NUCLEOTIDE-SEQUENCE ANALYSIS OF THE PRECORE REGION IN PATIENTS WITH SPONTANEOUS REACTIVATION OF CHRONIC HEPATITIS-B

The role of HBV precore mutations in the spontaneous reactivation of c hronic hepatitis B (CHB) is currently unknown. We studied 10 patients with CHB; five were HBeAg+ (group I) and five were anti-HBe+ (group II ). AU 10 had spontaneous reactivation of CHB as defined by the appeara nce of clinical symptoms along with an increase of serum ALT activity at least 5x above baseline values, in the absence of any other known c auses of liver disease or CHB reactivation. The precore (87 nt) and pr oximal core (81 nt) regions were sequenced after PCR amplification. Fr om each patient three serum samples were studied: one 3-12 months befo re, one during, and one six months after reactivation. Prior to reacti vation, none of the group I patients harbored an HBV strain having a m utation that prevented HBeAg synthesis; however, 2/5 developed such a mutation during reactivation (G to A transition at nt 1896). Among the group II patients, three harbored an HBeAg defective mutant both befo re and during reactivation; after six months, two of these three patie nts were HBV DNA negative in serum by PCR. Several other sequence poly merphisms, some of which changed the predicted amino acid sequence, we re either present initially or developed during reactivation. In concl usion, in this small group of CHB patients who were HBeAg+ spontaneous reactivation was accompanied in some cases by a shift to an HBeAg def ective mutant, while in patients who were anti-HBe+, such mutations we re frequently present prior to reactivation. In patients already harbo ring precore defective mutants, spontaneous reactivation may precede a n attenuation of viral replication.