A case-control study for early prediction of hepatitis B e antigen seroconversion by hepatitis B virus DNA levels and mutations in the precore region and core promoter.
Factors influencing and predictive of seroconversion from hepatitis B e antigen (HBeAg) to antibody (anti-HBe) were sought in a case-control study of 61 patients with chronic hepatitis B who had been observed from 5 years before to 1 year after seroconversion, and 32 patients who did not seroconvert during the entire 6-year period. Almost all of the patients (96%) were infected with HBV genotype C. HBV DNA levels began to decrease 3 years before seroconversion in the seroconverters, while they remained high in the non-converters. The frequency of precore mutation and the loss of HBeAg (A1896) started to increase 1 year before in the converters, and became significantly higher at seroconversion (23 vs. 3%, P = 0.030) than that in the non-converters. Double mutation in the core promoter (T1762/A1764) was more common in the seroconverters than in the non-converters 5 years before seroconversion (48 vs. 28%), and became significantly more frequent at seroconversion (65 vs. 41%, P = 0.046). Seroconversion occurred in 75% of the patients with at least HBV DNA levels <5.5 logarithmic equivalents/mL; precore mutation in 20% or more of HBV DNA; or core promoter mutation. Seroconversion occurred in 50% of those patients within 1 year, 88% within 2 years, and 93% within 5 years. These results indicate that a decrease in HBV DNA levels and mutations in the precore region and the core promoter were associated significantly and complementarily with seroconversion, and each of them or a combination thereof was predictive of seroconversion years ahead.
Yamaura
Takahiro
T
Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Tanaka
Eiji
E
Matsumoto
Akihiro
A
Rokuhara
Akinori
A
Orii
Koji
K
Yoshizawa
Kaname
K
Miyakawa
Yuzo
Y
Kiyosawa
Kendo
K
D000328:Adult; D016022:Case-Control Studies; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D005838:Genotype; D006510:Hepatitis B Antibodies / Q000097:blood*; D006512:Hepatitis B Core Antigens / Q000235:genetics; D006513:Hepatitis B e Antigens / Q000097:blood* / Q000276:immunology; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D008297:Male; D009154:Mutation; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D012680:Sensitivity and Specificity
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D011498:Protein Precursors