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Journal of Gastroenterology

, Volume 52, Issue 2, pp 164–174 | Cite as

Nonalcoholic fatty liver disease in Asia: emerging perspectives

  • Wai-Kay Seto
  • Man-Fung Yuen
Review

Abstract

As in the West, nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease in Asia, with a prevalence higher than 40 % in some countries. The risk factors for NAFLD development are similar to those in Western countries, including increased body mass index, diabetes, insulin resistance, and metabolic syndrome. NAFLD in Asians is associated with different extrahepatic manifestations involving the cardiovascular, gastrointestinal, and renal systems. A considerable proportion of Asians with NAFLD are described as having “lean” NAFLD. Present in approximately 20 % of the Asian population, lean NAFLD is closely linked with insulin resistance, diabetes, and other metabolic complications, but its association with disease progression to nonalcoholic steatohepatitis and cirrhosis remains to be defined. There is emerging evidence of the interactions of NAFLD with hepatitis B virus and hepatitis C virus infection in Asia. Unlike in Western countries, NAFLD constitutes only a minority of cirrhosis and hepatocellular carcinoma cases in Asia. Possible explanations are the lower prevalence of obesity and the overwhelming problem of viral hepatitis in Asia. With aging of the obesity cohort in Asia, NAFLD-related liver complications are expected to increase.

Keywords

Nonalcoholic fatty liver disease Steatosis Obesity Metabolic Nonalcoholic steatohepatitis Hepatitis B virus Hepatitis C virus Cirrhosis Asian 

Abbreviations

BMI

Body mass index

DAA

Direct-acting antiviral

HBV

Hepatitis B virus

HCC

Hepatocellular carcinoma

HCV

Hepatitis C virus

NAFLD

Nonalcoholic fatty liver disease

NASH

Nonalcoholic steatohepatitis

Notes

Compliance with ethical standards

Conflict of interest

The authors declares no conflicts of interest.

