23 results on '"Krishnamoorthy TL"'
Search Results
2. Inflammasome-Driven Fatal Acute-on-Chronic Liver Failure Triggered by Mild COVID-19.
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Chen VC, Joseph CR, Chan WOY, Sia WR, Su Q, Sam XX, Tamilarasan H, Mah YY, Ng WL, Yeong J, Wang LF, Krishnamoorthy TL, Leow WQ, Ahn M, and Chow WC
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- Humans, Fatal Outcome, Liver pathology, Liver virology, Hepatitis, Autoimmune pathology, Male, Middle Aged, Cytokines metabolism, Female, Macrophages immunology, COVID-19 complications, COVID-19 immunology, COVID-19 pathology, Acute-On-Chronic Liver Failure etiology, Acute-On-Chronic Liver Failure virology, Inflammasomes metabolism, SARS-CoV-2
- Abstract
Inflammasome is linked to many inflammatory diseases, including COVID-19 and autoimmune liver diseases. While severe COVID-19 was reported to exacerbate liver failure, we report a fatal acute-on-chronic liver failure (ACLF) in a stable primary biliary cholangitis-autoimmune hepatitis overlap syndrome patient triggered by a mild COVID-19 infection. Postmortem liver biopsy showed sparse SARS-CoV-2-infected macrophages with extensive ASC (apoptosis-associated speck-like protein containing a CARD) speck-positive hepatocytes, correlating with elevated circulating ASC specks and inflammatory cytokines, and depleted blood monocyte subsets, indicating widespread liver inflammasome activation. This first report of a fatal inflammatory cascade in an autoimmune liver disease triggered by a mild remote viral infection hopes to elucidate a less-described pathophysiology of ACLF that could prompt consideration of new diagnostic and therapeutic options.
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- 2024
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3. A rapid method to assess the in vivo multi-functionality of adoptively transferred engineered TCR T cells.
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Tan AT, Hang SK, Tan N, Krishnamoorthy TL, Chow WC, Wong RW, Wai LE, and Bertoletti A
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Introduction: The clinical efficacy of chimeric antigen and T cell receptor (TCR) T cell immunotherapies is attributed to their ability to proliferate and persist in vivo . Since the interaction of the engineered T cells with the targeted tumour or its environment might suppress their function, their functionality should be characterized not only before but also after adoptive transfer., Materials and Methods: We sought to achieve this by adapting a recently developed Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapid whole blood T cell assay to stimulate engineered TCR T cells in small volumes of whole blood (<1 ml) without in vitro cellular purification. As a proof-of-concept, we used this method to longitudinally study two patients with primary Hepatitis B Virus (HBV)-related hepatocellular carcinoma who received multiple dose-escalating infusions of transiently functional mRNA-engineered HBV-TCR T cells., Results: We demonstrated that a simple pulsing of whole blood with a peptide corresponding to the epitope recognized by the specific HBV-TCR elicited Th1 cytokine secretion in both patients only after HBV-TCR T cell treatment and not before. The amount of cytokines secreted also showed an infusion-dose-dependent association., Discussions: These findings support the utility of the whole blood cytokine release assay in monitoring the in vivo function and quantity of engineered T cell products following adoptive transfer., Competing Interests: The authors disclose the following: A.B. and A.T.T. are the Scientific Founder and the Scientific Consultant of Lion TCR Pte. Ltd. respectively, a biotech company developing T cell receptors for treatment of virus-related diseases and cancers. R.W.W and L-E.W. are employees of Lion TCR Pte. Ltd. All other authors disclose no conflicts. Lion TCR Pte. Ltd. has a patent application related to this work (WO2021148110A1)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology.)
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- 2024
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4. Outpatient screening with the Royal Free Hospital-Nutrition Prioritizing Tool for patients with cirrhosis at risk of malnutrition.
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Tan JYT, Cheah CCM, Wang YT, Chang PEJ, Krishnamoorthy TL, Tan HK, and Salazar E
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- Humans, Nutrition Assessment, Nutritional Status, Liver Cirrhosis complications, Hospitals, Outpatients, Malnutrition diagnosis, Malnutrition epidemiology, Malnutrition etiology
- Abstract
Objectives: Malnutrition is common among inpatients with cirrhosis. However, data on the prevalence of malnutrition among stable ambulatory patients with cirrhosis is lacking. We sought to investigate the prevalence of patents at risk of malnutrition (ARMN) among ambulatory patients with cirrhosis using the Royal Free Hospital-Nutrition Prioritizing Tool (RFH-NPT) and the Malnutrition Universal Screening Tool (MUST) and compare their correlation to clinical outcomes., Methods: Patients attending an outpatient liver cirrhosis clinic at a tertiary hospital were screened for ARMN using both the RFH-NPT and MUST (defined by a score of ≥2 for either tool). Differences in clinical outcomes after 6 mo were compared., Results: There were 134 patients recruited. The RFH-NPT identified more ARMN patients compared with MUST (32.8% versus 8.2%; P < 0.01; Cohen κ, 0.27 [95% CI, 0.12-0.42]; P < 0.001). Fluid overload at recruitment was the only independent predictor of disagreement between the RFH-NPT and MUST (odds ratio [OR], 43.14; 95% CI, 8.70-214.00; P < 0.001). There was a trend toward an increased risk of mortality for ARMN patients by the RFH-NPT (hazard ratio, 3.58; 95% CI, 0.81-15.83; P = 0.06) but not by the MUST (P = 0.62). The incidence of hospital admissions in ARMN patients was higher by the RFH-NPT, with an incidence rate ratio of 13.27 (95% CI, 5.11-43.70; P < 0.001), but not in ARMN patients by the MUST (P = 0.85). Being ARMN by the RFH-NPT was the only independent predictor of hospital admissions (OR, 15.08; 95% CI, 2.47-91.98; P = 0.003)., Conclusions: The RFH-NPT identified more ARMN patients when compared with the MUST, especially among patients with fluid overload. Patients at risk of malnutrition were at an increased risk of hospital admissions and possibly death., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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5. Virtual monitoring for stable chronic hepatitis B patients does not reduce adherence to medications: A randomised controlled study.
