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Di Marco L, Cannova S, Ferrigno E, Landro G, Nonni R, Mantia CL, Cartabellotta F, Calvaruso V, Di Marco V. A Comprehensive Review of Antiviral Therapy for Hepatitis C: The Long Journey from Interferon to Pan-Genotypic Direct-Acting Antivirals (DAAs). Viruses 2025; 17:163. [PMID: 40006918 PMCID: PMC11860415 DOI: 10.3390/v17020163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 01/19/2025] [Accepted: 01/20/2025] [Indexed: 02/27/2025] Open
Abstract
The treatment landscape for hepatitis C virus (HCV) infection has transformed over the past few decades, evolving from the limited efficacy of interferon (IFN) monotherapy to the highly successful pan-genotypic direct-acting antivirals (DAAs) used today. Initially, alpha-interferon monotherapy, introduced in the 1990s, was the standard treatment, yet it provided low sustained virological response (SVR) rates and caused significant adverse effects, limiting its utility. The development of pegylated interferon (peg-IFN) improved the pharmacokinetic profile of IFN, allowing for less frequent dosing and modestly improved response rates. When combined with ribavirin, peg-IFN achieved higher SVR rates, especially in non-genotype 1 HCV infections, but the combination also brought additional side effects, such as anemia and depression. The advent of the first-generation DAAs, such as telaprevir and boceprevir, marked a significant milestone. Combined with peg-IFN and ribavirin, these protease inhibitors boosted response rates in patients with genotype 1 HCV. However, high rates of adverse effects and drug resistance remained challenges. Second-generation DAAs, like sofosbuvir and ledipasvir, introduced IFN-free regimens with improved safety profiles and efficacy. The most recent advances are pan-genotypic DAAs, including glecaprevir-pibrentasvir and sofosbuvir-velpatasvir, which offer high SVR rates across all genotypes, shorter treatment durations, and fewer side effects. Current pan-genotypic regimens represent a cornerstone in HCV therapy, providing an accessible and effective solution globally.
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Affiliation(s)
- Lorenza Di Marco
- SIcilian Network for Therapy, Epidemiology and Screening In Hepatology (SINTESI), 90127 Palermo, Italy; (L.D.M.); (F.C.); (V.C.)
- Department of Oncology and Hematology, Azienda Ospedaliero-University Hospital of Mod, 41124 Modena, Italy
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41100 Modena, Italy
| | - Simona Cannova
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy; (S.C.); (E.F.); (G.L.); (R.N.); (C.L.M.)
| | - Emanuele Ferrigno
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy; (S.C.); (E.F.); (G.L.); (R.N.); (C.L.M.)
| | - Giuseppe Landro
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy; (S.C.); (E.F.); (G.L.); (R.N.); (C.L.M.)
| | - Rosario Nonni
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy; (S.C.); (E.F.); (G.L.); (R.N.); (C.L.M.)
| | - Claudia La Mantia
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy; (S.C.); (E.F.); (G.L.); (R.N.); (C.L.M.)
| | - Fabio Cartabellotta
- SIcilian Network for Therapy, Epidemiology and Screening In Hepatology (SINTESI), 90127 Palermo, Italy; (L.D.M.); (F.C.); (V.C.)
- Department of Medicine, Buccheri-La Ferla Hospital, 90123 Palermo, Italy
| | - Vincenza Calvaruso
- SIcilian Network for Therapy, Epidemiology and Screening In Hepatology (SINTESI), 90127 Palermo, Italy; (L.D.M.); (F.C.); (V.C.)
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy; (S.C.); (E.F.); (G.L.); (R.N.); (C.L.M.)
| | - Vito Di Marco
- SIcilian Network for Therapy, Epidemiology and Screening In Hepatology (SINTESI), 90127 Palermo, Italy; (L.D.M.); (F.C.); (V.C.)
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy; (S.C.); (E.F.); (G.L.); (R.N.); (C.L.M.)
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Smirne C, Crobu MG, Landi I, Vercellino N, Apostolo D, Pinato DJ, Vincenzi F, Minisini R, Tonello S, D’Onghia D, Ottobrelli A, Martini S, Bracco C, Fenoglio LM, Campanini M, Berton AM, Ciancio A, Pirisi M. Chronic Hepatitis C Infection Treated with Direct-Acting Antiviral Agents and Occurrence/Recurrence of Hepatocellular Carcinoma: Does It Still Matter? Viruses 2024; 16:1899. [PMID: 39772206 PMCID: PMC11680226 DOI: 10.3390/v16121899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 12/05/2024] [Accepted: 12/06/2024] [Indexed: 01/03/2025] Open
Abstract
Hepatitis C virus (HCV) infection is a significant risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). Traditionally, the primary prevention strategy for HCV-associated HCC has focused on removing infection through antiviral regimes. Currently, highly effective direct-acting antivirals (DAAs) offer extraordinary success across all patient categories, including cirrhotics. Despite these advancements, recent studies have reported that even after sustained virologic response (SVR), individuals with advanced liver disease/cirrhosis at the time of DAA treatment may still face risks of HCC occurrence or recurrence. Based on this premise, this review tries to shed light on the multiple mechanisms that establish a tumorigenic environment, first, during chronic HCV infection and then, after eventual viral eradication by DAAs. Furthermore, it reviews evidence reported by recent observational studies stating that the use of DAAs is not associated with an increased risk of HCC development but rather, with a significantly lower chance of liver cancer compared with DAA-untreated patients. In addition, it seeks to provide some practical guidance for clinicians, helping them to manage HCC surveillance of patients who have achieved SVR with DAAs.
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Affiliation(s)
- Carlo Smirne
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy
| | - Maria Grazia Crobu
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy;
- Clinical Biochemistry Laboratory, City of Health and Science University Hospital, 10126 Turin, Italy
| | - Irene Landi
- Emergency Medicine Department, Michele e Pietro Ferrero Hospital, 12060 Verduno, Italy;
| | - Nicole Vercellino
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
| | - Daria Apostolo
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
| | - David James Pinato
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London SW7 2AZ, UK
| | - Federica Vincenzi
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
| | - Rosalba Minisini
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
| | - Stelvio Tonello
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
| | - Davide D’Onghia
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
| | - Antonio Ottobrelli
- Gastroenterology Unit, City of Health and Science University Hospital, 10126 Turin, Italy; (A.O.); (S.M.); (A.C.)
| | - Silvia Martini
- Gastroenterology Unit, City of Health and Science University Hospital, 10126 Turin, Italy; (A.O.); (S.M.); (A.C.)
| | - Christian Bracco
- Department of Internal Medicine, Santa Croce e Carle Hospital, 12100 Cuneo, Italy; (C.B.); (L.M.F.)
| | - Luigi Maria Fenoglio
- Department of Internal Medicine, Santa Croce e Carle Hospital, 12100 Cuneo, Italy; (C.B.); (L.M.F.)
| | - Mauro Campanini
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy
| | - Alessandro Maria Berton
- Division of Endocrinology, Diabetes and Metabolism, City of Health and Science University Hospital, 10126 Turin, Italy;
| | - Alessia Ciancio
- Gastroenterology Unit, City of Health and Science University Hospital, 10126 Turin, Italy; (A.O.); (S.M.); (A.C.)
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy
| | - Mario Pirisi
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (N.V.); (D.A.); (D.J.P.); (F.V.); (R.M.); (S.T.); (D.D.); (M.C.); (M.P.)
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy
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Lee HA, Kim MN, Lee HA, Choi M, Yu JH, Jin YJ, Kim HY, Han JW, Kim SU, An J, Chon YE. Non-invasive prediction of post-sustained virological response hepatocellular carcinoma in hepatitis C virus: A systematic review and meta-analysis. Clin Mol Hepatol 2024; 30:S172-S185. [PMID: 39134075 PMCID: PMC11493359 DOI: 10.3350/cmh.2024.0262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 08/06/2024] [Accepted: 08/12/2024] [Indexed: 10/17/2024] Open
Abstract
BACKGROUNDS/AIMS Despite advances in antiviral therapy for hepatitis C virus (HCV) infection, hepatocellular carcinoma (HCC) still develops even after sustained viral response (SVR) in patients with advanced liver fibrosis or cirrhosis. This meta-analysis investigated the predictive performance of vibration-controlled transient elastography (VCTE) and fibrosis 4-index (FIB-4) for the development of HCC after SVR. METHODS We searched PubMed, MEDLINE, EMBASE, and the Cochrane Library for studies examining the predictive performance of these tests in adult patients with HCV. Two authors independently screened the studies' methodological quality and extracted data. Pooled estimates of sensitivity, specificity, and area under the curve (AUC) were calculated for HCC development using random-effects bivariate logit normal and linear-mixed effect models. RESULTS We included 27 studies (169,911 patients). Meta-analysis of HCC after SVR was possible in nine VCTE and 15 FIB-4 studies. Regarding the prediction of HCC development after SVR, the pooled AUCs of pre-treatment VCTE >9.2-13 kPa and FIB-4 >3.25 were 0.79 and 0.73, respectively. VCTE >8.4-11 kPa and FIB-4 >3.25 measured after SVR maintained good predictive performance, albeit slightly reduced (pooled AUCs: 0.77 and 0.70, respectively). The identified optimal cut-off value for HCC development after SVR was 12.6 kPa for pre-treatment VCTE. That of VCTE measured after the SVR was 11.2 kPa. CONCLUSION VCTE and FIB-4 showed acceptable predictive performance for HCC development in patients with HCV who achieved SVR, underscoring their utility in clinical practice for guiding surveillance strategies. Future studies are needed to validate these findings prospectively and validate their clinical impact.
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Affiliation(s)
- Han Ah Lee
- Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea
| | - Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Hye Ah Lee
- Clinical Trial Center, Ewha Womans University Seoul Hospital, Seoul, Korea
| | - Miyoung Choi
- Division of Health Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency, Seoul, Korea
| | - Jung Hwan Yu
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Young-Joo Jin
- Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Hee Yeon Kim
- Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ji Won Han
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Jihyun An
- Department of Gastroenterology and Hepatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Young Eun Chon
- Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
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Hamza A, Ahmad I, Uneeb M. Fuzzy logic and Lyapunov-based non-linear controllers for HCV infection. IET Syst Biol 2021; 15:53-71. [PMID: 33780147 PMCID: PMC8675797 DOI: 10.1049/syb2.12014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 12/15/2020] [Indexed: 11/19/2022] Open
Abstract
Hepatitis C is the liver disease caused by the Hepatitis C virus (HCV) which can lead to serious health problems such as liver cancer. In this research work, the non‐linear model of HCV having three state variables (uninfected hepatocytes, infected hepatocytes and virions) and two control inputs has been taken into account, and four non‐linear controllers namely non‐linear PID controller, Lyapunov Redesign controller, Synergetic controller and Fuzzy Logic‐Based controller have been proposed to control HCV infection inside the human body. The controllers have been designed for the anti‐viral therapy in order to control the amount of uninfected hepatocytes to the desired safe limit and to track the amount of infected hepatocytes and virions to their reference value which is zero. One control input is the Pegylated interferon (peg‐IFN‐α) which acts in reducing the infected hepatocytes and the other input is ribavirin which blocks the production of virions. By doing so, the uninfected hepatocytes increase and achieve the required safe limit. Lyapunov stability analysis has been used to prove the stability of the whole system. The comparative analysis of the proposed nonlinear controllers using MATLAB/Simulink have been done with each other and with linear PID. These results depict that the infected hepatocytes and virions are reduced to the desired level, enhancing the rate of sustained virologic response (SVR) and reducing the treatment period as compared with previous strategies introduced in the literature.
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Affiliation(s)
- Ali Hamza
- Department of Electrical Engineering, School of Electrical Engineering and Computer Science, National University of Sciences and Technology (NUST), Islamabad, Pakistan
| | - Iftikhar Ahmad
- Department of Electrical Engineering, School of Electrical Engineering and Computer Science, National University of Sciences and Technology (NUST), Islamabad, Pakistan
| | - Muhammad Uneeb
- Department of Electrical Engineering, School of Electrical Engineering and Computer Science, National University of Sciences and Technology (NUST), Islamabad, Pakistan
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Alonso López S, Manzano ML, Gea F, Gutiérrez ML, Ahumada AM, Devesa MJ, Olveira A, Polo BA, Márquez L, Fernández I, Cobo JCR, Rayón L, Riado D, Izquierdo S, Usón C, Real Y, Rincón D, Fernández-Rodríguez CM, Bañares R. A Model Based on Noninvasive Markers Predicts Very Low Hepatocellular Carcinoma Risk After Viral Response in Hepatitis C Virus-Advanced Fibrosis. Hepatology 2020; 72:1924-1934. [PMID: 33022803 DOI: 10.1002/hep.31588] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 09/15/2020] [Accepted: 09/22/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS Patients with hepatitis C virus (HCV) and advanced fibrosis remain at risk of hepatocellular carcinoma (HCC) after sustained viral response (SVR) and need lifelong surveillance. Because HCC risk is not homogenous and may decrease with fibrosis regression, we aimed to identify patients with low HCC risk based on the prediction of noninvasive markers and its changes after SVR. APPROACH AND RESULTS This is a multicenter cohort study, including patients with HCV and compensated advanced fibrosis that achieved SVR after direct antivirals. Clinical and transient elastography (TE) data were registered at baseline, 1 year, and 3 years after the end of treatment (EOT). All patients underwent liver ultrasound scan every 6 months. Patients with clinical evaluation 1 year after EOT were eligible. Univariate and multivariate Cox regression analysis were performed, and predictive models were constructed. HCC occurrence rates were evaluated by Kaplan-Meier. Nine hundred and ninety-three patients were eligible (56% male; 44% female; median age 62 years), 35 developed HCC (3.9%), and the median follow-up was 45 months (range 13-53). Baseline liver stiffness measurement (LSM) (HR 1.040; 95% CI 1.017-1.064), serum albumin (HR 0.400; 95% CI 0.174-0.923), 1-year DeltaLSM (HR 0.993; 95% CI 0.987-0.998), and 1-year FIB-4 score (HR 1.095; 95% CI 1.046-1.146) were independent factors associated with HCC. The TE-based HCC risk model predicted 0% of HCC occurrence at 3 years in patients with score 0 (baseline LSM ≤ 17.3 kPa, albumin >4.2 g/dL, and 1-year DeltaLSM > 25.5%) versus 5.2% in patients with score 1-3 (Harrell's C 0.779; log-rank 0.002). An alternative model with FIB-4 similarly predicted HCC risk. CONCLUSIONS A combination of baseline and dynamic changes in noninvasive markers may help to identify patients with a very low risk of HCC development after SVR.
