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Effect of antiviral therapy on the immunohistochemical expression of bcl-xL and bax protein in patients with HBeAg-negative chronic hepatitis B.

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.
AuthorsEvangelos Cholongitas, George V Papatheodoridis, Emanuel K Manesis, Kaliopi Petraki, Dina Tiniakos, Stephanos J Hadziyannis
JournalJournal of medical virology (J Med Virol) Vol. 83 Issue 7 Pg. 1165-71 (Jul 2011) ISSN: 1096-9071 [Electronic] United States
PMID21567420 (Publication Type: Journal Article)
CopyrightCopyright © 2011 Wiley-Liss, Inc.
Chemical References
  • Antiviral Agents
  • Hepatitis B e Antigens
  • Interferon-alpha
  • Organophosphonates
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • adefovir
  • Adenine
Topics
  • Adenine (administration & dosage, analogs & derivatives)
  • Adult
  • Antiviral Agents (administration & dosage)
  • Apoptosis (drug effects)
  • Biopsy
  • Female
  • Fibrosis (etiology, pathology)
  • Hepatitis B e Antigens (analysis)
  • Hepatitis B virus (growth & development)
  • Hepatitis B, Chronic (complications, drug therapy, metabolism, pathology, virology)
  • Humans
  • Immunohistochemistry
  • Inflammation (etiology, pathology)
  • Interferon-alpha (administration & dosage)
  • Liver (drug effects, pathology, virology)
  • Male
  • Middle Aged
  • Organophosphonates (administration & dosage)
  • Retrospective Studies
  • Severity of Illness Index
  • bcl-2-Associated X Protein (analysis, biosynthesis)
  • bcl-X Protein (analysis, biosynthesis)

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