麻豆传媒

DENVER -- Semaglutide (Ozempic) reduced the amount of liver fat by nearly a third in people with HIV and metabolic dysfunction-associated steatotic liver disease (MASLD), the open-label phase IIb SLIM LIVER study showed.

In the single-arm trial, the absolute change in intrahepatic triglyceride (IHTG) content across all participants was -4.2% (95% CI -5.4 to -3.1, P<0.001) following 6 months of weekly injections, equivalent to a relative reduction of 31.3% (95% CI -39 to -23.6, P<0.001), reported Jordan Lake, MD, MSc, of UTHealth Houston, at the Conference on Retroviruses and Opportunistic Infections.

Improvements in IHTG correlated with weight loss and other metabolic measures.

MASLD, formerly called nonalcoholic fatty liver disease, is common among people with HIV and likely acts with HIV infection to accelerate hepatic injury and organ dysfunction, Lake said. Accumulation of fat deposits in the liver can cause inflammation and cellular damage that can contribute to cardiovascular and liver disease.

, MASLD is the leading reason in the U.S. for liver transplantation. It affects an estimated 30% to 40% of people with HIV, slightly higher than the average among people without HIV.

Semaglutide has shown benefits in people with nonalcoholic steatohepatitis (now metabolic dysfunction-associated steatohepatitis), and the SLIM LIVER study aimed to determine whether it could improve liver metrics in people with HIV.

David Lee Thomas, MD, MPH, of the Johns Hopkins School of Medicine in Baltimore, who was not involved in the study, said it is "very exciting to see the impact of this new class of medications on a clinically significant and previously difficult-to-treat problem."

"HIV is pro-fibrogenic, so with hep C, hep B, alcohol, and fat, there's more cirrhosis in people with HIV," Thomas said. "We know we can treat two of the four -- hepatitis B and hepatitis C -- and prevent those outcomes, but we haven't really had a treatment until now for fatty liver disease. We'll probably look to this study as one of the more important, pivotal moments when we reframed how we approached steatotic liver disease."

Thomas acknowledged, however, that there remains a lot to learn. "There's a lot of questions we have about stopping doses, about whom to treat and how long to treat, and that sort of thing," he told 麻豆传媒. "But, in the beginning, to see that there is a clear association with reductions in fat is terrific. Now we need to ask, is that also associated with reductions in inflammation? Is that also associated with reductions in fibrosis accumulation?"

enrolled 51 adults with HIV on suppressive antiretroviral therapy (ART) who had an elevated waist circumference of at least 95 cm for men and 94 cm for women. Enrollees had insulin resistance or pre-diabetes and at least 5% IHTG content on MRI-proton density fat fraction (PDFF).

Participants included 57% men, 37% cis women, and 6% transgender women. They had an average age of 52, an average body mass index (BMI) of 35, and an average waist circumference of 114 cm. One-third of participants were Black, 39% were Hispanic, 27% were white, and 2% were Native American/Alaskan Native.

The mean CD4 T counts was 701 cells/mm³ at baseline, and 8% of participants had a history of hepatitis C. ART regimens included integrase strand-transfer inhibitors in 82%, non-nucleoside reverse transcriptase inhibitors in 22%, and protease inhibitors in 4%.

A total of 49 participants completed the study, which involved weekly subcutaneous semaglutide at escalating doses: 0.29 mg for 2 weeks, followed by 0.5 mg for 2 weeks, and then 1 mg for 20 weeks.

More than half the participants (58%) had at least a 30% relative reduction in IHTG content, and 29% of participants had complete resolution of MASLD, defined by an IHTG content less than 5%. The greatest reductions in IHTG were seen in women, Hispanic and non-Hispanic white participants, and people ages 60 and older.

Participants experienced a mean weight loss of 7.8 kg (17 lbs) over 24 weeks. Improvements in IHTG correlated with weight loss (r=0.54, P<0.0001). The 38 participants who lost more than 2.27 kg (5 lbs) had a mean absolute loss of 5.1% IHTG, a 39% relative reduction.

Other metabolic parameters improved significantly as well. The change in glucose was -9.9 mg/dL (P<0.001), and the change in HbA1c was -0.3% (P<0.001). Insulin resistance improved with a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) change of -1.5 (P<0.001). The change in triglycerides was -26.8 mg/dL (P<0.007). Total cholesterol fell by 4 mg/dL, with a 1 mg/dL reduction in LDL and a 2 mg/dL increase in HDL, but none of the lipid changes were significant.

While larger glucose reductions were seen in women, Black participants, and people 40 and older, larger triglyceride reductions occurred in men, Hispanic participants, and people under age 40.

One participant dropped out due to nausea, but semaglutide was generally well-tolerated, with two possibly-related grade 3 adverse events and none that were grade 4.

Future work will assess immunologic and inflammatory pathway changes from GLP-1 receptor agonists in this population, Lake said. It's important to determine secondary effects like lean mass loss, durability of benefit, and strategies to maintain benefit, she added.

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