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MESH Headings
- Adult
- Aged
- Aged, 80 and over
- Antiviral Agents/therapeutic use
- Biomarkers, Tumor/blood
- Carcinoma, Hepatocellular/blood
- Carcinoma, Hepatocellular/epidemiology
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/virology
- Disease Progression
- Elasticity Imaging Techniques
- Female
- Follow-Up Studies
- Hepacivirus/isolation & purification
- Hepatitis C, Chronic/blood
- Hepatitis C, Chronic/drug therapy
- Hepatitis C, Chronic/pathology
- Hepatitis C, Chronic/virology
- Humans
- Liver/diagnostic imaging
- Liver/pathology
- Liver Cirrhosis/blood
- Liver Cirrhosis/drug therapy
- Liver Cirrhosis/pathology
- Liver Cirrhosis/virology
- Liver Neoplasms/blood
- Liver Neoplasms/epidemiology
- Liver Neoplasms/pathology
- Liver Neoplasms/virology
- Male
- Middle Aged
- Retrospective Studies
- Risk Assessment/methods
- Risk Factors
- Sustained Virologic Response
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Affiliation(s)
- Sonia Alonso López
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Instituto De Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | | | - Francisco Gea
- Liver Unit, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | | | | | - María José Devesa
- Gastroenterology Unit, Hospital Universitario Clínico San Carlos, Madrid, Spain
| | - Antonio Olveira
- Hepatology Unit, Hospital Universitario La Paz, Madrid, Spain
| | - Benjamin Arturo Polo
- Gastroenterology Unit, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
| | - Laura Márquez
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | | | | | - Laura Rayón
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Daniel Riado
- Gastroenterology Unit, Hospital Universitario Fundación Alcorcón, Madrid, Spain
| | - Sonia Izquierdo
- Gastroenterology Unit, Hospital Universitario Clínico San Carlos, Madrid, Spain
| | - Clara Usón
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Yolanda Real
- Gastroenterology Unit, Hospital Universitario La Princesa Madrid, Madrid, Spain
| | - Diego Rincón
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Instituto De Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Universidad Complutense de Madrid, Madrid, Spain
- Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Conrado M Fernández-Rodríguez
- Gastroenterology Unit, Hospital Universitario Fundación Alcorcón, Madrid, Spain
- Universidad Rey Juan Carlos Madrid, Madrid, Spain
| | - Rafael Bañares
- Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Instituto De Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Universidad Complutense de Madrid, Madrid, Spain
- Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
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Nagaoki Y, Imamura M, Teraoka Y, Morio K, Fujino H, Ono A, Nakahara T, Murakami E, Yamauchi M, Kawaoka T, Miki D, Tsuge M, Hiramatsu A, Hayes CN, Chayama K, Aikata H. Impact of viral eradication by direct-acting antivirals on the risk of hepatocellular carcinoma development, prognosis, and portal hypertension in hepatitis C virus-related compensated cirrhosis patients. Hepatol Res 2020; 50:1222-1233. [PMID: 32767446 DOI: 10.1111/hepr.13554] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 06/30/2020] [Accepted: 08/04/2020] [Indexed: 02/06/2023]
Abstract
AIM We analyzed the impact of hepatitis C virus eradication by direct-acting antiviral (DAA) therapy on the risk of development of hepatocellular carcinoma (HCC), prognosis, and portal hypertension in patients with liver cirrhosis. METHODS The rate of HCC development and overall survival after achievement of sustained virological response (SVR) in 173 DAA-treated compensated cirrhosis patients without HCC history were retrospectively compared with that of 125 cirrhosis patients who achieved SVR by interferon (IFN)-based therapy or that of 85 cirrhosis patients who failed to respond to anti-HCV therapy. Changes in esophagogastric varices (EGV) and incidence of portosystemic encephalopathy were analyzed in 87 consecutive cirrhosis patients. RESULTS The cumulative HCC development rates at 1, 3, and 5 years were 2%, 7%, and 7% for the DAA-SVR group, significantly lower than the 3%, 7%, and 18% for the non-SVR group (log-rank, P < 0.001). The cumulative overall survival rates were also significantly improved in the DAA-SVR group compared to the non-SVR group (log-rank, P < 0.001). These rates were similar between DAA-SVR and IFN-SVR groups (P = 0.121 and 0.261, respectively). Esophagogastric varices were aggravated, and portosystemic encephalopathy occurred in a subset of cirrhosis patients who achieved SVR by DAA therapy. These events were more frequent in patients with large feeding vessels for EGV and portosystemic shunts at the time of SVR. CONCLUSION Achievement of SVR by DAA therapy reduces the risk of HCC development and prolongs survival, similar to theresults achieved with IFN-based therapy, but portal hypertension is not immediately improved in compensated liver cirrhosis patients.
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Affiliation(s)
- Yuko Nagaoki
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
| | - Michio Imamura
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
| | - Yuji Teraoka
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
| | - Kei Morio
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
| | - Hatsue Fujino
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
| | - Atsushi Ono
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
| | - Takashi Nakahara
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
| | - Eisuke Murakami
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
| | - Masami Yamauchi
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
| | - Daiki Miki
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
| | - Masataka Tsuge
- Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan.,Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan
| | - Akira Hiramatsu
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
| | - C Nelson Hayes
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan.,RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.,Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
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7
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Nayyar SS, Thiagarajan S, Malik A, D'Cruz A, Chaukar D, Patil P, Alahari AD, Lashkar SG, Prabhash K. Head and neck squamous cell carcinoma in HIV, HBV and HCV seropositive patients - Prognosis and its predictors. J Cancer Res Ther 2020; 16:619-623. [PMID: 32719277 DOI: 10.4103/jcrt.jcrt_166_19] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Introduction Patients receiving treatment for head-and-neck squamous cell carcinoma (HNSCC) also may have coexisting viral infections caused by HIV, HBV, and HCV (seropositive). There is scarce literature regarding the clinical presentation and treatment outcomes for these patients with coexisting viral infections (seropositive HNSCC). We conducted this study to assess the clinical presentation and treatment outcomes (overall survival [OS] and disease-specific survival [DSS]) of seropositive HNSCC patients. Methodology This was a retrospective cohort study on seropositive HNSCC patients registered at our center from 2012 to 2014. The viral infections were identified by the presence of the antibodies to these viruses in the patient's blood samples. Results Out of the 19,137 HNSCC patients registered, 156 patients had HBV, HCV, and/or HIV infection. Among these, HBV infection was the most common (n = 86/156, 55.1%) followed by HIV infection (n = 36/156, 23.1%) and HCV infection (n = 29/156, 18.6%). The oral cavity was the most common subsite involved. Majority of these patients presented at an advanced stage (advanced T stage - 71.8% and node positive - 62.2%). The majority of the patients received curative-intent treatment (65.4%). The OS at 3 years for these HNSCC patients with coexisting HIV, HBV, and HCV infection was 60%, 62.6%, and 57.5%, respectively, and their DSS at 3 years was 58.8%, 78.6%, and 53.8%, respectively. Conclusions Seropositive patients with HNSCC often present in the advanced stage but have a good survival if treated appropriately.
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Affiliation(s)
- Supreet Singh Nayyar
- Department of Head and Neck Oncology, Tata Memorial Centre, Homibhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Shivakumar Thiagarajan
- Department of Head and Neck Oncology, Tata Memorial Centre, Homibhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Akshat Malik
- Department of Head and Neck Oncology, Tata Memorial Centre, Homibhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Anil D'Cruz
- Department of Head and Neck Oncology, Tata Memorial Centre, Homibhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Devendra Chaukar
- Department of Head and Neck Oncology, Tata Memorial Centre, Homibhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Prachi Patil
- Department of Medical Gastroenterology, Tata Memorial Centre, Homibhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Aruna Dhir Alahari
- Department of Medicine, Tata Memorial Centre, Homibhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Sarbani Ghosh Lashkar
- Department of Radiation Oncology, Tata Memorial Centre, Homibhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Kumar Prabhash
- Department of Radiation Oncology, Tata Memorial Centre, Homibhabha National Institute (HBNI), Mumbai, Maharashtra, India
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8
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Li CF, Tsao SM, Liao HH, Chen SC, Lee YT. Treatment of chronic hepatitis C regiments containing with recombinant interferon in patients with sustained virological response predicts risk of hepatocellular carcinoma: A meta-analysis. Medicine (Baltimore) 2020; 99:e22435. [PMID: 33019424 PMCID: PMC7535677 DOI: 10.1097/md.0000000000022435] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Given that evidence supporting chronic hepatitis C (CHC) infection developed chance for hepatocellular carcinoma (HCC) following antiviral agents therapy is controversial. We conducted a meta-analysis to examine the risk.We evaluated 20 retrospective and prospective cohort studies published up to 31 December 2017 which investigated the association between sustained virological response (SVR) and incidence of HCC patients treated with monotherapy interferon (IFN) or IFN plus ribavirin (RBV) therapy. The primary outcome of the study was the cumulative incidence of HCC. Odds ratio (OR) was used to evaluate the index of effect size for the association between SVR and treatment with IFN alone or IFN/RBV in CHC patients.SVR patients demonstrated a lower incidence of HCC compared to non-SVR patients. Non-SVR patients had greater odds of HCC incidence compared to SVR patients in the treatment of IFN plus RBV (pooled OR = 7.405, 95% CI = 4.689 to 11.694, P < .001). Non-SVR patients had greater odds of HCC incidence compared to SVR patients in the treatment of IFN monotherapy (pooled OR = 4.135, 95% CI = 3.009 to 5.682, P < .001). Lack of SVR to IFN therapy was significantly associated with greater risk of HCC incidence (pooled OR = 5.035, 95% CI = 3.915 to 6.474, P < .001).SVR could be as a predictor of HCC in CHC patients treated with IFN or IFN plus RBV, and have important implications during HCC screening, whereby patients who fail to achieve SVR need to be screened more rigorously.
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Affiliation(s)
- Chien-Feng Li
- School of Medicine, Chung Shan Medical University
- Division of Infectious Diseases, Department of Internal Medicine
| | - Shih-Ming Tsao
- School of Medicine, Chung Shan Medical University
- Division of Infectious Diseases, Department of Internal Medicine
| | - Hsien-Hua Liao
- School of Medicine, Chung Shan Medical University
- Department of Plastic Surgery
| | - Shiuan-Chih Chen
- School of Medicine, Chung Shan Medical University
- Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Yuan-Ti Lee
- School of Medicine, Chung Shan Medical University
- Division of Infectious Diseases, Department of Internal Medicine
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9
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Wang Q, Yu CR. Association between liver targeted antiviral therapy in colorectal cancer and survival benefits: An appraisal. World J Clin Cases 2020; 8:2111-2115. [PMID: 32548140 PMCID: PMC7281048 DOI: 10.12998/wjcc.v8.i11.2111] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Revised: 04/10/2020] [Accepted: 04/30/2020] [Indexed: 02/05/2023] Open
Abstract
In colorectal cancer (CRC), liver metastasis remains a major contributor to the cause of cancer-related death. Putative biomarkers, therapeutic efficacy, and drug insensitivity still pose clinical challenges for metastatic CRC patients. Interestingly, previous studies indicated that tumor cells in CRC did not metastasize to the injured liver, which included hepatitis or cirrhotic liver. The benefits of antiviral therapy on hepatocellular carcinoma have also been identified. This review discusses the role of antiviral therapy on the liver. Antiviral therapy may reduce potential liver metastasis associated with CRC in several mechanistic aspects.
