China’s Fatty Liver Crisis: A Looming Public Health Emergency

See “Prevalence of liver steatosis and fibrosis in the general population and various high-risk populations: a nationwide study with 5.7 million adults in China” by Man S, Deng Y, Ma Y, et al, on page 1025. See “Prevalence of liver steatosis and fibrosis in the general population and various high-risk populations: a nationwide study with 5.7 million adults in China” by Man S, Deng Y, Ma Y, et al, on page 1025. As of today, nonalcoholic fatty liver disease (NAFLD) is estimated to affect ∼30% of the global adult population.1Yip T.C. Vilar-Gomez E. Petta S. et al.Geographical similarity and differences in the burden and genetic predisposition of NAFLD.Hepatology. 2023; 77: 1404-1427Crossref PubMed Scopus (23) Google Scholar Originally considered a Western disease, studies in the past 2 decades have firmly established that NAFLD is also the most common chronic liver disease in Asia.2Fan J.G. Kim S.U. Wong V.W. New trends on obesity and NAFLD in Asia.J Hepatol. 2017; 67: 862-873Abstract Full Text Full Text PDF PubMed Scopus (669) Google Scholar,3Li J. Zou B. Yeo Y.H. et al.Prevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999–2019: a systematic review and meta-analysis.Lancet Gastroenterol Hepatol. 2019; 4: 389-398Abstract Full Text Full Text PDF PubMed Scopus (523) Google Scholar In the United States, nonalcoholic steatohepatitis (NASH), the active form of NAFLD with faster fibrosis progression, has become one of the leading causes of cirrhosis and hepatocellular carcinoma (HCC).4Younossi Z.M. Harring M. Younossi Y. et al.The impact of NASH to liver transplantations with hepatocellular carcinoma in the United States.Clin Gastroenterol Hepatol. 2022; 20: 2915-2917.e1Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Traditionally, research in NAFLD requires careful exclusion of concomitant liver diseases and excessive alcohol consumption. This creates an artificial situation and limits the external validity of study findings. In the real world, patients with fatty liver and metabolic risk factors often have concomitant chronic viral hepatitis and harmful drinking, and emerging data suggest that these concomitant risk factors can have additive or synergistic effects on adverse liver-related outcomes.5Younossi Z.M. Stepanova M. Ong J. et al.Effects of alcohol consumption and metabolic syndrome on mortality in patients with nonalcoholic and alcohol-related fatty liver disease.Clin Gastroenterol Hepatol. 2019; 17: 1625-1633.e1Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar,6Yip T.C. Wong V.W. Lai M.S. et al.Diabetes mellitus impacts on the performance of hepatocellular carcinoma risk scores in chronic hepatitis B patients [published online ahead of print February 22, 2023]. Clin Gastroenterol Hepatol.https://doi.org/10.1016/j.cgh.2023.02.004Google Scholar Currently, a joint-society working group led by the American Association for the Study of Liver Diseases, European Association for the Study of the Liver, and Latin American Association for the Study of the Liver is in the final stage of issuing consensus statements on the nomenclature and definition of fatty liver diseases. With this background, the study by Man et al7Man S. Deng Y. Ma Y. et al.Prevalence of liver steatosis and fibrosis in the general population and various high-risk populations: a nationwide study with 5.7 million adults in China.Gastroenterology. 2023; 165: 1025-1040Abstract Full Text Full Text PDF Google Scholar in this issue of Gastroenterology is of particular interest. The study used a large health checkup database of 5,757,335 individuals from 30 of 31 provinces in mainland China.7Man S. Deng Y. Ma Y. et al.Prevalence of liver steatosis and fibrosis in the general population and various high-risk populations: a nationwide study with 5.7 million adults in China.Gastroenterology. 2023; 165: 1025-1040Abstract Full Text Full Text PDF Google Scholar Apart from routine anthropometric and laboratory assessments, the participants also underwent transient elastography using the FibroTouch machine (Hisky, Wuxi, China). Limited data in the literature suggest that the machine has a similar performance to FibroScan, with ultrasound attenuation parameter and liver stiffness measurement reflecting the degree of hepatic steatosis and fibrosis, respectively.8Qu Y. Song Y.Y. Chen C.W. et al.Diagnostic performance of FibroTouch ultrasound attenuation parameter and liver stiffness measurement in assessing hepatic steatosis and fibrosis in patients with nonalcoholic fatty liver disease.Clin Transl Gastroenterol. 