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Barcelona Clinic Liver Cancer outperforms Hong Kong Liver Cancer staging of hepatocellular carcinoma in multiethnic Asians: Real-world perspective

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World Journal of Gastroenterology 2017年第22期23卷 4054-4063页

作者： James Weiquan Li boon-bee george goh Pik-Eu Chang Chee-Kiat Tan Department of Gastroenterology and Hepatology Duke-NUS Medical School

To compare the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC) classification systems when applied to HCC patients from the largest tertiary-level centre in *** thousand two hundred and seventy hepatocellular carcinoma (HCC) patients prospectively enrolled in a tertiary-level centre registry in Singapore since 1988 were studied. Patients were grouped into their respective BCLC and HKLC stages. Data such as demography, aetiology of HCC and type of treatment were collected. Survival data was based on census with the National Registry of Births and Deaths on 31st October 2015. Statistical analyses were done using SPSS version 21 (Chicago, IL, United States). Survival analyses were done by the Kaplan-Meier method. Differences in survival rates were compared using the log-rank *** median age at presentation was 63 years (range 13-94); male 82.4%; Chinese 89.4%, Malay 7.1%, Indian, 2.8%. Hepatitis B was the predominant aetiology (75.0%; Hepatitis C 7.2%, Hepatitis B and C co-infection 3.8%, non-viral 14.0%). Both BCLC and HKLC staging systems showed good separation with overall log rank test confirming significant survival differences between stages in our cohort (P < 0.001). 206 out of the 240 patients (85.8%) assigned for curative treatment by the BCLC treatment algorithm received curative therapy for HCC [Stage 0 93.2% (68/73); Stage A 82.6% (138/167)]. In contrast, only 341/558 (61.1%) patients received curative treatment despite being assigned for curative treatment by the HKLC treatment algorithm [Stage I 72.7% (264/363); Stage II 40.2% (66/164); Stage Va 35.5% (11/31)]. Patients who were assigned to curative treatment by HKLC but did not receive curative treatment had significantly poorer ECOG (P < 0.001), higher Child-Pugh status (P < 0.001) and were older (median age 66 vs 61, P < 0.001) than those who received curative therapy. Median overall survival in patients assigned to curative treatment groups

关键词： Hepatocellular carcinoma Barcelona Clinic Liver Cancer Hong Kong Liver Cancer Staging systems Prognosis Survival

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Low serum albumin predicts early mortality in patients with severe hypoxic hepatitis

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World Journal of Hepatology 2017年第22期9卷 959-966页

作者： Pik-Eu Chang boon-bee george goh Victoria Ekstrom Ming-Liang Ong Chee-Kiat Tan Department of Gastro enterology and Hepatology Singapore General Hospital Duke-NUS Medical School

To evaluate the incidence, etiology, and predictors of mortality of severe hypoxic hepatitis. METHODSWe used computerized patient records to identify consecutive cases of severe hypoxic hepatitis admitted to a tertiary hospital in Singapore over a one-year period. We defined severe hypoxic hepatitis as elevation of serum transaminases more than 100 times upper limit of normal in the clinical setting of cardiac, circulatory or respiratory failure after exclusion of other causes of hepatitis. We used multivariable regression analysis to determine predictors for mortality. RESULTSWe identified 75 cases of severe hypoxic hepatitis out of 71380 hospital admissions over one year, providing an incidence of 1.05 cases per 1000 admissions. Median age was 65 years (range 19-88); 57.3% males. The most common etiologies of severe hypoxic hepatitis were acute myocardial infarction and sepsis. Fifty-three patients (71%) died during the hospitalization. The sole independent predictive factor for mortality was serum albumin measured at the onset of severe hypoxic hepatitis. Patients with low serum albumin of less than 28 g/L have more than five-fold increase risk of death (OR = 5.39, 95%CI: 1.85-15.71). CONCLUSIONSevere hypoxic hepatitis is uncommon but has a high mortality rate. Patients with low serum albumin are at highest risk of death.