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Kumar R, Yee ML, Goh GB, Chia PY, Lee HL, Xin X, Teo PS, Ekstrom VS, Tan JY, Cheah MC, Wang YT, Chang JP, Tan CK, Tan HK, Krishnamoorthy TL, and Chow WC
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- Male, Humans, Middle Aged, Aged, Female, Antiviral Agents therapeutic use, Incidence, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular epidemiology, Carcinoma, Hepatocellular etiology, Liver Neoplasms drug therapy, Liver Neoplasms epidemiology, Liver Neoplasms etiology, Hepatitis B, Chronic drug therapy, Hepatitis B, Chronic complications, Hepatitis B, Chronic epidemiology
- Abstract
Introduction: Chronic hepatitis B (CHB) remains common in endemic regions, causing significant healthcare burden. Patients with CHB may need to be adherent to nucleoside analogue (NA) for a long period of time to prevent complications. This study aims to investigate the safety, efficacy and patient experience of a virtual monitoring clinic (VMC) in monitoring stable patients taking NA for CHB., Methods: Patients on NA and regular follow-up were randomised to either VMC alternating with doctors' clinic visit or to a control group in which they continued standard follow-up by doctors. Therapy adherence was measured by medication possession ratio (MPR) for NA therapy, incidence of virological breakthrough and hepatocellular carcinoma (HCC) development at two years of follow-up. Patient acceptance was measured on a Likert scale of 1-10., Results: A total 192 patients completed follow-up: 94 and 98 patients in the VMC and control groups, respectively. Mean age was 60.6 ± 10.8 years, with 95.3% Chinese ethnicity and 64.1% males. Age, gender, race, educational, employment and financial status were similar in both groups. Upon study completion, the majority of patients - 76 (80.9%) in VMC group and 74 (75.5%) in control group - had MPR ≥0.8; 88.8% were satisfied and rated VMC better than a traditional follow-up clinic with doctors only. More than 85% of patients rated ≥8/10 on the Likert scale for VMC, and preferred VMC over traditional clinic visits. Clinical outcomes observed were HCC development in one (1.1%) in the VMC group and four (4.1%) in the control group ( p = 0.369). Two (2.1%) and one (1.0%) virological breakthroughs were observed in the VMC and control groups, respectively ( p = 0.615). No incidence of HCC or abnormal blood tests were missed in the VMC arm., Discussion: VMC is a viable and safe clinical model for monitoring stable CHB patients on NA therapy without compromising patients' adherence to medications and is preferred by patients.
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- 2023
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6. The role of PIVKA-II in hepatocellular carcinoma surveillance in an Asian population.
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Ng WY, Lim DYZ, Tan SY, Chang JPE, Krishnamoorthy TL, Lim CH, Tan DMY, Ekstrom VSM, Goh GBB, Cheah MCC, Kumar R, Yeo CP, and Tan CK
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- Humans, Prothrombin, Biomarkers, Carcinoma, Hepatocellular epidemiology, Liver Neoplasms epidemiology
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- 2023
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7. Perception of disease, well-being and financial burden by patients with chronic hepatitis B: A self-reported assessment.
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Ding R, Morvil G, Goh BBG, Krishnamoorthy TL, Chia PY, Tan HK, Ekstrom VSM, Cheah CCM, Tan JYT, Teo PSE, Chang PEJ, Tan CK, Xin X, Chow WC, and Kumar R
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- Cost of Illness, Humans, Perception, Self Report, Financial Stress, Hepatitis B, Chronic
- Published
- 2022
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8. Cytomegalovirus-associated pseudomembranous colitis in a kidney transplant recipient.
