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World Journal of Gastroenterology 2013年第39期19卷 6515-6522页

作者： grace lai-hung wong Vincent Wai-Sun wong Institute of Digestive Disease and Department of Medicine and Therapeutics The Chinese University of Hong Kong

Chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC)is a major health problem in AsianPacific *** therapy reduces,but does not eliminate the risk of *** would be a heavy financial burden in most low and middle economic countries if all CHB patients received antiviral therapy and HCC ***,there is a need for accurate risk prediction to assist prognostication,decisions on the need for antiviral therapy and HCC surveillance.A few wellestablished risk factors for HCC,namely advanced age,male gender,high viral load,cirrhosis etc.,are the core components of three HCC risk scores:CU-HCC,GAGHCC and REACH-B *** 3 scores were confirmed to be accurate in predicting HCC up to 10 years in treatment-na ve *** validity and applicability have recently been demonstrated in a large cohort of entecavir treatment patients.A decrease in risk scores after antiviral therapy translates to a lower risk of *** findings support the application of HCC risk scores in all CHB *** levels of care and different intensities of HCC surveillance should be offered according to the risk profile of *** at risk of HCC should undergo regular HCC surveillance,even when they are receiving antiviral treatment.

关键词： Antiviral therapy Cirrhosis Hepatitis B virus DNA Hepatocellular carcinoma Risk prediction score Transient elastography

Transient elastography: Kill two birds with one stone?

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World Journal of Hepatology 2013年第5期5卷 264-274页

作者： grace lai-hung wong Department of Medicine and Therapeutics and Institute of Digestive DiseaseThe Chinese University of Hong Kong

Assessment of liver fibrosis and steatosis is crucial in chronic liver diseases in order to determine the prognosis, the need of treatment, as well as monitor disease progression and response to treatment. Liver biopsy is limited by its invasiveness and patient acceptability. Transient elastography (TE, Fibroscan ) is a non-invasive tool with satisfactory accuracy and reproducibility to estimate liver fibrosis and steatosis. TE has been well validated in major liver diseases including chronic hepatitis B and C, non-alcoholic fatty liver disease, alcoholic liver disease, primary biliary cirrhosis, and primary sclerosing cholangitis. As alanine aminotransferase (ALT) is one of the major confounding factors of liver stiffness in chronic hepatitis B, an ALT-based algorithm has been developed and higher liver stiffness measurements (LSM) cutoff values for different stages of liver fibrosis should be used in patients with elevated ALT levels up to 5 times of the upper limit of normal. Otherwise falsely-high LSM results up to cirrhotic range may occur during ALT flare. TE is also useful in predicting patient prognosis such as development of hepatocellular carcinoma (HCC), portal hypertension, post-operative complications in HCC patients, and also survival. Unfortunately, failed acquisition of TE is common in obese patients. Furthermore,obese patients may have higher LSM results even in the same stage of liver fibrosis. The new XL probe, a larger probe with lower ultrasound frequency and deeper penetration, increases the success rate of TE in obese patients. The median LSM value with XL probe was found to be lower than that by the conventional M probe, hence cutoff values approximately 1.2 to 1.3 kPa lower than those of M probe should be adopted. Recent studies revealed a novel ultrasonic controlled attenuation parameter (CAP) of the machine is a useful parameter to detect even low-grade steatosis noninvasively. CAP may also be used to quantify liver steatosis by applying d

关键词： Biopsy Cirrhosis Fibrosis Hepatitis Fatty liver Steatosis of liver

Impact of antiviral therapy on post-hepatectomy outcome for hepatitis B-related hepatocellular carcinoma

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World Journal of Gastroenterology 2014年第20期20卷 6006-6012页

作者： Charing Ching Ning Chong grace lai hung wong Paul Bo San lai Division of Hepato-biliary and Pancreatic Surgery Department of Surgery Prince of Wales Hospital the Chinese University of Hong Kong Institute of Digestive Disease and Department of Medicine and Therapeutics Prince of Wales Hospital the Chinese University of Hong Kong

The outcome after curative resection for hepatocellular carcinoma(HCC)remains unsatisfactory due to the high recurrence rate after *** patients with hepatitis B virus(HBV)-related HCC,which is the majority of patients with HCC in Asia,a high viral load is a strong risk factor for HCC *** is logical to believe that antiviral therapy may improve the postoperative outcome by promoting viral clearance and hepatocyte regeneration,as well as improving residual liver volume in HCC patients with hepatitis ***,the effect of antiviral therapy on clinical outcomes after liver resection in patients with HBV-related HCC remains to be *** are two main groups of antiviral treatment for HBV-oral nucleos(t)ide analogues and *** treatment reduces the overall incidence of HBV-related HCC in sustained ***,side effects may limit its long-term clinical ***(t)ide analogues carry fewer side effects and are potent in terms of viral suppression when compared to interferon and are typically implemented for patients with more advanced liver *** may also improve the outcome after curative resection for HBV-related *** are increasing evidence to suggest that antiviral therapy could suppress HBV,decrease the perioperative reactivation of viral replication,reduce liver injury,preserve the liver function before and after operation,and may lower the risk of HCC *** all,antiviral therapy may improve the survival after liver resection by reducing recurrence and delaying the liver damage by the virus,resulting in a higher chance of receiving aggressive salvage therapy during HCC recurrence.

