Semaglutide significantly reduces liver fibrosis scores in people with HIV and moderate-to-advanced MASLD.
Background
Metabolic dysfunction-associated steatotic liver disease (MASLD) and subsequent liver fibrosis are major contributors to morbidity and mortality among people with HIV (PWH). PWH often experience higher rates of cardiometabolic conditions, exacerbating liver health issues. Current management strategies for MASLD and fibrosis in this specific population are limited, creating a significant clinical gap. Semaglutide, a GLP-1 receptor agonist, has shown promise in the general population for improving metabolic parameters and liver health, but its impact on liver fibrosis in PWH remained underexplored. This study addresses this critical evidence gap.
Study Design
Researchers conducted a quasi-experimental, pre-/post-, new-user analysis using data from 1850 adult PWH across 10 CFAR Network of Integrated Clinical Systems sites. Participants initiated semaglutide for diabetes and/or weight loss, with a mean treatment duration of 218 days. The primary endpoint was change in liver fibrosis score (FIB-4), with data collected from 4/2018 to 11/2024. Adjusted linear mixed models were employed to assess semaglutide's impact on FIB-4, with a priori stratifications based on baseline fibrosis category (no/low, moderate, advanced) and other clinical factors.
Results
Among the 1850 PWH at baseline, 1368 had FIB-4 <1.3 (no/low fibrosis), 428 had FIB-4 1.3-2.67 (moderate fibrosis), and 54 had FIB-4 >2.67 (advanced fibrosis). The cohort exhibited high rates of cardiometabolic conditions, including diabetes (59%), dyslipidemia (62%), hypertension (80%), and a BMI ≥30 (80%). Most PWH had low alcohol use (57%, mean AUDIT-C 1.6) and did not have hepatitis B (93%) or hepatitis C (86%). > Semaglutide treatment was associated with significant reductions in liver fibrosis score in PWH with baseline moderate-to-advanced fibrosis (FIB-4 ≥1.3), showing a mean change (ΔFIB-4) of -0.11 (P < 0.01). The most pronounced decreases were observed in those with advanced fibrosis (FIB-4 >2.67), where the mean change (ΔFIB-4) was -0.64 (P < 0.001). These findings suggest a direct benefit of semaglutide on liver health in a vulnerable population with significant metabolic burden.
Key Findings
- Semaglutide reduced liver fibrosis scores (FIB-4) in people with HIV with moderate-to-advanced fibrosis (ΔFIB-4: -0.11, P < 0.01).
- Greatest reductions seen in PWH with advanced fibrosis (ΔFIB-4: -0.64, P < 0.001).
- The study included 1850 PWH, with 428 having moderate and 54 advanced baseline fibrosis.
- The cohort had high rates of cardiometabolic conditions (e.g., hypertension 80%, BMI ≥30 80%).
Why It Matters
Semaglutide offers a crucial therapeutic option for PWH who frequently face co-occurring MASLD and liver fibrosis alongside high rates of cardiometabolic conditions. Given that PWH are aging and experiencing more metabolic complications, this finding suggests that semaglutide could serve as a dual-purpose agent, simultaneously managing diabetes/obesity and mitigating progressive liver disease. For clinicians, this supports integrating semaglutide into treatment protocols for PWH with elevated FIB-4 scores, potentially slowing fibrosis progression and reducing long-term morbidity and mortality. This moves beyond general population data, providing specific evidence for a high-risk group.