Clinical implications of mutations C-to-T 1653 and T-to-C/A/G 1753 of hepatitis B virus genotype C genome in chronic liver disease

Clinical implications of mutations C-to-T 1653 and T-to-C/A/G 1753 of hepatitis B virus genotype... Among many mutational “hot spots” on hepatitis B virus (HBV) genome, A-to-T 1762 and G-to-A 1764 within the core promoter have been underscored in view of disease association as well as viral expression/replication. Although to a lesser extent, C-to-T 1653 and T-to-V(C/A/G) 1753 were also noteworthy in our previous study. To assess the clinical significance of these mutations, we determined the nucleotide sequence of an HBV DNA fragment covering these sites in HBsAg-positive blood donors (n=160) and patients with chronic hepatitis (n=66), liver cirrhosis (n=45), and hepatocellular carcinoma (n=58), most of whom were infected with genotype C HBV (subtype adr ). In cases where HBe antigen was positive, the frequency of T 1653 and/or V 1753 showed a striking increment from chronic hepatitis patients (18%) to liver cirrhosis and/or hep- atoma patients (82%), whereas that of T 1762 /A 1764 was already high in chronic hepatitis patients (76%). In HBe antigen-negative cases, by contrast, significant difference in the frequency of T 1653 /V 1753 mutants was found between blood donors (22%) and chronic hepatitis patients (67%). Our results suggest that T 1653 /V(particularly C) 1753 mutants are more closely associated than T 1762 /A 1764 with the progression of liver disease from chronic hepatitis to cirrhosis in HBe antigen-positive patients. A system of site-directed mutagenesis PCR RFLP was constructed to diagnose T 1653 and C/A 1753 more conveniently. Detecting T 1653 and C/A 1753 by this method would contribute to the differential diagnosis of HBV-associated liver disease. Archives of Virology Springer Journals

Clinical implications of mutations C-to-T 1653 and T-to-C/A/G 1753 of hepatitis B virus genotype C genome in chronic liver disease

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