The risks of hepatocellular carcinoma development after HCV eradication are similar between patients treated with peg-interferon plus ribavirin and direct-acting antiviral therapy

The risk of hepatocellular carcinoma (HCC) development is reduced following viral elimination by interferon therapy in chronic hepatitis C patients. However, the risk in patients treated with interferon-free direct-acting antivirals (DAAs) is unknown. We evaluated chronic hepatitis C patients who achieved viral eradication by pegylated-interferon plus ribavirin (PEG-IFN/RBV, n = 244) or daclatasvir plus asunaprevir (DCV/ASV, n = 154) therapy. None of the patients had prior history of HCC or antiviral therapy. The median observation period after the end of treatment for the PEG-IFN/RBV and DCV/ASV groups were 96 (range 10–196) and 23 (range 4–78) months, respectively. During the observation period, HCC developed in 13 (5.3%) and 7 (4.5%) patients in the PEG-IFN/RBV and DCV/ASV groups, respectively. The cumulative HCC development rate after 1-, 3- and 5-years (0.4%, 3% and 5% for the PEG-IFN/RBV group and 0.6%, 9% and 9% for the DAA group, respectively) were similar between the two groups. Propensity score matching analysis also showed no significant difference in HCC development rates between the two groups. Serum AFP levels decreased to similar levels between PEG-IFN/RBV and DCV/ASV groups following the achievement of viral eradication. The risk for HCC development following viral eradication by IFN-free DAA therapy may be similar to that in IFN-based therapy.

[1]  H. Yoshiji,et al.  Genome-Wide Association Study Identifies TLL1 Variant Associated With Development of Hepatocellular Carcinoma After Eradication of Hepatitis C Virus Infection. , 2017, Gastroenterology.

[2]  Yoshiyuki Suzuki,et al.  Sustained virologic response by direct antiviral agents reduces the incidence of hepatocellular carcinoma in patients with HCV infection , 2017, Journal of medical virology.

[3]  A. Gasbarrini,et al.  Hepatocellular carcinoma recurrence in patients with curative resection or ablation: impact of HCV eradication does not depend on the use of interferon , 2017, Alimentary pharmacology & therapeutics.

[4]  M. Imamura,et al.  Safety and efficacy of dual therapy with daclatasvir and asunaprevir for older patients with chronic hepatitis C , 2017, Journal of Gastroenterology.

[5]  L. Bolondi,et al.  Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. , 2016, Journal of hepatology.

[6]  Yoshiyuki Suzuki,et al.  Liver Fibrosis and Body Mass Index Predict Hepatocarcinogenesis following Eradication of Hepatitis C Virus RNA by Direct-Acting Antivirals , 2016, Oncology.

[7]  J. Bruix,et al.  Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. , 2016, Journal of hepatology.

[8]  M. Imamura,et al.  Daclatasvir and asunaprevir treatment improves liver function parameters and reduces liver fibrosis markers in chronic hepatitis C patients , 2016, Hepatology research : the official journal of the Japan Society of Hepatology.

[9]  M. Imamura,et al.  Development of hepatocellular carcinoma in patients with hepatitis C virus infection who achieved sustained virological response following interferon therapy: A large‐scale, long‐term cohort study , 2016, Journal of gastroenterology and hepatology.

[10]  Peter J. Richardson,et al.  Risk of hepatocellular carcinoma after sustained virological response in Veterans with hepatitis C virus infection , 2016, Hepatology.

[11]  K. Chayama,et al.  Randomized phase 3 trial of ombitasvir/paritaprevir/ritonavir for hepatitis C virus genotype 1b–infected Japanese patients with or without cirrhosis , 2015, Hepatology.

[12]  T. Ide,et al.  Ledipasvir and sofosbuvir fixed-dose combination with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with genotype 1 hepatitis C: an open-label, randomised, phase 3 trial. , 2015, The Lancet. Infectious diseases.

