Increased visceral fat predicts both the presence of hepatic fibrosis in HIV patients with nonalcoholic fatty liver disease and also its progression, according to a report at the Conference on Retroviruses & Opportunistic Infections.
Dr. Lindsay Fourman
Among 58 people with NAFLD and well-controlled HIV, mostly men, a “striking 43% had evidence of fibrosis” on liver biopsy, a quarter with severe stage 3 fibrosis. Visceral fat content on MRI predicted fibrosis (284 cm2 among fibrotic patients vs. 212 cm2 among nonfibrotic patients, P = .005), but body mass index (BMI), waist circumference, subcutaneous fat, and hepatic fat content did not, said investigators led by Lindsay Fourman, MD, an attending physician at the Neuroendocrine & Pituitary Tumor Clinical Center at Massachusetts General Hospital, Boston.
Among 24 subjects with a second liver biopsy a year later, 38% had fibrosis progression, more than half from no fibrosis at baseline. Baseline visceral fat (306 cm2 among progressors versus 212 cm2, P = .04) again predicted progression, after adjustment for baseline BMI, hepatic fat content, and NAFLD activity score.
For every 25 cm2 rise in baseline visceral fat, the team found a 40% increased odds of fibrosis progression (P = .03). Body mass index was stable among subjects, so progression was not related to sudden weight gain. Dr. Fourman noted that people with HIV can have normal BMIs, but still significant accumulation of visceral fat.
The mean rate of progression was 0.2 stages per year. “To put this into perspective, the rate of fibrosis progression among NAFLD in the general population has been quoted to be about 0.03 stages per year.” Among HIV patients, it’s “more than sixfold higher,” she said in a video presentation of her research at the meeting, which was presented online this year. CROI organizers chose to hold a virtual meeting due to concerns about the spread of COVID-19.
Overall, visceral adiposity is “a novel clinical predictor of accelerated” progression in people with HIV. “Therapies to reduce visceral fat may be particularly effective in HIV-associated NAFLD,” she said.
The findings come from a trial of one such therapy, the growth hormone releasing hormone analogue tesamorelin (Egrifta). It’s approved for reduction of excess abdominal fat in HIV patients with lipodystrophy. Dr. Fourman and her colleagues recently reported a more than 30% reduction in liver fat, versus placebo, among HIV patients with NAFLD after a year of treatment, and a lower rate of fibrosis progression at 10.5% versus 37.5% (Lancet HIV. 2019 Dec;6[12]:e821-30).
In their follow-up study reported at the meeting, people with fibrosis at baseline also had higher NAFLD activity scores (3.6 points vs. 2.0 points; P < .0001), as well as higher ALT (41 U/L vs. 23 U/L, P = .002) and AST levels (44 U/L vs. 24 U/L; P = .0003).
Baseline BMI, liver fat content, NAFLD activity score, liver enzymes, waist circumference, CD4 count, and HIV duration, a median of 16 years in the study, did not predict progression, but activity scores, hemoglobin A1C, and C-reactive protein increased as fibrosis progressed.
“We really can’t speak from our own data” if HIV regimens might have had a role in progression. Sixty-two percent of the subjects were on integrase inhibitors, and integrase inhibitors are associated with weight gain, but their effect on visceral weight gain is unclear, plus BMIs were stable. Also, there was no difference in HIV regimens among the more than 100 people screened for the study between those with NAFDL and those without.
The subjects were 54 years old, on average. The average liver fat content at baseline was about 14%, and average baseline BMI just over 30 kg/m2. In addition to the 62% on integrase inhibitors, 40% were on nonnucleoside reverse transcriptase inhibitors, and 24% were on protease inhibitors.
The work was funded by the National Institutes of Health. Dr. Fourman is a paid consultant to Theratechnologies, maker of tesamorelin.
SOURCE: Fourman LT et al. CROI 2020, Abstract 128