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Metabolic dysfunction associated fatty liver disease: The new nomenclature and its impact

World Journal of Gastroenterology 2023年第3期29卷 549-560页

作者： Si-Ying Tang Jian Shiun Tan Xian-Zheng Pang guan-huei lee Division of Gastroenterology and Hepatology National University HospitalSingapore 119228Singapore Yong Loo Lin School of Medicine Singapore 117597Singapore

BACKGROUND In 2020,an international expert panel proposed a new definition of fatty liver:Metabolic dysfunction-associated fatty liver disease(MAFLD).The MAFLD added the criteria for defining metabolic dysfunctions,which are high-risk factors for liver-related and cardiovascular *** to the non-alcoholic fatty liver disease(NAFLD)definition,it allows the coexistence of MAFLD and significant alcohol use in the same *** To review the existing data that evaluate the clinical profile and long-term outcome difference between the patients identified as MAFLD and *** Databases MEDLINE via PubMed and EMBASE were searched and relevant publications up to June 28,2022 were *** were included if they involved human participants diagnosed with *** A total of 2324 records were reviewed,of which 1575 duplicate citations were *** the 2324 records screened,207 articles were excluded,and 542 articles were assessed for their eligibility,for which 511 were *** remaining 31 articles were selected for *** diagnostic criteria were able to identify more individuals with fatty *** have shown that patients included using the MAFLD criteria were associated with higher risks of hepatic fibrosis when compared to ***-cause mortality,cardiovascular diseaserelated,and cancer-related mortality were shown to be higher in MAFLD *** patients also had higher baseline metabolic derangement,and risks of developing obesity,diabetes,and cardiovascular *** the 3 subtypes,diabetes mellitus has the strongest association with negative outcomes,followed by metabolic dysfunction and elevated body mass *** the subtypes of MAFLD,patients with more metabolic conditions at the time of diagnosis had worse hepatic and liver injury compared to those with a single metabolic *** MAFLD is a new definition of fatty liver disease that is gaining increasing *** is based on empirical

关键词： Hepatic steatosis Liver fibrosis Cardiovascular events Alcohol liver disease Obesity

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Plasma exchange in patients with acute and acute-on-chronic liver failure: A systematic review

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World Journal of Gastroenterology 2020年第2期26卷 219-245页

作者： Eunice Xiang-Xuan Tan Min-Xian Wang Junxiong Pang guan-huei lee National University Health System Singapore 119228Singapore Centre for Infectious Disease Epidemiology and Research Saw Swee Hock School of Public HealthNational University of SingaporeSingapore 119077Singapore National University of Singapore Singapore 119077Singapore

BACKGROUND Acute liver failure(ALF)and acute-on-chronic liver(ACLF)carry high short-term mortality rate,and may result from a wide variety of *** exchange has been shown in a randomized control trial to improve survival in ALF especially in patients who did not receive a liver *** cohort studies demonstrated potential improvement in survival in patients with *** To assess utility of plasma exchange in liver failure and its effect on mortality in patients who do not undergo liver *** Databases MEDLINE via PubMed,and EMBASE were searched and relevant publications up to 30 March,2019 were *** were included if they involved human participants diagnosed with liver failure who underwent plasma exchange,with or without another alternative non-bioartificial liver assist *** Three hundred twenty four records were reviewed,of which 62 studies were found to be *** the 262 records screened,211 studies were ***-one articles were assessed for eligibility,for which 7 were ***-nine studies were included for ALF only,and 9 studies for ACLF *** studies included both ALF and ACLF patients.A total of 44 publications were *** the included publications,2 were randomized controlled trials,14 cohort studies,12 case series,16 case *** of three ALF studies which looked at survival rate or survival days reported improvement in outcome with plasma *** two out of four studies where plasma exchange-based liver support systems were compared to standard medical treatment(SMT)for ACLF,a biochemical improvement was *** in the non-transplanted patients was improved in all four studies in patients with ACLF comparing plasma exchange vs *** the aforementioned studies,plasma exchange based therapy in ACLF compared to SMT improved survival in non-transplanted patients at 30 and 90-d with a pooled OR of 0.60(95%CI 0.46-0.77,P<0.01).CONCLUSION The level of ev

关键词： Acute-on-chronic liver failure Acute liver failure Plasmapheresis Plasma exchange Liver failure

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Alanine aminotransferase is an inadequate surrogate marker for detecting lamivudine resistance

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World Journal of Gastroenterology 2010年第37期16卷 4691-4696页

