Researchers Recommend Screening All People With HIV for Elevated Liver Function Values

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In people living with HIV, "Liver function [testing] should be performed at ART initiation and patients with symptoms associated with liver damage should be regularly scheduled for ALT [alanine aminotransferase] and AST [aspartate aminotransferase]," the authors of a research review recommend in an April 16 article in AIDS.

Nancy Crum-Cianflone, M.D., and Caryn Gee Morse, M.D., M.P.H., authors of studies reviewed in the article, believe in routine testing for these markers, independent of symptoms. "Often, liver issues are asymptomatic, so relying on symptoms would not be suggested," Crum-Cianflone noted.

"Because of the high prevalence of comorbid liver diseases and risk of medication toxicity in PLWH [people living with HIV], I agree with the routine liver-associated enzyme testing at the time of HIV diagnosis and every six months, in keeping with the IDSA [Infectious Diseases Society of America] primary care guidelines (Clinical Infectious Diseases 2013)," Morse commented.

ALT and AST are the two commonly tested biomarkers for liver health. Their levels can also be influenced by ethnicity, gender, and metabolic and other factors. Thus, study results among various groups differ. An estimated 10% to 20% of the general population has elevated ALT and AST levels, while 6% to 32% of people living with HIV showed higher-than-normal aminotransferase levels in various studies. Up to 64% of the estimated 11% to 14% of people living with HIV worldwide who also have hepatitis C have such elevated levels.

In addition to hepatitis coinfection, non-alcoholic fatty liver disease (NAFLD) can cause higher ALT and AST levels and can lead to liver fibrosis or cirrhosis.

"Cirrhosis and its complications now represent a leading cause of death in HIV-[positive] patients," study authors noted. NAFLD affects 13% to 65% of people living with HIV. In industrialized nations, around 25% of the general population now has the disease, the rate driven by the rise of obesity and type 2 diabetes.

If elevated AST or ALT levels are found in people living with HIV, study authors propose a step-by-step approach:

  1. Take a full demographic profile, including body mass index, and check for risk factors, such as certain antiretroviral or tuberculosis medications, alcohol, and herbal medications, as well as hepatitis C or B coinfection

  2. Calculate fibrosis biomarkers, such as FIB-4, and order liver ultrasound

  3. Depending on outcome of 1 and 2:

a. If low fibrosis: Repeat markers annually and consider transient elastography as a diagnostic tool

b. If indeterminate fibrosis: Order transient elastography, consider referral to specialist and/or liver biopsy

c. If high fibrosis: Order transient elastography, refer to specialist, perform liver biopsy

d. At fibrosis stage 4 (highest): In addition to taking the steps for high fibrosis, screen for hepatocellular carcinoma and esophageal varices

If the clinician determines in step 1 that elevated AST/ALT levels are drug-induced, they should create a timeline of liver values and medications taken and eliminate any non-essential medications or supplements from the patient's list of drugs, study authors recommend.

"The stepwise approach to the evaluation of abnormal liver-associated enzymes in persons living with HIV (PLWH) outlined by Dr. Cai and colleagues is reasonable and appropriate," Morse says, referring to the study authors. "The approach mirrors guidelines for management of incidentally noted liver enzyme abnormalities in HIV-negative populations and is indicated in PLWH given the high prevalence and incidence of liver disease." Such an approach can help clinical providers determine whom to monitor more closely or refer to specialists, she added.

Study authors also recommend using ALT and AST testing to guide patient care, urging that elevated levels receive quick attention.

"Overall, clinicians practicing HIV care should promptly approach the finding of elevated liver transaminases for its diagnostic and prognostic implications," they concluded.