The Course of Hepatitis C Infection and Response to Anti-viral Therapy in Patients with Thalassemia major and Hepatitis C Infection: A Longitudinal, Prospective Study

BACKGROUND: The course of hepatitis C infection (HCV) in patients with thalassemia has not been adequately studied, and management has not been optimized. The current prospective longitudinal study assessed the clinical course, outcome, progression, and management of recently acquired HCV in patients with transfusion-dependent thalassemia major versus acute HCV without thalassemia. METHODS: A well-characterized cohort of patients with thalassemia and recent HCV infection or recent HCV without thalassemia were enrolled and prospectively followed. The blood transfusion needs and chelating agents were determined. Liver functions tests, HCV-RNA, iron, and ferritin levels were measured. Patients with chronic HCV evolution received treatment for HCV. The fibrosis progression rate was determined in chronic HCV patients with or without thalassemia by paired liver biopsies or serial transient elastography (TE), or serum markers of liver fibrosis. Liver iron content (LIC) was assessed by R2 MRI. RESULTS: Self-limited acute HCV was observed in 17% of patients with acute HCV and thalassemia versus 35% of patients without thalassemia (P=0.031). The fibrosis progression rates were significantly higher in patients with chronic HCV and thalassemia compared to those with chronic HCV alone (1.14±0.48) and (0.35±0.14) (P<0.0001), respectively. A direct linear correlation was observed between the fibrosis progression rate and each of LIC (R=+0.67; P=0.01) and ferritin (R=0.77; P<0.01). In patients with chronic HCV and thalassemia, the sustained virologic response (SVR) to pegylated interferon-based therapy and direct antiviral agents (DAAS) were 33% and 82% respectively (P<0.0001), while in chronic HCV patients without thalassemia, the SVR rates to PEG-IFN/RBV and DAAs were 51% and 92% respectively. Five patients with concomitant HCV and thalassemia died during the study due to cardiac causes (n=3) and liver cancer (n=2). CONCLUSIONS: Patients with acute HCV and thalassemia have low rates of spontaneous resolution of HCV infection, and the majority develop chronic HCV. Direct-acting antiviral combinations are associated with high SVR rates and low adverse event in treatment naïve and experienced patients with chronic HCV and thalassemia. Liver fibrosis is accelerated in thalassemia patients with chronic HCV; therefore, early diagnosis, treatment with DAAs, adequate iron chelation, and non-invasive monitoring liver status are recommended to prevent cirrhosis and hepatocellular carcinoma.