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Lege artis - Das Magazin zur ärztlichen Weiterbildung 2016; 6(02): 94-99
DOI: 10.1055/s-0041-106344
Fachwissen
Titelthema: Hepatitis
© Georg Thieme Verlag Stuttgart · New York

Hepatitis C – Diagnostik und Therapie

Maximilian David Schneider
,
Stefan Zeuzem
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Publication History

Publication Date:
11 May 2016 (online)

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Abstract

Die Therapie der chronischen Virushepatitis C wurde in den letzten Jahren durch die Zulassung direkt antiviral wirksamer Substanzen revolutioniert. Mussten die ErstgenerationsproteaseinhibitorenTelaprevir und Boceprevir noch mit dem nebenwirkungsreichen Interferon kombiniert werden, so besteht die moderne HCV-Therapie nun aus Kombinationen verschiedener direkt antiviraler Wirkstoffe und erhöht die Heilungsraten in fast allen Patientenkollektiven auf mehr als 90%. Gleichzeitig ist die Therapiedauer verkürzt und das Nebenwirkungsspektrum deutlich reduziert worden. Bei schwierig zu behandelnden Patienten kann die Hinzunahme von Ribavirin erforderlich sein. Der Beitrag gibt einen Überblick zur Hepatitis C Infektion mit einem Schwerpunkt auf den aktuellen Therapieempfehlungen.

Kernaussagen

  • Die Prävalenz der HCV-assoziierten Folgeerkrankungen wird in den kommenden Jahren noch steigen.

  • Für fast jeden Patienten ergeben sich hocheffektive und nebenwirkungsarme Therapieoptionen mit einer Dauer von zumeist 12 Wochen.

  • Zur Behandlung des in Deutschland dominierenden Genotyp 1 sind die Kombinationen Ledipasvir/ Sofosbuvir oder Paritaprevir/Ritonavir + Ombitasvir + Dasabuvir primär empfohlen.

  • Die Zulassung neuer direkt antiviraler Substanzen wird 2016 das Spektrum und damit die Effektivität der Therapie erweitern.

Schlüsselwörter:

Hepatitis CVirus - akute HCV-Infektion - chronische HCV-Infektion - Diagnostik - antivirale Therapie

Ergänzendes Material

 

