Epidemiology of NAFLD in China Jian-Gao Fan MD, PhD.

Transcription

1 Epidemiology of NAFLD in China Jian-Gao Fan MD, PhD. Professor and Director Department of Gastroenterology Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai , China

2 Epidemiological studies in FLD Case definition Liver biopsy CT scan Ultrasound FibroScan/FibroTouch FLI, HSI Sampling frame Population Community Clinical based Hospital based --Consecutive/Non-consecutive

3 Ultrasound of fatty liver

4 Fatty liver in given specific Chinese population Labor workers in Daqing, Liaonin (n=4100): 5% Labor workers in Beijing (n=1050): 11% Employees in Shaoxing, Zhejiang (n=11372): 10% White collars in Beijing (n=818): 18% White collars in Shanghai (n=4009): 13% Among 6553 employees in Lianyungang, Jiangsu: retired cadre 10%, policemen 9%, clerk 6%, workmen 4% Fan JG. Review. Shijie Huaren Xiaohua Zazhi 2001;9:6-10.

5 Increased prevalence of fatty liver in China City Period Subjects Trend *Beijing Administrative officers 23% to 26% Shanghai Factory workers 4% to 14% Wuhan Office workers 12.5% to 24.5% Fan JG, JGH 2007;22: Wang Z. Postgrad Med J 2007;83: * unpublished

6 Increased prevalence of FL in Shanghai factory workers between 1995 and % 50% 40% 30% 20% 10% 0% Fatty liver Habitual drinking FL/Abnormal ALT Obesity Daibetes Hypertension Hyper-TG Hyper-TC Fan JG, et al. J Gastroenterol Hepatol 2007;22:

7 Consensus of management of FLD by Chinese Society of Medicine Guideline for the diagnosis of NAFLD and ALD. Chin J Hepatol 2001 & 2003 Guidelines for diagnosis and treatment of NAFLD & ALD. J Dig Dis 2008; 9: Chinese Guidelines for diagnosis and management of NAFLD & ALD: update J Dig Dis 2011; 12:

8 Definition of NAFLD There is evidence of hepatic steatosis, either by imaging or by histology, and no causes for secondary steatosis. NAFLD is a highly prevalent form of FLD caused by over-nutrition. NAFLD is an acquired metabolic stressinduced liver diseases associated with insulin resistance and genetic susceptibility.

9 Fatty liver in general population in China City/Year Prevalence Etiology Others Shanghai/ % AFL 0.8%, NAFL 15% Other 1.2% Guangzhou/ % AFL 0.5%, NAFL 11.7% Other 1.8% Drinking 13% Children 1.3% Xi an/ % AFL 8.7% (?), NAFL 14.7% Drinking 66% Chengdu/ % AFL 2.6%, NAFL 6.3% Other 3.6% Beijing/ % AFL 4.1%, NAFL 31.3% Shanghai/ /8810 (40-70 yrs in Chongming Island) NAFLD 42.2% 27.6% in NGT, 45.7% in pre-diabetes, 62.5% in diabetes persons Fan, J Hepatol 2005; 43: Zhou, WJG 2007;13: Yan, Hepatol Int 2008; 2:S86-S87. Li, HBPD Int. 2009;8: Yan, JGH; 2013, 28: Yang Z, Sci Rep. 2016;6:37886.

10 Prevalence of Fatty Liver in Shanghai Adults Total 17% Male 19% Female 15% 5% 7% AFL Mixed FL NAFLD 15% AFL 0.8% Mixed FL 1.2% NAFLD 88% Fan JG, et al. J Hepatol 2005; 43:

11 Criteria for obesity and MetS Only 2-3% of Asians classified as obesity by Western criteria. ethnic differences All Asian populations studied had a higher BF% at a lower BMI compared to Caucasians For the same BF%, their BMI was 3-5 units lower compared to Caucasians.

12 Modified definition for Asians Three or more of the following: Central obesity and/or obesity: Waistline >90 cm (M), >80 cm (F) and/or BMI > 25 kg/m 2 Hypertriglyceridaemia: TG 1.7 mmol/l Low HDL-C: <1.03 mmol/l (M), <1.29 mmol/l (F) High blood pressure: 130/85 mmhg. High fasting glucose: FPG 6.1 mmol/l. Fan JG & Pen YD. HBPT Int 2007

13 Fan JG, World J Gastroenterol, 2008; 14:

14 Prevalence of NAFLD/NASH in Shanghai Prevalence of fatty liver and the metabolic syndrome(%) Fatty liver Metabolic syndrome Both prevalence of MetS and NAFLD was 15.3% in Shanghai adults in In NAFLD, prevalence of MetS and abnormal ALT was 52.9% and 12.7%, respectively. Prevalence of NASH might be between 1.9% and 4.1% in Shanghai adults BMI<23 BMI BMI>=25 Fan JG, J Gastroenterol Hepatol 2005 with some data unpublished

15 Prevalence of Lean NAFLD Lean NAFLD is more common in Asia Prevalence of Lean NAFLD in General Population Proportion of Lean NAFLD over all NAFLD USA (Younossi 2012) KOREA (Cho HC 2016) KOREA (Kim HJ 2004) INDIA (Das K 2010) China (Fan 2007)

