Metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated alcohol-related liver disease in human immunodeficiency virus

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated alcohol-related liver disease (MetALD) have emerged as increasingly important sources of morbidity among people living with human immunodeficiency virus (HIV). Advances in antiretroviral therapy have substantially improved life expectancy in people living with HIV (PLWH), but have also unmasked a growing burden of metabolic comorbidities which contribute to steatotic liver disease. Recent shifts in nomenclature and the introduction of MetALD emphasize metabolic dysfunction and graded alcohol exposure as central drivers of disease and are particularly relevant to PLWH, a population in whom overlapping metabolic and behavioral risk factors are common. Epidemiologic studies demonstrate that MASLD affects approximately one-third to one-half of PLWH worldwide, often occurring at younger ages and lower body mass index thresholds than in HIV-negative individuals. Emerging data further highlight the synergistic contribution of metabolic dysfunction and alcohol use to accelerated fibrosis progression in PLWH. Pathophysiologic mechanisms linking HIV infection to MASLD and MetALD include chronic immune activation and systemic inflammation, antiretroviral therapy-associated metabolic effects, altered adipose tissue distribution, gut-liver axis dysregulation, and alcohol-metabolic synergy. This review synthesizes contemporary evidence on the definitions, epidemiology, pathogenesis, clinical assessment, and management of MASLD and MetALD in PLWH.

Keywords: Metabolic dysfunction-associated steatotic liver disease; Metabolic dysfunction-associated alcohol-related liver disease; Steatotic liver disease; People living with human immunodeficiency virus; Antiretroviral therapy; Metabolic syndrome; Gut-liver axis; Chronic inflammation

Core Tip: This review synthesizes emerging evidence on metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated alcohol-related liver disease in people living with human immunodeficiency virus. The authors highlight the implications of recent nomenclature changes and critically evaluate non-invasive fibrosis tools. The review advances a multi-hit conceptual model integrating antiretroviral therapy effects, immune activation, metabolic dysfunction, and alcohol effects to guide future research and clinical care.