Histopathological features of hepatocellular carcinoma in patients with hepatitis B and hepatitis D viruses infection: A single-institution study from Mongolia

Viral hepatitis, particularly hepatitis B (HBV) and hepatitis C (HCV), is highly prevalent in Mongolia. Moreover, Mongolia has the highest prevalence of hepatitis delta virus (HDV) globally, with over 60% of HBV-infected individuals also co-infected with HDV. Since HBV/HDV infections accelerate liver disease progression more compared to HBV infection alone, urgent national health measures are required. This study presents a clinicopathological analysis of 49 hepatocellular carcinoma cases surgically resected at the Mongolia-Japan Hospital of the Mongolian National University of Medical Sciences. HBV infection was found in 27 (55.1%) cases of all HCC cases. Immunohistochemical staining of the liver revealed that 14 (28.6%) among the HBV infected tissues were HDV antigen-positive in the HCC cases. HDV-positive cases exhibited significantly higher inflammatory activity compared to HDV-negative cases, with lymphocytic infiltrates predominantly composed of CD4-positive cells. Furthermore, HDV-positive cells were spatially distinct from HBs antigen-positive cells, suggesting that HDV-infected cells may interfere with HBV replication. No significant differences in fibrosis or in tumor characteristics were observed between the HDV-positive and -negative cases. Early diagnosis of HBV/HDV infections is essential for appropriate treatment and to prevent further domestic transmission of the virus. However, routine testing for HDV infection is rarely conducted in Mongolia. Since HDV-positive cells are morphologically indistinguishable from surrounding HDV-negative cells, routine histopathological analysis may not be sufficient to detect HDV infection. Based on this clinicopathological study, CD4 and CD8 immunostaining can be considered as an adjunctive diagnostic tool in cases with significant lymphocytic infiltration and hepatocellular damage. Additionally, HDV screening using blood and tissue samples may be recommended to ensure accurate diagnosis.