Letter: MASLD in people with HIV exhibits higher fibrosis stage despite lower disease activity than in matched controls

In recent years, increasing attention has been given to the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH) and the immune system. The immune environment in people living with HIV infection (PWH) is particularly complex, influenced by both viral factors and host immune responses. This results in a combination of immunodeficiency, immune activation, chronic inflammation and incomplete immune reconstitution, which altogether interact to accelerate the progression of liver fibrosis.^{1, 2}

The study by Allende et al. utilized multicentre liver biopsy data from the NASH Clinical Research Network (NASH CRN) and the HIV NASH CRN to compare the histological features of MASLD in HIV-infected and non-infected individuals.³ Results indicated that although PWH with MASLD (MASLD-PWH) presented with less hepatic steatosis, inflammation and hepatocellular ballooning (i.e. lower NAFLD activity scores), their fibrosis stages were significantly higher than those of individuals with MASLD and without HIV (MASLD controls). This suggests that liver fibrosis progression in PWH is likely associated with HIV-related immune responses, providing important insights for managing liver disease progression in these patients.

However, there are several areas where this study could be improved. Firstly, compared to NAFLD/NASH, MAFLD/MASH is regarded as a systemic disease driven by metabolic dysfunction, with a greater emphasis on metabolic disturbances (e.g. insulin resistance, obesity and dyslipidaemia) in disease pathophysiology.⁴ The NAFLD activity score (NAS) used in the study primarily depends on steatosis, hepatocellular ballooning and inflammation. It cannot incorporate other pathophysiological mechanisms such as immune response and metabolism and may not fully reflect the complex pathophysiological characteristics of MASLD-PWH.^{5, 6} This could partly explain the possible reasons for the inconsistency with the findings of Vodkin et al.⁷ that the two studies selected different study populations (MASLD and NAFLD), yet both were evaluated using NAS. Future studies should consider a multidimensional scoring system incorporating metabolic and immune-specific parameters to more accurately represent the overall disease burden of MASLD/MASH in HIV patients.

Secondly, the study did not sufficiently evaluate the impact of metabolic syndrome heterogeneity on MASLD. Differences in metabolic syndrome components (e.g. insulin resistance, dyslipidaemia and hypertension) between PWH and controls were not thoroughly discussed, potentially affecting the interpretation of the results. Moreover, the study was based on retrospective data analysis, which may introduce confounding factors, and its conclusions require further validation through prospective studies to enhance causal inference and clinical applicability.

Nevertheless, this study provides valuable insights into the management of MASLD/MASH in PWH. Future research should more comprehensively explore the interplay between HIV and metabolic disorders to develop more individualized therapeutic strategies aimed at slowing liver fibrosis progression in HIV-infected individuals, optimizing both antiviral and metabolic interventions.

Junbin Yan: Writing – original draft. Yunmeng Nie: Writing – review and editing; supervision. Shuo Zhang: Writing – review and editing; supervision.

None.

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