Skip to main content
    • Aa
    • Aa

Effectiveness and cost-effectiveness of initial combination therapy with interferon/peginterferon plus ribavirin in patients with chronic hepatitis C in Germany: A health technology assessment commissioned by the German Federal Ministry of Health and Social Security


Objectives: The purpose of this health technology assessment (HTA), commissioned by the German Federal Ministry of Health and Social Security, was to systematically review the evidence for the effectiveness and cost-effectiveness of antiviral treatment (AVT) with interferon (INF) or peginterferon (PegIFN) in combination with ribavirin (RBV) in treatment-naïve patients with chronic hepatitis C (CHC) and to apply these data in the context of the German health-care system.

Methods: We performed a systematic literature search on effectiveness and cost-effectiveness of AVT and summarized results using meta-analysis and evidence tables. We applied the German Hepatitis C Model (GEHMO), a decision-analytic Markov model, to determine long-term clinical effectiveness, costs, and incremental cost-effectiveness ratios (ICER) of the examined treatment strategies. Model parameters were derived from German databases, published international randomized clinical trials (RCT), and a Cochrane Review.

Results: Overall, nine RCTs, two HTA reports, one Cochrane review, two meta-analyses, and seven economic evaluations met the inclusion criteria. These studies indicate that PegIFN+RBV achieved the highest sustained virological response rates (SVR) (54–61 percent), followed by IFN+RBV (38–54 percent) and IFN monotherapy (11–21 percent). Based on our meta-analysis, PegIFN+RBV reduced cases without SVR by 17 percent compared with INF+RBV. International cost-effectiveness studies indicate that INF+RBV is cost-effective when compared with INF monotherapy. For PegIFN+RBV, our decision analysis yielded an ICER of €9,800 per quality-adjusted life-year gained.

Conclusions: This HTA suggests that initial combination therapy prolongs life, improves quality of life, and is cost-effective in patients with CHC. Peginterferon plus ribavirin is the most effective and efficient treatment among the examined options. However, because not all chronic hepatitis C patients will develop progressive liver disease, a thorough assessment of the eligibility and appropriateness of treatment with combination therapy must be performed in each individual patient.

Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

AlterH, SeeffL. 2000Recovery, persistence, and sequelae in hepatitis C virus infection: A perspective on long-term outcome. Semin Liver Dis. 20: 1735.

AlterM, Kruskon-MoranD, NainanO, et al. 1999The prevalence of hepatitis C virus infection in the United States 1988 through 1994. N Engl J Med. 341: 556562.

BaltussenR, AmentA, LeidlR. 1996Making cost assessments based on RCTs more useful to decision-makers. Health Policy. 37: 163183.

BarbaroG, DiLorenzo G, SoldiniM, et al. 2000Evaluation of long-term efficacy of interferon alpha-2b and ribavirin in combination in naive patients with chronic hepatitis C: An Italian multicenter experience. Ribavirin-Interferon in Chronic Hepatitis Italian Group Investigators. J Hepatol. 33: 448455.

BennettWG, InoueY, BeckJR, et al. 1997Estimates of the cost-effectiveness of a single course of interferon-alpha 2b in patients with histologically mild chronic hepatitis C. Ann Intern Med. 127: 855865.

ButiM, CasadoM, FosbrookL, WongJB, EstebanR. Cost-effectiveness of combination therapy for naive patients with chronic hepatitis CJ Hepatol. 2000; 33: 651658.

DesmetVJ, GerberM, HoofnagleJH, MannsM, ScheuerPJ. 1994Classification of chronic hepatitis: Diagnosis, grading, and staging. Hepatology. 19: 15131520.

DoreG, FreemanA, LawM, KaldorJM. 2002Is severe liver disease a common outcome for people with chronic hepatitis C? J Gastroenterol Hepatol. 17: 423430.

DrummondM, BloomBS, CarrinG, et al. 1992Issues in the cross-national assessment of health technology. Int J Technol Assess Health Care. 8: 671682.

FreemanA, DoreG, LawM, et al. 2001Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology. 34: 809816.

FriedM, ShiffmanM, ReddyR, et al. 2002Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 347: 975982.

HaycoxA, DuboisD, ButterworthM. 1998Customising an international disease management model to the needs of individual countries. Pharmacoeconomics14(Suppl 2): 3956.

HopfU, MollerB, KutherD, et al. 1990Long-term follow-up of posttransfusion and sporadic chronic hepatitis non-A, non-B and frequency of circulating antibodies to hepatitis C virus (HCV). J Hepatol. 10: 6976.