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Affiliation(s)
- Qiang Wang
- Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Shanghai 200025, China
| | - Chao-Ran Yu
- Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Shanghai 200025, China
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10
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Screening for Hepatocellular Carcinoma in HIV-Infected Patients: Current Evidence and Controversies. Curr HIV/AIDS Rep 2020; 17:6-17. [PMID: 31933273 DOI: 10.1007/s11904-019-00475-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
PURPOSE OF REVIEW This review aims to summarize evidence regarding hepatocellular carcinoma (HCC) screening in the specific context of HIV infection and discuss areas of uncertainty. RECENT FINDINGS It has not been definitely established if HCC incidence in HIV/HCV-coinfected patients with cirrhosis is above the 1.5%/year threshold that makes screening cost-effective. Outside cirrhosis or HBV infection, available data do not support surveillance. The performance of currently recommended ultrasound (US) screening strategy is poor in HIV-infected patients, as rates of early-stage HCC detection are low. Magnetic resonance imaging-based surveillance strategies or liquid biopsy are innovative approaches that should be specifically tested in this setting. HIV-infected patients with cirrhosis are at risk of HCC. US surveillance identifies patients with early-stage HCC who will benefit of curative therapies, although the quality of the evidence supporting screening remains limited. The HIV population should be a priority group to assess and validate new surveillance strategies.
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11
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Wake T, Tateishi R, Fukumoto T, Nakagomi R, Kinoshita MN, Nakatsuka T, Sato M, Minami T, Uchino K, Enooku K, Nakagawa H, Fujinaga H, Asaoka Y, Tanaka Y, Otsuka M, Koike K. Improved liver function in patients with cirrhosis due to chronic hepatitis C virus who achieve sustained virologic response is not accompanied by increased liver volume. PLoS One 2020; 15:e0231836. [PMID: 32310974 PMCID: PMC7170262 DOI: 10.1371/journal.pone.0231836] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Accepted: 04/01/2020] [Indexed: 12/14/2022] Open
Abstract
Background Serum albumin level improves in patients with chronic hepatitis C virus (HCV) infection who achieve sustained virologic response (SVR) with antiviral therapy. However, it remains controversial whether liver volume increases along with SVR. Methods Patients with chronic HCV infection with a history of hepatocellular carcinoma (HCC) who achieved SVR with anti-HCV treatment from March 2003 to November 2017 were enrolled. Patients were followed up with periodic computed tomography (CT) scans to detect HCC recurrence. Patients who underwent treatment for HCC recurrence within 1 year after initiation of anti-HCV treatment were excluded. Laboratory data, including alanine aminotransferase (ALT) level, serum albumin level, and platelet count, were collected at baseline and timepoints after treatment initiation. Liver volume was evaluated at baseline and 24 and 48 weeks after treatment initiation using a CT volume analyzer. A linear mixed-effects model was applied to analyze the chronologic change in liver volume. The correlations between changes in ALT level, albumin level, and liver volume were also evaluated. Results Of 108 enrolled patients, 78 had cirrhosis. Serum albumin level continued to increase through 48 weeks after treatment initiation. A significant increase in liver volume was observed only in patients without cirrhosis (P = 0.005). There was a significant correlation between ALT level decrease and albumin level increase (P = 0.018). Conclusions Improved liver albumin production with SVR was contributed by improved liver cell function rather than increased liver volume in patients with cirrhosis.
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Affiliation(s)
- Taijiro Wake
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- * E-mail:
| | - Tsuyoshi Fukumoto
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryo Nakagomi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | | | - Takuma Nakatsuka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masaya Sato
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tatsuya Minami
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Koji Uchino
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kenichiro Enooku
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hayato Nakagawa
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hidetaka Fujinaga
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yoshinari Asaoka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Gastroenterology, Teikyo University, Tokyo, Japan
| | - Yasuo Tanaka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Motoyuki Otsuka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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12
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Merchante N, Rivero-Juárez A, Téllez F, Merino D, Ríos-Villegas MJ, Villalobos M, Omar M, Rincón P, Rivero A, Pérez-Pérez M, Raffo M, López-Montesinos I, Palacios R, Gómez-Vidal MA, Macías J, Pineda JA. Sustained virological response to direct-acting antiviral regimens reduces the risk of hepatocellular carcinoma in HIV/HCV-coinfected patients with cirrhosis. J Antimicrob Chemother 2019; 73:2435-2443. [PMID: 29982683 DOI: 10.1093/jac/dky234] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2018] [Accepted: 05/22/2018] [Indexed: 12/30/2022] Open
Abstract
Objectives To assess the impact of all-oral direct-acting antiviral agent (DAA) regimens on the risk of hepatocellular carcinoma (HCC) in HIV/HCV-coinfected patients with cirrhosis. Methods This was a multicentre prospective cohort study recruiting HIV/HCV-coinfected patients with a new diagnosis of compensated cirrhosis. Patients were followed up until HCC, death or the censoring date (March 2017). The primary endpoint was the emergence of HCC. The incidence rate (IR) (95% CI) of HCC in different groups was computed. Time-to-event analyses were performed to identify predictors of HCC emergence. Results The study included 495 HIV/HCV-coinfected patients with cirrhosis. After a median (IQR) follow-up of 59 (27-84) months, 22 (4.4%; 95% CI 2.6-6.3) patients developed an HCC. The IR (95% CI) of HCC was 0.93 (0.06-1.42) per 100 person-years (PY). Three hundred and three (61%) patients achieved sustained virological response (SVR) during follow-up, 79 after interferon (IFN)-based regimens and 224 after an all-oral DAA regimen. The IR (95% CI) of HCC after all-oral DAA was 0.35 (0.14-0.85) per 100 PY whereas it was 1.79 (1.11-2.88) per 100 PY in the remaining cohort (P = 0.0005). When only patients with SVR were considered, the IR (95% CI) of HCC after all-oral DAA was 0.32 (0.12-0.86) whereas it was 0 per 100 PY among those with SVR after IFN-based therapies (P = 0.27). Achieving SVR with an all-oral DAA regimen during follow-up was independently associated with a lower risk of HCC emergence (subhazard ratio 0.264; 95% CI 0.070-0.991; P = 0.049). Conclusions SVR with all-oral DAA regimens reduces the risk of HCC in HIV/HCV-coinfected patients with compensated cirrhosis.
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Affiliation(s)
- Nicolás Merchante
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario de Valme, Sevilla, Spain
| | - Antonio Rivero-Juárez
- Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Francisco Téllez
- Unidad de Enfermedades Infecciosas, Hospital Universitario de Puerto Real, Cádiz, Spain
| | - Dolores Merino
- Unidad de Gestión Clínica de Enfermedades Infecciosas, Hospitales Juan Ramón Jiménez e Infanta Elena, Huelva, Spain
| | - María J Ríos-Villegas
- Unidad de Enfermedades Infecciosas, Hospital Universitario Virgen Macarena, Sevilla, Spain
| | - Marina Villalobos
- Unidad de Gestión Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Instituto de Biomedicina de Málaga (IBIMA), Hospital Virgen de la Victoria, Málaga, Spain
| | - Mohamed Omar
- Unidad de Enfermedades Infecciosas, Complejo Hospitalario de Jaén, Jaén, Spain
| | - Pilar Rincón
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario de Valme, Sevilla, Spain
| | - Antonio Rivero
- Unidad de Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain
| | - Montserrat Pérez-Pérez
- Unidad de Gestión Clínica de Enfermedades Infecciosas y Microbiología, Hospital de La Línea de la Concepción, AGS Campo de Gibraltar, Cádiz, Spain
| | - Miguel Raffo
- Unidad de Gestión Clínica de Enfermedades Infecciosas, Hospitales Juan Ramón Jiménez e Infanta Elena, Huelva, Spain
| | | | - Rosario Palacios
- Unidad de Gestión Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Instituto de Biomedicina de Málaga (IBIMA), Hospital Virgen de la Victoria, Málaga, Spain
| | - María A Gómez-Vidal
- Unidad de Enfermedades Infecciosas, Complejo Hospitalario de Jaén, Jaén, Spain
| | - Juan Macías
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario de Valme, Sevilla, Spain
| | - Juan A Pineda
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario de Valme, Sevilla, Spain
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Jain A, Miller D, Schreibman I, Riley TR, Krok KL, Dohi T, Sharma R, Kadry Z. Is there increased risk of hepatocellular carcinoma recurrence in liver transplant patients with direct-acting antiviral therapy? Hepatol Int 2019; 13:190-198. [PMID: 30680672 DOI: 10.1007/s12072-019-09930-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Accepted: 01/10/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Recently, a controversy has emerged: is the rate of recurrence of hepatocellular carcinoma (HCC) higher following treatment of hepatitis C virus (HCV) with direct-acting antiviral (DAA) therapy? However, the risk of HCC recurrence has not been studied in liver transplant (LTx) recipients who received DAA therapy. The aim of the present study is to compare the rate of HCC recurrence in LTx recipients who did or did not receive DAA therapy. PATIENTS AND METHODS Sixty-three patients received LTx with HCC. Twenty-seven (42.9%) with HCV received DAA therapy (Group A), 20 (31.7%) with HCV did not receive DAA therapy (Group B), and 16 (25.4%) did not have HCV (Group C). RESULTS In group A, three (11%), in group B, one (5%), and in group C, none had recurrence of HCC. Actuarial 4-year recurrence-free survival was 88.9, 95, and 100% in group A, B, and C, respectively (p = 0.37). Group A was subdivided into two groups for comparison with Group B: A1 included five patients who had end of treatment response (ETR) without sustained virological response (SVR), and A2 included 20 patients who achieved SVR. Three patients from A1 had HCC recurrence and no patients from A2 had HCC recurrence. (p = 0.0038; group A1, A2, and B). CONCLUSIONS The rate of HCC recurrence in LTx patients with DAA therapy was significantly higher with ETR, without SVR, after DAA therapy compared to patients with SVR or patients who did not receive DAA therapy. LTx recipients with HCC receiving DAA therapy requires further studies.
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Affiliation(s)
- Ashokkumar Jain
- Division of Transplantation, Department of Surgery, College of Medicine, Pennsylvania State University, Mail Code H062, 500 University Drive, PO Box 850, Hershey, PA, 17033-0850, USA.
| | - Danielle Miller
- Division of Transplantation, Department of Surgery, College of Medicine, Pennsylvania State University, Mail Code H062, 500 University Drive, PO Box 850, Hershey, PA, 17033-0850, USA
| | - Ian Schreibman
- Division of Gastroenterology, Department of Medicine, College of Medicine, Pennsylvania State University, Hershey, PA, USA
| | - Thomas R Riley
- Division of Gastroenterology, Department of Medicine, College of Medicine, Pennsylvania State University, Hershey, PA, USA
| | - Karen L Krok
- Division of Gastroenterology, Department of Medicine, College of Medicine, Pennsylvania State University, Hershey, PA, USA
| | - Takehiko Dohi
- Division of Transplantation, Department of Surgery, College of Medicine, Pennsylvania State University, Mail Code H062, 500 University Drive, PO Box 850, Hershey, PA, 17033-0850, USA
| | - Rajeev Sharma
- CSL Behring, 1020 First Ave, King of Prussia, PA, USA
| | - Zakiyah Kadry
- Division of Transplantation, Department of Surgery, College of Medicine, Pennsylvania State University, Mail Code H062, 500 University Drive, PO Box 850, Hershey, PA, 17033-0850, USA
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14
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Na SK, Song BC. Development and surveillance of hepatocellular carcinoma in patients with sustained virologic response after antiviral therapy for chronic hepatitis C. Clin Mol Hepatol 2019; 25:234-244. [PMID: 30661334 PMCID: PMC6759435 DOI: 10.3350/cmh.2018.0108] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Accepted: 12/17/2018] [Indexed: 12/12/2022] Open
Abstract
Hepatitis C virus (HCV) infection is a major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC), and is a leading cause of liver-related deaths worldwide. Recently available direct-acting antiviral agent is very safe and highly effective (>95% sustained virologic response, SVR) against all genotypes of HCV. Achievement of SVR has been associated with a significant reduction of hepatic decompensation, development of HCC, and liver-related mortality. However, HCC risk is not eliminated even after SVR. The annual incidences of HCC in advanced fibrosis or cirrhosis have been estimated to be up to 2.5-4.5% even in patients with SVR. Therefore, surveillance for HCC is recommended in this high-risk patients. In this review, we will describe the clinical outcomes and the risk of HCC in patients with SVR and suggest who should receive surveillance for HCC.
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Affiliation(s)
- Seong Kyun Na
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea
| | - Byung-Cheol Song
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea
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15
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Finianos A, Matar CF, Taher A. Hepatocellular Carcinoma in β-Thalassemia Patients: Review of the Literature with Molecular Insight into Liver Carcinogenesis. Int J Mol Sci 2018; 19:ijms19124070. [PMID: 30562917 PMCID: PMC6321074 DOI: 10.3390/ijms19124070] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Revised: 12/08/2018] [Accepted: 12/11/2018] [Indexed: 12/18/2022] Open
Abstract
With the continuing progress in managing patients with thalassemia, especially in the setting of iron overload and iron chelation, the life span of these patients is increasing, while concomitantly increasing incidences of many diseases that were less likely to show when survival was rather limited. Hepatocellular carcinoma (HCC) is a major life-threatening cancer that is becoming more frequently identified in this population of patients. The two established risk factors for the development of HCC in thalassemia include iron overload and viral hepatitis with or without cirrhosis. Increased iron burden is becoming a major HCC risk factor in this patient population, especially in those in the older age group. As such, screening thalassemia patients using liver iron concentration (LIC) measurement by means of magnetic resonance imaging (MRI) and liver ultrasound is strongly recommended for the early detection of iron overload and for implementation of early iron chelation in an attempt to prevent organ-damaging iron overload and possibly HCC. There remain lacking data on HCC treatment outcomes in patients who have thalassemia. However, a personalized approach tailored to each patient’s comorbidities is essential to treatment success. Multicenter studies investigating the long-term outcomes of currently available therapeutic options in the thalassemia realm, in addition to novel HCC therapeutic targets, are needed to further improve the prognosis of these patients.
