Treating viral hepatitis C: efficacy, side effects, and complications

The treatment of hepatitis C has dramatically improved over the past decade. Unlike any other chronic viral infection, a significant proportion of patients with chronic hepatitis C can be cured. However, the current standard therapy--pegylated interferon alpha and ribavirin--has its limitations. Limited efficacy in patients with hepatitis C virus (HCV) genotype 1 and the side effect profile will necessitate the development of new therapeutic approaches. This review describes the efficacy and optimisation of the current standard therapy of hepatitis C and its problems in special patient populations. New treatment directions beyond interferon alpha based therapies are on the horizon.

[1]  A. Perelson,et al.  Mutagenic effects of ribavirin in vivo. , 2005, Journal of hepatology.

[2]  M. Manns,et al.  Treatment of chronic hepatitis C with PEGylated interferon and ribavirin , 2002, Current gastroenterology reports.

[3]  P. Farmer,et al.  Scaling-up HIV treatment programmes in resource-limited settings: the rural Haiti experience , 2004, AIDS.

[4]  D. Hüppe,et al.  Therapie der chronischen Hepatitis C mit PEG-Interferon alpha-2b und Ribavirin: 24 Wochen Behandlung sind ausreichend bei HCV-Genotyp 2 und 3 , 2003 .

[5]  G. Everson.  Treatment of chronic hepatitis C in patients with decompensated cirrhosis. , 2004, Reviews in gastroenterological disorders.

[6]  J. Hoofnagle.  Course and outcome of hepatitis C , 2002, Hepatology.

[7]  P. Marcellin,et al.  Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. , 2004, Annals of internal medicine.

[8]  X. Forns,et al.  Short-term antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype 1 patients. , 2004, Gastroenterology.

[9]  P. Marcellin,et al.  Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3. , 2004, Journal of hepatology.

[10]  M. Manns,et al.  Treatment of hepatitis C in HIV-infected patients: significant progress but not the final step. , 2004, JAMA.

[11]  C. Graham,et al.  Pegylated interferon α therapy in acute hepatitis C: Relation to hepatitis C virus–specific T cell response kinetics , 2004, Hepatology.

[12]  Kenneth Koury,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[13]  R. Howard,et al.  Interferon Alfacon-1 and Ribavirin Versus Interferon α-2b and Ribavirin in the Treatment of Chronic Hepatitis C , 2005, Digestive Diseases and Sciences.

[14]  J. Montaner,et al.  Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. , 2004, The New England journal of medicine.

[15]  A. Bruchfeld,et al.  Dosage of Ribavirin in Patients With Hepatitis C Should Be Based on Renal Function: A Population Pharmacokinetic Analysis , 2002, Therapeutic drug monitoring.

[16]  H. Janssen,et al.  Suicide associated with alfa-interferon therapy for chronic viral hepatitis. , 1994, Journal of hepatology.

[17]  M. Manns,et al.  Treatment with daily consensus interferon (CIFN) plus ribavirin in non-responder patients with chronic hepatitis C: a randomized open-label pilot study. , 2006, Journal of hepatology.

[18]  L. Bolondi,et al.  Triple Antiviral Therapy as a New Option for Patients With Interferon Nonresponsive Chronic Hepatitis C , 2000, Hepatology.

[19]  E. Penner,et al.  Spontaneous viral clearance in patients with acute hepatitis C can be predicted by repeated measurements of serum viral load , 2003, Hepatology.

[20]  J. Reichen,et al.  Peginterferon alfa-2a in patients with chronic hepatitis C. , 2000, The New England journal of medicine.

[21]  D. Dieterich,et al.  Risk factors for hepatic decompensation in patients with HIV/HCV coinfection and liver cirrhosis during interferon-based therapy , 2004, AIDS.

[22]  T. Nakano,et al.  Peginterferon α-2b and ribavirin therapy in chronic hepatitis C genotype 4: impact of treatment duration and viral kinetics on sustained virological response , 2005, Gut.

[23]  V. Balan,et al.  Treatment of recurrent hepatitis C infection after liver transplantation with combination of pegylated interferon &agr;2b and ribavirin: an open-label series1 , 2004, Transplantation.

[24]  N. Gruener,et al.  Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance. , 2003, Gastroenterology.

[25]  C. Giffen,et al.  Treatment of chronic hepatitis C in HIV/HCV‐coinfection with interferon α‐2b+ full‐course vs. 16‐week delayed ribavirin , 2004, Hepatology.

[26]  K. Do,et al.  Linkage disequilibrium analysis in Australian haemochromatosis patients indicates bipartite association with clinical expression. , 1999, Journal of hepatology.

