Observations on the epidemiology of gastrointestinal and liver cancers in the Asia–Pacific region

bs_bs_banner doi: 10.1111/1751-2980.12164 Journal of Digestive Diseases 2014; 15; 463–468 Leading article Observations on the epidemiology of gastrointestinal and liver cancers in the Asia–Pacific region Li-Yen GOH,* Alex Hwong Ruey LEOW† & Khean-Lee GOH† *Faculty of Medicine, University of Nottingham, Nottingham, United Kingdom and †Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Gastric cancer (GC) has long been thought to be an highest CRC ASR have been reported from Asian Asian type of cancer that is broadly associated with countries, in many of which it has now surpassed poverty, whereas colorectal cancer (CRC) has been that of GC. Liver cancer is also an important cancer thought to be a Western type of cancer associated in the Asia–Pacific region. The highest ASR world- with affluence. The incidence of GC has declined wide is reported from the Asian countries of Mongo- dramatically in the West but has a very high inci- lia, Korea and Japan. The predominant underlying dence in East Asia. The age-standardized incidence etiology across the region has been hepatitis B virus rates (ASR) have also declined. The decrease in the infection, except in Japan, where hepatitis C is an incidence of GC is associated with the decrease in important cause of hepatocellular carcinoma (HCC). the prevalence of Helicobacter pylori (H. pylori ) infec- With mass vaccination of hepatitis B at birth and tion worldwide. The discrepancy between a high improved public health measures in many countries, H. pylori infection rate and a low GC incidence is hepatitis B and C are set to decline with time. seen chiefly among southern Asians of Indian origin However, the exponential increase in obesity and and has been aptly termed the “Indian enigma”. CRC consequent non-alcoholic fatty liver disease portends is a new emerging cancer in this region. Some of the a future epidemic of fatty liver-related HCC. KEY WORDS: Asia–Pacific region, colorectal neoplasms, gastric neoplasms, liver neoplasms, obesity. INTRODUCTION poverty-related diseases are declining steadily while those of affluence-associated new diseases are increas- The Asia–Pacific region faces dramatic changes in the ing. A continuous decline in the incidences of gastric epidemiology of gastrointestinal (GI) and liver dis- cancer (GC) and peptic ulcer disease (PUD) but an eases during the new millennium. With the rapid increase in gastroesophageal reflux disease (GERD) socioeconomic changes and growing affluence in most and colorectal cancer (CRC) have been reported. At of the region, the incidence and prevalence of old the same time, the occurrence of liver cancer and non- alcohol fatty liver disease (NAFLD) is increasing as Correspondence to: Khean-Lee GOH, Division of Gastroenterology and well.1 The disappearance of old diseases and the emer- Hepatology, Faculty of Medicine, University of Malaya, 50603, Kuala gence of new diseases pose a challenge in the way Lumpur, Malaysia. Email: [email protected] physicians think, diagnose and treat GI and liver dis- eases in the Asia–Pacific region. Conflict of interest: None. In this review we aimed to summarize and discuss the © 2014 Chinese Medical Association Shanghai Branch, Chinese continuous changes that have taken place in the epi- Society of Gastroenterology, Renji Hospital Affiliated to Shanghai demiology of major GI cancers such as GC, CRC and Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd 463