References

  1. 1.
    Farrell GC, Wong VW, Chitturi S. NAFLD in Asia—as common and important as in the West. Nat Rev Gastroenterol Hepatol. 2013;10(5):307–18.PubMedCrossRefGoogle Scholar
  2. 2.
    Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40(6):1387–95.PubMedCrossRefGoogle Scholar
  3. 3.
    Williams CD, Stengel J, Asike MI, et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology. 2011;140(1):124–31.PubMedCrossRefGoogle Scholar
  4. 4.
    Caballeria L, Pera G, Auladell MA, et al. Prevalence and factors associated with the presence of nonalcoholic fatty liver disease in an adult population in Spain. Eur J Gastroenterol Hepatol. 2010;22(1):24–32.PubMedCrossRefGoogle Scholar
  5. 5.
    Watanabe S, Hashimoto E, Ikejima K, et al. Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. J Gastroenterol. 2015;50(4):364–77.PubMedCrossRefGoogle Scholar
  6. 6.
    Eguchi Y, Hyogo H, Ono M, et al. Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2009 to 2010 in Japan: a multicenter large retrospective study. J Gastroenterol. 2012;47(5):586–95.PubMedCrossRefGoogle Scholar
  7. 7.
    Jeong EH, Jun DW, Cho YK, et al. Regional prevalence of non-alcoholic fatty liver disease in Seoul and Gyeonggi-do, Korea. Clin Mol Hepatol. 2013;19(3):266–72.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Fung J, Lee CK, Chan M, et al. High prevalence of non-alcoholic fatty liver disease in the Chinese—results from the Hong Kong liver health census. Liver Int. 2015;35(2):542–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Li Z, Xue J, Chen P, et al. Prevalence of nonalcoholic fatty liver disease in mainland of China: a meta-analysis of published studies. J Gastroenterol Hepatol. 2014;29(1):42–51.PubMedCrossRefGoogle Scholar
  10. 10.
    Yan J, Xie W, Ou WN, et al. Epidemiological survey and risk factor analysis of fatty liver disease of adult residents, Beijing, China. J Gastroenterol Hepatol. 2013;28(10):1654–9.PubMedGoogle Scholar
  11. 11.
    Zhai HL, Wang NJ, Han B, et al. Low vitamin D levels and non-alcoholic fatty liver disease, evidence for their independent association in men in East China: a cross-sectional study (Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China)). Br J Nutr. 2016;115:1352–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Chen CH, Huang MH, Yang JC, et al. Prevalence and risk factors of nonalcoholic fatty liver disease in an adult population of Taiwan: metabolic significance of nonalcoholic fatty liver disease in nonobese adults. J Clin Gastroenterol. 2006;40(8):745–52.PubMedCrossRefGoogle Scholar
  13. 13.
    Hung SC, Lai SW, Chen MC, et al. Prevalence and related factors of non-alcoholic fatty liver disease among the elderly in Taiwan. Eur Geriatr Med. 2013;4(2):78–81.CrossRefGoogle Scholar
  14. 14.
    Goh SC, Ho EL, Goh KL. Prevalence and risk factors of non-alcoholic fatty liver disease in a multiracial suburban Asian population in Malaysia. Hepatol Int. 2013;7(2):548–54.PubMedCrossRefGoogle Scholar
  15. 15.
    Goh GB, Kwan C, Lim SY, et al. Perceptions of non-alcoholic fatty liver disease – an Asian community-based study. Gastroenterol Rep (Oxf). 2016;4:131–5.CrossRefGoogle Scholar
  16. 16.
    Cahyono SB, Bayupurnama P, Ratnasari N, et al. Ultrasound-diagnosed non-alcoholic fatty liver disease among medical check up patients. Indones J Gastroenterol Hepatol Dis Endosc. 2013;14(3):145–9.Google Scholar
  17. 17.
    Dassanayake AS, Kasturiratne A, Rajindrajith S, et al. Prevalence and risk factors for non-alcoholic fatty liver disease among adults in an urban Sri Lankan population. J Gastroenterol Hepatol. 2009;24(7):1284–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Amarapurkar D, Kamani P, Patel N, et al. Prevalence of non-alcoholic fatty liver disease: population based study. Ann Hepatol. 2007;6(3):161–3.PubMedGoogle Scholar
  19. 19.
    Wong VW, Chu WC, Wong GL, et al. Prevalence of non-alcoholic fatty liver disease and advanced fibrosis in Hong Kong Chinese: a population study using proton-magnetic resonance spectroscopy and transient elastography. Gut. 2012;61(3):409–15.PubMedCrossRefGoogle Scholar
  20. 20.
