‘Significant’ Excess Mortality Risk Seen Across All NAFLD Stages

Investigators studied the risk of overall and cause-specific mortality across the histological spectrum in individuals with non-alcoholic fatty liver disease.

All non-alcoholic fatty liver disease (NAFLD) histological stages were found to be associated with significantly increased overall mortality, according to findings from a population-based matched cohort study published in Gut. This risk “increased progressively with worsening NAFLD histology,” and most excess mortality was associated with extrahepatic cancer and cirrhosis, the investigators said.

The study used data from the Epidemiology Strengthened by Histopathology Reports in Sweden (ESPRESSO) database, which includes prospectively recorded liver histopathology information from all 28 pathology departments in Sweden from 1966 to 2017. The analysis included biopsies from 10,568 adults with histologically confirmed NAFLD.

Patients were matched for age, gender, collection year, and geographical area with up to 5 individuals from the general population (n=49,925) and categorized by NAFLD group: simple steatosis (67.2%), non-alcoholic steatohepatitis (NASH) without fibrosis (11.5%), non-cirrhotic fibrosis (15.7%), and cirrhosis (5.6%).The investigators assessed patients and their matched cohorts for disease prevalence and all-cause mortality. Among patients with NAFLD, the average age at index biopsy was 52 years, and 44.8% were women.

Compared with the general population, patients with NAFLD were found to have higher rates of cardiovascular disease than patients in the general population (20.1% vs 11.7%), dyslipidemia (7.1% vs 3.8%), diabetes (11.2% vs 2.8%), hypertension (9.8% vs 4.8%), obesity (4.4% vs 0.4%), and metabolic syndrome (2.8% vs 0.7%).

A total of 4338 patients with NAFLD and 13,911 patients in the general population died during the study period, which corresponded with a 20-year absolute risk difference of 15.3% (95% CI, 13.3-17.3). This translated to a 1.93-fold increased risk for overall mortality compared with the general population sample (95% CI, 1.86-2.00; P <.01).

Excess mortality was observed among all NAFLD subtypes. The adjusted hazard ratio (aHR) for simple steatosis was 1.71 (95% CI, 1.64-1.79); 2.14 (95% CI, 1.93-2.38) NASH without fibrosis; 2.44 (95% CI, 2.22-2.69) for non-cirrhotic fibrosis; and 3.79 (95% CI, 3.34-4.30) for cirrhosis. The severity of NAFLD histology correlated with increased mortality (all P <.01).

In patients with NAFLD and patients from the general population, extrahepatic cancer and cardiovascular disease were the 2 most common causes of death. Compared with the general population, the NAFLD group had higher rates of cause-specific mortality due to extrahepatic cancer (4.8 vs 9.3/1000 person-years [PY]; aHR, 2.16; 95% CI, 2.03-2.30) and cirrhosis (0.2 vs 2.8/1000 PY aHR, 18.15; 95% CI, 14.78-22.30). This trend continued with respect to cardiovascular disease (6.9 vs 8.3/1000 PY; aHR, 1.35; 95% CI, 1.26-1.44) and hepatocellular carcinoma (0.1 vs 1.3/1000 PY; aHR, 11.12; 95% CI, 8.65-14.30).

The investigators cited several potential study limitations, including the Swedish population’s primarily White makeup, making it unclear whether the findings could be generalizable for a more diverse population. Additionally, pathology data might have been subject to sampling error and interobserver variability.

Nevertheless, the data indicated that all histological stages of NAFLD were associated with increased risk for mortality, which rose in a dose-dependent manner with worsening NAFLD severity. “Our findings underscore the importance of reversing all stages of NAFLD, while also highlighting the need for effective public health strategies designed to prevent cancer and cirrhosis, in this high-risk and growing population,” the investigators concluded.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of the authors’ disclosures.

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Simon TG, Roelstraete B, Khalili H, Hagström H, Ludvigsson JF, et al. Mortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort. Gut. Published October 9, 2020. doi: 10.1136/gutjnl-2020-322786