464 L-Y Goh et al. Journal of Digestive Diseases 2014; 15; 463–468 liver cancer. Concomitant changes in the epidemiol- tion is a necessary but not sufficient risk factor in gastric ogy of gastric acid-related diseases, such as GERD and carcinogenesis. The interaction of other putative factors PUD, as well as NAFLD are also discussed. including bacterial virulence, host genetic factors and diet is also vital in tumor carcinogenesis. In contrast, GC protective factors including dietary ingredients such as curcumin, which is commonplace in the Indian diet, GC remains one of the most common cancers in the have been thought to be gastroprotective agents.4 Thais Asia–Pacific region. In 2012, the highest incidence of and Malays from Malaysia and Indonesia share a GC for males and females was reported by Korea, broadly similar diet rich in spices and chili, and both Mongolia and Japan, with an age-standardized rate had a low prevalence of H. pylori infection, resulting in (ASR) (per 100 000) of 41.8 in Korea, 32.5 in Mon- a low incidence of GC.5 golia and 29.9 in Japan, respectively,2 in contradistinc- tion to many Western countries where GC is an Nonetheless, the incidence of GC has, to some extent, uncommon cancer with an ASR of less than 10 per started to decline in some areas of Asia such as China 100 000 (Table 1). and Japan, where GC used to be highly prevalent, especially in young populations, which may be attri- GC has always been considered as an Asian type of buted to the changes of lifestyle and countermeasures cancer that is associated with poverty and appears to be against H. pylori infection that have developed during more strongly correlated with the occurrence of the past decades.6–8 However, there were still approxi- Helicobacter pylori (H. pylori) infection than other types mately half a million newly diagnosed cases of GC in of cancers.3 However, Japan, one of the most developed China and Japan in 2012.2 The healthcare burden in and affluent Asian countries, also has a high ASR of GC terms of the actual number of GC patients will still and a high prevalence of H. pylori infection. Although remain high or even increase because of the increase in the prevalence of GC is decreasing, H. pylori infection elderly populations and the long life expectancy in rate in Japan is persistently high, pointing to a large Japan. reservoir of infection with intra-community spread. In Malaysia and Singapore, the two multiracial countries While the incidence of GC has been decreasing in where Malays, Chinese and Indians are the three main Western populations, cancer of the cardioesophageal ethnicities, H. pylori infection has been reported to be junction has increased dramatically.9 A proximal shift prevalent mostly among Chinese and Indians rather in GC is not widely seen in Asia, although reports have than Malays.4 This interesting and peculiar observation shown that the proportion of these cancers has has been explained by us as the racial cohort phenom- increased by up to 20%.10,11 enon. However, a high H. pylori infection rate does not appear to be correlated with a high incidence of GC in CRC Indians, which has been referred to as the Indian enigma.5 This is observed not only in multiracial Asian CRC has long been considered a Western disease and a countries such as Singapore and Malaysia but also in disease of affluence, which was used to be uncommon India itself, emphasizing the point that H. pylori infec- among Asians. There has, however, been clear evidence that the incidence of CRC has been increasing in the Table 1. Estimated age-standardized rate (ASR) of gastric Asia–Pacific region in recent years.12 According to the cancer with all ages for both genders in selected countries1 GLOBOCAN 2012,2 Korea had the highest ASR world- wide of 45.0 per 100 000 (Table 2), and the ASR in Country Patients ASR Singapore and Japan was reported to be 33.7 and 32.2 (n) (per 100 000) per 100 000, respectively. The ASR of most Western countries was over 20.0 per 100 000. Republic of Korea 31 269 41.8 Mongolia 646 32.5 Except India, almost all the Asia–Pacific countries Japan 29.9 recorded an ASR in excess of 10 per 100 000. In mul- China 107 898 22.7 tiracial Southeast Asian countries, Chinese had a India 404 996 higher ASR of CRC than Malays and Indians for both Indonesia 6.1 males and females.13,14 Again these geographical or Thailand 63 097 2.8 ethnic differences are intriguing, showing the interact- Sweden 6 011 3.1 ing roles of variable host genetic factors and environ- Canada 2 841 3.7 mental factors. 811 4.9 3 342 © 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd

