Sofosbuvir/velpatasvir for chronic hepatitis C infection in patients with transfusion‐dependent thalassemia
Authors: Ala I. Sharara, Luma Basma O. Rustom, Majd Marrache, Hussein H. Rimmani, Halim Bou Daher, Suzanne Koussa, Ali Taher
Journal: American Journal of Hematology (2018)

The life-long need for blood transfusions in thalassemia patients makes them vulnerable to transfusion-transmitted hepatitis C virus (HCV). The prevalence of hepatitis C in thalassemia patients is variable depending on local disease prevalence but can be as high as 85.4%.1 Traditionally, the main impediment to the treatment of HCV infection in transfusion-dependent thalassemia has been the risk of ribavirin-associated hemolysis.2 Although the natural history of HCV infection in these patients is unclear, morbidity and mortality is thought to be increased. Liver disease is more severe in HCV-infected patients and may be compounded by hepatic siderosis.3 Another concern has been the effect of iron overload on response rates and the potential risk of drug-drug interactions with various iron chelators. The introduction of highly effective and safe direct-acting antivirals (DAAs) has largely addressed the needs of other special groups within the HCV-infected population including those with chronic kidney disease, decompensated cirrhosis, HIV coinfection, PWIDs, and organ transplantation recipients. Emerging evidence has also confirmed the efficacy of DAAs in patients with inherited blood disorders, including thalassemia.4, 5 Sofosbuvir/velpatasvir (SOF/VEL) is the first once daily single fixed-dose pangenotypic regimen approved for treatment of HCV infection. Registration trials have shown that SOF/VEL for 12 weeks leads to an overall SVR of 99% independent of presence of cirrhosis or prior treatment-experience with a safety profile similar to placebo. Herein, we report the results of an open-label prospective observational trial conducted at the American University of Beirut Medical Center (clinicaltrials.gov identifier: NCT03032666). Adult transfusion-dependent thalassemia patients with known HCV infection were referred for evaluation from the Lebanese Chronic Care Center. After informed consent, patients had baseline blood tests including HCV RNA and genotype, CBC, creatinine, liver function tests (LFTS) and serum ferritin, as well as abdominal ultrasonography, and liver elastography (Fibroscan, Echosens, Paris, France). Viremic patients received SOF/VEL (400 mg/100 mg daily, Gilead Sciences International Ltd. Cambridge, United Kingdom) for a total period of 12 weeks. Clinic follow-up was scheduled at weeks 4, and 8 (with dispensing of medications), 12, and 24 and included compliance assessment by pill count, monitoring of adverse events, transfusion requirements, and blood tests. SVR12 was measured 12 weeks after the end of the treatment using quantitative real-time PCR (Cobas AmpliPrep/Cobas TaqMan48). The Institutional Review Board (IRB) approved the study. All visits, tests, and medications were provided free of charge. Twelve transfusion-dependent thalassemia patients with positive HCV antibodies were evaluated. Seven patients were HCV-RNA positive (5 males; mean age 28.9 ± 9.0 years) and all had genotype 4. Four patients (57.1%) were treatment-experienced (peginterferon and ribavirin). All patients were on chronic chelation therapy and 3 had Liver Iron Concentration (LIC) tests on T2*MRI (mean LIC of 10.82 ± 6.29 μmol Fe/g). Mean baseline ferritin was 2049 ± 669.63 ng/mL (range 1111-2817). Four patients (57.1%) had significant liver fibrosis (≥F2) at baseline and one patient had cirrhosis. All patients completed the 24-week study and SVR12 was confirmed in all seven (100%). Mean baseline hemoglobin was 8.8 ± 2.1 g/dL and became 9.7 ± 2.4 g/dL in week 4, 8.3 ± 2.0 g/dL in week 8, 8.9 ± 1.4 g/dL in week 12 and 8.5 ± 2.0 g/dL in week 24 (P = .7). Transfusion requirements did not change significantly between baseline and week 12 (1.1 ± 0.7 vs 1.7 ± 0.7, P = .052). There was significant change in means of ALT levels between baseline and week 24 (52.9 ± 28.6 vs 28.0 ± 21.5, P = .006) and in AST levels (57.7 ± 36.8 vs 38.1 ± 23.2, P = .018). No adverse events were reported during the study period. Adherence was excellent with a mean of 96.1% (range 95.2%-100%) of pills consumed over the 12-week treatment. The results of this study add to the existing new evidence of the efficacy of DAAs in patients with inherited blood disorders including thalassemia. Table 1 summarizes the studies treating HCV in thalassemia patients using DAAs.1, 4-8 Importantly, the efficacy of these DAA regimens is not impacted by iron overload and is further supported by the high safety profile and lack of evidence of any significant drug–drug interaction. Early treatment of chronic HCV in patients with blood disorders should be considered in attempt to reduce liver-related morbidity and mortality.