Clinical relevance of precore mutations of hepatitis B virus in chronic liver disease

Introduction: Hepatitis B is one of the most frequent etiological factors for chronic liver diseases worldwide. Recent studies have suggested the important role of the genetic diversity of the virus on natural course of hepatitis B. Hepatitis B e-antigen negative type of chronic hepatitis is associated with mutations in the precore region and basic core promoter of hepatitis B viral genome. Aim of study was to identify precore mutations in viral genome of patients with chronic hepatitis B and to evaluate clinical patterns of liver disease related to this type of hepatitis B. Methods: Sixty seven patients with hepatitis B were included in the study. In order to evaluate the clinical patterns of chronic liver disease related to hepatitis B viral infection, biochemical and virological investigations were done, as well as a quantification of serum viral load. All patients underwent liver biopsy and semiquantification of necroinflammation and/or fibrosis according to Knodell scoring was done. In the group of e antigen-negative patients, molecular analysis was performed in order to identify presence of mutations in precore region of the virus. Results: Study group was divided in 25 HBeAg-positive and 42 HBeAg-negative subjects. Al anin-aminotransferase activity and level of viral load were higher in HBeAg-positive (p < 0.05), but average age and histology activity index were significantly higher in the HBeAg-negative patients (p < 0.01). Precore mutants were found in 38 of 42 patients with HBeAg-negative hepatitis (90%). Fibrosis was found in 30/38 cases with mutations. Discussion: Mutations in precore region of HBV in HBeAg-negative patients were more prevalent in older age and were associated with higher rate of fibrosis in liver tissue, meaning more advanced stage of the disease. This could be a consequence of longer duration of HBV infection or more severe clinical course of the disease. Conclusion: Our results suggest that precore mutations are highly responsible for the development of hepatitis B e antigen-negative chronic liver disease in our patients. These mutations are associated with more progressive liver disease and with older age of the patients