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Tada T, Kurosaki M, Toyoda H, Tamaki N, Yasui Y, Nakamura S, Mori N, Tsuji K, Ochi H, Akahane T, Kobashi H, Fujii H, Marusawa H, Kondo M, Urawa N, Yoshida H, Uchida Y, Morita A, Hasebe C, Mitsuda A, Ogawa C, Narita R, Kubotsu Y, Matsushita T, Shigeno M, Okamoto E, Okada K, Kasai T, Ishii T, Nonogi M, Yasuda S, Koshiyama Y, Kumada T, Izumi N. Viral eradication reduces all-cause mortality in patients with chronic hepatitis C virus infection who had received direct-acting antiviral therapy. Liver Int 2024; 44:3060-3071. [PMID: 39223936 DOI: 10.1111/liv.16093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 08/01/2024] [Accepted: 08/22/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND AND AIMS The impact of hepatitis C virus (HCV) eradication via direct-acting antiviral (DAA) therapy on overall mortality, particularly non-liver-related mortality, is understudied. METHODS We recruited 4180 patients with chronic HCV infection who achieved sustained virological response (SVR) (HCV eradication) through DAA therapy (n = 2501, SVR group) or who did not receive antiviral therapy (n = 1679, non-SVR group); 1236 from each group were chosen using propensity score matching. Causes of death and all-cause mortality, including non-liver-related diseases, were investigated. RESULTS Of the 4180 patients, 592 died during the follow-up period. In the SVR group, the mortality rates from liver-related and non-liver-related diseases were 16.5% and 83.5%, respectively. Compared to the non-SVR group, mortality rates from liver-related and non-liver-related diseases were 50.1% and 49.9%, respectively (p < .001). In non-cirrhotic patients, multivariable analysis revealed that SVR was an independent factor associated with both liver-related (hazard ratio [HR], .251; 95% confidence interval [CI], .092-.686) and non-liver-related (HR, .641; 95% CI, .415-.990) mortalities. In cirrhotic patients, multivariable analysis revealed that SVR remained an independent factor significantly associated with liver-related mortality (HR, .151; 95% CI, .081-.279). In propensity score-matched patients, the eradication of HCV (SVR group) decreased both liver-related (p < .001) and non-liver-related mortality (p = .008) rates compared to persistent HCV infection (non-SVR group). CONCLUSIONS The elimination of HCV via DAA therapy reduced not only liver-related mortality but also non-liver-related mortality in patients with chronic HCV.
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Affiliation(s)
- Toshifumi Tada
- Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital, Himeji, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Shinichiro Nakamura
- Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital, Himeji, Japan
| | - Nami Mori
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Keiji Tsuji
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Hironori Ochi
- Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - Takehiro Akahane
- Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Japan
| | - Haruhiko Kobashi
- Department of Gastroenterology, Japanese Red Cross Okayama Hospital, Okayama, Japan
| | - Hideki Fujii
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Hiroyuki Marusawa
- Department of Gastroenterology and Hepatology, Japanese Red Cross Osaka Hospital, Osaka, Japan
| | - Masahiko Kondo
- Department of Gastroenterology, Japanese Red Cross Otsu Hospital, Otsu, Japan
| | - Naohito Urawa
- Department of Hepatology, Japanese Red Cross Ise Hospital, Ise, Japan
| | - Hideo Yoshida
- Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Yasushi Uchida
- Department of Gastroenterology, Japanese Red Cross Matsue Hospital, Matsue, Japan
| | - Atsuhiro Morita
- Department of Gastroenterology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan
| | - Chitomi Hasebe
- Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Asahikawa, Japan
| | - Akeri Mitsuda
- Department of Gastroenterology, Tottori Red Cross Hospital, Tottori, Japan
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Ryoichi Narita
- Department of Gastroenterology, Oita Red Cross Hospital, Oita, Japan
| | - Yoshihito Kubotsu
- Department of Internal Medicine, Karatsu Red Cross Hospital, Saga, Japan
| | | | - Masaya Shigeno
- Department of Gastroenterology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan
| | - Eisuke Okamoto
- Department of Gastroenterology, Masuda Red Cross Hospital, Masuda, Japan
| | - Kazuhiko Okada
- Department of Gastroenterology, Toyama Red Cross Hospital, Toyama, Japan
| | - Toyotaka Kasai
- Department of Gastroenterology, Fukaya Red Cross Hospital, Saitama, Japan
| | - Toru Ishii
- Department of Gastroenterology, Japanese Red Cross Akita Hospital, Akita, Japan
| | - Michiko Nonogi
- Department of Gastroenterology, Tokushima Red Cross Hospital, Tokushima, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
| | - Yuichi Koshiyama
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Gifu, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
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Papasavvas E, Lu L, Fair M, Oliva I, Cassel J, Majumdar S, Mounzer K, Kostman JR, Tebas P, Bar-Or A, Muthumani K, Montaner LJ. Cloning and Functional Characterization of Novel Human Neutralizing Anti-IFN-α and Anti-IFN-β Antibodies. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2024; 213:808-822. [PMID: 39109927 PMCID: PMC11575944 DOI: 10.4049/jimmunol.2400265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 07/15/2024] [Indexed: 09/05/2024]
Abstract
Type I IFNs play a pivotal role in immune response modulation, yet dysregulation is implicated in various disorders. Therefore, it is crucial to develop tools that facilitate the understanding of their mechanism of action and enable the development of more effective anti-IFN therapeutic strategies. In this study, we isolated, cloned, and characterized anti-IFN-α and anti-IFN-β Abs from PBMCs of individuals treated with IFN-α or IFN-β, harboring confirmed neutralizing Abs. Clones AH07856 and AH07857 were identified as neutralizing anti-IFN-α-specific with inhibition against IFN-α2a, -α2b, and -αK subtypes. Clones AH07859 and AH07866 were identified as neutralizing anti-IFN-β1a-specific signaling and able to block lipopolysaccharide or S100 calcium-binding protein A14-induced IFN-β signaling effects. Cloned Abs bind rhesus but not murine IFNs. The specificity of inhibition between IFN-α and IFN-β suggests potential for diverse research and clinical applications.
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Affiliation(s)
- Emmanouil Papasavvas
- The Wistar Institute, Philadelphia, Pennsylvania, 19104, United States of America
| | - Lily Lu
- The Wistar Institute, Philadelphia, Pennsylvania, 19104, United States of America
| | - Matthew Fair
- The Wistar Institute, Philadelphia, Pennsylvania, 19104, United States of America
| | - Isabela Oliva
- The Wistar Institute, Philadelphia, Pennsylvania, 19104, United States of America
| | - Joel Cassel
- The Wistar Institute, Philadelphia, Pennsylvania, 19104, United States of America
| | - Sonali Majumdar
- The Wistar Institute, Philadelphia, Pennsylvania, 19104, United States of America
| | - Karam Mounzer
- Jonathan Lax Immune Disorders Treatment Center, Philadelphia Field Initiating Group for HIV-1 Trials, Philadelphia, Pennsylvania, 19107, USA
| | - Jay R. Kostman
- Jonathan Lax Immune Disorders Treatment Center, Philadelphia Field Initiating Group for HIV-1 Trials, Philadelphia, Pennsylvania, 19107, USA
- John Bell Health Center, Philadelphia Field Initiating Group for HIV-1 Trials, Philadelphia, Pennsylvania, 19107, USA
| | - Pablo Tebas
- Department of Medicine, Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
| | - Amit Bar-Or
- Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics, Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
| | - Kar Muthumani
- The Wistar Institute, Philadelphia, Pennsylvania, 19104, United States of America
- Current Address: GeneOne Life Science Inc, Fort Washington, Pennsylvania, 19034, USA
| | - Luis J. Montaner
- The Wistar Institute, Philadelphia, Pennsylvania, 19104, United States of America
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Papasavvas E, Lu L, Fair M, Oliva I, Cassel J, Majumdar S, Mounzer K, Kostman JR, Tebas P, Bar-Or A, Muthumani K, Montaner LJ. Cloning and functional characterization of novel human neutralizing anti-interferon-alpha and anti-interferon-beta antibodies. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.05.05.591636. [PMID: 38746170 PMCID: PMC11092762 DOI: 10.1101/2024.05.05.591636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/16/2024]
Abstract
Type I interferons (IFNs) play a pivotal role in immune response modulation, yet dysregulation is implicated in various disorders. Therefore, it is crucial to develop tools that facilitate the understanding of their mechanism of action and enable the development of more effective anti-IFN therapeutic strategies. In this study, we isolated, cloned, and characterized anti-IFN-α and anti-IFN-β antibodies (Abs) from peripheral blood mononuclear cells of individuals treated with IFN-α or IFN-β, harboring confirmed neutralizing Abs. Clones AH07856 and AH07857 were identified as neutralizing anti-IFN-α-specific with inhibition against IFN-α2a, -α2b, and -αK subtypes. Clones AH07859 and AH07866 were identified as neutralizing anti-IFN-β1a-specific signaling, and able to block Lipopolysaccharide or S100 calcium binding protein A14-induced IFN-β signaling effects. Cloned Abs bind rhesus but not murine IFNs. The specificity of inhibition between IFN-α and IFN-β suggests potential for diverse research and clinical applications.
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Masaoka R, Gyotoku Y, Shirahashi R, Suda T, Tamano M. Combining the age-male-albumin-bilirubin-platelets score and shear wave elastography stratifies carcinogenic risk in hepatitis C patients after viral clearance. World J Clin Cases 2023; 11:5204-5214. [PMID: 37621583 PMCID: PMC10445062 DOI: 10.12998/wjcc.v11.i22.5204] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/23/2023] [Accepted: 07/07/2023] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND The treatment of hepatitis C with direct-acting antiviral agents (DAAs) produces a high rate of sustained virological response (SVR) with fewer adverse events than interferon (IFN) therapy with a similar effect in inhibiting carcinogenesis as IFN therapy. The age-male-albumin-bilirubin-platelets (aMAP) score is useful for stratifying the risk of hepatocellular carcinoma in chronic hepatitis patients, and the velocity of shear waves (Vs) measured by shear wave elastography has also been shown to be useful for diagnosing the level of fibrotic progression in hepatitis C and predicting carcinogenic risk. Combining these two may improve the prediction of carcinogenic risk. AIM To determine whether combining the aMAP score with Vs improves carcinogenic risk stratification in medium-to-high-risk hepatitis C patients. METHODS This retrospective, observational study involved hepatitis C patients treated with DAAs who achieved SVR. Vs was measured before treatment (baseline), at the end of treatment (EOT), and 12 wk (follow-up 12) and 24 wk (follow-up 24) after treatment. The patients were followed for at least six months after EOT to determine whether cancer developed. Multiple regression analysis was used to identify factors contributing to hepatic carcinogenesis. The diagnostic performances of clinical parameters for predicting the presence of hepatocellular carcinoma were evaluated using receiver-operating characteristic (ROC) curve analyses. RESULTS A total of 279 patients (mean age 65.9 years, 118 males, 161 females) were included in the analysis. Multiple regression analysis was performed with carcinogenesis as the target variable and alanine aminotransferase, platelets, α-fetoprotein, Vs, and the Fib-4 index as explanatory variables; only Vs was found to be significant (P = 0.0296). The cut-off value for Vs for liver carcinogenesis calculated using the ROC curve was 1.53 m/s. Carcinoma developed in 2.0% (3/151) of those with Vs < 1.53 m/s and in 10.5% (9/86) of those with Vs ≥ 1.53 m/s. CONCLUSION In hepatitis C patients after SVR, combining the aMAP score and Vs to stratify the risk of carcinogenesis is more efficient than uniform surveillance of all patients.
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Affiliation(s)
- Rion Masaoka
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
| | - Yoshinori Gyotoku
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
| | - Ryosaku Shirahashi
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
| | - Toshikuni Suda
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
| | - Masaya Tamano
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
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Tada T, Kurosaki M, Tamaki N, Yasui Y, Mori N, Tsuji K, Hasebe C, Joko K, Akahane T, Furuta K, Kobashi H, Fujii H, Ishii T, Marusawa H, Kondo M, Kojima Y, Yoshida H, Uchida Y, Nakamura S, Izumi N. General evaluation score
for predicting the development of
hepatocellular carcinoma
in patients with advanced liver fibrosis associated with
hepatitis C virus
genotype 1 or 2 after
direct‐acting antiviral
therapy. JGH Open 2022; 6:487-495. [PMID: 35822118 PMCID: PMC9260214 DOI: 10.1002/jgh3.12778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 05/05/2022] [Accepted: 05/24/2022] [Indexed: 11/28/2022]
Abstract
Background and Aim To validate a composite predictive model for hepatocellular carcinoma (HCC) development in patients with advanced liver fibrosis associated with chronic hepatitis C virus (HCV) who have received direct‐acting antiviral (DAA) therapy and achieved sustained virologic response (SVR). Methods This study included 1258 patients with advanced liver fibrosis associated with HCV genotype 1, 2, or both. General evaluation score (GES), which is based on sex, age, fibrosis stage, albumin, and α‐fetoprotein, was used as a composite predictive model. Results There were 645 (51.3%) patients in the low‐risk group, 228 (18.1%) in the intermediate‐risk group, and 385 (30.6%) in the high‐risk group based on GES categories. The 12‐, 36‐, and 60‐month cumulative incidence of HCC was 0.7%, 5.3%, and 13.0%, respectively. Multivariable analysis with Cox proportional hazards models showed that male sex (hazard ratio [HR], 1.863; 95% confidence interval [CI], 1.204–2.883), F4 fibrosis stage (HR, 3.199; 95% CI, 1.696–6.036), and albumin (HR, 0.489; 95% CI, 0.288–0.828) are independently associated with HCC development. The incidence of HCC differed significantly by GES‐based risk category (P < 0.001). Cox proportional hazards models showed that, with the low‐risk group as the referent, the HR for HCC development was 1.875 (95% CI, 1.000–3.514) in the intermediate‐risk group and 2.819 (95% CI, 1.716–4.630) in the high‐risk group. GES had better predictive ability for HCC development than fibrosis‐4 index according to time‐dependent receiver operating characteristic analysis. Conclusion GES is useful for predicting HCC development in patients with advanced liver fibrosis after SVR.
