Improvement of liver metabolic activity in people with advanced HIV after antiretroviral therapy initiation

Evaluating hepatic metabolic changes in people with HIV (PWH) with advanced disease, before and after antiretroviral therapy (ART) initiation, using [(18)F]-fluorodeoxyglucose (FDG) PET-computed tomography (PET/CT). FDG PET/CT noninvasively quantifies glucose metabolism in organs. DESIGN/METHODS: Forty-eight viremic PWH (CD4(+) cell counts <100 cells/μl) underwent FDG PET/CT at baseline and approximately 6 weeks after ART initiation (short-term). Twenty-seven PWH participants underwent follow-up scans 2 years after treatment (long-term). FDG PET/CT scans from 20 healthy controls were used for comparison. Liver FDG uptake was quantified from the PET/CT scans. Imaging findings as well as clinical, laboratory, and immune markers were compared longitudinally and cross-sectionally to healthy controls. RESULTS: Liver FDG uptake was lower at baseline and short-term in PWH compared with controls (P < 0.0001). At the long-term scan, liver FDG uptake of PWH increased relative to baseline and short-term (P = 0.0083 and 0.0052) but remained lower than controls’ values (P = 0.004). Changes in FDG uptake correlated negatively with levels of glucagon, myeloperoxidase, sCD14, and MCP-1 and positively with markers of recovery (BMI, albumin, and CD4(+) cell counts) (P < 0.01). In multivariable analyses of PWH values across timepoints, BMI and glucagon were the best set of predictors for liver FDG uptake (P < 0.0001). CONCLUSION: Using FDG PET/CT, we found decreased liver glucose metabolism in PWH that could reflect hepatocytes/lymphocytes/myeloid cell loss and metabolic dysfunction because of inflammation. Although long-term ART seems to reverse many hepatic abnormalities, residual liver injury may still exist within 2 years of treatment initiation, especially in PWH who present with low nadir CD4(+) cell counts.