The significance of the presence of gilbert’s syndrome in patients with metabolic dysfunction-associated steatotic liver disease (MASLD): a retrospective cohort study

Abstract

Introduction Metabolic dysfunction-associated steatotic liver disease (MASLD) appears to be gaining increased attention as a potential global health issue. Closely associated with cardiometabolic risk factors, MASLD can progress to more advanced liver conditions, including fibrosis, cirrhosis, and hepatocellular carcinoma. It is characterized by the accumulation of lipids within hepatocytes, which leads to oxidative stress and hepatic inflammation. Gilbert's syndrome (GS) is a benign hereditary condition marked by elevated levels of unconjugated bilirubin (UCB), a compound believed to possess antioxidant and anti-inflammatory properties. This study aims to explore the potential relationship between GS and MASLD, specifically investigating whether the presence of GS, and the consequent higher levels of UCB may influence the development or progression of liver fibrosis. It compares liver fibrosis and disease severity between MASLD patients with and without GS, using liver stiffness measurement (LSM), controlled attenuation parameter (CAP) score, Fibrosis-4 (FIB-4) index, and FibroScan-AST score (FAST score) as indicators of fibrosis and steatosis, with the goal of providing insight into the possible protective role of GS in the pathogenesis of MASLD. Methods This retrospective cohort study was conducted at Nawaloka Hospital, Sri Lanka, using medical records from 2022 to 2024. Data collected included anthropometric, biochemical, and sociodemographic parameters. Liver fibrosis was assessed using vibration-controlled transient elastography (VCTE) with the FibroScan® 502 device to measure liver stiffness. Metabolic dysfunction-associated steatohepatitis (MASH) with significant activity and fibrosis was assessed by FAST score. A power calculation was performed and a sample size of 189 participants was estimated to detect a mean difference in LSMs. Data analysis was performed using SPSS version 28 (IBM SPSS Statistics, Armonk, NY). Univariate analyses were conducted using the independent samples t-test and chi-square test, as appropriate. Results A total of 243 patients were initially screened, and following exclusion, 180 patients with MASLD were included, of whom 36 were identified as having GS (defined by total bilirubin >1 mg/dL with elevated UCB) and 144 without. No statistically significant difference in LSM was observed between participants with and without GS (P = 0.8919). GS was not significantly associated with the presence or severity of liver fibrosis. Similarly, GS showed no significant association with at-risk MASH (0.72). Increasing age (P = 0.0278), body mass index (BMI) (P = 0.0330), and blood sugar levels (P = 0.0257) were positively associated with liver fibrosis. Conclusion This retrospective cohort study, conducted at the largest private hospital in Sri Lanka, found no significant association between GS and the progression of MASLD, including the presence of MASH or the severity of hepatic fibrosis. Larger, prospective studies are needed to further investigate the potential role of GS in MASLD progression.