Faisal M. Sanai, Adnan AlZanbagi, Mohammed A. Babatin, Abdullah S. Alghamdi, Hamdan Alghamdi, Khalid A. Alswat, Abdulrahman A. Aljumah, Abduljaleel M. Al Alwan, Ayman Abdo, Waleed K. Al-Hamoudi, Abdullah Alaseeri, Yaser Dahlan, Ashwaq Alsahafi, Hammad S. Alothmani, Haziz Albiladi, Ibrahim H. Altraif
Department of Medicine, Gastroenterology Unit, King Abdulaziz Medical City, Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Department of Medicine, Gastroenterology Unit, King Abdullah Medical City, Makkah, Department of Hepatobiliary Science and Liver Transplantation, King Abdulaziz Medical City, Department of Medicine, Liver Disease Research Center, Gastroenterology Unit, College of Medicine, King Saud University, Department of Infectious Disease, King Fahd Medical City, Riyadh, Kingdom of Saudi Arabia
E-mail: sanaifa@ngha.med.sa
Background: Limited clinical trial data has shown high efficacy of co-formulated ledipasvir/sofosbuvir (LDV/SOF) in the treatment of patients infected with hepatitis C virus (HCV) genotype (GT)-4 infected patients, although the data is limited in cirrhotic patients. This study assessed real-world safety and efficacy of co-formulated ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin (RBV) in GT4 infected patients with compensated and decompensated cirrhosis.
Methods: In this ongoing, observational cohort, we included HCV GT4 treatment naïve and- experienced patients with (n = 40) and without (n = 118) decompensated cirrhosis for a 12-24 week treatment regimen with LDV/SOF. RBV (55.7% of patients) was dosed by physician discretion between 600–1200 mg daily. Patients with prior DAA failure were excluded from the analysis. Compensated cirrhosis (F4, Metavir) was ascertained by Fibroscan. Decompensated cirrhosis (Child's - Pugh score ≥7) was ascertained by established clinical, biochemical and radiological criteria. The primary efficacy endpoint was SVR12 and drug discontinuation and/or occurrence of grade 3/4 adverse events.
Results: A total of 158 adult patients with a mean age of 59.0 ± 29.7 years, and HCV RNA 5.8 ± 0.8 IU/mL were enrolled, 94 (59.5%) were female, and 73 (46.2%) were treatment-experienced to pegylated interferon ± RBV. All patients have completed ≥4 weeks on therapy, with HCV RNA undetectable (<15 IU/mL) in 84/158 (53.1%) patients, and all 129 had reached end-of-therapy with undetectable/below range HCV RNA. No virologic breakthroughs were observed in any of the patients. Overall 81/87 (93.1%) patients who had completed 12 weeks of post treatment follow up achieved SVR12 (compensated cirrhosis, n = 57 [SVR12 91.9%], decompensated cirrhosis, n = 24 [SVR12 96.0%]). Of the 6 patients who failed therapy (all relapsed), one had decompensated cirrhosis while the other 5 had compensated cirrhosis, including 5 who were treatment naïve and 1 being treatment experienced. Four of the 6 patients who failed therapy received concomitant RBV. Adverse events were grade 1 or 2 and there were no drug discontinuations related to side effects. Two patients with decompensated (1 Child's B and 1 Child's C) cirrhosis died from underlying disease progression while on therapy.
Conclusion: The interim analysis of this cohort shows that LDV/SOF with or without RBV is highly effective with a favorable safety profile in HCV GT4 patients with underlying cirrhosis. SVR12 rates were high in all patient categories regardless of the presence of decompensated cirrhosis or prior treatment experience. Treatment was generally well-tolerated with few side effects.