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Affiliation(s)
- Antoine Finianos
- Division of Hematology/Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut 11-0236, Lebanon.
| | - Charbel F Matar
- Division of Hematology/Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut 11-0236, Lebanon.
| | - Ali Taher
- Division of Hematology/Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut 11-0236, Lebanon.
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16
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Chang KC, Ye YH, Wu CK, Lin MT, Tsai MC, Tseng PL, Hu TH. Risk factors for development of hepatocellular carcinoma in patients with chronic hepatitis C without sustained response to combination therapy. J Formos Med Assoc 2018; 117:1011-1018. [PMID: 29254684 DOI: 10.1016/j.jfma.2017.11.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 11/08/2017] [Accepted: 11/14/2017] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND/PURPOSE Although antiviral therapy reduces development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC), HCC often develops in patients with non-sustained virologic response (non-SVR). We aimed to evaluate risk factors for HCC in HCV patients with non-SVR. METHODS From March 2002 to December 2013, 800 patients with CHC who had received combined pegylated interferon (peg-IFN)/ribavirin (RBV) therapy without achieving SVR were enrolled. Main outcome measure was HCC development. Variables were cirrhosis, platelet count, α-fetoprotein (AFP) levels, aspartate aminotransferase (AST) to platelet ratio index (APRI), and IL28B polymorphism (CT + TT). RESULTS One-hundred of 800 non-SVR patients developed HCC within a median 53.5-months follow-up. Cumulative incidence of HCC for all patients was 1.4%, 5.6% and 12.3%, respectively, at 1st, 3rd and 5th years of follow-up. In univariate analysis, patients who developed HCC tended to have LC (p< 0.001), lower platelet counts (<150 × 109/l, p < 0.001), higher AFP levels (≥20 ng/ml, p < 0.001), higher Fib-4 levels (p < 0.001), higher APRI levels (p < 0.001), IL 28B polymorphism (CT + TT) (p < 0.001) and higher incidence of diabetes mellitus (DM) (p = 0.019). Multivariate analysis in overall patients revealed that cirrhosis (HR: 2.94, 95% CI: 1.81-4.77, p < 0.001), IL28B rs12979860 (CT + TT) polymorphisms (HR: 3.22, 95% CI: 2.17-4.78, p < 0.001), and high APRI levels (≥2.57) (HR: 2.32, 95% CI: 1.47-3.67, p < 0.001) were independent risk factors for HCC. CONCLUSION Liver cirrhosis, high APRI levels, and IL28B rs12979860 at baseline are independent risk factors for HCC development in patients without SVR after peg-IFN combination therapy.
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Affiliation(s)
- Kuo-Chin Chang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.
| | - Yi-Hao Ye
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC
| | - Cheng-Kun Wu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC
| | - Ming-Tsung Lin
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC
| | - Ming-Chao Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC
| | - Po-Lin Tseng
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC
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Molecular Mechanisms of Hepatocarcinogenesis Following Sustained Virological Response in Patients with Chronic Hepatitis C Virus Infection. Viruses 2018; 10:v10100531. [PMID: 30274202 PMCID: PMC6212901 DOI: 10.3390/v10100531] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 09/25/2018] [Accepted: 09/27/2018] [Indexed: 02/07/2023] Open
Abstract
Despite the success of direct-acting antiviral (DAA) agents in treating chronic hepatitis C virus (HCV) infection, the number of cases of HCV-related hepatocellular carcinoma (HCC) is expected to increase over the next five years. HCC develops over the span of decades and is closely associated with fibrosis stage. HCV both directly and indirectly establishes a pro-inflammatory environment favorable for viral replication. Repeated cycles of cell death and regeneration lead to genomic instability and loss of cell cycle control. DAA therapy offers >90% sustained virological response (SVR) rates with fewer side effects and restrictions than interferon. While elimination of HCV helps to restore liver function and reverse mild fibrosis, post-SVR patients remain at elevated risk of HCC. A series of studies reporting higher than expected rates of HCC development among DAA-treated patients ignited debate over whether use of DAAs elevates HCC risk compared to interferon. However, recent prospective and retrospective studies based on larger patient cohorts have found no significant difference in risk between DAA and interferon therapy once other factors are taken into account. Although many mechanisms and pathways involved in hepatocarcinogenesis have been elucidated, our understanding of drivers specific to post-SVR hepatocarcinogenesis is still limited, and lack of suitable in vivo and in vitro experimental systems has hampered efforts to examine etiology-specific mechanisms that might serve to answer this question more thoroughly. Further research is needed to identify risk factors and biomarkers for post-SVR HCC and to develop targeted therapies based on more complete understanding of the molecules and pathways implicated in hepatocarcinogenesis.
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18
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Younossi ZM, Tanaka A, Eguchi Y, Henry L, Beckerman R, Mizokami M. Treatment of hepatitis C virus leads to economic gains related to reduction in cases of hepatocellular carcinoma and decompensated cirrhosis in Japan. J Viral Hepat 2018; 25:945-951. [PMID: 29478258 DOI: 10.1111/jvh.12886] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2017] [Accepted: 01/17/2018] [Indexed: 12/11/2022]
Abstract
Hepatocellular carcinoma (HCC) is a serious complication of hepatitis C virus (HCV) infection. Sustained virologic response (SVR) for HCV is associated with a reduction in cirrhosis, HCC and mortality and their associated costs. Japanese HCV patients are older with higher prevalence of HCC. Here we used a decision-analytic Markov model to estimate the economic benefit of HCV cure by reducing HCC and DCC burden in Japan. A cohort of 10 000 HCV genotype 1b (GT1b) Japanese patients was modelled with a hybrid decision tree and Markov state-transition model capturing natural history of HCV over a lifetime horizon. Treatment options were approved all-oral direct-acting anti-virals (DAAs) vs no treatment. Treatment efficacy was based on clinical trials and transition rates and costs obtained from Japan-specific data. Cases of HCC, decompensated cirrhosis (DCC) and quality-adjusted life years (QALYs) were projected for patients treated with DAAs vs NT. QALYs were monetized using a willingness-to-pay threshold of ¥4-to-¥6 million. Incremental savings with treatment were calculated by adding the projected cost of complications avoided to the monetized gains in QALYs. The model showed that DAA treatment vs no treatment, reduces 2057 cases of HCC and 1478 cases of decompensated cirrhosis and saves ¥850 446.73 and ¥338 229.90 per patient (ppt). Additionally, treatment can lead to additional 2.64 QALYs gained per patient. The indirect economic gains associated with treatment-related QALY improvements were ¥10 576 000, ¥13 220 000 and ¥15 864 000 ppt (willingness-to-pay thresholds of ¥4 million, ¥5 million and ¥6 million). Total economic savings of treatment with DAAs (vs no treatment) was ¥7 526 372.63, ¥10 170 372.63 and ¥12 814 372.63, at these different willingness-to-pay thresholds. In conclusion treatment of HCV GT1b with all-oral DAAs in Japan can lead to significant direct and indirect savings related to avoidance of HCC and DCC.
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Affiliation(s)
- Z M Younossi
- Inova Health System, Betty and Guy Beatty Center for Integrated Research, Falls Church, VA, USA.,Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA
| | - A Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Y Eguchi
- Liver Center, Saga University Hospital, Saga University, Saga, Japan
| | - L Henry
- Center for Outcomes Research in Liver Diseases, Washington, DC, USA
| | | | - M Mizokami
- National Center for Global Health and Medicine, Tokyo, Japan
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19
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Hepatocellular carcinoma after sustained virological response with interferon-free regimens in HIV/hepatitis C virus-coinfected patients. AIDS 2018; 32:1423-1430. [PMID: 29596108 DOI: 10.1097/qad.0000000000001809] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To assess the possible association between the use of direct antiviral agents (DAA) and the risk of hepatocellular carcinoma (HCC) in HIV/hepatitis C virus (HCV)-coinfected patients. METHODS The GEHEP-002 cohort recruits HCC cases in HIV-infected patients from 32 centers from Spain. Three analyses were performed: the proportion of HCC cases after sustained virological response (SVR) and the evolution of this proportion over time, the frequency of HCC after SVR in HIV/HCV-coinfected patients with cirrhosis, and the probability of HCC recurrence after curative therapies among those undergoing HCV therapy. RESULTS Forty-two (13%) out of 322 HCC cases in HIV/HCV-coinfected patients occurred after SVR. Twenty-eight (10%) out of 279 HCC cases diagnosed during the years of use of IFN-based regimens occurred after SVR whereas this occurred in 14 (32.6%) out of the 43 HCC cases diagnosed in the all-oral DAA period (P < 0.0001). One thousand, three hundred and thirty-seven HIV/HCV-coinfected patients with cirrhosis achieved SVR in the cohort. The frequency of HCC after SVR declined from 15% among those cured with pegylated-IFN with ribavirin to 1.62 and 0.87% among those cured with DAA with and without IFN, respectively. In patients with previous HCC treated with curative therapies, HCC recurrence occurred in two (25%) out of eight patients treated with IFN-based regimens and four (21%) out of 19 treated with DAA-IFN-free regimens (P = 1.0). CONCLUSION The frequency of HCC emergence after SVR has not increased after widespread use of DAA in HIV/HCV-coinfected patients. DAA do not seem to impact on HCC recurrence in the short-term among those with previously treated HCC.
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20
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Mazzarelli C, Considine A, Childs K, Carey I, Manini MA, Suddle A, Dusheiko G, Agarwal K, Cannon MD. Efficacy and Tolerability of Direct-Acting Antivirals for Hepatitis C in Older Adults. J Am Geriatr Soc 2018; 66:1339-1345. [PMID: 29799112 DOI: 10.1111/jgs.15392] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVES To evaluate the efficacy and tolerability of direct-acting antiviral (DAA) therapy in individuals aged 65 and older. DESIGN Retrospective review between June 2014 and January 2017. SETTING Viral hepatitis outpatient clinic. PARTICIPANTS Individuals aged 65 and older treated with DAA therapy for hepatitis C virus (HCV) during the study period (N=113) divided into 2 cohorts: aged 65 to 74 (n=88) and aged 75 and older (n=25). MEASUREMENTS Drug-drug interactions (DDIs), adverse events (AEs), and rates of sustained virologic response with DAA therapy were assessed. RESULTS Sustained virologic response rate was 97.7% in individuals aged 65 to 74 and 95.8% in those aged 75 and older. Individuals aged 75 and older were more likely to be taking more than 2 medications per day for chronic conditions (84% vs 62%, p=.02) and more likely to have clinically significant DDIs necessitating cessation or adjustment of medications before commencement of DAA therapy (80% vs 36%, p=.001). Moreover, individuals aged 75 and older were more likely to experience an AE during therapy (50% vs 26%, p=.03) and were more susceptible to developing anemia secondary to ribavirin (60% vs 20%, p=.02). CONCLUSION DAA therapy is highly efficacious for the treatment of HCV in older adults, but those aged 75 and older are more likely to have clinically significant pretreatment DDIs and experience AEs, including ribavirin-induced anemia, during therapy.
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Affiliation(s)
- Chiara Mazzarelli
- Institute of Liver Studies, King's College Hospital, London, United Kingdom.,Hepatology and Gastroenterology Unit, ASST Ospedale Niguarda, Milan, Italy
| | - Aisling Considine
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Kate Childs
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Ivana Carey
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | | | - Abid Suddle
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Geoffrey Dusheiko
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Kosh Agarwal
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Mary D Cannon
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
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21
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Hu CC, Weng CH, Chang LC, Lin CL, Chen YT, Hu CF, Hua MC, Chen LW, Chien RN. Simple score to predict risk of hepatocellular carcinoma in chronic hepatitis C patients with advanced fibrosis after pegylated interferon and ribavirin therapy. Ther Clin Risk Manag 2018; 14:783-791. [PMID: 29750037 PMCID: PMC5933468 DOI: 10.2147/tcrm.s158424] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Purpose Eradication of chronic hepatitis C virus (HCV) after interferon-based therapy and its association with the reduction of risk of hepatocellular carcinoma (HCC) in HCV-infected patients with advanced fibrosis is controversial. The study is aimed to develop a simple scoring model for HCC prediction among advanced fibrotic chronic hepatitis C (CHC) patients after pegylated interferon (pegIFN) and ribavirin (RBV) therapy. Patients and methods We enrolled 271 biopsy-proven CHC patients with advanced fibrosis between 2003 and 2016, and divided them into non-HCC (n=211) and HCC (n=60) groups. The median observation duration was 6.0 years (range: 0.9–12.6 years). Results The HCC prevalence after pegIFN and RBV therapy in CHC patients with sustained virologic response (SVR) and without SVR was 14.7% and 32.2%, respectively. Multivariate Cox regression showed age ≥59.5 years old at initiation of therapy (HR: 2.542, 95% CI: 1.390–4.650, P=0.002), pretreatment total bilirubin ≥1.1 mg/dL (HR: 2.630, 95% CI: 1.420–4.871, P=0.002), pretreatment platelet counts <146.5 × 103/μL (HR: 2.751, 95% CI: 1.373–5.511, P=0.004), no achievement of SVR (HR: 2.331, 95% CI: 1.277–4.253, P=0.006), and no diabetes at treatment initiation (HR: 3.085, 95% CI: 1.283–7.418, P=0.012) were significant predictors of HCC development. The scoring model consisted of the five categorical predictors and had an optimal cutoff point of 2.5. The area under receiver operating characteristic (AUROC) of the scoring model was 0.774±0.035 (P<0.001). The sensitivity and specificity of the cutoff value to detect HCC were 81.3% and 57.5%. The 5-year and 10-year cumulative incidence of HCC was 4.9% and 10.0% in patients with simple score ≤2; and 25.9% and 44.6% in patients with simple score ≥3 (P<0.001). Conclusion The simple clinical-guided score has high discriminatory power for HCC prediction in advanced fibrotic CHC patients after pegIFN and RBV therapy.
