George Boon-Bee Goh

Changing epidemiology of hepatocellular carcinoma in Asia

Hepatocellular carcinoma is a major problem in Asia because of the presence of multiple risk factors in the region such as endemicity of hepatitis B and significant contamination of foodstuff by aflatoxin in some areas. Another risk factor for HCC, chronic hepatitis C infection, in Asia is most significant in Japan, the only Asian country with more HCV than HBV-related hepatocellular carcinoma. As these risk factors can and are being modified by measures such as universal hepatitis B immunisation, successful treatment of HCV infections, reduction and improved surveillance of aflatoxin contamination of foodstuff, it is not surprising that the epidemiology of HCC in Asia is changing. All these are offset by the rising importance of NAFLD and NASH as chronic liver diseases and risk factors for HCC which contributes to the changing epidemiology of HCC in Asia.

Natural History of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) remains among the most common liver diseases worldwide, with increasing prevalence in concert with the obesity and metabolic syndrome epidemic. The evidence on the natural history, albeit with some ambiguity, suggests the potential for some subsets of NAFLD to progress to cirrhosis, liver-related complications and mortality with fibrosis being the most important predictor of hard long-term endpoints such as mortality and liver complications. In this setting, NAFLD proves to be a formidable disease entity, with considerable clinical burden, for both the present and the future. Our understanding of the natural history of NAFLD is constantly evolving, with nascent data challenging current dogma. Further clarification of the natural history is required with well-designed, well-defined studies using prospectively collected data. Identifying the predictors of long-term outcomes should be used to direct development of clinical trial endpoints in NAFLD.

Coffee, alcohol and other beverages in relation to cirrhosis mortality: the Singapore Chinese Health Study.

Limited experimental and epidemiologic data suggest that coffee may reduce hepatic damage in chronic liver disease. The association between consumption of coffee and other beverages and risk of cirrhosis mortality was evaluated in the Singapore Chinese Health Study. This is a prospective population‐based cohort of 63,275 middle‐aged and older Chinese subjects who provided data on diet, lifestyle, and medical histories through in‐person interviews using a structured questionnaire at enrollment between 1993 and 1998. Mortality from cirrhosis in the cohort was ascertained through linkage analysis with nationwide death registry. After a mean follow‐up of 14.7 years, 114 subjects died from cirrhosis; 33 of them from viral hepatitis B (29%), two from hepatitis C (2%), and 14 from alcohol‐related cirrhosis (12%). Compared to nondrinkers, daily alcohol drinkers had a strong dose‐dependent positive association between amount of alcohol and risk of cirrhosis mortality. Conversely, there was a strong dose‐dependent inverse association between coffee intake and risk of nonviral hepatitis‐related cirrhosis mortality (P for trend = 0.014). Compared to non‐daily coffee drinkers, those who drank two or more cups per day had a 66% reduction in mortality risk (hazard ratio [HR] = 0.34, 95% confidence interval [CI] = 0.14‐0.81). However, coffee intake was not associated with hepatitis B‐related cirrhosis mortality. The inverse relationship between caffeine intake and nonviral hepatitis‐related cirrhosis mortality became null after adjustment for coffee drinking. The consumption of black tea, green tea, fruit juices, or soft drinks was not associated with risk of cirrhosis death. Conclusion: This study demonstrates the protective effect of coffee on nonviral hepatitis‐related cirrhosis mortality, and provides further impetus to evaluate coffee as a potential therapeutic agent in patients with cirrhosis. (Hepatology 2014;60:661–669)

Perceptions of non-alcoholic fatty liver disease – an Asian community-based study

Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is closely related to metabolic syndrome and its risk factors. Worldwide, epidemiological studies have reported NAFLD prevalence rates of 5% to 30% depending on geographical variations. While epidemiological data suggest a progressively increasing prevalence of metabolic risk factors in Singapore, there are limited data about NAFLD per se in the community. We aim to explore the prevalence and perceptions of NAFLD in Singapore. Methods: Attendees at a gastroenterology public forum were enrolled in a cross-sectional observational study evaluating demographic, anthropometric and clinical information. The diagnosis of NAFLD was based on sonographic criteria. Metabolic syndrome was defined according to International Diabetes Federation guidelines. Perceptions of NAFLD were explored using a self-administered survey questionnaire. Results: A total of 227 subjects were recruited, with NAFLD being diagnosed in 40% of the cohort. Relative to those without NAFLD, subjects with NAFLD had higher male preponderance, older age, higher body mass index, waist circumference and more metabolic syndrome (all P < 0.05). Although 71.2% subjects had heard about NAFLD before, only 25.4% of them felt that they were at risk of NAFLD. Comparable responses were observed in subjects with no metabolic risk factors relative to subjects with one or more metabolic risk factors (P > 0.05). Of note, 75.6% of subjects with one or more metabolic risk factors did not think that they were at risk of NAFLD. Conclusion: Our study suggests a significant local prevalence of NAFLD in the community including non-obese individuals. Considering the tendency to underestimate risk of NAFLD, enhanced public education about NAFLD is warranted to improve understanding.

Dietary fatty acids and risk of hepatocellular carcinoma in the Singapore Chinese health study.

Lipidomic signature of lipid metabolism suggests that omega‐6 polyunsaturated fatty acids (PUFA) may play a role in oncogenesis of hepatocellular carcinoma (HCC). Hence, we examined the association between dietary fatty acids and risk of HCC.

