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. 2024 Nov;60(10):1351-1360.
doi: 10.1111/apt.18236. Epub 2024 Sep 5.

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

Daniela S Allende  1 , Oscar Cummings  2 , Alice L Sternberg  3 , Cynthia A Behling  4 , Danielle Carpenter  5 , Ryan M Gill  6 , Cynthia D Guy  7 , Matthew M Yeh  8 , Samer Gawrieh  9 , Richard K Sterling  10 , Susanna Naggie  11 , Rohit Loomba  12 , Jennifer C Price  6 , Mary McLaughlin  13 , Colleen Hadigan  13 , Holly Crandall  2 , Patricia Belt  3 , Laura Wilson  3 , Naga P Chalasani  9 , David E Kleiner  14 ; HIV NASH and NASH Clinical Research Groups
Affiliations

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

Daniela S Allende et al. Aliment Pharmacol Ther. 2024 Nov.

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in people with HIV (PWH). The morphological spectrum of MASLD compared to matched controls and of the correlation between the NAFLD activity score (NAS) and fibrosis stage in PWH remains unknown.

Methods: Overall, 107 liver biopsies from PWH with MASLD (MASLD-PWH) were matched to 107 biopsies from individuals with MASLD and without HIV (MASLD controls) on age at biopsy, race/ethnicity, sex, type 2 diabetes, body mass index (BMI) and alanine aminotransferase (ALT) level. Biopsies were scored using NAS.

Results: Compared to MASLD-controls, MASLD-PWH had lower steatosis grade (OR: 0.65, 95% CI: (0.47-0.90), p = 0.01), lower lobular inflammation grade (OR: 0.55, 95% CI: (0.34-0.89), p = 0.02), less portal inflammation (OR: 0.42, 95% CI: (0.25-0.72), p = 0.002) and less ballooned hepatocytes (OR: 0.60, 95% CI: (0.41-0.88), p = 0.01). Thus, NAS was lower in MASLD-PWH (OR: 0.69, 95% CI: (0.56-0.85), p < 0.001) than in MASLD controls. There was a trend towards lower prevalence of steatohepatitis in MASLD-PWH (OR: 0.84, 95% CI: (0.68-1.03), p = 0.09). A multivariate analysis demonstrated that MASLD-PWH cases had significantly less steatosis (OR: 0.66, p = 0.03), portal inflammation (OR: 0.34, p = 0.001) and ballooned hepatocytes (OR: 0.55, p = 0.01), yet higher stage fibrosis (OR: 1.42, p = 0.03) compared to MASLD controls.

Conclusion: The NAS and histological drivers of fibrosis (e.g. inflammation and hepatocyte ballooning) are less pronounced in MASLD-PWH, and yet fibrosis stage was generally higher when compared to matched controls with MASLD without HIV. This suggests HIV-specific factors beyond hepatic necroinflammation may contribute to fibrosis progression in MASLD-PWH.

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Conflict of interest statement

Conflict of interest:

Dr. Behling’s institution provides contract services for ICON, Covance and Sharp Healthcare Laboratories. Dr. Behling has received speaker fees from Pfizer and Alimentiv for NASH related topics.

Dr. Chalasani reports no conflicts of interest relevant for this paper. For full disclosure, he reports paid consulting agreements with Madrigal, Zydus, Ipsen, Pfizer, Merck, Altimmune, BioMea and GSK, He receives research grant support from Exact Sciences and Zydus. He reports equity interest in Avant Sante Therapeutics, LLC, a contract clinical research organization and Heligenics, a drug discovery start-up.

Other authors report no conflicts related to this paper.

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