Association between hepatitis delta virus with liver morbidity and mortality: A systematic literature review and meta-analysis

Background & Aims: Studies have suggested that patients with chronic hepatitis B (CHB), either co-, or super infected, have more aggressive liver disease progression than those with the hepatitis delta virus (HDV). This systematic literature review and meta-analysis examined whether HDV RNA status is associated with increased risk of advanced liver disease events (ALDEs), in patients who are HBsAg and HDV antibody positive.Approach & Results: A total of 12 publications were included. Relative rates of progression to ALDE for HDV RNA+/detectable versus HDV RNA-/undetectable were extracted for analysis. Reported odds (OR) and hazard ratios (HRs) with 95% confidence intervals (CI) were pooled using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. Presence of HDV RNA+ was associated with an increased risk of any ALDE (random effect [95% CI]: risk ratio (RR): 1.48 [0.93, 2.33]; HR: 2.62 [1.55, 4.44]). When compared to HDV RNA- patients, HDV RNA+ was associated with a significantly higher risk of progressing to compensated cirrhosis (RR 1.74 [1.24, 2.45]), decompensated cirrhosis (HR 3.82 [1.60, 9.10]), hepatocellular carcinoma (HR 2.97 [1.87, 4.70]), liver transplantation (HR 7.07 [1.61, 30.99]), and liver-related mortality (HR 3.78 [2.18, 6.56]).Conclusion: Patients with HDV RNA+ status have a significantly greater risk of liver disease progression than patients who are HDV RNA-. These findings highlight the need for improved HDV screening and linkage to treatment to reduce the risk of liver-related morbidity and mortality.