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Hepatitis B virus reactivation during immunosuppressive therapy: Appropriate risk stratification

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World Journal of Hepatology 2015年第6期7卷 825-830页

Our understanding of hepatitis B virus(HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen(HBs Ag)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosisfactor(anti-TNF) and hematopoietic stem cell transplantation(HSCT). HBV reactivation could also occur in HBs Ag-negative, antibody to hepatitis B core antigen(anti-HBc) positive individuals during therapies containing rituximab, anti-TNF or *** HBs Ag-positive patients, prophylactic antiviral therapy is proven to the effective in preventing HBV reactivation. Recent evidence also demonstrated entecavir to be more effective than lamivudine in this aspect. For HBs Ag-negative, antiHBc positive individuals, the risk of reactivations differs with the type of immunosuppression. For rituximab, a prospective study demonstrated the 2-year cumulative risk of reactivation to be 41.5%, but prospective data is still lacking for other immunosupressive regimes. The optimal management in preventing HBV reactivation would involve appropriate risk stratification for different immunosuppressive regimes in both HBs Ag-positive and HBs Ag-negative, anti-HBc positive individuals.

关键词： Hepatitis B virus Antibody to hepatitis Bcore antigen Hepatitis B surface antigen Rituximab Antigen CD20 Hematopoietic stem cell transplantation Antibody to tumor necrosis factor Occult

Application of Big Data analysis in gastrointestinal research

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World Journal of Gastroenterology 2019年第24期25卷 2990-3008页

作者： Ka-Shing Cheung wai K Leung wai-kay seto Department of Medicine The University of Hong KongQueen Mary HospitalHong KongChina Department of Medicine The University of Hong Kong- Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina

Big Data,which are characterized by certain unique traits like volume,velocity and value,have revolutionized the research of multiple fields including *** Data in health care are defined as large datasets that are collected routinely or automatically,and stored *** the rapidly expanding volume of health data collection,it is envisioned that the Big Data approach can improve not only individual health,but also the performance of health care *** application of Big Data analysis in the field of gastroenterology and hepatology research has also opened new research *** it retains most of the advantages and avoids some of the disadvantages of traditional observational studies(case-control and prospective cohort studies),it allows for phenomapping of disease heterogeneity,enhancement of drug safety,as well as development of precision medicine,prediction models and personalized *** randomized controlled trials,it reflects the real-world situation and studies patients who are often under-represented in randomized controlled ***,residual and/or unmeasured confounding remains a major concern,which requires meticulous study design and various statistical adjustment *** potential drawbacks include data validity,missing data,incomplete data capture due to the unavailability of diagnosis codes for certain clinical situations,and individual *** continuous technological advances,some of the current limitations with Big Data may be further *** review will illustrate the use of Big Data research on gastrointestinal and liver diseases using recently published examples.

关键词： Healthcare dataset Epidemiology Gastric cancer Inflammatory bowel disease Colorectal cancer Hepatocellular carcinoma Gastrointestinal bleeding

Prevention of hepatocellular carcinoma in chronic viral hepatitis B and C infection

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World Journal of Gastroenterology 2013年第47期19卷 8887-8894页

作者： Tao Lu wai-kay seto Ran-Xu Zhu Ching-Lung Lai Man-Fung Yuen Department of Medicine The University of Hong Kong-Shenzhen Hospital Department of Medicine The University of Hong KongQueen Mary Hospital

Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality worldwide,with the majority of cases associated with persistent infection from hepatitis B virus(HBV)or hepatitis C virus(HCV).Natural history studies have identified risk factors associated with HCC development among chronic HBV and HCV ***-risk infected individuals can now be identified by the usage of risk predictive *** plays a central role in the prevention of HBV-related *** of chronic HBV infection,especially by nucleoside analogue therapy,could also reduce the risk of HBV-related *** HCV infection,besides the advocation of universal precautions to reduce the rate of infection,pegylated interferon and ribavirin could also reduce the risk of HCV-related HCC among those achieving a sustained virologic *** there has been mounting evidence on the role of chemopreventive agents in reducing HBV-and HCV-related *** continued advances in the understanding of the molecular pathogenesis of HCC would hold promise in preventing this highly lethal cancer.