作者： lee guan Lim Myat Oo Aung Bee Leng Seet Cindy Tan Yock Young Dan Yin Mei lee Dede Selamat Sutedja Mark Fernandes guan huei lee Evelyn Koay Seng Gee Lim Department of Gastroenterology and Hepatology National University Health System Yong Yoo Lin School of Medicine National University of Singapore Department of Medicine National University Health System Yong Yoo Lin School of Medicine National University of Singapore Molecular Diagnostic Centre National University Health System Yong Yoo Lin School of Medicine National University of Singapore Investigative Medicine Unit National University Health System Yong Yoo Lin School of Medicine National University of Singapore

AIM: To investigate the accuracy of serum alanine aminotransferase (ALT) in diagnosing lamivudine resistance and factors that contributed to abnormal serum ***: This was a retrospective study of chronic hepatitis B patients on lamivudine therapy who were followed for 3-mo with liver function tests and hepatitis B virus (HBV) DNA measurement. Lamivudine resistance was defined as HBV DNA ≥ 1 log from nadir on at least 2 occasions, confirmed by genotyping. Serum ALT levels in patients with lamivudine resistance were compared to serum ALT levels in those without lamivudine resistance. RESULTS: There were 111 patients with and 117 without lamivudine resistance. The area under the receiver operating characteristic of serum ALT to diagnose lamivudine resistance was 0.645 ± 0.037. Serum ALT > 42.5 U/L gave the best diagnostic accuracy with sensitivity = 61%, specificity = 60%, positive predictive value = 60%, negative predictive value = 61%, positive likelihood ratio = 1.53 and negative likelihood ratio = 0.65 for predicting lamivudine resistance, missing 39% of resistant patients. Using other serum ALT cutoffs, diagnostic accuracy was lower. By multivariate analysis, baseline abnormal serum ALT was associated with abnormal ALT during resistance (OR = 5.98, P = 0.003), and males were associated with serum ALT flares during resistance (OR = 8.9, P = 0.016). CONCLUSION: Serum ALT is inadequate for diagnosing lamivudine resistance and has implications where viral resistance testing is suboptimal and for reimbursement of rescue therapy.

关键词： Antiviral therapy Chronic hepatitis B Sensitivity Specificity YMDD mutants

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Acute-on-chronic liver failure in a multi-ethnic Asian city:A comparison of patients identified by Asia-Pacific Association for the Study of the Liver and European Association for the Study of the Liver definitions

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World Journal of Hepatology 2017年第28期9卷 1133-1140页

作者： Anandraj Selva Rajoo Seng-Gee Lim Wah Wah Phyo Thandar Tun Yock-Young Dan Yin-Mei lee How-Cheng Low Kieron Lim Poh-Seng Tan guan-huei lee Yong Loo Lin School of Medicine National University of SingaporeSingapore 119077Singapore Institute of Molecular and Cell Biology ASTARSingapore 138668Singapore Division of Gastroenterology and Hepatology Department of MedicineNational University HospitalSingapore 119228Singapore Department of Hepatology Mandalay General Hospital30th StChan Aye Tharsan TownshipMandalayMyanmar

AIM To explore the applicability of the Asia-Pacific Association for the Study of the Liver(APASL) and European Association for the Study of the Liver(EASL) guidelines for acute-on-chronic liver failure(ACLF) in profiling patients and determining the *** Patients admitted to a tertiary hospital in Singapore with acute decompensation of liver disease from January 2004to July 2014 are screened for ACLF according to the APASL and EASL criteria. The patients' data(including basic demographics, information about existing chronic liver disease, information about the acute decompensation, relevant laboratory values during admission, treatment, and outcome) are retrospectively analyzed to determine the background, precipitating factors and *** A total of 458 liver patients is analyzed, and 78 patients with ACLF are identified. Sixty-three patients(80.8%) meet the APASL criteria, 64 patients(82.1%) meet the EASL criteria, and 49 patients(62.8%) fulfilled both criteria. The most common causes of acute liver injury are bacterial infections(59.0%), hepatitis B flare(29.5%), and variceal bleeding(24.4%). The common aetiologies of the underlying chronic disease included hepatitis B(43.6%), alcoholic(20.5%) and cryptogenic(11.5%) liver disease. The overall mortality rate is 61.5%. Increased age, the number of organ failures(as per CLIF-SOFA score), peak creatinine, INR, and amylase levels are associated with increased mortality or the need for liver transplantation. 14.3% of patients undergo liver transplantation with a 100% 1-year survival rate. CONCLUSION Both APASL and EASL criteria have identified ACLF patients with high three-month mortality, but those who fulfill APASL criteria alone have a better survival.

