1.Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region
Do Young KIM ; Bao Nguyen TOAN ; Chee-Kiat TAN ; Irsan HASAN ; Lyana SETIAWAN ; Ming-Lung YU ; Namiki IZUMI ; Nguyen Nguyen HUYEN ; Pierce Kah-Hoe CHOW ; Rosmawati MOHAMED ; Stephen Lam CHAN ; Tawesak TANWANDEE ; Teng-Yu LEE ; Thi Thanh Nguyen HAI ; Tian YANG ; Woo-Chang LEE ; Henry Lik Yuen CHAN
Clinical and Molecular Hepatology 2023;29(2):277-292
Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP has its challenges, including accuracy dependent on its cut-off levels, degree of liver necroinflammation, and etiology of liver disease. Though various studies have demonstrated the utility of protein induced by vitamin K absence II (PIVKA-II) in surveillance, treatment monitoring, and predicting recurrence, it is still not recommended as a routine biomarker test. A panel of 17 experts from Asia-Pacific, gathered to discuss and reach a consensus on the clinical usefulness and value of PIVKA-II for the surveillance and treatment monitoring of HCC, based on six predetermined statements. The experts agreed that PIVKA-II was valuable in the detection of HCC in AFP-negative patients, and could potentially benefit detection of early HCC in combination with AFP. PIVKA-II is clinically useful for monitoring curative and intra-arterial locoregional treatments, outcomes, and recurrence, and could potentially predict microvascular invasion risk and facilitate patient selection for liver transplant. However, combining PIVKA-II with US and AFP for HCC surveillance, including small HCC, still requires more evidence, whilst its role in detecting AFP-negative HCC will potentially increase as more patients are treated for hepatitis-related HCC. PIVKA-II in combination with AFP and US has a clinical role in the Asia-Pacific region for surveillance. However, implementation of PIVKA-II in the region will have some challenges, such as requiring standardization of cut-off values, its cost-effectiveness and improving awareness among healthcare providers.
2.Clinical efficacy and long-term immunogenicity of an early triple dose regimen of SARS-CoV-2 mRNA vaccination in cancer patients.
Matilda Xinwei LEE ; Siyu PENG ; Ainsley Ryan Yan Bin LEE ; Shi Yin WONG ; Ryan Yong Kiat TAY ; Jiaqi LI ; Areeba TARIQ ; Claire Xin Yi GOH ; Ying Kiat TAN ; Benjamin Kye Jyn TAN ; Chong Boon TEO ; Esther CHAN ; Melissa OOI ; Wee Joo CHNG ; Cheng Ean CHEE ; Carol L F HO ; Robert John WALSH ; Maggie WONG ; Yan SU ; Lezhava ALEXANDER ; Sunil Kumar SETHI ; Shaun Shi Yan TAN ; Yiong Huak CHAN ; Kelvin Bryan TAN ; Soo Chin LEE ; Louis Yi Ann CHAI ; Raghav SUNDAR
Annals of the Academy of Medicine, Singapore 2023;52(1):8-16
INTRODUCTION:
Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity.
METHOD:
Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases.
RESULTS:
A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection.
CONCLUSION
This study demonstrates the benefit of early administration of the third dose among cancer patients.
Humans
;
SARS-CoV-2
;
COVID-19/prevention & control*
;
Treatment Outcome
;
Neoplasms/drug therapy*
;
Hematologic Neoplasms
;
Vaccination
;
RNA, Messenger
;
Antibodies, Viral
;
Immunogenicity, Vaccine
3.The role of PIVKA-II in hepatocellular carcinoma surveillance in an Asian population.
Wai Yoong NG ; Daniel Yan Zheng LIM ; Si Yu TAN ; Jason Pik Eu CHANG ; Thinesh Lee KRISHNAMOORTHY ; Chee Hooi LIM ; Damien Meng Yew TAN ; Victoria Sze Min EKSTROM ; George Boon Bee GOH ; Mark Chang Chuen CHEAH ; Rajneesh KUMAR ; Chin Pin YEO ; Chee Kiat TAN
Annals of the Academy of Medicine, Singapore 2023;52(2):108-110
4.Perception of disease, well-being and financial burden by patients with chronic hepatitis B: A self-reported assessment.
Ruojun DING ; Gayathry MORVIL ; Boon Bee George GOH ; Thinesh Lee KRISHNAMOORTHY ; Pei Yuh CHIA ; Hiang Keat TAN ; Victoria Sze Min EKSTROM ; Chang Chuen Mark CHEAH ; Jin Yang Terence TAN ; Pek Siang Edmund TEO ; Pik Eu Jason CHANG ; Chee Kiat TAN ; Xiaohui XIN ; Wan Cheng CHOW ; Rajneesh KUMAR
Annals of the Academy of Medicine, Singapore 2022;51(6):378-380
5.Chapter of Gastroenterologists professional guidance for management of patients with liver disease in Singapore during the COVID-19 pandemic.
Jason Pik Eu CHANG ; Yu Jun WONG ; Wei Lyn YANG ; Kieron Boon Leng LIM ; Poh Seng TAN ; Gim Hin HO ; Benjamin Cherng Hann YIP ; James Weiquan LI ; Chern Hao CHONG ; David Eng Hui ONG ; Tju Siang CHUA ; Charles Kien Fong VU ; Kok Ann GWEE ; Tiing Leong ANG ; Chee Kiat TAN
Singapore medical journal 2020;61(12):619-623
In this paper, we aim to provide professional guidance to clinicians who are managing patients with chronic liver disease during the current coronavirus disease 2019 (COVID-19) pandemic in Singapore. We reviewed and summarised the available relevant published data on liver disease in COVID-19 and the advisory statements that were issued by major professional bodies, such as the American Association for the Study of Liver Diseases and European Association for the Study of the Liver, contextualising the recommendations to our local situation.