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Chua YY, Ho QY, Ngo NT, Krishnamoorthy TL, Thangaraju S, Kee T, and Wong HM
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- Antiviral Agents therapeutic use, Cytomegalovirus, Female, Humans, Middle Aged, Clostridioides difficile, Colitis diagnosis, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections drug therapy, Enterocolitis, Pseudomembranous diagnosis, Enterocolitis, Pseudomembranous drug therapy, Kidney Transplantation adverse effects
- Abstract
Pseudomembranous colitis (PMC) is classically associated with Clostridium difficile infection. We report a rare case of cytomegalovirus (CMV)-associated PMC in a 52-year-old female patient who had undergone kidney transplantation more than 20 years ago and was on low dose prednisolone and ciclosporin. She presented with an acute history of fever, lethargy, vomiting and diarrhoea on admission. Computed tomography of the abdomen showed extensive colitis, and colonoscopy revealed extensive pseudomembrane formation. Multiple tests for Clostridium difficile and other common microbiological causes of colitis were negative. CMV DNAemia and colonic biopsies confirmed the diagnosis of CMV colitis. The patient responded to prompt CMV treatment, as demonstrated by clinical, endoscopic, and histological response. While CMV is a common pathogen in the solid organ transplant population that is familiar to most transplant physicians, it may present atypically as PMC. Here, we review the literature on CMV-associated PMC and its relevance to solid organ transplant recipients. To our knowledge, this is the first reported case of CMV-associated PMC in a kidney transplant recipient., (© 2021 Wiley Periodicals LLC.)
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- 2021
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9. Immunosuppressive Drug-Resistant Armored T-Cell Receptor T Cells for Immune Therapy of HCC in Liver Transplant Patients.
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Hafezi M, Lin M, Chia A, Chua A, Ho ZZ, Fam R, Tan D, Aw J, Pavesi A, Krishnamoorthy TL, Chow WC, Chen W, Zhang Q, Wai LE, Koh S, Tan AT, and Bertoletti A
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- Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular virology, Coculture Techniques, Drug Resistance genetics, Graft Rejection immunology, Graft Rejection pathology, Hep G2 Cells, Hepatitis B pathology, Hepatitis B surgery, Hepatitis B virology, Hepatitis B virus immunology, Hepatitis B virus metabolism, Humans, Immunotherapy, Adoptive methods, Liver drug effects, Liver immunology, Liver pathology, Liver virology, Liver Neoplasms pathology, Liver Neoplasms virology, Liver Transplantation adverse effects, Mycophenolic Acid pharmacology, Mycophenolic Acid therapeutic use, Neoplasm Recurrence, Local immunology, Neoplasm Recurrence, Local pathology, Protein Engineering, Receptors, Antigen, T-Cell genetics, Receptors, Antigen, T-Cell metabolism, Tacrolimus pharmacology, Tacrolimus therapeutic use, Carcinoma, Hepatocellular surgery, Graft Rejection prevention & control, Liver Neoplasms surgery, Neoplasm Recurrence, Local therapy, T-Lymphocytes transplantation
- Abstract
Background and Aims: HBV-specific T-cell receptor (HBV-TCR) engineered T cells have the potential for treating HCC relapses after liver transplantation, but their efficacy can be hampered by the concomitant immunosuppressive treatment required to prevent graft rejection. Our aim is to molecularly engineer TCR-T cells that could retain their polyfunctionality in such patients while minimizing the associated risk of organ rejection., Approach and Results: We first analyzed how immunosuppressive drugs can interfere with the in vivo function of TCR-T cells in liver transplanted patients with HBV-HCC recurrence receiving HBV-TCR T cells and in vitro in the presence of clinically relevant concentrations of immunosuppressive tacrolimus (TAC) and mycophenolate mofetil (MMF). Immunosuppressive Drug Resistant Armored TCR-T cells of desired specificity (HBV or Epstein-Barr virus) were then engineered by concomitantly electroporating mRNA encoding specific TCRs and mutated variants of calcineurin B (CnB) and inosine-5'-monophosphate dehydrogenase (IMPDH), and their function was assessed through intracellular cytokine staining and cytotoxicity assays in the presence of TAC and MMF. Liver transplanted HBV-HCC patients receiving different immunosuppressant drugs exhibited varying levels of activated (CD39
+ Ki67+ ) peripheral blood mononuclear cells after HBV-TCR T-cell infusions that positively correlate with clinical efficacy. In vitro experiments with TAC and MMF showed a potent inhibition of TCR-T cell polyfunctionality. This inhibition can be effectively negated by the transient overexpression of mutated variants of CnB and IMPDH. Importantly, the resistance only lasted for 3-5 days, after which sensitivity was restored., Conclusions: We engineered TCR-T cells of desired specificities that transiently escape the immunosuppressive effects of TAC and MMF. This finding has important clinical applications for the treatment of HBV-HCC relapses and other pathologies occurring in organ transplanted patients., (© 2020 by the American Association for the Study of Liver Diseases.)- Published
- 2021
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10. Description of parallel and sequential configurations for concurrent therapeutic plasma exchange and continuous kidney replacement therapy in adults.
