Editorial: Enhancing targeted screening of people living with HIV for liver fibrosis

Antiretroviral therapy (ART) has revolutionised the clinical management of HIV infection. With access and adherence to ART, people living with HIV (PLHIV) are having much improved life expectancy, albeit challenged by earlier onset and higher prevalence of comorbidities, including liver diseases. In the current issue of the Journal, Allende et al compares liver biopsies of 107 PLHIV with metabolic dysfunction-associated steatotic liver disease (MASLD) to matched controls,¹ concluding that PLHIV had less pronounced steatohepatitis but higher grade fibrosis. Notably, 21% of PLHIV had advanced fibrosis, and PLHIV had a 42% higher risk of fibrosis compared with matched controls.

The association of HIV infection with liver fibrosis has long been known. The actual incidence and its variation with populations is still far from clear. In an European multi-centre prospective cohort study, steatosis was present in two thirds of PLHIV (who had risk factors for MASLD), of whom 11.3% had advanced fibrosis.² In a systematic review involving 10 studies from six countries, the prevalence of NAFLD and fibrosis among PLHIV were 35% and 22%, respectively.³ Targeting low-and-middle-income countries, a prospective cohort enrolling over 2000 PLHIV reported an overall prevalence of 28.4% and 7.6% for steatosis and fibrosis, respectively.⁴ Comparability of these studies is low because of the differences in recruitment criteria, measures of steatosis/fibrosis, timing in relation to the HIV diagnosis and probable differences in population characteristics. Prospective cohort studies and the standardised adoption of the new term MASLD could hopefully clarify the situation from ongoing and future studies.

A more important implication from the study by Allende et al is that HIV-specific factors are at play that contribute to fibrosis in HIV-associated MASLD,¹ making it an important metabolic comorbidity in the ART era. For PLHIV, liver fibrosis could arise from viral hepatitis co-infections, be related to concurrent metabolic disease conditions (diabetes, metabolic syndrome, obesity, drug and alcohol exposure), and HIV-related factors, including chronic inflammation, immune activation, exposure of older generations of nucleotide reverse transcriptase inhibitors and changes in intestinal microbiota. In particular, 9.7% of PLHIV in this cohort had normal body mass index (compared with 3.9% in controls).¹ HIV-related factors may play a more important role in MASLD among lean than obese PLHIV.

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The screening of PLHIV for liver fibrosis could be an effective strategy to reduce morbidity, though specific pharmacological treatment for fibrosis is yet to be available.⁵ The European AIDS Clinical Society guidelines recommend case-based screening of PLHIV at risk of MASLD, and reassessment every 2–3 years.⁶ Targeted screening of at-risk populations is also stipulated in the latest European clinical practice guidelines on the management of MASLD,⁷ but HIV infection has not been included as a risk condition.⁸ Universal or mass screening of selected population, exemplified by PLHIV in this discussion, has the dual advantage of capturing a higher proportion of people with advanced diseases and also motivating beneficial lifestyle changes in patients.⁹ The optimal strategy, its potential benefits and cost-effectiveness are the knowledge gaps which could hopefully be filled with research in the not-too-distant future.

Shui-Shan Lee: Conceptualization; writing – original draft. Grace Chung-Yan Lui: Writing – review and editing; conceptualization.

The authors declare no conflicts of interest.

This article is linked to Allende et al paper. To view this article, visit https://doi.org/10.1111/apt.18236.