关键词： Antiviral therapy Hepatitis B infection Hepatocellular carcinoma Hepatectomy Liver resection Outcome

Epidemiology and Clinical Outcomes of Metabolic(Dysfunction)-associated Fatty Liver Disease

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Journal of Clinical and Translational Hepatology 2021年第6期9卷 972-982页

作者： Huapeng Lin Xinrong Zhang Guanlin Li grace lai-hung wong Vincent Wai-Sun wong Department of Medicine and Therapeutics State Key Laboratory of Digestive diseaseand Medical Data Analytics CentreThe Chinese University of Hong KongHong KongChina

Metabolic(dysfunction)-associated fatty liver disease(MAFLD)is currently the most common chronic liver disease and affects at least a quarter of the global adult *** has rapidly become one of the leading causes of hepatocellular carcinoma and cirrhosis in Western *** this review,we discuss the nomenclature and definition of MAFLD as well as its prevalence and incidence in different geographical *** cardiovascular disease remains the leading cause of death in MAFLD patients,the proportion of patients dying from hepatic complications increases sharply as the disease progresses to advanced liver fibrosis and *** addition,patients with MAFLD are at increased risk of various extrahepatic *** a causal relationship between MAFLD and extrahepatic cancers has not been established,clinicians should recognize the association and consider cancer screening(e.g.,for colorectal cancer)as appropriate.

关键词： Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Obesity Prevalence Incidence Hepatocellular carcinoma Cirrhosis

Update of liver fibrosis and steatosis with transient elastography (Fibroscan)

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Gastroenterology Report 2013年第1期1卷 19-26页

作者： grace lai-hung wong Institute of Digestive Disease The Chinese University of Hong KongHong Kong SARChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong Kong SARChina

Background:Assessment of liver fibrosis and steatosis is now almost indispensable in most of the chronic liver diseases in order to determine prognosis and need for treatment,and to monitor disease progression and response to *** biopsy is limited by its invasiveness and patient *** elastography(TE;Fibroscan)is a non-invasive tool with satisfactory accuracy and reproducibility to estimate liver ***&Methods:To review the existing evidence concerning the clinical applications of TE in major liver diseases,including chronic hepatitis B and-C,non-alcoholic fatty liver disease(NAFLD),alcoholic liver disease,primary biliary cirrhosis and primary sclerosing ***:As alanine aminotransferase(ALT)is one of the major confounding factors of liver stiffness in chronic hepatitis B,an ALT-based algorithm has been developed and higher liver stiffness measurements(LSM)cut-off values for different stages of liver fibrosis should be used in patients with elevated ALT levels up to five times the upper limit of ***,falsely-high LSM results up to the cirrhotic range may occur during ALT *** is also useful predicting patient prognosis in the development of hepatocellular carcinoma(HCC),portal hypertension,postoperative complications in HCC patients and ***,failed acquisition of TE is common in obese ***,obese patients may have higher LSM results,even in the same stage of liver *** better evaluate NAFLD a new XL probe,with a larger probe with lower ultrasound frequency and deeper penetration,increases the success rate of TE in obese *** median LSM value with the XL probe was found to be lower than that by the conventional M probe,hence cut-off values were approximately 1.2 to 1.3 kilopascals lower than those of the M probe,suggesting its *** reveal that a novel ultrasonic controlled attenuation parameter is potentially useful to detect and quantify

关键词： cirrhosis hepatitis fatty liver histology liver biopsy liver stiffness measurement

Optimal surveillance program for hepatocellular carcinoma- getting ready, but not yet

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World Journal of Hepatology 2015年第18期7卷 2133-2135页

作者： grace lai-hung wong Department of Medicine and Thera- peutics 9/F Prince of Wales Hospital the Chinese University of Hong Kong Institute of Digestive Disease the Chinese University of Hong Kong State Key Laboratory of Digestive Disease the Chinese University of Hong Kong

