Occult hepatitis B virus (HBV) infection was detected in 50% of patients with chronic hepatitis C virus (HCV) infection who also have chronic HCV-related hepatocellular carcinoma (HCC), according to data published in the European Journal of Gastroenterology and Hepatology.

To clarify the clinical and pathologic characteristics of occult HBV infection in patients with chronic HCV-related HCC, researchers sampled DNA from serum and tumor tissue. The virus was detected using quantitative polymerase chain reaction, and clinicopathologic features were compared between patients with HCC who also have occult HBV infection and those without occult HBV infection.

Overall, the frequency of occult HBV infection was 50% in patients with HCV-related HCC. The HBV genotype D was found in 35% of those with HCC and was the most dominant genotype in the study. Approximately 80% of patients with occult HBV infection had anti-hepatitis B core (HBc) antibodies, while 20% had no serologic markers. The results also revealed a significant association between tissue HBV-DNA and positive serum HBV-DNA, anti-HBc, and genotype D.

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No clinical differences between patients with HCC with and without occult HBV infection were observed except that patients with occult HBV infection tended to be younger. Those with HCC and occult HBV infection demonstrated significant association with positive anti-HBc antibodies and late histologic grade disease. A multivariate logistic regression analysis showed that the presence of occult HBV infection was a predictor of more advanced HCC histologic grades in those with HCV infection.

The study investigators noted that this study is limited by a relatively small sample size and by being conducted at only a single center. Researchers also noted that while some previous studies have reported an association between occult HBV infection and HCC, others have not. However, the study authors adhere to their finding that patients with occult HBV infection have more advanced HCC histologic grades, which “supports the potential involvement of [occult HBV infection] in hepatocarcinogenesis.”

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This work revealed that a high frequency of occult HBV infection may be occurring in people with HCV with related HCC and that the presence of occult HBV infection is most reliably predicted by the positive anti-HBc status of a patient. The study did not find any significant effect on clinical consequences in patients with chronic HCV infection with HCC, but the study investigators suggested that status of occult HBV infection in the context of HCC warrants further study using well-designed multicenter studies.


El-Maksoud MA, Habeeb MR, Ghazy HF, et al. Clinicopathological study of occult hepatitis B virus infection in hepatitis C virus-associated hepatocellular carcinoma [published online March 11, 2019]. Eur J Gastroenterol Hepatol. doi:10.1097/MEG.0000000000001388