2021; 12e00323Crossref Scopus (15) Google Scholar,9Duan W.J. Wang X.Z. Ma A.L. et al.Multicenter prospective study to validate a new transient elastography device for staging liver fibrosis in patients with chronic hepatitis B.J Dig Dis. 2020; 21: 519-525Crossref PubMed Scopus (14) Google Scholar Using published cutoffs, the authors estimated that 44.4% of the study population had fatty liver, 2.9% had advanced fibrosis, and 0.87% had cirrhosis. With a wealth of data from such a huge cohort, the authors7Man S. Deng Y. Ma Y. et al.Prevalence of liver steatosis and fibrosis in the general population and various high-risk populations: a nationwide study with 5.7 million adults in China.Gastroenterology. 2023; 165: 1025-1040Abstract Full Text Full Text PDF Google Scholar were able to evaluate the epidemiology of fatty liver and liver fibrosis in various subgroups and identify independent risk factors for liver disease (Figure 1). A few patterns clearly stood out. Geographically, although fatty liver was highly prevalent in essentially all regions of China, the prevalence was >50% in Northern China but was closer to 35% in the South and Southwest. In contrast, there appears to be a disconnect between fatty liver and liver fibrosis. Although advanced fibrosis was also common in Northern China, it was equally prevalent in some parts of Eastern and Central China. Of course, fatty liver is not the only driver of liver fibrosis in such a big country. It would be very interesting if other risk factors of liver injury, such as the prevalence of chronic viral hepatitis and alcohol consumption in each region and province, were considered as well. In the current study, advanced fibrosis was found in 7.2% of participants with chronic hepatitis B virus infection and in 2.9% of uninfected individuals. Not surprisingly, older age, male sex, metabolic risk factors, and increased serum alanine aminotransferase level were associated with fatty liver, whereas the same factors, together with elevated aspartate aminotransferase level, thrombocytopenia, hypoalbuminemia, and radiologic fatty liver, were associated with fibrosis. The negative association between elevated aspartate aminotransferase and fatty liver might be explained by the classification of some patients with burnt-out NASH as not having fatty liver. Curiously, among the metabolic risk factors, obesity had the strongest association with fatty liver, with adjusted odds ratios of 7.9 to 15.1 compared with 1.3 to 2.0 for the other metabolic conditions. In previous studies, diabetes was a more important risk factor for both NAFLD and its severity.10Lee H.W. Wong G.L. Kwok R. et al.Serial transient elastography examinations to monitor patients with type 2 diabetes: a prospective cohort study.Hepatology. 2020; 72: 1230-1241Crossref PubMed Scopus (47) Google Scholar,11Zhang X. Wong G.L. Yip T.C. et al.Risk of liver-related events by age and diabetes duration in patients with diabetes and nonalcoholic fatty liver disease.Hepatology. 2022; 76: 1409-1422Crossref PubMed Scopus (11) Google Scholar It would be important to determine whether the measurements were confounded by obesity. It is, however, important to understand that a health checkup cohort could be different from a true population -prevalence study. For example, the National Health and Nutrition Examination Surveys in the United States and some previous population studies in Asia attempted to minimize selection bias through random sampling.12Vilar-Gomez E. Vuppalanchi R. Mladenovic A. et al.Prevalence of high-risk nonalcoholic steatohepatitis (NASH) in the United States: results from NHANES 2017–2018.Clin Gastroenterol Hepatol. 2023; 21: 115-124.e7Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar,13Wong V.W. Wong G.L. Yeung D.K. et al.Incidence of non-alcoholic fatty liver disease in Hong Kong: a population study with paired proton-magnetic resonance spectroscopy.J Hepatol. 