    Weston SR, Leyden W, Murphy R, et al. Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly diagnosed chronic liver disease. Hepatology. 2005;41(2):372–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Kojima S, Watanabe N, Numata M, et al. Increase in the prevalence of fatty liver in Japan over the past 12 years: analysis of clinical background. J Gastroenterol. 2003;38(10):954–61.PubMedCrossRefGoogle Scholar
  22. 22.
    Zhu JZ, Zhou QY, Wang YM, et al. Prevalence of fatty liver disease and the economy in China: a systematic review. World J Gastroenterol. 2015;21(18):5695–706.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Shi L, Liu ZW, Li Y, et al. The prevalence of nonalcoholic fatty liver disease and its association with lifestyle/dietary habits among university faculty and staff in Chengdu. Biomed Environ Sci. 2012;25(4):383–91.PubMedGoogle Scholar
  24. 24.
    Nseir W, Hellou E, Assy N. Role of diet and lifestyle changes in nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20(28):9338–44.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Wong VW, Wong GL, Yeung DK, 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(1):182–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Bedogni G, Miglioli L, Masutti F, et al. Incidence and natural course of fatty liver in the general population: the Dionysos study. Hepatology. 2007;46(5):1387–91.PubMedCrossRefGoogle Scholar
  27. 27.
    Zelber-Sagi S, Lotan R, Shlomai A, et al. Predictors for incidence and remission of NAFLD in the general population during a seven-year prospective follow-up. J Hepatol. 2012;56(5):1145–51.PubMedCrossRefGoogle Scholar
  28. 28.
    Tao Y, Gu H, Wu J, et al. Thyroid function is associated with non-alcoholic fatty liver disease in euthyroid subjects. Endocr Res. 2015;40(2):74–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Chou TC, Liang WM, Wang CB, et al. Obstructive sleep apnea is associated with liver disease: a population-based cohort study. Sleep Med. 2015;16(8):955–60.PubMedCrossRefGoogle Scholar
  30. 30.
    Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40(12):1461–5.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Li Y, Xing C, Tian Z, et al. Genetic variant I148M in PNPLA3 is associated with the ultrasonography-determined steatosis degree in a Chinese population. BMC Med Genet. 2012;13:113.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Kawaguchi T, Sumida Y, Umemura A, et al. Genetic polymorphisms of the human PNPLA3 gene are strongly associated with severity of non-alcoholic fatty liver disease in Japanese. PLoS One. 2012;7(6):e38322.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Bhatt SP, Nigam P, Misra A, et al. Genetic variation in the patatin-like phospholipase domain-containing protein-3 (PNPLA-3) gene in Asian Indians with nonalcoholic fatty liver disease. Metab Syndr Relat Disord. 2013;11(5):329–35.PubMedCrossRefGoogle Scholar
  34. 34.
    Zain SM, Mohamed R, Mahadeva S, et al. A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease. Hum Genet. 2012;131(7):1145–52.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Speliotes EK, Butler JL, Palmer CD, et al. PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease. Hepatology. 2010;52(3):904–12.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Singal AG, Manjunath H, Yopp AC, et al. The effect of PNPLA3 on fibrosis progression and development of hepatocellular carcinoma: a meta-analysis. Am J Gastroenterol. 2014;109(3):325–34.PubMedCrossRefGoogle Scholar
  37. 37.
    Guyot E, Sutton A, Rufat P, et al. PNPLA3 rs738409, hepatocellular carcinoma occurrence and risk model prediction in patients with cirrhosis. J Hepatol. 2013;58(2):312–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Hotta K, Yoneda M, Hyogo H, et al. Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease. BMC Med Genet. 2010;11:172.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Anstee QM, Day CP. The genetics of NAFLD. Nat Rev Gastroenterol Hepatol. 2013;10(11):645–55.PubMedCrossRefGoogle Scholar
  40. 40.
    Guo Y, Xiong Y, Sheng Q, et al. A micro-RNA expression signature for human NAFLD progression. J Gastroenterol. 2016. doi: 10.1007/s00535-016-1178-0.
  41. 41.
