OTU-08 HeAL (HIV non-virAl liver disease) study: the role of alcohol, metabolic syndrome or HIV itself?

Introduction In view of advances in viral hepatitis treatment, future chronic liver disease (CLD) in people living with HIV (PLWH) is likely to be due to non-viral hepatitis aetiologies. Potential contributors include alcohol, metabolic syndrome (MS) or antiretrovirals (ARV). Understanding risk factors and early recognition of CLD is essential to prevent long-term morbidity and mortality. This prospective cohort study investigates the prevalence and predictors of CLD in PLWH with abnormal liver function. Methods Inclusion criteria were PLWH, negative viral hepatitis serology and elevated transaminases over 6 months. Consenting individuals completed an Alcohol Use Disorders Identification Test (AUDIT), underwent MS assessment and transient elastography. Study definitions: significant hepatic steatosis (SHS) - controlled attenuation parameter (CAP) ≥237dB/m; significant hepatic fibrosis (SHF) and cirrhosis - liver stiffness measurement ≥7.1 kPa and ≥11.5 kPa respectively. SHF risk factors consisted of MS, hazardous drinking (AUDIT≥8) and hepatotoxic ARV use. Results Of 429 eligible individuals, 219 have been recruited. Mean age was 52.3±9.8 years, 92.2% were male, 96.3% with undetectable viral load, mean HIV duration of 15.8±7.6 years. Overall prevalence of SHS was 63% (n=137), and SHF was 21% (n=47), of whom 35 (74%) had SHS and 17 (36%) had cirrhosis. On binary logistic regression, HDL and AUDIT score were significantly associated with SHF whereas CD4 baseline, HIV duration, BMI, hypertension, diabetes, and duration on ARV were not. Predictors of SHS included BMI, HDL and AUDIT score. No classical risk factors were identified in 8 (17%) individuals with SHF but they had significantly shorter HIV duration and higher peak ALT compared to those with risk factors for SHF (table 1). Conclusion There is considerable liver disease burden in PLWH with elevated transaminases, with nearly 2/3 having SHS and 1/5 SHF. MS risk factors and alcohol use appear to predict both SHS and SHF. However, one fifth of individuals with SHF have no identifiable risk factors, raising the real possibility of immune dysregulation or direct hepatotoxicity of HIV in this subpopulation. Our data highlights the need to implement screening strategies for CLD in PLWH alone to ensure timely Hepatology input, and the importance of providing appropriate advice regarding alcohol intake and weight loss.