Association between diabetes mellitus and cirrhosis mortality: the Singapore Chinese Health Study.

Diabetes mellitus has been linked to cirrhosis‐related mortality in Western populations, but less is known about this relationship in Asian populations. We studied the impact of diabetes on the risk of cirrhosis mortality in a population‐based cohort among Chinese in Singapore.

Deciphering the epidemiology of hepatocellular carcinoma through the passage of time: A study of 1,401 patients across 3 decades

Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers globally. With advances in therapy for chronic viral hepatitis, changing social circumstances, and increasing practice of HCC surveillance, the epidemiology of HCC is expected to change over time. We explored the temporal trends in HCC in Singapore, a multiethnic Asian country, over the last 3 decades. Patients with HCC were prospectively enrolled and stratified into two cohorts (C1, 1988‐2002; C2, 2003‐2016). Patient and tumor characteristics, management, and survival were compared between the two cohorts, and a survival census was performed on October 31, 2015. There were 1,401 patients, and the mean age at diagnosis of HCC for C1 and C2 was 60.1 and 63.5 years, respectively. Male patient preponderance decreased significantly, with the male to female ratio falling from 5.2:1 to 3.9:1 between C1 and C2. Hepatitis B, although still the predominant risk factor for HCC, showed a significant decline from C1 to C2 (76.5% to 68.2%), while the nonviral etiology increased significantly over the same period (14.4% versus 25.0%, respectively). Significantly more patients in C2 than C1 were diagnosed through surveillance (39.2% versus 11.3%, respectively) and had better physical performance (Eastern Cooperative Oncology Group 0, 62.1% versus 20.4%, respectively). While Child‐Pugh status was comparable, significantly more patients in C2 than C1 had early stage disease (Barcelona Clinic Liver Cancer 0‐A, 39.5% versus 7.4%, respectively), which translated into significantly higher median survival (18.6 months versus 3.8 months, respectively). Conclusion: Over the past 3 decades, hepatitis B‐related HCC has been decreasing while HCC due to nonviral etiology has been increasing significantly. Surveillance to diagnose early stage HCC is important in improving the outcome of HCC. (Hepatology Communications 2017;1:564–571)

Enhanced Liver Fibrosis Score as a Predictor of Hepatocellular Carcinoma

To the Editor: Hepatocellular carcinoma (HCC)1 is a major cause of cancer mortality worldwide (1). There remains a need for noninvasive tests to identify patients in the community at risk of developing HCC, especially that resulting from underlying nonalcoholic fatty liver disease (NAFLD) (2). The Enhanced Liver Fibrosis (ELF) test consists of 3 direct markers of liver extracellular matrix: hyaluronic acid (HA), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), and amino-terminal propeptide of type III procollagen (PIIINP). The ELF score has been validated in diagnosis of advanced fibrosis and predicting complications in patients with established chronic liver disease (3, 4). In this prospective study, we evaluated the use of the ELF score as a predictor of HCC in a population-based cohort of Chinese in Singapore. The Singapore Chinese Health Study recruited 63257 Chinese men and women, of age between 45 and 74 years, in Singapore between 1993 and 1998 (5) and blood samples were collected using plain tubes from 32543 subjects between 1999 and 2005. Serum from each blood sample was prepared by centrifugation and stored at −80 °C for an average of 14 years before chemical analysis. After a mean of 11.5 years of follow-up, among the 394 incident cases of HCC identified in this cohort through linkage with …

‘Broken heart’ in acute-on-chronic liver failure

Takotsubo cardiomyopathy usually occurs as a result of catecholamine release causing myocardial ‘stunning’ during physical or emotional stress. Typically coronary angiogram shows normal or minor coronary artery disease and echocardiogram shows apical ballooning with basal wall hyperkinesia. The prognosis is excellent with good cardiac functional recovery within days to weeks. We report the first case of takotsubo cardiomyopathy in a patient with acute-on-chronic liver failure.

Reponse to the association between diabetes mellitus and cirrhosis mortality

To the Editor: We thank Hu, Tang and Fu for their interest in our study and their thoughtful comments. We agree that as in other diseases on diabetes as a risk factor, the lack of information on medication limits the extrapolation of the results to the effects of statins or antidiabetes medication. A study on how the use of statin or other antidiabetes medication may affect risk of cirrhosis or mortality would require a study that included diabetic patients with detailed information on different type of medication use. We did not collect information about the use of medication, and were therefore unable to include medication use within the scope of our study. While statin therapy has demonstrated beneficial effects in cirrhosis,1,2 other medications have also been shown to exert beneficial effects in risk of liver disease, such as ACEinhibitors in NAFLD associated fibrosis,3 and metformin in hepatocellular carcinoma.4 However, the majority of these studies are limited by their observational nature. The second point to address is the possible confounding effect of coffee consumption on the diabetescirrhosis mortality association. We have previously published a protective effect of coffee consumption in reducing the risk of cirrhosis mortality in this Singapore Chinese Health Study cohort.5 Hence, in this current analysis, we were careful to adjust for coffee consumption in all the models. Finally, the prevalence of HIV infection in our resident population is very low; the prevalence of HIV in Singapore was 117 per million resident population in 2015.6 Hence, HIV coinfection is unlikely to have significant impact on the risk of cirrhosis in this cohort, or in other countries with relatively low prevalence of HIV.