The burden of cardiovascular disease and mortality across a spectrum of non-alcoholic fatty liver disease: A 14-year follow-up population study of 929,465 individuals

Background and Aims: Non-alcoholic fatty liver disease (NAFLD)is recognised as a risk factor for cardiovascular disease (CVD)with some evidence, albeit from small studies, that non-alcoholicsteatohepatitis (NASH) conveys greater risk than NAFLD. In thislarge UK study we studied the overall burden of CVD and all-causemortality across the spectrum of NAFLD.Methods: Anonymous data was obtained from a local computerisedhospital activity analysis register regarding a total population of929,465 patients in England area during 2000–2013. Data was processedusing the ACALM (Algorithm for Co-morbidity, Associations,Length of stay and Mortality) study protocol, using ICD-10 codesto identify patients with NAFLD (K76.0), NASH (75.8), and NAFLDcirrhosis [cryptogenic cirrhosis (K74.6)] throughout the studyperiod. Cardiovascular comorbidities were coded according to theICD-10 criteria and their prevalence were analysed over 14-years.Results: During the 14-year study period, 2701 patients werediagnosed with NAFLD-spectrum conditions: 1294 with NAFLD,122 with NASH, and 1285 with cirrhosis. Mean ages at diagnosiswere 51±0.4, 52±2 and 59±0.4 years, respectively. All groups hada male predominance (56–58%) and were 78–80% Caucasian. Allcausemortality was higher in NASH than NAFLD (22.1% vs. 14.5%,p = 0.025), and in cirrhosis than NAFLD (53.1% vs. 14.5%, p < 0.001).Congestive cardiac failure (CCF) was less prevalent in NAFLD thanNASH (p = 0.001) and cirrhosis (p < 0.001). The prevalence of type 2diabetes mellitus, atrial fibrillation, hyperlipidaemia, chronic kidneydisease were higher in the advanced stages of NAFLD (Table 1).There was no difference in the prevalence of hypertension betweenthe groups.Table 1. Prevalence of mortality, metabolic and cardiovascular outcomes forpatients within the spectrum of NAFLD during a 14-year study periodClinical outcome Number (%)NAFLD(n = 1294)NASH(n = =122)Cirrhosis(n = 1285)Congestive cardiac failure 49 (3.8) 11 (9.0)‡ 85 (6.6)*Atrial fibrillation 64 (4.9) 10 (8.2) 107 (8.3)**Type 2 diabetes 271 (20.9) 30 (24.6) 401 (31.2)**Chronic kidney disease 40 (3.1) 6 (4.9) 89 (6.9)**Hyperlipidaemia 156 (12.1) 21 (17.2) 64 (5.0)**Hypertension 381 (29.4) 42 (34.4) 351 (27.3)Mortality 188 (14.5) 27 (22.1)† 682 (53.1)**For NAFLD vs. NASH: †p < 0.05, ‡p < 0.01. For NAFLD vs. cirrhosis: *p < 0.001,**p < 0.0001.Conclusions: By utilising a large population based cohort this studyprovides important new insights into mortality and cardiovasculardisease in patients with NAFLD. Notably, during a 14-year studyperiod, death occurs in over 20% of patients diagnosed with NASHand 50% with related-cirrhosis.