Patterns and Predictors of Mortality and Disease Progression Among Patients With Non-alcoholic Fatty Liver Sisease

Ali Canbay; Nandita Kachru; Jennifer Scarlet Haas; Jan-Peter Sowa; Dominic Meise; Ahmet Burak Ozbay


Aliment Pharmacol Ther. 2020;52(7):1185-1194. 

In This Article

Abstract and Introduction


Background: Factors associated with mortality and disease progression in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are poorly understood.

Aims: To assess the impact of liver disease severity, demographics and comorbidities on all-cause mortality and liver disease progression in a large, real-world cohort of NAFLD patients.

Methods: Claims data from the German Institut für angewandte Gesundheitsforschung database between 2011 and 2016 were analyzed retrospectively. Adult patients diagnosed with NAFLD and/or NASH were categorised as NAFLD, NAFLD non-progressors, compensated cirrhosis, decompensated cirrhosis, liver transplant or hepatocellular carcinoma (HCC). The longitudinal probability of mortality and incidence of progression were calculated for disease severity cohorts and multivariable analyses performed for adjusted mortality.

Results: Among 4 580 434 patients in the database, prevalence of NAFLD was 4.7% (n = 215 655). Of those, 36.8% were non-progressors, 0.2% compensated cirrhosis, 9.6% decompensated cirrhosis, 0.0005% liver transplant and 0.2% HCC. Comorbidity rates were significantly higher in compensated cirrhosis, decompensated cirrhosis and HCC compared with non-progressors. The longitudinal probability of mortality for non-progressors, compensated cirrhosis, decompensated cirrhosis and HCC was 3.6%, 18.7%, 28.8% and 68%, respectively. Independent predictors of mortality included cardiovascular disease, type 2 diabetes mellitus, hypertension, obesity and renal impairment. The cumulative incidence of progression in NAFLD and compensated cirrhosis patients was 10.7% and 16.7%, respectively, over 5 years of follow-up.

Conclusion: NAFLD patients were severely under-diagnosed and had a high probability of mortality that increased with disease progression. Early identification and effective management to halt or reverse fibrosis are essential to prevent progression.


Non-alcoholic fatty liver disease (NAFLD), today, is one of the leading causes of chronic liver diseases worldwide.[1,2] Consequently, the more progressive form of NAFLD—non-alcoholic steatohepatitis (NASH)—has become one of the most common etiologies of hepatocellular carcinoma (HCC) and a leading indication for liver transplant. Both conditions are frequently associated with metabolic comorbidities, including diabetes, dyslipidemia and obesity.[3–6] NAFLD and NASH patients are also at an increased risk for progression to advanced liver diseases including compensated cirrhosis, decompensated cirrhosis and HCC or liver transplant.[1,4,7–9]

The global prevalence of NAFLD is estimated at 25.2%, with a pooled overall prevalence of NASH in 29.9% of NAFLD patients in North America in the absence of a liver biopsy.[1] The prevalence of NASH rises to 59.1% in NAFLD patients undergoing biopsy.[1] There were an estimated 18.4 million cases of NAFLD in Germany in 2016, with modelling projections suggesting a 13.5% increase to 20.95 million total NAFLD cases by 2030. NASH cases in Germany for 2016 are estimated at 3.33 million, and this is projected to increase 43% to 4.74 million total cases by 2030.[2]

The development and progression through fibrosis stages are considered as the most important predictors of outcomes such as decompensation, HCC or liver transplant in NAFLD.[10,11] However, our current understanding of the natural history of NAFLD is incomplete due to a limited knowledge of patient and clinical factors in addition to fibrosis stages[10–12] that are associated with progression to advanced liver diseases and death. Most studies do not adjust for patient demographics or comorbid health conditions, do not evaluate risk associated with advanced liver diseases and are based on small sample sizes.[11,12] In addition, there are limited real-world data specific to the German population that accurately characterize disease progression and all-cause mortality rates. Thus, the aims of the presented analysis were twofold—firstly, to evaluate the probability of all-cause mortality and determine the impact of liver disease severity, demographics and comorbidities on the risk of all-cause mortality and secondly, to evaluate the probability of liver disease progression in a large real-world cohort of NAFLD patients in Germany.