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Prevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999–2019: a systematic review and meta-analysis

https://doi.org/10.1016/S2468-1253(19)30039-1Get rights and content

Summary

Background

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Asia is a large, heterogeneous area with substantial variation in socioeconomic status and prevalence of obesity. We estimated the prevalence, incidence, and outcomes of NAFLD in the Asian population to assist stakeholders in understanding NAFLD disease burden.

Methods

We searched PubMed, EMBASE, and the Cochrane Library from database inception to Jan 17, 2019, for studies reporting NAFLD prevalence, incidence, or outcome in Asia. We included only cross-sectional and longitudinal observational studies of patients with NAFLD diagnosed by imaging, serum-based indices, or liver biopsy. Studies that included patients with overlapping liver disease or that did not screen for excess alcohol consumption were excluded. Two investigators independently screened and extracted data. The main outcomes were pooled NAFLD prevalence, incidence, and hepatocellular carcinoma incidence and overall mortality in patients with NAFLD. Summary estimates were calculated using a random-effects model. This study is registered with PROSPERO, number CRD42018088468.

Findings

Of 4995 records identified, 237 studies (13 044 518 participants) were included for analysis. The overall prevalence of NAFLD regardless of diagnostic method was 29·62% (95% CI 28·13–31·15). NAFLD prevalence increased significantly over time (25·28% [22·42–28·37] between 1999 and 2005, 28·46% [26·70–30·29] between 2006 and 2011, and 33·90% [31·74–36·12] between 2012 and 2017; p<0·0001). The pooled annual NAFLD incidence rate was 50·9 cases per 1000 person-years (95% CI 44·8–57·4). In patients with NAFLD, the annual incidence of hepatocellular carcinoma was 1·8 cases per 1000 person-years (0·8–3·1) and overall mortality rate was 5·3 deaths per 1000 person-years (1·5–11·4).

Interpretation

NAFLD prevalence in Asia is increasing and is associated with poor outcomes including hepatocellular carcinoma and death. Targeted public health strategies must be developed in Asia to target the drivers of this rising epidemic and its associated complications, especially in high-risk groups, such as older obese men.

Funding

None.

Introduction

Non-alcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally.1, 2 NAFLD is a progressive disease, ranging from steatosis to non-alcoholic steato-hepatitis (NASH), cirrhosis, hepatocellular carcinoma, liver transplantation, and death.3, 4 NASH has become the second leading cause of liver transplantation in the USA and the incidence of hepatocellular carcinoma in patients with NAFLD has also increased substantially worldwide since 2000.5, 6, 7

NAFLD was historically considered a disease of the industrialised world, primarily associated with obesity, diabetes, and metabolic syndrome.8, 9 In recent years, with the improvement of living standards and changes in lifestyle and dietary habits, the prevalence of NAFLD has increased rapidly in Asia, becoming an important public health issue.10, 11, 12 Additionally, NAFLD can be diagnosed in so-called lean (non-obese) individuals who are metabolically different from non-obese people without NAFLD. NAFLD in lean individuals is associated with higher mortality than is NAFLD in obese individuals13, 14, 15 and has been described in Asian populations.16

Since Asia is a large and heterogeneous area with substantial variation in socioeconomic status and prevalence of obesity,17 the reported overall prevalence of NAFLD is widely variable, ranging from 15% to 40%.18, 19 The prevalence of NAFLD among so-called lean individuals in Asia with a body-mass index of less than 25 kg/m2 ranges between 7·0% and 20·0%.16, 19, 20, 21

Research in context

Evidence before this study

Non-alcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and is considered a disease of industrialised countries that is primarily associated with obesity, diabetes, and metabolic syndrome. Since Asia is a large and heterogeneous region with considerable variation in socioeconomic status and obesity prevalence, the reported overall prevalence of NAFLD is widely variable. We did a broad search of the scientific literature before intitiating this study to identify articles on NAFLD in Asia. We identified one meta-analysis on the global epidemiology of NAFLD published in 2016, the estimated pooled overall prevalence of NAFLD diagnosed by imaging in Asia was 27·37% (95% CI 23·29–31·88). We identified no systematic reviews of NAFLD prevalence, incidence, or outcome in Asia that specifically focused on NAFLD prevalence over time or the differences in prevalence between countries and regions of Asia.