COVID-19/epidemiology*
;
Carcinoma, Hepatocellular/therapy*
;
Chronic Disease
;
Hepatitis B, Chronic/therapy*
;
Hepatitis C, Chronic/therapy*
;
Humans
;
Liver Cirrhosis/therapy*
;
Liver Diseases/therapy*
;
Liver Neoplasms/therapy*
;
Liver Transplantation
;
Singapore/epidemiology*
6.Comparisons between non-alcoholic steatohepatitisand alcohol-related hepatocellular carcinoma
Rahul KUMAR ; Boon-Bee George GOH ; Jia-Wen KAM ; Pik-Eu CHANG ; Chee-Kiat TAN
Clinical and Molecular Hepatology 2020;26(2):196-208
Background/Aims:
Non-alcoholic liver disease and alcoholic liver disease begin as simple steatosis that may progress to steatohepatitis and ensuing liver-related complications such as cirrhosis and hepatocellular carcinoma (HCC). We explored differences in characteristics between non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitisrelated (ASH) HCC.
Methods:
NASH and ASH patients were identified from our department’s prospective HCC database. A total of 54 and 45 patients met predefined inclusion and exclusion criteria for the NASH-HCC and ASH-HCC groups, respectively. Clinical, biochemical and tumor characteristics were studied.
Results:
NASH-HCC patients were older compared to ASH-HCC patients (72±9 vs. 66±9 years, P<0.001) and less male predominant (65% vs. 98%, P<0.001). Prevalence of diabetes mellitus (78% vs. 36%, P<0.001) and hypertension (80% vs. 58%, P<0.001) were significantly higher in the NASH-HCC group. Liver function tests and Child-Pugh scores were similar. There were no differences in alpha-fetoprotein level, lesions found at diagnosis (unifocal/multifocal) or prevalence of portal vein invasion. In both groups, almost half of the patients were in TNM stage 4 at the time of diagnosis and more than 50% of patients were not suitable for any therapy. Median survival in the NASH-HCC and ASH-HCC groups were 13 and 7 months respectively (P=0.113).
Conclusions
Despite significant differences in demography of the NASH-HCC and ASH-HCC groups, liver and tumor characteristics were comparable. Most patients were diagnosed late and were not amenable to curative or locoregional therapies. Better characterization of patients with NASH and ASH at risk of HCC is necessary to optimize screening, surveillance, and management strategies.
7.Cytomegalovirus (CMV) hepatitis: an uncommon complication of CMV reactivation in drug reaction with eosinophilia and systemic symptoms.
Yu Jun WONG ; Karen Jui Lin CHOO ; Jade Xiao Jue SOH ; Chee Kiat TAN
Singapore medical journal 2018;59(1):112-113
Adult
;
Cytomegalovirus
;
Cytomegalovirus Infections
;
complications
;
Drug Hypersensitivity Syndrome
;
complications
;
virology
;
Eosinophilia
;
complications
;
virology
;
Fatal Outcome
;
Female
;
Gout
;
drug therapy
;
Hepatitis
;
complications
;
virology
;
Humans
;
Liver
;
physiopathology
;
Viremia
9.Epidemiology and Clinical Evolution of Liver Cirrhosis in Singapore.
Pik Eu CHANG ; Guan Wee WONG ; James Wq LI ; Hock Foong LUI ; Wan Cheng CHOW ; Chee Kiat TAN
Annals of the Academy of Medicine, Singapore 2015;44(6):218-225
INTRODUCTIONLiver cirrhosis is a common cause of morbidity and mortality and an important burden on the healthcare system. There is limited literature on liver cirrhosis in Singapore. We aimed to describe the epidemiology and clinical characteristics of cirrhotic patients seen in an ambulatory setting in a tertiary referral centre.
MATERIALS AND METHODSThis is a retrospective observational cohort study of cirrhotic patients attending the ambulatory clinic of Singapore's largest tertiary hospital over 5 years. Cirrhosis was diagnosed on characteristic radiological features and/or histology. Aetiology of cirrhosis was determined by history, serology, biochemistry and/or histology. Data on decompensation events and death were retrieved from computerised hospital records.
RESULTSThe study included 564 patients with median follow-up of 85 months. Mean age was 60.9 ± 12.5 years with 63.8% males. Main aetiologies of cirrhosis were chronic hepatitis B (CHB) (63.3%), alcohol (11.2%), cryptogenic (9%) and chronic hepatitis C (CHC) (6.9%). CHB was the predominant aetiology in Chinese and Malays whereas alcohol was the main aetiology in Indians. CHC cirrhosis was more common in Malays than other races. Majority had compensated cirrhosis with 76.8%/18.3%/5%; Child-Pugh A/B/C respectively. Decompensation events occurred in 155 patients (27.5%) and 106 of them (18.8%) died. Diagnosis of cirrhosis via surveillance ultrasound was associated with improved 10-year survival. Age at diagnosis, portal vein thrombosis, Child-Pugh class and decompensation within 1 year of diagnosis were independent predictors of mortality.
CONCLUSIONCHB is the primary cause of liver cirrhosis in Singapore. The major aetiologies of cirrhosis vary amongst the different ethnic groups. Cirrhotics with advanced age, portal vein thrombosis, poorer liver function and early decompensation have a higher mortality risk.
Adult ; Aged ; Ambulatory Care ; Female ; Follow-Up Studies ; Humans ; Liver Cirrhosis ; diagnosis ; epidemiology ; etiology ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Singapore ; epidemiology

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