Pioglitazone for the Treatment of Metabolic-Associated Fatty Liver Disease in People Living With HIV and Prediabetes.

Background Metabolic-associated fatty liver disease (MAFLD) is increasingly common among people living with the human immunodeficiency virus (PLHIV) and can progress to cirrhosis and cirrhotic-related complications. Pioglitazone is known to improve insulin sensitivity that results in decreasing serum fatty acids and resolution of non-alcoholic steatohepatitis. This study was aimed to evaluate the efficacy of pioglitazone for the treatment of MAFLD in PLHIV and prediabetes. Methods A randomized controlled trial was conducted in HIV-positive individuals with prediabetes who had evidence of a fatty liver by abdominal ultrasonography or controlled attenuation parameter (CAP) ≥ 238 decibels per meter (dB/m) through using transient elastography. Participants were randomized to take pioglitazone, 30 mg/day, (pioglitazone group) or placebo (control group) and were followed up and assessed for 48 weeks. Results  A total of 98 participants were enrolled, 49 in each group. The mean age was 50.8 years and 66.3% were males. All participants had received antiretroviral therapy with undetectable HIV ribonucleic acid (RNA) and the mean CD4 cell count was 463.2 cells/mm. The mean baseline CAP and liver stiffness were 285.7 dB/m and 5.4 kilopascals (kPa), respectively. At 24 weeks, the mean change of the CAP level was -25.7 dB/m in the pioglitazone group and -5.6 dB/m in the control group (= 0.040); the mean change of liver stiffness was 0.014 kPa in the pioglitazone group and 0.403 kPa in the control group (= 0.199). At 48 weeks, the mean change of the CAP level was -23.5 dB/m in the pioglitazone group and 10.2 dB/m in the control group (< 0.001); the mean change of liver stiffness was -0.184 kPa in the pioglitazone group and 0.554 kPa in the control group (= 0.016). The mean changes of fasting plasma glucose (FPG) at 24 and 48 weeks were -14.9 and -17.5 mg/dL in the pioglitazone group, respectively, and -3.6 and 4.5 mg/dL in the control group, respectively (< 0.05). The mean change of the body mass index, lipid profiles, and liver enzymes were not different between the two groups at both time points (> 0.05). No serious adverse effects were observed in either group. Conclusions  Pioglitazone significantly reduces CAP, liver stiffness, and FPG in PLHIV with prediabetes and MAFLD. Further studies with long-term follow-up duration are warranted to determine the role of pioglitazone for clinical use in this population.