关键词： Hepatitis B virus Hepatitis C virus Hepatocellular carcinoma Vaccination Prevention

Epidemiology and natural history of Wilson's disease in the Chinese: A territory-based study in Hong Kong between 2000 and 2016

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World Journal of Gastroenterology 2017年第43期23卷 7716-7726页

作者： Ka-Shing Cheung wai-kay seto James Fung Lung-Yi Mak Ching-Lung Lai Man-Fung Yuen Department of Medicine The University of Hong KongQueen Mary Hospital State Key Laboratory for Liver Research The University of Hong Kong

AIM To investigate the epidemiology and natural history of Wilson's disease in the *** Data were retrieved via electronic search of hospital medical registry of the Hong Kong Hospital Authority,which covers all the public healthcare services. We identified cases of Wilson's disease between 2000 and 2016 by the International Classification of Diseases(ICD)-9 code. We analyzed the incidence rate,prevalence and adverse outcomes of Wilson's *** We identified 211 patients(male cases 104; female cases 107; median age 27.2 years,IQR: 17.1-38.6 years; duration of follow-up 8.0 years,IQR: 5.0-14.0 years). The average annual incidence rate was 1.44 per million person-years while the prevalence was 17.93 per million. Between 2000 and 2016,there was a decrease in the annual incidence rate from 1.65 to 1.23 per million person-years(P = 0.010),whereas there was an increase in the annual prevalence from 7.80 to 25.20 per million(P < 0.001). Among the 176 cases with hepatic involvement,38(21.6%) had cirrhosis,three(1.7%) developed hepatocellular carcinoma,24(13.6%) underwent liver transplantations,and 26(14.8%) died. Seven patients had concomitant chronic viral hepatitis B or C. The 5-year and 10-years rates of overall survival were 92.6% and 89.5%,and for transplant-free survival rates 91.8% and 87.4%,respectively. Cirrhosis and possibly chronic viral hepatitis were associated with poorer overall survival. CONCLUSION There was a significant increase in the prevalence of Wilson's disease in Hong Kong. The prognosis was favorable except for those with cirrhosis or concomitant viral hepatitis.

关键词： Hepaticolenticular degeneration Cirrhosis Hepatocellular carcinoma Transplantation

Growth arrest-specific gene 2 suppresses hepatocarcinogenesis by intervention of cell cycle and p53-dependent apoptosis

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World Journal of Gastroenterology 2019年第32期25卷 4715-4726页

作者： Ran-Xu Zhu Alfred Sze Lok Cheng Henry Lik Yuen Chan Dong-Ye Yang wai-kay seto Department of Gastroenterology and Hepatology The University of Hong Kong–Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina

BACKGROUND Growth arrest-specific gene 2(GAS2)plays a role in modulating in reversible growth arrest cell cycle,apoptosis,and cell ***2 protein is universally expressed in most normal tissues,particularly in the liver,but is depleted in some tumor ***,the functional mechanisms of GAS2 in hepatocellular carcinoma(HCC)are not fully *** To investigate the function and mechanism of GAS2 in *** GAS2 expression in clinic liver and HCC specimens was analyzed by real-time PCR and western *** proliferation was analyzed by counting,MTS,and colony formation *** cycle analysis was performed by flow *** apoptosis was investigated by Annexin V apoptosis assay and western *** GAS2 protein expression was lower in HCC than in normal *** of GAS2 inhibited the proliferation of HCC cells with wide-type p53,while knockdown of GAS2 promoted the proliferation of hepatocytes(P<0.05).Furthermore,GAS2 overexpression impeded the G1-to-S cell cycle transition and arrested more G1 cells,particularly the elevation of sub G1(P<0.01).Apoptosis induced by GAS2 was dependent on p53,which was increased by etoposide *** expression of p53 and apoptosis markers was further enhanced when GAS2 was upregulated,but became diminished upon downregulation of *** the clinic specimen,GAS2 was downregulated in more than 60%of *** average fold changes of GAS2 expression in tumor tissues were significantly lower than those in paired non-tumor tissues(P<0.05).CONCLUSION GAS2 plays a vital role in HCC cell proliferation and apoptosis,possibly by regulating the cell cycle and p53-dependent apoptosis pathway.

