Comparative and Predictive Significance of Serum Leptin Levels in Non-alcoholic Fatty Liver Disease

Abstract

BackgroundNon-alcoholic fatty liver disease (NAFLD) has emerged as the single most common chronic non-viral liver disease. The burden of the disease on healthcare-providing services has increased tremendously. Although a liver biopsy is the most authentic laboratory investigation for scoring the disease progression, it is an invasive technique. Researchers are vigorously working to find alternate markers for the scoring purpose. Despite the importance and association of leptin with metabolic syndrome and its related disorders, there have been relatively fewer studies on serum leptin and its association with NAFLD. ObjectiveThis study aimed to investigate variations in serum leptin levels between subjects with and without fibrosis in NAFLD and to assess the predictive value of serum leptin levels in NAFLD subjects. Materials and methodsThe study comprised 130 NAFLD subjects from two tertiary care hospitals in Lahore along with 86 healthy controls that were age, gender, and BMI matched with the subjects. Based on the NAFLD fibrosis score (NFS), the subjects were divided into two sub-groups, subjects with simple steatosis and those with fibrosis. Fasting serum leptin, glucose, and insulin levels were measured using enzyme-linked immunosorbent assay (ELISA). The Kruskal-Wallis test was applied to find differences between the three groups and Fisher's exact test for categorical comparison. To assess the predictive value of serum leptin for steatosis and fibrosis in NAFLD subjects, receiver operation characteristic (ROC) curve analysis was implemented. ResultsThe difference in serum leptin level was statistically highly significant (p-value <0.001), with leptin levels of 10 (17.1) ng/mL among controls, 20.5 (21) ng/mL in simple steatosis, and 21 (28.6) ng/mL in fibrosis. The area under the ROC curve was 0.67 and 0.52 for steatosis and fibrosis, respectively. The cut-off value of 12.2 ng/mL showed 70% sensitivity and 50% specificity for steatosis, while at a threshold of 18 ng/mL, leptin demonstrated 40% sensitivity and specificity for fibrosis. ConclusionIn conclusion, this study found that serum leptin levels are higher in NAFLD subjects compared to healthy controls, and it is a good independent predictor for the detection of liver steatosis.

Evidence That Peripheral Leptin Resistance in Omental Adipose Tissue and Liver Correlates with MASLD in Humans

“…In this study, the control group had averages of 20.4 ± 2.5 ng/mL, and those with MASH had levels up to 37.4 ± 9 ng/mL; participants had BMI > 25 kg/m 2 and were mostly female, and even the controls were overweight. Estrogen can increase leptin levels in rats and humans [ 88 ]; females exhibit leptin and insulin resistance rather than sensitization to leptin’s sympathoexcitatory actions [ 40 ], and threshold levels are unknown [ 87 , 89 ]. Hyperleptinemia itself can cause leptin resistance [ 14 , 84 ].…”

“…The plasma leptin concentration in the cerebral spinal fluid either hits a plateau without change or does not increase when levels rise over 25 to 30 ng/mL [15,86]. Quamar et al found that normal-weight controls had leptin levels of 10 (17.1) ng/mL, while individuals with MASLD had levels of 20.5 (21) ng/mL [87]. In this study, the control group had averages of 20.4 ± 2.5 ng/mL, and those with MASH had levels up to 37.4 ± 9 ng/mL; participants had BMI > 25 kg/m 2 and were mostly female, and even the controls were overweight.…”