关键词： Severe Mortality Albumin Incidence Hypoxic hepatitis Predictors Etiology Prognosis

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Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 241-248页

作者： Chao Sun george boon-bee goh Wan-Cheng Chow Wah-Kheong Chan Grace Lai-Hung Wong Wai-Kay Seto Yi-Hsiang Huang Han-Chieh Lin I-Cheng Lee Hye Won Lee Seung Up Kim Vincent Wai-Sun Wong Jian-Gao Fan Center for Fatty Liver Disease Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and NutritionShanghai 200092China Department of Gastroenterology&Hepatology Singapore General HospitalSingaporeSingapore Gastroenterology and Hepatology Unit Department of MedicineFaculty of MedicineUniversity of MalayaKuala LumpurMalaysia Department of Medicine and Therapeutics and State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong KongChina Department of Medicine The University of Hong KongHong KongChina Institute of Clinical Medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina Division of Gastroenterology and Hepatology Taipei Veterans General HospitalTaipeiTaiwanChina Faculty of Medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina Department of Internal Medicine Yonsei University College of MedicineSeoulKorea

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic ***,the prevalence and risk factors for impaired renal function in patients with NAFLD remain *** objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD ***:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective *** fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 *** renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)***:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,*** multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of *** glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

关键词： Nonalcoholic fatty liver disease Impaired renal function Agile 3+ Agile 4 Metabolic syndrome

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Considerations for bariatric surgery in patients with cirrhosis

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World Journal of Gastroenterology 2018年第28期24卷 3112-3119页

作者： george boon-bee goh Philip R Schauer Arthur J McCullough Department of Gastroenterology and Hepatology Singapore General HospitalSingapore 169608Singapore Duke-NUS Graduate Medical School Singapore 169608Singapore Bariatric and Metabolic Institute Cleveland ClinicClevelandOH 44195United States Department of Gastroenterology Cleveland ClinicClevelandOH 44195United States Department of Pathobiology Cleveland ClinicClevelandOH 44195United States

With the ever increasing global obesity pandemic, clinical burden from obesity related complications are anticipated in parallel. Bariatric surgery, a treatment approved for weight loss in morbidly obese patients, has reported to be associated with good outcomes, such as reversal of type two diabetes mellitus and reducing all-cause mortality on a long term basis. However, complications from bariatric surgery have similarly been reported. In particular, with the onslaught of non-alcoholic fatty liver disease(NAFLD) epidemic, in associated with obesity and metabolic syndrome, there is increasing prevalence of NAFLD related liver cirrhosis, which potentially connotes more risk of specific complications for surgery. Bariatric surgeons may encounter, either expectedly or unexpectedly, patients with non-alcoholic steatohepatitis(NASH) and NASH related cirrhosis more frequently. As such, the issues and considerations surrounding their medical care/surgery warrant careful deliberation to ensure the best outcomes. These considerations include severity of cirrhosis, liver synthetic function, portal hypertension and the impact of surgical factors. This review explores these considerations comprehensively and emphasizes the best approach to managing cirrhotic patients in the context of bariatric surgery.

关键词： Cirrhosis Portal hypertension Non-alcoholic fatty liver disease Bariatric surgery Complications

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Current Modalities of Fibrosis Assessment in Non-alcoholic Fatty Liver Disease

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Journal of Clinical and Translational Hepatology 2017年第3期5卷 261-271页

作者： Mark CC Cheah Arthur J McCullough george boon-bee goh Department of Gastroenterology & Hepatology Singapore General Hospital Singapore Department of Gastroenterology Cleveland Clinic Ohio USA Department of Pathobiology Cleveland Clinic Ohio USA Department of Gastroenterology & Hepatology Singapore General Hospital Singapore Duke-NUS Medical School Singapore

Non-alcoholic fatty liver disease (NAFLD) is a burgeoning global health *** the subset of NAFLD patients with non-alcoholic steatohepatitis (NASH),the presence of significant fibrosis at index assessment is associated with poor prognosis and increased ***,there is a growing need to accurately assess and stage *** biopsy,the current gold standard,has limitations with sampling error and is invasive,with associated inherent *** has led to a host of non-invasive means of assessing fibrosis,which has garnered relevance in a disease that requires serial assessment of fibrosis longitudinally over *** review discusses,comprehensively,the various tools available to the clinician for the assessment of fibrosis,including the various scoring systems used in liver biopsy,the non-invasive means of serum biomarkers,such as the highly-validated NAFLD fibrosis score,and the imaging-based modalities,such as transient elastography and magnetic resonance elastography.

