Anthropometry, laboratory, and PNPLA3 polymorphisms in a novel model for early identification and evaluation of nonalcoholic fatty liver disease

Abstract

Some anthropometric, laboratory, and genetic variations, such as patatin-like phospholipase domain-containing protein 3 (PNPLA3) genetic variants, have been associated with nonalcoholic fatty liver disease (NAFLD). Liver biopsy is the most accurate NAFLD diagnostic method, but it is invasive; hence, noninvasive diagnostics are required for the early diagnosis and assessment of NAFLD. This prospective case-control study included 107 NAFLD patients and 107 healthy controls. All individuals underwent anthropometric measurements, abdominal ultrasonography, laboratory tests, and evaluation for PNPLA3 polymorphisms. Patients with NAFLD had higher levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) than healthy individuals (p = 0.03, p < 0.0001). Additionally, patients with NAFLD had substantially lower albumin (P = 0.01) and leptin (P < 0.0001) levels than healthy individuals. BMI leptin and CRP levels were independent indicators of NAFLD severity (p = 0.05–0.004). GG is the most prevalent genotype in patients with moderate to severe NAFLD. A novel model based on four markers (leptin, CRP, BMI, and PNPLA3 polymorphism) was developed. The AUC values for distinguishing between the healthy subjects and those with varying degrees of NAFLD severity (mild, moderate, and severe) were 0.99, 0.99, and 1.0, respectively. Anthropometric measurements, such as BMI and laboratory results, including liver enzymes, CRP, inflammatory markers, lipid parameters, and genetic markers, especially PNPLA3 polymorphisms, can provide an accurate, sensitive, and specific noninvasive approach for the early identification and assessment of NAFLD and can guide its management. This may minimize the need for liver biopsy to assess NAFLD. Further large-scale studies are needed to confirm these findings and verify the model in larger studies.

Keywords: PNPLA3, C-reactive protein, Diagnosis, Leptin, Nonalcoholic fatty liver disease, Polymorphisms