Global incidence of adverse clinical events in non-alcoholic fatty liver disease: A systematic review and meta-analysis

Abstract

Background/aims: Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events.

Methods: We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events.

Results: 19,406 articles were screened, 409 full-text articles reviewed, and 79 eligible studies (1,377,466 persons) were included. Mean age was 51.47 years and body mass index 28.90 kg/m2. Baseline comorbidities included metabolic syndrome (41.73%), cardiovascular disease (CVD) (16.83%), cirrhosis (21.97%), and nonalcoholic steatohepatitis (NASH) (58.85%). Incidence rate per 1,000 person-years for mortality included: all-cause (14.6), CVD-related (4.53), non-liver cancer-related (4.53), and liver-related (3.10). Incidence for liver-related events included overall (24.3), fibrosis progression (49.0), cirrhosis (10.9), liver transplant (12.0), and hepatocellular carcinoma (HCC) (3.39). Incidence for non-liver events included metabolic syndrome (25.4), hypertension (25.8), dyslipidemia (26.4), diabetes (19.0), CVD (24.77), renal impairment (30.3), depression/anxiety (29.1), and non-liver cancer (10.5). Biopsy-proven NASH had higher incidence of HCC (P=0.043) compared to non-NASH. Higher rates of CVD and mortality were observed in North America and Europe, hypertension and non-liver cancer in North America, and HCC in Western Pacific/Southeast Asia (P<0.05). No significant differences were observed by sex. Time-period analyses showed decreasing rates of cardiovascular and non-liver cancer mortality and increasing rates of decompensated cirrhosis (P<0.05).

Conclusion: People with NAFLD have high incidence of liver and non-liver adverse clinical events, varying by NASH, geographic region, and time-period, but not sex.

Keywords: Cirrhosis; Epidemiology; Meta-analysis; NAFLD.

Figure 1.

Study selection flowchart and subgroups by NAFLD diagnostic method. NAFLD, nonalcoholic fatty liver disease.

Figure 2.

Clinical outcomes among NAFLD participants stratified by region (see corresponding forest plots in Supplementary Figure 2A–M and additional details in Supplementary Table 4). (A) Mortality, (B) Liver-related events, (C) Decompensation events, (D) Metabolic events, (E) Cardiovascular events, (F) Other events. NAFLD, nonalcoholic fatty liver disease; CVD, cardiovascular disease; DM, diabetes mellitus; HLD/DLD, hyperlipidemia/dyslipidemia; HTN, hypertension; MI, myocardial infarction; CAD/CHF, coronary artery disease/congestive heart failure.

Figure 3.

Clinical outcomes among NAFLD participants with liver biopsy, stratified by biopsy proven NASH (additional details in Supplementary Table 5). (A) Mortality, (B) Liver-related events, (C) Nonliver events. NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; CVD, cardiovascular disease; HCC, hepatocellular carcinoma; HLD/DLD, hyperlipidemia/dyslipidemia; DM, diabetes mellitus.