COMMENTARY

A Future Without Hepatitis C?

The Liver Meeting 2014: American Association for the Study of Liver Diseases (AASLD)

William F. Balistreri, MD

Disclosures

December 16, 2014

In This Article

Ledipasvir/Sofosbuvir (With or Without Ribavirin)

Patients With Compensated Cirrhosis

Bourlière and colleagues[1] reported results of phase 2 and 3 trials with the single-tablet combination of LDV/SOF with or without ribavirin (RBV). In studies involving 514 patients with compensated cirrhosis, safety and efficacy data were similar to those from patients without cirrhosis. Overall, 95% of genotype 1 patients achieved SVR at 12 weeks (SVR12). Adverse events (including anemia) were more frequent in patients who received RBV. This team also assessed the safety and efficacy of LDV/SOF in 155 genotype 1 patients with compensated cirrhosis who did not respond to triple therapy (protease inhibitor/peg-IFN/RBV).[2] In this subgroup, LDV/SOF with RBV for 12 weeks and LDV/SOF for 24 weeks resulted in similarly high SVR rates and were well tolerated.

Patients With Decompensated Cirrhosis

The patient population with end-stage liver disease nearing liver transplantation has not been investigated in the context of carefully controlled clinical trials. In patients with HCV-related decompensated cirrhosis, therapeutic options are limited owing to the lack of proven efficacy and the potential for severe adverse events. Flamm and colleagues[3] now report that LDV/SOF coadministered with RBV in genotype 1 and 4 patients with cirrhosis was well tolerated and resulted in high SVR rates (87-89%).

Re-treatment of Patients Who Did Not Respond to Sofosbuvir-Based Regimens

Wyles and colleagues[4] reported 100% efficacy at 12 weeks following treatment with LDV/SOF/RBV in 50 genotype 1 patients (15 with cirrhosis) who had participated in previous sofosbuvir-based phase 2/3 studies and failed to achieve SVR12. The regimen was fairly well tolerated.

Black Patients

SVR rates among black persons with genotype 1 have historically been lower than those reported for other races or ethnicities. Jeffers and colleagues[5] retrospectively evaluated the safety and efficacy of LDV/SOF in a clinical cohort that included more than 300 black persons. Overall, 95% of black and 97% of non-black patients achieved SVR12, including patients with compensated cirrhosis and those who had previously not responded to triple therapy with a protease inhibitor/peg-IFN/RBV regimen. The addition of RBV did not increase SVR rates but did lead to higher rates of adverse events.

Genotype 4 Chronic HCV Infection

In genotype 1 patients, studies of direct-acting antivirals have shown high cure rates with high tolerability, but this has not been reported in patients with genotype 4, the most common subtype in the Middle East and Africa. Kapoor and colleagues[6] evaluated the safety, efficacy, and tolerability of 12-week combination therapy with sofosbuvir and ledipasvir in treatment-naive and -experienced genotype 4 patients. SOF/LDV for 12 weeks was well tolerated and resulted in high viral suppression rates regardless of previous treatment status and underlying liver fibrosis.

Genotype 1 in Patients Coinfected With HIV

HIV/HCV coinfected patients have historically responded poorly to IFN-based HCV treatment, and liver disease is now a leading cause of death in these patients. Regimens that can be safely coadministered with antiretroviral therapy (ART) are needed.

Rockstroh and colleagues[7] achieved high SVR12 rates with an IFN-free, all-oral regimen of SOF with RBV in individuals coinfected with HIV and HCV genotype 1-4. This pooled analysis from two phase 3 studies further demonstrated that SOF/RBV treatment was well tolerated and could be safely coadministered with multiple ART regimens.

Townsend and colleagues[8] also confirmed the safety and efficacy of the SOF/LDV combination in 50 HIV/HCV coinfected patients. In ART-naive patients the SVR12 was 100%, and in ART recipients it was 97%. In this study, SOF/LDV was well tolerated; no serious adverse events or discontinuations related to these study drugs occurred.

These two studies indicate that concurrent HIV infection does not reduce SVR12 rates with SOF-based regimens. Therefore, HIV infection may no longer be a major determinant of treatment outcome.

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