KjaergardL, KrogsgaardK, GluudC. 2001Interferon alfa with or without ribavirin for chronic hepatitis C: Systematic review of randomised trials. BMJ. 323: 11511155.

KnodellRG, IshakKG, BlackWC, et al. 1981Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology. 1: 431435.

KoretzR, AbbeyH, ColemanE, GitnickG. 1993Non-A, non-B post-transfusion hepatitis. Looking back in the second decade. Ann Intern Med. 119: 110115.

LaiMY, KaoJH, YangPM, et al. 1996Long-term efficacy of ribavirin plus interferon alfa in the treatment of chronic hepatitis C. Gastroenterology. 111: 13071312.

LiangTJ, RehermannB, SeeffLB, HoofnagleJH. 2000Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann Intern Med. 132: 296305.

MangiaA, VillaniMR, MinervaN, et al. 2001Efficacy of 5 MU of interferon in combination with ribavirin for naive patients with chronic hepatitis C virus: A randomized controlled trial. J. Hepatol. 34: 441446.

MannsM, McHutchisonJ, GordonS, et al. 2001Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: A randomised trial. Lancet. 358: 958965.

MarcellinP, AsselahT, BoyerN. 2002Fibrosis and disease progression in hepatitis C. Hepatology. 36(Suppl): S47S56.

MattssonL. 1993Outcome of acute symptomatic non-A, non-B hepatitis: A 13-year follow-up study of hepatitis C virus markers. Liver. 13: 274278.

McHutchisonJ, GordonS, SchiffE, et al. 1998Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med. 339: 14851492.

PoynardT, MarcellinP, LeeS, et al. 1998Randomised 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). Lancet. 352: 14261432.

ReichardO, NorkransG, FrydenA, et al. 1998Randomised, double-blind, placebo-controlled trial of interferon alpha-2b with and without ribavirin for chronic hepatitis C. The Swedish Study Group. Lancet. 351: 8387.

SagmeisterM, WongJ, MullhauptB, RennerE. 2001A pragmatic and cost-effective strategy of a combination therapy of interferon alpha-2b and ribavirin for the treatment of chronic hepatitis C. Eur J Gastroenterol Hepatol. 13: 483438.

SchreierE, HöhneM. 2001Hepatitis C—Epidemiologie und Prävention. Bundesgesundheitsblatt. 44: 554561.

SennfältK, ReichardO, HultkrantzR, WongJ, JonssonD. 2001Cost-effectiveness of interferon alfa-2b with and without ribavirin as therapy for chronic hepatitis C in Sweden. Scand J Gastroenterol. 36: 870876.

SiebertU, GreinerW, Ravens-SiebererU, et al. 2003Preference-based quality-of-life values in patients with chronic hepatitis C: Results from the German hepatitis C quality-of-life study. Abstract. J Hepatol. 38(Suppl 2): 596.

SteinK, RosenbergW, WongJ. 2002Cost effectiveness of combination therapy for hepatitis C: A decision analytic model. Gut. 50: 253258.

TremoladaF, CasarinC, AlbertiA, et al. 1992Long-term follow-up of non-A, non-B (type C) post-transfusion hepatitis. J Hepatol. 16: 273281.

WeinsteinMC. 1999High-priced technology can be good value for money. Ann Intern Med. 130: 857858.

WillkeRJ, GlickHA, PolskyD, SchulmanK. 1998Estimating country-specific cost-effectiveness from multinational clinical trials. Health Econ. 7: 481493.

WongJ, PoynardT, LingM, AlbrechtJ, PaukerS. 2000Cost-effectiveness of 24 or 48 weeks of interferon alpha-2b alone or with ribavirin as initial treatment of chronic hepatitis C. International Hepatitis Interventional Therapy Group. Am J Gastroenterol. 95: 15241530.

WongJB, SonnenbergFA, SalemDN, PaukerSG. 1990Myocardial revascularization for chronic stable angina. Analysis of the role of percutaneous transluminal coronary angioplasty based on data available in 1989. Ann Intern Med. 113: 852871.

YounossiZ, SingerM, McHutchisonJ, ShermockK. 1999Cost effectiveness of interferon alpha2b combined with ribavirin for the treatment of chronic hepatitis C. Hepatology. 30: 13181324.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

International Journal of Technology Assessment in Health Care
  • ISSN: 0266-4623
  • EISSN: 1471-6348
  • URL: /core/journals/international-journal-of-technology-assessment-in-health-care
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 1
Total number of PDF views: 14 *
Loading metrics...

Abstract views

Total abstract views: 95 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 25th May 2017. This data will be updated every 24 hours.