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Background: Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have a higher risk of osteoporosis/fractures; however, the causal relationship remains unclear. Methods: Publicly available genome‐wide association studies (GWASs) were used for Mendelian randomization (MR) analysis. GWASs of NAFLD and fractures were obtained from the FinnGen Consortium. GWASs of bone mineral density (BMD) were derived from a meta‐analysis. GWASs of obesity, diabetes, liver function, and serum lipid‐related metrics were used to clarify whether the accompanying NAFLD symptoms contributed to fractures. Moreover, two additional GWASs of NAFLD were applied. Results: A causal association was not observed between NAFLD and BMD using GWASs from the FinnGen Consortium. However, a causal relationship between NAFLD and femoral neck‐BMD (FN‐BMD), a suggestive relationship between fibrosis and FN‐BMD, and between NAFLD and osteoporosis were identified in replication GWASs. Genetically proxied body mass index (BMI), high‐density lipoprotein (HDL), and hip circumference increased the likelihood of lower limb fractures. The waist‐to‐hip ratio decreased, whereas glycated hemoglobin (HbA1C) and homeostasis model assessment of β‐cell function (HOMA‐B) increased the risk of forearm fractures. Low‐density lipoprotein (LDL) reduced, whereas HbA1C increased the incidence of femoral fractures. Alkaline phosphatase (ALP) raised the risk of foot fractures. However, after a multivariate MR analysis (adjusted for BMI), all the relationships became insignificant. Conclusions: NAFLD caused reduced BMD, and genetically predicted HDL, LDL, HbA1C, HOMA‐B, ALP, hip circumference, and waist‐to‐hip ratio causally increased the risk of fractures. BMI may mediate causal relationships. Larger GWASs are required to verify this finding. [ABSTRACT FROM AUTHOR]

Background and Aim: There is debate among the hepatology community regarding the simple non‐invasive scoring systems and histological scores (even it was developed for histological classification) in predicting clinical outcomes in patients with non‐alcoholic fatty liver disease (NAFLD). This study aimed to determine whether the presence of simple non‐invasive scoring systems and histological scores could predict all‐cause mortality, liver‐related mortality, and liver disease decompensation (liver failure, cirrhosis, hepatocellular carcinoma, or decompensated liver disease). Methods: The pooled hazard ratio of prognostic factors and incidence rate per 1000 person‐years in patients with NAFLD was calculated and further adjusted by two different models of handling the duplicated data. Results: A total of 19 longitudinal studies were included. Most simple non‐invasive scoring systems (Fibrosis‐4 Score, BARD, and aspartate aminotransferase‐to‐platelet ratio index) and histological scores (NAFLD activity score, Brunt, and "steatosis, activity, and fibrosis") failed in predicting mortality, and only the NAFLD fibrosis score > 0.676 showed prognostic ability to all‐cause mortality (four studies, 7564 patients, 118 352 person‐years followed up, pooled hazard ratio 1.44, 95% confidence interval [CI] 1.05–1.96). The incidence rate per 1000 person‐years of all‐cause mortality, liver‐related mortality, cardiovascular‐related mortality, and liver disease decompensation resulted in a pooled incidence rate per 1000 person‐years of 22.65 (14 studies, 95% CI 9.62–53.31), 3.19 (7 studies, 95% CI 1.14–8.93), 6.02 (6 studies, 95% CI 4.69–7.74), and 11.46 (4 studies, 95% CI 5.33–24.63), respectively. Conclusion: Non‐alcoholic fatty liver disease fibrosis score showed promising prognostic value to all‐cause mortality. Most present simple non‐invasive scoring systems and histological scores failed to predict clinical outcomes. [ABSTRACT FROM AUTHOR]