  • Literatur

  • 1 World Health Organization (WHO). Fact sheet No 164, Hepatitis C. Im Internet: http://www.who.int/mediacentre/factsheets/fs164/en Stand 12.01.2016
  • 2 Moradpour D, Penin F, Rice CM. Replication of hepatitis C virus. Nat Rev Microbiol 2007; 5: 453-463
    CrossrefSearch in Google Scholar
  • 3 Lozano R, Naghavi M, Foreman K et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2095-2128
    CrossrefPubMedSearch in Google Scholar
  • 4 Razavi H, Waked I, Sarrazin C et al. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm. J Viral Hepat 2014; 21 (Suppl. 01) 34-59
    Search in Google Scholar
  • 5 Gower E, Estes C, Blach S et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 2014; 61: 45-57
    CrossrefPubMedSearch in Google Scholar
  • 6 Mauss S, Berg T, Rockstroh J et al. Hepatology 2015 – A Clinical Textbook. Im Internet: http://www.hepatologytextbook.com Stand 12.01.2015
  • 7 Friedrich-Rust M, Ong MF, Martens S et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology 2008; 134: 960-974
    CrossrefPubMedSearch in Google Scholar
  • 8 Nierhoff J, Chavez Ortiz AA, Herrmann E et al. The efficiency of acoustic radiation force impulse imaging for the staging of liver fibrosis: a meta-analysis. EurRadiol 2013; 23: 3040-3053
    Search in Google Scholar
  • 9 Maheshwari A, Ray S, Thuluvath PJ. Acute hepatitis C. Lancet 2008; 372: 321-332
    CrossrefSearch in Google Scholar
  • 10 Sarrazin C, Berg T, Ross RS et al. Update der S 3-Leitlinie Prophylaxe, Diagnostik und Therapie der Hepatitis-C-Virus(HCV)-Infektion, AWMF-Register-Nr.: 021 / 012. Z Gastroenterol 2010; 48: 289-351
    Search in Google Scholar
  • 11 Basu P, Shah N, John N et al. Sofosbuvir and Ledipasvir versus Sofosbuvir and Simeprevir combination therapy in the management of acute hepatitis C: A randomized open label prospective clinical pilot study. SLAM C study. Interim data. Hepatology 2015; 62
    Search in Google Scholar
  • 12 Sarrazin C, Berg T, Buggisch P et al. Aktuelle Empfehlung zur Therapie der chronischen Hepatitis C. Z Gastroenterol 2015; 53: 320-334
    Thieme ConnectPubMedSearch in Google Scholar
  • 13 EASL Recommendations on treatment of hepatitis C 2015. J Hepatol 2015; 63: 199-236
    CrossrefSearch in Google Scholar
  • 14 Afdhal N, Zeuzem S, Kwo P et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 2014; 370: 1889-1898
    CrossrefPubMedSearch in Google Scholar
  • 15 Afdhal N, Reddy KR, Nelson DR et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med 2014; 370: 1483-1493
    CrossrefPubMedSearch in Google Scholar
  • 16 Kowdley KV, Gordon SC, Reddy KR et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med 2014; 370: 1879-1888
    CrossrefSearch in Google Scholar
  • 17 Jacobson I, Kwo P, Kowdley K et al. Virologic response rates to all oral fixed-dose combination Ledipasvir/Sofosbuvir regimens are similar in patients with and without traditional negative predictive factors in phase 3 clinical trials. Hepatology 2014; 60
    Search in Google Scholar
  • 18 Bourliere M, Bronowicki JP, de Ledinghen V et al. Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: a randomised, double-blind, phase 2 trial (SIRIUS). Lancet Infect Dis 2015; 15: 397-404
    CrossrefSearch in Google Scholar
  • 19 Reddy KR, Bourliere M, Sulkowski M et al. Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection and compensated cirrhosis: An integrated safety and efficacy analysis. Hepatology 2015; 62: 79-86
    CrossrefSearch in Google Scholar
  • 20 Feld JJ, Kowdley KV, Coakley E et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014; 370: 1594-1603
    CrossrefPubMedSearch in Google Scholar
  • 21 Poordad F, Hezode C, Trinh R et al. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med 2014; 370: 1973-1982
    CrossrefPubMedSearch in Google Scholar
  • 22 Zeuzem S, Jacobson IM, Baykal T et al. Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med 2014; 370: 1604-1614
    CrossrefSearch in Google Scholar
  • 23 Feld JJ, Moreno C, Trinh R et al. Sustained virologic response of 100% in HCV genotype 1b patients with cirrhosis receiving ombitasvir/paritaprevir/r and Dasabuvir for 12 weeks. J Hepatol [Epub ahead of print] 2015;
    Search in Google Scholar
  • 24 Andreone P, Colombo MG, Enejosa JV et al. ABT-450, ritonavir, ombitasvir, and dasabuvirachieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection. Gastroenterology 2014; 147: 359-365
    CrossrefSearch in Google Scholar
  • 25 Ferenci P, Bernstein D, Lalezari J et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med 2014; 370: 1983-1992
    CrossrefPubMedSearch in Google Scholar