Hepatocellular carcinoma(HCC) secondary to chronic viral hepatitis is a major health problem in AsianPacific regions due to the endemics of chronic hepatitis B and C virus infection. HCC surveillance has been recommended to patients who are at risk to develop HCC. Unfortunately, a significant proportion of patients still died in long run due to tumor recurrence. The key components of an optimal surveillance program include an accurate tumor biomarker and optimal surveillance interval. Serum alpha-fetoprotein(AFP), despite of being the most widely used biomarker for HCC surveillance, it was criticized as neither sensitive nor specific. Other HCC biomarkers, including lectin-reactive AFP(AFP-L3), des-gamma carboxyprothrombin, are still under investigations. Recent study showed cancerassociated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing to be accurate with both sensitivity and specificity close to 90% in detecting HCC in a case-control study. Concerning the optimal surveillance interval, we believe one size does not fit all patients. Accurate risk prediction to assist prognostication with well-validated HCC risk scores would be useful to decide the need for HCC surveillance. These key components of an optimal HCC surveillance program should be further validated at a surveillance setting.

关键词： Antiviral therapy Biomarkers Hepatocellular carcin

Overview of methodologies and statistical strategies in observational studies and meta-analyses on the risk of hepatocellular carcinoma in patients with chronic hepatitis B on entecavir or tenofovir therapy

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Hepatoma Research 2022年第1期8卷 143-156页

作者： Terry Cheuk-Fung Yip Vincent Wai-Sun wong Mandy Sze-Man lai Vicki Wing-Ki Hui Yee-KitTse grace lai-hung wong Medical Data Analytics Centre Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics 9/F Lui Che Woo Clinical Sciences BuildingPrince of Wales Hospital30-32 Ngan Shing StreetShatinHong KongChina Institute of Digestive Disease The Chinese University of Hong KongHong KongChina

Entecavir(ETV)and tenofovir disoproxil fumarate(TDF)are first-line antiviral therapies for patients with chronic hepatitis B(CHB)and reduce the risk of disease progression and liver-related complications,as well as improve survival by effectively suppressing viral ***,since the first publication in 2019 on a lower risk of hepatocellular carcinoma(HCC)in Korean patients receiving TDF than those receiving ETV,the topic has remained a hot and unsettled *** studies and meta-analyses have yielded conflicting *** HCC takes time to develop,studies are mainly observational to benefit from a larger sample size and longer follow-up that provides a higher statistical power to compare the two ***,TDF was available to CHB patients a few years later than ETV in most countries,thus leading to a difference in follow-up ***,despite studying the same topic,the difference in data sources and available parameters,inclusion and exclusion criteria,and use of statistical methods complicated the interpretation and comparison of the findings and contributed to between-study heterogeneity in *** review describes some caveats in interpreting and comparing the results from these observational studies and *** studies should explore better designed observational studies with high-quality data sources,and aggregation of patient data in metaanalysis to tackle between-study heterogeneity.

关键词： Bias confounding hepatitis B virus hepatocellular carcinoma liver cancer nucleos(t)ide analogues propensity score

Validation model of fibrosis-8 index score to predict significant fibrosis among patients with nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2022年第15期28卷 1563-1573页

作者： Thaninee Prasoppokakorn Wah-Kheong Chan Vincent Wai-Sun wong Panyavee Pitisuttithum Sanjiv Mahadeva Nik Raihan Nik Mustapha grace lai-hung wong Howard Ho-Wai Leung Pimsiri Sripongpun Sombat Treeprasertsuk Department of Medicine Division of GastroenterologyFaculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalThai Red Cross SocietyBangkok 10330Thailand Department of Medicine Division of GastroenterologyDivision of Gastroenterology and Hepatology UnitFaculty of MedicineUniversity of MalayaKuala Lumpur 50603Malaysia Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina Department of Medicine Division of General Internal MedicineFaculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalThai Red Cross SocietyBangkok 10330Thailand Department of Pathology Hospital Sultanah BahiyahAlor SetarKedah 05460Malaysia Department of Anatomical and Cellular Pathology The Chinese University of Hong KongHong KongChina Department of Internal Medicine Prince of Songkla UniversityHat Yai 90110Thailand Department of Medicine Division of Gastroenterology and HepatologyStanford University School of MedicinePalo AltoCA 94305United States