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Kaushik M, Liew ZH, Sewa DW, Phua GC, Cao L, Krishnamoorthy TL, Ng SY, Lim AEL, Ng LC, Koniman R, Teo SH, and Tan HK
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- Adult, Female, Humans, Centrifugation methods, Plasma Exchange methods, Renal Replacement Therapy
- Abstract
Therapeutic plasma exchange (TPE) and continuous kidney replacement therapy (CKRT) are extracorporeal therapeutic procedures often implemented in management of patients. Critically ill patients may be afflicted with disease processes that require both TPE and CKRT. Performing TPE discontinuous with CKRT is technically easier, however, it disrupts CKRT and may compromise with CKRT efficiency or hemofilter life. Concurrent TPE with CKRT offers several advantages including simultaneous control of disease process and correction of electrolyte, fluid, and acid-base disturbances that may accompany TPE. Additionally, TPE may be performed by either centrifugation method or membrane plasma separation method. The technical specifications of these methods may influence the methodology of concurrent connections. This report describes and reviews two different approaches to circuit arrangements when establishing concurrent TPE and CKRT., (© 2020 Wiley Periodicals LLC.)
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- 2021
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11. Waitlisted Transplant Candidates' Attitudes and Concerns Toward Transplantation During COVID-19.
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Tan EK, Koh YX, Kee T, Juhari JB, Tan TE, Sim DKL, Ho AYL, Krishnan L, Tee PS, Krishnamoorthy TL, Goh BKP, Tan BH, Chung SJ, Phua GC, and Jeyaraj PR
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- Adult, Aged, Aged, 80 and over, COVID-19 epidemiology, COVID-19 etiology, COVID-19 prevention & control, Female, Global Health, Health Care Surveys, Health Literacy, Humans, Male, Middle Aged, Pandemics, Patient Preference statistics & numerical data, Postoperative Complications prevention & control, Postoperative Complications psychology, Singapore epidemiology, COVID-19 psychology, Health Knowledge, Attitudes, Practice, Hematopoietic Stem Cell Transplantation psychology, Organ Transplantation psychology, Patient Preference psychology, Waiting Lists
- Abstract
BACKGROUND In solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, coronavirus disease 2019 (COVID-19) can contribute to a severe clinical course and an increased risk of death. Thus, patients awaiting a SOT or HSCT face the dilemma of choosing between a life-saving treatment that presents a significant threat of COVID-19 and the risk of waitlist dropout, progression of disease, or mortality. The lack of established literature on COVID-19 complicates the issue as patients, particularly those with inadequate health literacy, may not have the resources needed to navigate these decisions. MATERIAL AND METHODS We conducted a standardized phone survey of patients awaiting SOT or HSCT to assess the prevalence of inadequate health literacy and attitudes toward transplant during the COVID-19 pandemic. RESULTS Seventy-one patients completed the survey, with a response rate of 84.5%. Regardless of health literacy, most waitlisted candidates recognized that the current pandemic is a serious situation affecting their care and that COVID-19 poses a significant risk to their health. Despite the increased risks, most patients reported they would choose immediate transplantation if there was no foreseeable end to the pandemic, and especially if the medical urgency did not permit further delay. There were no differences in responses across the patient waitlist groups for heart, kidney, liver, and stem cell transplant. CONCLUSIONS These findings can help transplant centers decide how transplantation services should proceed during this pandemic and can be used to educate patients and guide discussions about informed consent for transplant during the COVID-19 pandemic.
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- 2020
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12. Practical Considerations for Solid Organ Transplantation During the COVID-19 Global Outbreak: The Experience from Singapore.
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Chung SJ, Tan EK, Kee T, Krishnamoorthy TL, Phua GC, Sewa DW, Ong BH, Tan TE, Sivathasan C, Gan HLV, Goh BKP, Jeyaraj PR, and Tan BH
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The current coronavirus disease 2019 (COVID-19) pandemic has not only caused global social disruptions but has also put tremendous strain on healthcare systems worldwide. With all attention and significant effort diverted to containing and managing the COVID-19 outbreak (and understandably so), essential medical services such as transplant services are likely to be affected. Closure of transplant programs in an outbreak caused by a highly transmissible novel pathogen may be inevitable owing to patient safety. Yet program closure is not without harm; patients on the transplant waitlist may die before the program reopens. By adopting a tiered approach based on outbreak disease alert levels, and having hospital guidelines based on the best available evidence, life-saving transplants can still be safely performed. We performed a lung transplant and a liver transplant successfully during the COVID-19 era. We present our guidelines and experience on managing the transplant service as well as the selection and management of donors and recipients. We also discuss clinical dilemmas in the management COVID-19 in the posttransplant recipient., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2020 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)
- Published
- 2020
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13. Repeat liver resection versus salvage liver transplant for recurrent hepatocellular carcinoma: A propensity score-adjusted and -matched comparison analysis.
