HIV Med. 2025 Sep 20.
OBJECTIVES: Despite effective antiretroviral therapy (ART), chronic liver diseases remain a leading cause of morbidity and mortality among people with HIV, with metabolic dysfunction-associated steatotic liver disease (MASLD) now the predominant etiology. Vitamin D deficiency is also highly prevalent in this population. We synthesize current evidence on the interplay between HIV, liver disease, and vitamin D deficiency, and highlight implications for risk stratification and therapeutic research in this population.
METHODS: A targeted PubMed search was conducted using terms for HIV, liver disease, fibrosis, and vitamin D, supplemented by reference screening. We prioritized peer-reviewed studies and guidelines addressing liver disease epidemiology and mechanisms in people with HIV, vitamin D biology, and associations between vitamin D status and hepatic injury. Comparative data from non-HIV populations were also reviewed.
RESULTS: People with HIV face a high burden for chronic liver diseases due to MASLD, viral hepatitis coinfections, and hepatotoxic exposures such as alcohol and ART. Pathogenesis involve persistent immune activation, hepatic stellate cell activation, and systemic inflammation. Vitamin D deficiency is frequent in people with HIV and, in non-HIV populations, correlates with higher prevalence of MASLD and fibrosis. Emerging evidence suggests plausible links through immune modulation, oxidative stress, and fibrogenesis, though causality remains unproven.
CONCLUSIONS: The intersection of HIV, MASLD, and vitamin D deficiency is biologically plausible and clinically relevant yet underexplored. Longitudinal studies with standardized MASLD phenotyping and vitamin D assessment are warranted. Meanwhile, integrating metabolic risk assessment with vitamin D evaluation may support more holistic liver care in people with HIV, while interventional trials should clarify whether vitamin D optimization improves hepatic and extrahepatic outcomes.
Keywords: antiretroviral therapy; immune activation; liver fibrosis; metabolic dysfunction‐associated steatotic liver disease; viral hepatitis