Hepatitis B virus and hepatitis D virus co-infection complicated by autoimmune hepatitis: Two case reports

Hepatitis D virus-hepatitis B virus (HDV-HBV) co-infection accelerates liver disease progression and increases the risk of hepatocellular carcinoma, but the immunopathogenic mechanism of its combination with autoimmune hepatitis (AIH) has not been clarified. This study reveals for the first time that HDV may induce AIH through abnormalities in immunoregulation in two specific cases. This is the first report of HDV-HBV co-infected patients who did not receive interferon therapy and achieved serological conversion and histological remission by combining antiviral (entecavir) with immunosuppression (prednisone + azathioprine) therapy, providing new evidence of the mechanism of this complex disease.

A 40-year-old female developed malaise and jaundice with an alanine aminotransferase/aspartate aminotransferase > 20 upper limit of normal (ULN), total bilirubin: 97.20 μmol/L, immunoglobulin G (IgG) 47.1 g/L (> 3 × ULN), HDV RNA 1.6 × 10⁷ copies/mL and liver biopsy showed G3S4. Tenofovir alafenamide combined with prednisone and azathioprine was administered, and three months later the Child-Turcotte-Pugh class C was reduced to class B and IgG decreased to 13.62 g/L. Another 58-year-old male complained of pain in the liver area, anti-nuclear antibody was 1:320, IgG 22.6 g/L (> 1.3 × ULN), and liver biopsy showed G2S3. Entecavir was administered in combination with prednisone and azathioprine, and after 3 months, liver function returned to normal, and IgG reduced to 14.22 g/L.

Patients with HDV-HBV co-infection combined with AIH can achieve clinical remission following combination therapy, and the study of immunomodulatory mechanisms should be emphasized.