Review
Liver Disease in the HIV–Infected Individual

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Since the advent of effective antiretroviral therapy (ART) for human immunodeficiency virus-1 (HIV), there has been a substantial decrease in deaths related to acquired immunodeficiency syndrome (AIDS). However, in the ART era, liver disease is now the most common non-AIDS–related cause of death among HIV-infected patients, accounting for 14%–18% of all deaths in this population and almost half of deaths among hospitalized HIV-infected patients. Just as the burden of non-AIDS morbidity and mortality has changed in the ART era, the types of liver disease the clinician is likely to encounter among these patients have changed as well. This review will discuss the causes of liver disease in the HIV-infected population in the ART era, including chronic hepatitis C virus, chronic hepatitis B virus, medication-related hepatotoxicity, alcohol abuse, nonalcoholic fatty liver disease, and AIDS-related liver diseases.

Section snippets

Hepatitis C Virus

Most liver disease among HIV-infected individuals is secondary to coinfection with HCV and/or HBV.12 Because of shared risk factors, coinfection with HCV and HIV is common. Reported prevalence rates of HIV-HCV coinfection vary depending on the route of HIV transmission, from 10% among those with high-risk sexual behavior to 90% with injection drug use.13 Overall, approximately 30% of HIV-infected individuals in the United States and Europe are coinfected with HCV.14

HIV infection alters the

Antiretroviral Therapy–Related Medication Toxicity

Liver toxicity is one of the most common serious adverse events associated with ART.57 The clinical presentation can range from mild asymptomatic increases in serum transaminases to overt liver failure.58 In retrospective studies, the incidence of ART-related severe hepatotoxicity is approximately 10%, and life-threatening events occur at a rate of 2.6 per 100 person-years.59, 60

There are 4 primary mechanisms by which ART can lead to liver damage: direct drug toxicity and/or drug metabolism,

Alcoholic Liver Disease

Although alcoholic liver disease is responsible for nearly half of all deaths due to chronic liver disease in the United States, the role of alcohol abuse on liver disease in HIV-infected populations has not been well-defined. In one study of 2864 HIV-infected adults in the United States, 8% of the entire cohort and 15% of current alcohol drinkers were classified as heavy drinkers, which is almost twice as prevalent as in the general population.69

Active alcohol intake is known to be associated

Nonalcoholic Fatty Liver Disease

NAFLD refers to fat deposition in hepatocytes, or steatosis, in individuals with little or no alcohol use. When accompanied by inflammation and fibrosis, it is referred to as nonalcoholic steatohepatitis (NASH). The prevalence of NAFLD in the U.S. population ranges from 17%–33%, and risk factors include obesity, hyperglycemia, diabetes mellitus, and hypertriglyceridemia.73 Recently, mounting evidence suggests that the prevalence of hepatic steatosis in HIV-infected patients is high, especially

Nodular Regenerative Hyperplasia

Nodular regenerative hyperplasia (NRH) is a rare condition characterized by multiple small regenerative nodules in the liver parenchyma. NRH has recently become increasingly recognized in HIV-infected patients with cryptogenic liver disease.82 Although the etiology is unclear, both ddI use and thrombophilia have been associated with the disease.82, 83 NRH should be considered in HIV-infected patients with portal hypertension of unclear etiology, especially those on ddI.

Acquired Immunodeficiency Syndrome Cholangiopathy

AIDS cholangiopathy occurs when infection-related strictures in the biliary tract lead to biliary obstruction. It typically presents with right upper quadrant (RUQ) pain and a markedly increased alkaline phosphatase level, with less elevated bilirubin and normal or slightly increased transaminase levels. Patients might also have fever, nausea, vomiting, and diarrhea; jaundice is uncommon.84 It is usually seen in low CD4 counts (<100/mm3). Consequently, although previously relatively common

Conclusions

Liver disease among HIV-infected individuals is a common and important cause of non-AIDS–related morbidity and mortality. In the ART era, the spectrum of liver disease among patients with HIV infection has changed dramatically, shifting from opportunistic infections to sequelae of chronic infections, medication toxicities, alcohol use, and fatty liver. Management of HIV-infected patients requires recognition of these conditions and targeted diagnosis and treatment.

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    Conflicts of interest The authors disclose no conflicts.

    Funding This publication was made possible by grants 1KL2RR025006-01 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research (J.C.P.), NIH R01 AI071820 (C.L.T.), and NIH R01 AI060449 (C.L.T.). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Information on NCRR is available at http://www.ncrr.nih.gov/.

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