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MASLD in people with HIV exhibits higher fibrosis stage despite lower disease activity than in matched controls
Daniela S Allende1, Oscar Cummings2, Alice L Sternberg3
1Cleveland Clinic, Cleveland, Ohio, USA.
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.
Insights
Metabolic dysfunction-associated steatotic liver disease (MASLD) in people with HIV (PWH) shows less liver inflammation and cell damage but higher fibrosis. This suggests HIV-specific factors accelerate fibrosis progression in MASLD-PWH.
Area of Science:
- Hepatology
- Virology
- Metabolic Diseases
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is prevalent in people with HIV (PWH).
- The histological characteristics of MASLD in PWH and their correlation with fibrosis remain unclear.
- Understanding these differences is crucial for managing liver disease in PWH.
Purpose of the Study:
- To compare the histological features of MASLD in PWH with matched controls without HIV.
- To investigate the relationship between the NAFLD activity score (NAS) and fibrosis stage in PWH with MASLD.
- To identify potential HIV-specific factors influencing liver disease progression.
Main Methods:
- 107 liver biopsies from PWH with MASLD were matched to 107 biopsies from MASLD controls without HIV.
- Matching criteria included age, race, sex, type 2 diabetes, BMI, and ALT levels.
- Liver biopsies were scored using the NAFLD activity score (NAS).
Main Results:
- MASLD-PWH exhibited lower grades of steatosis, lobular inflammation, portal inflammation, and hepatocyte ballooning compared to MASLD controls.
- The overall NAS was significantly lower in MASLD-PWH.
- Despite less inflammation and ballooning, MASLD-PWH showed a higher stage of fibrosis.
Conclusions:
- MASLD in PWH demonstrates less hepatic necroinflammation but a higher degree of fibrosis compared to non-HIV MASLD controls.
- These findings suggest that factors beyond traditional histological drivers of fibrosis, potentially HIV-specific, contribute to advanced fibrosis in PWH.
- Further research is needed to elucidate these HIV-specific mechanisms driving fibrosis progression.