  • 26 Kwo P, Gitlin N, Nahass R et al. A Phase 3, randomised, open-label study to evaluate the efficacy and safety of 12 and 8 weeks of simeprevir (SMV) plus sofosbuvir (SOF) in treatment-naïve and -experienced patients with chronic HCV genotype 1 infection without cirrhosis: OPTIMIST-1. Journal of Hepatology 2015; 62
    Search in Google Scholar
  • 27 Lawitz E, Matusow G, DeJesus E et al. A Phase 3, open-label, single-arm study to evaluate the efficacy and safety of 12 weeks of simeprevir (SMV) plus sofosbuvir (SOF) in treatment-naïve or -experienced patients with chronic HCV genotype 1 infection and cirrhosis: OPTIMIST-2. Journal of Hepatology 2015; 62
    Search in Google Scholar
  • 28 Jensen D, O'Leary J, Pockros P et al. Safety and efficacy of Sofosbuvir-containing regimens for hepatitis C: real-world experience in a diverse, longitudinal observational cohort. Hepatology 2014; 58
    Search in Google Scholar
  • 29 Sulkowski MS, Gardiner DF, Rodriguez-Torres M et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med 2014; 370: 211-221
    CrossrefPubMedSearch in Google Scholar
  • 30 Poordad F, Schiff E, Vierling J et al. Daclatasvir, sofosbuvir, and ribavirin combination for HCV patients with advanced cirrhosis or post-transplant recurrence: phase 3 ALLY-1 study. Journal of Viral Hepatitis 2015; 22: 30-31
    Search in Google Scholar
  • 31 Jacobson IM, Gordon SC, Kowdley KV et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med 2013; 368: 1867-1877
    CrossrefPubMedSearch in Google Scholar
  • 32 Lawitz E, Mangia A, Wyles D et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013; 368: 1878-1887
    CrossrefPubMedSearch in Google Scholar
  • 33 Zeuzem S, Dusheiko GM, Salupere R et al. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med 2014; 370: 1993-2001
    CrossrefPubMedSearch in Google Scholar
  • 34 Zeuzem S, Dusheiko G, Salupere R et al. Sofosbuvir+Ribavirin for 12 or 24 weeks for patients with HCV genotype 2 or 3: the VALENCE trial. Hepatology 2013; 58
    Search in Google Scholar
  • 35 Nelson DR, Cooper JN, Lalezari JP et al. All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study. Hepatology 2015; 61: 1127-1135
    CrossrefSearch in Google Scholar
  • 36 Leroy V, Angus P, Bronowicki J et al. All-Oral Treatment with Daclatasvir plus sofosbuvir plus Ribavirin for 12 or 16 weeks in HCV genotype 3-infected patients with advanced fibrosis or cirrhosis: The ALLY-3+ phase 3 study. The Liver Meeting 2015. San Francisco, CA, 13–17 November 2015, Oral LB-3 2015 2015
    Search in Google Scholar
  • 37 Kohli A, Kapoor R, Sims Z et al. Ledipasvir and sofosbuvir for hepatitis C genotype 4: a proof-of-concept, single-centre, open-label phase 2a cohort study. Lancet Infectious Diseases 2015; 15: 1049-1054
    CrossrefSearch in Google Scholar
  • 38 Abergel A, Loustaud-Ratti V, Metivier S et al. Ledipasvir/sofosbuvir treatment results in high SVR rates in patients with chronic genotype 4 and 5 HCV infection. Journal of Hepatology 2015; 62
    Search in Google Scholar
  • 39 Hezode C, Asselah T, Reddy KR et al. Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial. Lancet 2015; 385: 2502-2509
    CrossrefSearch in Google Scholar
  • 40 Asselah TH, Hassanein T, Qaqish RB et al. Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir co-administered with Ribavirin in adults with genotype 4 chronic hepatitis C infection and cirrhosis (AGATE-I). Hepatology 2015; 62
    Search in Google Scholar
  • 41 Gane EJ, Hyland RH, An D et al. High efficacy of LDV/SOF Regimens for 12 weeks for patients with HCV genotype 3 or 6 infection. Hepatology 2014; 60
    Search in Google Scholar
  • 42 Foster GR, Afdhal N, Roberts SK et al. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med 2015;
    Search in Google Scholar
  • 43 Feld JJ, Jacobson IM, Hezode C et al. Sofosbuvir and Velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med 2015;
    Search in Google Scholar
  • 44 Kwo PY, Gane E, Peng CY et al. Efficacy and safety of Grazoprevir/Elbasvir +/- Ribavirin (RBV) for 12 or 16 weeks in patients with HCV G1, G4, or G6 infection who previously failed Peginterferon/RBV: C-EDGE treatment-experienced trial. Gastroenterology 2015; 148
    Search in Google Scholar
  • 45 Zeuzem S, Ghalib R, Reddy KR et al. Grazoprevir-Elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis C virus genotype 1, 4, or 6 infection: A randomized trial. Ann Intern Med 2015; 163: 1-13
    CrossrefSearch in Google Scholar
  • 46 Roth D, Nelson DR, Bruchfeld A et al. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet 2015; 386: 1537-1545
    CrossrefSearch in Google Scholar