Editorial Commentary: Elevated Aminotransferase Levels Among HIV-Infected Persons: What's Lurking Under the Surface?

Individuals infected with the human immunodeficiency virus (HIV) have experienced an unprecedented increase in life expectancy as a result of extraordinary advances in treatment and care. Nonetheless, they remain at an elevated risk for several comorbidities, one of the most important being liver disease [1]. Liver disease is common among HIV-infected persons—partly due to the shared routes of transmission of HIV and viral hepatitides. Several studies have also highlighted that HIV-monoinfected adults without hepatitis B virus (HBV) or hepatitis C virus (HCV) frequently have elevated aminotransferase levels and underlying liver disease [2, 3]. The etiology of these elevations often remains unknown and is presumptively attributed to substance use, possible antiretroviral medication effects, or HIV infection itself. A handful of studies have investigated the causes of elevated aminotransferases among HIV-monoinfected patients, demonstrating that the most common cause is nonalcoholic fatty liver disease (NAFLD) [4–7]. NAFLD is a clinicopathologic disorder defined by the presence of fat in >5% of hepatocytes in the absence of other secondary causes (eg, alcohol use, hereditary disorders, steatogenic medications, or viral hepatitis) [8]. Nonalcoholic steatohepatitis (NASH), a subgroup of NAFLD, is defined by the presence of inflammation (ie, lobular inflammation, hepatocellular ballooning, and/or fibrosis) in addition to steatosis. Because most prior studies evaluating the causes of aminotransferase elevations among HIV patients were small [5, 6] or did not evaluate biopsy-confirmed cases [7], further studies regarding the precise etiology and pathogenesis of aminotransferase elevations among HIV-monoinfected adults are needed. The study byMorse et al [9] in this issue of Clinical Infectious Diseases evaluated 62 HIV-infected adults with persistently (≥6 months) elevated aminotransferase levels. Participants were receiving antiretroviral therapy for ≥1 year and were without viral coinfections (negative for HBV and HCV, and in some cases hepatitis E virus) or other known causes of liver disease. Each participant completed a robust battery of questionnaires/interviews, metabolic tests, computed tomographic (CT) imaging, and a liver biopsy. The study found that nearly 75% of participants had NAFLD, >50% had NASH, and nearly 20% had bridging fibrosis by liver biopsy. The presence of NASH and fibrosis are especially important given their greater likelihood of progressing to liver dysfunction and hepatocellular carcinoma, and because they represent a major cause of cirrhosis of “unknown” etiology. The high prevalence of fatty liver disease found in this study is clearly eye-opening. Prior studies among HIV patients have found notable, albeit lower, rates of NAFLD (31%–65%) and NASH (6%–26%) [4, 5, 7]. The high rates in the current study should be contextualized within study population characteristics as the prevalence of NAFLD increases with age, male sex, and specific underlying conditions. In the present study [9], the median age of participants was 50 years; 94% were men, 30% were obese, and nearly 50% had the metabolic syndrome. As many of these characteristics mirror those of today’s HIV patients, this study’s findings are relevant to practicing clinicians. Finally, although not addressed by the current study, NAFLD and NASH may exist in the setting of normal aminotransferase levels; hence, the impact of these disorders may be even greater than shown by Morse et al. In the current study [9], NASH was associated with “traditional” risk factors of obesity and insulin resistance, findings consistent with the literature [5, 6, 8, 10]. Prior studies have additionally shown Received 2 February 2015; accepted 4 February 2015; electronically published 13 February 2015. Correspondence: Nancy F. Crum-Cianflone, MD, MPH, Scripps Mercy Hospital, 4077 Fifth Ave, San Diego, CA 92103 (nancy32red@yahoo.com). Clinical Infectious Diseases 2015;60(10):1579–81 © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/cid/civ106