关键词： Growth arrest-specific gene 2 Cell cycle Apoptosis Hepatocellular carcinoma p53-dependent signaling pathway

Prediction of hepatocellular carcinoma development by aminotransferase to platelet ratio index in primary biliary cholangitis

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World Journal of Gastroenterology 2017年第44期23卷 7863-7874页

作者： Ka-Shing Cheung wai-kay seto James Fung Lung-Yi Mak Ching-Lung Lai Man-Fung Yuen Department of Medicine The University of Hong Kong Queen Mary Hospital State Key Laboratory for Liver Research The University of Hong Kong

AIM To investigate the usefulness of aspartate aminotransferase to platelet ratio index(APRI) in predicting hepatocellular carcinoma(HCC) risk in primary biliary cholangitis(PBC).METHODS We identified PBC patients between 2000 and 2015 by searching the electronic medical database of a tertiary center. The hazard ratio(HR) of HCC with different risk factors was determined by Cox proportional hazards model. RESULTS One hundred and forty-four PBC patients were recru-ited. Patients were diagnosed at a median age of 57.8 years [interquartile range(IQR): 48.7-71.5 years), and 41(28.5%) patients had cirrhosis at baseline. The median follow-up duration was 6.9 years(range: 1.0-26.3 years). Twelve patients developed HCC, with an incidence rate of 10.6 cases per 1000 patient-years. The overall 5-, 10-and 15-year cumulative incidences of HCC were 2.3% 95%CI: 0%-4.8%), 8.4%(95%CI: 1.8%-14.5%) and 21.6%(6.8%-34.1%), respectively. Older age(HR = 1.07), cirrhosis(HR = 4.38) and APRI at 1 year after treatment(APRI-r1) > 0.54(HR = 3.94) were independent factors for HCC development. APRI-r1, when combined with treatment response, further stratified HCC risk(log rank P < 0.05). The area under receiver operating curve of APRI-r1 in predicting HCC was 0.77(95%CI: 0.64-0.88).CONCLUSION APRI-r1 can be used to predict the development of HCC in PBC patients. Combination of APRI-r1 with treatment response can further stratify the HCC risk.

关键词： Aspartate aminotransferase Platelet ratio index Hepatocellular carcinoma Primary biliary cholangitis Ursodeoxycholic acid Cirrhosis

Serum Mac-2 binding protein glycosylation isomer level predicts hepatocellular carcinoma development in E-negative chronic hepatitis B patients

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World Journal of Gastroenterology 2019年第11期25卷 1398-1408页

作者： Lung-Yi Mak wai-Pan To Danny Ka-Ho Wong James Fung Fen Liu wai-kay seto Ching-Lung Lai Man-Fung Yuen Department of Medicine Queen Mary Hospital Department of Medicine The University of Hong Kong State Key Laboratory for Liver Research The University of Hong Kong

BACKGROUND Liver cirrhosis is a major risk factor for hepatocellular carcinoma(HCC)development in chronic hepatitis B(CHB). Serum Mac-2 binding protein glycosylation isomer(M2 BPGi) is a novel serological marker for fibrosis. The role of M2 BPGi in prediction of HCC is *** To examine the role of serum M2 BPGi in predicting HCC development in hepatitis B e antigen(HBeAg)-negative *** Treatment-naive CHB patients with documented spontaneous HBeAg seroconversion were recruited. Serum M2 BPGi was measured at baseline(within3 years from HBeAg seroconversion), at 5 years and 10 years after HBeAg seroconversion and expressed as cut-off index(COI). Multivariate cox regression was performed to identify predictors for HCC development. ROC analysis was used to determine the cut-off value of M2 *** Among 207 patients(57% male, median age at HBeAg seroconversion 40 years old) with median follow-up of 13.1(11.8-15.5) years, the cumulative incidence of HCC at 15 years was 7%. Median M2 BPGi levels were significantly higher in patients with HCC compared to those without HCC(baseline: 1.39 COI vs 0.38 COI, P < 0.001; 5-year: 1.45 COI vs 0.47 COI, P < 0.001; 10-year: 1.20 COI vs 0.55 COI, P = 0.001). Multivariate analysis revealed age at HBeAg seroconversion[odds ratio(OR) = 1.196, 95% confidence interval(CI): 1.034-1.382, P = 0.016] and baseline M2 BPGi(OR = 4.666, 95%CI: 1.296-16.802, P = 0.018) were significant factors predictive of HCC. Using a cut-off value of 0.68 COI, baseline M2 BPGi yielded AUROC of 0.883 with 91.7% sensitivity and 80.8% *** High serum M2 BPGi within 3 years after HBeAg seroconversion was a strong predictor for subsequent HCC development in treatment-naive HBeAg-negative CHB patients.

