Hepatitis delta genotype 5 is associated with favourable disease outcome and better response to treatment compared to genotype 1

Abstract Background and aims Co-infection with HDV causes rapid progression to liver cirrhosis and hepatic decompensation. Factors that are associated with disease progression are poorly understood. In this study we aim to identify risk factors associated with disease progression and better characterise clinical differences and treatment response between HDV genotype 1 and 5. Methods In this retrospective study, all patients under our care between 2005 and 2016 with HBV/ HDV co-infection (HBsAg+, anti-HDV antibodies positive) were analysed. Patients were excluded if follow-up was less than 6 months, if they had HCV and/or HIV co-infection or an acute HDV infection. Demographic data, stage of liver disease, development of liver complications and treatment response were recorded. Results One-hundred seven patients (mean age 36.0yr, 57% male) were followed for a median period of 4.4yr (range 0.6-28.1yr). 64% was of African and 17% of European origin with 28% of patients being cirrhotic at first visit. 43% patients had actively replicating HDV virus (anti-HDV-IgG+, anti-HDV-IgM+ or HDV RNA+) and 57% of patients were HDV exposed (anti-HDV-IgG+, HDV RNA-). Actively replicating HDV patients more often developed liver complications compared to patients with exposed HDV (p=0.002), but no differences in baseline characteristics were observed. HDV patients with genotype 5 less often developed cirrhosis or hepatic decompensation compared to patients with genotype 1. Twenty-four patients were treated with peg-IFN and post-treatment response was significantly better in patients infected with genotype 5 (10% GT1 vs 64% GT5, p=0.013). Conclusion Patients infected with hepatitis delta genotype 5 appear to have a better prognosis with fewer episodes of hepatic decompensation and better response to peg-IFN treatment compared to HDV patients with genotype 1.