Background: Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat in the hepatic cells. Based on genetic and environmental factors, it can progress to nonalcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma. Till now, liver biopsy is the only diagnostic tool considered the “gold standard” to confirm or rule out NASH, but it is an invasive and painful procedure. Therefore, biomarkers that can be used non-invasively for diagnosing NASH are urgently needed.
Objectives: To explore the role of BMP8B as a prognostic biomarker in patients with NAFLD/NASH.
Methods: A total of 200 subjects (44 healthy control, 76 NAFLD patients, and 80 NASH patients), both male and female aged between 30-70 years were included. Serum circulatory BMP8B levels were measured in control, NAFLD, and NASH patients by using an ELISA technique. In addition, hepatic mRNA expression of BMP8B was measured in control and NASH patients, then immunohistochemistry analysis was performed to confirm BMP8B expression in hepatic tissues of NASH patients. Next, we assessed the discriminatory ability of BMP8B using ROC curves and we also performed univariate and multivariate logistic regression analyses to know the association between disease and covariates. Furthermore, hepatic BMP8B mRNA expression was measured in high-fat high-fructose (HFHFr) diet rat NAFLD model and choline-deficient high-fat (CDHF) diet mice NAFLD model.
Results: Serum BMP8B levels were significantly higher in NAFLD and NASH patients as compared with the control subjects. Similarly, hepatic BMP8B mRNA expression was significantly higher in NASH patients and immunohistochemistry analysis confirmed that BMP8b expression was increased parallel to the fibrosis score in the hepatic tissues of NASH patients. To discriminate control subjects from NASH patients, the area under the ROC curve provided an excellent result of 0.98 (95% CI: 0.95-1.00; p< 0.0001) with a sensitivity and specificity of 93.42% and 93.02% respectively. It was observed that serum BMP8B levels are significantly associated with some of the biochemical parameters. Furthermore, increased hepatic BMP8B mRNA levels were observed in the progressive stages of animal NAFLD models.
Conclusions: Our study findings confirmed that BMP8B can be used as a prognostic biomarker to identify NAFLD progression and can also differentiate control, NAFLD, and NASH patients. The data indicated that the increased serum BMP8b levels in NAFLD patients are due to increased mRNA expression of BMP8B in the liver. However, future studies should investigate BMP8B levels in circulation with more patients and validate to use as a prognostic non-invasive biomarker.