared to those with F2-F3 (8.9 [7.1-12.4] kPa and 8.8 [4.2-29.1]; P = .060) or F0-F1 (5.3 [1.7-7] kPa and 5.2 [1.7-7.7]; P = .064). In cirrhotic patients, low platelets were significantly associated with lack of liver stiffness improvement, both at EOT (P = .018) and at FU24 (P = .012). LS significantly correlated with ALT (r = .371), AST (r = .552), platelets (r = -.499), GGT (r = .250), bilirubin (r = .230), APRI score (r = .512), FIB-4 score (r = .517) and FORNS index (r = .562); P < .0001. Liver elastography improved significantly in our real-world cohort after DAA-based therapy. As LS correlates similarly with transaminase levels and serum fibrosis markers, it might reflect both reduction of necroinflammation and fibrosis regression.
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Affiliation(s)
- Viola Knop
- Department of Internal Medicine I, Goethe University Hospital, Frankfurt, Germany
| | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Düsseldorf, Germany
| | | | | | - Tim Zimmermann
- I. Department of Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Kerstin Herzer
- Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg, Essen, Germany
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- Leberstiftungs-GmbH Deutschland, Hannover, Germany
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Dash S, Aydin Y, Wu T. Integrated stress response in hepatitis C promotes Nrf2-related chaperone-mediated autophagy: A novel mechanism for host-microbe survival and HCC development in liver cirrhosis. Semin Cell Dev Biol 2020; 101:20-35. [PMID: 31386899 PMCID: PMC7007355 DOI: 10.1016/j.semcdb.2019.07.015] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 06/26/2019] [Accepted: 07/30/2019] [Indexed: 02/06/2023]
Abstract
The molecular mechanism(s) how liver damage during the chronic hepatitis C virus (HCV) infection evolve into cirrhosis and hepatocellular carcinoma (HCC) is unclear. HCV infects hepatocyte, the major cell types in the liver. During infection, large amounts of viral proteins and RNA replication intermediates accumulate in the endoplasmic reticulum (ER) of the infected hepatocyte, which creates a substantial amount of stress response. Infected hepatocyte activates a different type of stress adaptive mechanisms such as unfolded protein response (UPR), antioxidant response (AR), and the integrated stress response (ISR) to promote virus-host cell survival. The hepatic stress is also amplified by another layer of innate and inflammatory response associated with cellular sensing of virus infection through the production of interferon (IFN) and inflammatory cytokines. The interplay between various types of cellular stress signal leads to different forms of cell death such as apoptosis, necrosis, and autophagy depending on the intensity of the stress and nature of the adaptive cellular response. How do the adaptive cellular responses decode such death programs that promote host-microbe survival leading to the establishment of chronic liver disease? In this review, we discuss how the adaptive cellular response through the Nrf2 pathway that promotes virus and cell survival. Furthermore, we provide a glimpse of novel stress-induced Nrf2 mediated compensatory autophagy mechanisms in virus-cell survival that degrade tumor suppressor gene and activation of oncogenic signaling during HCV infection. Based on these facts, we hypothesize that the balance between hepatic stress, inflammation and different types of cell death determines liver disease progression outcomes. We propose that a more nuanced understanding of virus-host interactions under excessive cellular stress may provide an answer to the fundamental questions why some individuals with chronic HCV infection remain at risk of developing cirrhosis, cancer and some do not.
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Affiliation(s)
- Srikanta Dash
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA.