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Affiliation(s)
- Toshifumi Tada
- Department of Internal Medicine Japanese Red Cross Society Himeji Hospital Himeji Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Nami Mori
- Department of Gastroenterology Hiroshima Red Cross Hospital and Atomic‐Bomb Survivors Hospital Hiroshima Japan
| | - Keiji Tsuji
- Department of Gastroenterology Hiroshima Red Cross Hospital and Atomic‐Bomb Survivors Hospital Hiroshima Japan
| | - Chitomi Hasebe
- Department of Gastroenterology Japanese Red Cross Asahikawa Hospital Asahikawa Japan
| | - Koji Joko
- Center for Liver‐Biliary‐Pancreatic Disease Matsuyama Red Cross Hospital Matsuyama Japan
| | - Takehiro Akahane
- Department of Gastroenterology Japanese Red Cross Ishinomaki Hospital Ishinomaki Japan
| | - Koichiro Furuta
- Department of Gastroenterology Masuda Red Cross Hospital Masuda Japan
| | - Haruhiko Kobashi
- Department of Gastroenterology Japanese Red Cross Okayama Hospital Okayama Japan
| | - Hideki Fujii
- Department of Gastroenterology Japanese Red Cross Kyoto Daiichi Hospital Kyoto Japan
| | - Toru Ishii
- Department of Gastroenterology Japanese Red Cross Akita Hospital Akita Japan
| | - Hiroyuki Marusawa
- Department of Gastroenterology and Hepatology Japanese Red Cross Osaka Hospital Osaka Japan
| | - Masahiko Kondo
- Department of Gastroenterology Japanese Red Cross Otsu Hospital Otsu Shiga Japan
| | - Yuji Kojima
- Department of Hepatology Japanese Red Cross Ise Hospital Ise Japan
| | - Hideo Yoshida
- Department of Gastroenterology Japanese Red Cross Medical Center Tokyo Japan
| | - Yasushi Uchida
- Department of Gastroenterology Japanese Red Cross Matsue Hospital Matsue Japan
| | - Shinichiro Nakamura
- Department of Internal Medicine Japanese Red Cross Society Himeji Hospital Himeji Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
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Poordad F, Felizarta F, Yao BB, Overcash JS, Hassanein T, Agarwal K, Gane E, Shaw D, Waters M, Krishnan P, Topp A, Burroughs M, Nevens F. Durability of sustained virological response to glecaprevir/pibrentasvir and resistance development: A long-term follow-up study. Liver Int 2022; 42:1278-1286. [PMID: 35220658 DOI: 10.1111/liv.15211] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 01/14/2022] [Accepted: 02/16/2022] [Indexed: 02/13/2023]
Abstract
BACKGROUND AND AIMS This study aimed to determine durability of sustained virologic response (SVR) in hepatitis C virus-infected participants treated with glecaprevir- and/or pibrentasvir-containing regimens. METHODS M13-576, a rollover study, evaluated the durability of SVR in a follow-up period of approximately 3 years after hepatitis C virus genotype 1-6-infected participants received a glecaprevir- and/or pibrentasvir-containing regimen in previous phase 2/3 clinical trials. The primary efficacy endpoint was the percentage of participants maintaining SVR and the percentage of participants experiencing relapse or reinfections. Resistance-associated substitutions and safety outcomes related to liver progression were also assessed. RESULTS Of 384 participants enroled, 377 participants were included in the as-observed population and 287 participants completed the study. In prior studies, 99.7% (376/377) of participants achieved SVR12; of those, an observed 99.5% (374/376) and 100% (286/286) completing the study, maintained SVR. After non-responder imputation of missing data, 286/376 participants (76%) maintained SVR. The participant previously not achieving SVR was a treatment-experienced male with compensated cirrhosis who had NS3 and NS5A substitutions at enrolment, which remained detectable for 12 months. Of the two participants not maintaining SVR, one was re-infected and one experienced late relapse at post-treatment week 60. Five participants (all with a fibrosis stage ≥F3) had hepatocellular carcinoma. No events were deemed related to glecaprevir/pibrentasvir. CONCLUSIONS Glecaprevir/pibrentasvir demonstrated long-term durability of efficacy after SVR12 was achieved. Hepatic-related decompensation events were not seen. Owing to low incidence of virologic failure, conclusions were not drawn on persistence of resistance-associated substitutions.
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Affiliation(s)
- Fred Poordad
- The Texas Liver Institute, University of Texas Health, San Antonio, Texas, USA
| | | | | | | | - Tarek Hassanein
- Southern California GI and Liver Centers and Southern California Research Center, Coronado, California, USA
| | - Kosh Agarwal
- Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London, UK
| | - Edward Gane
- New Zealand Liver Transplant Unit, University of Auckland, Auckland, New Zealand
| | - David Shaw
- Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | | | | | | | | | - Frederik Nevens
- Department of Gastroenterology and Hepatology, University Hospital KULeuven, Leuven, Belgium
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Negm EM. Does mass management of chronic hepatitis C protect the Egyptian population against fulminant coronavirus disease-2019? “Postulating a hypothesis”. THE EGYPTIAN JOURNAL OF BRONCHOLOGY 2022. [PMCID: PMC8961476 DOI: 10.1186/s43168-022-00120-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Coronavirus disease (COVID-19) is caused by the pathogenic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Egypt has launched a national treatment program to provide a cure for Egyptian patients infected with hepatitis C virus (HCV). A common mechanism is shared between both the anticipated and unexpected aspects of COVID-19. The activity of the renin-angiotensin system (RAS) is intrinsically high in the lungs, which is a major source of ACE and hence a significant site of systemic synthesis of Ang II. Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS-CoV-2, the etiological agent of the COVID-19 disease. ACE-2 and its angiotensin 1–7 (Ang 1–7) product, which acts on the Mas oncogene receptor, have been shown to play a protective role in fibrogenesis and inflammation of many organs, including the liver and lung. Antiviral treatment with interferon (IFN) in conjunction with ribavirin in patients with chronic hepatitis C reduces serum ACE activity and indirectly affects liver parenchyma fibrogenesis. The antifibrotic activity of sofosbuvir plus daclatasvir (SOF/DAC) is independent of its antiviral action. Elimination of HCV infection by DAA therapy in patients with chronic hepatitis C could improve natural killer (NK) activity by increasing the frequency of CD 16+ CD 56+ NK cells. COVID-19 individuals exhibit enhanced platelet activation and aggregation, as well as platelet-monocyte aggregation, which is linked to coagulative disorders. Lower systemic inflammation and enhanced hepatic synthesis of both pro- and anti-coagulant factors were noticed soon after antiviral therapy. In order to protect against the severity of COVID-19, treatment of chronic hepatitis C has been observed as a possible key as a prophylaxis beside the vaccine and should be tested for evidence or rejection of observation.
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Trifan A, Stratina E, Rotaru A, Stafie R, Zenovia S, Nastasa R, Huiban L, Sfarti C, Cojocariu C, Cuciureanu T, Muzica C, Chiriac S, Girleanu I, Singeap AM, Stanciu C. Changes in Liver Steatosis Using Controlled Attenuation Parameter among Patients with Chronic Hepatitis C Infection Treated with Direct-Acting Antivirals Therapy Who Achieved Sustained Virological Response. Diagnostics (Basel) 2022; 12:702. [PMID: 35328255 PMCID: PMC8947513 DOI: 10.3390/diagnostics12030702] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection induces hepatic steatosis due to viral and host factors. However, information regarding the effects of direct-acting antivirals (DAAs) therapy on liver steatosis and fibrosis is limited. Vibration-controlled transient elastography (VCTE) with a controlled attenuation parameter (CAP) represents a non-invasive method, which has been used in the last few years for the detection of hepatic steatosis and fibrosis before and at a sustained virological response at 12 weeks (SVR12). The aim of this study was to assess the modifications of liver steatosis and fibrosis in HCV-infected patients who achieved SVR12. Consecutive patients with chronic HCV infection that were treated with DAAs in a tertiary gastroenterology center from Romania were included. Demographics, laboratory data, and VCTE evaluation were recorded in all patients. Patients with previous hepatic decompensation and those who did not achieve SVR were excluded. Two hundred and eighty patients (67.1% females) who achieved SVR12 were included. Regarding the changes in biological parameters, including liver enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), reduced to normal levels at SVR12 compared to the baseline (28.72 ± 24.71 U/L vs. 40.72 ± 27.34 U/L for ALT, p < 0.013 and 27.21 ± 11.15 U/L vs. 33.35 ± 23.37 U/L for AST, p = 0.029). On the contrary, the levels of triglycerides increased significantly from the baseline to SVR12 (124.03 ± 113.49 mg/dL to 153.78 ± 94.53, p = 0.004). Regarding hepatic steatosis by CAP evaluation, at SVR12, 186 (66.4%) of the individuals had a CAP score of ≥248 dB/m, an increase of 4.6% from the baseline. After viral eradication with DAAs, we observed an increase in hepatic steatosis. Hence, a long-term follow-up is mandatory to identify HCV-infected patients with hepatic steatosis post-SVR and the risk factors for more severe outcomes.
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Affiliation(s)
- Anca Trifan
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Ermina Stratina
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Adrian Rotaru
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Remus Stafie
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Sebastian Zenovia
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Robert Nastasa
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Laura Huiban
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Catalin Sfarti
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Tudor Cuciureanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Cristina Muzica
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Stefan Chiriac
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Irina Girleanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Ana-Maria Singeap
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
| | - Carol Stanciu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 700111 Iasi, Romania; (A.T.); (A.R.); (R.S.); (S.Z.); (L.H.); (C.S.); (C.C.); (T.C.); (C.M.); (S.C.); (I.G.); (A.-M.S.); (C.S.)
- Department of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700115 Iasi, Romania
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9
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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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10
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Tada T, Kurosaki M, Tamaki N, Yasui Y, Mori N, Tsuji K, Hasebe C, Joko K, Akahane T, Furuta K, Kobashi H, Kimura H, Yagisawa H, Marusawa H, Kondo M, Kojima Y, Yoshida H, Uchida Y, Nakamura S, Izumi N. A validation study of after direct-acting antivirals recommendation for surveillance score for the development of hepatocellular carcinoma in patients with hepatitis C virus infection who had received direct-acting antiviral therapy and achieved sustained virological response. JGH Open 2022; 6:20-28. [PMID: 35071784 PMCID: PMC8762616 DOI: 10.1002/jgh3.12690] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 11/25/2021] [Accepted: 11/28/2021] [Indexed: 12/19/2022]
Abstract
Background and Aim The pathogenic process underlying the development of hepatocellular carcinoma (HCC) is not yet clear in patients with hepatitis C virus (HCV) who have received direct-acting antiviral (DAA) therapy and achieved sustained virological response (SVR). This study validated a composite predictive model for HCC in these patients. Methods This study included 3058 patients in whom HCV was eradicated with DAA therapy. After DAAs recommendation for surveillance (ADRES) score, which is based on sex, FIB-4 index, and α-fetoprotein, was used as a composite predictive model for HCC development. Results The 1-, 3-, and 5-year cumulative incidence rates of HCC were 0.9, 4.5, and 15.2%, respectively. Multivariate analysis with Cox proportional hazards models showed that male sex (hazard ratio [HR], 2.646; 95% confidence interval [CI], 1.790-3.911), FIB-4 index >3.25 (HR, 2.891; 95% CI, 1.947-4.293), and α-fetoprotein >5 ng/mL (HR, 2.835; 95% CI, 1.914-4.200) are independently associated with HCC development. The incidence of HCC differed significantly by ADRES score (P < 0.001). Cox proportional hazards models showed that compared to the ADRES score 0 group, the HR for HCC development was 2.947 (95% CI, 1.367-6.354) in the ADRES score 1 group, 9.171 (95% CI, 4.339-19.380) in the ADRES score 2 group, and 20.630 (95% CI, 8.641-49.230) in the ADRES score 3 group. ADRES score had superior predictive power for HCC development compared with the FIB-4 index and α-fetoprotein according to time-dependent receiver operating characteristic analysis. Conclusion The ADRES score is useful for predicting HCC development after SVR.
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Affiliation(s)
- Toshifumi Tada
- Department of Internal Medicine Japanese Red Cross Society Himeji Hospital Himeji Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Yutaka Yasui
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
| | - Nami Mori
- Department of Gastroenterology Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital Hiroshima Hiroshima Japan
| | - Keiji Tsuji
- Department of Gastroenterology Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital Hiroshima Hiroshima Japan
| | - Chitomi Hasebe
- Department of Gastroenterology Japanese Red Cross Asahikawa Hospital Asahikawa Hokkaido Japan
| | - Koji Joko
- Center for Liver-Biliary-Pancreatic Disease Matsuyama Red Cross Hospital Matsuyama Ehime Japan
| | - Takehiro Akahane
- Department of Gastroenterology Japanese Red Cross Ishinomaki Hospital Ishinomaki Miyagi Japan
| | - Koichiro Furuta
- Department of Gastroenterology Masuda Red Cross Hospital Masuda Shimane Japan
| | - Haruhiko Kobashi
- Department of Gastroenterology Japanese Red Cross Okayama Hospital Okayama Okayama Japan
| | - Hiroyuki Kimura
- Department of Gastroenterology Japanese Red Cross Kyoto Daiichi Hospital Kyoto Japan
| | - Hitoshi Yagisawa
- Department of Gastroenterology Japanese Red Cross Akita Hospital Akita Akita Japan
| | - Hiroyuki Marusawa
- Department of Gastroenterology and Hepatology Japanese Red Cross Osaka Hospital Osaka Japan
| | - Masahiko Kondo
- Department of Gastroenterology Japanese Red Cross Otsu Hospital Otsu Shiga Japan
| | - Yuji Kojima
- Department of Hepatology Japanese Red Cross Ise Hospital Ise Mie Japan
| | - Hideo Yoshida
- Department of Gastroenterology Japanese Red Cross Medical Center Tokyo Japan
| | - Yasushi Uchida
- Department of Gastroenterology Japanese Red Cross Matsue Hospital Matsue Shimane Japan
| | - Shinichiro Nakamura
- Department of Internal Medicine Japanese Red Cross Society Himeji Hospital Himeji Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan
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11
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Abstract
In the 1970s, an unknown virus was suspected for documented cases of transfusion-associated hepatitis, a phenomenon called non-A, non-B hepatitis. In 1989, the infectious transmissible agent was identified and named hepatitis C virus (HCV) and, soon enough, the first diagnostic HCV antibody test was developed, which led to a dramatic decrease in new infections. Today, HCV infection remains a global health burden and a major cause of liver cirrhosis, hepatocellular carcinoma and liver transplantation. However, tremendous advances have been made over the decades, and HCV became the first curable, chronic viral infection. The introduction of direct antiviral agents revolutionized antiviral treatment, leading to viral eradication in more than 98% of all patients infected with HCV. This Perspective discusses the history of HCV research, which reads like a role model for successful translational research: starting from a clinical observation, specific therapeutic agents were developed, which finally were implemented in national and global elimination programmes.
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Affiliation(s)
- Michael P. Manns
- grid.10423.340000 0000 9529 9877Hannover Medical School, Hannover, Germany
| | - Benjamin Maasoumy
- grid.10423.340000 0000 9529 9877Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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12
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Conway B, Smyth D, Thomas R, Wong A, Sebastiani G, Cooper C, Shah H, Kumar R, Deutsch G, Watson T. Characterizing risk behaviour and reinfection rates for successful programs to engage core transmitters in HCV elimination (C-RESPECT). CANADIAN LIVER JOURNAL 2021; 4:346-359. [PMID: 35989890 PMCID: PMC9235128 DOI: 10.3138/canlivj-2021-0005] [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: 03/14/2021] [Accepted: 03/14/2021] [Indexed: 10/21/2024]
Abstract
BACKGROUND Development of robust treatment programs among core transmitters (CT) of hepatitis C virus (HCV) are needed, including strategies to address reinfection risk. The aim of this study was to describe the effectiveness of direct-acting antiviral (DAA) treatment in CT versus non-CT populations and assess reinfection rates after successful treatment. METHODS Characterizing Risk Behaviour and Reinfection Rates for Successful Programs to Engage Core Transmitters in HCV Elimination (C-RESPECT) was a prospective, observational study of HCV-infected Canadian adult patients (genotypes 1, 3, and 4) treated with DAAs between 2017 and 2020. RESULTS The full analysis set included 429 participants (259 CT, 170 non-CT). Key differences were observed in baseline profiles: CT participants were younger (mean 42.3 [SD 11.2] y versus 55.0 [SD 11.1] y, respectively) and reported higher rates of social assistance (35.7% versus 14.8%), smoking (83.7% versus 52.4%), low socioeconomic status (yearly income <$15,000: 69.6% versus 43.9%), illicit drug use (83.7% versus 34.3%), and previous incarcerations (62.7% versus 36.9%). DAA treatment adherence was similar; 93 .5% versus 98.3% of CT versus non-CT participants completed the assigned treatment duration. Cure rates (sustained virologic response) were comparable, ranging from 94.9% to 98.1%. All reinfections were among CT participants, with a rate of 13.8/100 person-years (95% CI 9.2-20.8) with mean time to reinfection of 24.6 (SD 0.6) months. CONCLUSIONS CT and non-CT participants respond equally well to DAA treatment; however, with some reinfections among CT participants. Innovative multidisciplinary programs must be developed to mitigate this risk in this key population.
