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Natural history of hepatitis-related hepatocellular carcinoma

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World Journal of Gastroenterology 2008年第11期14卷 1652-1656页

作者： David Yiu-Kuen But ching-lung lai Man-Fung Yuen Department of Medicine The University of Hong KongQueenMary HospitalHong KongChina

Hepatocellular carcinoma （HCC） is an important cause of cancer death in the world. It has great regional differences in the pathology and epidemiology. The variation is greatly influenced by the aetiologies of the disease. Hepatitis B and C infection are the most important risk factors. HCC incidence rates are higher but in decreasing trend in developing countries. However, the figures in the developed countries are contrary. Successful hepatitis B virus （HBV） vacdnation programs, better food hygiene, increased global hepatitis C virus {HCV） prevalence and population migration are the possible explanations. A number of clinical and pathogenic differences exist between HBV- and HCV- related HCC. HBV infection leads to the development of HCC through direct and indirect pathways as it has the ability to integrate into the host genome affecting cellular signaling and growth control. HCV causes HCC mainly through indirect pathways： chronic inflammation, cell deaths and proliferation. As a result, HCC is almost exclusively found in cirrhotic HCV patients while HCC is sometimes found in HBV patients without significant liver cirrhosis. Due to the different severities of liver cirrhosis and HCC extent, therapeutic strategies from resection, liver transplantation to symptoms palliation are available. Poorly differentiated histology, lack of fibrous capsule, large tumour size, early vascular invasion and elevated serum levels of alpha fetoprotein （AFP） are the features for more aggressive disease. Combined with markers of liver reserve and performance status, accurate scoring systems and models have been developed to predict patients＇ survival and match best treatment option.

关键词： Natural history Hepatitis Hepatocellular carcinoma

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

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

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

Psychometrics of the chronic liver disease questionnaire for Southern Chinese patients with chronic hepatitis B virus infection

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World Journal of Gastroenterology 2009年第26期15卷 3288-3297页

作者： Elegance Ting Pui Lam Cindy Lo Kuen Lam ching lung lai Man Fung Yuen Daniel Yee Tak Fong Department of Medicine The University of Hong Kong Department of Nursing Studies The University of Hong Kong

AIM： To test the psychometric properties of a Chinese [（Hong Kong） HK] translation of the chronic liver disease questionnaire （CLDQ）. METHODS： A Chinese （HK） translation of the CLDQ was developed by iterative translation and cognitive debriefing. It was then administered to 72 uncomplicated and 78 complicated chronic hepatitis B （CriB） patients in Hong Kong together with a structured questionnaire on service utilization, and the Chinese （HK） SF-36 Health Survey Version 2 （SF-36v2）. RESULTS： Scaling success was ≥ 80% for all but three items. A new factor assessing sleep was found and items of two （Fatigue and Systemic Symptoms） subscales tended to load on the same factor. Internal consistency and test-retest reliabilities ranged from 0.58-0.90 for different subscales. Construct validity was confirmed by the expected correlations between the SF-36v2 Health Survey and CLDQ scores. Mean scores of CLDQ were significantly lower in complicated compared with uncomplicated CHB, supporting sensitivity in detecting differences between groups.CONCLUSION： The Chinese （HK） CLDQ is valid, reliable and sensitive for patients with CHB. Some modifications to the scaling structure might further improve its psychometric properties,

关键词： Chronic liver disease Health-related quality of life Hepatitis B Southern Chinese Validity

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

Quantitative hepatitis B surface antigen in predicting recurrence of hepatitis B-related hepatocellular carcinoma after liver transplantation

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Hepatoma Research 2018年第9期4卷 159-170页

作者： James Fung Danny Ka-Ho Wong Yasuhito Tanaka Regina Lo Tiffany Wong Kenneth Siu-Ho Chok AIbert Chi-Yan Chan Tan-To Cheung Wing-Chiu Dai KeIvin Ng Kevin Ng Man Kwan Irene Ng Wai-Kay Seto ching-lung lai Man-Fung Yuen Chung-Mau Lo The Liver Transplant Center Queen Mary HospitalHong KongChina Department of Medicine the University of Hong KongHong KongChina State Key Laboratory for Liver Research the University of Hong KongHong KongChina Department of Virology and Liver Unit Graduate School of Medical sciencesNagoya City UniversityNagoya 467-8601Japan Department of Pathology the University of Hong KongHong KongChina Department of Surgery the University of Hong KongHong KongChina

Aim:Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) for chronic hepatitis B (CHB) can be associated with reappearance of hepatitis B surface antigen (HBsAg). The current study determined the significance of HBsAg qualitatively and quantitatively using a highly sensitive assay in recurrent HCC after transplantation. Methods:Consecutive patients with HBV-related HCC with LT were included. Oral nucleos(t)ide analogues without hepatitis B immune globulin were used as hepatitis B virus (HBV) prophylaxis. Quantitative HBsAg levels were performed at time of transplant, at 1 month, 3 and 6 months post transplant using a highly sensitive (hs)-HBsAg assay. Results:One hundred and fourteen patients were included, with a median follow-up of 80 months, with 24 cases of HCC recurrence, and a cumulative rate of 20.7% at 5 years. There was significant correlation between time of tumor recurrence and time of HBsAg reappearance (r = 0.551,P = 0.027). Early HCC recurrence was associated with higher median level of hs-HBsAg at the time of transplant (72.85vs. 69.70 IU/mL,P = 0.018). Using a hs-HBsAg cut-off level of 0.0005 IU/mL, patients with levels above this threshold at 3 and 6 months were associated with higher rate of early HCC recurrence (28.6%vs. 3.0% and 26.9%vs. 2.9% respectively, bothP =0.0006). There was no significant difference in HCC recurrence between positive and negative HBsAg using the conventional qualitative HBsAg assay. Conclusion:Serum hs-HBsAg levels of≥ 0.0005 IU/mL at 3 to 6 months after LT is associated with higher rates of early HCC recurrence, and may be useful as an early tumor marker.

关键词： Hepatitis B hepatocellular carcinoma transplantation hepatitis B surface antigen recurrence

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慢性乙肝治疗的新目标及新方案

中国处方药 2008年第12期7卷 10-10页

作者： ching-lung lai Man-Fung Yuen 海燕

慢性HBV感染的治疗目标,除了达到HBeAg转换,更重要的是将HBV DNA水平持续控制到极低的水平,最好是低于敏感PCR所能检测出来的水平,而ALT的水平也要低于正常值上限的一半。

关键词：慢性HBV感染乙肝治疗 DNA水平 HBeAg 正常值上限 HEV PCR ALT

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

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Neural Regeneration Research 2025年第4期20卷 917-935页

作者： Dian Jiao lai Xu Zhen Gu Hua Yan Dingding Shen Xiaosong Gu Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang UniversityHangzhouZhejiang ProvinceChina Affiliated Hospital of Nantong University NantongJiangsu ProvinceChina

Epilepsy is a severe,relapsing,and multifactorial neurological *** regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of *** pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota *** results are lacking for conventional treatments for *** resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with ***-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research *** review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of *** also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current *** studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic ***,many new technologies for the diagnosis and treatment of epilepsy are being ***,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

关键词： diagnosis drug treatment electroencephalography epilepsy monitoring epilepsy nerve regeneration neurostimulation non-drug interventions pathogenesis prediction