关键词： Acute-on-chronic liver failure Survival Prognosis Liver decompensation Liver cirrhosis

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Risk factors for ribavirin treatment failure in Asian organ transplant recipients with chronic hepatitis E infection

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World Journal of Hepatology 2019年第6期11卷 553-561页

作者： En Xian Sarah Low Edhel Tripon Kieron Lim Poh Seng Tan How Cheng Low Yock Young Dan Yin Mei lee Mark Muthiah Wai Mun Loo Calvin Jianyi Koh Wah Wah Phyo JunXiong Pang Seng Gee Lim guan-huei lee Department of Medicine Ng Teng Fong General HospitalNational University Health SystemSingapore 609606Singapore Centre for Liver Disease Management and Transplant of Medical City Manila 1605Philippines Mount Elizabeth Medical Centre Singapore 228510Singapore Division of Gastroenterology and Hepatology National University Health SystemSingapore 119228Singapore Department of Medicine National University of SingaporeSingapore 119077Singapore Centre for Infectious Disease Epidemiology and Research National University of SingaporeSingapore 117549Singapore Department of Medicine Yong Loo Lin School of MedicineNational University of SingaporeSingapore 119228Singapore

BACKGROUND Hepatitis E virus(HEV)infection is a cause of chronic hepatitis in immunosuppressed *** virologic response rates to a 12-wk course of ribavirin therapy were reported to be>70%in the *** study describes the outcome of HEV treatment in a transplant center in *** To study the outcome of ribavirin treatment in a series of chronic HEV patients,and the cause of treatment *** We studied all of the transplant recipients who were diagnosed with HEV infection between 2012 to *** outcome of therapy and virologic relapse are monitored for three years after the end of *** Ten transplant recipients(4 liver,5 kidney,and 1 bone marrow transplantation)with positive HEV RNA were *** patients received at least 12 wk of ribavirin therapy,and the remaining patient resolved after reducing immunosuppression *** subjects had prolonged viremia that lasted more than one year,despite continuous ribavirin *** ribavirin-treated patients(44.4%)had HEV RNA relapse after achieving a virologic response by the end of *** overall failure rate is 66.7%.Being a kidney transplant recipient is the strongest risk factor for not achieving an initial sustained virologic response(0/5 treated,Chi-Square test,P<0.05).The most common side effect of ribavirin is anemia(100%)(haemoglobin reduction of 3-6.2 g/dL).Seven patients required either a blood transfusion or erythropoietin *** The sustained virologic response rate of 12-wk ribavirin therapy for HEV infection in this Asian series was lower than *** transplant recipients had a higher rate of treatment failure due to higher immunosuppression requirements and adverse effects.

关键词： Toxicity Antiviral agents Hepatitis E virus Virus classification Systemic immunity Immune responses Persistent infection

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Validation of genetic variants associated with metabolic dysfunctionassociated fatty liver disease in an ethnic Chinese population

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World Journal of Hepatology 2020年第12期12卷 1228-1238页

作者： guan huei lee Wah Wah Phyo Wai Mun Loo Raymond Kwok Taufique Ahmed Asim Shabbir Jimmy So Calvin Jianyi Koh Juanda Leo Hartono Mark Muthiah Kieron Lim Poh Seng Tan Yin Mei lee Seng GeeLim Yock Young Dan Division of Gastroenterology and Hepatology Department of MedicineNational University Health SystemSingapore 119228Singapore Yong Loo Lin School of Medicine National University of SingaporeSingapore 117597Singapore Department of Medicine Khoo Teck Puat HospitalSingapore 768828Singapore Department of Surgery National University Health SystemSingapore 119228Singapore