2015; 62: 182-189Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar Individuals at health check-ups could be more health conscious on one hand and might know they had certain diseases on the other. In the current study in particular, participants had to pay for the additional transient elastography examination, and the motivation behind the choice is difficult to discern. Furthermore, two-thirds of the participants were male, and the vast majority were working age. Unlike the National Health and Nutrition Examination Surveys, there was no effort to enrich the cohort with ethnic minorities or people from rural areas. Therefore, despite the large sample size, segments of the Chinese population remained underrepresented, and one cannot reliably calculate the age- and sex-standardized prevalence rate to fully understand the burden of NAFLD in China. Despite these caveats, the study undoubtedly confirms that NAFLD has reached a colossal magnitude in China. Besides, with a population of 1.4 billion, every 1% increase in the prevalence of NAFLD or advanced fibrosis would translate into 14 million more people having the conditions. The compound effect of childhood obesity and population aging also means that Chinese people will live with NAFLD for a longer duration than any time in history and thus are more likely to progress to advanced liver disease and develop cirrhotic complications and HCC.14Lin H. Yip T.C. Zhang X. et al.Age and the relative importance of liver-related deaths in nonalcoholic fatty liver disease.Hepatology. 2023; 77: 573-584Crossref PubMed Scopus (11) Google Scholar In fact, a modeling study suggests that the number of people in mainland China having NAFLD, NASH, NASH-related HCC, and NASH mortality would increase by 22%, 48%, 86%, and 118%, respectively, from 2016 to 2030.15Estes C. Anstee Q.M. Arias-Loste M.T. et al.Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016–2030.J Hepatol. 2018; 69: 896-904Abstract Full Text Full Text PDF PubMed Scopus (962) Google Scholar Similar trends are seen in Hong Kong, Taiwan, Singapore, and South Korea.16Estes C. Chan H.L.Y. Chien R.N. et al.Modelling NAFLD disease burden in four Asian regions—2019-2030.Aliment Pharmacol Ther. 2020; 51: 801-811Crossref PubMed Scopus (74) Google Scholar Unfortunately, a recent survey indicates that no country has a national plan to combat this growing epidemic.17Lazarus J.V. Mark H.E. Villota-Rivas M. et al.The global NAFLD policy review and preparedness index: are countries ready to address this silent public health challenge?.J Hepatol. 2022; 76: 771-780Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar It is thus imperative that we hepatologists work with different stakeholders to improve NAFLD care. Above all, policymakers should recognize NAFLD as an important chronic noncommunicable disease. Primary prevention of NAFLD and metabolic dysfunction through healthy lifestyle at the societal level cannot be overemphasized.18Expert Committee of Fatty Liver Prevention and Treatment Fund of China Health Promotion Foundation, Chronic Disease Management Branch of China Medical Biotechnology Association. Brief version of health management service package of metabolic dysfunction associated fatty liver disease.Chin J Health Manage. 2023; 17: 169-179Google Scholar We should also build clinical care pathways with a focus on the link between primary care and specialists and effective use of noninvasive tests of NAFLD.19Kanwal F. Shubrook J.H. Adams L.A. et al.Clinical care pathway for the risk stratification and management of patients with nonalcoholic fatty liver disease.Gastroenterology. 2021; 161: 1657-1669Abstract Full Text Full Text PDF PubMed Google Scholar,20Wong V.W.S. Zelber-Sagi S. Cusi K. et al.Management of NAFLD in primary care settings.Liver Int. 2022; 42: 2377-2389Crossref PubMed Scopus (11) Google Scholar Prevalence of Liver Steatosis and Fibrosis in the General Population and Various High-Risk Populations: A Nationwide Study With 5.7 Million Adults in ChinaGastroenterologyVol. 165Issue 4PreviewA considerable burden of liver steatosis and fibrosis exists in China, especially in populations with cardiovascular and chronic liver disease risk factors, such as obesity, diabetes, metabolic syndrome, and hepatitis B virus infection. Full-Text PDF Open Access