Long-Term Follow-Up of Chronic Hepatitis C Patients Treated with Interferon-Alpha: Risk of Cirrhosis and Hepatocellular Carcinoma in a Single Center over 10 Years

Objectives: Interferon (IFN)-based therapy for chronic hepatitis C (CHC) is cost-effective and is associated with reduced risk of disease progression. We aimed to assess the incidence of cirrhosis and hepatocellular carcinoma (HCC) and to identify risk factors associated with disease progression. Methods: We retrospectively reviewed 280 CHC patients who were registered at our hospital between 2001 and 2010. Results: About 80% of patients received antiviral treatment. The 10-year cumulative incidence of cirrhosis was significantly lower among patients who received antiviral therapy than among those who did not (8.3 vs. 44.0%; p = 0.001). Among them, patients with sustained virological response (SVR) had a significantly lower incidence of cirrhosis than those without SVR (0.6 vs. 33.9%; p < 0.001). Cox proportional hazards regression showed that SVR was the significant independent factor for reducing the risk of cirrhosis (hazard ratio, HR = 0.03; p = 0.034). The 10-year cumulative incidence of HCC was higher among patients who did not receive antiviral therapy than among those who did (43.9 vs. 6.1%; p < 0.001). Multivariate analysis showed that underlying cirrhosis was the only independent risk factor associated with HCC development (HR = 7.70; p = 0.010). Conclusions: SVR secondary to IFN-based therapy could reduce cirrhosis development in CHC patients. Underlying cirrhosis was the strongest predictor of HCC development.

[1]  H. Lee,et al.  Clinical and epidemiological features of hepatitis C virus infection in South Korea: A prospective, multicenter cohort study , 2013, Journal of medical virology.

[2]  Sung‐Min Ahn,et al.  Role of Interleukin 28B-related Gene Polymorphisms in Chronic Hepatitis C and the Response to Antiviral Therapy in Koreans , 2013, Journal of clinical gastroenterology.

[3]  J. Murray,et al.  Earlier sustained virologic response end points for regulatory approval and dose selection of hepatitis C therapies. , 2013, Gastroenterology.

[4]  F. François,et al.  Association of tattooing and hepatitis C virus infection: A multicenter case‐control study , 2013, Hepatology.

[5]  N. Caporaso,et al.  Sustained virological response: a milestone in the treatment of chronic hepatitis C. , 2013, World journal of gastroenterology.

[6]  Bryce D. Smith,et al.  Eradication of Hepatitis C Virus Infection and the Development of Hepatocellular Carcinoma , 2013, Annals of Internal Medicine.

[7]  K. Chayama,et al.  Impact of Pegylated Interferon Therapy on Outcomes of Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma After Curative Hepatic Resection , 2012, Annals of Surgical Oncology.

[8]  June-Sung Lee,et al.  Efficacy and Tolerability of Peginterferon Alpha Plus Ribavirin in the Routine Daily Treatment of Chronic Hepatitis C Patients in Korea: A Multi-Center, Retrospective Observational Study , 2012, Gut and liver.

[9]  S. Saab,et al.  Effects of a sustained virologic response on outcomes of patients with chronic hepatitis C. , 2011, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[10]  M. Ghany,et al.  An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection: 2011 Practice Guideline by the American Association for the Study of Liver Diseases , 2011, Hepatology.

[11]  Sheng-Nan Lu,et al.  Impact of diabetes mellitus on incidence of hepatocellular carcinoma in chronic hepatitis C patients treated with interferon‐based antiviral therapy , 2011, International journal of cancer.

[12]  Yoshiyuki Suzuki,et al.  Diabetes enhances hepatocarcinogenesis in noncirrhotic, interferon-treated hepatitis C patients. , 2010, The American journal of medicine.

[13]  N. Enomoto,et al.  Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection , 2010, Hepatology.

[14]  S. Saab,et al.  Timing of hepatitis C antiviral therapy in patients with advanced liver disease: A decision analysis model , 2010, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[15]  G. Borgia,et al.  Surrogate endpoints and non-inferiority trials in chronic viral hepatitis. , 2010, Journal of hepatology.

[16]  A. Chiesa,et al.  Predicting Mortality Risk in Patients With Compensated HCV-Induced Cirrhosis: A Long-Term Prospective Study , 2009, The American Journal of Gastroenterology.

