Hospital admission with non-alcoholic fatty liver disease is associated with increased all-cause mortality independent of cardiovascular risk factors

Abstract

Non-alcoholic fatty liver disease (NAFLD) is common and strongly associated with the metabolic syndrome. Though NAFLD may progress to end-stage liver disease, the top cause of mortality in NAFLD is cardiovascular disease (CVD). Most of the data on liver-related mortality in NAFLD derives from specialist liver centres. It is not clear if the higher reported mortality rates in individuals with non-cirrhotic NAFLD are entirely accounted for by complications of atherosclerosis and diabetes. Therefore, we aimed to describe the CVD burden and mortality in NAFLD when adjusting for metabolic risk factors using a ‘real world’ cohort. We performed a retrospective study of patients followed-up after an admission to non-specialist hospitals with a NAFLD-spectrum diagnosis. Non-cirrhotic NAFLD and NAFLD-cirrhosis patients were defined by ICD-10 codes. Cases were age-/sex-matched with non-NAFLD hospitalised patients. All-cause mortality over 14-years follow-up after discharge was compared between groups using Cox proportional hazard models adjusted for demographics, CVD, and metabolic syndrome components. We identified 1,802 patients with NAFLD-diagnoses: 1,091 with non-cirrhotic NAFLD and 711 with NAFLD-cirrhosis, matched to 24,737 controls. There was an increasing burden of CVD with progression of NAFLD: for congestive heart failure 3.5% control, 4.2% non-cirrhotic NAFLD, 6.6% NAFLD-cirrhosis; and for atrial fibrillation 4.7% control, 5.9% non-cirrhotic NAFLD, 12.1% NAFLD-cirrhosis. Over 14-years follow-up, crude mortality rates were 14.7% control, 13.7% non-cirrhotic NAFLD, and 40.5% NAFLD-cirrhosis. However, after adjusting for demographics, non-cirrhotic NAFLD (HR 1.3 (95% CI 1.1–1.5)) as well as NAFLD-cirrhosis (HR 3.7 (95% CI 3.0–4.5)) patients had higher mortality compared to controls. These differences remained after adjusting for CVD and metabolic syndrome components: non-cirrhotic NAFLD (HR 1.2 (95% CI 1.0–1.4)) and NAFLD-cirrhosis (HR 3.4 (95% CI 2.8–4.2)). In conclusion, from a large non-specialist registry of hospitalised patients, those with non-cirrhotic NAFLD had increased overall mortality compared to controls even after adjusting for CVD.

Metabolic-Associated Fatty Liver Disease (MAFLD), Diabetes, and Cardiovascular Disease: Associations with Fructose Metabolism and Gut Microbiota

“…One retrospective, “real world” cohort study aimed to describe the CVD burden and mortality in patients with NAFLD during 14-years follow-up observation following hospital discharge, showing that in patients with non–cirrhotic NAFLD, the condition was associated with increased overall mortality [ 137 ]. In contrast, other studies have stated that NAFLD was not correlated with CVD mortality [ 138 , 139 , 140 ] nor an increased risk of acute myocardial infarction or stroke [ 141 ].…”

Trends in hospital admissions and prescribing due to diseases of the digestive system in England and Wales between 1999 and 2019: An ecological study

“…[ 36 ] Patients with NAFLD are also more prone to comorbidities, hospital admissions and mortality. [ 39 , 40 ] This could also be a reason for the rise in hospital admission which was noticed in the findings of this study.…”

Identification of key modules and driving genes in nonalcoholic fatty liver disease by weighted gene co-expression network analysis

“…NAFLD represents a spectrum of disease severity, ranging from simple steatosis to NASH, cirrhosis, and hepatocellular carcinoma (HCC) [ 28 ]. Compared with the general population, NAFLD patients are at increased risk of liver-related, kidney-related, cardiovascular and all-cause mortality [ 29 , 30 ]. However, with complex multifactorial pathogenesis, the genes or proteins related to progression of NAFLD remain obscure.…”