Rapid detection of genotypes and mutations in the pre-core promoter and the pre-core region of hepatitis B virus genome: correlation with viral persistence and disease severity

Backguound/Aim: We aimed to clarify the clinical relevance of hepatitis B v irus pre-core mutant detection in patients with chronic hepatitis B using a newly developed assay. Methods: Viral genotypes and pre-core mutations were studied in relation to viral persistence and liver disease severity using INNO-LiPA methodology. The study group included 151 patients with chronic hepatitis B, 85 positive for HBeAg (group I) and 66 positive for anti-HBe (group LT). Results: The prevalence of viral genotypes in group I was: 64% A, 1% B, 15% C, 19% D, 0% E, 0% F and in group II: 39% A, 0% B, 2% C, 56% D, 2% E, 2% F (p<0.001). The prevalence of mutations at pre-core codon 28 (M2) was lower in group I (5%) than in group II (64%) (p<0.001). The prevalence of pre-co re promoter mutations was also lower in group I (21%) than in group II (61% ) (p <0.001). M2 mutations were more frequently detected in genotype D than in genotype A (p<0.001), while the other mutations were not influenced by viral genotype. Serum HBV DNA levels were significantly lower in group II v el sus group I (p<0.001), and in patients with any of the pre-core mutation s versus wild-type sequence (p<0.01). Although cirrhosis was more frequent in group II (37%) versus group I (22%) and in patients with either one of t he pre-core mutation (31%) versus wild-type sequence (25%), there was no st atistical difference in liver severity assessed by ALT levels and Knodell s core. Conclusion: Pre-core mutants, whose molecular pattern is strongly dependent on viral genotypes, are associated with viral persistence in anti-HBe posi tive patients with ongoing chronic hepatitis 13. The availability of this r apid assay should allow a precise monitoring of viral pre-core mutants duri ng the course of chronic hepatitis B.