Added value of this study

Understanding the disease burden within Asia has become imperative. Our systematic review and meta-analysis provides the most comprehensive assessment and robust evidence to date of the prevalence of NAFLD in Asia overall and in subgroups. Overall NAFLD prevalence in Asia regardless of diagnostic method was 29·62%, and prevalence was highest in Indonesia (51·04%) and lowest in Japan (22·28%). The overall incidence rate of NAFLD within the Asian population was 50·9 cases per 1000 person-years, the incidence rate of hepatocellular carcinoma was 1·8 cases per 1000 person-years, and overall mortality among study participants with NAFLD was 5·3 per 1000 person-years. The high prevalence of NAFLD observed in southeast Asia indicates that NAFLD is a disease that affects both individuals in areas that are rapidly becoming industrialised, suggesting that all Asian populations might be at risk. We also determined the incidence of NAFLD and the incidence of hepatocellular carcinoma and overall mortality in patients with NAFLD in the Asian population, for whom little data on NAFLD is available. We found that a large number of patients with NAFLD develop progressive liver disease, which creates challenges for screening.

Implications of all the available evidence

In this study, the prevalence of NAFLD was high in all Asian regions included and was found to be similar to that reported for western countries. The findings of our study will help stakeholders to better understand the current disease burden of NAFLD in Asia, which could lead to the development of strategies to increase disease awareness and interventions to decrease the disease burden. Future study should be devoted to defining the economic and public health burden of the NAFLD pandemic.

However, to date, no systematic reviews of the prevalence and outcome of NAFLD in Asia have been published. One meta-analysis2 on the global epidemiology of NAFLD was published in 2016, however, this analysis only included 20 studies from Asia, of which only 14 studies analysed overall prevalence. Therefore, we did a systematic review and meta-analysis to establish the overall NAFLD prevalence, incidence, and hepatocellular carcinoma incidence and overall mortality in patients with NAFLD in Asia. Additionally, we aimed to determine prevalence of NAFLD stratified by age, sex, country or region, income, and assessment method, and aimed to determine prevalence of NAFLD in obese and non-obese individuals and individuals with type 2 diabetes in Asia. We also investigated differences in various anthropometric measurements associated with NAFLD in individuals with and without NAFLD.

Section snippets

Search strategy and selection criteria

For this systematic review and meta-analysis, two authors (JL and BZ) independently searched PubMed, EMBASE, and the Cochrane Library from database inception to Jan 17, 2019, using search terms developed in collaboration with a medical librarian (CDS), without language restrictions. We searched for cross-sectional and longitudinal observational studies that included patients with NAFLD diagnosed by imaging, serum-based indices, or liver biopsy, and provided data on prevalence, incidence, or

Results

We identified 4995 records. After removal of duplicates, 3914 records were retained. We screened the titles and abstracts and excluded 3225 ineligible records. Full texts of the remaining 689 records were assessed for eligibility, of which 452 were excluded. 237 articles from 16 countries or regions (mainland China [n=93], South Korea [n=61], Japan [n=29], Taiwan [n=15], Iran [n=9], India [n=7], Hong Kong [n=6], Sri Lanka [n=3], Malaysia [n=3], Pakistan [n=3], Bangladesh [n=2], Indonesia [n=2],

Discussion

Asia is a growing epicentre for industrialisation and changing lifestyles with the potential for an increasing prevalence of NAFLD.24, 25, 26 In this systematic review and meta-analysis, we determined that the overall prevalence of NAFLD in adults in Asia, regardless of diagnostic method, was 29·62%. The pooled prevalence was 30·55% for NAFLD diagnosed by ultrasound, 24·83% for NAFLD diagnosed by MRI or CT, and 15·82% for NAFLD diagnosed by fatty liver index or hepatic steatosis index. When

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