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Affiliation(s)
- Brian Conway
- Vancouver Infectious Diseases Centre, Vancouver, British Columbia, Canada
| | - Dan Smyth
- Centre for Research, Education and Clinical Care of At-Risk Populations (RECAP), Moncton, New Brunswick, Canada
| | | | - Alex Wong
- Saskatchewan Health Authority, Regina, Saskatchewan, Canada
| | | | - Curtis Cooper
- Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Hemant Shah
- University Health Network, Toronto, Ontario, Canada
| | | | | | - Ted Watson
- Merck Canada Inc., Kirkland, Quebec, Canada
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13
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Tada T, Kurosaki M, Nakamura S, Hasebe C, Kojima Y, Furuta K, Kobashi H, Kimura H, Ogawa C, Yagisawa H, Uchida Y, Joko K, Akahane T, Arai H, Marusawa H, Narita R, Ide Y, Sato T, Kusakabe A, Tsuji K, Mori N, Kondo M, Mitsuda A, Izumi N. Real-world clinical outcomes of sofosbuvir and velpatasvir treatment in HCV genotype 1- and 2-infected patients with decompensated cirrhosis: A nationwide multicenter study by the Japanese Red Cross Liver Study Group. J Med Virol 2021; 93:6247-6256. [PMID: 34170517 DOI: 10.1002/jmv.27157] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Accepted: 06/22/2021] [Indexed: 11/12/2022]
Abstract
The real-world virological efficacy and safety of interferon-free direct-acting antiviral (DAA) therapy with sofosbuvir (SOF) and velpatasvir (VEL) were assessed in hepatitis C virus (HCV) genotype 1- and 2-infected patients with decompensated cirrhosis. A total of 65 patients with HCV-related decompensated cirrhosis (Child-Pugh score of 7 points or more) who were treated with the SOF/VEL regimen were enrolled. The sustained virological response (SVR) rate and safety profile were analyzed. SVR was defined as undetectable serum HCV RNA at 12 weeks after the end of treatment (SVR12). The percentages of patients with undetectable HCV RNA at 4, 8, and 12 weeks after the start of therapy were 81.2% (95% confidence interval [CI], 69.5-89.9) (52/64), 98.4% (95% CI, 91.2-100.0) (60/61), and 98.5% (95% CI, 91.7-100.0) (64/65), respectively. The overall SVR rate was 92.3% (95% CI, 83.0-97.5) (60/65). Albumin-bilirubin (ALBI) scores decreased during and after treatment (p < 0.001), and there were significant differences between baseline and end of treatment and between baseline and SVR12. Subgroup analyses showed no significant differences in SVR rates according to patient age, sex, HCV genotype (subtype), Child-Pugh classification, modified ALBI grade, presence of ascites, presence of hepatic coma, or history of hepatocellular carcinoma. In all subpopulations, the SVR rates were higher than 80%. There were no severe adverse events associated with the treatment. The SOF/VEL regimen showed good virological efficacy and acceptable safety even in patients with HCV-related decompensated cirrhosis.
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Affiliation(s)
- Toshifumi Tada
- Department of Internal medicine, Japanese Red Cross Himeji Hospital, Hyogo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Japanese Red Cross Musashino Hospital, Tokyo, Japan
| | - Shinichiro Nakamura
- Department of Internal medicine, Japanese Red Cross Himeji Hospital, Hyogo, Japan
| | - Chitomi Hasebe
- Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Hokkaido, Japan
| | - Yuji Kojima
- Department of Hepatology, Japanese Red Cross Ise Hospital, Ise, Mie, Japan
| | - Koichiro Furuta
- Department of Gastroenterology, Japanese Red Cross Masuda Hospital, Shimane, Japan
| | - Haruhiko Kobashi
- Department of Hepatology, Japanese Red Cross Okayama Hospital, Okayama, Japan
| | - Hiroyuki Kimura
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Chikara Ogawa
- Department of Gastroenterology, Takamatsu Red Cross Hospital, Kagawa, Japan
| | - Hitoshi Yagisawa
- Department of Gastroenterology, Japanese Red Cross Akita Hospital, Akita, Japan
| | - Yasushi Uchida
- Department of Gastroenterology, Japanese Red Cross Matsue Hospital, Shimane, Japan
| | - Kouji Joko
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Takehiro Akahane
- Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Miyagi, Japan
| | - Hirotaka Arai
- Department of Gastroenterology, Japanese Red Cross Maebashi Hospital,, Gunma, Japan
| | - Hiroyuki Marusawa
- Department of Gastroenterology, Japanese Red Cross Osaka Hospital, Osaka, Japan
| | - Ryoichi Narita
- Department of Gastroenterology, Japanese Red Cross Oita Hospital, Oita, Japan
| | - Yasushi Ide
- Department of Gastroenterology, Japanese Red Cross Karatsu Hospital, Saga, Japan
| | - Takashi Sato
- Department of Gastroenterology, Japanese Red Cross Nasu Hospital, Tochigi, Japan
| | - Atsunori Kusakabe
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan
| | - Keiji Tsuji
- Department of Gastroenterology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Nami Mori
- Department of Gastroenterology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Masahiko Kondo
- Department of Gastroenterology, Japanese Red Cross Otsu Hospital, Shiga, Japan
| | - Akeri Mitsuda
- Department of Internal Medicine, Japanese Red Cross Tottori Hospital, Tottori, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Japanese Red Cross Musashino Hospital, Tokyo, Japan
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14
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Tada T, Toyoda H, Kumada T, Kurisu A, Sugiyama A, Akita T, Ohisa M, Aikata H, Miki D, Chayama K, Tanaka J. Comparison of liver disease state progression in patients with eradication of versus persistent infection with hepatitis C virus: Markov chain analysis. J Viral Hepat 2021; 28:538-547. [PMID: 33215790 DOI: 10.1111/jvh.13444] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 10/11/2020] [Accepted: 11/11/2020] [Indexed: 12/30/2022]
Abstract
To investigate the long-term prognosis of liver disease in patients with hepatitis C virus (HCV) eradication after antiviral therapy versus those with persistent HCV infection. Four hundred and eighty patients (5259 person-years [PYs]) who received interferon-based therapy and achieved sustained virologic response and 848 patients (3853 PYs) with persistent HCV infection were included. In the analysis of 1-year liver disease state transition probability matrices using Markov chain models, progression to cirrhosis from the chronic hepatitis state was observed (0.00%-0.63%) in patients with HCV eradication. Among patients with chronic hepatitis or cirrhosis and HCV eradication, hepatocellular carcinoma (HCC) development was observed in males aged ≥ 50 years (0.97%-1.96%) and females aged ≥ 60 years (0.26%-5.00%). Additionally, in patients with cirrhosis and HCV eradication, improvement to chronic hepatitis was also observed (4.94%-10.64%). Conversely, in patients with chronic hepatitis and persistent HCV infection, progression to cirrhosis was observed in males aged ≥ 30 years and female aged ≥ 40 years (0.44%-1.99%). In males aged ≥ 40 years and female aged ≥ 50 years with cirrhosis, the transition probability for HCC was relatively high (4.17%-14.02%). Under the assumption of either chronic hepatitis or cirrhosis at age 40 or 60 years as the starting condition for simulation over the next 30 or 40 years, respectively, the probability of HCC was higher in patients with persistent HCV infection than those with HCV eradication. In conclusion, HCV eradication can reduce the risk of developing cirrhosis or HCC in patients with chronic HCV infection.
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Affiliation(s)
- Toshifumi Tada
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital, Himeji, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Kumada
- Faculty of Nursing, Gifu Kyoritsu University, Ogaki, Japan
| | - Akemi Kurisu
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Aya Sugiyama
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Masayuki Ohisa
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Daiki Miki
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Project Research Center for Epidemiology and Prevention of Viral Hepatitis and Hepatocellular Carcinoma, Hiroshima University, Hiroshima, Japan
- Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
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15
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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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Toyoda H, Tada T, Yasuda S, Mizuno K, Ito T, Kumada T. Dynamic Evaluation of Liver Fibrosis to Assess the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis C Who Achieved Sustained Virologic Response. Clin Infect Dis 2021; 70:1208-1214. [PMID: 31056696 DOI: 10.1093/cid/ciz359] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Accepted: 04/30/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Liver fibrosis is an important risk factor for the development of hepatocellular carcinoma (HCC) after sustained virologic response (SVR) in patients with persistent hepatitis C virus (HCV) infection. However, as the degree of liver fibrosis changes following the eradication of HCV after SVR, it is unclear whether the prediction of HCC development based on liver fibrosis at baseline remains valid. METHODS In 522 patients who achieved SVR by interferon-based anti-HCV therapy, the Fibrosis-4 Index for Liver Fibrosis (FIB-4 index) was updated annually by recalculation based on laboratory values after SVR. The incidence of HCC was reassessed annually based on the updated FIB-4 index. RESULTS The percentage of patients with mild liver fibrosis (FIB-4 index <1.45) increased annually after SVR, whereas the percentage of patients with advanced liver fibrosis (FIB-4 index ≥3.25) decreased. The incidences of HCC based on the FIB-4 index remained constant between the time of SVR and subsequent annual updates. No patients developed HCC after SVR if the FIB-4 index decreased to <1.45. CONCLUSIONS The FIB-4 index retained its predictive ability for the risk of HCC when recalculated after SVR, despite the decrease in patients with high FIB-4 index values. Dynamic assessment of the FIB-4 index can be useful in the surveillance of HCC after SVR. Patients with a FIB-4 index <1.45 did not develop HCC even by the regression from advanced fibrosis after SVR. Further studies will be necessary to confirm these findings, which may result in a decrease in the number of patients in whom surveillance is required.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kazuyuki Mizuno
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takanori Ito
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
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17
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Noninvasive biomarkers predict improvement in liver fibrosis after successful generic DAAs based therapy of chronic hepatitis C in Egypt. CLINICAL EPIDEMIOLOGY AND GLOBAL HEALTH 2020. [DOI: 10.1016/j.cegh.2020.04.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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18
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Real-World Virological Efficacy and Safety of Ledipasvir and Sofosbuvir in Patients with Chronic Hepatitis C Virus Genotype 2 Infection: A Multicenter Study. Infect Dis Ther 2020; 10:269-280. [PMID: 33141401 PMCID: PMC7954884 DOI: 10.1007/s40121-020-00364-9] [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: 09/26/2020] [Accepted: 10/20/2020] [Indexed: 10/26/2022] Open
Abstract
INTRODUCTION The real-world virological efficacy and safety of interferon-free direct-acting antiviral (DAA) therapy with ledipasvir (LDV) plus sofosbuvir (SOF) were assessed in patients who were chronically infected with hepatitis C virus (HCV) genotype 2. METHODS A total of 126 patients with chronic hepatitis C due to HCV genotype 2 infection who were treated with the LDV/SOF regimen were enrolled. The sustained virological response (SVR) rate and safety were analyzed. SVR was assessed in the intention-to-treat (ITT) population as well as in the modified intention-to-treat (mITT) population, which excluded patients with non-virological failure, including those who dropped out before the SVR assessment. RESULTS The overall SVR rates of the ITT and mITT populations were 87.3% (95% confidence interval [CI] 80.2-92.6) (110/126) and 97.3% (95% CI 92.4-99.4) (110/113), respectively. In the mITT population, the percentages of patients with undetectable HCV RNA at 4, 8, and 12 weeks after the start of therapy were 92.9% (95% CI 86.5-96.9) (105/113), 99.1% (95% CI 95.2-100.0) (112/113), and 100.0% (95% CI 97.4-100.0) (113/113), respectively. Subgroup analyses of the mITT population showed no significant differences in SVR rates according to age, sex, HCV genotype (subtype), history of interferon-based therapy, baseline FIB-4 index, or baseline estimated glomerular filtration rate. In all subpopulations, the SVR rates were > 90%. There were no severe adverse events associated with the treatment. CONCLUSION The LDV/SOF regimen showed high virological efficacy and acceptable safety in patients with HCV genotype 2 infection. TRIAL REGISTRATION UMIN registration no. 000038604.
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Tada T, Toyoda H, Yasuda S, Kumada T, Kurisu A, Ohisa M, Akita T, Tanaka J. Long-term prognosis of liver disease in patients with eradicated chronic hepatitis C virus: An analysis using a Markov chain model. Hepatol Res 2020; 50:936-946. [PMID: 32401388 DOI: 10.1111/hepr.13512] [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: 03/11/2020] [Revised: 04/21/2020] [Accepted: 04/27/2020] [Indexed: 02/08/2023]
Abstract
AIM The long-term prognosis of patients with chronic hepatitis C virus (HCV) infection who have received antiviral therapy and who demonstrate HCV eradication remains incompletely characterized. In this study, we investigated the long-term prognosis of liver disease in patients with eradication of HCV. METHODS A total of 552 patients with chronic HCV infection (6815 person-years) who were treated with interferon-based therapy and who achieved sustained virologic response were included. Yearly transition probabilities for each liver state (chronic hepatitis, cirrhosis, and hepatocellular carcinoma [HCC]) were calculated using a Markov chain model. RESULTS In the analysis of 1-year liver disease state transition probabilities, progression to cirrhosis occurred in 0.5-2.1% of male patients with chronic hepatitis across all age groups. In male patients with cirrhosis, HCC developed in 0.6-1.9% of patients over the age of 50 years. In female patients with chronic hepatitis, progression to cirrhosis occurred in 0.4-2.1% of patients across all age groups. In addition, in female patients with cirrhosis, HCC developed in those aged 60-69 (0.4%) and 70-79 (0.4%) years. Under the assumption of either a chronic hepatitis or cirrhosis state at age 40 or 60 years as the starting condition for simulation over the next 40 or 20 years, respectively, the probability of HCC gradually increased with age and was higher in male patients. CONCLUSIONS The development or progression of cirrhosis and the development of HCC are risks in HCV patients despite HCV eradication, not only in those with cirrhosis but also in those with chronic hepatitis.