| | - Yucel Aydin
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA
| | - Tong Wu
- Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA
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Diagnostic performance of real-time tissue elastography in chronic hepatitis C patients with sustained virological response. Eur J Gastroenterol Hepatol 2020; 32:609-615. [PMID: 31688308 DOI: 10.1097/meg.0000000000001539] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Real-time tissue elastography is a non-invasive method for measuring liver elasticity. However, there are no reports evaluating the value of real-time tissue elastography for liver fibrosis in hepatitis C virus-infected patients with sustained virological response. The aim of this study is to clarify the diagnostic performance of real-time tissue elastography in patients with sustained virological response. METHODS In this prospective study, we enrolled 425 chronic hepatitis C patients who underwent liver biopsy: 118 patients with sustained virological response (45.8% women) and 307 patients with hepatitis C virus (51.1% women). The post-sustained virological response biopsy was performed 5.9 ± 1.8 years after the therapy. Liver fibrosis index measurements as assessed using real-time tissue elastography were performed on the same day of biopsy. RESULTS The respective mean liver fibrosis index values for fibrosis stages F0, F1, F2, F3, and F4 were 2.82 ± 0.33, 2.90 ± 0.51, 3.06 ± 0.58, 3.65 ± 0.24, and 3.83 ± 0.65, respectively, in patients with sustained virological response. The diagnostic accuracies expressed as areas under the receiver operating characteristic curves in patients with sustained virological response were 0.776 for the diagnosis of significant fibrosis (≥F2), 0.885 for severe fibrosis (≥F3), and 0.860 for cirrhosis (F4), respectively. The optimum cut-off values liver fibrosis index were 3.14 for ≥F2, 3.24 for ≥F3, and 3.30 for F4 in patients with sustained virological response. CONCLUSION Real-time tissue elastography is an acceptable method for predicting the severity of fibrosis in hepatitis C virus patients with sustained virological response.
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Paternostro R, Pfeiffenberger J, Ferenci P, Stättermayer AF, Stauber RE, Wrba F, Longerich T, Lackner K, Trauner M, Ferlitsch A, Reiberger T, Weiss KH. Non-invasive diagnosis of cirrhosis and long-term disease monitoring by transient elastography in patients with Wilson disease. Liver Int 2020; 40:894-904. [PMID: 31898387 PMCID: PMC7187206 DOI: 10.1111/liv.14368] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Revised: 12/05/2019] [Accepted: 12/30/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS The value of liver stiffness measurement (LSM) by transient elastography (TE) for non-invasive fibrosis staging and disease monitoring has not been established in patients with Wilson disease (WD). METHODS Liver stiffness measurement by TE and non-invasive fibrosis scores (APRI, FIB-4) were analysed from 188 WD patients with liver biopsy (LBX). Longitudinal LSM was performed in 128 (68.1%) patients. RESULTS One hundred and eighty-eight patients (mean age: 35 ± 14 years, 54.8% women; 27.1% with histological cirrhosis) were studied. Forty-four[23.4%] patients were recently diagnosed with WD, while 144[76.6%] were previously diagnosed (>1 year between LBX and LSM). Overall, LSM (11.3 vs 6.1 kPa, P < .001), APRI (0.72 vs 0.38, P < .001) and FIB-4 (1.54 vs 0.89, P < .001) were higher in cirrhotic than in non-cirrhotic patients. This was even more pronounced in recently diagnosed patients (35.2 kPa vs 6.4 kPa, P < .001). Accuracy for diagnosing cirrhosis at an LSM cut-off ≥9.9 kPa was better in recently diagnosed (PPV: 74%, NPV: 100%) vs previously diagnosed (PPV: 53%, NPV: 82%) patients. Recently diagnosed patients had higher Area Under the Curve (AUC) for APRI (0.79 vs 0.61) and FIB-4 (0.84 vs 0.65) than previously diagnosed patients. At APRI <1.5 and FIB-4 <3.25 cirrhosis was ruled out with a specificity of 93% and 95% respectively. During a median follow-up of 46 (24-66) months, only 5.9% (5/85) of non-cirrhotic WD patients showed progression to cirrhotic LSM values, while 30.8% (4/13) of cirrhotic WD patients showed LSM suggestive of cirrhosis regression. CONCLUSION TE-based LSM ≥9.9 kPa accurately identifies cirrhosis in WD patients. Next to TE-LSM <9.9 kPa, APRI <1.5 and FIB-4 <3.25 values assist to non-invasively rule out cirrhosis. LSM remains stable in most non-cirrhotic patients on WD therapy, while one-third of cirrhotic patients present clinically relevant decreases in LSM.