16 Prevalence of NASH in Shanghai Bao-Steel Company A total of employees of Shanghai Bao-Steel Company were undergone biannual health check-up. Prevalence of abnormal ALT was 4.6%, without obvious changes between 1995 and Prevalence of fatty liver in patients with abnormal ALT was increased between from 25.9% to 51.4%. Prevalence of NAFLD among subjects was 13.1% in 2002, percentage of abnormal ALT among NAFLD patients was 16.4%. Prevalence of NASH might be around 2.2% in health check-up adults in Fan JG, J Gastroenterol Hepatol 2007 with some data unpublished

17 Incidence of NAFLD in Shanghai 5,226 non-drinking workers without US-fatty liver at baseline. After 2-year follow-up, 310 pts (6.2%) were found to have NAFLD. Incidence of NAFLD (3 new cases/100 people/ year) is equal to that in Dionysos study. The baseline BMI, serum triglyceride and their subtle gain during follow-up were independent predictors of incident of NAFLD. Fan JG, et al. Hepatol International, 2010

18 Impact of BMI on incidence and remission of NAFLD < > 30 Incidence of FL Changes of BMI with FL Changes of BMI without FL < > 30 Remission rate of FL Changes of BMI with FL remission Changes of BMI persistent with FL 13.6% (60/440) NAFLD was recovery at the end of 2-year follow-up. Zhou C Fan JG. Chin J Intern Med Chin J Hepatol 2010

19 Increased prevalence of obesity in Asia 8% 7% 6% 5% 4% 3% 2% China Japan Korea India Indonesia 1% 0% Year Fan JG, et al. J Hepatol 2017

20 Global prevalence of NAFLD Younossi Z, et al. Gastroenterology.2016;150:

21 Wang FS, Fan JG, et al. Hepatology 2014; 60:

22 Etiology of fatty liver in liver clinic in Shanghai 6.4% 7.2% 8.3% Non-alcoholic Alcoholic Virus hepatitis Miscellous % 90.00% 80.00% 70.00% 60.00% 50.00% 40.00% 30.00% Percent of abnormal ALT Percent 78.1% 20.00% 10.00% 0.00% NAFLD AFL HBV with FL DILI-FL Percent of NASH might be 20% in out-patients with NAFLD. Fan JG, et al. Shanghai Med J, 1998;21:68-70

23 Liver biopsy from 11 year old male with abnormal LFTs

24 Histological changes in 152 Chinese pts with NAFLD 100% % 60% 40% 20% 0% steatosis(1/2/3) ballonning degeneration (y/n) NAS(1-3;3-4;5) fibrosis(0-4) Male 73.8%, Age :37±10 yrs, BMI: 26±3 kg/m 2 Percent of NASH in biopsy-proven NAFLD was 41.4%. Advanced fibrosis was 15.8%, associated with MetS and severe inflammation. Xun YH, Fan JG, et al. J Dig Dis, 2012; 13:

25 Histological changes of 101 patients with NAFLD Characteristics NAFLD (n=101) None-NASH (n=15) Borderline NASH (n=32) Definitive NASH (n=54) P Steatosis grade,n (%) <0.001 S1 (5-33%) 32 (31.7) 15 (100) 15 (46.9) 2 (3.7) S2 (34-66%) 45 (44.6) 0 17(53.1) 28(51.9) S3 (>66%) 24 (23.8) (44.4) Fibrosis stage, n (%) <0.001 F0 18 (17.8) 7(46.7) 9(28.1) 2(3.7) F1 44 (43.6) 5(33.3) 21(65.6) 18(33.3) F2 26 (25.7) 1(6.7) 1(3.1) 24(44.4) F3 10 (9.9) 2 (13.3) 1(3.1) 7(13.0) F4 3 (3.0) (5.6) Percent of NASH and cirrhosis was 54% and 3%, respectively Both were associated with T2DM and MetS. Shen F, Fan JG. Liver Int 2015; 35:

26 Study profile of NAFLD across the Asia Pacific region the GO ASIA initiative Chan WK,.Fan JG,. Wong VWS. Aliment Pharmacol Ther. 2018; 47:

27 Percentage of patients with NASH by country the GO ASIA initiative Chan WK,.Fan JG,. Wong VWS. Aliment Pharmacol Ther. 2018; 47:

28 Percentage of patients with advanced fibrosis by country the GO ASIA initiative Chan WK,.Fan JG,. Wong VWS. Aliment Pharmacol Ther. 2018; 47:

29 Independent factors discriminating the different histological subgroups the GO ASIA initiative Chan WK,.Fan JG,. Wong VWS. Aliment Pharmacol Ther. 2018; 47:

30 Natural history of NAFLD according to data from Asia Annual incidence of NAFLD 3-4% 60% can reverse NAFLD by lifestyle intervention 25% progress from NAFL to NASH and have fibrosis progression in 3 yrs Spontaneous reversal of NASH uncommon without intervention Fibrosis progression 1 stage in 7 yrs in NASH; 1 stage in 14 yrs in NAFL No data on reversal of cirrhosis Normal liver NAFL NASH ± fibrosis Cirrhosis Absence of cirrhosis reported in 30-50% of NAFLD-associated HCC in Asians The absolute risk of HCC in noncirrhotic patients is <0.1% per year HCC 1-4% per year Fan JG, Kim SU, Wong WS. J Hepatol 2017

