CHANGES IN THE PREVALENCE OF HBEAG-NEGATIVE MUTANT HEPATITIS-B VIRUS DURING THE COURSE OF CHRONIC HEPATITIS-B

Hepatitis B virus with a G-to-A point mutation at nucleotide 83 in the precore region (mutant hepatitis B virus 83), which cannot produce HBeAg, is commonly found in HBe antibody-positive hepatitis B virus carriers. We analyzed the consecutive changes in the prevalence of mutant hepatitis B virus 83 during the course of chronic hepatitis B who were followed up for more than 2 yr in our hospital were studied by polymerase chain reaction in combination with a restriction fragment length polymorphism assay. Mutant hepatitis B virus 83 was found in 14 of 18 (78%) HBe antibody-positive patients and in 8 of 27 (30%) HBeAg-positive patients at baseline. Eighteen of the 22 patients who had mutant hepatitis B virus 83 (82%) showed mixed viral populations of wild-type hepatitis B virus and mutant hepatitis B virus 83, whereas 4 (18%) had only mutant hepatitis B virus 83 and were positive for HBe antibody. During a 2 yr follow-up period, mutant hepatitis B virus 83 was newly detected in 9 of 23 (39%) patients who had wild-type hepatitis B virus alone at baseline. The proportion of mutant hepatitis B virus 83 to whole hepatitis B virus in the serum of 18 patients with mixed viral populations at baseline fluctuate during follow-up. In contrast, wild-type hepatitis B virus was never detected throughout the study in all four patients who had only mutant hepatitis B virus 83 at baseline. These results suggest that mutant hepatitis B virus 83 is prevalent even in HBeAg-positive patients with chronic hepatitis B. The presence of mutant hepatitis B virus 83 leads to complete and irreversible displacement of wild-type virus in some cases.