Background Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and affects approximately 25% of the general global adult population. The prognosis of NAFLD patients with advanced liver fibrosis is known to be poor. It is difficult to assess disease progression in all patients with NAFLD; thus, it is necessary to identify patients who will show poor prognosis. Aim To investigate the efficacy of non-invasive biomarkers for predicting disease progression in patients with NAFLD. Methods We investigated biomarkers associated with mortality in patients with NAFLD who visited the Kawasaki Medical School General Medical Center from 1996 to 2018 and underwent liver biopsy and had been followed-up for > 1 year. Cumulative overall mortality and liver-related events during follow-up were calculated using the Kaplan-Meier analysis and compared using log-rank testing. We calculated the odds ratio and performed receiver operating characteristic curve analysis with logistic regression analysis to determine the optimal cut-off value with the highest prognostic ability. Results We enrolled 489 patients who were followed-up for a period of 1-22.2 years. In total, 13 patients died (2.7% of total patients enrolled); 7 patients died due to liver-related causes. Poor prognosis was associated with liver fibrosis on histological examination but not with inflammation or steatosis. Blood biomarkers associated with mortality were platelet counts, albumin levels, and type IV collagen 7S levels. The optimal cutoff index for predicting total mortality was a platelet count of 15 × 104/μL, albumin level of 3.5 g/dL, and type IV collagen 7S level of 5 mg/dL. In particular, only one-factor patients with NAFLD presenting with platelet counts ≤ 15 × 104/μL, albumin levels ≤ 3.5 g/dL, or type IV collagen 7S ≥ 5 mg/dL showed 5-year, 10-year, and 15-year survival rates of 99.7%, 98.3%, and 94%, respectively. However, patients with two factors had lower 5-year and 10-year survival rates of 98% and 43%, respectively. Similarly, patients with all three factors showed the lowest 5-year and 10-year survival rates of 53% and 26%, respectively. Conclusion A combination of the three non-invasive biomarkers is a useful predictor of NAFLD prognosis and can help identify patients with NAFLD who are at a high risk of all-cause mortality.