    Huang HL, Lin WY, Lee LT, et al. Metabolic syndrome is related to nonalcoholic steatohepatitis in severely obese subjects. Obes Surg. 2007;17(11):1457–63.PubMedCrossRefGoogle Scholar
  42. 42.
    Park SH, Kim BI, Yun JW, et al. Insulin resistance and C-reactive protein as independent risk factors for non-alcoholic fatty liver disease in non-obese Asian men. J Gastroenterol Hepatol. 2004;19(6):694–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Chang Y, Jung HS, Yun KE, et al. Cohort study of non-alcoholic fatty liver disease, NAFLD fibrosis score, and the risk of incident diabetes in a Korean population. Am J Gastroenterol. 2013;108(12):1861–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Nishioji K, Sumida Y, Kamaguchi M, et al. Prevalence of and risk factors for non-alcoholic fatty liver disease in a non-obese Japanese population, 2011–2012. J Gastroenterol. 2015;50(1):95–108.PubMedCrossRefGoogle Scholar
  45. 45.
    Nakahara T, Hyogo H, Yoneda M, et al. Type 2 diabetes mellitus is associated with the fibrosis severity in patients with nonalcoholic fatty liver disease in a large retrospective cohort of Japanese patients. J Gastroenterol. 2014;49(11):1477–84.PubMedCrossRefGoogle Scholar
  46. 46.
    WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363(9403):157–63.CrossRefGoogle Scholar
  47. 47.
    Das K, Das K, Mukherjee PS, et al. Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease. Hepatology. 2010;51(5):1593–602.PubMedCrossRefGoogle Scholar
  48. 48.
    Liu CJ. Prevalence and risk factors for non-alcoholic fatty liver disease in Asian people who are not obese. J Gastroenterol Hepatol. 2012;27(10):1555–60.PubMedCrossRefGoogle Scholar
  49. 49.
    Miyake T, Kumagi T, Hirooka M, et al. Significance of exercise in nonalcoholic fatty liver disease in men: a community-based large cross-sectional study. J Gastroenterol. 2015;50(2):230–7.PubMedCrossRefGoogle Scholar
  50. 50.
    Takahashi H, Ono M, Hyogo H, et al. Biphasic effect of alcohol intake on the development of fatty liver disease. J Gastroenterol. 2015;50(11):1114–23.PubMedCrossRefGoogle Scholar
  51. 51.
    Cauley JA, Danielson ME, Boudreau R, et al. Serum 25-hydroxyvitamin D and clinical fracture risk in a multiethnic cohort of women: the Women’s Health Initiative (WHI). J Bone Miner Res. 2011;26(10):2378–88.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Adams LA, Waters OR, Knuiman MW, et al. NAFLD as a risk factor for the development of diabetes and the metabolic syndrome: an eleven-year follow-up study. Am J Gastroenterol. 2009;104(4):861–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Hsiao PJ, Kuo KK, Shin SJ, et al. Significant correlations between severe fatty liver and risk factors for metabolic syndrome. J Gastroenterol Hepatol. 2007;22(12):2118–23.PubMedCrossRefGoogle Scholar
  54. 54.
    Fan JG, Farrell GC. Epidemiology of non-alcoholic fatty liver disease in China. J Hepatol. 2009;50(1):204–10.PubMedCrossRefGoogle Scholar
  55. 55.
    Wong VW, Wong GL, Yip GW, et al. Coronary artery disease and cardiovascular outcomes in patients with non-alcoholic fatty liver disease. Gut. 2011;60(12):1721–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Wong VW, Wong GL, Yeung JC, et al. Long-term clinical outcomes after fatty liver screening in patients undergoing coronary angiogram: a prospective cohort study. Hepatology. 2016;63(3):754–63.PubMedCrossRefGoogle Scholar
  57. 57.
    Kim D, Choi SY, Park EH, et al. Nonalcoholic fatty liver disease is associated with coronary artery calcification. Hepatology. 2012;56(2):605–13.PubMedCrossRefGoogle Scholar
  58. 58.
    Kim NH, Park J, Kim SH, et al. Non-alcoholic fatty liver disease, metabolic syndrome and subclinical cardiovascular changes in the general population. Heart. 2014;100(12):938–43.PubMedCrossRefGoogle Scholar
  59. 59.
    Kim BJ, Kim NH, Kim BS, et al. The association between nonalcoholic fatty liver disease, metabolic syndrome and arterial stiffness in nondiabetic, nonhypertensive individuals. Cardiology. 2012;123(1):54–61.PubMedCrossRefGoogle Scholar
  60. 60.
    Kim HC, Kim DJ, Huh KB. Association between nonalcoholic fatty liver disease and carotid intima-media thickness according to the presence of metabolic syndrome. Atherosclerosis. 2009;204(2):521–5.PubMedCrossRefGoogle Scholar