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Affiliation(s)
- Toshifumi Tada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.,Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.,Department of Internal Medicine, Himeji Red Cross Hospital, Himeji, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Kumada
- Faculty of Nursing, Gifu Kyoritsu University, Ogaki, Japan
| | - Akemi Kurisu
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Masayuki Ohisa
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
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20
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Giuffrè M, Fouraki S, Comar M, Masutti F, Crocè LS. The Importance of Transaminases Flare in Liver Elastography: Characterization of the Probability of Liver Fibrosis Overestimation by Hepatitis C Virus-Induced Cytolysis. Microorganisms 2020; 8:E348. [PMID: 32121404 PMCID: PMC7142454 DOI: 10.3390/microorganisms8030348] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 02/25/2020] [Accepted: 02/27/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Liver stiffness measurement (LSM) is crucial for appropriate fibrosis staging in patients with ongoing hepatitis C virus (HCV) infection. However, there is still an ongoing debate on the impact of serum transaminases (aspartate-aminotransferase, AST; alanine-aminotransferase, ALT) on LSM. METHODS We selected 110 patients undergoing HCV eradication therapy with LSM compatible with significant liver fibrosis. LSM was evaluated prior to therapy and one year after HCV eradication. RESULTS LSM showed a median decrease of 35% from baseline values, and 67 (61%) patients showed posttreatment values compatible with lower fibrosis stages. We developed two logistic regression models to determine the probability of liver fibrosis overestimation according to serum transaminase. The probability of overestimation of two or more fibrosis grade is equal to (1) 50% for AST of 99 IU/L (2.2 ULN) and ALT of 90.5 IU/L (2 ULN), (2) 80% for AST of 123.5 IU/L (2.74 ULN) and ALT of 101.5 IU/L (2.25 ULN), and (3) reaches 100% for AST of 211 IU/L (4.7 ULN) and ALT of 140 IU/L (3.1 ULN). CONCLUSIONS This study highlights the impact of serum transaminases on LSM. We believe that our findings may serve as a reference point for appropriate fibrosis stratification by liver elastography in patients with HCV infection.
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Affiliation(s)
- Mauro Giuffrè
- Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, 34149, Italy; (S.F.); (M.C.); (L.S.C.)
- Italian Liver Foundation, Basovizza (Trieste) 34149, Italy
| | - Sofia Fouraki
- Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, 34149, Italy; (S.F.); (M.C.); (L.S.C.)
| | - Manola Comar
- Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, 34149, Italy; (S.F.); (M.C.); (L.S.C.)
- Institute for Maternal and Child Health-IRCCS “Burlo Garofolo”, Trieste 34137, Italy
| | - Flora Masutti
- Liver Clinic, Azienda Sanitaria Universitaria Giuliano-Isontina, Cattinara Hospital, Trieste 34149, Italy;
| | - Lory Saveria Crocè
- Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, 34149, Italy; (S.F.); (M.C.); (L.S.C.)
- Italian Liver Foundation, Basovizza (Trieste) 34149, Italy
- Liver Clinic, Azienda Sanitaria Universitaria Giuliano-Isontina, Cattinara Hospital, Trieste 34149, Italy;
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21
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Strazzabosco M, Cortesi PA, Conti S, Okolicsanyi S, Rota M, Ciaccio A, Cozzolino P, Fornari C, Gemma M, Scalone L, Cesana G, Fabris L, Colledan M, Fagiuoli S, Ideo G, Zavaglia C, Perricone G, Munari LM, Mantovani LG, Belli LS. Clinical outcome indicators in chronic hepatitis B and C: A primer for value-based medicine in hepatology. Liver Int 2020; 40:60-73. [PMID: 31654608 PMCID: PMC10916792 DOI: 10.1111/liv.14285] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 10/03/2019] [Accepted: 10/22/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Chronic liver diseases (CLDs) are major health problems that require complex and costly treatments. Liver-specific clinical outcome indicators (COIs) able to assist both clinicians and administrators in improving the value of care are presently lacking. The Value-Based Medicine in Hepatology (VBMH) study aims to fill this gap, devising and testing a set of COIs for CLD, that could be easily collected during clinical practice. Here we report the COIs generated and recorded for patients with HBV or HCV infection at different stages of the disease. METHODS/RESULTS In the first phase of VBMH study, COIs were identified, based on current international guidelines and literature, using a modified Delphi method and a RAND 9-point appropriateness scale. In the second phase, COIs were tested in an observational, longitudinal, prospective, multicentre study based in Lombardy, Italy. Eighteen COIs were identified for HBV and HCV patients. Patients with CLD secondary to HBV (547) or HCV (1391) were enrolled over an 18-month period and followed for a median of 4 years. The estimation of the proposed COIs was feasible in the real-word clinical practice and COI values compared well with literature data. Further, the COIs were able to capture the impact of new effective treatments like direct-acting antivirals (DAAs) in the clinical practice. CONCLUSIONS The COIs efficiently measured clinical outcomes at different stages of CLDs. While specific clinical practice settings and related healthcare systems may modify their implementation, these indicators will represent an important component of the tools for a value-based approach in hepatology and will positively affect care delivery.
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Affiliation(s)
- Mario Strazzabosco
- Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
- International Center for Digestive Health, University of Milan-Bicocca, Milan, Italy
- Liver Center & Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - Paolo A. Cortesi
- Research Centre on Public Health (CESP), University of Milan-Bicocca, Milan, Italy
| | - Sara Conti
- Research Centre on Public Health (CESP), University of Milan-Bicocca, Milan, Italy
| | - Stefano Okolicsanyi
- Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
- International Center for Digestive Health, University of Milan-Bicocca, Milan, Italy
| | - Matteo Rota
- Research Centre on Public Health (CESP), University of Milan-Bicocca, Milan, Italy
- Department of Molecular and Traslational Medicine, University of Brescia, Brescia, Italy
| | - Antonio Ciaccio
- Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
- International Center for Digestive Health, University of Milan-Bicocca, Milan, Italy
| | - Paolo Cozzolino
- Research Centre on Public Health (CESP), University of Milan-Bicocca, Milan, Italy
| | - Carla Fornari
- Research Centre on Public Health (CESP), University of Milan-Bicocca, Milan, Italy
| | - Marta Gemma
- Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
- International Center for Digestive Health, University of Milan-Bicocca, Milan, Italy
| | - Luciana Scalone
- Research Centre on Public Health (CESP), University of Milan-Bicocca, Milan, Italy
| | - Giancarlo Cesana
- Research Centre on Public Health (CESP), University of Milan-Bicocca, Milan, Italy
| | - Luca Fabris
- International Center for Digestive Health, University of Milan-Bicocca, Milan, Italy
- Liver Center & Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
- Department of Molecular Medicine, University of Padua School of Medicine, Padua, Italy
| | - Michele Colledan
- Department of Surgery, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Stefano Fagiuoli
- Department of Gastroenterology, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | | | - Claudio Zavaglia
- Hepatology and Gastroenterology Unit - Liver Unit, ASST GOM Niguarda, Milan, Italy
| | - Giovanni Perricone
- Hepatology and Gastroenterology Unit - Liver Unit, ASST GOM Niguarda, Milan, Italy
| | | | - Lorenzo G. Mantovani
- Research Centre on Public Health (CESP), University of Milan-Bicocca, Milan, Italy
| | - Luca S. Belli
- International Center for Digestive Health, University of Milan-Bicocca, Milan, Italy
- Hepatology and Gastroenterology Unit - Liver Unit, ASST GOM Niguarda, Milan, Italy
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El-Shabrawi M, Hassanin F. Paediatric hepatitis C virus infection and its treatment: Present, past, and future. Arab J Gastroenterol 2019; 20:163-174. [PMID: 31585703 DOI: 10.1016/j.ajg.2019.09.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 06/01/2019] [Accepted: 09/15/2019] [Indexed: 01/08/2023]
Abstract
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease in the world. It is a challenging medico-social problem in the paediatric population. High HCV infection rates are reported in low and middle incomes countries. From the health economic point of view treatment of hepatitis C virus (HCV) with subsequent virus eradication is very effective as it eliminates the long-term sequelae of untreated or maltreated HCV. In this review we summarize the updates and highlight the historical approach of treatment of chronic HCV infection in children in the new era of directly acting antiviral (DAA) agents.
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23
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Tada T, Toyoda H, Yasuda S, Miyake N, Kumada T, Kurisu A, Ohisa M, Akita T, Tanaka J. Natural history of liver-related disease in patients with chronic hepatitis C virus infection: An analysis using a Markov chain model. J Med Virol 2019; 91:1837-1844. [PMID: 31254403 PMCID: PMC6771942 DOI: 10.1002/jmv.25533] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Accepted: 06/24/2019] [Indexed: 12/24/2022]
Abstract
BACKGROUND Long-term prognosis of patients with chronic hepatitis C infection (HCV) remains incompletely characterized. We investigated the long-term prognosis of liver disease in patients with chronic HCV infection who have not received antiviral therapy. METHODS A total of 2304 patients with chronic HCV who were not received interferon-based therapy were included. RESULTS In the assessment of 1-year disease state of liver transition probabilities, progression to chronic hepatitis occurred in 12% to 14% of patients across all age groups in male asymptomatic carriers. In male patients with chronic hepatitis, progression to cirrhosis was observed mostly in the 60 to 69 (7.6%) and ≥70 age groups (9.6%). In addition, in male patients with cirrhosis, HCC development occurred in approximately 5% of patients over the age of 40. In female asymptomatic carriers, progression to chronic hepatitis was observed in 6% to 14% of patients across all age groups. In female patients with chronic hepatitis, progression to cirrhosis was observed mostly in the 60 to 69 (8.7%) and ≥70 (7.4%) age groups. In addition, in female patients with cirrhosis, HCC development occurred in 0.9% to 3.3% of patients over the age of 50. Under assumptions of either chronic hepatitis or asymptomatic carrier state at age 40 as the starting condition for simulation over the following 40 years, the probability of HCC gradually increased with age and was higher in male patients. CONCLUSIONS There is a risk of cirrhosis or HCC development in HCV patients with not only chronic hepatitis but the asymptomatic carrier state as well.
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Affiliation(s)
- Toshifumi Tada
- Department of Gastroenterology and HepatologyOgaki Municipal HospitalOgakiGifuJapan
- Department of Epidemiology, Infectious Disease Control, and PreventionHiroshima University Institute of Biomedical and Health SciencesHiroshimaJapan
| | - Hidenori Toyoda
- Department of Gastroenterology and HepatologyOgaki Municipal HospitalOgakiGifuJapan
| | - Satoshi Yasuda
- Department of Gastroenterology and HepatologyOgaki Municipal HospitalOgakiGifuJapan
| | - Nozomi Miyake
- Department of Gastroenterology and HepatologyOgaki Municipal HospitalOgakiGifuJapan
| | - Takashi Kumada
- Faculty of NursingGifu Kyoritsu UniversityOgakiGifuJapan
| | - Akemi Kurisu
- Department of Epidemiology, Infectious Disease Control, and PreventionHiroshima University Institute of Biomedical and Health SciencesHiroshimaJapan
| | - Masayuki Ohisa
- Department of Epidemiology, Infectious Disease Control, and PreventionHiroshima University Institute of Biomedical and Health SciencesHiroshimaJapan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control, and PreventionHiroshima University Institute of Biomedical and Health SciencesHiroshimaJapan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and PreventionHiroshima University Institute of Biomedical and Health SciencesHiroshimaJapan
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24
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The course of elderly patients with persistent hepatitis C virus infection without hepatocellular carcinoma. J Gastroenterol 2019; 54:829-836. [PMID: 31161311 DOI: 10.1007/s00535-019-01595-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 05/27/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND Little is known about the course of elderly patients with persistent hepatitis C virus (HCV) infection. We investigated the course of HCV infection in this patient population. METHODS Among 9,126 HCV antibody-positive patients who visited our hospital between 1995 and 2015, there were 453 patients with continuous follow-up who survived to age 80. They were included in the study following the inclusion criteria: confirmed persistent detection of HCV RNA, no HCV eradication if anti-HCV therapy occurred before enrollment, and no development of hepatocellular carcinoma (HCC) before enrollment. For all study patients, baseline was defined as the date when they turned 80. Mortality rates after the age of 80 years and cause of death were analyzed. RESULTS During the study period, 155 patients (34.2%) died. Median survival time (MST) after age 80 was 8.8 years, which was comparable to that of the general population (10.1 years). Among 155 deceased patients, the majority (115 patients, 74.2%) died due to non-liver-related disease, followed by HCC (28 patients, 18.1%) and liver-related disease other than HCC (12 patients, 7.7%). Patients with advanced liver fibrosis (FIB-4 index > 3.25, n = 245) had shorter MST than patients with mild liver fibrosis (FIB-4 index ≤ 3.25, n = 208) (7.1 vs. 10.2 years; p = 0.020) due to a higher mortality rate from liver-related complications, including HCC. CONCLUSION Most elderly HCV patients die from non-liver-related disease, especially those with less advanced liver fibrosis.
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25
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Pisaturo M, Minichini C, Starace M, Caroprese M, Macera M, Brancaccio G, De Pascalis S, Santonicola A, Galeota Lanza A, Zampino R, Cotticelli G, Sagnelli E, Gaeta GB, Coppola N. Hepatitis C late relapse in patients with directly acting antiviral-related sustained virological response at week 12. Liver Int 2019; 39:844-853. [PMID: 30554459 DOI: 10.1111/liv.14025] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 11/21/2018] [Accepted: 12/02/2018] [Indexed: 12/15/2022]
Abstract
AIM The aim of the present study was to identify, among the patients with failure to DAA regimen, those with a late relapse (after the achievement of a sustained virological response at week 12) and to characterize the clinical, epidemiological and virological features of these patients. MATERIAL AND METHODS A total of 129 HCV patients with non-response to an IFN-free regimen were enrolled. Sanger sequencing of NS3, NS5A and NS5B was performed at failure by home-made protocols. RESULTS Of the 129 patients enrolled, 8 (6.2%) experienced a breakthrough, 15 (11.7%) non-response, 99 (76.7%) a relapse by week 12 after the end of DAA therapy, and 7 (5.4%) a late relapse (after week 12; median 24 weeks, range 24-72). For two of the seven patients with a late relapse, a serum sample collected before the start of the DAA regimen was available; phylogenetic analysis showed no change in sequences of NS3, NS5A and NS5B regions, suggesting a reactivation of the initial HCV strain; for the remaining five patients, no serum collected before the DAA regimen was available, and thus, a re-infection cannot be excluded. CONCLUSIONS Although a late relapse is infrequent, the study suggests a post-treatment follow-up of 72 weeks.