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Affiliation(s)
- Rafael Paternostro
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Jan Pfeiffenberger
- Department of Internal Medicine IVUniversity Hospital HeidelbergHeidelbergGermany
| | - Peter Ferenci
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Albert F. Stättermayer
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Rudolf E. Stauber
- Division of Gastroenterology and HepatologyDepartment of Internal MedicineMedical University of GrazGrazAustria
| | - Fritz Wrba
- Department of PathologyMedical University of ViennaViennaAustria
| | - Thomas Longerich
- Institute of PathologyUniversity Hospital HeidelbergHeidelbergGermany
| | | | - Michael Trauner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Arnulf Ferlitsch
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Thomas Reiberger
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Ludwig Boltzmann Institute for Rare and Undiagnosed DiseasesViennaAustria,CeMM Research Center for Molecular Medicine of the Austrian Academy of SciencesViennaAustria
| | - Karl Heinz Weiss
- Department of Internal Medicine IVUniversity Hospital HeidelbergHeidelbergGermany
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Tojima H, Kakizaki S, Takakusagi S, Hoshino T, Naganuma A, Nagashima T, Namikawa M, Ueno T, Shimada Y, Hatanaka T, Takizawa D, Arai H, Sato K, Takagi H, Uraoka T. Favorable outcome of retreatment by direct-acting antivirals for hepatitis C patients with daclatasvir plus asunaprevir combination therapy failure. Hepatol Res 2020; 50:303-312. [PMID: 31750974 DOI: 10.1111/hepr.13462] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 10/23/2019] [Accepted: 11/01/2019] [Indexed: 12/13/2022]
Abstract
AIM In patients with hepatitis C virus, treatment failure of daclatasvir plus asunaprevir combination therapy (DCV + ASV) seems to become intractable due to the induction of resistance-associated substitutions. This study aimed to investigate the outcomes of retreatment with direct-acting antivirals (DAAs) in patients with DCV + ASV therapy failure, as well as changes in drug resistance mutations. METHODS We retrospectively analyzed 44 patients re-treated with DAAs after DCV + ASV failure between December 2015 and April 2018. All patients were analyzed for amino acid substitutions, and additional treatment regimens were selected based on the results and current treatment guidelines. RESULTS The sustained virological response rate with second-line treatment was 81.8% (36/44), and relapse occurred in five of 16 patients who received sofosbuvir/ledipasvir and three of seven patients who received DCV/ASV/beclabuvir. Third- and fourth-line treatments were also tried in relapsed cases, and the overall sustained virological response rates were 90.9% (40/44) and 93.2% (41/44), respectively. A high rate of viral clearance was eventually observed. Before second-line treatment, the prevalence of mutations in the NS5A and NS3/4A regions was 100% (44/44) and 86.4% (38/44), respectively. There was no significant increase in the number of amino acid substitutions in patients for whom second-line treatment failed. CONCLUSIONS Amino acid substitutions were frequently observed in patients with DCV + ASV failure, but most patients achieved a sustained virological response after retreatment with DAAs. Although the spread of drug-resistant viruses due to unsuccessful DAA treatment was a matter of concern, most cases of DCV + ASV failure were overcome with additional treatment.
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Affiliation(s)
- Hiroki Tojima
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Satoru Kakizaki
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | | | - Takashi Hoshino
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Tamon Nagashima
- Department of Gastroenterology, National Hospital Organization Shibukawa Medical Center, Shibukawa, Japan
| | - Masashi Namikawa
- Department of Internal Medicine, Kiryu Kosei General Hospital, Kiryu, Japan
| | - Takashi Ueno
- Department of Internal Medicine, Isesaki Municipal Hospital, Isesaki, Japan
| | - Yasushi Shimada
- Department of Internal Medicine, Isesaki Municipal Hospital, Isesaki, Japan
| | - Takeshi Hatanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Japan
| | - Daichi Takizawa
- Department of Gastroenterology, Maebashi Red Cross Hospital, Maebashi, Japan
| | - Hirotaka Arai
- Department of Gastroenterology, Maebashi Red Cross Hospital, Maebashi, Japan
| | - Ken Sato
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Hitoshi Takagi
- Department of Gastroenterology, Kusunoki Hospital, Fujioka, Japan
| | - Toshio Uraoka
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Japan