BACKGROUND Genetic factors play an important role in the pathogenesis and development of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To study the association of single nucleotide polymorphisms(SNPs),previously identified in Western populations,with the risk of MAFLD in a Singapore Chinese population and their interactions with environmental and medical risk *** A retrospective case-control study was conducted with 72 MAFLD cases and 72 controls with no hepatic steatosis on computed tomography,magnetic resonance imaging,or controlled attenuation parameter *** were recruited from two tertiary *** alleles such as NCAN,GCKR,LYPLAL1,PNPLA3,PPP1R3B,FDFT1,COL13A1,EFCAB4B,PZP,and TM6SF2 were genotyped using the TaqMan®Predesigned SNP Genotyping *** Weight and body mass index(BMI)were 1.2-times higher in patients(70.6 kg,95%confidence interval[CI]:57.1-84.1 vs 60.8 kg,95%CI:48.5-73.1,P<0.001 and 26.9 kg,95%CI:23-40.8 vs 23.3 kg 95%CI:19-27.6,P<0.001 respectively).The prevalence of diabetes mellitus in patients was 40.3%and 20.8%in controls(P=0.011).Patients had higher mean triglycerides than controls(P<0.001).PNPLA3 GG was more likely to be associated with MAFLD(43.4%CC vs 69.7%GG,P=0.017,and 44.8%CG vs 69.7%GG,P=0.022).In multivariable analysis,hypertriglyceridemia(odds ratio[OR]:2.0495%CI:1.3-3.1,P=0.001),BMI(OR:1.295%CI:1.1-1.4,P<0.001)and PNPLA3 GG(OR:3.495%CI:1.3-9.2,P=0.014)were associated with MAFLD(area under the receiver operating characteristic curve of 0.823).CONCLUSION Among the Chinese population of Singapore,PNPLA3 homozygous GG allele is a strong predictor of MAFLD,whereas LYPLAL1,GCKR,FDFT1,COL13A1,PZP,and TM6SF2 are not significantly ***,high BMI,and PNPLA3 GG are independent predictors of MAFLD.

关键词： Single nucleotide polymorphism PNPLA3 Genotyping Metabolic dysfunction-associated fatty liver disease Non-alcoholic steatohepatitis Hypertriglyceridemia Body mass index Waist-hip ratio,Screening Hepatic steatosis

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Search for a cure for chronic hepatitis B infection: How close are we?

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World Journal of Hepatology 2015年第9期7卷 1272-1281页

作者： Wah Wah Phyo Alex Yu Sen Soh Seng Gee Lim guan huei lee Department of Gastroenterology and Hepatology University Medicine Cluster National University Hospital of Singapore

Chronic hepatitis B(CHB) remains a significant unmet medical need, with 240 million chronically infected persons worldwide. It can be controlled effectively with either nucleoside/nucleotide-based or interferonbased therapies. However, most patients receiving these therapies will relapse after treatment withdrawal. During recent years, the advances in molecular biology and immunology have enabled a better understanding of the viral-host interaction and inspired new treatment approaches to achieve either elimination of the virus from the liver or durable immune control of the infection. This review aims to provide a brief overview on the potential new therapies that may overcome the challenge of persistent CHB infection in the near future.

关键词： Hepatitis B Antiviral therapy Covalentlyclosed circular DNA Drug target Immunomodulator

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Occupational physical activity, all-cause, cardiovascular disease, and cancer mortality in 349,248 adults: Prospective and longitudinal analyses of the MJ Cohort

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Journal of Sport and Health Science 2024年第4期13卷 579-589页

作者： Emmanuel Stamatakis Matthew N.Ahmadi Tiana-lee Elphick Bo-huei Huang Susan Paudel Armando Teixeira-Pinto Li-Jung Chen Borja del Pozo Cruz Yun-Ju Lai Andreas Holtermann Po-Wen Ku Sydney School of Health Sciences Faculty of Medicine and HealthCharles Perkins CentreUniversity of SydneySydneyNSW 2006Australia Sydney School of Public Health Faculty of Medicine and HealthUniversity of SydneySydneyNSW 2006Australia Department of Exercise Health Science “National”Taiwan University of SportTaichung 40404China Department of Sports Science and Clinical Biomechanics University of Southern DenmarkOdense 5230Denmark Division of Endocrinology and Metabolism Department of Internal MedicinePuli Branch of Taichung Veterans General HospitalNantou 54552China National Research Centre for the Working Environment Copenhagen 2100Denmark Graduate Institute of Sports and Health Management “National”Chung Hsing UniversityTaichung 40227China

Background:Evidence on the health benefits of occupational physical activity(OPA)is *** examined the associations of baseline OPA and OPA changes with all-cause,cardiovascular disease(CVD),and cancer mortality and survival ***:This study included prospective and longitudinal data from the MJ Cohort,comprising adults over 18 years recruited in 1998-2016,349,248 adults(177,314 women)with baseline OPA,of whom 105,715(52,503 women)had 2 OPA measures at 6.3±4.2 years(mean±SD)*** were baseline OPA,OPA changes,and baseline leisure-time physical ***:Over a mean mortality follow-up of 16.2±5.5 years for men and 16.4±5.4 years for women,11,696 deaths(2033 of CVD and 4631 of cancer causes)in men and 8980 deaths(1475 of CVD and 3689 of cancer causes)in women *** moderately heavy/heavy baseline OPA was beneficially associated with all-cause mortality in men(multivariable-adjusted hazard ratio(HR)=0.93,95%confidence interval(95%CI):0.89-0.98 compared to light OPA)and women(HR=0.86,95%CI:0.79-0.93).Over a mean mortality follow-up of 12.5±4.6 years for men and 12.6±4.6 years for women,OPA decreases in men were detrimentally associated(HR=1.16,95%CI:1.01-1.33)with all-cause mortality,while OPA increases in women were beneficially(HR=0.83,95%CI:0.70-0.97)associated with the same *** or changes in OPA showed no associations with CVD or cancer ***:Higher baseline OPA was beneficially associated with all-cause mortality risk in both men and *** longitudinal OPA analyses partly confirmed the prospective findings,with some discordance between sex groups.