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Guo Y, Tan EK, Syn NL, Krishnamoorthy TL, Tan CK, Lim R, Lee SY, Chan CY, Cheow PC, Chung AYF, Jeyaraj PR, and Goh BKP
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Backgrounds/aims: Repeat liver resection (RLR) and salvage liver transplantation (SLT) are viable treatment options for recurrent hepatocellular carcinoma (HCC). With possibly superior survival outcomes than RLR, SLT is however, limited by liver graft availability and poses increased perioperative morbidity. In this study, we seek to compare the outcomes of RLR and SLT for patients with recurrent HCC., Methods: Between 1999 and 2018, 94 and 16 consecutive patients who underwent RLR and SLT respectively were identified. Further retrospective subgroup analysis was conducted, comparing 16 RLR with 16 SLT patients via propensity-score matching., Results: After propensity-score adjusted analyses, SLT demonstrated inferior short-term perioperative outcomes than RLR, with increased major morbidity (57.8% vs 5.4 %, p =0.0001), reoperations (39.1% vs 0, p <0.0001), renal insufficiency (30.1% vs 3%, p =0.0071), bleeding (19.8% vs 2.2%, p =0.0289), prolonged intensive care unit stay (median=4 vs 0 days, p <0.0001) and hospital stay (median=19.8 vs 7.1days, p <0.001). However, SLT showed significantly lower recurrence rate (15.4% versus 70.3%, p =0.0005) and 5-year cumulative incidence of recurrences (19.4% versus 68.4%, p =0.005). Propensity-matched subgroup analysis showed concordant findings., Conclusions: While SLT offers potentially reduced risks of recurrence and trended towards improved long-term survival outcomes relative to RLR, it has poorer short-term perioperative outcomes. Patient selection is prudent amidst organ shortages to maximise allocated resources and optimise patient outcomes., (Copyright © 2019 by The Korean Association of Hepato-Biliary-Pancreatic Surgery.)
- Published
- 2019
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14. Circulating microRNAs as Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma.
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Jin Y, Wong YS, Goh BKP, Chan CY, Cheow PC, Chow PKH, Lim TKH, Goh GBB, Krishnamoorthy TL, Kumar R, Ng TP, Chong SS, Tan HH, Chung AYF, Ooi LLPJ, Chang JPE, Tan CK, and Lee CGL
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- Biomarkers, Tumor blood, Carcinoma, Hepatocellular blood, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular virology, Case-Control Studies, Disease Progression, Female, Follow-Up Studies, Gene Expression Profiling, Hepatitis B virus isolation & purification, Hepatitis B, Chronic virology, Humans, Liver Cirrhosis blood, Liver Cirrhosis genetics, Liver Cirrhosis virology, Liver Neoplasms blood, Liver Neoplasms genetics, Liver Neoplasms pathology, Liver Neoplasms virology, Male, MicroRNAs blood, Middle Aged, Prognosis, Survival Rate, Biomarkers, Tumor genetics, Carcinoma, Hepatocellular pathology, Early Detection of Cancer methods, Gene Expression Regulation, Neoplastic, Hepatitis B, Chronic complications, Liver Cirrhosis pathology, MicroRNAs genetics
- Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer with high mortality, due to late diagnosis and limited treatment options. Blood miRNAs, which circulate in a highly stable, cell-free form, show promise as novel potential biomarkers for early detection of HCC. Whole miRNome profiling was performed to identify deregulated miRNAs between HCC and normal healthy (NH) volunteers. These deregulated miRNAs were validated in an independent cohort of HCC, NH and chronic Hepatitis B (CHB) volunteers and finally in a 3
rd cohort comprising NH, CHB, cirrhotic and HCC volunteers to evaluate miRNA changes during disease progression. The associations between circulating miRNAs and liver-damage markers, clinicopathological characteristics and survival outcomes were analysed to identify prognostic markers. Twelve miRNAs are differentially expressed between HCC and NH individuals in all three cohorts. Five upregulated miRNAs (miR-122-5p, miR-125b-5p, miR-885-5p, miR-100-5p and miR-148a-3p) in CHB, cirrhosis and HCC patients are potential biomarkers for CHB infection, while miR-34a-5p can be a biomarker for cirrhosis. Notably, four miRNAs (miR-1972, miR-193a-5p, miR-214-3p and miR-365a-3p) can distinguish HCC from other non-HCC individuals. Six miRNAs are potential prognostic markers for overall survival.- Published
- 2019
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15. Outcomes of salvage liver transplant for recurrent hepatocellular carcinoma: A comparison with primary liver transplant.
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Guo Y, Tan EK, Krishnamoorthy TL, Tan CK, Tan BH, Tan TT, Lee SY, Chan CY, Cheow PC, Chung AYF, Jeyaraj PR, and Goh BKP
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Backgrounds/aims: Salvage liver transplantation (SLT) is a therapeutic strategy for recurrent hepatocellular carcinoma (HCC). However, it remains controversial with compromised survival outcomes and increased perioperative morbidity compared to primary liver transplant (PLT). In the present work, we describe our institution's experience on SLT by comparing outcomes of SLT to PLT for HCCs., Methods: Retrospective analysis was conducted for 49 transplant patients from 2006-2017. A comparative analysis was carried out between 14 SLT patients and 35 PLT patients., Results: SLT patients demonstrated significantly shorter time to recurrence than PLT patients (median=5.5 versus 23 months, p <0.001) with a trend towards increased perioperative major morbidity (42.9% versus 37%, p =0.711), inferior 5-year overall survival (61% versus 75%, p =0.345) and inferior 5-year recurrence-free survival (57% versus 72%, p =0.263). However, overall survival from the point of primary resection over a 10-year period showed no statistical difference between the 2 groups (SLT=60% versus PLT=61%, p =0.685)., Conclusions: SLT is a viable treatment strategy for HCCs. However, it exhibited poorer short-term perioperative and oncologic outcomes than PLT. SLT requires better patient selection with liver donor grafts for optimization of resource allocation in this era of organ shortage. Considering the worldwide shortages in liver grafts, it is hypothesized that optimization of a salvage transplant strategy may improve resource allocation and reap optimal patient outcomes.
