Abstract
Over the last few years, the treatment of hepatitis C has evolved dramatically with the introduction of direct-acting antivirals to the regimen. Now with the anticipated approval of multiple all-oral regimens, the use of interferon is likely to disappear in many countries. Already approved are simeprevir and sofosbuvir, and in the coming months, several additional drugs and regimens are expected to become part of clinical practice. The American Association for the Study of Liver Diseases and the Infectious Disease Society of America are assisting health care professionals by providing a nonpharmaceutical sponsored web-based Guidance document for management issues ranging from testing to treatment of hepatitis C-infected individuals. The Guidance is expected to be constantly updated as new information becomes available. This article will review the currently published treatment recommendations in the Guidance.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Armstrong GL, Wasley A, Simard EP, Mcquillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2014;144:705–15.
Lavanchy D. The global burden of hepatitis C. Liver Int. 2009;29:74–81.
Hajarizadeh B, Grebely J, Dore GJ. Epidemiology and natural history of HCV infection. Nat Rev Gastroenterol Hepatol. 2013;10:553–62.
Poenisch M, Bartenschlager R. New insights into structure and replication of the hepatitis C virus and clinical implications. Semin Liver Dis. 2010;30:333–47.
Scheel TKH, Rice CM. Understanding the hepatitis C virus life cycle paves the way for highly effective therapies. Nat Med. 2013;19:837–49.
Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368:1878–87. The only phase 3 study of PEG IFN, RBV and SOF in patients, leading to its approval for treatment of HCV.
Jacobson IM, Dore GJ, Foster GR, Fried MW, Radu M, Rafalsky VV, et al. Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2014;6736:1–11.
Manns M, Marcellin P, Poordad F, de Araujo ESA, Buti M, Horsmans Y, et al. Simeprevir with pegylated interferon alfa 2a or 2b plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-2): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2014;6736:1–13.
Forns X, Lawitz E, Zeuzem S, Gane E, Bronowicki JP, Andreone P, et al. Simeprevir with peginterferon and ribavirin leads to high rates of SVR in patients with HCV genotype 1 who relapsed after previous therapy: a phase 3 trial. Gastroenterology. 2014;146:1669–1679.e3.
Lawitz E, Sulkowski MS, Ghalib R, Rodriguez-Torres M, Younossi ZM, Corregidor A, et al. Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study. Lancet. 2014;6736:1–10. Phase 2 to study leading to the clinical use of the first all oral regimen to treat genotype 1 HCV.
Lalezari JP, Nelson DR, Hyland RH, Lin M, Rossi SJ, Symonds WT, et al. Once daily sofosbuvir plus ribavirin for 12 and 24 weeks in treatment-naïve patients with HCV infection: the QUANTUM Study. J Hepatol. 2013;58:S346.
Osinusi A, Meissner EG, Lee Y-J, Bon D, Heytens L, Nelson A, et al. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA. 2013;310:804–11.
Gane EJ, Stedman CA, Hyland RH, Ding X, Svarovskaia E, Symonds WT, et al. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med. 2013;368:34–44.
Sulkowski MS, Rodriguez-Torres M, Lalezari J, Fessel WJ, Mounzer K, Shuhart MC, et al. Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection. JAMA. 2014;312:353–61. Important study treating HCV/HIV coinfected patients with an all oral DAA regimen.
Gane EJ, Stedman CA, Hyland RH, Pang PS, Ding X, Symonds WT, et al. All-oral sofosbuvir-based 12-week regimens for the treatment of chronic HCV infection: the ELECTRON Study. J Hepatol. 2013;58:S6–7.
Lawitz E, Poordad FF, Pang PS, Hyland RH, Ding X, Mo H, et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014;383:515–23.
Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;:140411220115009. Ledipasvir/sofosbuvir is anticipated to be approved in the near future, becoming one of the first all oral regimen to be approved by the FDA for genotype 1 HCV.
Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370:1483–93. The same regimen as above, with data in previously treated patients.
Kowdley KV, Gordon SC, Reddy KR, Rossaro L, Bernstein DE, Lawitz E, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370:1879–88.
Guedj J, Dahari H, Rong L, Sansone ND, Nettles RE, Cotler SJ, et al. Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life. Proc Natl Acad Sci U S A. 2013;110:3991–6.
Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson I, et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014;370:211–21.
Everson GT, Sims KD, Rodriguez-Torres M, Hézode C, Lawitz E, Bourlière M, et al. Efficacy of an interferon- and ribavirin-free regimen of daclatasvir, asunaprevir, and BMS-791325 in treatment-naive patients with HCV genotype 1 infection. Gastroenterology. 2014;146:420–9.
Manns M, Pol S, Jacobson I, Marcellin P, Gordon SC, Peng C-Y, et al. All-oral dual therapy with daclatasvir and asunaprevir in patients with HCV genotype 1b infection: phase 3 HALLMARK-DUAL Study results. J Hepatol. 2014;60:O166.
Kowdley KV, Lawitz E, Poordad F, Cohen DE, Nelson DR, Zeuzem S, et al. Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1. N Engl J Med. 2014;370:222–32.
Feld JJ, Kowdley KV, Coakley E, Sigal S, Nelson DR, Crawford D, et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370:1594–603. Another important regimen providing an all-oral treatment option for patients with genotype 1 HCV.
Zeuzem S, Jacobson IM, Baykal T, Marinho RT, Poordad F, Bourlière M, et al. Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370:1604–14. The same regimen mentioned above, in the treatment experienced population.
Poordad F, Hezode C, Trinh R, Kowdley KV, Zeuzem S, Agarwal K, et al. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med. 2014;370:1973–82. One of the anticipated all oral regimens to be approved in the near future, providing some of the highest SVR rates for genotype 1.
