Immunopathogenesis and prognostic immune markers of chronic hepatitis B

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FULL TEXT:

http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1746.2011.06940.x/pdf

Received date: 21-Jul-2011; Accepted date: 06-Sep-2011

Article Type: Solicited Review

Immunopathogenesis and prognostic immune markers of chronic hepatitis B

virus infection

*

Zheng Zhang, Ji-Yuan Zhang, Li-Feng Wang, Fu-Sheng Wang

Research Center for Biological Therapy, Beijing 302 Hospital, Beijing 100039,

China

Correspondence:

Fu-Sheng Wang, PhD, MD

Research Center for Biological Therapy, Beijing 302 Hospital, 100039, China

Phone: 86-010-63879735; Fax: 86-010-63879735

Email: fswang@...

Abstract

Host immune responses induced by hepatitis B virus (HBV) infection not

only

substantially drive disease progression, but also significantly influence

efficacy of

antiviral treatments in HBV-infected individuals. Therefore, it is

important to fully

understand the course of immune pathogenesis and to find efficient

immunological

markers that can predict the disease progression of chronic HBV

infection.

This is an Accepted Article that has been peer-reviewed and

approved for publication in the Journal of Gastroenterology

and Hepatology, but has yet to undergo copy-editing and proof

correction. Please cite this article as an “Accepted

Article”; doi: 10.1111/j.1440-1746.2011.06940.x

This review introduces the current progress in clinical immunology and

analyzes the

mechanisms of antiviral effects and liver injury which are induced by both

innate and

adaptive immune responses. The recently identified immunological markers

indicated

to be closely correlated with disease progression and antiviral

efficacy during HBV

infection are also summarized. Careful monitoring of these immune markers may

help

physicians to make decisions on when to begin or withdraw antiviral

drugs, or to

formulate the prognosis of acute-on-chronic liver failure (ACLF) patients in the

clinic.

Finally, this review highlights some novel therapeutic strategies to

modulate host

immunity which have been proposed to sustain antiviral control of

chronic HBV

infection, as well as the challenges that we are presently facing in the field.

Introduction

Patients with chronic hepatitis B virus (HBV) infection carry a significant risk

of

developing severe liver disease, including chronic hepatitis B (CHB), liver

cirrhosis,

liver failure and hepatocellular carcinoma (HCC). Although HBV

is not

cytopathogenic, it is generally accepted that host immune responses induced by

viral

persistence are responsible for the liver pathogenesis. 1 For example,

HBV-specific T

cell-mediated immune responses play an important role in inducing

hepatocellular

damage during chronic HBV infection. 2 However, recent studies have shown that

the

infiltration of non-virus-specific inflammatory cells within the liver

may also

participate actively in HBV-associated liver pathogenesis. In addition, some

immune

components have recently been found to correlate with natural

progression of the

disease and therapeutic efficacy of agents used to control it.

Several reviews have recently summarized the characteristics of four

immune

phases during the natural course of CHB infection. These include the immune

tolerant

(IT) phase, immune clearance (or immunoactive, IA) phase, low replicative phase

and

asymptomatic chronic carrier state. 1,3 The reviews by us and others

have also

introduced various aspects of clinical immunology of HBV infection. 4-6

To avoid

repetition and to provide clinicians with a comprehensive understanding

of the

progress in the field, this review is focused on the current

challenges of: (1)

identifying immune components which mediate liver pathogenesis and

antiviral

treatment failure; and (2) discovering novel immune components

correlating with

disease progression and antiviral efficacy that may serve as clinical

predictors.