PNPLA3 PROTEIN EXPRESSION IN RELATION TO FIBROSIS SEVERITY MEASURED BY FIB-4 AND APRI IN NON ALCOHOLIC FATTY LIVER DISEASE

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease, with hepatic fibrosis being an important determinant of disease progression and long-term outcomes. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) has an established role in hepatic lipid metabolism and fibrogenesis; however, the relationship between circulating PNPLA3 protein expression and fibrosis severity remains uncertain. Objective: To evaluate the relationship between serum PNPLA3 protein expression and liver fibrosis severity assessed using the Fibrosis-4 (FIB-4) index and Aspartate Aminotransferase to Platelet Ratio Index (APRI) among patients with NAFLD. Methods: A cross-sectional analytical study was conducted among 120 adult patients with ultrasound-confirmed NAFLD at Asian Hospital, Hyderabad, Pakistan, from March to August 2025. Serum PNPLA3 protein concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Participants were categorized into low, moderate, and high PNPLA3 expression groups. Liver fibrosis was assessed using FIB-4 and APRI scores. Associations between PNPLA3 expression categories and fibrosis categories were assessed using one-way analysis of variance, while correlations between serum PNPLA3 levels and fibrosis indices were evaluated using Spearman’s rank correlation coefficient. A p-value <0.05 was considered statistically significant. Results: Of the 120 participants, 74 (61.7%) were male and 46 (38.3%) were female. Low, moderate, and high PNPLA3 expression was observed in 52 (43.3%), 22 (18.3%), and 46 (38.3%) participants, respectively. According to FIB-4, 79 (65.8%) participants had scores <1.45, 34 (28.3%) had scores of 1.45–3.25, and 7 (5.8%) had scores >3.25. According to APRI, 73 (60.8%) had scores <0.5, 27 (22.5%) had scores of 0.5–1.0, 13 (10.8%) had scores of 1.0–2.0, and 7 (5.8%) had scores >2.0. PNPLA3 expression was not significantly associated with FIB-4 categories (p=0.098) or APRI categories (p=0.24). No significant correlation was observed between PNPLA3 and FIB-4 (r=−0.03, p=0.735) or APRI (r=0.06, p=0.513). Conclusion: Serum PNPLA3 protein expression was not significantly associated with fibrosis severity assessed by FIB-4 or APRI in this cohort of patients with NAFLD. Circulating PNPLA3 protein expression alone may have limited utility as an independent marker of fibrosis severity when evaluated against conventional non-invasive fibrosis indices. Further longitudinal studies involving larger populations and complementary fibrosis assessments are warranted.