[13]  K. Chayama,et al.  Randomized trial of interferon‐ and ribavirin‐free ombitasvir/paritaprevir/ritonavir in treatment‐experienced hepatitis C virus–infected patients , 2015, Hepatology.

[14]  M. Kubo,et al.  IFNL4/IL-28B haplotype structure and its impact on susceptibility to hepatitis C virus and treatment response in the Japanese population. , 2014, The Journal of general virology.

[15]  K. Chayama,et al.  Daclatasvir Plus Asunaprevir for Chronic HCV Genotype 1b Infection , 2014, Hepatology.

[16]  N. Enomoto,et al.  α‐fetoprotein levels after interferon therapy and risk of hepatocarcinogenesis in chronic hepatitis C , 2013, Hepatology.

[17]  Yusuke Nakamura,et al.  Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers , 2011, Nature Genetics.

[18]  Yusuke Nakamura,et al.  ITPA polymorphism affects ribavirin-induced anemia and outcomes of therapy--a genome-wide study of Japanese HCV virus patients. , 2010, Gastroenterology.

[19]  A. Koike,et al.  Genome-wide association of IL28B with response to pegylated interferon-α and ribavirin therapy for chronic hepatitis C , 2009, Nature Genetics.

[20]  A. Zinsmeister,et al.  Ten Common Statistical Errors and How to Avoid Them , 2008, American Journal of Gastroenterology.

[21]  A. Tamori,et al.  Development of hepatocellular carcinoma in patients with chronic hepatitis C who had a sustained virological response to interferon therapy: a multicenter, retrospective cohort study of 1124 patients , 2007, Liver international : official journal of the International Association for the Study of the Liver.

[22]  J. Montaner,et al.  Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection , 2006, Hepatology.

[23]  M. Sata,et al.  Answer , 2004, Gut.

[24]  Yoshiyuki Suzuki,et al.  Recurrence Rate and Prognosis of Patients with Hepatocellular Carcinoma That Developed after Elimination of Hepatitis C Virus RNA by Interferon Therapy , 2003, Oncology.

[25]  T. Poynard,et al.  Effect of interferon therapy on the natural history of hepatitis C virus-related cirrhosis and hepatocellular carcinoma. , 1999, Clinics in liver disease.

[26]  Yasuyuki Arakawa,et al.  Interferon Therapy Reduces the Risk for Hepatocellular Carcinoma: National Surveillance Program of Cirrhotic and Noncirrhotic Patients with Chronic Hepatitis C in Japan , 1999, Annals of Internal Medicine.

[27]  K. Chayama,et al.  Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: A long‐term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis , 1999, Hepatology.

[28]  D. Häussinger,et al.  Prognosis of chronic hepatitis c: Results of a large, prospective cohort study , 1998, Hepatology.

[29]  R. D'Agostino Adjustment Methods: Propensity Score Methods for Bias Reduction in the Comparison of a Treatment to a Non‐Randomized Control Group , 2005 .

[30]  N. Hayashi,et al.  Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C , 1998, Hepatology.

[31]  Donald Rubin,et al.  Estimating Causal Effects from Large Data Sets Using Propensity Scores , 1997, Annals of Internal Medicine.

[32]  A. Bhalla,et al.  Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. , 1997, Gastroenterology.

[33]  K. Chayama,et al.  A multivariate analysis of risk factors for hepatocellular carcinogenesis: A prospective observation of 795 patients with viral and alcoholic cirrhosis , 1993, Hepatology.

[34]  R. Purcell,et al.  Interrelationship of blood transfusion, non‐A, non‐B hepatitis and hepatocellular carcinoma: Analysis by detection of antibody to hepatitis C virus , 1990, Hepatology.

[35]  A. Zinsmeister,et al.  Effects of decreasing intraluminal amylase activity on starch digestion and postprandial gastrointestinal function in humans. , 1986, Gastroenterology.