- Published
- 2019
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16. Liver Transplant Waitlist Outcomes and the Allocation of Hepatocellular Carcinoma Model for End-Stage Liver Disease Exception Points at a Low-Volume Center.
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Tan EK, Goh BKP, Lee SY, Krishnamoorthy TL, Tan CK, and Jeyaraj PR
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- Disease Progression, Female, Humans, Male, Middle Aged, Registries, Severity of Illness Index, Tissue and Organ Procurement, Carcinoma, Hepatocellular, Liver Neoplasms, Liver Transplantation, Tissue Donors supply & distribution, Waiting Lists mortality
- Abstract
Background: Organ scarcity continues to be the main problem limiting the number of liver transplants performed. Outcomes of patients waitlisted for an organ in an Asian country with low organ donation rate have not been well evaluated. Our current policy of allocating 15 exception points to patients with hepatocellular carcinoma (HCC) to render them competitive for a transplant also requires review., Methods: The waiting list registry and the organ transplant registry of a single institution in Asia were reviewed from December 2005 to June 2016 for all patients who underwent liver transplantation. Patient characteristics and outcomes of waitlist dropouts were evaluated. Statistical analyses were performed using SPSS version 20.0., Results: One hundred seventy-three patients were waitlisted for a deceased donor liver-only transplant. The most common etiology of liver disease was hepatitis B, followed by cholestatic diseases. Approximately half of the patients had HCC (45.6%). Priority listing for transplant comprised 15.6% of cases. Median Model for End-Stage Liver Disease (MELD) at listing was 15, and median waiting time to transplant was 17 weeks (interquartile range = 6.5-43.5). Overall, 89 (51.4%) patients underwent liver transplantation and 68 (39.3%) dropped out. For patients with HCC, the most common cause of dropout was progression beyond University of California San Francisco transplant criteria (62.5%). The cumulative incidence of dropout at 3 months among patients with HCC who received exception MELD scores was 11%. This was higher than those listed with physiologic MELD of 14-16 points (7%) but lower than those with 17-19 points (16%)., Conclusions: Hepatitis B-related liver disease and HCC comprise the majority of patients listed for liver transplant. Dropout rates are high and this is due to the lack of donor organs. The current policy of allocating 15 exception MELD points to patients with HCC within transplant criteria may underestimate the dropout risk of patients with HCC in our population., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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17. Large intramural hematoma and gastric ulcer after EMR of a small gastric polyp.
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Teh J, Krishnamoorthy TL, Hooi LC, and Asokkumar R
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- Coronary Artery Disease complications, Humans, Hyperplasia, Liver Cirrhosis complications, Male, Middle Aged, Polyps complications, Renal Insufficiency, Chronic complications, Stomach Diseases complications, Endoscopic Mucosal Resection, Gastrointestinal Hemorrhage diagnosis, Hematoma diagnosis, Polyps surgery, Postoperative Complications diagnosis, Postoperative Hemorrhage diagnostic imaging, Stomach Diseases surgery, Stomach Ulcer diagnosis
- Published
- 2018
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18. Perceptions of non-alcoholic fatty liver disease - an Asian community-based study.
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Goh GB, Kwan C, Lim SY, Venkatanarasimha NK, Abu-Bakar R, Krishnamoorthy TL, Shim HH, Tay KH, and Chow WC
- Abstract
Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is closely related to metabolic syndrome and its risk factors. Worldwide, epidemiological studies have reported NAFLD prevalence rates of 5% to 30% depending on geographical variations. While epidemiological data suggest a progressively increasing prevalence of metabolic risk factors in Singapore, there are limited data about NAFLD per se in the community. We aim to explore the prevalence and perceptions of NAFLD in Singapore., Methods: Attendees at a gastroenterology public forum were enrolled in a cross-sectional observational study evaluating demographic, anthropometric and clinical information. The diagnosis of NAFLD was based on sonographic criteria. Metabolic syndrome was defined according to International Diabetes Federation guidelines. Perceptions of NAFLD were explored using a self-administered survey questionnaire., Results: A total of 227 subjects were recruited, with NAFLD being diagnosed in 40% of the cohort. Relative to those without NAFLD, subjects with NAFLD had higher male preponderance, older age, higher body mass index, waist circumference and more metabolic syndrome (all P < 0.05). Although 71.2% subjects had heard about NAFLD before, only 25.4% of them felt that they were at risk of NAFLD. Comparable responses were observed in subjects with no metabolic risk factors relative to subjects with one or more metabolic risk factors (P > 0.05). Of note, 75.6% of subjects with one or more metabolic risk factors did not think that they were at risk of NAFLD., Conclusion: Our study suggests a significant local prevalence of NAFLD in the community including non-obese individuals. Considering the tendency to underestimate risk of NAFLD, enhanced public education about NAFLD is warranted to improve understanding., (© The Author(s) 2015. Published by Oxford University Press and the Digestive Science Publishing Co. Limited.)