Journal of Digestive Diseases 2014; 15; 463–468 GI and liver cancer in Asia 465 Table 2. Estimated age-standardized rate (ASR) of Table 3. Estimated age-standardized rate (ASR) of colorectal cancer with all ages for both genders in selected hepatocellular carcinoma with all ages for both genders in countries1 selected countries1 Country Patients ASR Country Patients ASR (n) (per 100 000) (n) (per 100 000) Republic of Korea 33 773 45.0 Mongolia 1 518 78.1 Japan 112 675 32.2 Lao PDR 2 116 52.6 China 253 427 14.2 Vietnam 21 997 24.6 Singapore 33.7 Republic of Korea 16 900 22.8 India 2 662 Thailand 20 455 22.3 Indonesia 64 332 6.1 China 394 770 22.3 Thailand 27 772 12.8 Indonesia 18 121 Sweden 11 493 12.4 Singapore 8.4 Canada 29.2 Japan 763 9.7 6 358 35.2 Sweden 36 168 9.3 23 769 Canada 2.5 490 3.6 2 261 In many Asian countries the ASR of CRC has now to the high prevalence of hepatitis B virus (HBV) surpassed that of GC,2 and CRC is one of the leading infection.19 However, chronic hepatitis C is more GI cancers among Asians. With an increased life expec- commonly related to liver cancer in Japan, which tancy in Asian populations and a markedly elevated accounts for up to 70% of these cases.20 This might ASR of CRC with age, the absolute numbers of CRC mainly be due to the widespread use of contami- would be considerably higher. nated syringes for treating Schistosoma japonicum infection that was endemic in Japan in the 1920s. Another interesting observation is the anatomical left The use of injected amphetamines during and after to right shift in the location of CRC, which has been World War II might have also contributed to this noted in Western countries for many years. Although high rate. reports from Asia have shown the overwhelming occur- rence of left-sided CRC,15 several studies have shown a Country-specific differences in the etiologies of HCC proximal shift. A study from Hong Kong SAR, China in particular multiracial Asian countries are interest- showed an increased proportion of proximal polyps,16 ing. In a report on the etiology of liver cirrhosis, Qua and a similar finding of increased proximal tumors was and Goh21 observed that HBV infection was the observed in Korea and Japan, especially among females predominant underlying etiology in Malays and and elderly populations.17,18 Takada et al.18 demon- Chinese, accounting for 47.9% and 58.8% of these strated a markedly elevated incidence of proximal CRC patients, respectively, while heavy alcohol consump- with aging, particularly in elderly Japanese women. tion was the predominant cause in Indians (51.1%). Hepatitis C-induced HCC was observed in 25.0% of LIVER CANCER Malay patients and cryptogenic cause (mostly associ- ated with diabetes mellitus) accounted for more than Liver cancer is a common cancer in the Asia–Pacific 20% of Malay and Indian patients. In a large-sample- region and is considered an Asian cancer. Mongolia sized study specifically on HCC patients, we recorded an exceedingly high ASR of liver cancer of 78.1 observed a similar etiological pattern among differ- per 100 000, while several other Asia–Pacific countries, ent ethnic groups (unpublished data, Table 4). including China, Korea and Thailand, recorded an ASR of more than 20 per 100 000.2 Some African countries In Mongolia, which has the highest ASR of liver cancer such as Egypt and the Gambia have also recorded a high worldwide, the prevalence of both chronic hepatitis B ASR for hepatocellular carcinoma (HCC), but most and hepatitis C is equally high. The problem is further Western countries had a low incidence of less than 10.0 compounded by the inordinately high alcohol con- per 100 000. In terms of absolute numbers of cases, sumption and widespread poverty in these popula- China, Japan and Korea recorded almost half a million tions, resulting in an enormously high mortality with cases in 2012 (Table 3).2 this cancer in the country.22 The high incidence of liver cancer, especially HCC, in the Asia–Pacific region has been overwhelmingly due © 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd