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Affiliation(s)
- Mariantonietta Pisaturo
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania, Naples, Italy
| | - Carmine Minichini
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania, Naples, Italy
| | - Mario Starace
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania, Naples, Italy
| | - Mara Caroprese
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania, Naples, Italy
| | - Margherita Macera
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania, Naples, Italy
| | - Giuseppina Brancaccio
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania, Naples, Italy
| | - Stefania De Pascalis
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania, Naples, Italy
| | | | | | - Rosa Zampino
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, University of Campania "L. Vanvitelli", Naples, Italy
| | - Gaetano Cotticelli
- Internal Medicine and Hepatology, Department of Clinical and Experimental Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Evangelista Sagnelli
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania, Naples, Italy
| | - Giovanni Battista Gaeta
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania, Naples, Italy
| | - Nicola Coppola
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania, Naples, Italy.,Infectious Diseases Unit, AO Caserta, Caserta, Italy
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Toyoda H, Atsukawa M, Uojima H, Nozaki A, Tamai H, Takaguchi K, Fujioka S, Nakamuta M, Tada T, Yasuda S, Chuma M, Senoh T, Tsutsui A, Yamashita N, Hiraoka A, Michitaka K, Shima T, Akahane T, Itobayashi E, Watanabe T, Ikeda H, Iio E, Fukunishi S, Asano T, Tachi Y, Ikegami T, Tsuji K, Abe H, Kato K, Mikami S, Okubo H, Shimada N, Ishikawa T, Matsumoto Y, Itokawa N, Arai T, Tsubota A, Iwakiri K, Tanaka Y, Kumada T. Trends and Efficacy of Interferon-Free Anti-hepatitis C Virus Therapy in the Region of High Prevalence of Elderly Patients, Cirrhosis, and Hepatocellular Carcinoma: A Real-World, Nationwide, Multicenter Study of 10 688 Patients in Japan. Open Forum Infect Dis 2019; 6:ofz185. [PMID: 31123693 PMCID: PMC6524830 DOI: 10.1093/ofid/ofz185] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 04/10/2019] [Indexed: 12/12/2022] Open
Abstract
Background We investigated changes in patient characteristics, rate of sustained virologic response (SVR), and factors associated with SVR after anti-hepatitis C virus (HCV) therapy with direct-acting antiviral (DAA) regimens in real-world practice in Japan, where patients with HCV are characterized by older age and high prevalence of cirrhosis and hepatocellular carcinoma (HCC). Methods Changes in patient characteristics and SVR rates were evaluated from medical records among 10 688 patients who started interferon (IFN)-free DAA therapy between September 2014 and June 2018 in a nationwide, multicenter study. Factors associated with failure of SVR were analyzed. In particular, effects of cirrhosis or history of HCC on SVR were assessed by exact matching. Results Patient age was becoming younger and baseline liver fibrosis was becoming milder over time. Overall SVR rate was 95.4%. The SVR rates increased over time in patients without a history of IFN-free DAA therapy. Multivariate analysis revealed that cirrhosis was unfavorably associated with achievement of SVR in both patients with genotype 1 (odds ratio, 1.68; 95% confidence interval [CI], 1.27–2.21) and genotype 2 (odds ratio, 1.69; 95% CI, 1.01–2.78). Comparisons after exact matching showed that the SVR rate was significantly lower in patients with cirrhosis than without it, whereas patients with and without a history of HCC had similar SVR rates. Conclusions Background characteristics of patients who undergo IFN-free DAA therapy are changing in Japan. Patients without a history of IFN-free DAA therapy have high SVR rates. Exact matching confirmed that cirrhosis significantly influences the achievement of SVR in real-world settings.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Japan
| | - Masanori Atsukawa
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Haruki Uojima
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Akito Nozaki
- Gastroenterology Center, Yokohama City University Medical Center, Japan
| | - Hideyuki Tamai
- Department of Hepatology, Wakayama Rosai Hospital, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Shinichi Fujioka
- Department of Gastroenterology, Okayama Saiseikai General Hospital, , Japan
| | - Makoto Nakamuta
- National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Ogaki Municipal Hospital, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital, Japan
| | - Makoto Chuma
- Gastroenterology Center, Yokohama City University Medical Center, Japan
| | - Tomonori Senoh
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Akemi Tsutsui
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Naoki Yamashita
- National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Kojiro Michitaka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Toshihide Shima
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Japan
| | - Takehiro Akahane
- Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Japan
| | - Tsunamasa Watanabe
- Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Hiroki Ikeda
- Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Etsuko Iio
- Department of Virology and Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Japan
| | - Shinya Fukunishi
- Second Department of Internal Medicine, Osaka Medical College, Japan
| | - Toru Asano
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Tokyo Metropolitan Bokuto Hospital, Japan
| | - Yoshihiko Tachi
- Department of Gastroenterology and Hepatology, Komaki City Hospital, Japan
| | | | - Kunihiko Tsuji
- Center for Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Hiroshi Abe
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Keizo Kato
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Shigeru Mikami
- Department of Internal Medicine, Division of Gastroenterology, Kikkoman General Hospital, Noda, Japan
| | - Hironao Okubo
- Department of Gastroenterology, Juntendo University Nerima Hospital, Tokyo, Japan
| | - Noritomo Shimada
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan
| | - Toru Ishikawa
- Department of Hepatology, Saiseikai Niigata Daini Hospital, Japan
| | - Yoshihiro Matsumoto
- Department of Gastroenterology and Hepatology, Jikei University School of Medicine Kashiwa Hospital, , Japan
| | - Norio Itokawa
- Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Taeang Arai
- Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Akihito Tsubota
- Core Research Facilities for Basic Science, Jikei University School of Medicine, Tokyo, Japan
| | - Katsuhiko Iwakiri
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University, Graduate School of Medical Sciences, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Japan
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Long-term follow-up after cure from chronic hepatitis C virus infection shows occult hepatitis and a risk of hepatocellular carcinoma in noncirrhotic patients. Eur J Gastroenterol Hepatol 2019; 31:506-513. [PMID: 30461522 PMCID: PMC6416012 DOI: 10.1097/meg.0000000000001316] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVES Curing of hepatitis C virus (HCV) infection primarily aims to prevent severe liver complications. Our objectives were to investigate the long-term presence and impact of occult HCV infection (OCI) and to study the outcomes in terms of liver disease after virological cure. PATIENTS AND METHODS A total of 97 patients with achieved sustained virological response (SVR) during 1990-2005 were followed either by a clinical follow-up (FU) visit with blood sampling and liver elastography (n=54) or through national registries for outcomes (n=43). To diagnose OCI among patients with SVR, a highly sensitive method was used to detect HCV-RNA traces in whole blood. The FU duration was a median of 10.5 years, with samples up to 21.5 years after the end of treatment (EOT). RESULTS The majority of patients [52 (96%)] were HCV-RNA negative at FU, and regression of fibrosis was statistically significant. OCI was found in two (4%) of them at 8 and 9 years after EOT. These patients had F1 and F2 fibrosis before treatment and F2 at FU, but no other abnormal findings. Three previously noncirrhotic men were diagnosed with hepatocellular carcinoma 8-11 years after EOT. CONCLUSION Occult infection could be detected many years after the achievement of SVR but was not associated with serious liver disease. The majority had persistent viral eradication and regression of fibrosis after SVR. However, an increased risk of hepatocellular carcinoma may persist in the long term after SVR even in noncirrhotic patients. Further studies with FU after direct-acting antiviral therapy and on the long-term impact after cure are needed.
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Fofiu C, Boeriu A, Coman F, Fofiu A, Panic N, Bulajic M, Dobru D. Interferon-Free Regimen: Equally Effective in Treatment Naive and Experienced HCV Patients. Ann Hepatol 2019; 18:137-143. [PMID: 31113582 DOI: 10.5604/01.3001.0012.7905] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 01/31/2018] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Interferon-free regimen has been reported to be highly efficient in treatment of HCV infection, including patients with compensated cirrhosis. We compared the efficacy of Ombitasvir, Paritaprevir, Ritonavir, Dasabuvir and Ribavirin (OBT/PTV/r, with DSV and RBV) therapy in patients with chronic HCV genotype 1b infection and compensated cirrhosis with and without prior treatment experience with pegylated interferon and ribavirin (IFN/RBV). MATERIAL AND METHODS A prospective two-center study was conducted in Mures County Hospital and Brasov County Hospital, Romania in period November 2015-July 2016. Both treatment naïve and PegIFN/RBV experienced patients with chronic HCV genotype 1b infection received 12 weeks of OBT/PTV/r, with DSV and RBV. Sustained virologic response 12 weeks after the treatment and eventual discontinuation of therapy due to adverse events were assessed in order to estimate safety and efficiency of therapeutic regimen. RESULTS Fifty nine patients were included in study, 35 (59.3%) of them were previously treated with IFN/RBV. Forty four (74.5%) patients were previously diag-nosed with cirrhosis Child Pugh score 5, while 15 (25.4%) with Child Pugh score 6. All 59 patients achieved a SVR12 of 100% and one patient from treatment naïve cohort discontinued the therapy due to hyperbilirubinemia and encephalopathy. However viral load assessed at 12 weeks after discontinuation of therapy in this patient was undetectable. Conclusion An all-oral regimen of co-for-mulated OBT/PTV/r with DSV and RBV results in high rate of sustained virologic response at post-treatment week 12 among HCV GT1b infected patients associated with compensated cirrhosis, regardless of previous treatment experience with PegIFN/RBV.
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Affiliation(s)
- Crina Fofiu
- Department of Gastroenterology, University of Medicine and Pharmacy Tirgu Mures, Romania
| | - Alina Boeriu
- Department of Gastroenterology, University of Medicine and Pharmacy Tirgu Mures, Romania.
| | | | | | - Nikola Panic
- University Clinic "Dr Dragisa Misovic-Dedinje", Belgrade, Serbia
| | - Milutin Bulajic
- Department of Gastroenterology, University Clinical Hospital Santa Maria della Misericordia, Udine, Italy
| | - Daniela Dobru
- Department of Gastroenterology, University of Medicine and Pharmacy Tirgu Mures, Romania
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Toyoda H, Atsukawa M, Takaguchi K, Senoh T, Michitaka K, Hiraoka A, Fujioka S, Kondo C, Okubo T, Uojima H, Tada T, Yoneyama H, Watanabe T, Asano T, Ishikawa T, Tamai H, Abe H, Kato K, Tsuji K, Ogawa C, Shimada N, Iio E, Deguchi A, Itobayashi E, Mikami S, Moriya A, Okubo H, Tani J, Tsubota A, Tanaka Y, Masaki T, Iwakiri K, Kumada T. Real-world virological efficacy and safety of elbasvir and grazoprevir in patients with chronic hepatitis C virus genotype 1 infection in Japan. J Gastroenterol 2018; 53:1276-1284. [PMID: 29740665 DOI: 10.1007/s00535-018-1473-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Accepted: 04/30/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND The real-world virological efficacy and safety of an interferon (IFN)-free direct-acting antiviral (DAA) therapy with elbasvir (EBR) and grazoprevir (GZR) were evaluated in Japanese patients chronically infected with hepatitis C virus (HCV) genotype 1. METHODS The rate of sustained virologic response (SVR) and safety were analyzed in patients who started the EBR/GZR regimen between November 2016 and July 2017. SVR rates were compared based on patient baseline characteristics. RESULTS Overall, 371 of 381 patients (97.4%) achieved SVR. Multivariate analysis identified a history of failure to IFN-free DAA therapy and the presence of double resistance-associated substitutions (RASs) in HCV non-structural protein 5A (NS5A) as factors significantly associated with failure to EBR/GZR treatment. The SVR rates of patients with a history of IFN-free DAA therapy and those with double RASs were 55.6 and 63.6%, respectively. In all other subpopulations, the SVR rates were more than 90%. There were no severe adverse events associated with the treatment. CONCLUSIONS The EBR/GZR regimen yielded high virological efficacy with acceptable safety. Patients with a history of failure to IFN-free DAA therapy or with double RASs in HCV-NS5A remained difficult to treat with this regimen.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu, 503-8502, Japan.
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Tomonori Senoh
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Kojiro Michitaka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Shinichi Fujioka
- Department of Gastroenterology, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Chisa Kondo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Tomomi Okubo
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan
| | - Haruki Uojima
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu, 503-8502, Japan
| | - Hirohito Yoneyama
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kida, Japan
| | - Tsunamasa Watanabe
- Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Toru Asano
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan
| | - Toru Ishikawa
- Department of Hepatology, Saiseikai Niigata Daini Hospital, Niigata, Japan
| | - Hideyuki Tamai
- Department of Hepatology, Wakayama Rosai Hospital, Wakayama, Japan
| | - Hiroshi Abe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Keizo Kato
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shinmatusdo Central General Hospital, Matsudo, Japan
| | - Kunihiko Tsuji
- Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Noritomo Shimada
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Otakanomori Hospital, Kashiwa, Japan
| | - Etsuko Iio
- Department of Virology and Liver Unit, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Akihiro Deguchi
- Department of Gastroenterology, Kagawa Rosai Hospital, Marugame, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Asahi, Japan
| | - Shigeru Mikami
- Division of Gastroenterology, Department of Internal Medicine, Kikkoman General Hospital, Noda, Japan
| | - Akio Moriya
- Department of Gastroenterology, Mitoyo General Hospital, Kannonji, Japan
| | - Hironao Okubo
- Department of Gastroenterology, Juntendo University Nerima Hospital, Tokyo, Japan
| | - Joji Tani
- Department of Internal Medicine, Yashima General Hospital, Takamatsu, Japan
| | - Akihito Tsubota
- Core Research Facilities for Basic Science, The Jikei University School of Medicine, Tokyo, Japan
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kida, Japan
| | - Katsuhiko Iwakiri
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu, 503-8502, Japan
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Chung RT, Ghany MG, Kim AY, Marks KM, Naggie S, Vargas HE, Aronsohn AI, Bhattacharya D, Broder T, Falade-Nwulia OO, Fontana RJ, Gordon SC, Heller T, Holmberg SD, Jhaveri R, Jonas MM, Kiser JJ, Linas BP, Lo Re V, Morgan TR, Nahass RG, Peters MG, Reddy KR, Reynolds A, Scott JD, Searson G, Swan T, Terrault NA, Trooskin SB, Wong JB, Workowski KA. Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Clin Infect Dis 2018; 67:1477-1492. [PMID: 30215672 PMCID: PMC7190892 DOI: 10.1093/cid/ciy585] [Citation(s) in RCA: 469] [Impact Index Per Article: 67.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Accepted: 07/14/2018] [Indexed: 11/13/2022] Open
Abstract
Recognizing the importance of timely guidance regarding the rapidly evolving field of hepatitis C management, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) developed a web-based process for the expeditious formulation and dissemination of evidence-based recommendations. Launched in 2014, the hepatitis C virus (HCV) guidance website undergoes periodic updates as necessitated by availability of new therapeutic agents and/or research data. A major update was released electronically in September 2017, prompted primarily by approval of new direct-acting antiviral agents and expansion of the guidance's scope. This update summarizes the latest release of the HCV guidance and focuses on new or amended recommendations since the previous September 2015 print publication. The recommendations herein were developed by volunteer hepatology and infectious disease experts representing AASLD and IDSA and have been peer reviewed and approved by each society's governing board.