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Kohla MAS, Fayoumi AE, Akl M, Abdelkareem M, Elsakhawy M, Waheed S, Abozeid M. Early fibrosis regression by shear wave elastography after successful direct-acting anti-HCV therapy. Clin Exp Med 2020; 20:143-148. [PMID: 31792631 DOI: 10.1007/s10238-019-00597-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Accepted: 11/27/2019] [Indexed: 12/17/2022]
Abstract
Shear wave elastography (SWE) is a noninvasive ultrasound-based marker of hepatic fibrosis not requiring a special device. Successful direct-acting anti-HCV therapy was associated with hepatic fibrosis regression assessed by transient elastography (FibroScan). Data on the utility of SWE in these patients and how early fibrosis can regress after treatment are still lacking. To assess liver fibrosis by SWE before and after direct-acting antiviral treatment of chronic hepatitis C (CHC), we enrolled 165 CHC genotype 4 Egyptian patients treated with different Sofosbuvir-based regimens. Patients' laboratory characteristics, fibrosis biomarkers, namely Fibrosis-4 (FIB-4) index and AST/platelet ratio index (APRI) and liver stiffness measurements (LSM) by SWE were evaluated at baseline, end of treatment (EOT at week 12), week 24 and week 36. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as well as FIB-4 and APRI indices decreased significantly at EOT, week 24 and week 36 in comparison to baseline (P value < 0.001). Although platelet counts did not significantly differ between baseline and EOT, they increased significantly from EOT to week 24 and week 36 with a P value < 0.001. The mean LSM showed improvement at EOT (7.01 ± 3.59 kpa), week 24 (6.18 ± 3.39 kpa) and week 36 (5.74 ± 3.21 kpa) in comparison to baseline (8.49 ± 0.83 kpa) (P value < 0.001). There is early liver fibrosis regression at EOT and throughout the time after successful treatment with direct-acting antiviral agents (DAAs). SWE is a feasible, easily applicable noninvasive relatively inexpensive assessment method of liver fibrosis.
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Affiliation(s)
- Mohamed Ahmed Samy Kohla
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt.
| | - Ahmed El Fayoumi
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
| | - Mohamed Akl
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
| | - Mervat Abdelkareem
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
| | - Mahmoud Elsakhawy
- Department of Diagnostic and Interventional Radiology and Medical Imaging, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
| | - Sally Waheed
- Department of Epidemiology and Preventive Medicine, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
| | - Mai Abozeid
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
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Stasi C, Sadalla S, Carradori E, Monti M, Petraccia L, Madia F, Gragnani L, Zignego AL. Longitudinal evaluation of liver stiffness and outcomes in patients with chronic hepatitis C before and after short- and long-term IFN-free antiviral treatment. Curr Med Res Opin 2020; 36:245-249. [PMID: 31702411 DOI: 10.1080/03007995.2019.1691517] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Background: New direct-acting antiviral drugs can eradicate hepatitis C virus (HCV) infection in over 90% of patients and can even reduce the risk of complications in advanced fibrosis/cirrhosis. The aims of this study were to evaluate (1) changes in fibrosis during and after antiviral treatment and (2) incidence of hepatocarcinoma and mortality in various fibrosis stages.Methods: This is a longitudinal monocentric prospective study. Blood and instrumental examinations were evaluated at baseline, at the end of therapy, and 1 and 2 years following treatment.Results: Two hundred and ninety-six patients with chronic HCV were evaluated, of whom 115 were experienced, 181 were treatment-naïve, and 2 had previous hepatocellular carcinoma (HCC) and were therefore excluded from the study. At baseline, stiffness values were 13.46 ± 9.97 kPa. Out of the 294 HCV patients enrolled, 100 had lymphoproliferative disorders and were evaluated separately. This group of patients showed stiffness values pertaining to the F0-F2 group (mean stiffness values were 6.07 ± 1.68 kPa). All other patients showed stiffness values pertaining to the F3-F4 group (mean stiffness values were 17.93 ± 10.23). No statistically significant difference was found between stiffness at baseline compared to the end of treatment (EOT), while significant differences were found between the baseline, 1 year (p = .05), and 2 year follow-ups (p < .01). Significant differences were found between baseline and EOT, as well as 1 and 2 years after the end of treatment (p < .001) in the F3-F4 group. Four out of 140 patients with baseline cirrhosis developed HCC during the post-treatment follow-up, 1 of whom died.Conclusions: Non-invasive methods provide important prognostic information, particularly concerning the observed regression of fibrosis and could be extremely useful for monitoring patients with long life expectancies after direct-acting antiviral treatment.