466 L-Y Goh et al. Journal of Digestive Diseases 2014; 15; 463–468 Table 4. Etiology of liver cancer according to races (n = 348, %) (Goh et al., unpublished data) Etiology, n (%) Malay Chinese Indian Overall Hepatitis B 43 (60.6) 157 (65.7) 6 (15.8) 206 (59.2) Hepatitis C 13 (18.3) 22 (9.2) 2 (5.3) 37 (10.6) Cryptogenic cause 13 (18.3) 33 (13.8) 11 (28.9) 57 (16.4) Alcohol 10 (4.2) 10 (26.3) 21 (6.0) Hepatitis B + C 1 (1.4) 6 (2.5) 1 (2.6) 7 (2.0) Alcohol + hepatitis B 0 (0) 7 (2.9) 3 (7.9) 11 (3.2) Alcohol + hepatitis C 1 (1.4) 3 (1.3) 4 (10.6) 7 (2.0) Primary biliary cirrhosis 0 (0) 1 (0.4) 0 (0) 1 (0.3) Autoimmune hepatitis 0 (0) 0 (0) 1 (2.6) 1 (0.3) Total 0 (0) 38 (100) 71 (100) 239 (100) 348 (100) DISCUSSION The incidence of CRC has been increasing in the Asia– Pacific region during the past decades, which may be Changes in the epidemiology of GI diseases in the due to rising affluence and an increase in obesity but a Asia–Pacific region mirror those that have taken place decrease in physical activity.33–35 The adoption of a in Western populations about 30–40 years ago. westernized diet with high protein and fat has Growing affluence and rapid urbanization in this also been implicated as a cause of this increase.36,37 whole region underlie the changes that we observe Undoubtedly, CRC will be the major GI cancer in the today. A westernized lifestyle accompanied by a Asia–Pacific region in the near future. marked increase in calorie-rich diet results in an expo- nential increase in the overweight and obese popula- Obesity has contributed significantly to the rise of tions in the Asia–Pacific region.23,24 Obesity is linked another new disease in the Asia–Pacific region, that is, to several GI cancers,25 including CRC and liver cancer, fatty liver (FL) or NAFLD.38,39 FL is associated with as well as GERD. An improvement in personal and metabolic syndrome, diabetes mellitus and cardiovas- community hygiene has also been observed in these cular diseases. In a study from Malaysia, although the populations, leading to a marked decline in infectious overall prevalence of NAFLD was 22.7%, the prevalence diseases including H. pylori infection. among Malay and Indian men aged ≥45 years was inordinately high (64.7% and 68.2%, respectively).40 The decline in the incidence of GC, a cancer that is This is a worrying finding as the proportion of patients often associated with poverty, is consistent with the with liver cirrhosis and liver cancer might increase in observed trend in Western countries where GC started the future, which is consistent with the increase in FL to decline from the 1940s,26 which may be attributed and obesity. At the same time, with mass vaccination to the changes of lifestyle including the use of food against HBV at birth instituted in many Asian countries preservatives as well as a reduced salt intake following since the 1980s, a decline in chronic hepatitis B-related the advent of refrigeration, which allows a high intake liver cancers has already been reported in children41 of fresh vegetables and fruit with a high level of and will continue to decline with time in the adult antioxidants.27,28 population as well. With aggressive public health poli- cies against contaminated needle use, the prevalence of H. pylori infection has now been regarded as a vital hepatitis C will also be reduced. The etiological pattern factor in gastric carcinogenesis.29 Paradoxically, the of liver cancer will change, as it did in the Western H. pylori infection rate may have also started to decline world. The disappearance of HBV as an etiological before its discovery because it is a predictor of patients’ factor will, however, take a whole generation (to socioeconomic status. The overall improvement in perhaps 2030) and in the meantime HBV will remain a living conditions with better personal and community major health problem in the region. hygiene may be a more important factor for the decreased infection rate than the detection of and A higher standard of living together with the avai- treatment for active infection. With the increase in lability of good healthcare has resulted in the awareness, diagnosis and treatment of H. pylori, infec- improved longevity of the population. The incidences tion rate has also been decreased in tandem with that of CRC and liver cancer, as with most other cancers, in GC incidence worldwide.30–32 rise exponentially with age. This has major implica- © 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd