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Miyasaka A, Yoshida Y, Yoshida T, Murakami A, Abe K, Ohuchi K, Kawakami T, Watanabe D, Hoshino T, Sawara K, Takikawa Y. The Real-world Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir for Hepatitis C Genotype 1. Intern Med 2018; 57:2807-2812. [PMID: 29780135 PMCID: PMC6207834 DOI: 10.2169/internalmedicine.0810-18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Objective There are few reports on the outcomes of 12-week paritaprevir, ombitasvir, and ritonavir (PTV/OBV/r) treatment in real-world clinical settings. We aimed to evaluate the efficacy and safety of 12-week treatment with ritonavir-boosted paritaprevir and ombitasvir in patients with hepatitis C virus (HCV) genotype 1 infection in a real-world setting. Methods Fifty-eight patients with chronic hepatitis or compensated hepatic cirrhosis and genotype-1 HCV infection were treated with PTV/OBV/r and followed for 24 weeks after the completion of treatment in 10 centers in northern Tohoku. The efficacy and safety of this 12-week treatment regimen was analyzed. Results Among the 58 treated patients, 18 (31%) had compensated liver cirrhosis, while 11 (19%) patients had experienced treatment failure with another treatment regimen. NS5A resistance-associated variants (RAVs) were detected at baseline in 3 patients (5.2%), including Y93H in two patients and L31M in two patients. One patient had NS5A RAVs at both positions 93 and 31. The overall sustained virological response (SVR) 24 rate was 96.6%. Three patients with NS5A RAVs also achieved an SVR24. The SVR24 rate was not significantly affected by age, sex, prior treatment, prior history of HCC, or liver stiffness. The mean alanine aminotransferase (ALT) levels decreased significantly during this treatment. Adverse events occurred in 15 patients (26%), 26% of which were grade 1 or 2. No severe adverse events occurred. Conclusion In this real-world study, 12-week PTV/OBV/r treatment was effective and safe for treating patients with HCV-1 infection who had chronic hepatitis or compensated hepatic cirrhosis.
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Affiliation(s)
- Akio Miyasaka
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Japan
| | - Yuichi Yoshida
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Japan
| | | | - Akihiko Murakami
- Department of Gastroenterology, Iwate Prefectural Miyako Hospital, Japan
| | | | | | | | - Daisuke Watanabe
- Department of Gastroenterology, Noshiro Yamamoto Medical Association Hospital, Japan
| | - Takao Hoshino
- Department of Gastroenterology, Akita Kosei Medical Center, Japan
| | - Kei Sawara
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Japan
- Department of Gastroenterology, Iwate Prefectural Kamaishi Hospital, Japan
| | - Yasuhiro Takikawa
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Japan
- Department of Hepatology, San-ai Hospital, Japan
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Dias C, Duarte-Ribeiro F, Pipa S, Barbosa AR, Mota M, Rosas Vieira F. Hepatocellular carcinoma after direct-acting antiviral therapy for chronic HCV infection: Is it a real risk? IDCases 2018; 14:e00450. [PMID: 30191133 PMCID: PMC6125765 DOI: 10.1016/j.idcr.2018.e00450] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 08/29/2018] [Accepted: 08/29/2018] [Indexed: 01/05/2023] Open
Abstract
The newer oral treatments for chronic hepatitis C virus infection are one of the greatest revolutions in modern medicine. These drugs promise to eradicate the infection, showing high cure rates even in difficult to treat populations with very few side effects. Nevertheless, some cases of recurrence and de novo hepatocellular carcinoma after treatment with these drugs have been reported. We describe two cases of patients treated with direct-acting antiviral agents that developed hepatocarcinoma during follow-up post-treatment.
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Affiliation(s)
- Cátia Dias
- Corresponding author at: Rua Dr.º Francisco Sá Carneiro, 1228 1º esquerdo, São Cosme, 4420-132 Gondomar, Porto, Portugal.
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Toyoda H, Kumada T, Tada T, Mizuno K, Sone Y, Kaneoka Y, Maeda A, Akita T, Tanaka J. Impact of previously cured hepatocellular carcinoma (HCC) on new development of HCC after eradication of hepatitis C infection with non-interferon-based treatments. Aliment Pharmacol Ther 2018; 48:664-670. [PMID: 30047149 DOI: 10.1111/apt.14914] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 06/29/2018] [Accepted: 06/29/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND The incidence of hepatocellular carcinoma (HCC) in patients with a history of curatively-treated HCC is higher than in patients with no history of HCC even after sustained virologic response (SVR). AIM To investigate differences in the patterns of HCC development after SVR in patients with a history of curatively-treated HCC and those with no history of HCC, based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) findings. METHODS EOB-MRI was performed in 164 patients with HCV cirrhosis who achieved SVR by interferon-free direct-acting antiviral (DAA) therapy just before the start of therapy. Changes in EOB-MRI findings after SVR were compared prospectively between patients with (n = 62) and without (n = 102) a history of HCC. RESULTS The incidence of HCC after SVR was higher in patients with a history of HCC (P < 0.0001). The prevalence of nonhypervascular hypointense nodules (NHHNs) by EOB-MRI was significantly higher in patients with a history of HCC at baseline (P = 0.05). Although there was no difference in the incidence of the hypervascularisation of baseline NHHNs to typical hypervascular HCC between patients with and without a history of HCC, the incidence of direct emergence of hypervascular HCC despite the absence of NHHNs at baseline was significantly higher in patients with a history of HCC (P < 0.0001). CONCLUSION Direct emergence of hypervascular HCC and a higher prevalence of NHHNs before DD therapy contributed to the higher incidence of HCC after SVR. (UMIN000017020).
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kazuyuki Mizuno
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yasuhiro Sone
- Department of Radiology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yuji Kaneoka
- Department of Surgery, Ogaki Municipal Hospital, Ogaki, Japan
| | - Atsuyuki Maeda
- Department of Surgery, Ogaki Municipal Hospital, Ogaki, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
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Olveira A, Domínguez L, Troya J, Arias A, Pulido F, Ryan P, Benítez LM, González-García J, Montes ML. Persistently altered liver test results in hepatitis C patients after sustained virological response with direct-acting antivirals. J Viral Hepat 2018; 25:818-824. [PMID: 29476581 DOI: 10.1111/jvh.12883] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 01/16/2018] [Indexed: 12/30/2022]
Abstract
Guidelines recommend evaluating persistent alteration of liver tests in HCV-infected patients after sustained virological response (SVR) and its influence on liver disease progression. We studied the prevalence, etiology, associated factors and evolutionary implications of persistent alteration of liver tests in HCV patients after direct-acting antivirals (DAA)-induced SVR. This was a prospective study of HCV-infected patients and SVR after DAA. Those with another previously diagnosed liver disease were excluded. Persistent alteration of liver tests was defined as any increase in ALT, AST or GGT at SVR12 and SVR24. Causes were determined according to standard clinical practice, including liver biopsy and follow-up transient elastography. A total of 1112 patients were included (70.8% males, median age 53 years, 38.8% cirrhosis, 34.9% interferon-experienced, 56.8% HIV-coinfected). Persistent alteration of liver tests was detected in 130/1112 patients (11.7% [95%CI: 9.7-13.6]). Its frequency differed between HCV-monoinfected (45/480: 9.4% [95%CI: 6.7-12.1]) and HIV-coinfected (85/632: 13.5% [95%CI: 10.7-16.2]) (P = .046). In multivariable analysis, cirrhosis (OR 2.12; 95%CI: 1.28-3.53; P = .004) and baseline transient elastography values (OR 1.03; 95%CI: 1.01-1.04; P = .000) were associated with persistent alteration of liver tests. The main etiologies were clinical diagnosis suggestive of nonalcoholic fatty liver disease in 47 (36.2%), alcohol in 30 (23.1%) and drug consumption in 19 (14.6%). Baseline and follow-up transient elastography was performed in 594 patients and showed a significantly different decrease in patients who did or did not have a persistent alteration of liver tests (-21.1% vs -30%, respectively; P = .003), independently of sex, HIV status or baseline TE value. In conclusion, persistent alteration of liver tests is not infrequent after SVR. It is associated with cirrhosis and baseline transient elastography, and the main cause is fatty liver. According to transient elastography changes, persistent alteration of liver tests seems to affect the course of liver disease.
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Affiliation(s)
- A Olveira
- Servicio de Aparato Digestivo, Hospital La Paz, Madrid, Spain
| | - L Domínguez
- Unidad VIH, Servicio de Medicina Interna, Instituto de Investigación Biomédica del Hospital 12 de Octubre (imas12), Madrid, Spain
| | - J Troya
- Servicio de Medicina Interna, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - A Arias
- Servicio Medicina Interna, Unidad de trasplante hepático, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - F Pulido
- Unidad VIH, Servicio de Medicina Interna, Instituto de Investigación Biomédica del Hospital 12 de Octubre (imas12), Madrid, Spain
| | - P Ryan
- Servicio de Medicina Interna, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - L M Benítez
- Servicio Medicina Interna, Unidad de trasplante hepático, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - J González-García
- Unidad VIH, Servicio de Medicina Interna, Hospital Universitario La Paz, IdiPaz, Madrid, Spain
| | - M L Montes
- Unidad VIH, Servicio de Medicina Interna, Hospital Universitario La Paz, IdiPaz, Madrid, Spain
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Kozbial K, Moser S, Al-Zoairy R, Schwarzer R, Datz C, Stauber R, Laferl H, Strasser M, Beinhardt S, Stättermayer AF, Gschwantler M, Zoller H, Maieron A, Graziadei I, Trauner M, Steindl-Munda P, Hofer H, Ferenci P. Follow-up of sustained virological responders with hepatitis C and advanced liver disease after interferon/ribavirin-free treatment. Liver Int 2018; 38:1028-1035. [PMID: 29136329 DOI: 10.1111/liv.13629] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Accepted: 10/27/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND The introduction of direct-acting antivirals (DAA) has increased sustained virological response (SVR) rates in patients with advanced liver disease and chronic hepatitis C(CHC)infection. At present, data on clinical outcome and long-term durability of viral eradication after successful DAA therapy are scarce. AIM To evaluate the long-term success of viral eradication in patients with advanced fibrosis or cirrhosis treated with DAAs. METHODS Five hundred and fifty-one patients with advanced fibrosis (n = 158) or cirrhosis (CPS-A:317,CPS-B/C:76) and SVR after interferon and ribavirin-free DAA therapy treated between October 2013 and April 2016 were studied with a median follow-up of 65.6 (13.0-155.3) weeks. Only patients without hepatocellular carcinoma (HCC) at baseline and without liver transplantation were included. RESULTS Twelve patients (2.2%) died during follow-up: the mortality rate was 0.6% in F3, 2.2% in CPS-A and 5.3% in CPS-B/C patients (P = .08). During follow-up 36 patients with cirrhosis (9.1%) developed a liver related event, including 16 with de-novo HCC (4.1%). Seven patients were transplanted at a median of 9.7 (range 3.8-21.7) months after EOT. History of decompensation was significantly associated with liver related events during follow-up (HR 7.9; 95% CI 2.7-22.6; P < .001), and with mortality (HR 5.5; 95% CI 1.5-20.2, P = .01). CONCLUSIONS Eradication of HCV by DAA therapy was durable irrespective of the DAA combination used. Most of the cured patients had an excellent long-term clinical prognosis. Nevertheless, the risk of new occurrence of HCC remains worrisome and thus regular surveillance is obligatory even after clinical stabilization and improvement of the patient.
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Affiliation(s)
- Karin Kozbial
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Stephan Moser
- Department of Internal Medicine IV, Wilhelminenspital, Vienna, Austria
| | - Ramona Al-Zoairy
- Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria
| | - Remy Schwarzer
- Department of Internal Medicine IV, Ordensklinikum Linz, Elisabethinen, Linz, Austria
| | - Christian Datz
- Department of Internal Medicine, Krankenhaus Oberndorf, Teaching hospital of the Paracelsus Private Medical University of Salzburg, Oberndorf, Austria
| | - Rudolf Stauber
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Hermann Laferl
- Department of Internal Medicine, Kaiser-Franz-Josef-Spital, Vienna, Austria
| | - Michael Strasser
- Department of Internal Medicine I, Paracelsus University of Salzburg, Salzburg, Austria
| | - Sandra Beinhardt
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Albert F Stättermayer
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | | | - Heinz Zoller
- Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria
| | - Andreas Maieron
- Department of Internal Medicine IV, Ordensklinikum Linz, Elisabethinen, Linz, Austria.,Department of Internal Medicine II, University Clinics St. Pölten, St. Pölten, Austria
| | - Ivo Graziadei
- Department of Internal Medicine, Landeskrankenhaus Hall, Tirol, Austria
| | - Michael Trauner
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Petra Steindl-Munda
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Harald Hofer
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.,Department of Internal Medicine I, Klinikum Wels-Grieskirchen, Wels, Austria
| | - Peter Ferenci
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
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Changes in liver stiffness and steatosis among patients with hepatitis C virus infection who received direct-acting antiviral therapy and achieved sustained virological response. Eur J Gastroenterol Hepatol 2018; 30:546-551. [PMID: 29494353 DOI: 10.1097/meg.0000000000001106] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
AIM Whether direct-acting antiviral (DAA) therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection remains unclear. We evaluated sequential changes in liver stiffness and steatosis using transient elastography (TE) and the TE-based controlled attenuation parameter (CAP) in patients with HCV who received DAA therapy. PATIENTS AND METHODS A total of 57 patients with HCV who received DAA therapy and achieved sustained virological response (SVR) were analyzed. Liver stiffness as evaluated with TE, steatosis as evaluated with CAP, and laboratory data were assessed before treatment (baseline), at end of treatment (EOT), 24 weeks after EOT (SVR24), and 48 weeks after EOT (SVR48). RESULTS Alanine aminotransferase levels, corresponding to the presence of necroinflammatory activity, significantly decreased overall, with significant differences between baseline and EOT, EOT, and SVR24, and baseline and SVR48. However, alanine aminotransferase levels showed no significant changes between SVR24 and SVR48. Median (interquartile range) liver stiffness values at baseline, EOT, SVR24, and SVR48 were 8.3 (5.0-14.8), 7.4 (4.6-14.7), 5.3 (4.1-11.8), and 5.4 (4.0-13.4) kPa, respectively (baseline vs. EOT, P=0.044; EOT vs. SVR24, P=0.011; and SVR24 vs. SVR48, P=0.054). In patients with fatty liver (CAP≥236 dB/m, n=14), CAP values at baseline and SVR48 were 253 (245-278) and 229 (209-249) dB/m, respectively (P=0.020). CONCLUSION Liver stiffness at SVR24 might reflect liver fibrosis in the patients who received DAA therapy and achieved SVR. In addition, liver steatosis reduces in the same cohort with fatty liver.