关键词： Cancer Cardiovascular disease Epidemiology Mortality

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The need for pre-emptive control strategies for mpox in Asia and Oceania

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Infectious Disease Modelling 2024年第1期9卷 214-223页

作者： Gregory Gan AJanhavi guan Tong Jue Tao Lim Borame L.Dickens Saw Swee Hock School of Public Health National University of SingaporeSingapore lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore

Introduction:The transmission dynamics of the recent mpox outbreak highlights the lack of infrastructure available to rapidly respond to novel STI outbreaks,of which Asia and Oceania remains particularly ***,we simulate outbreaks in this setting and propose the use of pre-emptive vaccination within the men who have sex with men(MSM)community before the arrival and establishment of the *** and methods Using data driven heterogeneous sexual contact networks,we simulated outbreaks of mpox in Singapore,Hong Kong,and *** individual based SEIR compartmental model was used to simulate epidemic trajectories and the impact of different vaccination uptakes was assessed in their ability to avert or suppress outbreaks upon the arrival of mpox within the MSM ***:The highly dense sexual networks of Singapore and Sydney experience rapid outbreaks,with infection peaks occurring at day 41 and 23 respectively,compared to Hong Kong which occurs at day *** the simulations with no vaccination,68.2%–89.7%of the MSM community will become infected with mpox across the different cities,over a simulation period of 1 *** implementing vaccination strategies,the infection rate across the cities can be reduced to as low as 3.1%of the population(range:3.1%–82.2%)depending on the implementation and uptake of the *** is also extremely effective in slowing the start of the epidemic,delaying the epidemic peak by 36–50 days in Hong Kong,or even preventing the outbreak of ***:With extremely dense and well-connected sexual contact networks,where 65.2%–83.2%of the population are connected to a super-spreader in the different contact networks,pre-emptive or immediate vaccination upon identification of the first case is strongly recommended to help better manage the outbreak of mpox and prevent potential straining of healthcare systems.

关键词： Monkeypox virus Modelling Network model Mpox Contact matrix Sexual contact

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Fermi level tuning in Sn_(1-x)Pb_(x)Te/Pb heterostructure via changing interface roughness

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Science China(Physics,Mechanics & Astronomy) 2024年第8期67卷 118-125页

作者： Tengteng Liu Zhaoxia Yi Bangjin Xie Weiyan Zheng Dandan guan Shiyong Wang Hao Zheng Canhua Liu Hao Yang Yaoyi Li Jinfeng Jia Key Laboratory of Artificial Structures and Quantum Control(Ministry of Education) Tsung-Dao Lee InstituteSchool of Physics and AstronomyShanghai Jiao Tong UniversityShanghai 200240China Shanghai Research Center for Quantum Sciences Shanghai 201315China Hefei National Laboratory Hefei 230088China

Superconducting SnTe-type topological crystalline insulators(TCIs)are predicted to host multiple Majorana zero modes(MZMs)which can coexist in a single *** level(FL)close to the Dirac points of topological surface states is helpful for detecting ***,the TCI SnTe is a heavily p-type semiconductor which is very difficult to modify to n-type via doping or *** this work,we fabricate the atomically flat Sn_(1-x)Pb_(x)Te/Pb heterostructure by molecular beam epitaxy,and make the p-type Sn_(1-x)Pb_(x)Te become n-type through changing the interface *** scanning tunnelling microscope,we find the Dirac points of Sn_(1-x)Pb_(x)Te/Pb heterostructure are always above the FL due to the Fermi level pinning(FLP)induced by topological surface states at atomically flat *** increasing the interface roughness,the FLP effect is suppressed and then the Dirac points of p-type Sn_(1-x)Pb_(x)Te can be tuned very close to or even below the *** work provides a new method for tuning the FL of SnTe-type TCI which has potential application in novel topological superconductor device.

关键词： topological crystalline insulator superconductor heterostructure Fermi level pinning interface roughness

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