Journal of Digestive Diseases 2014; 15; 463–468 GI and liver cancer in Asia 467 tions for healthcare as the burden on medical services 16 Sung JJY, Leung WK, Suen BY et al. Proximal migration of will increase tremendously and pose a major chal- adenomas in the colon: a survey of 3,126 cases of colorectal lenge to the developing countries in the Asia–Pacific adenoma over 10 years. Gut 2004; 53: A30. region with less than adequate resources. 17 Kim DH, Shin MH, Ahn YO. Incidence pattern of colorectal REFERENCES cancer in Korea by subsite of origin. J Korean Med Sci 2000; 15: 675–81. 1 Goh KL. Changing trends in gastrointestinal disease in the Asia–Pacific region. J Dig Dis 2007; 8: 179–85. 18 Takada H, Ohsawa T, Iwamoto S et al. Changing site distribution of colorectal cancer in Japan. Dis Colon Rectum 2 Ferlay J, Soerjomataram I, Ervik M et al. GLOBOCAN 2012: 2002; 45: 1249–54. estimated cancer incidence, mortality and prevalence worldwide in 2012: IARC Cancer Base No. 11. Lyons: 19 Yuen MF, Hou JL, Chutaputti A; Asia Pacific Working Party International Agency for Research on Cancer; 2013 Cited: 2 on Prevention of Hepatocellular Carcinoma. Hepatocellular May 2014. Available from: http://globocan.iarc.fr. carcinoma in the Asia pacific region. J Gastroenterol Hepatol 2009; 24: 346–53. 3 Forman D, Sitas F, Newell DG et al. Geographic association of Helicobacter pylori antibody prevalence and gastric 20 Chung H, Ueda T, Kudo M. Changing trends in hepatitis C cancer mortality in rural China. Int J Cancer 1990; 46: infection over the past 50 years in Japan. Intervirology 2010; 608–11. 53: 39–43. 4 Goh KL, Parasakthi N. The racial cohort phenomenon: 21 Qua CS, Goh KL. Liver cirrhosis in Malaysia: peculiar seroepidemiology of Helicobacter pylori infection in a epidemiology in a multiracial Asian country. J Gastroenterol multiracial South-East Asian country. Eur J Gastroenterol Hepatol 2011; 26: 1333–7. Hepatol 2001; 13: 177–83. 22 Dondog B, Lise M, Dondov O, Baldandorj B, Franceschi S. 5 Goh KL, Cheah PL, Md N, Quek KF, Parasakthi N. Ethnicity Hepatitis B and C virus infections in hepatocellular and H. pylori as risk factors for gastric cancer in Malaysia: A carcinoma and cirrhosis in Mongolia. Eur J Cancer Prev prospective case control study. Am J Gastroenterol 2007; 102: 2011; 20: 33–9. 40–5. 23 Gu D, Reynolds K, Wu X et al. Prevalence of the metabolic 6 Chen JG, Zhu J, Parkin DM et al. Trends in the incidence of syndrome and overweight among adults in China. Lancet cancer in Qidong, China, 1978–2002. Int J Cancer 2006; 2005; 365: 1398–405. 119: 1447–54. 24 Yoon KH, Lee JH, Kim JW et al. Epidemic obesity and type 2 7 Kobayashi T, Kikuchi S, Lin Y et al. Trends in the incidence diabetes in Asia. Lancet 2006; 368: 1681–8. of gastric cancer in Japan and their associations with Helicobacter pylori infection and gastric mucosal atrophy. 25 Goh LY, Goh KL. Obesity: an epidemiological perspective Gastric Cancer 2004; 7: 233–9. from Asia and its relationship to gastrointestinal and liver cancers. J Gastroenterol Hepatol 2013; 28 Suppl 4: 8 Inoue M, Tsugane S. Epidemiology of gastric cancer in 54–8. Japan. Postgrad Med J 2005; 81: 419–24. 26 Howson CP, Hiyama T, Wynder EL. The decline in gastric 9 Devesa SS, Blot WJ, Fraumeni JF Jr. Changing patterns in the cancer: epidemiology of an unplanned triumph. Epidemiol incidence of esophageal and gastric carcinoma in the United Rev 1986; 8: 1–27. States. Cancer 1998; 83: 2049–53. 