Role of hepatitis B virus mutant forms in progressive course of chronic hepatitis B

The aim of the study was to determine the prevalence of HBV genotypes in the North-West of Russia (St. Petersburg, Leningrad region, and Republic of Karelia), to identify mutations responsible for resistance to nucleotide/nucleoside analogs (AN), preS/Smutations, canceling the HBsAg synthesis, and to detect the preS/S-mutations influence on the CHB course. HBV was analysed in plasma and/or in the liver biopsy materials of 579 patients with CHB; the genetic type was revealed in 226 patients; sequence analysis of polymerase gen was performed in 49 patients; peculiarities of CHB clinical course were studied in 67 patients: in 26 with HBsAg and in 41 patients with serological marker of preS/S-mutations. Viral DNA was detected in 323 (55,8 %) CHB patients, D genotype was revealed in 183 (81,0 %), A genotype - in 37 (16,4 %) and mixed D+А - in 6 (2,7 %) patients. Primary, secondary and pattern-mutations of resistance to drugs (nucleotide/nucleoside analogs) were detected in 14 (28,6 %) from 49 patients. These mutations caused the HBV-infection relapse. PreS/S-mutations, responsible for the HBsAg disappearance, were revealed in 2 (4,1 %) patients. PreS/S-mutation viral infection caused progressive liver necroinflammation, fibrosis, and transformation of CHB in liver cirrhosis after more than 20 years of clinical course. The estimation of the viral genetic structure has special significance for diagnosis, antiviral treatment, and prognosis of chronic hepatitis B clinical course.