- Published
- 2016
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19. Longterm corticosteroid use after liver transplantation for autoimmune hepatitis is safe and associated with a lower incidence of recurrent disease.
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Krishnamoorthy TL, Miezynska-Kurtycz J, Hodson J, Gunson BK, Neuberger J, Milkiewicz P, and Oo YH
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- Adult, Female, Glucocorticoids adverse effects, Graft Rejection epidemiology, Hepatitis, Autoimmune epidemiology, Hepatitis, Autoimmune surgery, Humans, Immunosuppressive Agents administration & dosage, Incidence, Male, Middle Aged, Osteoporosis chemically induced, Osteoporosis epidemiology, Prednisolone adverse effects, Recurrence, Retrospective Studies, Sepsis chemically induced, Sepsis epidemiology, United Kingdom epidemiology, Glucocorticoids administration & dosage, Hepatitis, Autoimmune prevention & control, Liver Transplantation mortality, Postoperative Complications prevention & control, Prednisolone administration & dosage
- Abstract
Patients transplanted for autoimmune hepatitis (AIH) are at risk of recurrent disease. Our current practice is to maintain long-term low-dose corticosteroids with additional immunosuppressive agents. This study describes the implications on patients' outcomes, sepsis, and osteoporosis. We collected data on patients transplanted between January 1999 and October 2014 in a single center who survived for more than 6 months. AIH recurrence was diagnosed by a combination of histology, raised immunoglobulin G levels, and exclusion of other etiologies. Sepsis was defined as any infection that resulted in significant morbidity or mortality. Osteoporosis was defined as a bone densitometry T score of less than -2.0 or evidence of osteoporosis-related fractures. Outcomes were assessed using Kaplan-Meier survival analysis methods. Seventy-three AIH patients underwent liver transplantation with a median follow-up of 94 months (interquartile range, 55-144). The cohort was mainly Caucasian (78%), female (79%), with type 1 AIH (90%), and a mean age of 43 ± 15 years. Overall survival was 92%, 90%, 86%, and 73%, and regraft-free survival was 86%, 81%, 78%, and 64% at 1, 3, 5, and 10 years, respectively. Five patients developed AIH recurrence, giving recurrence rates of 0%, 4%, 6%, and 11% at 1, 3, 5, and 10 years, respectively. Pneumonia was the most common infection, but gastroenteritis and cholangitis were the most recurrent. Freedom from sepsis was 91%, 82%, 80%, and 63%, and freedom from osteoporosis was 100%, 94%, 82%, and 58% at 1, 3, 5, and 10 years, respectively. Longterm low-dose corticosteroid in combination with other immunosuppressive agents seems to reduce AIH recurrence without jeopardizing patient and graft survival. Sepsis and osteoporosis did not occur more often compared to the published literature on liver transplant recipients., (© 2015 American Association for the Study of Liver Diseases.)
- Published
- 2016
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20. Hepatitis B: encouraging the use of interferon.
- Author
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Krishnamoorthy TL and Mutimer D
- Subjects
- Adjuvants, Immunologic therapeutic use, Contraindications, Drug Administration Schedule, Drug Therapy, Combination, Guanine analogs & derivatives, Guanine therapeutic use, Hepatitis B e Antigens blood, Hepatitis B, Chronic blood, Hepatitis B, Chronic physiopathology, Humans, Interferon-alpha therapeutic use, Telbivudine, Thymidine analogs & derivatives, Antiviral Agents therapeutic use, Carcinoma, Hepatocellular prevention & control, Hepatitis B e Antigens drug effects, Hepatitis B virus drug effects, Hepatitis B, Chronic drug therapy, Liver Cirrhosis prevention & control, Liver Neoplasms prevention & control
- Abstract
Purpose of Review: Hepatitis B is a major cause of hepatocellular carcinoma and liver cirrhosis. Interferon (IFN)-based therapies provide the highest likelihood of achieving off-treatment virological and serological control although their use is often avoided because of the side-effect profile. We review recent developments regarding the use of IFN in the treatment of chronic hepatitis B, including proposed strategies to enhance efficacy while limiting treatment exposure for patients who are unlikely to achieve acceptable treatment endpoints., Recent Findings: The utility of host genetics (human leukocyte antigen associations and interleukin 28B) is yet to be defined. In hepatitis B e antigen (HBeAg)-positive disease, add-on IFN therapy to patients on entecavir may allow curtailment of nucleos(t)ide analogue treatment. In HBeAg-negative disease, an on-treatment stopping rule that measures decline of hepatitis B surface antigen and hepatitis B virus DNA at 12 and 24 weeks may identify up to two-thirds of poor responders. Prolonging IFN therapy to 96 weeks in patients with HBeAg-negative disease may improve virological and serological response rates. The combination of telbivudine and IFN therapy is contraindicated because of high rates of peripheral neuropathy., Summary: These findings need to be confirmed in larger trials before they can be instituted into routine clinical practice.