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Affiliation(s)
- Ching-Chih Hu
- Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan.,College of Medicine, Chang Gung University, Linkou, Taiwan
| | - Cheng-Hao Weng
- College of Medicine, Chang Gung University, Linkou, Taiwan.,Department of Nephrology and Poison Center, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Liang-Che Chang
- Department of Pathology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chih-Lang Lin
- Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan.,College of Medicine, Chang Gung University, Linkou, Taiwan
| | - Yen-Ting Chen
- Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Ching-Fang Hu
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Man-Chin Hua
- College of Medicine, Chang Gung University, Linkou, Taiwan.,Department of Pediatrics, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Li-Wei Chen
- Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Rong-Nan Chien
- College of Medicine, Chang Gung University, Linkou, Taiwan.,Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Linkou, Taiwan
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22
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Schietroma I, Scheri GC, Pinacchio C, Statzu M, Petruzziello A, Vullo V. Hepatitis C Virus and Hepatocellular Carcinoma: Pathogenetic Mechanisms and Impact of Direct-Acting Antivirals. Open Virol J 2018; 12:16-25. [PMID: 29541275 PMCID: PMC5842384 DOI: 10.2174/1874357901812010016] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Revised: 09/26/2017] [Accepted: 02/02/2018] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Globally, between 64 and 103 million people are chronically infected with Hepatitis C virus (HCV), with more than 4.6 million people in the United States and is associated with more than 15.000 deaths annually. Chronic infection can result in cirrhosis and hepatocellular carcinoma. EXPLANATION Epidemiological studies have indicated that persistent infection with hepatitis C virus (HCV) is a major risk for the development of hepatocellular carcinoma (HCC), mainly through chronic inflammation, cell deaths, and proliferation. Despite the new direct-acting antiviral drugs (DAA's) being able to clear the HCV, HCC recurrence rate in these patients is still observed. CONCLUSION In this review we highlighted some aspects that could be involved in the onset of HCV-induced HCC such as immune system, viral factors and host genetics factors.Moreover, we focused on some of the last reports about the effects of DAA's on the HCV clearance and their potential implications in HCC recurrence.
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Affiliation(s)
- Ivan Schietroma
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, Rome, Italy
| | - Giuseppe Corano Scheri
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, Rome, Italy
| | - Claudia Pinacchio
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, Rome, Italy
| | - Maura Statzu
- Department of Molecular Medicine, Laboratory of Virology, “Sapienza” University of Rome, Rome, Italy
| | - Arnolfo Petruzziello
- Virology and Molecular Biology Unit, Department of Diagnostic Pathology, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy
| | - Vincenzo Vullo
- Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, Rome, Italy
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23
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Wedemeyer H, Reimer J, Sandow P, Hueppe D, Lutz T, Gruengreiff K, Goelz J, Christensen S, Pfeiffer-Vornkahl H, Alshuth U, Manns MP. Long-term outcome of chronic hepatitis C virus infection in a real-world setting: The German LOTOS study. Liver Int 2017; 37:1468-1475. [PMID: 28247572 DOI: 10.1111/liv.13399] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Accepted: 02/11/2017] [Indexed: 01/08/2023]
Abstract
BACKGROUND & AIMS There are few large-scale, prospective studies comparing liver-associated events in treated and untreated patients with CHC managed in routine clinical practice. METHODS Patients with CHC were prospectively enrolled in a non-interventional study. Data from patients with available documentation who had either achieved a sustained virological response, or were non-responders, relapsers, or had virological breakthrough following treatment with peginterferon alfa-2a±ribavirin, or who had been diagnosed but never treated at least 3 years previously, and who remained under medical observation were analyzed. Primary endpoint was liver-associated events (composite of decompensation/liver failure, ascites, hepatocellular carcinoma, or liver transplant/placement on a transplant list). RESULTS In all, 1444 eligible patients were identified. Mean follow-up was 4.7 (standard deviation; SD 1.1) years. Patients with sustained virological response had a lower incidence of liver-associated events vs non-responders, relapsers, or virological breakthrough and never treated patients (1.7% vs 4.7% and 4.7% respectively). The proportion of patients with cirrhosis increased from baseline in the non-responders, relapsers, or virological breakthrough (6.8%-10.5%) and never treated group (3.7%-8.4%), with an associated increase in severity, but was unchanged in the sustained virological response group (2.1%). Event-free survival was significantly higher in sustained virological response patients (P=.0082). CONCLUSIONS In this "real-world" cohort, the achievement of sustained virological response almost eliminated liver-related morbidity and mortality compared with patients who failed to achieve sustained virological response and those who were untreated. Overall, the LOTOS cohort highlights the importance of timely and effective treatment for patients with CHC.
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Affiliation(s)
- Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Jens Reimer
- Centre for Interdisciplinary Addiction Research, University of Hamburg, Hamburg, Germany
| | | | | | | | | | | | | | | | | | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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24
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The in vivo antitumor effects of type I-interferon against hepatocellular carcinoma: the suppression of tumor cell growth and angiogenesis. Sci Rep 2017; 7:12189. [PMID: 28939881 PMCID: PMC5610170 DOI: 10.1038/s41598-017-12414-3] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 09/07/2017] [Indexed: 12/19/2022] Open
Abstract
Type I-interferon (IFN) is considered to exert antitumor effects through the inhibition of cancer cell proliferation and angiogenesis. Based on the species-specific biological activity of IFN, we evaluated each antitumor mechanism separately. We further examined the antitumor effects of type I-IFN combined with sorafenib. Human IFN (hIFN) significantly inhibited the proliferation of human hepatocellular carcinoma (HCC) Hep3B cells and the tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Although mouse IFN (mIFN) did not inhibit the proliferation of Hep3B cells in vitro, mIFN, as well as hIFN, showed significant antitumor effects in mouse Hep3B cell-xenograft model. Furthermore, mIFN treatment amplified the antitumor effects of sorafenib in vivo with the suppression of angiogenesis. The DNA chip analysis showed that the mIFN treatment promoted the antitumor signal pathways of sorafenib, including anti-angiogenic effects. Unlike the effects observed in in vitro experiments, mIFN showed an antitumor effect in the mouse Hep3B cell-xenograft model, suggesting a role of the anti-angiogenic activity in the in vivo tumoricidal effects of type I-IFN. In addition, our findings suggested the clinical utility of combination therapy with type І-IFN and sorafenib for HCC.
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25
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Mantravadi S. Patterns in Liver-Related Health Outcomes with Hepatitis C Virus Treatments and Health Equity Implications for Decision Makers: A Cohort Analysis of Medicaid Patients. Health Equity 2017; 1:156-164. [PMID: 30283843 PMCID: PMC6071889 DOI: 10.1089/heq.2017.0018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Introduction: Hepatitis C virus (HCV) infection is a blood-borne communicable disease that, in perhaps 20% of cases, results in a chronic disease. However, traditional peginterferon/ribavirin therapies pose many adverse side effects that are difficult to tolerate, and many patients do not complete the therapy. However, healthcare access to these newer, efficacious treatments are reduced, due to inadequate or lack of coverage of direct acting antiviral (DAA) medication. The objective of this study was to evaluate the impact of HCV treatment regimens on outcomes of care for HCV-infected Medicaid beneficiaries without cirrhosis/liver disease scarring. Methods: A cohort analysis was performed to evaluate the changes in cirrhosis, hepatocellular carcinoma (liver cancer), and liver transplantation with use of HCV treatments in Medicaid beneficiaries with HCV, and was followed over a period of 10 years. The cohort of Medicaid beneficiaries and relevant variables were generated from published literature. Results: Finally, considering the impact on health expenditures due to improved access to new treatments in Medicaid beneficiaries, DAAs resulted in the lowest decompensated cirrhosis and hepatocellular carcinoma-related healthcare cost per person over the 10-year time frame the cohort was followed. Conclusions: The risk of liver-related disease is higher in patients with cirrhosis, as reaching treatment success results in continued disease progression, not normal health status; thus, liver cancer healthcare costs are higher in patients with cirrhosis, compared to those without cirrhosis.
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Abstract
PURPOSE OF REVIEW Hepatocellular carcinoma (HCC) is becoming an important cause of mortality in patients with HIV, attributed to coinfection with hepatitis C virus, hepatitis B virus, and the longer survival advantage these patients are achieving after introducing the highly active antiretroviral therapy (HAART) regimens. RECENT FINDINGS In addition to hepatitis infection, immunosuppression secondary to HIV infection, direct impact of the virus on liver parenchyma, and the use of hepatotoxic antiretroviral drugs, all contribute to HCC pathogenesis. Screening is very important in this particular population; data on population-specific guidelines are still controversial and scarce. Liver transplantation remains the treatment of choice in eligible patients. Trials on sorafenib have not included patients with HIV; yet, we know from small retrospective series that it might be safe and effective. SUMMARY In the HAART era, HCC is arising as a common non-AIDS defining cancer with high impact on morbidity and mortality of HIV-infected patients. Candidates for liver transplantation should be offered this option regardless of HIV infection. Safety and efficacy of sorafenib and other treatment modalities should be further studied and offered as deemed applicable to HIV patients diagnosed with HCC.
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27
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Abstract
There is great geographical variation in the distribution of hepatocellular carcinoma (HCC), with the majority of all cases worldwide found in the Asia–Pacific region, where HCC is one of the leading public health problems. Since the “Toward Revision of the Asian Pacific Association for the Study of the Liver (APASL) HCC Guidelines” meeting held at the 25th annual conference of the APASL in Tokyo, the newest guidelines for the treatment of HCC published by the APASL has been discussed. This latest guidelines recommend evidence-based management of HCC and are considered suitable for universal use in the Asia–Pacific region, which has a diversity of medical environments.
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28
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Bang CS, Song IH. Impact of antiviral therapy on hepatocellular carcinoma and mortality in patients with chronic hepatitis C: systematic review and meta-analysis. BMC Gastroenterol 2017; 17:46. [PMID: 28376711 PMCID: PMC5379714 DOI: 10.1186/s12876-017-0606-9] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2017] [Accepted: 03/28/2017] [Indexed: 12/17/2022] Open
Abstract
Background The long-term clinical outcomes of antiviral therapy for patients with chronic hepatitis C are uncertain in terms of hepatitis C virus (HCV)-related morbidity and mortality according to the response to antiviral therapy. This study aimed to assess the impact of antiviral treatment on the development of HCC and mortality in patients with chronic HCV infection. Methods A systematic review was conducted for studies that evaluated the antiviral efficacy for patients with chronic hepatitis C or assessed the development of HCC or mortality between SVR (sustained virologic response) and non-SVR patients. The methodological quality of the enrolled publications was evaluated using Risk of Bias table or Newcastle-Ottawa scale. Random-effect model meta-analyses and meta-regression were performed. Publication bias was assessed. Results In total, 59 studies (4 RCTs, 15 prospective and 40 retrospective cohort studies) were included. Antiviral treatment was associated with reduced development of HCC (vs. no treatment; OR 0.392, 95% CI 0.275–0.557), and this effect was intensified when SVR was achieved (vs. no SVR, OR: 0.203, 95% CI 0.164–0.251). Antiviral treatment was associated with lower all-cause mortality (vs. no treatment; OR 0.380, 95% CI 0.295–0.489) and liver-specific mortality (OR 0.363, 95% CI 0.260–0.508). This rate was also intensified when SVR was achieved [all-cause mortality (vs. no SVR, OR 0.255, 95% CI 0.199–0.326), liver-specific mortality (OR 0.126, 95% CI 0.094–0.169)]. Sensitivity analyses revealed robust results, and a small study effect was minimal. Conclusions In patients with chronic hepatitis C, antiviral therapy can reduce the development of HCC and mortality, especially when SVR is achieved. Electronic supplementary material The online version of this article (doi:10.1186/s12876-017-0606-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Chang Seok Bang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Republic of Korea
| | - Il Han Song
- Division of Hepatology, Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea, Republic of Korea.
