Effect of antiviral therapy on the immunohistochemical expression of bcl-xL and bax protein in patients with HBeAg-negative chronic hepatitis B
✍ Scribed by Evangelos Cholongitas; George V. Papatheodoridis; Emanuel K. Manesis; Kaliopi Petraki; Dina Tiniakos; Stephanos J. Hadziyannis
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 212 KB
- Volume
- 83
- Category
- Article
- ISSN
- 0146-6615
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✦ Synopsis
Abstract
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. J. Med. Virol. 83:1165–1171, 2011. © 2011 Wiley‐Liss, Inc.