Background
In general population adults with metabolic dysfunction-associated steatotic liver disease (MASLD) and non-cirrhotic liver fibrosis, the glucagon-like peptide-1 receptor agonist semaglutide (SEMA) improves steatohepatitis (MASH) but not liver fibrosis. The OWLiver metabolomics algorithm is validated against liver biopsy in general population cohorts and uses serum profiling to distinguish MASLD from No MASLD. Among persons with MASLD, it can also distinguish MASH and MASH with significant fibrosis (at-risk MASH) from No MASH. We previously reported that 24 weeks (W) of SEMA reduced magnetic resonance imaging (MRI)-quantified liver fat in people with HIV (PWH) that correlated strongly with weight loss. Here we report metabolomic profiles before and after SEMA.
Methods
In ACTG A5371, PWH >/= 18 years old on suppressive antiretroviral therapy (ART) with MRI-defined MASLD received SEMA 1mg sc weekly for 24 W. Of 51 participants, 36 US PWH with clinical response (>5 lb weight loss) to SEMA had serum analyzed by ultra-high performance liquid chromatography-mass spectrometry at OWL Metabolomics for OWLiver disease staging.
Results
Participants had: median age 52 years, BMI 34 kg/m2, 39% Hispanic ethnicity, 28% Black/African American race, 45% cis/trans female and 77% INSTI-based ART. At W0, OWLiver defined 69% as MASLD without MASH, 22% MASH and 3% at-risk MASH. Two PWH were re-classified as No MASLD (does not exclude early steatosis). After 24 W of SEMA, 31% of PWH and MASLD improved their disease severity category: 11% MASLD without MASH to No MASLD, 6% MASH to No MASLD, 11% MASH to MASLD without MASH and 3% at-risk MASH to MASH. However, 61% had no change in disease category and 8% worsened (latter despite steatosis improvement on MRI): 1 MASLD without MASH to at-risk MASH, 1 MASLD without MASH to MASH and 1 No MASLD to MASLD without MASH (Table).
Conclusions
Among PWH and MRI-defined MASLD, 24 W of low-dose SEMA led to significant improvement in MASLD disease severity in nearly 1/3 of participants and across all disease severity categories. While 61% did not change disease category, improvements within a category (such as from severe to mild MASLD) may have occurred. Studies of longer duration and higher dose SEMA for MASLD are needed to determine if additional benefit can be gained. Importantly, use of the OWLiver metabolomics algorithms provided evidence of improvement in predicted histology without a requirement for liver biopsy and should be considered for disease staging in PWH.
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