BACKGROUND Identifying hepatic fibrosis is crucial for nonalcoholic fatty liver disease(NAFLD)*** fibrosis-8(FIB-8)score,recently developed by incorporating four additional variables into the fibrosis-4(FIB-4)score,showed better performance in predicting significant fibrosis in *** To validate the FIB-8 score in a biopsy-proven NAFLD cohort and compare the diagnostic performance of the FIB-8 and FIB-4 scores and NAFLD fibrosis score(NFS)for predicting significant *** We collected the data of biopsy-proven NAFLD patients from three Asian centers in three *** the patients with available variables for the FIB-4 score(age,platelet count,and aspartate and alanine aminotransferase levels)and FIB-8 score(the FIB-4 variables plus 4 additional parameters:The body mass index(BMI),albumin to globulin ratio,gamma-glutamyl transferase level,and presence of diabetes mellitus)were *** fibrosis stage was scored using nonalcoholic steatohepatitis CRN criteria,and significant fibrosis was defined as at least fibrosis stage *** A total of 511 patients with biopsy-proven NAFLD and complete data were included for *** these 511 patients,271(53.0%)were female,with a median age of 51(interquartile range:41,58)*** median BMI was 29(26.3,32.6)kg/m2,and 268(52.4%)had *** the 511 NAFLD patients,157(30.7%)had significant fibrosis(≥F2).The areas under the receiver operating characteristic curves of the FIB-8 and FIB-4 scores and NFS for predicting significant fibrosis were 0.774,0.743,and 0.680,*** FIB-8 score demonstrated significantly better performance for predicting significant fibrosis than the NFS(P=0.001)and was also clinically superior to FIB-4,although statistical significance was not reached(P=0.073).The low cutoff point of the FIB-8 score for predicting significant fibrosis of 0.88 showed 92.36%sensitivity,and the high cutoff point of the FIB-8 score for predicting significant fibrosis of 1.

关键词： Nonalcoholic fatty liver disease Fibrosis-8 score Fibrosis-4 score Nonalcoholic fatty liver disease fibrosis score

Advances in the diagnosis and treatment of liver fibrosis

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Hepatoma Research 2017年第8期3卷 156-169页

作者： Jenny Yeuk-Ki Cheng grace lai-hung wong Institute of Digestive Disease The Chinese University of Hong KongShatinHong Kong 999077China Department of Medicine and Therapeutics 9/F Prince of Wales HospitalShatinHong Kong 999077China State Key Laboratory of Digestive Disease The Chinese University of Hong KongShatinHong Kong 999077China.

Liver fibrosis is the center of diagnosis and management of essentially all chronic liver diseases. While liver biopsy examination still has a role in diagnosis and drug development, it is replaced by non-invasive assessments of liver biopsy in majority of the clinical scenarios. Radiological approaches, namely transient elastography, acoustic radiation force impulse imaging, shear wave elastography, magnetic resonance elastography provide accurate diagnosis of advanced fibrosis and cirrhosis. Serum test formulae based on common laboratory parameters or more specialized parameters including those commercially available panels FibroTest?, FibroMeter? and Enhanced Liver Fibrosis are also available. Combining different modalities may further improve the accuracy. The role of all these non-invasive assessments has been further expanded from diagnostic to prognostic, e.g. risk prediction of hepatocellular carcinoma (HCC) by LSM-HCC score. Treatment of liver fibrosis can be achieved by controlling the underlying diseases, with chronic viral hepatitis as the most established disease model. Currently there are multiple clinical trials evaluating different treatment options to improve fibrosis in patients with non-alcoholic fatty liver disease. Specific anti-fibrotic treatment targets e.g. direct downregulation of hepatic stellate cell, collagen synthesis inhibitors and transforming growth factor-βantagonists have been tested in laboratory and pending further studies in clinical settings.

关键词： Chronic hepatitis B chronic hepatitis C fatty liver transient elastography

Non-invasive tests of non-alcoholic fatty liver disease

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Chinese Medical Journal 2022年第5期135卷 532-546页

作者： Guanlin Li Xinrong Zhang Huapeng Lin Lilian Yan Liang grace lai-hung wong Vincent Wai-Sun wong Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong KongChina Medical Data Analytics Centre The Chinese University of Hong KongHong KongChina

For the detection of steatosis,quantitative ultrasound imaging techniques have achieved great progress in past *** resonance imaging proton density fat fraction is currently the most accurate test to detect hepatic *** blood biomarkers correlate with non-alcoholic steatohepatitis,but the accuracy is *** liver fibrosis,liver stiffness measurement by transient elastography(TE)has high accuracy and is widely used across the *** resonance elastography is marginally better than TE but is limited by its cost and *** blood biomarkers of fibrosis have been used in clinical trials and hold promise for selecting patients for treatment and monitoring treatment *** article reviews new developments in the non-invasive assessment of non-alcoholic fatty liver disease(NAFLD).Accumulating evidence suggests that various non-invasive tests can be used to diagnose NAFLD,assess its severity,and predict the *** studies are needed to determine the role of the tests as monitoring *** cannot overemphasize the importance of context in selecting appropriate tests.

关键词： Fatty liver Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Liver fibrosis Cirrhosis Transient elastography FibroScan Magnetic resonance imaging