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NASH in PWH: Key Strategies for Screening and Identification

Jürgen K. Rockstroh, MD

Professor of Medicine
University Hospital Bonn
Department of Medicine I
Bonn, Germany


Jürgen K. Rockstroh, MD, has disclosed that he has received consulting fees from Abivax, Galapagos, Gilead Sciences, Merck, and ViiV and fees for non-CME/CE services from Gilead Sciences, Janssen, Merck, Theratechnologies, and ViiV.


View ClinicalThoughts from this Author

Released: January 7, 2022

The prevalence of nonalcoholic fatty liver disease (NAFLD) is higher in people with HIV (PWH) than in the general population—ranging from 13% to 65%—due to direct effects of HIV on the liver, weight and metabolic issues related to HIV treatments, and even metabolic comorbidities in our aging population. In addition, a substantial number of PWH—approximately 11.4%—also have nonalcoholic steatohepatitis (NASH).

In my opinion, the numerous reports on the development of NAFLD or NASH in aging PWH reinforce the importance of regular screening in PWH. To explore this, we must understand how NAFLD and NASH are defined.

  • NAFLD is defined as liver fat accumulation exceeding 5% of hepatocytes (hepatic steatosis) either on imaging or on liver histology after the exclusion of secondary causes of fat accumulation in the liver (eg, significant alcohol consumption, certain medications, and other medical conditions).
  • NASH is defined as the presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis. Inflammation and ballooning in the liver, however, can be diagnosed only by liver biopsy.

My Approach
Given the outsize impact of NAFLD and NASH in the setting of HIV, what is my approach to screening and diagnosis? After all, it’s impractical to perform a biopsy to look for NASH in any PWH with liver enzyme elevation. In clinical practice, noninvasive diagnostic tests, such as serum biomarkers and transient elastography, may help identify patients with NASH-related fibrosis who will then require further workup.

The European AIDS Clinical Society (EACS) guidelines include a diagnostic flowchart to assess and monitor disease severity in PWH and suspected NAFLD and metabolic risk factors. In the flowchart, ultrasound is the preferred first-line diagnostic procedure for imaging of NAFLD. [Link to mod3]

If an ultrasound suggests NAFLD, the guidelines recommend determining the risk of advanced fibrosis by calculating FIB-4 or NAFLD fibrosis score—2 scoring systems that are based on readings we already collect in the regular care of PWH.

  • FIB-4 is based on age, aspartate aminotransferase, platelets, and alanine aminotransferase
  • NAFLD fibrosis score is based on the same parameters but includes albumin, BMI, and presence of impaired fasting glucose/diabetes mellitus

Where available and in experienced centers, imaging through transient elastography with controlled attenuation parameter can be used to diagnose HIV-associated NAFLD. Although no optimal cutoff has been established, a few studies have validated a controlled attenuation parameter cutoff specifically in HIV-associated NAFLD using specific values of 248 dB/m or 285 dB/m. [link to mod3]

What Next?
Based on the level of hepatic steatosis and presence of concomitant fibrosis, a risk stratification can be performed, including referral to the hepatologist and potentially a liver biopsy in individuals with signs of advanced fibrosis.

Performing this sort of NAFLD assessment and metabolic risk factor determination also enhances clinical management decisions, allowing for early initiation of interventions such as lifestyle changes and potential pharmacologic interventions. Early interventions targeting lifestyle and weight control can help prevent more advanced courses of NAFLD/NASH in this at-risk population.

Although the best-validated noninvasive tool for NAFLD screening remains unclear, to me it is clear that screening can have a significant clinical impact and prevent a more severe disease course. In fact, EACS guidelines recommend a NAFLD rescreening and risk assessment every 2-5 years depending on clinical risk.

Your Thoughts?
Which tools do you use to evaluate risk of NAFLD fibrosis in patients with HIV? Answer the polling question and join the conversation by posting in the discussion section.

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