[27]  M. Manns,et al.  Autoimmunity and extrahepatic manifestations in hepatitis C virus infection. , 1999, Journal of hepatology.

[28]  X. Forns,et al.  Antiviral therapy of patients with decompensated cirrhosis to prevent recurrence of hepatitis C after liver transplantation. , 2003, Journal of hepatology.

[29]  M. Manns,et al.  Infection with GB virus C and reduced mortality among HIV-infected patients. , 2001, The New England journal of medicine.

[30]  P. Marcellin,et al.  Randomised trial of interferon α2b plus ribavirin for 48 weeks or for 24 weeks versus interferon α2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus , 1998, The Lancet.

[31]  A. Bruchfeld,et al.  Ribavirin treatment in dialysis patients with chronic hepatitis C virus infection – a pilot study , 2001, Journal of viral hepatitis.

[32]  M. Manns,et al.  Induction of autoantibodies to the adrenal cortex and pancreatic islet cells by interferon alpha therapy for chronic hepatitis C , 2001, Gut.

[33]  T. Berg,et al.  Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin. , 2006, Gastroenterology.

[34]  H. Wedemeyer,et al.  Epitope mapping of cytochrome P4502D6 autoantigen in patients with chronic hepatitis C during alpha-interferon treatment. , 1999, Journal of hepatology.

[35]  Milton W. Taylor,et al.  The biologic activity and molecular characterization of a novel synthetic interferon-alpha species, consensus interferon. , 1996, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[36]  M. Sintchak,et al.  The structure of inosine 5'-monophosphate dehydrogenase and the design of novel inhibitors. , 2000, Immunopharmacology.

[37]  D. Shaw,et al.  731 Interim results of a multiple ascending dose study of R1626, a novel nucleoside analog targeting hcv polymerase in chronic HCV patients , 2006 .

[38]  J. Watson.  Prospects for hepatitis C virus therapeutics: levovirin and viramidine as improved derivatives of ribavirin. , 2002, Current opinion in investigational drugs.

[39]  M. Marazuela,et al.  Thyroid autoimmune disorders in patients with chronic hepatitis C before and during interferon‐α therapy , 1996, Clinical endocrinology.

[40]  Peginterferon-α-2a (40KD) and Ribavirin for 16 or 24 Weeks in Patients With Genotype 2 or 3 Chronic Hepatitis C , 2005 .

[41]  J. Goff,et al.  Treatment of Chronic Hepatitis C with Amantadine , 2000, Digestive Diseases and Sciences.

[42]  Sanjeev Arora,et al.  Virological response and safety outcomes in therapy-nai ve patients treated for chronic hepatitis C with taribavirin or ribavirin in combination with pegylated interferon alfa-2a: a randomized, phase 2 study. , 2007, Journal of hepatology.

[43]  K. Bjøro,et al.  Treatment with pegylated interferon and ribavarin in HCV infection with genotype 2 or 3 for 14 weeks: A pilot study , 2004, Hepatology.

[44]  J. Hoofnagle,et al.  Neutropenia during combination therapy of interferon alfa and ribavirin for chronic hepatitis C , 2002, Hepatology.

[45]  T. Santantonio,et al.  Efficacy of a 24-week course of PEG-interferon alpha-2b monotherapy in patients with acute hepatitis C after failure of spontaneous clearance. , 2005, Journal of hepatology.

[46]  M P Manns,et al.  [Treatment of chronic hepatitis C with PEG-interferon alpha-2b and ribavirin: 24 weeks of therapy are sufficient for HCV genotype 2 and 3]. , 2003, Zeitschrift fur Gastroenterologie.

[47]  M. Manns,et al.  GB virus C/hepatitis G virus infection: a favorable prognostic factor in human immunodeficiency virus-infected patients? , 1998, The Journal of infectious diseases.

[48]  R. Bartenschlager,et al.  Production of infectious hepatitis C virus in tissue culture from a cloned viral genome , 2005, Nature Medicine.

[49]  K. Reddy,et al.  Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels. , 2004, Gastroenterology.

[50]  M. Houghton,et al.  Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. , 1989, Science.

[51]  M. Manns,et al.  Long‐term outcome of hepatitis C virus infection after liver transplantation , 1997, Hepatology.

[52]  oseph,et al.  PEGINTERFERON ALFA-2a IN PATIENTS WITH CHRONIC HEPATITIS C AND CIRRHOSIS PEGINTERFERON ALFA-2a IN PATIENTS WITH CHRONIC HEPATITIS C AND CIRRHOSIS , 2000 .

[53]  J. Dumortier,et al.  Treatment of recurrent hepatitis C after liver transplantation: a pilot study of peginterferon alfa-2b and ribavirin combination. , 2004, Journal of hepatology.

