Letter: Impact of Nonalcoholic Fatty Liver Disease on the Survival of People Living With HIV—Authors' Reply

Abstract

We thank Ng et al. [1] for their interest and comments on our research article [2]. They rightly point out the role of liver stiffness measurement (LSM) in the predictive value of the FAST score. Indeed, we proposed the use of LSM instead of the FAST score to assess the prognosis of PLWH with or at risk of NAFLD or MASLD in clinical practice, as a simpler and more convenient index. Moreover, LSM can be measured using different ultrasound-based elastography techniques, with similar diagnostic performance, which could be more accessible in certain settings. As Ng et al. also correctly comment, a two-step approach using FIB-4 to select PLWH for LSM could improve cost-effectiveness. However, FIB-4 was not an independent predictor of death after adjustment for other risk factors (last paragraph in the Results section) [2]. Therefore, we did not further evaluate FIB-4 to select PLWH at risk of NAFLD or MASLD.

The definition of MASLD in our paper was ‘… steatotic liver disease with one or more … cardiometabolic risk factors, without other concomitant causes of steatotic liver disease: …’, which agrees with the definition commented by Ng et al. We included in our analyses a group of PLWH that could be considered ‘at risk of MASLD’, but without MASLD at the date of entry in the cohort. Those were PLWH with one or more of cardiometabolic risk factors at inclusion in the cohort, regardless of the CAP value.

Ng et al. make the interesting point of the influence of antiretroviral therapy, namely the effect of tenofovir alafenamide (TAF) and integrase inhibitors (INI), on weight gain and, consequently, on liver disease progression. We agree that the role of TAF or INI-induced weight gain on liver disease deserves further evaluation. However, previous attempts to identify an effect of INI on adverse clinical outcomes have failed. The influence on cardiovascular outcomes of INI has been evaluated in the HIV-CAUSAL collaboration. The use of INI compared with other drug classes did not result in a clinical impact on cardiovascular outcomes [3]. The sample size that allowed reaching this conclusion, nearly 20,000 drug-naïve individuals and more than 40,000 drug-experienced individuals, is many times greater than the sample size of our study. In addition, previous cross-sectional reports in PLWH did not find associations between steatotic liver disease and antiretroviral therapy [4, 5].

We agree with the unmet needs in the field of steatotic liver disease in PLWH highlighted by Ng et al. First, there is a need for simple and cost-effective approaches to evaluate and manage liver health in PLWH. Second, while the role of antiretroviral therapy in steatotic liver disease needs elucidation, those with metabolic risk factors clearly should be evaluated and treated. Finally, PLWH without control of metabolic factors and increased LSM should be a priority for coming MASLD clinical trials.

Juan Macias: conceptualization, investigation, funding acquisition, writing – original draft, methodology, writing – review and editing, formal analysis, supervision. Mario Frias: investigation, data curation, writing – review and editing. Juan Antonio Pineda: conceptualization, investigation, writing – original draft, methodology, formal analysis, supervision. Miguel García-Deltoro: investigation, writing – review and editing, data curation. Luis Miguel Real: conceptualization, investigation, funding acquisition, writing – original draft, supervision.

The authors' declarations of personal and financial interests are unchanged from those in the original article [2].

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.70021.