31 NAFLD leads to liver cancer: do we have sufficient evidence? Duan XY, Qiao L, Fan JG. Cancer letter 2014

32 32

33 80% 70% 60% 50% 40% 30% 20% 10% 0% Obesity Hypertension High TG high TC Diabetes MetS NAFLD n=358 Controls n=788 80% 70% 60% 50% 40% 30% 20% 10% 0% hypertension high TG high TC Diabetes FL with Obesity n=274 FL without Obesity n=84 Obesity alone n=174 Nor FL or obesity n=614 Fan JG, et al. JGH 2007;22:

34 上海宝钢队列糖尿病发病率与危险度比 基线特征 DM 发病数 DM 发病率 (%) 危险度比 (HR) N=12438,follow-up 6 years 95% CI 下限 95% CI 上限 肥胖 BMI <25 kg/m BMI 25 kg/m IFG (-) (+) 高 TG 血症 (-) (+) 高 TC 血症 (-) (+) 脂肪肝 (-) (+) 高 Hb 血症 (-) (+) Fan JG, et al. J Diabetes Investig. 2016; 7:

35 上海崇明脂肪肝流行病学调查 Circulating periostin in relation to insulin resistance and NAFLD among overweight and obese subjects. Sci Rep. 2016;6: Plasma selenium levels and NAFLD in Chinese adults: a cross-sectional analysis. Sci Rep. 2016; 6: Plasma osteoprotegerin levels are inversely associated with NAFLD in patients with type 2 diabetes: A case-control study in China. Metabolism. 2016; 65(4): Association of calf circumference with insulin resistance and NAFLD: the REACTION study. BMC Endocr Disord. 2017;17(1):28. Impaired lung function is associated with NAFLD independently of metabolic syndrome features in middle-aged and elderly Chinese. BMC Endocr Disord. 2017; 17(1):18.

36 Fatty liver & HBV infection in Chinese Inverse association between HBsAg+ve and ultrasound-diagnosed fatty liver both in Shanghai and Taipei. Fan JG, et al. World J Gastroenterol Cheng YL, et al. Plos One 2013 Inverse association between HBV infection and MRS-diagnosed fatty liver in Hong Kong adults. Wong VWS, et al. J Hepatol 2012 Inverse association between HBV infection and hypertriglyceridemia and MetS. Luo et al. Clin Chim Acta. 2007; Jan et al. Int J Obes 2006; Wong et al. J Hepatol 2012

37 Ye DW, Fan JG, et al.aasld,2009

38 Fan JG, et al. AASLD 2016

39 Fatty liver & CHB in Our Group 1 Hepatitis B and fatty liver: causal or coincidental? J Gastroenterol Hepatol. 2008; 23(5): Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese patients with CHB infection. J Gastroenterol Hepatol. 2008; 23: Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic mice model. J Gastroenterol Hepatol. 2012; 27: Hepatic Steatosis Is Highly Prevalent in CHB Patients and Negatively Associated with Virological Factors. Dig Dis Sci. 2014; 59: Saturated fatty acid Inhibits Viral Replication in HBV Infection with NAFLD by TLR4 Mediated Innate Immune Response. Hepat Mon. 2015; 15:e CAP for noninvasive assessment of hepatic steatosis using Fibroscan: Validation in chronic hepatitis B. Dig Dis Sci 2015; 60: Thyroid function is associated with NAFLD in chronic hepatitis B infected subjects. J Gastroenterol Hepatol. 2015; 30: Linked polymorphisms of PNPLA3 confer susceptibility to NASH and decreased viral load in chronic hepatitis B. World J Gastroenterol. 2015; 21: PNPLA3 rs predisposes CHB to hepatic steatosis, but improves insulin resistance and glucose metabolism. J Diabetes Res. 2017; 2017: Serum Monounsaturated Triacylglycerol Predicts Steatohepatitis in Patients with NAFLD and CHB. Sci Rep. 2017, 7:10517.

40 What are the settings for NAFLD? Overweight/Central obesity 50% Steatosis 10%-40% Steatohepatitis 50% Liver fibrosis 15%~30% Cirrhosis & HCC 30%~40% MetS T2DM Cancer & CVD Liver-related mortality Patrick L. Altern Med Rev, 2002, 7: Fan JG. JGH, 2007;22: JDD 2008;9:63-70

41 NAFLD is not just a Western problem Prevalence of fatty liver increased rapidly in past decades with obesity and MetS pandemic in China. Fatty liver is more often associated with obesity than with alcoholism. Chronic HBV infection do not account for increased trend of fatty liver and fatty liver increased in CHB as well. Cardiovascular and diabetic risk may compete with liver disease-related risk in dictating the final outcome. NAFLD is emerging into a new and major health problem in Chinese. Fan JG. J Hepatol 2009; JGH 2013.

42 Thanks for for your attention!