Nonalcoholic Fatty Liver Disease and Fibrosis Associated With Increased Risk of Cardiovascular Events in a Prospective Study

Abstract Background & Aims Patients with non-alcoholic fatty liver disease (NAFLD) are at increased chance for cardiovascular events (CVEs). Severity of liver fibrosis is used to determine prognoses for patients with NAFLD, but little is known about the relationship between liver fibrosis and CVEs in the real world. Methods We analyzed data from the prospective observational progression of liver damage and cardiometabolic disorders in non-alcoholic fatty liver disease study, comprising 898 consecutive outpatients (mean age, 56.4±12.7 years; 37.5% women) screened for liver steatosis by ultrasound according to Hamagughi criteria. Liver fibrosis was defined as FIB-4 score greater than 2.67 and NAFLD fibrosis score greater than 0.676. After enrolment, patients were interviewed by phone every 6 months and examined every 12 months in the outpatient clinic, and CVEs were recorded (fatal or nonfatal ischemic stroke and myocardial infarction, cardiac or peripheral revascularization, new-onset arterial fibrillation and cardiovascular death). The primary outcomes were incidence rate of CVEs in patients with vs without NAFLD and factors associated with CVEs in patients with NAFLD. Results Over a median follow-up time of 41.4 months (3044.4 patient-years), 58 CVEs (1.9%/year) were registered. The rate of CVEs was higher in patients with (n=643, 2.1%/year) vs without NAFLD (n=255, 1.0%/year) (P=.066). In multivariable Cox proportional regression analysis, NAFLD increased risk for CVEs (hazard ratio [HR], 2.41; 95% CI, 1.06–5.47; P=.036), after adjustment for metabolic syndrome. Among patients with NAFLD, male sex, previous CVEs, metabolic syndrome and FIB-4 scores greater than 2.67 (HR, 4.02; 95% CI, 1.21–13.38; P=.023) were independently associated with risk of incident CVEs. NFS scores greater than 0.676 were also independently associated with risk of incident CVEs (HR, 2.35; 95% CI, 1.05–5.27; P=.038). Conclusions In an analysis of data from a study of patients screened for NAFLD and followed, individuals with NAFLD had more than a 2-fold increase in risk of CVEs, and those with liver fibrosis had a 4-fold increase in risk. In patients with NAFLD, liver fibrosis indexes were independently associated with risk of incident CVEs. ClinicalTrials.gov no:NCT04036357.