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Tada T, Kumada T, Toyoda H, Sone Y, Takeshima K, Ogawa S, Goto T, Wakahata A, Nakashima M, Nakamuta M, Tanaka J. Viral eradication reduces both liver stiffness and steatosis in patients with chronic hepatitis C virus infection who received direct-acting anti-viral therapy. Aliment Pharmacol Ther 2018; 47:1012-1022. [PMID: 29424449 DOI: 10.1111/apt.14554] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Revised: 12/28/2017] [Accepted: 01/16/2018] [Indexed: 12/19/2022]
Abstract
BACKGROUND Whether direct-acting anti-viral therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection is unclear. AIMS To evaluate changes in liver stiffness and steatosis in patients with HCV who received direct-acting anti-viral therapy and achieved sustained virological response (SVR). METHODS A total of 198 patients infected with HCV genotype 1 or 2 who achieved SVR after direct-acting anti-viral therapy were analysed. Liver stiffness as evaluated by magnetic resonance elastography, steatosis as evaluated by magnetic resonance imaging-determined proton density fat fraction (PDFF), insulin resistance, and laboratory data were assessed before treatment (baseline) and at 24 weeks after the end of treatment (SVR24). RESULTS Alanine aminotransferase and homeostatic model assessment-insulin resistance levels decreased significantly from baseline to SVR24. Conversely, platelet count, which is inversely associated with liver fibrosis, increased significantly from baseline to SVR24. In patients with high triglyceride levels (≥150 mg/dL), triglyceride levels significantly decreased from baseline to SVR24 (P = 0.004). The median (interquartile range) liver stiffness values at baseline and SVR24 were 3.10 (2.70-4.18) kPa and 2.80 (2.40-3.77) kPa respectively (P < 0.001). The PDFF values at baseline and SVR 24 were 2.4 (1.7-3.4)% and 1.9 (1.3-2.8)% respectively (P < 0.001). In addition, 68% (19/28) of patients with fatty liver at baseline (PDFF ≥5.2%; n = 28) no longer had fatty liver (PDFF <5.2%) at SVR24. CONCLUSION Viral eradication reduces both liver stiffness and steatosis in patients with chronic HCV who received direct-acting anti-viral therapy (UMIN000017020).
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Affiliation(s)
- T Tada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - T Kumada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - H Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Y Sone
- Department of Radiology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - K Takeshima
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - S Ogawa
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - T Goto
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - A Wakahata
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - M Nakashima
- Department of Pharmacy, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - M Nakamuta
- Department of Gastroenterology, Kyushu Medical Center, Fukuoka, Japan
| | - J Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
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Fabrizi F, Lunghi G, Martin P. Treatment of HCV-related Liver Disease in the Dialysis Population: A Novel Challenge for Clinical Nephrologists. Int J Artif Organs 2018. [DOI: 10.1177/039139880102400602] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- F. Fabrizi
- Division of Nephrology and Dialysis, Maggiore Hospital, IRCCS, Milan - Italy
| | - G. Lunghi
- Institute of Hygiene and Preventive Medicine, Maggiore Hospital, IRCCS, Milan - Italy
| | - P. Martin
- Liver Transplant Program, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA - USA
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Nirei K, Kanda T, Nakamura H, Matsuoka S, Takayama T, Sugitani M, Moriyama M. Persistent Hepatic Inflammation Plays a Role in Hepatocellular Carcinoma After Sustained Virological Response in Patients with HCV Infection. Int J Med Sci 2018; 15:466-474. [PMID: 29559835 PMCID: PMC5859769 DOI: 10.7150/ijms.23147] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 02/02/2018] [Indexed: 02/07/2023] Open
Abstract
Objective: Hepatitis C virus (HCV) infection has long been treated with interferon therapy (IFN). Currently, more than 90% of IFN-treated patients show a sustained virological response (SVR) when also treated with ribavirin and/or a protease inhibitor. Histological inflammation and fibrosis improve in IFN-treated patients, which indicates HCV clearance. IFN also reduces the incidence of hepatocellular carcinoma (HCC). However, a small proportion of patients with SVR develop HCC. To investigate the causes of hepatic carcinogenesis after SVR, we compared the liver histological findings before IFN to those after the development of HCC. Patients and methods: In total, 602 patients infected with type C chronic hepatitis or with liver cirrhosis who received IFN therapy during the period from 1992 through 2015 were included in this study. We assessed 14 of the 287 patients who achieved an SVR. Results: HCC was diagnosed by computed tomography, angiography or liver biopsy. The longest time from the SVR until HCC detection was 16.5 years, and the mean was 7.2±4.6 years. Nine of the 14 patients underwent surgery and one radiofrequency ablation. The histological findings of 10 patients were available for comparison. The comparison of the histological findings before treatment with those after the HCC diagnosis revealed an amelioration of liver fibrosis and other inflammatory changes. All ten patients showed improvements in fibrosis and steatosis. However, we observed that mild inflammatory change persisted from 1.8 years to 16.5 years after the confirmation of SVR in all cases. Conclusion: We suspect that persistent histological inflammation is one of the factors contributing to hepatocarcinogenesis (i.e., HCC development) even after successful treatment.
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Affiliation(s)
- Kazushige Nirei
- Division of Gastroenterology and Hepatology, Department of Internal Medicine
| | - Tatsuo Kanda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine
| | - Hitomi Nakamura
- Division of Gastroenterology and Hepatology, Department of Internal Medicine
| | - Shunichi Matsuoka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine
| | | | | | - Mitsuhiko Moriyama
- Division of Gastroenterology and Hepatology, Department of Internal Medicine
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40
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Tachi Y, Hirai T, Kojima Y, Ishizu Y, Honda T, Kuzuya T, Hayashi K, Ishigami M, Goto H. Liver stiffness reduction correlates with histological characteristics of hepatitis C patients with sustained virological response. Liver Int 2018; 38:59-67. [PMID: 28557143 DOI: 10.1111/liv.13486] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2017] [Accepted: 05/23/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS We investigated the correlation between histological characteristics and changes in liver stiffness (LS) in patients with sustained virological response (SVR) using acoustic radiation force impulse (ARFI) elastography. METHODS In this prospective study, we enrolled 176 hepatitis C patients with SVR who underwent ARFI elastography and liver biopsy before antiviral treatment, and serial ARFI elastography at the end of treatment (EOT) and at 24 weeks after the EOT. To compare the long-term changes in LS in patients with SVR using ARFI elastography, another group of 140 patients who had undergone paired biopsy after achieving SVR was included. RESULTS Mean LS values were 1.60±0.63 m/s, 1.48±0.56 m/s and 1.37±0.62 m/s at baseline, EOT and 24 weeks after EOT, respectively, P<.001. Higher inflammatory activity at baseline was associated with an improvement in LS at the EOT, with an odds ratio of 1.940. Significant fibrosis at baseline was associated with an improvement in LS at 24 weeks after the EOT, with an odds ratio of 2.617. Among patients in the paired biopsy group with baseline fibrosis stage identical to the ARFI group, LS values at 24 weeks after the EOT did not show any difference with values at 5 years after EOT. CONCLUSIONS Pre-treatment histological characteristics influence LS reduction after SVR is achieved.
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Affiliation(s)
- Yoshihiko Tachi
- Department of Gastroenterology, Komaki City Hospital, Komaki, Aichi, Japan
| | - Takanori Hirai
- Department of Gastroenterology, Komaki City Hospital, Komaki, Aichi, Japan
| | - Yuko Kojima
- Department of Gastroenterology, Komaki City Hospital, Komaki, Aichi, Japan
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Aichi, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Aichi, Japan
| | - Teiji Kuzuya
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Aichi, Japan
| | - Kazuhiko Hayashi
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Aichi, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Aichi, Japan
| | - Hidemi Goto
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Aichi, Japan
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Tada T, Kumada T, Toyoda H, Mizuno K, Sone Y, Kataoka S, Hashinokuchi S. Improvement of liver stiffness in patients with hepatitis C virus infection who received direct-acting antiviral therapy and achieved sustained virological response. J Gastroenterol Hepatol 2017; 32:1982-1988. [PMID: 28299813 DOI: 10.1111/jgh.13788] [Citation(s) in RCA: 82] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Revised: 02/25/2017] [Accepted: 03/12/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM There is insufficient research on whether direct-acting antiviral (DAA) therapy can improve liver fibrosis in patients with chronic hepatitis C virus (HCV). We evaluated sequential changes in liver stiffness using shear wave elastography in patients with HCV who received DAA therapy. METHODS A total of 210 patients with HCV who received daclatasvir and asunaprevir therapy and achieved sustained virological response (SVR) were analyzed. Liver stiffness, as evaluated by shear wave elastography, and laboratory data were assessed before treatment (baseline), at end of treatment (EOT), and at 24 weeks after EOT (SVR24). RESULTS Alanine aminotransferase levels (ALT) decreased over time, and there were significant differences between baseline and EOT and between EOT and SVR24. Although platelet counts did not significantly differ between baseline and EOT, they increased significantly from EOT to SVR24. The median (interquartile range) liver stiffness values at baseline, EOT, and SVR24 were 10.2 (7.7-14.7), 8.8 (7.1-12.1), and 7.6 (6.3-10.3) kPa, respectively (P < 0.001, baseline vs EOT; P < 0.001, EOT vs SVR24). Additionally, in patients with ALT ≤ 30 (indicating low necroinflammatory activity in the liver) and Fibrosis-4 index > 2.0 (n = 75), the liver stiffness values at baseline, EOT, and SVR24 were 9.6 (7.7-15.2), 9.2 (7.3-12.1), and 7.7 (6.3-10.1) kPa, respectively (P < 0.001, baseline vs EOT; P < 0.001, EOT vs SVR24). CONCLUSION These results suggest that early improvement of liver stiffness starts during the administration of DAAs in patients who achieve SVR, and this effect is particularly pronounced in patients with progressive liver fibrosis.
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Affiliation(s)
- Toshifumi Tada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Takashi Kumada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Kazuyuki Mizuno
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Yasuhiro Sone
- Department of Radiology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
| | - Saki Kataoka
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Gifu, Japan
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Papasavvas E, Azzoni L, Yin X, Liu Q, Joseph J, Mackiewicz A, Ross B, Lynn KM, Jacobson JM, Mounzer K, Kostman JR, Montaner LJ. HCV viraemia associates with NK cell activation and dysfunction in antiretroviral therapy-treated HIV/HCV-co-infected subjects. J Viral Hepat 2017; 24:865-876. [PMID: 28419653 PMCID: PMC5589504 DOI: 10.1111/jvh.12714] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Accepted: 03/21/2017] [Indexed: 12/12/2022]
Abstract
The impact of hepatitis C virus (HCV) RNA levels on immune status in chronically HCV mono-infected when compared to HIV/HCV co-infected on antiretroviral therapy (ART) remains poorly understood. A total of 78 African American subjects HCV viraemic/naïve to HCV treatment (33 HCV genotype 1 mono-infected, 45 ART-treated HIV/HCV genotype 1 co-infected) were studied. Clinical and liver enzyme measurements were performed. Whole blood was analysed for immune subset changes by flow cytometry. Peripheral blood mononuclear cells (PBMC) were used for same-day constitutive and in vitro Interferon (IFN)-α-induced signal transducer and activator of transcription (STAT) phosphorylation, K562 target cell lysis and K562 target cell recognition-mediated IFN-γ production. Statistical analysis was performed using R (2.5.1) or JMP Pro 11. While both groups did not differ in the level of liver enzymes, HIV/HCV had higher T-cell activation/exhaustion, and constitutive STAT-1 phosphorylation compared to HCV. In contrast, CD4+ FoxP3+ CD25+ frequency, IFN-αR expression on NK cells, as well as constitutive and IFN-α-induced direct cytotoxicity were lower in HIV/HCV. Linear regression models further supported these results. Finally, increase in HCV viral load and CD4+ T-cell count had an opposite effect between the two groups on NK cell activity and T-cell activation, respectively. HCV viral load in ART-treated HIV/HCV co-infection was associated with greater immune activation/exhaustion and NK dysfunction than HCV viral load alone in HCV mono-infection. The more pronounced immune modulation noted in ART-treated HIV-co-infected/untreated HCV viraemic subjects may impact HCV disease progression and/or response to immunotherapy.
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Affiliation(s)
| | - L. Azzoni
- The Wistar Institute, Philadelphia, PA, USA
| | - X. Yin
- The Wistar Institute, Philadelphia, PA, USA
| | - Q. Liu
- The Wistar Institute, Philadelphia, PA, USA
| | - J. Joseph
- The Wistar Institute, Philadelphia, PA, USA
| | | | - B. Ross
- The Wistar Institute, Philadelphia, PA, USA
| | - K. M. Lynn
- Presbyterian Hospital-University of Pennsylvania hospital, Philadelphia, PA, USA
| | - J. M. Jacobson
- Temple University, Lewis Katz School of Medicine, Philadelphia, PA, USA
| | - K. Mounzer
- Jonathan Lax Immune Disorders Treatment Center, Philadelphia Field Initiating Group for HIV-1 Trials, Philadelphia, PA, USA
| | - J. R. Kostman
- John Bell Health Center, Philadelphia Field Initiating Group for HIV-1 Trials, Philadelphia, PA, USA
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Elsharkawy A, Alem SA, Fouad R, El Raziky M, El Akel W, Abdo M, Tantawi O, AbdAllah M, Bourliere M, Esmat G. Changes in liver stiffness measurements and fibrosis scores following sofosbuvir based treatment regimens without interferon. J Gastroenterol Hepatol 2017; 32:1624-1630. [PMID: 28177543 DOI: 10.1111/jgh.13758] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Revised: 01/07/2017] [Accepted: 01/30/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Accurate evaluation of the degree of liver fibrosis in patients with chronic liver diseases is crucial, as liver fibrosis is important in order to make therapeutic decisions, determine prognosis of liver disease and to follow-up disease progression. Multiple non-invasive methods have been used successfully in the prediction of fibrosis; however, early changes in non-invasive biomarkers of hepatic fibrosis under effective antiviral therapy are widely unknown. The aim of this study is to evaluate changes of transient elastography values as well as FIB-4 and AST to platelet ratio index (APRI) in patients treated with Sofosbuvir-based treatment regimen. METHODS This is a retrospective study including 337 chronic HCV Egyptian patients with genotype 4 mainly. They were treated with Sofosbuvir-based treatment regimen. Transient elastography values were recorded as well as FIB-4 and APRI were calculated at baseline and SVR12. RESULTS There was a significant improvement of platelets counts, ALT and AST levels, which in turn cause significant improvement in FIB-4 and APRI scores at SVR12. Liver stiffness measurements were significantly lower in SVR12 (14.8 ± 10.7 vs 11.8 ± 8.8 kPa, P = 0.000). About 77% of responders and 81.1% of cirrhotic patients showed improvement in liver stiffness measurements at SVR12.Univariate and multivariate regression analysis showed that failure to achieve improvement in liver stiffness measurements were significantly associated with relapsers and low baseline liver stiffness measurement. CONCLUSION Sofosbuvir-based treatment resulted in a clinically significant improvement in parameters of liver fibrosis.