关键词： NAFLD Fibrosis assessment Modalities

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Validation of Non-invasive Fibrosis Scores for Predicting Advanced Fibrosis in Metabolic-associated Fatty Liver Disease

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Journal of Clinical and Translational Hepatology 2022年第4期10卷 589-594页

作者： Xiaoning Chen george boon-bee goh Jiaofeng Huang Yinlian Wu Mingfang Wang Rahul Kumar Su Lin Yueyong Zhu Department of Hepatology Hepatology Research InstituteThe First Affiliated Hospital of Fujian Medical UniversityFu-zhouFujianChina Department of Gastroenterology&Hepatology Singapore General HospitalSingapore Duke-NUS Medical School Singapore Department of Gastroenterology and Hepatology Duke-NUS Academic Medical CentreChangi General HospitalSingapore

Background and Aims:Metabolic-associated fatty liver disease(MAFLD)is a newly proposed terminology from 2020;yet,the applicability of conventional noninvasive fi-brosis models is still unknown for *** aimed to evaluate the performance of conventional noninvasive fibrosis scores in ***:The NHANES 2017-2018 datasets were used to compare the performances of different non-invasive fibrosis scores in MAFLD,including the aspartate aminotransferase(AST)to platelet ratio index(APRI),body mass index(BMI)-AST/alanine aminotransferase(ALT)ratio and diabetes score(BARD),fibrosis-4 index(FIB-4),and NAFLD fibrosis score(NFS).Moreover,Asian patients with biopsy-proven MAFLD were enrolled to further validate the ***:A total of 2,622 participants in the Na-tional Health and Nutrition Examination Survey(NHANES)cohort and 293 patients with MAFLD in the Asian cohort were *** in the Asian cohort had a lower BMI and higher liver enzymes(p<0.001).The area under the receiver operating characteristic curve(AUROC)of NFS was the largest in the NHANES cohort and Asian cohorts(0.679 and 0.699,respectively).The AUROC of NFS was followed by APRI,FIB-4,and BARD in the NHANES cohort(0.616,0.601,and 0.589,respectively).In the Asian cohort,the AUROC of APRI,FIB-4,and BARD for predicting advanced fibrosis were 0.625,0.683,and 0.615,*** performance of FIB-4 was better in the Asian cohort than that in the NHANES ***:NFS is better for predicting advanced fibrosis in ***-4 can be an al-ternative choice for MAFLD with high liver enzymes when NFS is *** efficient noninvasive fibrosis scor-ing systems are highly required for patients with MAFLD.

关键词： FIB-4 Metabolic-associated fatty liver disease Liver fibrosis NFS Noninvasive fibrosis scores

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Immunoglobulin G in non-alcoholic steatohepatitis predicts clinical outcome:A prospective multi-centre cohort study

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World Journal of Gastroenterology 2021年第43期27卷 7563-7571页

作者： Marianne Anastasia De Roza Mehul Lamba george boon-bee goh Johnathan Huey-Ming Lum Mark Chang-Chuen Cheah Jing Hieng Jeffrey Ngu Department of Gastroenterology and Hepatology Sengkang General HospitalSinghealthSingapore 544886Singapore Department of Gastroenterology and Hepatology Christchurch HospitalChristchurch 8011New Zealand Department of Gastroenterology and Hepatology Singapore General HospitalSingapore 169608Singapore Duke-NUS Medical School Singapore 169608Singapore

BACKGROUND Autoimmune markers including plasma cells(PC),anti-smooth-muscle antibody(ASMA),anti-nuclear antibody(ANA),and raised immunoglobulin G(IgG)are commonly observed in non-alcoholic steatohepatitis(NASH),however their clinical significance is *** To determine if autoimmune markers in NASH patients are independently associated with poorer clinical *** Consecutive patients with biopsy proven NASH from Christchurch Hospital,New Zealand and Singapore General Hospital(SGH)were included between 2005 to 2016 in a prospective multi-centre cohort *** with other causes of chronic liver disease were ***>14 g/L or globulin fraction>50%,ANA≥1:40,SMA≥1:40 were considered *** analysis was performed to assess which markers were independently associated with mortality and hepatic *** Total 261 patients were included of which 201 were from *** median age was 53 and 51.9%were *** fibrosis was present in 31.4%at ***,ASMA,ANA and raised IgG were observed in 13.1%,4.9%,27.8%and 30.1%of patients *** multivariate analysis,elevated IgG[Hazard Ratio(HR)6.79,95%CI:2.93-17.15]and fibrosis stage(HR 1.37,95%CI:1.03-1.87)were found to be independently associated with increased risk of liver ***(HR 1.06,95%CI:1.02-1.10)and elevated IgG(HR 3.79,95%CI:1.90-7.68)were independent factors associated with higher mortality *** Elevated IgG,rather than ANA,ASMA or plasma cells,is independently associated with increased risk of hepatic decompensation and mortality in *** could hence be important for prognostication.