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29
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Favorable Outcomes of Chinese HCV-Related Cirrhotic Patients with Sustained Virological Response after Pegylated Interferon Plus Ribavirin Treatment. BIOMED RESEARCH INTERNATIONAL 2017; 2017:8061091. [PMID: 28232944 PMCID: PMC5292367 DOI: 10.1155/2017/8061091] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/20/2016] [Revised: 12/08/2016] [Accepted: 01/04/2017] [Indexed: 02/07/2023]
Abstract
Few studies have conducted follow-up investigations of the clinical course in HCV-related cirrhotic patients who achieved a sustained virological response (SVR) with pegylated interferon plus ribavirin treatment (PegIFN + RBV). We investigated the clinical course and laboratory data in a prospective cohort study enrolling HCV-related cirrhotic patients who received PegIFN + RBV between August 2008 and July 2013 in China. Complete blood counts, liver function tests, and HCV-RNA were serially examined. Liver-related complications were recorded. To detect hepatocellular carcinoma (HCC), alpha-fetoprotein assays, and ultrasound scans were repeated at 6-month intervals. Twenty-five patients were enrolled, including 8 patients with decompensation events before treatment. Eighteen patients achieved SVR with a mean follow-up period of 25.78 months. During the follow-up period, only one patient exhibited HCV-RNA positivity and no decompensation events were detected, but 4 patients developed HCC after SVR. APRI decreased more in patients with SVR than in patients with non-SVR (median, -1.33 versus 0.86, P < 0.001). The albumin levels and platelet counts significantly increased during the follow-up period after SVR (44.27 ± 4.09 versus 42.63 ± 4.37, P = 0.037 and 173.89 ± 87.36 versus 160.11 ± 77.97, P = 0.047). These data indicated that HCV-related cirrhotic patients with SVR after PegIFN + RBV may have a favorable clinical course and improvements in laboratory data. Moreover, HCC should be monitored.
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Kim KA. [Renewed 2015 Clinical Practice Guidelines for Management of Hepatitis C by Korean Association for the Study of the Liver; What Has Been Changed? - Indications for Treatment]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2017; 67:123-6. [PMID: 26996180 DOI: 10.4166/kjg.2016.67.3.123] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The landscape of treatment for HCV infection has evolved substantially with the advent of highly effective direct-acting antiviral agents (DAA). The Korean Association for the Study of the Liver updated guideline for managemnt of hepatitis C in accordance with the introduction of DAA into practice in late 2015. Due to high effectiveness and few side effects of DAA, indications for treatment has been widened to include patients who had been contraindicated for the combination treatment of peginterferon-α and ribavirin, i.e. decompensated cirrhosis and pre- and post-liver transplant setting. As succeesul treatment of HCV can reduce complications of cirrhosis, development of hepatocelluar carcinoma and liver-related mortality, and improve extrahepatic manifestions, all HCV-infected patients with no contraindication should be considered for treatment. Considering the risk for morbidity and mortality and benefit of treatment, patients with advanced fibrosis ≥F3 including compensated and decompensated cirrhosis, those in the pre- and post-tranplasnt setting, and those with severe extrahepatic manifestations including HCV-related mixed cryoglobulinemia and glomerulonephritis should be given priority for treatment.
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Affiliation(s)
- Kyung-Ah Kim
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
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Prediction of Hepatocellular Carcinoma Development after Hepatitis C Virus Eradication Using Serum Wisteria floribunda Agglutinin-Positive Mac-2-Binding Protein. Int J Mol Sci 2016; 17:ijms17122143. [PMID: 27999409 PMCID: PMC5187943 DOI: 10.3390/ijms17122143] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Revised: 11/30/2016] [Accepted: 12/14/2016] [Indexed: 01/06/2023] Open
Abstract
We aimed to clarify the association between a novel serum fibrosis marker, Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP), and hepatocellular carcinoma (HCC) development in 355 patients with chronic hepatitis C who achieved sustained virologic response (SVR) through interferon-based antiviral therapy. Pretreatment serum WFA+-M2BP levels were quantified and the hazard ratios (HRs) for HCC development were retrospectively analyzed by Cox proportional hazard analysis. During the median follow-up time of 2.9 years, 12 patients developed HCC. Multivariate analysis demonstrated that high serum WFA+-M2BP (≥2.80 cut off index (COI), HR = 15.20, p = 0.013) and high fibrosis-4 (FIB-4) index (≥3.7, HR = 5.62, p = 0.034) were independent risk factors for HCC development. The three- and five-year cumulative incidence of HCC in patients with low WFA+-M2BP were 0.4% and 0.4%, respectively, whereas those of patients with high WFA+-M2BP were 7.7% and 17.6%, respectively (p < 0.001). In addition, combination of serum WFA+-M2BP and FIB-4 indices successfully stratified the risk of HCC: the five-year cumulative incidences of HCC were 26.9%, 6.8%, and 0.0% in patients with both, either, and none of these risk factors, respectively (p < 0.001). In conclusion, pretreatment serum WFA+-M2BP level is a useful predictor for HCC development after achieving SVR.
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Cheung MCM, Walker AJ, Hudson BE, Verma S, McLauchlan J, Mutimer DJ, Brown A, Gelson WTH, MacDonald DC, Agarwal K, Foster GR, Irving WL. Outcomes after successful direct-acting antiviral therapy for patients with chronic hepatitis C and decompensated cirrhosis. J Hepatol 2016; 65:741-747. [PMID: 27388925 DOI: 10.1016/j.jhep.2016.06.019] [Citation(s) in RCA: 308] [Impact Index Per Article: 34.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Revised: 06/10/2016] [Accepted: 06/18/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Direct-acting antivirals have become widely used for patients with chronic hepatitis C virus infection with decompensated cirrhosis. Virological responses are excellent and early improvements in liver function, at least in a proportion of patients, have been observed but the longer term impact of viral clearance on end-stage liver disease complications is unclear. METHODS Prospective study of patients with decompensated cirrhosis who received 12weeks of all-oral direct-acting antivirals through the English Expanded Access Programme. Endpoints were deaths, liver transplantation, hepatocellular carcinoma, serious decompensation events, sepsis or hospitalisations, and MELD scores between start of therapy to 15months post-treatment start. An untreated cohort of patients was retrospectively studied over 6months for comparison. RESULTS Amongst 317/406 patients who achieved sustained virological response at 24weeks post-treatment, there were 9 deaths (3%), 17 new liver cancers (5%), 39 transplantations (12%) and 52 with serious decompensations (16%), over 15months. When compared to the first six months from treatment start and to untreated patients, there was a reduction in incidence of decompensations [30/406 (7%) in months 6-15 and 72/406 (18%) in months 0-6 for treated patients vs. 73/261 (28%) in untreated patients]. There was no significant difference in liver cancer incidence (10/406 (2.5%) in months 6-15 and 17/406 (4%) in months 0-6 for treated patients vs. 11/261 (4%) in untreated patients). CONCLUSIONS This study suggests that antiviral therapy in patients with decompensated cirrhosis led to prolonged improvement in liver function, with no evidence of paradoxical adverse impact nor increase in liver malignancy. LAY SUMMARY This is a report of a large group of patients in England who have hepatitis C virus (HCV) infection with advanced liver disease. They have been treated with new anti-HCV drugs, which cured the infection in the majority. This study looks at their outcomes a year following treatment, in terms of deaths, cancers and other complications of advanced liver disease. We conclude that in most patients anti-HCV treatment is beneficial even in advanced liver disease.
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Affiliation(s)
- Michelle C M Cheung
- Liver Unit, Blizard Insitute, Queen Mary University of London, United Kingdom
| | - Alex J Walker
- Faculty of Medicine & Health Sciences, University of Nottingham, United Kingdom
| | | | - Suman Verma
- Institute of Liver Studies, King's College London, United Kingdom
| | - John McLauchlan
- MRC-University of Glasgow Centre for Virus Research, United Kingdom
| | - David J Mutimer
- Centre for Liver Research and NIHR Biomedical Research Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom
| | - Ashley Brown
- Department of Hepatology, St Mary's Hospital, Imperial College London, United Kingdom
| | - William T H Gelson
- Department of Hepatology, Cambridge University Hospitals NHS Foundation Trust, United Kingdom
| | - Douglas C MacDonald
- UCL Institute for Liver and Digestive Health, University College London, United Kingdom
| | - Kosh Agarwal
- Institute of Liver Studies, King's College London, United Kingdom
| | | | - William L Irving
- NIHR Nottingham Digestive Diseases Biomedical Research Unit, United Kingdom
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Murata A, Genda T, Ichida T, Amano N, Sato S, Tsuzura H, Sato S, Narita Y, Kanemitsu Y, Shimada Y, Hirano K, Iijima K, Wada R, Nagahara A, Watanabe S. Pretreatment AKR1B10 expression predicts the risk of hepatocellular carcinoma development after hepatitis C virus eradication. World J Gastroenterol 2016; 22:7569-7578. [PMID: 27672277 PMCID: PMC5011670 DOI: 10.3748/wjg.v22.i33.7569] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2016] [Revised: 07/04/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To clarify the association between aldo-keto reductase family 1 member B10 (AKR1B10) expression and hepatocarcinogenesis after hepatitis C virus eradication.
METHODS In this study, we enrolled 303 chronic hepatitis C patients who had achieved sustained virological response (SVR) through interferon-based antiviral therapy. Pretreatment AKR1B10 expression in the liver was immunohistochemically assessed and quantified as a percentage of positive staining area by using image-analysis software. A multivariate Cox analysis was used to estimate the hazard ratios (HRs) of AKR1B10 expression for hepatocellular carcinoma (HCC) development after achieving SVR. The cumulative incidences of HCC development were evaluated using Kaplan-Meier analysis and the log-rank test.
RESULTS Of the 303 chronic hepatitis C patients, 153 (50.5%) showed scarce hepatic AKR1B10 expression, quantified as 0%, which was similar to the expression in control normal liver tissues. However, the remaining 150 patients (49.5%) exhibited various degrees of AKR1B10 expression in the liver, with a maximal AKR1B10 expression of 73%. During the median follow-up time of 3.6 years (range 1.0-10.0 years), 8/303 patients developed HCC. Multivariate analysis revealed that only high AKR1B10 expression (≥ 8%) was an independent risk factor for HCC development (HR = 15.4, 95%CI: 1.8-132.5, P = 0.012). The 5-year cumulative incidences of HCC development were 13.7% and 0.5% in patients with high and low AKR1B10 expression, respectively (P < 0.001). During the follow-up period after viral eradication, patients expressing high levels of AKR1B10 expressed markedly higher levels of alanine aminotransferase and α-fetoprotein than did patients exhibiting low AKR1B10 expression.
CONCLUSION Chronic hepatitis C patients expressing high levels of hepatic AKR1B10 had an increased risk of HCC development even after SVR.
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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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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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Lu M, Li J, Rupp LB, Holmberg SD, Moorman AC, Spradling PR, Teshale EH, Zhou Y, Boscarino JA, Schmidt MA, Lamerato LE, Trinacty C, Trudeau S, Gordon SC. Hepatitis C treatment failure is associated with increased risk of hepatocellular carcinoma. J Viral Hepat 2016; 23:718-29. [PMID: 27028626 PMCID: PMC5724043 DOI: 10.1111/jvh.12538] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Accepted: 02/18/2016] [Indexed: 12/11/2022]
Abstract
Sustained virological response (SVR) to antiviral therapy for hepatitis C (HCV) reduces risk of hepatocellular carcinoma (HCC), but there is little information regarding how treatment failure (TF) compares to lack of treatment. We evaluated the impact of treatment status on risk of HCC using data from the Chronic Hepatitis Cohort Study (CHeCS-an observational study based in four large US health systems, with up to 7 years of follow-up on patients). Multivariable analyses were used to adjust for bias in treatment selection, as well as other covariates, followed by sensitivity analyses. Among 10 091 HCV patients, 3681 (36%) received treatment, 2099 (57%) experienced treatment failure (TF), and 1582 (43%) of these achieved sustained virological response (SVR). TF patients demonstrated almost twice the risk of HCC than untreated patients [adjusted hazard ratio (aHR) = 1.95, 95% confidence interval (CI) 1.50-2.53]; this risk persisted across all stages of fibrosis. Several sensitivity analyses validated these results. Although African Americans were at increased risk of treatment failure, they were at lower risk for HCC and all-cause mortality compared to White patients. SVR patients had lower risk of HCC than TF patients (aHR = 0.48, CI 0.31-0.73), whereas treatment - regardless of outcome - reduced all-cause mortality (aHR = 0.45, CI 0.34-0.60 for SVR patients; aHR = 0.78, CI 0.65-0.93 for TF patients).