[54]  A. León,et al.  Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for treatment of HIV/HCV co-infected patients , 2004, AIDS.

[55]  E. Keeffe,et al.  Treatment of chronic hepatitis C with consensus interferon: a multicenter, randomized, controlled trial. Consensus Interferon Study Group. , 1997, Hepatology.

[56]  William M. Lee,et al.  Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. , 1998, The New England journal of medicine.

[57]  B. Rehermann,et al.  Immunology of hepatitis B virus and hepatitis C virus infection , 2005, Nature Reviews Immunology.

[58]  J. Hoofnagle,et al.  Treatment of chronic non-A,non-B hepatitis with recombinant human alpha interferon. A preliminary report. , 1986, The New England journal of medicine.

[59]  J. Hoefs,et al.  Treatment of chronic hepatitis C with consensus interferon: A multicenter, randomized, controlled trial , 1997 .

[60]  A. Sanyal,et al.  Use of granulocyte macrophage colony stimulating factor alone or in combination with interferon-alpha-2b for treatment of chronic hepatitis C. , 1998, Journal of hepatology.

[61]  P. Marcellin,et al.  Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT) , 1998, Lancet.

[62]  B. Bacon.  Treatment of patients with hepatitis C and normal serum aminotransferase levels , 2002, Hepatology.

[63]  N. Chalasani,et al.  Peginterferon alfa‐2a for hepatitis C after liver transplantation: Two randomized, controlled trials , 2005, Hepatology.

[64]  A. Heinz,et al.  Prevention of interferon-alpha associated depression in psychiatric risk patients with chronic hepatitis C. , 2005, Journal of hepatology.

[65]  Dieter Häussinger,et al.  Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. , 2002, The New England journal of medicine.

[66]  A. Andriulli,et al.  Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. , 2005, The New England journal of medicine.

[67]  N. Terrault.  Prophylactic and preemptive therapies for hepatitis C virus‐infected patients undergoing liver transplantation , 2003, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[68]  E. Schiff,et al.  Treatment of Established Recurrent Hepatitis C in Liver-Transplant Recipients with Pegylated Interferon-alfa-2b and Ribavirin Therapy , 2004, Transplantation.

[69]  M. Fried,et al.  Side effects of therapy of hepatitis C and their management , 2002, Hepatology.

[70]  D. Dieterich,et al.  736 Early clearance of HCV RNA with valopicitabine (NM283) plus PEG-Interferon in treatment-naïve patients with HCV-1 infection: First results from a phase IIb trial , 2006 .

[71]  H. Van Vlierberghe,et al.  A pilot study of therapeutic vaccination with envelope protein E1 in 35 patients with chronic hepatitis C , 2003, Hepatology.

[72]  M. Ghany,et al.  Pushing the treatment envelope for chronic hepatitis C—is more necessarily better? , 2005, Hepatology.

[73]  M. Berenguer.  What determines the natural history of recurrent hepatitis C after liver transplantation? , 2005, Journal of hepatology.

[74]  N. Tassopoulos.  Treatment of patients with chronic hepatitis C and normal ALT levels. , 1999, Journal of hepatology.

[75]  S. Wünschmann,et al.  Effect of coinfection with GB virus C on survival among patients with HIV infection. , 2001, The New England journal of medicine.

[76]  F. Carrat,et al.  Risk Factors for Symptomatic Mitochondrial Toxicity in HIV/Hepatitis C Virus-Coinfected Patients During Interferon Plus Ribavirin-Based Therapy , 2005, Journal of acquired immune deficiency syndromes.

[77]  Z. Hong,et al.  Mechanism of action of ribavirin in the combination treatment of chronic HCV infection , 2002, Hepatology.

[78]  J. Silver,et al.  Replication of Subgenomic Hepatitis C Virus Rnas in a Hepatoma Cell Line , 1999 .

[79]  M. Kudo,et al.  Risk of HCV transmission after needlestick injury, and the efficacy of short-duration interferon administration to prevent HCV transmission to medical personnel , 2003, Journal of Gastroenterology.

[80]  J. Margolick,et al.  Persistent GB virus C infection and survival in HIV-infected men. , 2004, The New England journal of medicine.

[81]  M. Manns,et al.  The German network of excellence for viral hepatitis (Hep‐Net) , 2003, Hepatology.

[82]  G. Davis,et al.  Projecting future complications of chronic hepatitis C in the United States , 2003, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[83]  E. Schiff,et al.  Epoetin alfa maintains ribavirin dose in HCV-infected patients: a prospective, double-blind, randomized controlled study. , 2004, Gastroenterology.

[84]  T. Berg,et al.  Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C. , 2005, Gastroenterology.