[17]  Y. Imai,et al.  Effect of interferon α‐2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with chronic hepatitis , 2009, Hepatology research : the official journal of the Japan Society of Hepatology.

[18]  D. Lavanchy,et al.  The global burden of hepatitis C , 2009, Liver international : official journal of the International Association for the Study of the Liver.

[19]  S. Pol,et al.  Effect of sustained virological response on long-term clinical outcome in 113 patients with compensated hepatitis C-related cirrhosis treated by interferon alpha and ribavirin. , 2007, World journal of gastroenterology.

[20]  G. Alaimo,et al.  Peg-interferon alone or combined with ribavirin in HCV cirrhosis with portal hypertension: a randomized controlled trial. , 2007, Journal of hepatology.

[21]  P. Hewson,et al.  Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and economic analysis. , 2007, Health technology assessment.

[22]  T. Arenovich,et al.  Impact of Asian Race on Response to Combination Therapy With Peginterferon Alfa-2a and Ribavirin in Chronic Hepatitis C , 2007, The American Journal of Gastroenterology.

[23]  I. Sheen,et al.  Sustained virological response to interferon reduces cirrhosis in chronic hepatitis C: a 1386‐patient study from Taiwan , 2007, Alimentary pharmacology & therapeutics.

[24]  M. Omura,et al.  Long‐term clinical and virological outcomes of chronic hepatitis C after successful interferon therapy , 2004, Journal of medical virology.

[25]  L. Seeff,et al.  Aasld Practice Guideline Diagnosis, Management, and Treatment of Hepatitis C , 2003 .

[26]  T. Hassanein,et al.  Serum aminotransferase levels and platelet counts as predictors of degree of fibrosis in chronic hepatitis C virus infection , 2001, American Journal of Gastroenterology.

[27]  P. Lopalco,et al.  Risk of parenterally transmitted hepatitis following exposure to surgery or other invasive procedures: results from the hepatitis surveillance system in Italy. , 2001, Journal of hepatology.

[28]  S. Hadziyannis,et al.  Effect of interferon therapy on the development of hepatocellular carcinoma in patients with hepatitis C virus‐related cirrhosis: a meta‐analysis , 2001, Alimentary pharmacology & therapeutics.

[29]  A. Tamori,et al.  Prevention of hepatocellular carcinoma in patients with chronic active hepatitis C and cirrhosis , 2001, The Lancet.

[30]  Arakawa,et al.  Natural course of progression of liver fibrosis in Japanese patients with chronic liver disease type C – a study of 527 patients at one establishment , 2000, Journal of viral hepatitis.

[31]  M. Sata,et al.  Histologic Improvement of Fibrosis in Patients with Hepatitis C Who Have Sustained Response to Interferon Therapy , 2000, Annals of Internal Medicine.

[32]  M. Shindo,et al.  Varying incidence of cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis C responding differently to interferon therapy , 1999, Cancer.

[33]  F. Bonino Effect of interferon-α on progression of cirrhosis to hepatocellular carcinoma: a retrospective cohort study , 1998, The Lancet.

[34]  Hirokazu TakahashiToshihiko,et al.  Post-challenge hyperglycemia is a significant risk factor for the development of hepatocellular carcinoma in patients with chronic hepatitis C , 2011 .

[35]  Niu Jun-q Interpretation:An update on treatment of genotype 1 chronic hepatitis C virus infection:2011 practice guideline by the American Association for the Study of Liver Diseases , 2011 .

[36]  K. Migita,et al.  Alpha-fetoprotein above normal levels as a risk factor for the development of hepatocellular carcinoma in patients infected with hepatitis C virus , 2010, Journal of Gastroenterology.

[37]  D. Harnois,et al.  Aging of Hepatitis C Virus (HCV)-Infected Persons in the United States: A Multiple Cohort Model of HCV Prevalence and Disease Progression , 2010 .

[38]  [Practice guidelines for management of hepatocellular carcinoma 2009]. , 2009, The Korean journal of hepatology.

[39]  N. Afdhal The natural history of hepatitis C. , 2004, Seminars in liver disease.

[40]  L. Benvegnu' Effect of interferon-alpha on progression of cirrhosis to hepatocellular carcinoma: a retrospective cohort study. International Interferon-alpha Hepatocellular Carcinoma Study Group. , 1998, Lancet.