关键词： Hepatocellular carcinoma Hepatitis B Liver fibrosis Mac-2 binding protein glycosylation isomer Biomarker

Carvedilol Versus Other Nonselective Beta Blockers for Variceal Bleeding Prophylaxis and Death: A Network Meta-analysis

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Journal of Clinical and Translational Hepatology 2023年第5期11卷 1143-1149页

作者： Ka-Shing Cheung Chiu-Hang Mok Lok-Ka Lam Xian-Hua Mao Lung-Yi Mak wai-kay seto Man-Fung Yuen Department of Medicine School of Clinical MedicineThe University of Hong KongQueen Mary HospitalHong KongChina Department of Medicine The University of Hong Kong-Shenzhen HospitalShenzhenGuangdongChina School of Clinical Medicine The University of Hong KongHong KongChina State Key Laboratory of Liver Research The University of Hong KongHong KongChina

Background and Aims:We aimed to perform a network meta-analysis(NWM)to examine comparative effectiveness of non-selective beta blockers(NSBBs)on prophylaxis of gastroesophageal variceal bleeding(GVB)and mortality ***:MEDLINE(OVID)and EMBASE databases were searched for eligible randomized clinical trials(RCTs)from inception to July 3,*** of interest included primary/secondary prophylaxis of GVB,failure to achieve hepatic venous pressure gradient(HVPG)decremental response,liver-related and all-cause mortality.A Bayesian NWM was performed to derive relative risk(RR)with 95%credible intervals(CrIs).The ranking probability of each NSBB was assessed by surface under cumulative ranking curve(SUCRA).Results:Thirty-three RCTs including 3,188 cirrhosis patients with gastroesophageal varices were *** with placebo,nadolol ranked first for reducing variceal bleeding[RR:0.25,(95%CrI:0.11–0.51);SUCRA:0.898],followed by carvedilol[RR:0.33,(95%CrI:0.11–0.88);SUCRA:0.692]and propranolol[RR:0.52,(95%CrI:0.37–0.75);SUCRA:0.405].Carvedilol was more effective than propranolol in achieving HVPG decremental response[RR:0.43,(95%CrI:0.26–0.69)].Carvedilol ranked first for reducing all-cause mortality[RR:0.32,(95%CrI:0.17–0.57);SUCRA:0.963],followed by nadolol[RR:0.48,(95%CI:0.29–0.77);SUCRA:0.688],and propranolol[RR:0.77,(95%CI:0.58–1.02);SUCRA:0.337].Similar findings were observed for liver-related *** ranked the *** RR of adverse events was 4.38,(95%CrI:0.33–161.4);SUCRA:0.530,followed by propranolol[RR:7.54,(95%CrI:1.90–47.89);SUCRA:0.360],and nadolol[RR:18.24,(95%CrI:91.51–390.90);SUCRA:0.158].Conclusions:Carvedilol is the preferred NSBB with better survival benefit and lower occurrence of adverse events among patients with gastroesophageal varices.

关键词： NSBB Carvedilol Nadolol Propranolol Varices Cirrhosis CPSH

Studies GS-US-320-0108 and GS-US-320-0110:Hepatocellular Carcinoma(HCC) Overview

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Studies GS-US-320-0108 and GS-US-320-0110:Hepatocellular Car...