Letter: Impact of Nonalcoholic Fatty Liver Disease on the Survival of People Living With HIV

We read with great interest the cohort study by Macias and colleagues [1] demonstrating that liver stiffness measurement (LSM) and the FAST score independently predicted mortality in people living with HIV (PLWH). Nonalcoholic fatty liver disease (NAFLD) is an emerging concern in PLWH, with a prevalence ranging from 13% to 72%, associated with accelerated liver fibrosis and increased mortality, driven by metabolic risk factors like obesity, diabetes and antiretroviral therapy (ART)-related side effects like weight gain and insulin resistance [1-3]. Despite its clinical significance, PLWH are often excluded from NAFLD research or clinical trials, leading to gaps in understanding its natural history and optimal management [4].

From a methodological perspective, the predictive capability of the FAST score (calculated using CAP, AST and LSM) observed in this study likely stemmed primarily from its liver stiffness measurement component. Liver fibrosis has long been recognised as an important predictor of liver-related and all-cause mortality in patients with NAFLD [5]. The finding from this study highlighted the importance of assessment of liver fibrosis in PLHIV. On this note, we wonder if the author had looked at a two-step approach (i.e., liver stiffness measurement in persons with elevated fibrosis-4 score) for prognostication in their cohort of PLHIV, which could improve the cost-effectiveness of liver health screening in this population [6]. The authors have made a commendable effort presenting the findings of their study in line with the recent nomenclature change [7]. However, an analysis on PLHIV with steatotic liver disease based on CAP, following the exclusion of other causes of chronic liver disease and in the presence of at least one cardiometabolic criterion would be most consistent with the current definition of MASLD. Studies have shown that a significant proportion of people with at least one cardiometabolic criterion (used to define those with potential MASLD in this study) do not have steatotic liver disease [8].

From a clinical point of view, most PLHIV had suppressed HIV viral load in this cohort. At baseline, participants received integrase inhibitors (InI) (24%), protease inhibitors (PI) (39%) and non-nucleoside reverse transcriptase inhibitors (NNRTI) (32%). Notably, 78% transitioned to InI-based therapy during follow-up.

InI and tenofovir alafenamide (TAF), although improving HIV outcomes, are associated with weight gain and metabolic disturbances that can potentially contribute to liver disease progression [9]. Continuation of PI- and NNRTI-based regimens may also impact liver health [10]. On this note, the influence of ART regimen changes on liver disease trajectories deserves further exploration.

In conclusion, while the study by Macias and colleagues provided crucial insights into the prognostic role of LSM and FAST scores, critical questions remain. We propose areas for future research: (1) investigate the longitudinal impact of specific ART regimens (including two-drug combinations) on steatotic liver disease in PLWH, (2) include PLHIV in MASLD therapy trials [4] and (3) explore a two-step approach for liver health screening in PLHIV [6]. Addressing these gaps, including consideration of social determinant factors [4], is essential for optimising liver disease management in PLHIV.

W.-K.C. conceptualized the paper. R.-X.N. and W.-K.C. drafted the paper. All authors reviewed the paper for important intellectual content and approved the final paper.

W.-K.C. has served as a consultant or advisory board member for Abbott, Abbvie, Boehringer Ingelheim, Novo Nordisk, Roche and Viatris; and a speaker for Abbott, Echosens, Hisky Medical, Novo Nordisk and Viatris. R.-X.N. and R.I.S.R.A. have no conflicts of interest to disclose.

This article is linked to Macias et al papers. To view these articles, visit https://doi.org/10.1111/apt.18413 and https://doi.org/10.1111/apt.70082.