Long-term Prognosis of Patients With Alcohol-related Liver Disease or Non-alcoholic Fatty Liver Disease According to Metabolic Syndrome or Alcohol Use

Marie Decraecker; Dan Dutartre; Jean-Baptiste Hiriart; Marie Irles-Depé; Hortense Marraud des Grottes; Faiza Chermak; Juliette Foucher; Adèle Delamarre; Victor de Ledinghen


Liver International. 2022;42(2):350-362. 

In This Article

Abstract and Introduction


Background & Aims: The boundary between non-alcoholic (NAFLD) and alcohol-related liver disease (ALD) is based on alcohol consumption. However, metabolic syndrome and alcohol use frequently co-exist. The aim of this study was to determine prognostic factors of long-term morbidity and mortality in patients with NAFLD or ALD.

Methods: From 2003 to 2016, all consecutive NAFLD or ALD patients were prospectively included in this cohort study. We evaluated overall survival, specific cause of mortality and occurrence of any complication. The primary endpoint was analysed by the Kaplan Meier method, secondary endpoints were estimated by Gray test method or logistic regressions. Factors independently associated with overall mortality and morbidity were identified by a multivariate Cox model.

Results: A total of 3365 patients (1667 with ALD and 1698 with NAFLD) were included. Median follow-up was 54 months (range: 30–86) and 563 subjects died.

In the overall population, overall mortality was higher in patients with ALD (HR: 10.1 [7.57–13.3]), and with weekly alcohol consumption >7 units (HR:1.66 [1.41–1.96]). Liver-related mortality was higher in patients with ALD (HR: 11 [7.27–16.5]). In the NAFLD group, weekly alcohol consumption >1 unit was associated with higher overall mortality (HR: 1.9 [1.1–3.4]), and weekly alcohol consumption >7 units was associated with higher overall morbidity (OR: 1.89 [1.61–2.21]). In the ALD group, the presence of metabolic syndrome was associated with higher overall (HR:1.27 [1.02–1.57]), and liver (HR: 1.47 [1.1–1.96]) mortalities, and overall (OR: 1.46 [1.14–1.88]), liver (OR: 1.46 [1.14–1.88]) morbidities.

Conclusion: In fatty liver diseases, light alcohol consumption and metabolic syndrome are prognosis cofactors.


Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries, with an estimated prevalence of 18.2% in France.[1] The condition is interlinked with features of metabolic syndrome including obesity, insulin resistance, type 2 diabetes mellitus (T2DM) and atherogenic dyslipidaemia.

Moderate alcohol consumption frequently coexists with NAFLD, and cohort studies estimate that 20% of patients may have characteristics of both NAFLD and (ALD).[2] However, current medical practice tends to dichotomize fatty liver diseases into ALD and NAFLD, based on an arbitrary threshold for alcohol consumption: set at 14 standard units per week for women and 21 units per week for men.[3] There are considerable interaction effects between alcohol use and metabolic abnormalities in the development and progression of fatty liver diseases.[4–6] Both conditions share many pathophysiological processes and have a wide spectrum of liver disorders ranging from simple steatosis to steatohepatitis, fibrosis and cirrhosis and its complications (such as hepatocellular carcinoma [HCC] and ascites). In this context, the potential benefit and harm of light to moderate alcohol use in NAFLD is therefore currently unclear. Indeed, while some studies have suggested protective effects of moderate alcohol consumption, particularly on the cardiovascular system, others have reported increased risks of moderate or excessive use in the presence of, or regardless of, metabolic syndrome.[7]

Furthermore, although its evolution towards liver-related complications is relatively slow, approximately one-third of NAFLD patients may eventually progress to non-alcoholic steatohepatitis, 20% of whom will develop liver fibrosis with an increased risk of cirrhosis and liver failure.[8,9] Similarly, only 15–20% of heavy alcohol drinkers ever develop cirrhosis.[10] A study by Chang demonstrated that moderate alcohol consumption, lower than 30 g/day for men and 20 g/day for women, was associated with fibrosis in the presence of NAFLD, measured with non-invasive methods.[11] Liver fibrosis evaluation is a key step in determining the prognosis of fatty liver diseases.[12,13] In the past decade, non-invasive methods, especially liver stiffness measurement (LSM), have been developed to evaluate the severity of chronic liver diseases.[14–17] Recently, Shili-Masmoudi et al. showed that LSM could be used to predict survival and complications in NAFLD patients.

The aim of the study was to assess overall survival in patients with NAFLD according to alcohol use and ALD according to the presence of the metabolic syndrome.