Nucleos(t)ide analogue treatment reduces apoptotic activity in patients with chronic hepatitis B

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http://www.journalofclinicalvirology.com/article/PIIS138665321100326X/abstract?r\

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Journal of Clinical Virology

Article in Press

Nucleos(t)ide analogue treatment reduces apoptotic activity in patients with

chronic hepatitis B

Harald Farnik

, Christian Markus Lange

, Wolf Hofmann

, Annemarie Berger

, Regina Allwinn

, -Walter Welker

, Jörg Trojan

, Christoph Sarrazin

, Eva Herrmann

, Stefan Zeuzem

, Bernd Kronenberger

Received 10 February 2011; received in revised form 23 June 2011; accepted 8

August 2011. published online 07 September 2011.

Corrected Proof

Abstract

Background

Reduction of necroinflammatory activity is a major goal of antiviral therapy of

patients with chronic hepatitis B. Serum ALT does not detect all forms of cell

death.

Objectives

To analyze dynamics of novel serum cell death markers for apoptosis and necrosis

in association with virologic response to nucleos(t)ide (Nuc) analogue

treatment.

Study design

Quantification of the M30-apoptosis neoepitope and the cytokeratin-18

(M65-necrosis) serum levels before and during treatment of patients with chronic

hepatitis B with Nuc (n=26).

Results

Before treatment, M30-apoptotic activity was significantly correlated with

M65-necrosis and fibrosis but not with serum ALT. During therapy with Nucs, cell

death parameters M30-apoptosis, M65-necrosis, and ALT declined in association

with virologic response. The most frequent cell death pattern was simultaneous

decline of ALT and M30-apoptosis which occurred more frequently in patients with

HBs-Antigen decline than in patients with HBs-Antigen increase during treatment

(87.5% vs. 40.0%; p=0.024). ALT decline in association with increase of M30

apoptosis was frequent in patients with HBs-Antigen increase during treatment

(36.3%) but was not observed in patients with HBs-Antigen decline during

treatment.

Conclusion

Decline of cell death parameters in association with decline of HBV-DNA and

HBs-Antigen indicates a reduction in overall cell death activity during Nuc

treatment supporting the concept that response to Nuc therapy reduces

necroinflammatory activity and progression of liver disease.