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Hepatitis virus immune restoration disease of the liver

Crane, Megana; Matthews, Gailb; Lewin, Sharon Ra,c

Current Opinion in HIV and AIDS: July 2008 - Volume 3 - Issue 4 - p 446–452
doi: 10.1097/COH.0b013e3282fdc953
Immune restoration disease: Edited by Robert Colebunders and Martyn French

Purpose of review Co-infection of HIV with hepatitis B virus or hepatitis C virus is common. Hepatotoxicity (grade 3 or 4 transaminitis) after highly active antiretroviral therapy occurs more frequently in either hepatitis B virus or hepatitis C virus co-infection. The cause of abnormal alanine aminotransferase following the initiation of highly active antiretroviral therapy is often multifactorial, and may include immune restoration disease. Since the widespread use of highly active antiretroviral therapy, liver disease secondary to viral hepatitis has become one of the most common causes of death in HIV infected individuals. A better understanding of the immunopathogenesis, diagnosis and treatment of hepatitis immune restoration disease is urgently needed, therefore.

Recent findings Our current understanding of the immunopathogenesis of hepatitis immune restoration disease is limited but it is likely that hepatic damage is secondary to recruitment of both antigen-specific and nonantigen-specific mononuclear cells to the liver, possibly mediated by IFN-γ. HIV–hepatitis B virus co-infected individuals with low CD4+ T-cells and elevated hepatitis B virus DNA and alanine aminotransferase prior to initiation of highly active antiretroviral therapy are at increased risk of hepatitis B virus immune restoration disease. Risk factors for hepatitis C virus immune restoration disease are less well defined. Although clinical deterioration can occur, hepatitis immune restoration disease has also been associated with successful clearance of both hepatitis B virus and hepatitis C virus.

Summary Further randomized clinical trials are needed to develop improved management strategies for hepatitis immune restoration disease.

aDepartment of Medicine, Monash University, Melbourne, Sydney

bNational Centre for HIV Epidemiology and Clinical Research and St Vincent's Hospital, Sydney

cInfectious Diseases Unit, Alfred Hospital, Melbourne, Australia

Correspondence to Professor Sharon R. Lewin, Infectious Diseases Unit, Alfred Hospital, Burnet Institute, Level 2, Commercial Road, Melbourne, Vic 3004, Australia Tel: +61 9076 8491; fax: +61 9076 2431; e-mail:

© 2008 Lippincott Williams & Wilkins, Inc.