  61. 61.
    Liccardo D, Mosca A, Petroni S, et al. The association between retinal microvascular changes, metabolic risk factors, and liver histology in pediatric patients with non-alcoholic fatty liver disease (NAFLD). J Gastroenterol. 2015;50(8):903–12.PubMedCrossRefGoogle Scholar
  62. 62.
    Wong VW, Wong GL, Tsang SW, et al. High prevalence of colorectal neoplasm in patients with non-alcoholic steatohepatitis. Gut. 2011;60(6):829–36.PubMedCrossRefGoogle Scholar
  63. 63.
    Lin XF, Shi KQ, You J, et al. Increased risk of colorectal malignant neoplasm in patients with nonalcoholic fatty liver disease: a large study. Mol Biol Rep. 2014;41(5):2989–97.PubMedCrossRefGoogle Scholar
  64. 64.
    Huang KW, Leu HB, Wang YJ, et al. Patients with nonalcoholic fatty liver disease have higher risk of colorectal adenoma after negative baseline colonoscopy. Colorectal Dis. 2013;15(7):830–5.PubMedCrossRefGoogle Scholar
  65. 65.
    Lee YI, Lim YS, Park HS. Colorectal neoplasms in relation to non-alcoholic fatty liver disease in Korean women: a retrospective cohort study. J Gastroenterol Hepatol. 2012;27(1):91–5.PubMedCrossRefGoogle Scholar
  66. 66.
    Akiyama T, Yoneda M, Inamori M, et al. Visceral obesity and the risk of Barrett’s esophagus in Japanese patients with non-alcoholic fatty liver disease. BMC Gastroenterol. 2009;9:56.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Chang Y, Ryu S, Sung E, et al. Nonalcoholic fatty liver disease predicts chronic kidney disease in nonhypertensive and nondiabetic Korean men. Metabolism. 2008;57(4):569–76.PubMedCrossRefGoogle Scholar
  68. 68.
    Arase Y, Suzuki F, Kobayashi M, et al. The development of chronic kidney disease in Japanese patients with non-alcoholic fatty liver disease. Intern Med. 2011;50(10):1081–7.PubMedCrossRefGoogle Scholar
  69. 69.
    Younossi ZM, Stepanova M, Negro F, et al. Nonalcoholic fatty liver disease in lean individuals in the United States. Medicine (Baltimore). 2012;91(6):319–27.CrossRefGoogle Scholar
  70. 70.
    Sinn DH, Gwak GY, Park HN, et al. Ultrasonographically detected non-alcoholic fatty liver disease is an independent predictor for identifying patients with insulin resistance in non-obese, non-diabetic middle-aged Asian adults. Am J Gastroenterol. 2012;107(4):561–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Wei JL, Leung JC, Loong TC, et al. Prevalence and severity of nonalcoholic fatty liver disease in non-obese patients: a population study using proton-magnetic resonance spectroscopy. Am J Gastroenterol. 2015;110(9):1306–14.PubMedCrossRefGoogle Scholar
  72. 72.
    Xu C, Yu C, Ma H, et al. Prevalence and risk factors for the development of nonalcoholic fatty liver disease in a nonobese Chinese population: the Zhejiang Zhenhai Study. Am J Gastroenterol. 2013;108(8):1299–304.PubMedCrossRefGoogle Scholar
  73. 73.
    Feldman A, Eder SK, Felder TK, et al. Clinical and metabolic characterization of lean Caucasian subjects with non-alcoholic fatty liver. Am J Gastroenterol. 2016. doi: 10.1038/ajg.2016.318.
  74. 74.
    van der Poorten D, Milner KL, Hui J, et al. Visceral fat: a key mediator of steatohepatitis in metabolic liver disease. Hepatology. 2008;48(2):449–57.PubMedCrossRefGoogle Scholar
  75. 75.
    Feng RN, Du SS, Wang C, et al. Lean-non-alcoholic fatty liver disease increases risk for metabolic disorders in a normal weight Chinese population. World J Gastroenterol. 2014;20(47):17932–40.PubMedPubMedCentralGoogle Scholar
  76. 76.
    Sung KC, Ryan MC, Wilson AM. The severity of nonalcoholic fatty liver disease is associated with increased cardiovascular risk in a large cohort of non-obese Asian subjects. Atherosclerosis. 2009;203(2):581–6.PubMedCrossRefGoogle Scholar
  77. 77.
    Dela Cruz AC, Bugianesi E, George J, et al. Characteristics and long-term prognosis of lean patients with non-alcoholic fatty liver disease. Gastroenterology. 2014;146:S909.CrossRefGoogle Scholar
  78. 78.
    Castera L, Hezode C, Roudot-Thoraval F, et al. Worsening of steatosis is an independent factor of fibrosis progression in untreated patients with chronic hepatitis C and paired liver biopsies. Gut. 2003;52(2):288–92.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Poynard T, Ratziu V, McHutchison J, et al. Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C. Hepatology. 2003;38(1):75–85.PubMedCrossRefGoogle Scholar
