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

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J Med Virol. 2011 Jul;83(7):1165-71. doi: 10.1002/jmv.21780.

Effect of antiviral therapy on the immunohistochemical expression of bcl-xL and

bax protein in patients with HBeAg-negative chronic hepatitis B.

Cholongitas E, Papatheodoridis GV, Manesis EK, Petraki K, Tiniakos D,

Hadziyannis SJ.

Source

2nd Department of Internal Medicine, Hippokration General Hospital, National

University of Athens School of Medicine, Athens, Greece. cholongitas@....

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.

Copyright © 2011 Wiley-Liss, Inc.

PMID: 21567420 [PubMed - in process]

[Guest guest]

J Med Virol. 2011 Jul;83(7):1165-71. doi: 10.1002/jmv.21780.

Effect of antiviral therapy on the immunohistochemical expression of bcl-xL and

bax protein in patients with HBeAg-negative chronic hepatitis B.

Cholongitas E, Papatheodoridis GV, Manesis EK, Petraki K, Tiniakos D,

Hadziyannis SJ.

Source

2nd Department of Internal Medicine, Hippokration General Hospital, National

University of Athens School of Medicine, Athens, Greece. cholongitas@....

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.

Copyright © 2011 Wiley-Liss, Inc.

PMID: 21567420 [PubMed - in process]