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Affiliation(s)
- Mei Lu
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | - Jia Li
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | - Loralee B. Rupp
- Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA
| | - Scott D. Holmberg
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Anne C. Moorman
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Philip R. Spradling
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Eyasu H. Teshale
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Yueren Zhou
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | | | - Mark A. Schmidt
- Center for Health Research, Kaiser Permanente–Northwest, Portland, OR, Portland
| | - Lois E. Lamerato
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | - Connie Trinacty
- Center for Health Research, Kaiser Permanente–Hawai’i, Waipahu, HI, USA
| | - Sheri Trudeau
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | - Stuart C. Gordon
- Division of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, MI, USA
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Clinical Impact of Viral Load on the Development of Hepatocellular Carcinoma and Liver-Related Mortality in Patients with Hepatitis C Virus Infection. Gastroenterol Res Pract 2016; 2016:7476231. [PMID: 27656205 PMCID: PMC5021494 DOI: 10.1155/2016/7476231] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2016] [Revised: 07/15/2016] [Accepted: 08/03/2016] [Indexed: 01/16/2023] Open
Abstract
Aim. This study aimed to assess clinical impact of hepatitis C viral load on the development of hepatocellular carcinoma (HCC) and liver-related mortality in HCV-infected patients. Methods. A total of 111 subjects with chronic HCV infection who were available for serum quantitation of HCV RNA were recruited in this retrospective cohort. Cox-proportional hazards models were used to calculate hazard ratio (HR) of developing HCC and liver-related mortality according to serum HCV RNA titers. Results. HCC was developed in 14 patients during follow-up period. The cumulative risk of HCC development was higher in subjects with high HCV RNA titer (log HCV RNA IU/mL > 6) than subjects with low titer (log HCV RNA IU/mL ≦ 6) (HR = 4.63, P = 0.032), giving an incidence rate of 474.1 and 111.5 per 10,000 person-years, respectively. Old age (HR = 9.71, P = 0.014), accompanying cirrhosis (HR = 19.34, P = 0.004), and low platelet count (HR = 13.97, P = 0.009) were other independent risk factors for the development of HCC. Liver-related death occurred in 7 patients. Accompanying cirrhosis (HR = 6.13, P = 0.012) and low albumin level (HR = 9.17, P = 0.002), but not HCV RNA titer, were significant risk factors related to liver-related mortality. Conclusion. Serum HCV RNA titer may be considered an independent risk factor for the development of HCC but not liver-related mortality.
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38
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Velosa J. Why is viral eradication so important in patients with HCV-related cirrhosis? Antivir Ther 2016; 22:1-12. [PMID: 27553973 DOI: 10.3851/imp3077] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/18/2016] [Indexed: 02/07/2023]
Abstract
Approximately one-third of patients infected with chronic HCV have cirrhosis, and this is likely to increase in the near future. The risk of complications, mainly the development of hepatocellular carcinoma, depends on the presence of cirrhosis, and a significant increase in the incidence of cirrhosis-related events, including mortality, is likely in the following years. All-oral therapy with direct-acting antivirals (DAAs) offers a safe and short treatment, with cure rates over 90% in compensated cirrhosis. Cirrhotic patients should be given high priority for treatment because viral clearance has a significant impact on the natural history of HCV infection, halting the progression of the disease and inducing the regression of fibrosis, as well as reducing the need for liver transplantation and improving survival. The benefit of DAAs is great in patients with decompensated cirrhosis, up until recently a population for whom no alternative therapy was available. The efficacy of all-oral therapy has been reported to improve liver function in about 50% of Child-Pugh class C patients. The regression of cirrhosis observed in more than half of patients achieving viral eradication on prior interferon-based regimens still has to be demonstrated in patients treated with DAAs, although there is reason to believe that this will happen. Advanced cirrhosis will eventually become the last boundary of antiviral therapy that will soon be conquered with new drugs currently pending approval.
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Affiliation(s)
- José Velosa
- Hospital de Santa Maria - Gastroenterology and Hepatology, Lisbon, Portugal
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39
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Molecular mechanisms of hepatitis C virus-induced hepatocellular carcinoma. Clin Microbiol Infect 2016; 22:853-861. [PMID: 27476823 DOI: 10.1016/j.cmi.2016.07.019] [Citation(s) in RCA: 101] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2016] [Revised: 07/09/2016] [Accepted: 07/16/2016] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) is a major leading cause of hepatocellular carcinoma (HCC). HCV-induced hepatocarcinogenesis is a multistep process resulting from a combination of pathway alterations that are either caused directly by viral factors or immune mediated as a consequence of a chronic state of inflammation. Host genetic variation is now emerging as an additional element that contribute to increase the risk of developing HCC. The advent of direct-acting antiviral agents foresees a rapid decline of HCC rate in HCV patients. However, a full understanding of the HCV-mediated tumourigenic process is required to elucidate if pro-oncogenic signatures may persist after virus clearance, and to identify novel tools for HCC prevention and therapy. In this review, we summarize the current knowledge of the molecular mechanisms responsible for HCV-induced hepatocarcinogenesis.
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40
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Majumdar A, Kitson MT, Roberts SK. Systematic review: current concepts and challenges for the direct-acting antiviral era in hepatitis C cirrhosis. Aliment Pharmacol Ther 2016; 43:1276-92. [PMID: 27087015 DOI: 10.1111/apt.13633] [Citation(s) in RCA: 122] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Revised: 10/06/2015] [Accepted: 03/29/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND The burden of HCV cirrhosis is high and projected to increase significantly over the next decade. While interferon therapy is problematic in HCV cirrhosis, the era of direct-acting anti-viral (DAA) therapy provides effective treatment for patients with cirrhosis. AIM To systematically review the results of DAA therapy to date in patients with HCV cirrhosis, and highlight the ongoing challenges for DAA therapy in this population. METHODS A structured Medline search was conducted to obtain phase II and III HCV trials in patients with cirrhosis. Citations from review articles were cross-referenced and conference abstracts from EASL and AASLD liver meetings for the preceding 3 years were reviewed manually. Keywords used included hepatitis C, cirrhosis and the DAA's: sofosbuvir, ledipasvir, velpatasvir, grazoprevir, elbasvir, daclatasvir, beclabuvir, asunaprevir, simeprevir, paritaprevir, ombitasvir and dasabuvir. RESULTS Successful direct-acting anti-viral treatment is now possible in patients with HCV-related cirrhosis including those with liver decompensation with several regimens now offering sustained virological response (SVR) of 90-95%. Overall success rates in GT1 cirrhosis are excellent while GT3-infected patients with cirrhosis remain hard to cure. The pangenotypic combination of sofosbuvir and velpatasvir holds promise for GT3 cirrhosis achieving SVR of ~90%. CONCLUSIONS Potent DAA therapies provide much needed, safe and highly effective treatment options for persons with HCV cirrhosis including those previously deemed unsuitable for treatment. Combination therapy with two or more classes of drug is essential to achieve high efficacy and minimise viral resistance, with the role of ribavirin still under evaluation. However, several challenges remain including the hard-to-cure groups of GT3 cirrhosis and direct-acting anti-viral failures, and managing drug-drug interactions.
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Affiliation(s)
- A Majumdar
- Department of Gastroenterology, Alfred Hospital, Melbourne, Vic., Australia.,UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Centre Royal Free Hospital, London, UK
| | - M T Kitson
- Department of Gastroenterology, Alfred Hospital, Melbourne, Vic., Australia
| | - S K Roberts
- Department of Gastroenterology, Alfred Hospital, Melbourne, Vic., Australia
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41
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Izzy M, Jibara G, Aljanabi A, Alani M, Giannattasio E, Zaidi H, Said Z, Gaglio P, Wolkoff A, Reinus JF. Limited Fibrosis Progression but Significant Mortality in Patients Ineligible for Interferon-Based Hepatitis C Therapy. J Clin Exp Hepatol 2016; 6:100-8. [PMID: 27493457 PMCID: PMC4963315 DOI: 10.1016/j.jceh.2016.02.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2016] [Accepted: 02/25/2016] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Individuals ineligible for interferon-based hepatitis C therapy may have a worse prognosis than patients who have failed or not received treatment. AIMS To provide information about the limitations of medical treatment of hepatitis C in real-world patients. METHODS We studied 969 treatment-ineligible patients and 403 treated patients enrolled between 1/1/01 and 6/30/06; data were collected until 3/31/13. Treatment barriers were grouped into five categories and classified as health-related or health-unrelated. Fibrosis stage was assessed initially and at the end of follow-up. Mortality was determined by search of the Social Security database. Death certificates of treatment-ineligible patients were reviewed. RESULTS Initially, 288 individuals had advanced fibrosis and compensated disease; 87 untreated patients developed advanced fibrosis during follow-up. Health-related treatment barriers were more commonly associated with fibrosis progression and worse survival. During follow-up, 247 untreated patients died: 47% of liver-related and 53% of liver-unrelated causes. Patients with significant comorbid illness had the worst five- (70%) and ten-year (50.5%) survival. Despite high mortality (47%) in persons with decompensated liver disease, no treatment barrier was associated with a greater incidence of liver-related death. Only significant comorbid medical illness was an independent predictor of disease progression; however, it was not associated with a greater incidence of liver-related death. Furthermore, treated patients had better 10-year survival than untreated patients on Kaplan-Meier analysis (80.3% vs. 74.5%, P = 0.005). CONCLUSION Many patients with hepatitis C will die of non-liver-related causes and may not be helped by anti-viral treatment.
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Affiliation(s)
- Manhal Izzy
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx, NY, United States,Address for correspondence: Manhal Izzy, Montefiore Medical Center/Albert Einstein College Of Medicine, Division of Gastroenterology, 111 East 210th Street, Bronx, NY 10467, United States.
| | - Ghalib Jibara
- Department of Urology, The Brookdale University Hospital and Medical Center, Brooklyn, NY, United States
| | - Aws Aljanabi
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx, NY, United States
| | - Mustafa Alani
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx, NY, United States
| | - Emily Giannattasio
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx, NY, United States
| | - Hina Zaidi
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx, NY, United States
| | - Zaid Said
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx, NY, United States
| | - Paul Gaglio
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx, NY, United States
| | - Allan Wolkoff
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx, NY, United States
| | - John F. Reinus
- Department of Medicine, Division of Gastroenterology and Liver Diseases, Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx, NY, United States
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D'Ambrosio R, Colombo M. Should surveillance for liver cancer be modified in hepatitis C patients after treatment-related cirrhosis regression? Liver Int 2016; 36:783-90. [PMID: 26936383 DOI: 10.1111/liv.13106] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Accepted: 02/24/2016] [Indexed: 02/13/2023]
Abstract
Surveillance of hepatocellular carcinoma (HCC) with abdominal ultrasound (US) is recommended for patients with advanced liver fibrosis because of hepatitis C virus (HCV) infections who achieve a sustained virological response (SVR) to antiviral therapy. HCC, in fact, may still develop following SVR as a consequence of long-standing carcinogenic activity of either HCV or hepatic fibrosis, whereas HCC risk in non-viraemic patients may also be driven by cofactors like alcohol abuse or diabetes. This explains the debate on whether surveillance for HCC should be continued in patients with documented cirrhosis regression following a SVR too. While regression of cirrhosis was documented to occur in a majority of patients with compensated cirrhosis 5 years after an SVR to interferon, it should be noted that this clinical benefit could be the consequence of treating a selected population with well-compensated liver disease who in fact were interferon able. This may not be the case for most real-life patients with advanced cirrhosis receiving direct antivirals, in whom liver fibrosis may have reached a point of no-return thus potentially preventing the recovery of a normal liver architecture following SVR. Both invasive and non-invasive tools have suboptimal diagnostic accuracy for fibrosis regression in non-viraemic patients, and this prompts to follow international societies' recommendation to perform surveillance in patients with advanced liver fibrosis achieving a SVR, independently on liver histology outcome.
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Affiliation(s)
- Roberta D'Ambrosio
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico di Milano, Università degli Studi di Milano, Milan, Italy
| | - Massimo Colombo
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico di Milano, Università degli Studi di Milano, Milan, Italy
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43
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Joko K, Goto T, Watanabe H, Mitsuda A, Uchida Y, Hasebe C, Tsuruta S, Kimura H, Koike T, Akamatsu T, Mashiba T, Ochi H, Nakamura Y, Tsuchiya K, Kurosaki M, Izumi N. Effects of antiviral therapy for hepatitis C following treatment of hepatocellular carcinoma: survey findings of the Japanese Red Cross Liver Study Group. Hepatol Res 2016; 46:251-8. [PMID: 25753220 DOI: 10.1111/hepr.12515] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Revised: 02/25/2015] [Accepted: 02/27/2015] [Indexed: 02/08/2023]
Abstract
AIM To investigate, in a large number of cases at multiple institutions, the effects and limitations of antiviral therapy for hepatitis C following treatment of hepatocellular carcinoma (HCC) in clinical practice. METHODS Retrospective analysis was performed of 112 patients who had received interferon (IFN) for treating hepatitis C following treatment of HCC and were registered with the Japanese Red Cross Liver Study Group. Factors that may influence recurrence and survival rates were investigated. RESULTS Factors involved in prevention of recurrence were: surgical resection as HCC treatment, platelet and α-fetoprotein (AFP) levels prior to IFN administration, IFN adherence and post-IFN AFP level. Multivariate analysis showed post-IFN AFP level to be an independent factor. Factors involved in prolonging survival were: IFN adherence, IFN response (sustained viral response), pre-IFN alanine aminotransferase and AFP levels, post-IFN AFP level and absence of recurrence. Multivariate analysis showed absence of recurrence to be an independent factor. Although IFN adherence was involved in recurrence and survival, ribavirin adherence was not. IFN was suggested to be involved in preventing recurrence and improving survival due not only to its anti-viral effect, but also its antitumor effect. CONCLUSION Although complete prevention of HCC recurrence is difficult, the most important factor affecting first recurrence is the AFP level at 6 months after the conclusion of antiviral treatment. The survival rate improves dramatically if the hepatitis C virus is eliminated, but the most important factor for improving survival is absence of recurrence.