Ferenci P, Bernstein D, Lalezari J, Cohen D, Luo Y, Cooper C, et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014;370:1983–92.
Andreone P, Colombo MG, Enejosa J V, Koksal I, Ferenci P, Maieron A, et al. ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97 % and 100 % sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection. Gastroenterology. 2014.
Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, Sulkowski MS, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013;368:1867–77.
Zeuzem S, Dusheiko GM, Salupere R, Mangia A, Flisiak R, Hyland RH, et al. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med. 2014;370:1993–2001.
Lawitz E, Poordad F, Brainard D, Hyland RH, An D, Symonds WT, et al. Sofosbuvir in combination with PEGIFN and ribavirin for 12 weeks provides high SVR rates in HCV infected genotype 2 or 3 treatment experienced patients with and without compensated cirrhosis: results from the LONESTAR-2 study. In: 64th annual meeting of the American Association for the Study of Liver Diseases. 2013. p. LB4.
Esteban R, Nyberg L, Lalezari J, Ni L, Doehle B, Kanwar B, et al. Successful retreatment with sofosbuvir-containing regimens for HCV genotype 2 or 3 infected patients who failed prior sofosbuvir plus ribavirin therapy. J Hepatol. 2014;60:S4–5.
Everson GT, Tran TT, Towner WJ, Davis MN, Wyles D, Nahass R, et al. Safety and efficacy of treatment with the interferon-free, ribavirin-free combination of sofosbuvir + GS-5816 for 12 weeks in treatment naive patients with genotype 1–6 HCV infection. J Hepatol. 2014;60:S46.
Kanwal F, Kramer JR, Ilyas J, Duan Z, El-Serag HB. HCV genotype 3 is associated with an increased risk of cirrhosis and hepatocellular cancer in a national sample of U.S. Veterans with HCV. Hepatol. 2014;60:98–105.
Ruane PJ, Ain D, Meshrekey R, Riad J, Soliman M, Mikhail S, et al. Sofosbuvir plus ribavirin, an interferon-free regimen, in the treatment of treatment-naive and treatment-experienced patients with chronic genotype 4 HCV infection. J Hepatol. 2014;60:S503–4.
Moreno C, Berg T, Tanwandee T, Thongsawat S, Van Vlierberghe H, Zeuzem S, et al. Antiviral activity of TMC435 monotherapy in patients infected with HCV genotypes 2–6: TMC435-C202, a phase IIa, open-label study. J Hepatol. 2012;56:1247–53.
Moreno C, Hezode C, Marcellin P, Bourgeois S, Francque S, Samuel D, et al. Once-daily simeprevir (TMC435) with peginterferon/ribavirin in treatment-naive or treatment-experienced chronic Hcv genotype 4-infected patients: final results of a phase Iii trial. J Hepatol. 2014;60:S535.
Hezode C, Marcellin P, Pol S, Hassanein T, Fleischer-Stepniewska K, Baykal T, et al. Results from the phase 2 pearl-I study: interferon-free regimens of Abt-450/R + Abt-267 with or without ribavirin in patients with HCV genotype 4 infection. J Hepatol. 2014;60:S24.
Rodriguez-Torres M, Rodriguez-Orengo J, Gaggar A, Shen G, Symonds W, McHutchison J, et al. Sofosbuvir and peginterferon alfa-2a/ribavirin for treatment-naïve genotype 1–4 HCV-infected patients who are coinfected with HIV. In: 53rd ICAAC 2013. 2013.
Curry MP, Forns X, Chung RT, Terrault N, Brown RS, Fenkel JM, et al. Pretransplant sofosbuvir and ribavirin to prevent recurrence of HCV infection after liver transplantation. Hepatology. 2013;58:314–315A.
Gane EJ, Hyland RH, An D, Pang PS, Symonds WT, Mchutchison JG, et al. Sofosbuvir/ledipasvir fixed dose combination is safe and effective in difficult-to-treat populations including genotype-3 patients, decompensated genotype-1 patients, and genotype-1 patients with prior sofosbuvir treatment experience. J Hepatol. 2014;60:S3–4.
Forns X, Prieto M, Charlton M, McHutchison JG, Symonds WT, Denning J, et al. Sofosbuvir compassionate use program for patients with severe recurrent hepatitis C including fibrosing cholestatic hepatitis following liver transplantation. J Hepatol. 2014;60:S26.
Kwo P, Mantry P, Coakley E, Te H, Vargas H, Brown R, et al. Results of the phase 2 study M12-999: interferon-free regimen of Abt-450/R/Abt-267 + Abt-333 + ribavirin in liver transplant recipients with recurrent Hcv genotype 1 infection. J Hepatol. 2014;60:S47.
Compliance with Ethics Guidelines
Conflict of Interest
Dr. Ira Jacobson’s disclosures:
Grant/research support: Abbvie, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Novartis, Genentech, Merck, Janssen, Vertex
Consultant/advisor: Abbvie, Achillion, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Idenix, Genentech, Merck, Janssen, Vertex
AbbVie Speakers’ bureau: Bristol Myers Squibb, Gilead, Genentech, Vertex, Janssen
Dr. Kumar’s disclosures:
Grant/research support: Abbvie, Gilead, Bristol Myers Squibb, Merck, Janssen
Consultant/advisor: Gilead
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by the authors.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kumar, S., Jacobson, I. Optimal Management of the Hepatitis C Patient: Review of the AASLD/IDSA Guidelines. Curr Hepatology Rep 13, 314–320 (2014). https://doi.org/10.1007/s11901-014-0246-2
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11901-014-0246-2