Ledipasvir and sofosbuvir with or without ribavirin is an effective and tolerable treatment in patients with hepatitis C virus (HCV)-infection with advanced liver disease, according to a multicenter study published in the Journal of Viral Hepatitis.1
Although HCV cure rates with direct-acting antivirals (DAAs) quickly exceed 90%,2-9 data regarding the risk for hepatocellular carcinoma (HCC) in HCV-infected patients with cirrhosis treated with DAA therapy is controversial.10-20 Therefore, researchers evaluated the efficacy and tolerability of ledipasvir and sofosbuvir with or without ribavirin combination treatment in 200 patients with chronic hepatitis C with advanced liver disease to determine the association of ledipasvir and sofosbuvir treatment with a new occurrence and/or recurrence of HCC during and after antiviral treatment.1
The recommended treatment duration was 24 weeks with a median follow-up period of 22 months. Eighty-four percent of patients were infected with genotype 1b, and 24% had received a liver transplantation before treatment.
The researchers found that the sustained virologic response at 12 weeks (SVR12) was 86.0%, and that the SVR12 was similar in patients with Child-Pugh class A, B, and C disease and transplant recipients. In addition, ledipasvir and sofosbuvir treatment was generally well tolerated; only one patient developed newly diagnosed HCC. Seventeen of 35 patients who had a history of previous HCC developed HCC recurrence during treatment or by a median follow-up of 6 months after treatment. HCC recurrence was less common in patients who received curative treatment for HCC compared with those who received noncurative treatment (P =.007).
“In conclusion, a combination treatment of [ledipasvir and sofosbuvir] with or without [ribavirin] was an effective and tolerable treatment in [chronic hepatitis C] patients with advanced liver disease before and after [liver transplantation]” stated the study authors.1 They added that, “HCV eradication is associated with improvements in liver function and a reduction in the risk of developing newly diagnosed HCC.”
- Idilman R, Demir M, Aladag M, et al; Early Access Program (EAP) Study Group. Low recurrence rate of hepatocellular carcinoma following ledipasvir and sofosbuvir treatment in a real-world chronic hepatitis C patients cohort [published online February 11, 2019]. J Viral Hepat. doi: 10.1111/jvh.13075
- Kohli A, Shaffer A, Sherman A, Kottilil S. Treatment of hepatitis C: a systematic review. JAMA. 2014;312(6):631-640.
- AASLD/IDSA HCV Guidance Panel. Hepatitis C guidance: AASLD/IDSA recommendations for testing, managing and treating adults infected with hepatitis C. Hepatology. 2015;62(3):932-954.
- European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2018. J Hepatol. 2018;69(2):461-511.
- Afdhal N, Zeuzem S, Kwo P, et al; ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(20):1889-1898.
- Charlton M, Everson GT, Flamm SL, et al; SOLAR-1 Investigators. Ledipasvir and sofosbuvir plus ribavirin for treatment of HCV infection in patients with advanced liver disease. Gastroenterology. 2015;149(3):649-659.
- Falade-Nwulia O, Suarez-Cuervo C, Nelson DR, Fried MW, Segal JB, Sulkowski MS. Oral direct-acting agent therapy for hepatitis C virus infection: a systematic review. Ann Intern Med. 2017;166(9):637-648.
- Kwo PY, Mantry PS, Coakley E, et al. An interferon-free antiviral regimen for HCV after liver transplantation. N Engl J Med. 2014;371(25):2375-2382.
- Manns M, Samuel D, Gane EJ, et al; SOLAR-2 Investigators. Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicenter, open-label, randomized, phase 2 trial. Lancet Infect Dis. 2016;16(6):685-697.
- Morgan RL, Baack B, Smith BD, Yartel A, Pitasi M, Falck-Ytter Y. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med. 2013;158(5 Pt 1):329-337.
- van der Meer AJ, Veldt BJ, Feld JJ, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012;308(24):2584-2593.
- Cramp ME, Rosenberg WM, Ryder SD, Blach S, Parkes J. Modeling the impact of improving screening and treatment of chronic hepatitis C virus infection on future hepatocellular carcinoma rates and liver-related mortality. BMC Gastroenterol. 2014;14:137.
- Li DK, Ren Y, Fierer DS, et al. The short-term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct-acting antivirals: an ERCHIVES Study. Hepatology. 2018;67(6):2244-2253.
- Calvaruso V, Cabibbo G, Cacciola I, et al; Rete Sicilia Selezione Terapia-HCV (RESIST-HCV). Incidence of hepatocellular carcinoma in patients with HCV-associated cirrhosis treated with direct-acting antiviral agents. Gastroentrology. 2018;155(2):411-421.
- Reig M, Marino Z, Perello C, et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol. 2016;65(4):719-726.
- Conti F, Buonfiglioli F, Scuteri A, et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol. 2016;65(4):727-733.
- Kozbial K, Moser S, Schwarzer R, et al. Unexpected high incidence of hepatocellular carcinoma in cirrhotic patients with sustained virologic response following interferon-free direct-acting antiviral treatment. J Hepatol. 2016;65(4):856-858.
- Zeng Q-L, Li, ZQ, Liang HX, et al. Unexpected high incidence of hepatocellular carcinoma in patients with hepatitis C in the era of DAAs: too alarming? J Hepatol. 2016;65(5):1068-1069.
- Ravi S, Axley P, Jones D, et al. Unusually high rates of hepatocellular carcinoma after treatment with direct-acting antiviral therapy for hepatitis C related cirrhosis. Gastroenterology. 2017;152(4):911-912.
- Alberti A, Piovesan S. Increased incidence of liver cancer after successful DAA treatment of chronic hepatitis C: fact or fiction?Liver Int. 2017;37(6):802-808.