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Affiliation(s)
- Kouji Joko
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Matsuyama
| | - Tohru Goto
- Department of Gastroenterology, Japanese Red Cross Hospital Omori, Ootaku
| | | | - Akari Mitsuda
- Department of Internal Medicine, Tottori Red Cross Hospital, Tottori
| | - Yasushi Uchida
- Department of Gastroenterology, Matsue Red Cross Hospital, Matsue
| | - Chitomi Hasebe
- Department of Gastroenterology, Asahikawa Red Cross Hospital, Asahikawa
| | - Shotaro Tsuruta
- Department of Internal Medicine, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki
| | - Hiroyuki Kimura
- Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto
| | - Takero Koike
- Department of Internal Medicine, Japanese Red Cross Ashikaga Hospital, Ashikaga
| | - Takuji Akamatsu
- Department of Gastroenterology, Japan Red Cross Wakayama Medical Center, Wakayama
| | - Toshie Mashiba
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Matsuyama
| | - Hironori Ochi
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Matsuyama
| | - Yoshiko Nakamura
- Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Matsuyama
| | - Kaoru Tsuchiya
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Japan
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45
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Treatment of hepatitis C in patients with cirrhosis: remaining challenges for direct-acting antiviral therapy. Drugs 2016; 75:823-34. [PMID: 25943281 DOI: 10.1007/s40265-015-0401-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Chronic hepatitis C virus (HCV) infection is a major global health concern, resulting in significant morbidity and mortality. Treatment using interferon-based therapy in patients with HCV-related cirrhosis has been problematic due to toxicity and poor tolerability. Furthermore, interferon therapy is contraindicated in those with advanced cirrhosis or clinical decompensation, who are arguably the group most in need of viral eradication. The arrival of the direct-acting antiviral (DAA) era has resulted in the development of well-tolerated and highly effective interferon-free drug regimens that promise to dramatically change the therapeutic landscape for those with advanced HCV-related liver disease, including patients with clinical decompensation or pre-liver transplantation. Many successful DAA combinations have emerged; however, a number of challenges remain including the establishment of the optimal treatment duration, the ideal combination of drug classes and determining the role of ribavirin. Moreover, the identification of treatment-experienced patients with genotype 3 HCV cirrhosis as a difficult-to-treat subgroup is a significant impediment to overcome, as are those who have failed prior DAA therapy. Despite these barriers, the ongoing prolific development of safe and effective DAA combinations indicates the future is optimistic for the ultimate goal of HCV eradication.
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46
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Huang JF, Yeh ML, Yu ML, Dai CY, Huang CF, Huang CI, Tsai PC, Lin PC, Chen YL, Chang WT, Hou NJ, Lin ZY, Chen SC, Chuang WL. The tertiary prevention of hepatocellular carcinoma in chronic hepatitis C patients. J Gastroenterol Hepatol 2015; 30:1768-74. [PMID: 26094738 DOI: 10.1111/jgh.13012] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIM Pegylated interferon-alpha plus ribavirin combination (PegIFN/RBV) therapy possesses positive effect in the secondary prevention of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients. The current study aimed to assess its efficacy in the tertiary prevention and to validate the performance of the MHC class I polypeptide-related chain A (MICA) level in the prediction of hepatocellular carcinoma (HCC) recurrence. METHODS A multi-center study enrolling 105 consecutive HCC patients post curative therapies were prospectively recruited. The primary outcome measurement was recurrence of HCC. RESULTS The mean observational period was 52.7 months (range = 3.9-121.5 months). Fifty-six (53.3%) patients achieved sustained virological response (SVR). After completion of treatment, 43 (41.0%) patients developed HCC recurrence, and 24 (55.8%) of them had their recurrence within 6 months after completion of therapy. Thirty-three (76.7%) of the patients with HCC recurrence were of de novo pattern. Those responders tended to have a lower cumulative incidence of recurrence than those non-responders (43.2 vs 84.8/100 person-month, log-rank P = 0.13). Those non-responders with a high MICA level (>100 pg/mL) carried the lowest cancer-free survival than those non-responders with a low MICA level and those responders (P = 0.002). Cox regression hazard analysis showed high baseline MICA level (Odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.1-20.8, P = 0.04) and a low platelet count (<100 000/mm(3) ) (OR = 5.4, 95% CI = 1.1-27.0, P = 0.04) predicted HCC recurrence. CONCLUSIONS PegIFN/RBV therapy carried a limited effect in the tertiary prevention of HCC. A high MICA level predicted HCC recurrence, particularly among those non-responders.
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Affiliation(s)
- Jee-Fu Huang
- Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Pei-Chen Lin
- Center for Teaching and Research, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yao-Li Chen
- Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan.,School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Wen-Tsan Chang
- Division of HBP Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Nai-Jen Hou
- Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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47
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Kwo P, Agrawal S. Treating hepatitis C virus in patients with decompensated cirrhosis: Why is it so difficult and does a sustained response rate rescue the patient from liver transplantation? Clin Liver Dis (Hoboken) 2015; 6:133-135. [PMID: 31041009 PMCID: PMC6490662 DOI: 10.1002/cld.519] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Revised: 11/22/2015] [Accepted: 11/30/2015] [Indexed: 02/04/2023] Open
Affiliation(s)
- Paul Kwo
- Department of MedicineIndiana University School of MedicineIndianapolisIN46202
| | - Saurabh Agrawal
- Department of MedicineIndiana University School of MedicineIndianapolisIN46202
- Purdue UniversityWest LafayetteIN
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48
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Shakado S, Sakisaka S, Chayama K, Okanoue T, Toyoda J, Izumi N, Matsumoto A, Takehara T, Ido A, Hiasa Y, Yoshioka K, Nomura H, Ueno Y, Seike M, Kumada H. Alpha-fetoprotein and des-gamma-carboxy-prothrombin at twenty-four weeks after interferon-based therapy predict hepatocellular carcinoma development. World J Hepatol 2015; 7:2757-2764. [PMID: 26644819 PMCID: PMC4663395 DOI: 10.4254/wjh.v7.i27.2757] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2015] [Revised: 07/18/2015] [Accepted: 11/17/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate risk factors for development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus-related liver cirrhosis (LC-C).
METHODS: To evaluate the relationship between clinical factors including virological response and the development of HCC in patients with LC-C treated with interferon (IFN) and ribavirin, we conducted a multicenter, retrospective study in 14 hospitals in Japan. All patients had compensated LC-C with clinical or histological data available. HCC was diagnosed by the presence of typical hypervascular characteristics on computed tomography and/or magnetic resonance imaging.
RESULTS: HCC was diagnosis in 50 (21.6%) of 231 LC-C patients during a median observation period of 3.8 years after IFN and ribavirin therapy. Patients who developed HCC were older (P = 0.018) and had higher serum levels of pretreatment alpha-fetoprotein (AFP) (P = 0.038). Multivariate analysis revealed the following independent risk factors for HCC development: history of treatment for HCC [P < 0.001, odds ratio (OR) = 15.27, 95%CI: 4.98-59.51], AFP levels of ≥ 10 ng/mL (P = 0.009, OR = 3.89, 95%CI: 1.38-11.94), and des-γ-carboxy prothrombin (DCP) levels of ≥ 40 mAU/mL at 24 wk after the completion of IFN and ribavirin therapy (P < 0.001, OR = 24.43, 95%CI: 4.11-238.67).
CONCLUSION: We suggested that the elevation of AFP and DCP levels at 24 wk after the completion of IFN and ribavirin therapy were strongly associated with the incidence of HCC irrespective of virological response among Japanese LC-C patients.
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49
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Natarajan Y, Kanwal F. Pay for Performance in Chronic Liver Disease. Clin Gastroenterol Hepatol 2015; 13:2042-7. [PMID: 26164221 DOI: 10.1016/j.cgh.2015.06.038] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Revised: 06/29/2015] [Accepted: 06/30/2015] [Indexed: 02/07/2023]
Abstract
With the advent of the Affordable Care Act, pay-for-performance programs have become widespread in the United States and are here to stay. The Centers for Medicare and Medicaid Services started its pay-for-performance program, the Physician Quality Reporting Initiative, in 2007, and made it a permanent system, the Physician Quality Reporting System, in 2011. Although it started off as a pay-for-performance initiative, in which physicians and other health care professionals were rewarded for satisfactorily reporting on selected quality measures, it now has evolved into a penalty-based program. The Physician Quality Reporting System includes measures that target hepatitis C virus infection. It is important for gastroenterologists to be aware of these measures and the submission process to avoid penalties or other difficulties with reimbursement. This review describes the current measures in chronic liver disease, rates of submission, as well as the submission process and associated challenges.
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Affiliation(s)
- Yamini Natarajan
- Department of Gastroenterology, Baylor College of Medicine, Houston, Texas.
| | - Fasiha Kanwal
- Department of Gastroenterology, Baylor College of Medicine, Houston, Texas
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50
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Zuchowski JL, Hamilton AB, Pyne JM, Clark JA, Naik AD, Smith DL, Kanwal F. Qualitative analysis of patient-centered decision attributes associated with initiating hepatitis C treatment. BMC Gastroenterol 2015; 15:124. [PMID: 26429337 PMCID: PMC4591706 DOI: 10.1186/s12876-015-0356-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2014] [Accepted: 09/23/2015] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND In this era of a constantly changing landscape of antiviral treatment options for chronic viral hepatitis C (CHC), shared clinical decision-making addresses the need to engage patients in complex treatment decisions. However, little is known about the decision attributes that CHC patients consider when making treatment decisions. We identify key patient-centered decision attributes, and explore relationships among these attributes, to help inform the development of a future CHC shared decision-making aid. METHODS Semi-structured qualitative interviews with CHC patients at four Veterans Health Administration (VHA) hospitals, in three comparison groups: contemplating CHC treatment at the time of data collection (Group 1), recently declined CHC treatment (Group 2), or recently started CHC treatment (Group 3). Participant descriptions of decision attributes were analyzed for the entire sample as well as by patient group and by gender. RESULTS Twenty-nine Veteran patients participated (21 males, eight females): 12 were contemplating treatment, nine had recently declined treatment, and eight had recently started treatment. Patients on average described eight (range 5-13) decision attributes. The attributes most frequently reported overall were: physical side effects (83%); treatment efficacy (79%), new treatment drugs in development (55%); psychological side effects (55%); and condition of the liver (52%), with some variation based on group and gender. Personal life circumstance attributes (such as availability of family support and the burden of financial responsibilities) influencing treatment decisions were also noted by all participants. Multiple decision attributes were interrelated in highly complex ways. CONCLUSIONS Participants considered numerous attributes in their CHC treatment decisions. A better understanding of these attributes that influence patient decision-making is crucial in order to inform patient-centered clinical approaches to care (such as shared decision-making augmented with relevant decision-making aids) that respond to patients' needs, preferences, and circumstances.
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Affiliation(s)
- Jessica L Zuchowski
- VA HSR&D Center for the Study of Healthcare Innovation, Implementation & Policy, 16111 Plummer St. Bldg. 25, North Hills, CA, 91343, USA.
| | - Alison B Hamilton
- VA HSR&D Center for the Study of Healthcare Innovation, Implementation & Policy, 16111 Plummer St. Bldg. 25, North Hills, CA, 91343, USA. .,Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
| | - Jeffrey M Pyne
- Center for Mental Healthcare and Outcomes Research, Central Arkansas Veterans Healthcare System, 2200 Fort Roots Drive, North Little Rock, AR, 72114, USA. .,Psychiatric Research Institute, University of Arkansas for Medical Sciences, 4300 West 7th Street, Little Rock, AR, 72205, USA.
| | - Jack A Clark
- Center for Healthcare Organization and Implementation Research, Edith Nourse Rogers Memorial Veterans Hospital, 200 Springs Rd, Bedford, MA, 01730, USA. .,Department of Health Policy and Management, Boston University School of Public Health, 715 Albany St. #358w, Boston, MA, 02118, USA.
| | - Aanand D Naik
- VA HSR&D Center for Innovations in Quality, Effectiveness & Safety, Michael E DeBakey VA Medical Center, 2002 Holcombe Boulevard, Houston, TX, 77030, USA. .,Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
| | - Donna L Smith
- VA HSR&D Center for Innovations in Quality, Effectiveness & Safety, Michael E DeBakey VA Medical Center, 2002 Holcombe Boulevard, Houston, TX, 77030, USA.
| | - Fasiha Kanwal
- VA HSR&D Center for Innovations in Quality, Effectiveness & Safety, Michael E DeBakey VA Medical Center, 2002 Holcombe Boulevard, Houston, TX, 77030, USA. .,Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
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