Background: Nonalcoholic fatty liver disease (NAFLD) has reached pandemic proportions currently and may contribute to multiple extrahepatic outcomes. Aim:To comprehensively summarise evidence of associations between NAFLD and risk of extrahepatic outcomes. Methods:We conducted an umbrella review. We searched PubMed, Web of Science and Cochrane database from inception to 27 November 2021. Results:We included 22 meta-analyses with 374 original studies in our analysis.Subjects with NAFLD had an increased risk of mortality, multiple cardiovascular complications, extrahepatic cancers, diabetes and chronic kidney disease (CKD) than those without NAFLD. Excess risks of several other extrahepatic outcomes including hypothyroidism, urolithiasis, gastro-oesophageal reflux disease, gallstones, depression and worse maternal and foetal outcomes were also observed in this population. However, associations were not significant for prostate cancer, female organ genital cancer, haematological cancer, diabetic retinopathy or osteoporotic fracture.The risks of CVD, diabetes and CKD were similar in obese and non-obese patients.Most associations were heterogeneous across regions; significantly, Europeans with NAFLD were more prone to all-cause mortality than North Americans. The certainty of evidence was graded from only very low to moderate as all included studies were observational.

Backgrounds Cardiovascular disease (CVD) is suggested as a leading cause of death among patients with nonalcoholic fatty liver disease (NAFLD). The aim of this work was to clarify the role of noninvasive scoring systems (NSSs) in predicting CVD risk among this population. Methods The PubMed, Web of Science, and Cochrane databases were searched until 23 March 2022. Meta-analysis was performed for three most commonly used NSS separately, that is, fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and AST/platelet ratio index (APRI). Results Totally, nine studies including 155 382 patients with NAFLD were enrolled. Patients with NAFLD had a higher risk of CVD with increasing FIB-4 score (1.94, 1.52–2.46), the association remained significant after adjustment for age, sex, body mass index, hypertension, and diabetes (2.44, 1.85–3.22). Similarly, a higher risk of CVD was also observed in patients with increasing NFS (2.17, 1.58–2.98) and APRI scores (1.36, 1.04–1.79) in the unadjusted model. However, in the adjusted model, the association was significant only for NFS (3.83, 1.40–10.43), but not for APRI (1.41, 0.79–2.51). Additionally, the increment in CVD risk was most noticeable in subgroup of FIB > 2.67 vs. FIB ≤ 1.3 (6.52, 3.07–13.86) and subgroup of NFS > 0.676 vs. NFS ≤ −1.455 (16.88, 5.68–50.23). All subgroup analyses showed significant associations between FIB-4, NFS, and risk of CVD. Sensitivity analyses did not modify these results. Conclusions FIB-4 and NFS might be useful in identifying those who are at higher risk of CVD among patients with NAFLD. However, APRI was not recommended for this use.

Background Recent research has suggested that sarcopenia may have an impact on postoperative outcomes. The number of hepatocellular carcinoma (HCC) patients with metabolic dysfunction-associated fatty liver disease (MAFLD) has increased significantly over time. The main objective of this study was to investigate the impact of sarcopenia on the prognosis of HCC patients with MAFLD after hepatectomy. Methods A multivariate Cox proportional hazards model and a propensity score matching (PSM) analysis were conducted to ensure that the baseline characteristics were similar. Kaplan‒Meier survival curves were used to compare the prognosis of the two groups. Results This study involved 112 HCC patients with MAFLD undergoing hepatectomy. Sarcopenia was indicated as a risk factor for both recurrence-free survival (RFS) and overall survival (OS) in HCC patients with MAFLD after multivariate analysis (p=0.002 and 0.022, respectively). After conducting PSM analysis, Kaplan‒Meier survival curve analysis revealed significant differences in both the RFS and OS between the two groups (p=0.0002 and p=0.0047, respectively). All results showed that sarcopenia had a poor prognosis for HCC patients with MAFLD undergoing hepatectomy. Conclusion In summary, our study suggests that sarcopenia might be a risk factor for OS and RFS in HCC patients with MAFLD who underwent hepatectomy through multivariate analysis and PSM analysis. Sarcopenia imperils postoperative survival rates and this finding can guide clinical decision-making. For postoperative patients, preventing or treating sarcopenia can potentially improve survival outcomes for patients with HCC and MAFLD.