Elsevier

The Lancet

Volume 377, Issue 9772, 2–8 April 2011, Pages 1198-1209
The Lancet

Review
Increasing burden of liver disease in patients with HIV infection

https://doi.org/10.1016/S0140-6736(10)62001-6Get rights and content

Summary

Introduction of effective combined antiretroviral therapy has made HIV infection a chronic illness. Substantial reductions in the number of AIDS-related deaths have been accompanied by an increase in liver-related morbidity and mortality due to co-infection with chronic hepatitis B and C viruses. Increases in non-alcoholic fatty liver disease and drug-induced hepatotoxicity, together with development of hepatocellular carcinoma, also potentiate the burden of liver disease in individuals with HIV infection. We provide an overview of the key causes, disease mechanisms of pathogenesis, and recommendations for treatment options including the evolving role of liver transplantation.

Introduction

HIV is a major global health issue with an estimated 38·6 million people infected with HIV-1 worldwide.1 In developed countries, mortality from HIV infection has reduced substantially since the introduction of combined antiretroviral therapy (cART) in 1996, resulting in a pronounced decline in occurrence of AIDS and AIDS-related deaths.2, 3

More than 50% of deaths in patients on cART are not related to AIDS.2, 3, 4 Prospective data from the Data collection on adverse events of Anti-HIV Drugs (D:A:D) Study Group3 showed that mortality from liver disease was second only to AIDS-related mortality (figure 1). Of these liver-related deaths, 66% were secondary to hepatitis C virus (HCV), 17% were attributed to active hepatitis B virus (HBV), and 3% were directly related to cART.3 Other causes of liver disease in patients with HIV infection include alcohol, drug-induced hepatotoxicity, and non-alcoholic fatty liver disease (figure 2).

Section snippets

Signs and assessment of liver disease

HIV, HBV, and HCV infection share similar transmission routes and therefore co-infection is common.5 In patients co-infected with HIV plus HBV or HCV, fibrosis rates are accelerated compared with those infected with HBV or HCV alone, leading to faster progression to end-stage liver disease.6 Overall, the signs of end-stage liver disease in patients with HIV infection seem to be similar to the signs in patients without HIV infection, but survival after the first episode of decompensation is

HCV

A third of patients with HIV infection in Europe and the USA are co-infected with HCV, and up to 90% of deaths in HIV-positive patients with end-stage liver disease are attributed to HCV infection.13 HCV is usually transmitted via contaminated blood or blood products. At-risk groups include intravenous drug users, patients with haemophilia who were infected via contaminated infusions of plasma-derived factor VIII or IX concentrate during the 1970s and 1980s, men who have sex with men (MSM),

Alcohol

Alcohol use is as common in individuals infected with HIV as in the general population. Data from the French MORTAVIC studies13 show a progressive increase in the number of patients with HIV infection who excessively consume alcohol, which is a cofactor associated with HIV progression and inadequate viral suppression.75 Excessive alcohol consumption is also an important risk factor for progressive liver disease, particularly in HIV-positive patients who are not infected with HCV.76 In a study

Drug-induced hepatotoxicity

Awareness of cART-induced hepatotoxicty is increasing. Eliciting the culprit drug is often difficult for combination therapies. Hepatotoxicity in patients receiving cART might be under-reported because 50% of patients are asymptomatic when liver enzymes are raised.77 The severity of liver injury can be graded according to the concentration of aminotransferases (table 2). We recommend that liver function tests are done at baseline in all patients starting cART. High HIV viral loads might be

Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease is the hepatic manifestation of metabolic syndrome,109 and is characterised histologically by macrovesiscular steatosis in the absence of other causes. The progressive form of non-alcoholic fatty liver disease is non-alcoholic steatohepatitis, which combines macrovesicular steatosis, inflammation, hepatocellular ballooning, Mallory's hyaline, and fibrosis.110

Prevalence of non-alcoholic fatty liver disease is higher in individuals with HIV infection (30–40%)

Hepatocellular carcinoma

Hepatocellular carcinoma is expected to rise substantially in patients infected with HIV predominately because of co-infection with HBV and HCV. This disorder might also develop in patients with non-cirrhotic chronic HBV infection. Evidence from in-vitro and animal studies underscores the important role of HIV infection in viral hepatitis and alcohol-induced hepatocarcinogenesis mediated via the Tat protein.118 According to the MORTAVIC study and the French Mortalité study, hepatocellular

Liver transplantation

Liver transplantation in patients infected with HIV has been done successfully in several institutions worldwide with variable outcomes.121, 122, 123 In the UK, only small numbers of such patients are being referred for consideration of liver transplantation, according to defined criteria (panel 3). Although these criteria need further refinement, we believe that every effort to suppress HIV viral load is undertaken before patients are added to the transplant list, particularly in patients

Conclusion

End-stage liver disease is now a leading cause of mortality and morbidity in patients infected with HIV, with a range of causes from co-infection with chronic HBV and HCV infection to non-alcoholic fatty liver disease and hepatotoxicity induced by alcohol and drugs. As a result of advances in cART, many patients infected with HIV will potentially face long-term sequelae of chronic liver disease. These patients need to be managed in an expert multidisciplinary environment with specialists in

Search strategy and selection criteria

We searched Medline (Jan 1, 1966, to July 1, 2010) with the search terms “liver disease and HIV” in combination with “viral hepatitis” and “liver transplantation”. We selected publications predominately from the past 5 years, but did not exclude seminal older publications. We also reviewed the reference lists of articles identified by this search strategy and selected those judged to be relevant. Our reference list was modified on the basis of comments from peer reviewers.

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