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Immunoglobulin G Autoantibodies Mortality Hepatic decompensation

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Gamma-glutamyl transferase and cardiovascular risk in nonalcoholic fatty liver disease:The Gut and Obesity Asia initiative

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World Journal of Gastroenterology 2020年第19期26卷 2416-2426页

作者： Panyavee Pitisuttithum Wah-Kheong Chan george boon-bee goh Jian-Gao Fan Myeong Jun Song Phunchai Charatcharoenwitthaya Ajay Duseja Yock-Young Dan Kento Imajo Atsushi Nakajima Khek-Yu Ho Khean-Lee goh Vincent Wai-Sun Wong Sombat Treeprasertsuk Department of Medicine Faculty of MedicineChulalongkorn UniversityBangkok 10330Thailand Department of Medicine University of MalayaKuala Lumpur 50603Malaysia Department of Gastroenterology&Hepatology Singapore General HospitalSingapore 169608Singapore Department of Gastroenterology Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Internal Medicine The Catholic University of KoreaDaejeon 301-723South Korea Division of Gastroenterology Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand Department of Hepatology Post Graduate Institute of Medical Education and ResearchChandigarh 160012India Department of Medicine National University of Singapore 119228Singapore Department of Gastroenterology and Hepatology Yokohama City University Graduate School of MedicineYokohama 236-0004Japan Department of Medicine and Therapeutics The Chinese University of Hong KongHong Kong 999077China

BACKGROUND Gamma-glutamyl transferase(GGT)is associated with the risk of cardiovascular disease(CVD)in the general *** To identify the association of baseline GGT level and QRISK2 score among patients with biopsy-proven nonalcoholic fatty liver disease(NAFLD).METHODS This was a retrospective study involving 1535 biopsy-proven NAFLD patients from 10 Asian centers in 8 countries using data collected by the Gut and Obesity in Asia(referred to as“GO ASIA”)*** patients with available baseline GGT levels and all 16 variables for the QRISK2 calculation(QRISK2-2017;developed by researchers at the United Kingdom National Health Service;https://***/2017/;10-year cardiovascular risk estimation)were included and compared to healthy controls with the same age,sex,and *** risk was ***2 score>10%was defined as the high-CVD-risk *** stages 3 and 4(F3 and F4)were considered advanced *** A total of 1122 patients(73%)had complete data and were included in the final analysis;314(28%)had advanced *** median age(interquartile range[IQR])of the study population was 53(44-60)years,532(47.4%)were females,and 492(43.9%)were of Chinese *** median 10-year CVD risk(IQR)was 5.9%(2.6-10.9),and the median relative risk of CVD over 10 years(IQR)was 1.65(1.13-2.2)compared to healthy individuals with the same age,sex,and *** high-CVD-risk group was significantly older than the low-risk group(median[IQR]:63[59-67]vs 49[41-55]years;P<0.001).Higher fibrosis stages in biopsy-proven NAFLD patients brought a significantly higher CVD risk(P<0.001).Median GGT level was not different between the two groups(GGT[U/L]:Median[IQR],high risk 60[37-113]vs low risk 66[38-103],P=0.56).There was no correlation between baseline GGT level and 10-year CVD risk based on the QRISK2 score(r=0.02).CONCLUSION The CVD risk of NAFLD patients is higher than that of healthy *** GGT level cannot predict CVD ri

关键词： Nonalcoholic fatty liver disease Gamma glutamyl transferase QRISK Cardiovascular risk Gut and Obesity in Asia

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Clinical applications, limitations and future role of transient elastography in the management of liver disease

