The effect of
antiviral treatment on apoptosis in
chronic hepatitis B (CHB) has not been clarified. We evaluated the hepatic immunohistochemical expression of the pro-apoptotic bax and the antiapoptotic
bcl-xL protein in
HBeAg-negative CHB patients before and
after treatment. In our study we included 72 paired biopsies from 36
HBeAg-negative CHB patients: 29 treated (
interferon-alfa: 17,
adefovir: 12) and 7 untreated. Changes in expression of apoptotic
proteins (D-bax, D-bcl-xL), necroinflammation and
fibrosis (D-grade/D-stage) (Ishak classification) were evaluated. We found that Bax-positive compared to bax-negative biopsies had worse necroinflammation (8.2 vs. 6.7, P = 0.05) and
fibrosis score (3.9 vs. 3, P = 0.036). bcl-xL-positive compared to bcl-xL-negative biopsies had lower intralobular
inflammation (1.6 vs. 2.2, P = 0.03). Decreased compared to stable/increased D-bax was associated with greater improvement in necroinflammation only in treated patients (D-grade: -4.6 vs. -1.6, P = 0.05) and greater
fibrosis improvement in
interferon treated patients (D-stage: -0.4 vs. 0.55, P = 0.05). Increased compared to stable/decreased total apoptotic trend [D-apoptosis: (D-bax)-(D-bcl-xL)], was associated with worsening
fibrosis, particularly in
adefovir treated patients (D-stage: 2.3 vs. 0, P = 0.004). In the 11 patients without significant changes from 1st to 2nd biopsy, increased apoptosis was more frequent in treated than untreated cases (P = 0.046). In multivariate analysis, bax change was independently associated with change of grade (P = 0.038) and
antiviral therapy (P = 0.015). In conclusions, in
HBeAg-negative CHB, histological improvement
after treatment is associated with decreased hepatocyte apoptosis. In patients without substantial histological changes, treatment seems to increase the apoptosis of hepatocytes, thus having a possible protective effect on hepatocarcinogenesis.