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Nonalcoholic Steatohepatitis: Epidemiology, Screening, Risk Assessment, Diagnosis, and Management

Quentin M. Anstee, BSc, MB BS, PhD, MRCP(UK), FRCP
Program Director
Philip N. Newsome, PhD, FRCPE
Released: August 21, 2019

Epidemiology

To date, precisely estimating the prevalence of NAFLD and NASH has been challenged by the diversity and variable reliability of methods for diagnosing NAFLD, inconsistent record keeping, and the inherent difficulties in screening for NASH when biopsy remains the gold standard.[8] Commonly used methods for diagnosing NAFLD have included serum liver function tests for elevated serum aminotransferases and gamma-glutamyl transferase, along with ultrasonography for steatosis. However, serum liver enzymes show variable elevations in the setting of NAFLD, with up to 80% of patients exhibiting normal values whereas ultrasonography lacks sensitivity for milder steatosis.[9] Even liver biopsy can demonstrate marked variability due to the uneven distribution of NASH-related lesions throughout the liver parenchyma, leading to sampling error and misdiagnosis.[10]

Despite these challenges, the global prevalence of NAFLD and NASH were recently estimated in a 2016 meta-analysis by Younossi and colleagues.[11] Drawing from 85 studies covering 22 countries from 1989 to 2015, the investigators estimated a global NAFLD prevalence of 25.24%. The frequency of NAFLD was lowest in Africa (13.48%) and greatest in the Middle East (31.79%) and South America (30.45%). Of note, although NAFLD is prevalent worldwide, its epidemiology and associated demographic features can vary markedly. For example, in the United States and Europe, NAFLD is closely associated with obesity and insulin resistance, whereas in Southeast Asia, NAFLD can often be seen in the setting of a lower body mass index (BMI).[12]

The regional differences in NAFLD prevalence may be associated with ethnicity, although the exact relationship between ethnicity and NAFLD remains unresolved. Some studies suggest that there are markedly higher rates in Hispanic populations in the United States compared with non-Hispanic white and black individuals.[13,14] A 2018 meta-analysis of US-based studies reported that NAFLD prevalence was highest in Hispanic populations (22.9%), followed by white (14.4%) and then black populations (13.0%). The lower frequency of hepatic steatosis in black individuals does not appear to be explained by differences in BMI or insulin resistance. Instead, polymorphisms in genes such as the PNPLA3 gene encoding adiponutrin, which is involved in lipogenesis and lipolysis in hepatocytes and adipocytes, have been suggested to account for differences in the prevalence of NAFLD among different ethnic groups.[15,16]

NAFLD rates also differ by age and sex. The prevalence of NAFLD appears to plateau at approximately 27% between 40 and 69 years of age and then increases to approximately 34% in those 70 years of age or older.[11] Regarding sex, NAFLD is more common among men than women. For example, a Spanish cross-sectional study reported a significantly higher rate of NAFLD in men compared with women (33.4% vs 20.3%, respectively; P < .001) in 766 individuals randomly selected from 25 primary care centers in Barcelona.[17] Consistently higher rates have been reported in men vs women in populations worldwide.[18]

Accurate data on the prevalence of NASH are more limited, requiring modeling to derive population-level estimates. It is important to note, however, that these data are often generated in tertiary centers and consequently may reflect an element of ascertainment bias. As with NAFLD, the estimated prevalence of NASH in the general population varies among different regions of the world, with rates in the United States ranging from 1.50% to 6.45%; in the European Union, approximately 3.00%; and in Asia, 2.00% to 3.00%.[19] The meta-analysis by Younossi and colleagues described above estimated that among patients worldwide with NAFLD who had undergone biopsy, NASH was present in 59.10%.[11]

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