[85]  M. Rizzetto,et al.  Efficacy and safety of interferon alfa therapy in chronic hepatitis C with autoantibodies to liver‐kidney microsomes , 1995, Hepatology.

[86]  B. Weintraub,et al.  Development of thyroid disease during therapy of chronic viral hepatitis with interferon alfa. , 1992, Gastroenterology.

[87]  P. Caraceni,et al.  Combination treatment of advanced HCV associated liver disease with interferon and G-CSF. , 1995, Hepato-gastroenterology.

[88]  H. Chu,et al.  737 Initial results of a 14-day study of the hepatitis C virus inhibitor protease VX-950, in combination with peginterferon-alpha-2a , 2006 .

[89]  A. Bruchfeld,et al.  Determination of ribavirin in serum using highly selective solid-phase extraction and high-performance liquid chromatography. , 2000, Therapeutic drug monitoring.

[90]  N. Bräu.  Treatment of chronic hepatitis C in human immunodeficiency virus/hepatitis C virus-coinfected patients in the era of pegylated interferon and ribavirin. , 2005, Seminars in liver disease.

[91]  T. Berg,et al.  Triple therapy with amantadine in treatment‐naive patients with chronic hepatitis C: A placebo‐controlled trial , 2003, Hepatology.

[92]  D. Manzi,et al.  Adhesion-related colonic varices. , 1985, Journal of clinical gastroenterology.

[93]  Milton W. Taylor,et al.  A comparison of interferon-Con1 with natural recombinant interferons-alpha: antiviral, antiproliferative, and natural killer-inducing activities. , 1992, Journal of interferon research.

[94]  T. Berg,et al.  Prediction of treatment outcome in patients with chronic hepatitis C: significance of baseline parameters and viral dynamics during therapy. , 2002, Hepatology.

[95]  D. Dieterich,et al.  Daily Versus Thrice-Weekly Interferon Alfa-2b Plus Ribavirin for the Treatment of Chronic Hepatitis C in HIV-Infected Persons: A Multicenter Randomized Controlled Trial , 2004, Journal of acquired immune deficiency syndromes.

[96]  M. Manns,et al.  Mycophenolate mofetil in combination with recombinant interferon alfa-2a in interferon-nonresponder patients with chronic hepatitis C. , 2002, Journal of hepatology.

[97]  F. Carrat,et al.  Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. , 2004, JAMA.

[98]  M. Buti,et al.  Efficacy of 24 weeks treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C infected with genotype 1 and low pretreatment viremia. , 2006, Journal of hepatology.

[99]  Giorgio Palù,et al.  Short statement of the first European Consensus Conference on the treatment of chronic hepatitis B and C in HIV co-infected patients. , 2005, Journal of hepatology.

[100]  H. Wedemeyer,et al.  Antiviral efficacy of NS3‐serine protease inhibitor BILN‐2061 in patients with chronic genotype 2 and 3 hepatitis C , 2005, Hepatology.

[101]  M. Manns,et al.  Early virologic response to treatment with peginterferon alfa‐2b plus ribavirin in patients with chronic hepatitis C , 2003, Hepatology.

[102]  M. Shiffman,et al.  Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis. , 2000, The New England journal of medicine.

[103]  M. Manns,et al.  Early monotherapy with pegylated interferon alpha‐2b for acute hepatitis C infection: The HEP‐NET acute‐HCV‐II study , 2006, Hepatology.

[104]  M. Diago,et al.  311 Longer treatment duration with peginterferon alfa-2A (40KD) (Pegasys®) and ribavirin (Copegus®) in naive patients with chronic hepatitis C and detectable HCV RNA by week 4 of therapy: Preliminary results of the teravic-4 study , 2003 .

[105]  C. Trautwein,et al.  Treatment of acute hepatitis C with interferon alfa-2b. , 2001, The New England journal of medicine.

[106]  P. Volberding,et al.  Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. , 2004, The New England journal of medicine.

[107]  F. Fabrizi,et al.  Hepatitis C infection and the patient with end‐stage renal disease , 2002, Hepatology.

[108]  B. Murphy,et al.  751 The safety and efficacy of viramidine® plus pegylated interferon alpha-2B versus ribavirin plus pegylated interferon alpha-2B in therapy-naïve patients infected with HCV: Phase 3 results , 2006 .

[109]  William M. Lee,et al.  Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. , 2002, Gastroenterology.

[110]  S. Pedder.  Pegylation of Interferon Alfa: Structural and Pharmacokinetic Properties , 2003, Seminars in liver disease.

[111]  A K Manatunga,et al.  Paroxetine for the prevention of depression induced by high-dose interferon alfa. , 2001, The New England journal of medicine.