  80. 80.
    Shah SR, Patel K, Marcellin P, et al. Steatosis is an independent predictor of relapse following rapid virologic response in patients with HCV genotype 3. Clin Gastroenterol Hepatol. 2011;9(8):688–93.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Pekow JR, Bhan AK, Zheng H, et al. Hepatic steatosis is associated with increased frequency of hepatocellular carcinoma in patients with hepatitis C-related cirrhosis. Cancer. 2007;109(12):2490–6.PubMedCrossRefGoogle Scholar
  82. 82.
    Hwang SJ, Luo JC, Chu CW, et al. Hepatic steatosis in chronic hepatitis C virus infection: prevalence and clinical correlation. J Gastroenterol Hepatol. 2001;16(2):190–5.PubMedCrossRefGoogle Scholar
  83. 83.
    Yaginuma R, Ikejima K, Okumura K, et al. Hepatic steatosis is a predictor of poor response to interferon α-2b and ribavirin combination therapy in Japanese patients with chronic hepatitis C. Hepatol Res. 2006;35(1):19–25.PubMedCrossRefGoogle Scholar
  84. 84.
    Kurosaki M, Hosokawa T, Matsunaga K, et al. Hepatic steatosis in chronic hepatitis C is a significant risk factor for developing hepatocellular carcinoma independent of age, sex, obesity, fibrosis stage and response to interferon therapy. Hepatol Res. 2010;40(9):870–7.PubMedCrossRefGoogle Scholar
  85. 85.
    Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. New Engl J Med. 2014;370(20):1889–98.PubMedCrossRefGoogle Scholar
  86. 86.
    Ferenci P, Bernstein D, Lalezari J, et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. New Engl J Med. 2014;370(21):1983–92.PubMedCrossRefGoogle Scholar
  87. 87.
    Meissner EG, Lee YJ, Osinusi A, et al. Effect of sofosbuvir and ribavirin treatment on peripheral and hepatic lipid metabolism in chronic hepatitis C virus, genotype 1-infected patients. Hepatology. 2015;61(3):790–801.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Younossi ZM, Stepanova M, Estep M, et al. Dysregulation of distal cholesterol biosynthesis in association with relapse and advanced disease in CHC genotype 2 and 3 treated with sofosbuvir and ribavirin. J Hepatol. 2016;64(1):29–36.PubMedCrossRefGoogle Scholar
  89. 89.
    Lai CL, Wong VW, Yuen MF, et al. Sofosbuvir plus ribavirin for the treatment of patients with chronic genotype 1 or 6 hepatitis C virus infection in Hong Kong. Aliment Pharmacol Ther. 2016;43(1):96–101.PubMedCrossRefGoogle Scholar
  90. 90.
    Wong VW, Wong GL, Chu WC, et al. Hepatitis B virus infection and fatty liver in the general population. J Hepatol. 2012;56(3):533–40.PubMedCrossRefGoogle Scholar
  91. 91.
    Luo B, Wang Y, Wang K. Association of metabolic syndrome and hepatitis B infection in a Chinese population. Clin Chim Acta. 2007;380(1–2):238–40.PubMedCrossRefGoogle Scholar
  92. 92.
    Jan CF, Chen CJ, Chiu YH, et al. A population-based study investigating the association between metabolic syndrome and hepatitis B/C infection (Keelung community-based integrated screening study no. 10). Int J Obes (Lond). 2006;30(5):794–9.CrossRefGoogle Scholar
  93. 93.
    Machado MV, Oliveira AG, Cortez-Pinto H. Hepatic steatosis in hepatitis B virus infected patients: meta-analysis of risk factors and comparison with hepatitis C infected patients. J Gastroenterol Hepatol. 2011;26(9):1361–7.PubMedGoogle Scholar
  94. 94.
    Wong GL, Wong VW, Choi PC, et al. Metabolic syndrome increases the risk of liver cirrhosis in chronic hepatitis B. Gut. 2009;58(1):111–7.PubMedCrossRefGoogle Scholar
  95. 95.
    Kim KH, Shin HJ, Kim K, et al. Hepatitis B virus X protein induces hepatic steatosis via transcriptional activation of SREBP1 and PPARγ. Gastroenterology. 2007;132(5):1955–67.PubMedCrossRefGoogle Scholar
  96. 96.
    Shi JP, Fan JG, Wu R, et al. Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese patients with chronic hepatitis B infection. J Gastroenterol Hepatol. 2008;23(9):1419–25.PubMedCrossRefGoogle Scholar
  97. 97.
    Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381(9865):468–75.PubMedCrossRefGoogle Scholar