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Affiliation(s)
- Aisha Elsharkawy
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt
| | - Shereen Abdel Alem
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt
| | - Rabab Fouad
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt
| | - Maissa El Raziky
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt
| | - Wafaa El Akel
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt
| | - Mahmoud Abdo
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt
| | - Omnia Tantawi
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt
| | - Mohamed AbdAllah
- Medical Research Division, National Research Centre, Giza, Egypt
| | - Marc Bourliere
- Department of Hepato-Gastroenterology, Hospital Saint Joseph, Marseille, France
| | - Gamal Esmat
- Endemic Medicine and Hepatology Department, Faculty of medicine, Cairo University, Cairo, Egypt
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Tada T, Kumada T, Toyoda H, Kiriyama S, Tanikawa M, Hisanaga Y, Kanamori A, Kitabatake S, Yama T, Tanaka J. Post-treatment levels of α-fetoprotein predict long-term hepatocellular carcinoma development after sustained virological response in patients with hepatitis C. Hepatol Res 2017; 47:1021-1031. [PMID: 27859993 DOI: 10.1111/hepr.12839] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 10/17/2016] [Accepted: 11/06/2016] [Indexed: 02/08/2023]
Abstract
AIM The rate of hepatocellular carcinoma (HCC) development is reportedly lower in patients with chronic hepatitis C virus (HCV) who have achieved a sustained virological response (SVR) than in patients who were unresponsive to therapy. However, the development of HCC is sometimes observed in patients with SVR. Therefore, we clarified the predictive power of clinical factors for HCC incidence in patients with SVR using receiver operating characteristic (ROC) curve analysis that takes time dependence into account. METHODS A total of 571 patients with HCV who achieved SVR with interferon-based therapy were enrolled. Univariate and multivariate Cox proportional hazards models and time-dependent ROC curves were used to analyze clinical factors associated with the development of HCC. RESULTS Twenty-four patients developed HCC during the follow-up period (median duration, 9.0 years). The 5-, 10-, 15-, and 20-year cumulative incidence rates for HCC were 1.7%, 4.8%, 5.8%, and 6.6%, respectively. Multivariate Cox proportional hazards models showed that older age (hazard ratio [HR], 3.648), male sex (HR, 7.560), lower platelet count at 24 weeks after the end of treatment (SVR24) (HR, 3.939), and higher α-fetoprotein (AFP) at SVR24 (HR, 3.630) were independently associated with HCC development. In addition, time-dependent ROC analysis showed that, compared to platelet count at SVR24, AFP at SVR24 had higher predictive power for HCC incidence approximately 7 years after SVR. CONCLUSIONS Elevated AFP at SVR24 is a risk factor for HCC in patients with HCV, even those who achieve SVR. α-Fetoprotein is a good predictor of HCC development.
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Affiliation(s)
- Toshifumi Tada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Kumada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Seiki Kiriyama
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Makoto Tanikawa
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yasuhiro Hisanaga
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Akira Kanamori
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Shusuke Kitabatake
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Tsuyoki Yama
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
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Ahmed KT, Almashhrawi AA, Ibdah JA, Tahan V. Is the 25-year hepatitis C marathon coming to an end to declare victory? World J Hepatol 2017; 9:921-929. [PMID: 28824743 PMCID: PMC5545137 DOI: 10.4254/wjh.v9.i21.921] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Revised: 06/04/2017] [Accepted: 07/10/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) which was originally recognized as posttransfusion non-A, non-B hepatitis has been a major global health problem affecting 3% of the world population. Interferon/peginterferon and ribavirin combination therapy was the backbone of chronic HCV therapy for two decades of the journey. However, the interferon based treatment success rate was around 50% with many side effects. Many chronic HCV patients with psychiatric diseases, or even cytopenias, were ineligible for HCV treatment. Now, we no longer need any injectable medicine. New direct-acting antiviral agents against HCV allowed the advance of interferon-free and ribavirin-free oral regimens with high rates of response and tolerability. The cost of the medications should not be a barrier to their access in certain parts of the world. While we are getting closer, we should still focus on preventing the spread of the disease, screening and delivering the cure globally to those in need. In the near future, development of an effective vaccine against HCV would make it possible to eradicate HCV infection worldwide completely.
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Tada T, Kumada T, Toyoda H, Kiriyama S, Tanikawa M, Hisanaga Y, Kanamori A, Kitabatake S, Yama T, Tanaka J. Viral eradication reduces all-cause mortality, including non-liver-related disease, in patients with progressive hepatitis C virus-related fibrosis. J Gastroenterol Hepatol 2017; 32:687-694. [PMID: 27577675 DOI: 10.1111/jgh.13589] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/24/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Eradication of hepatitis C virus (HCV) with interferon (IFN)-based therapy has been reported to reduce all-cause mortality in patients with chronic HCV infection. However, the impact of HCV eradication on non-liver-related mortality and causes of death has not been sufficiently investigated in patients with progressive HCV-related fibrosis. METHODS We enrolled 784 chronic HCV patients with progressive liver fibrosis (aspartate aminotransferase to platelet ratio index >1). Cause of death, incidence of hepatocellular carcinoma, and all-cause mortality including non-liver-related mortality were analyzed. RESULTS Of these 784 patients, 170 achieved sustained virological response (SVR) (eradication of HCV) with IFN-based therapy (IFN-SVR), and 614 did not receive IFN-based therapy (non-IFN patients, chronic HCV infection). The median follow-up duration was 10.3 years. Two hundred seventy-three patients died during follow-up (liver-related death, n = 171; non-liver-related death, n = 102). The mortality rate from non-liver-related disease was 63.6% (7/11) in IFN-SVR patients and 36.3% (95/262) in non-IFN patients, respectively. In multivariate analysis, the eradication of HCV associated with not only hepatocellular carcinoma incidence (hazard ratio (HR), 0.162; 95% confidence interval (CI), 0.092-0.284), and all-cause mortality (HR, 0.094; 95% CI, 0.047-0.187), but non-liver-related mortality (HR, 0.286; 95% CI, 0.127-0.644) as well. CONCLUSIONS Eradication of HCV reduced both liver-related and non-liver-related mortality in patients with progressive HCV-related fibrosis.
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Affiliation(s)
- Toshifumi Tada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Kumada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Seiki Kiriyama
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Makoto Tanikawa
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yasuhiro Hisanaga
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Akira Kanamori
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Shusuke Kitabatake
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Tsuyoki Yama
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
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Wang X, Gao F, Yuan G, Shi K, Huang Y, Chen Y, Qiu R, Sun L, Liu J, Hu C, Zhou Y. Ten-year follow-up analysis of chronic hepatitis C patients after getting sustained virological response to pegylated interferon-α and ribavirin therapy. J Viral Hepat 2016; 23:971-976. [PMID: 27453300 DOI: 10.1111/jvh.12574] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2016] [Accepted: 07/07/2016] [Indexed: 01/23/2023]
Abstract
There is little data on the long-term follow-up outcomes of chronic hepatitis C patients achieving sustained virological response (SVR) after treatment with peglylated interferon-α plus ribavirin. We prospectively investigated the overall clinical, biochemical, virological and histological outcomes in a ten-year cohort study of 325 patients with chronic hepatitis C achieving SVR to pegylated interferon-α and ribavirin therapy. Patients underwent consistent clinical, biochemical and virological evaluation every six months, and patients with pretherapy Ishak fibrosis score ≥2 were invited to accept a second liver biopsy at the last follow-up. Liver biopsy specimens were evaluated using Ishak's scoring system. At the end of follow-up, five patients developed decompensated liver cirrhosis. One patient (0.3%) with pretherapy cirrhosis was diagnosed with hepatocellular carcinoma (HCC). A total of 305 patients (94%) had normal serum ALT and AST levels during the entire period of follow-up. Twenty-seven patients (8%) had conclusive evidence of virological relapse. Among the 117 patients with paired pretherapy and long-term follow-up biopsies, 96 (82%) had a decreased fibrosis score. Ninety-nine (79%) had a decrease in combined inflammation score. Thirty-seven (32%) had normal or nearly normal livers on long-term follow-up biopsy. SVR achieved with PEG-IFN-α and RBV combination therapy is durable, while late virological relapse may still occur in some patients. Clinical outcomes for patients who obtain SVR are excellent, although the patients with cirrhosis are still at a low risk of hepatocellular carcinoma.
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Affiliation(s)
- X Wang
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.,Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - F Gao
- Department of Infectious Diseases, Linyi People's Hospital, Linyi, Shandong, China
| | - G Yuan
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - K Shi
- Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Y Huang
- Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Y Chen
- Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - R Qiu
- Department of Infectious Diseases, The Affiliated Hospital of Putian University, Putian, Fujian, China
| | - L Sun
- Department of Pathology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - J Liu
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - C Hu
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Y Zhou
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
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48
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Treatment of hepatitis C in renal impairment and renal transplant. CURRENT TREATMENT OPTIONS IN INFECTIOUS DISEASES 2016. [DOI: 10.1007/s40506-016-0089-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Omata M, Kanda T, Wei L, Yu ML, Chuang WL, Ibrahim A, Lesmana CRA, Sollano J, Kumar M, Jindal A, Sharma BC, Hamid SS, Dokmeci AK, Al-Mahtab M, McCaughan GW, Wasim J, Crawford DHG, Kao JH, Yokosuka O, Lau GKK, Sarin SK. APASL consensus statements and recommendations for hepatitis C prevention, epidemiology, and laboratory testing. Hepatol Int 2016; 10:681-701. [PMID: 27229718 PMCID: PMC5003900 DOI: 10.1007/s12072-016-9736-3] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 04/20/2016] [Indexed: 02/06/2023]
Abstract
The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on "APASL consensus statements and recommendations for management of hepatitis C" in March 2015 to revise the "APASL consensus statements and management algorithms for hepatitis C virus infection" (Hepatol Int 6:409-435, 2012). The working party consisted of expert hepatologists from the Asian-Pacific region gathered at the Istanbul Congress Center, Istanbul, Turkey on 13 March 2015. New data were presented, discussed, and debated during the course of drafting a revision. Participants of the consensus meeting assessed the quality of the cited studies. The finalized recommendations for hepatitis C prevention, epidemiology, and laboratory testing are presented in this review.
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Affiliation(s)
- Masao Omata
- Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan.
- The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Tatsuo Kanda
- Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Lai Wei
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China
| | - Ming-Lung Yu
- Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Wang-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Alaaeldin Ibrahim
- GI/Liver Division, Department of Internal Medicine, University of Benha, Banha, Egypt
| | | | - Jose Sollano
- University Santo Tomas Hospital, Manila, Philippines
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Saeed S Hamid
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - A Kadir Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Mamun Al-Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, 1000, Bangladesh
| | - Geofferey W McCaughan
- Royal Prince Alfred Hospital, Centenary Institute, University of Sydney, Sydney, Australia
| | - Jafri Wasim
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - Darrell H G Crawford
- University of Queensland, School of Medicine, Woolloongabba, QLD, 4102, Australia
| | - Jia-Horng Kao
- National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Osamu Yokosuka
- Graduate School of Medicine, Chiba University, Chiba, Japan
| | - George K K Lau
- The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, China
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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50
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Vandenbulcke H, Moreno C, Colle I, Knebel JF, Francque S, Sersté T, George C, de Galocsy C, Laleman W, Delwaide J, Orlent H, Lasser L, Trépo E, Van Vlierberghe H, Michielsen P, van Gossum M, de Vos M, Marot A, Doerig C, Henrion J, Deltenre P. Alcohol intake increases the risk of HCC in hepatitis C virus-related compensated cirrhosis: A prospective study. J Hepatol 2016; 65:543-51. [PMID: 27180899 DOI: 10.1016/j.jhep.2016.04.031] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2015] [Revised: 04/05/2016] [Accepted: 04/27/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Whether alcohol intake increases the risk of complications in patients with HCV-related cirrhosis remains unclear. The aim of this study was to determine the impact of alcohol intake and viral eradication on the risk of hepatocellular carcinoma (HCC), decompensation of cirrhosis and death. METHODS Data on alcohol intake and viral eradication were prospectively collected in 192 patients with compensated HCV-related cirrhosis. RESULTS 74 patients consumed alcohol (median alcohol intake: 15g/day); 68 reached viral eradication. During a median follow-up of 58months, 33 patients developed HCC, 53 experienced at least one decompensation event, and 39 died. The 5-year cumulative incidence rate of HCC was 10.6% (95% CI: 4.6-16.6) in abstainers vs. 23.8% (95% CI: 13.5-34.1) in consumers (p=0.087), and 2.0% (95% CI: 0-5.8) vs. 21.7% (95% CI: 14.2-29.2) in patients with and without viral eradication (p=0.002), respectively. The lowest risk of HCC was observed for patients without alcohol intake and with viral eradication (0%) followed by patients with alcohol intake and viral eradication (6.2% [95% CI: 0-18.4]), patients without alcohol intake and no viral eradication (15.9% [95% CI: 7.1-24.7]), and patients with alcohol intake and no viral eradication (29.2% [95% CI: 16.5-41.9]) (p=0.009). In multivariate analysis, lack of viral eradication and alcohol consumption were associated with the risk of HCC (hazard ratio for alcohol consumption: 3.43, 95% CI: 1.49-7.92, p=0.004). Alcohol intake did not influence the risk of decompensation or death. CONCLUSIONS Light-to-moderate alcohol intake increases the risk of HCC in patients with HCV-related cirrhosis. Patient care should include measures to ensure abstinence. LAY SUMMARY Whether alcohol intake increases the risk of complications in patients with HCV-related cirrhosis remains unclear. In this prospective study, light-to-moderate alcohol intake was associated with the risk of hepatocellular carcinoma in multivariate analysis. No patients who did not use alcohol and who reached viral eradication developed hepatocellular carcinoma during follow-up. The risk of hepatocellular carcinoma increased with alcohol intake or in patients without viral eradication and was highest when alcohol intake was present in the absence of viral eradication. Patients with HCV-related cirrhosis should be strongly advised against any alcohol intake. Patient care should include measures to ensure abstinence.
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Affiliation(s)
- Hélène Vandenbulcke
- Departement of Gastroenterology and Hepatology, Hôpital de Jolimont, Haine-Saint-Paul, Belgium
| | - Christophe Moreno
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Isabelle Colle
- Departement of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Jean-François Knebel
- Laboratory for Investigative Neurophysiology (The LINE), Department of Radiology and Department of Clinical Neurosciences, University Hospital Center and University of Lausanne, 1011 Lausanne, Switzerland; EEG Brain Mapping Core, Centre for Biomedical Imaging (CIBM), 1011 Lausanne, Switzerland
| | - Sven Francque
- Departement of Gastroenterology and Hepatology, UZ Antwerpen, Edegem, Belgium
| | - Thomas Sersté
- Departement of Gastroenterology and Hepatology, CHU Saint-Pierre, Brussels, Belgium
| | - Christophe George
- Departement of Gastroenterology and Hepatology, AZ Groeninge, Kortrijk, Belgium
| | - Chantal de Galocsy
- Departement of Gastroenterology and Hepatology, Hôpitaux Iris Sud Bracops, Brussels, Belgium
| | - Wim Laleman
- Departement of Gastroenterology and Hepatology, KUL, Leuven, Belgium
| | - Jean Delwaide
- Departement of Gastroenterology and Hepatology, CHU Liège, Liège, Belgium
| | - Hans Orlent
- Departement of Gastroenterology and Hepatology, AZ St Jan, Brugge, Belgium
| | - Luc Lasser
- Departement of Gastroenterology and Hepatology, CHU Brugmann, Brussels, Belgium
| | - Eric Trépo
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Hans Van Vlierberghe
- Departement of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Peter Michielsen
- Departement of Gastroenterology and Hepatology, UZ Antwerpen, Edegem, Belgium
| | - Marc van Gossum
- Departement of Gastroenterology and Hepatology, CHU Saint-Pierre, Brussels, Belgium
| | - Marie de Vos
- Departement of Gastroenterology and Hepatology, Hôpital de Jolimont, Haine-Saint-Paul, Belgium
| | - Astrid Marot
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Christopher Doerig
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Jean Henrion
- Departement of Gastroenterology and Hepatology, Hôpital de Jolimont, Haine-Saint-Paul, Belgium
| | - Pierre Deltenre
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
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