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Affiliation(s)
- Cristina Stasi
- Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
| | - Sinan Sadalla
- Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
| | - Eleonora Carradori
- Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
| | - Monica Monti
- Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
| | - Luisa Petraccia
- Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
| | - Francesco Madia
- Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
| | - Laura Gragnani
- Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
| | - Anna Linda Zignego
- Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Internal Medicine and Liver Unit, Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy
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Liver stiffness in chronic hepatitis C virus infection. ACTA ACUST UNITED AC 2020; 57:85-98. [PMID: 30447147 DOI: 10.2478/rjim-2018-0034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Indexed: 11/20/2022]
Abstract
INTRODUCTION The severity of liver fibrosis can be assessed noninvasively today by liver stiffness measurements. Vibration-controlled transient elastography, shear wave elastography or magnetic resonance elastography are techniques increasingly used for this purpose. METHODS This article presents the recent advances in the use of new techniques for liver fibrosis assessment in chronic hepatitis C: the correlation between liver stiffness values and liver fibrosis estimated by liver biopsies, the prognosis role of liver stiffness values, their usefulness in monitoring the treatment response, in assessing the severity of portal hypertension and in estimating the presence of esophageal varices. Scientific articles from January 2017 to January 2018 were searched in PubMed and PubMed Central databases, using the terms "liver stiffness" and "hepatitis C". RESULTS The median liver stiffness values measured with different techniques are not identical, so that FibroScan thresholds cannot be used on any other elastographic machine. The higher the liver's stiffness measurement, the higher the liver-related events in patients with chronic hepatitis C. A liver stiffness measurement over 17 kPa could be an independent predictor for the presence of esophageal varices as well as a spleen with a longitudinal span ≥ 15 cm for patients with a value of liver stiffness < 17 kPa. A progressive and persistent decrease in liver stiffness is dependent on sustained virological response achievement. The lack of liver stiffness decrease has been associated with relapsers and a low value of liver stiffness at baseline. CONCLUSION Liver stiffness provides clues about the severity and evolution of liver disease.
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Lee SH, Shin HP, Lee JI. Real-world single-center experience with direct-acting antivirals for improvement of the liver fibrosis after chronic hepatitis C treatment. Antivir Chem Chemother 2020; 28:2040206620974835. [PMID: 33215505 PMCID: PMC7683836 DOI: 10.1177/2040206620974835] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 10/28/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Recently, new direct-acting antivirals (DAAs) are known to eradicate chronic hepatitis C (CHC) virus infection and prevent the progression of liver fibrosis. Liver fibrosis may predispose to liver cirrhosis or hepatocellular carcinoma. We investigated the effect of DAAs on liver fibrosis using non-invasive methods, and evaluated the correlations of these methods. METHODS We retrospectively analyzed 68 patients with CHC who were treated with DAAs and reached sustained virologic response at 12 weeks post-treatment from January 2016 to October 2018. The degree of liver fibrosis was assessed using serum biomarkers, such as AST-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) index. Liver stiffness was assessed using two-dimensional shear-wave elastography (2 D-SWE). The pre- and post-treatment serum biomarker levels and SWE findings were evaluated and compared. RESULTS A total of 68 patients with CHC were enrolled. The median age was 58 years (52.3-73 years) and 37 patients (54.4%) were female. After treatment, the median APRI was decreased from 0.701 to 0.328 (P < 0.0001), and the median FIB-4 was decreased from 2.355 to 1.860 (P < 0.0001). The median kPa in 2 D-SWE significantly reduced from 6.85 to 5.66 (P = 0.013). APRI and FIB-4 were significantly correlated pre- and post-treatment; however, the correlation between the serum biomarkers and 2 D-SWE was partially significant. CONCLUSION The serum fibrosis biomarkers and liver stiffness on 2 D-SWE were shown to be improved after the treatment with DAAs. Further research including larger number of patients is needed to compare the efficacy of each evaluating method.
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Affiliation(s)
| | - Hyun Phil Shin
- Hyun Phil Shin, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, 892 Dongnam-ro, Gangdong-gu, Seoul 05278, Republic of Korea.
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