- Published
- 2015
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21. Change in model for end-stage liver disease score at two weeks, as an indicator of mortality or liver transplantation at 60 days in acute-on-chronic liver failure.
- Author
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Kumar R, Krishnamoorthy TL, Tan HK, Lui HF, and Chow WC
- Abstract
Background: Acute-on-chronic liver failure (ACLF) is characterised by a sudden deterioration of underlying chronic liver disease, resulting in increased rates of mortality and liver transplantation. Early prognostication can benefit optimal allocation of resources., Methods: ACLF was defined as per the disease criteria of the Asian Pacific Association for the Study of the Liver. Inpatient discharge summaries from between January 2001 and April 2013 were reviewed. The primary outcome was mortality or liver transplantation within 60 days from onset of ACLF. Absolute 'model for end-stage liver disease' (MELD) score and change in MELD at Weeks 1, 2 and 4 were reviewed in order to identify the earliest point for prediction of mortality or liver transplantation., Results: Clinical data were collected on 53 subjects who fulfilled the inclusion and exclusion criteria. At 60 days from presentation, 20 patients (37.7%) died and 4 (7.5%) underwent liver transplantation. Increased MELD of ≥2 after 2 weeks was 75.0% sensitive and 75.9% specific for predicting mortality or liver transplantation. If the MELD score did not increase at 2 weeks, predictive chance of survival was 93.8% over the next 60 days. MELD change at 1 week showed poor sensitivity and specificity. Change at 4 weeks was too late for intervention., Conclusion: Change in MELD score at 2 weeks provides an early opportunity for prognostication in ACLF. A MELD score that does not deteriorate by Week 2 would predict 93.8% chance of survival for the next 60 days. This finding warrants further validation in larger cohort studies., (© The Author(s) 2014. Published by Oxford University Press and the Digestive Science Publishing Co. Limited.)
- Published
- 2015
- Full Text
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22. Symptomatic hepatic hydrothorax successfully treated with transjugular intrahepatic portosystemic shunt (TIPS)-role of titration of portosystemic gradient reduction to avoid post-TIPS encephalopathy.
- Author
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Krishnamoorthy TL, Taneja M, and Chang PE
- Abstract
Key Clinical Message: We describe a challenging case of hepatic hydrothorax secondary to nonalcoholic steatohepatitis cirrhosis. Our management involved successfully treating the hydrothorax with a transjugular intrahepatic porto-systemic shunt but having to manage the subsequent complication of hepatic encephalopathy. We conclude with a review of the available literature.
- Published
- 2014
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23. The impact of irritable bowel syndrome on health-related quality of life: a Singapore perspective.
- Author
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Wang YT, Lim HY, Tai D, Krishnamoorthy TL, Tan T, Barbier S, and Thumboo J
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Multivariate Analysis, Outcome Assessment, Health Care, Risk Factors, Singapore epidemiology, Surveys and Questionnaires, Irritable Bowel Syndrome epidemiology, Irritable Bowel Syndrome psychology, Quality of Life psychology
- Abstract
Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. The prevalence of IBS in Asian countries varies from 2.9% to 15.6%. IBS does not result in increased mortality, but is associated with psychological distress and disruption of work and sleep. Consequently, the evaluation of health-related quality of life (HRQoL) is an important outcome measure for patients with IBS since it provides a holistic assessment of the patient's emotional, social and physical function. However, some HRQoL tools can be time-consuming to apply. EQ-5D is a brief HRQoL tool which has been validated in the Western IBS population but has thus far not been used in Asia. This study was conducted to determine whether persons with self-reported symptoms that met the Rome III criteria for IBS had a poorer quality of life than those without these symptoms. We also aimed to determine which specific aspects of quality of life were most affected and whether any risk factors distinguished those with and without IBS., Methods: Self-administered questionnaires which included the Rome III diagnostic questionnaire modules for IBS and the EQ-5D questionnaire were obtained from participants of a health symposium in Singapore on 31th October 2010. IBS was diagnosed based on the Rome III Criteria. The main outcome measure was the EQ-5D index score. The relationship between the presence of IBS and the EQ-5D index score, individual dimensions of EQ-5D and demographic risk factors were examined., Results: 449 completed questionnaires were analyzed. The mean EQ-5D index score for IBS was 0.739 which was a significant reduction compared to non-IBS participants [-0.11 (95% CI: -0.15 to -0.07), p<0.001]. Multivariate analysis showed that IBS was significantly associated with younger age and higher education level. Of the five EQ-5D dimensions, IBS sufferers were significantly affected in mobility, anxiety or depression, usual activity and pain. There was a "dose related" increase in likelihood of having IBS with increased severity of pain and anxiety or depression., Conclusion: IBS sufferers have significantly poorer quality of life. Assessment of HRQoL in IBS using the EQ-5D should be considered in further studies and routine clinical practice.
- Published
- 2012
- Full Text
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