27 Coggon D, Barker DJ, Cole RB, Nelson M. Stomach cancer 10 Kusano C, Gotoda T, Khor CJ et al. Changing trends in the and food storage. J Natl Cancer Inst 1989; 81: 1178–82. proportion of adenocarcinoma of the esophagogastric junction in a large tertiary referral center in Japan. 28 La Vecchia C, Negri E, D’Avanzo B, Franceschi S. Electric J Gastroenterol Hepatol 2008; 23: 1662–5. refrigerator use and gastric cancer risk. Br J Cancer 1990; 62: 136–7. 11 Deans C, Yeo MS, Soe MY, Shabbir A, Ti TK, So JB. Cancer of the gastric cardia is rising in incidence in an Asian 29 International Agency for Research on Cancer. IARC population and is associated with adverse outcome. World J Monographs on the Evaluation of Carcinogenic Risks to Surg 2011; 35: 617–24. Humans. Volume 61: Schistosomes, liver flukes and Helicobacter pylori. World Health Organization, Paris. 12 Sung JJ, Lau JY, Goh KL, Leung WK; Asia Pacific Working [Updated: 26 August 1997; Cited 3 May 2014]. Available Group on Colorectal Cancer. Increasing incidence of from URL: http://monographs.iarc.fr/ENG/Monographs/ colorectal cancer in Asia: implications for screening. Lancet vol61/volume61.pdf Oncol 2005; 6: 871–6. 30 Haruma K, Okamoto S, Kawaguchi H et al. Reduced 13 National Registry of Diseases Office. Singapore Cancer incidence of Helicobacter pylori infection in young Japanese Registry. Interim Annual Registry Report. Trends in Cancer persons between the 1970s and the 1990s. J Clin incidence in Singapore 2008–2012 [Cited 3 May 2014]. Gastroenterol 1997; 25: 583–6. Available from URL: https://www.nrdo.gov.sg/ uploadedFiles/NRDO/Cancer_Trends_Report_08-12 31 Rehnberg-Laiho L, Rautelin H, Koskela P et al. Decreasing _website.pdf prevalence of helicobacter antibodies in Finland, with reference to the decreasing incidence of gastric cancer. 14 Zainal Ariffin O, Nor Saleha IT. NCR Report 2007, Ministry Epidemiol Infect 2001; 126: 37–42. of Health, Malaysia. 2011. [Cited 10 June 2014]. Available from URL: http://110.4.45.175/~radiolog/wp-content/ 32 Jacobson K. The changing prevalence of Helicobacter pylori uploads/2014/02/NCR2007.pdf infection in Canadian children: should screening be performed in high-risk children? Can J Gastroenterol 2005; 15 Goh KL, Quek KF, Yeo GT et al. Colorectal cancer in Asians: 19: 412–4. a demographic and anatomic survey in Malaysian patients undergoing colonoscopy. Aliment Pharmacol Ther 2005; 22: 33 Le Marchand L, Wilkens LR, Kolonel LN, Hankin JH, 859–64. Lyu LC. Associations of sedentary lifestyle, obesity, smoking, alcohol use, and diabetes with the risk of colorectal cancer. Cancer Res 1997; 57: 4787–94. 34 Slattery ML, Edwards SL, Boucher KM, Anderson K, Caan BJ. Lifestyle and colon cancer: an assessment of factors associated with risk. Am J Epidemiol 1999; 150: 869–77. © 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd

468 L-Y Goh et al. Journal of Digestive Diseases 2014; 15; 463–468 35 Wang YY, Lin SY, Lai WA, Liu PH, Sheu WH. Association 39 Chitturi S, Wong VW, Farrell G. Nonalcoholic fatty liver in between adenomas of rectosigmoid colon and metabolic Asia: firmly entrenched and rapidly gaining ground. syndrome features in a Chinese population. J Gastroenterol J Gastroenterol Hepatol 2011; 26 Suppl 1: 163–72. Hepatol 2005; 20: 1410–5. 40 Goh SC, Ho ELM, Goh KL. Prevalence and risk factors of 36 Whittemore AS, Wu-Williams AH, Lee M et al. Diet, physical non-alcoholic fatty liver disease in a multiracial suburban activity, and colorectal cancer among Chinese in North Asian population in Malaysia. Hepatol Int 2013; 7: America and China. J Natl Cancer Inst 1990; 82: 915–26. 548–54. 37 Levi F, Pasche C, La Vecchia C, Lucchini F, Franceschi S. 41 Chang MH, Chen CJ, Lai MS et al. Universal hepatitis B Food groups and colorectal cancer risk. Br J Cancer 1999; vaccination in Taiwan and the incidence of hepatocellular 79: 1283–7. carcinoma in children. N Engl J Med 1997; 336: 1855–9. 38 Chan WK, Goh KL. Epidemiology of a fast emerging disease in the Asia–Pacific region: non-alcoholic fatty liver disease. Hepatol Int 2013; 7: 65–71. © 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd