Diagnosis of liver fibrosis in ageing patients with HIV at risk for non-alcoholic fatty liver disease in Italy and Canada: assessment of a two-tier pathway

Since the introduction of effective antiretroviral therapy, liver-related mortality has increased ten-fold in ageing people with HIV. This trend is driven by ageing-related metabolic conditions that cause non-alcoholic fatty liver disease (NAFLD), which affects 35-65% of people with HIV. Clinically significant (stage 2–4) liver fibrosis develops in over 15% of people with HIV who have NAFLD. Strategies are needed to identify people with HIV at risk for significant liver fibrosis and reduce cirrhosis-related complications. Non-invasive tests to diagnose liver fibrosis include ultrasound-based transient elastography and serum biomarkers. Transient elastography is a feasible tool to assess liver fibrosis, but it is not largely accessible in HIV clinics. We aimed to determine whether a two-tier care pathway with assessment of simple serum biomarkers for fibrosis as first tier could reduce the need for the specialist transient elastography test (second tier). Patients were consecutively identified through a clinical programme for liver disease in people with HIV in Canada and Italy. We applied a two-tier care pathway to three prospective cohorts of people with HIV at risk for NAFLD, defined as those with elevated liver transaminases, body mass index (BMI) of 25 or greater, or diabetes. Patients with alcohol abuse or coinfection with hepatitis B or C viruses were excluded. Five simple serum biomarkers of fibrosis, based on liver transaminases, platelets, and BMI (fibrosis-4 index [FIB-4], BARD [BMI, AST to ALT ratio, diabetes] score, NAFLD fibrosis score, AST to ALT ratio, and AST-to-platelet ratio index [APRI]) were applied as a first-tier assessment to exclude significant liver fibrosis. All patients then received transient elastography. We assessed the decrease in referral for transient elastography that would have occurred based on biomarker assessment and discordance between high transient elastography (≥7·1 kPa), indicating significant liver fibrosis, and low serum fibrosis biomarkers (FIB-4