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2016年第1期7卷 91-106页

作者： Pik Eu Chang george boon-bee goh Jing Hieng Ngu Hiang Keat Tan Chee Kiat Tan Department of Gastroen- terology and Hepatology Singapore General Hospital george boon-bee goh Duke- NUS Graduate Medical School

Transient elastography(TE) is a reliable tool for the non-invasive assessment of liver fibrosis in routine clinical practice. TE is currently approved for use in Europe, Asia and the United States. The widespread adoption of this technology is certain to increase the use of TE worldwide. Although TE has been well validated in chronic viral hepatitis, its clinical role in other liver diseases remains less clear. The advent of new treatment for chronic hepatitis C and emerging prevalence of non-alcoholic steatohepatitis raises new questions on the role of TE in current clinical practice. This review aims to examine the clinical applications, limitations and future role of TE in current clinical practice in light of the changing epidemiology of liver diseases and new clinical management paradigms. In current clinical practice, TE is the most accurate noninvasive method for diagnosis of liver cirrhosis. TE is useful to rule out fibrosis and cirrhosis but does not have sufficient accuracy to discern between various stages of fibrosis. The clinical role of TE has evolved from cross-sectional point-in-time assessment of fibrosis and cirrhosis to the more relevant role of prediction of vital clinical end-points. This provides clinicians with the ability to modify treatment strategies based on the information provided by TE. TE has evolved over the past decade to become an essential tool to assist the clinician in the management of chronic liver disease.

关键词： Liver stiffness Transient elastography Non-invasive Fibrosis Chronic

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Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in hepatocellular carcinoma:the PLANET study

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National Science Review 2022年第3期9卷 96-109页

作者： Weiwei Zhai Hannah Lai Neslihan Arife Kaya Jianbin Chen Hechuan Yang Bingxin Lu Jia Qi Lim Siming Ma Sin Chi Chew Khi Pin Chua Jacob Josiah Santiago Alvarez Pauline Jieqi Chen Mei Mei Chang Lingyan Wu Brian K.P.goh Alexander Yaw-Fui Chung Chung Yip Chan Peng Chung Cheow Ser Yee Lee Juinn Huar Kam Alfred Wei-Chieh Kow Iyer Shridhar Ganpathi Rawisak Chanwat Jidapa Thammasiri boon Koon Yoong Diana bee-Lan Ong Vanessa H.de Villa Rouchelle D.Dela Cruz Tracy Jiezhen Loh Wei Keat Wan Zeng Zeng Anders Jacobsen Skanderup Yin Huei Pang Krishnakumar Madhavan Tony Kiat-Hon Lim Glenn Bonney Wei Qiang Leow Valerie Chew Yock Young Dan Wai Leong Tam Han Chong Toh Roger Sik-Yin Foo Pierce Kah-Hoe Chow Genome Institute of Singapore Agency for Science Technology and Research Key Laboratory of Zoological Systematics and Evolution Institute of Zoology Chinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences School of Biological Sciences Nanyang Technological University Division of Biosciences Faculty of Life Sciences Division of Surgery and Surgical Oncology National Cancer Centre Department of Hepato-Pancreato-Biliary and Transplant Surgery Singapore General Hospital Division of Hepatobiliary and Pancreatic Surgery Department of Surgery University Surgical Cluster National University Health System Hepato-Pancreato-Biliary Surgery Unit Department of Surgery National Cancer Institute Division of Pathology National Cancer Institute Department of Surgery Faculty of Medicine University of Malaya Department of Surgery and Center for Liver Disease Management and Transplantation The Medical City 13. Department of Laboratories The Medical City Department of Pathology Singapore General Hospital Institute for Infocomm Research ASTAR Department of Pathology National University Health System Translational Immunology Institute (TII) Sing Health Duke-NUS Academic Medical Centre Division of Gastroenterology and Hepatology University Medicine Cluster National University Hospital Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore Cancer Science Institute of Singapore National University of Singapore Division of Medical Oncology National Cancer Center Singapore Cardiovascular Research Institute National University of Singapore National University Healthcare System Singhealth-Duke-NUS Academic Surgery Program Duke-NUS Graduate Medical School Institute of Molecular and Cell Biology Agency for Science Technology and Research

Intra-tumor heterogeneity(ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic(transcriptomic and immune)heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma(HCC)with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients(331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage Ⅱ patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.

关键词： NADH oxidase H2O2 production oxidative phosphorylation

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