  98. 98.
    Charlton MR, Burns JM, Pedersen RA, et al. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology. 2011;141(4):1249–53.PubMedCrossRefGoogle Scholar
  99. 99.
    Ekstedt M, Franzen LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006;44(4):865–73.PubMedCrossRefGoogle Scholar
  100. 100.
    Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology. 2010;51(5):1820–32.PubMedCrossRefGoogle Scholar
  101. 101.
    Welzel TM, Graubard BI, Quraishi S, et al. Population-attributable fractions of risk factors for hepatocellular carcinoma in the United States. Am J Gastroenterol. 2013;108(8):1314–21.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149(2):389–97.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Michitaka K, Nishiguchi S, Aoyagi Y, et al. Etiology of liver cirrhosis in Japan: a nationwide survey. J Gastroenterol. 2010;45(1):86–94.PubMedCrossRefGoogle Scholar
  104. 104.
    Duseja A. Nonalcoholic fatty liver disease in India—a lot done, yet more required! Indian J Gastroenterol. 2010;29(6):217–25.PubMedCrossRefGoogle Scholar
  105. 105.
    Goh KL, Razlan H, Hartono JL, et al. Liver cancer in Malaysia: epidemiology and clinical presentation in a multiracial Asian population. J Dig Dis. 2015;16(3):152–8.PubMedCrossRefGoogle Scholar
  106. 106.
    Wong DK, Huang FY, Lai CL, et al. Occult hepatitis B infection and HBV replicative activity in patients with cryptogenic cause of hepatocellular carcinoma. Hepatology. 2011;54(3):829–36.PubMedCrossRefGoogle Scholar
  107. 107.
    Ng M, Fleming T, Robinson M, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766–81.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Ramos GA, Caughey AB. The interrelationship between ethnicity and obesity on obstetric outcomes. Am J Obstet Gynecol. 2005;193(3 Pt 2):1089–93.PubMedCrossRefGoogle Scholar
  109. 109.
    Corley DA, Kubo A, Zhao W. Abdominal obesity, ethnicity and gastro-oesophageal reflux symptoms. Gut. 2007;56(6):756–62.PubMedCrossRefGoogle Scholar
  110. 110.
    Oh SW, Yoon YS, Shin SA. Effects of excess weight on cancer incidences depending on cancer sites and histologic findings among men: Korea National Health Insurance Corporation Study. J Clin Oncol. 2005;23(21):4742–54.PubMedCrossRefGoogle Scholar
  111. 111.
    Wong VW, Wong GL, Choi PC, et al. Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. Gut. 2010;59(7):969–74.PubMedCrossRefGoogle Scholar
  112. 112.
    Yatsuji S, Hashimoto E, Tobari M, et al. Clinical features and outcomes of cirrhosis due to non-alcoholic steatohepatitis compared with cirrhosis caused by chronic hepatitis C. J Gastroenterol Hepatol. 2009;24(2):248–54.PubMedCrossRefGoogle Scholar
  113. 113.
    Kelly T, Yang W, Chen CS, et al. Global burden of obesity in 2005 and projections to 2030. Int J Obes (Lond). 2008;32(9):1431–7.CrossRefGoogle Scholar
  114. 114.
    Tokushige K, Hyogo H, Nakajima T, et al. Hepatocellular carcinoma in Japanese patients with nonalcoholic fatty liver disease and alcoholic liver disease: multicenter survey. J Gastroenterol. 2016;51(6):586–96.PubMedCrossRefGoogle Scholar
  115. 115.
    El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142(6):1264–73.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Sasso M, Beaugrand M, de Ledinghen V, et al. Controlled attenuation parameter (CAP): a novel VCTE guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes. Ultrasound Med Biol. 2010;36(11):1825–35.PubMedCrossRefGoogle Scholar
  117. 117.
    Banerjee R, Pavlides M, Tunnicliffe EM, et al. Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease. J Hepatol. 2014;60(1):69–77.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Imajo K, Yoneda M, Fujita K, et al. Oral choline tolerance test as a novel noninvasive method for predicting nonalcoholic steatohepatitis. J Gastroenterol. 2014;49(2):295–304.PubMedCrossRefGoogle Scholar

Copyright information

© Japanese Society of Gastroenterology 2016

Authors and Affiliations

  1. 1.Department of Medicine, Queen Mary HospitalThe University of Hong KongPok Fu LamHong Kong
  2. 2.State Key Laboratory for Liver ResearchThe University of Hong KongPok Fu LamHong Kong

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