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Donor-specific cell-free DNA as a biomarker in liver transplantation:A review

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World Journal of Transplantation 2020年第11期10卷 307-319页

作者： Tess McClure Su Kah goh Daniel Cox Vijayaragavan Muralidharan Alexander Dobrovic adam g testro Liver Transplant Unit Austin HealthHeidelberg 3084VICAustralia Department of Surgery Austin HealthHeidelberg 3084VICAustralia Department of Surgery The University of MelbourneHeidelberg 3084VICAustralia

Due to advances in modern medicine,liver transplantation has revolutionised the prognosis of many previously incurable liver *** progress has largely been due to advances in immunosuppressant ***,despite the judicious use of immunosuppression,many liver transplant recipients still experience complications such as rejection,which necessitates diagnosis via invasive liver *** is a clear need for novel,minimally-invasive tests to optimise immunosuppression and improve patient *** emerging biomarker in this‘‘precision medicine’‘liver transplantation field is that of donorspecific cell free *** this review,we detail the background and methods of detecting this biomarker,examine its utility in liver transplantation and discuss future research directions that may be most impactful.

关键词： Biomarkers Precision medicine Donor-specific cell-free DNA Liver transplantation Rejection Review

Reduced upper limb lean mass on dual energy X-ray absorptiometry predicts adverse outcomes in male liver transplant recipients

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World Journal of Transplantation 2022年第6期12卷 120-130页

作者： Penelope Hey Rudolf Hoermann Paul gow Timothy P Hanrahan adam g testro Ross Apostolov Marie Sinclair Liver Transplant Unit Austin HealthHeidelberg 3084Australia Department of Medicine University of MelbourneMelbourne 3052Australia

BACKgROUND Pre-transplant muscle wasting measured by computed tomography has been associated with adverse clinical outcomes after liver transplantation including increased rates of sepsis and hospitalisation *** limb lean mass(LM)measured by dual-energy X-ray absorptiometry(DEXA)was recently identified as a novel predictor of sarcopenia-associated mortality in men waitlisted for *** To investigate the use of DEXA LM in predicting gender-stratified early posttransplant *** Liver transplant recipients who underwent pre-transplant DEXA body composition imaging between 2002 and 2017 were *** included posttransplant mortality and graft failure,bacterial infections,acute cellular rejection(ACR)and intensive care and total hospital length of *** Four hundred and sixty-nine patients met inclusion criteria of which 338 were male(72%).Median age was 55.0 years(interquartile range 47.4,59.7)and model for end-stage liver disease(MELD)score *** time from assessment to transplantation was 7 mo(3.5,12).Upper limb LM was inversely associated with bacterial infections at 180 d post-transplant(hazard ratio=0.42;95%confidence interval:0.20-0.89;P=0.024)in males *** was a negative correlation between upper limb LM and intensive care(τb=-0.090,P=0.015)and total hospital length of stay(τb=-0.10,P=0.0078)in *** women,neither MELD nor body composition parameters were associated with post-transplant adverse outcomes or increased length of *** composition parameters,MELD and age were not associated with 90-d mortality or graft failure in either *** were no significant predictors of early *** Sarcopenia is an independent and potentially modifiable predictor of increased post-transplant bacterial infections and hospital length of stay in men with *** upper limb LM provides a novel measure of muscle wasting that has prognostic value in this *** lack of association in women req

关键词： Dual-energy X-ray absorptiometry Sarcopenia Body composition Liver transplantation Survival

Unpacking the challenge of gastric varices: A review on indication, timing and modality of therapy

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World Journal of Hepatology 2021年第8期13卷 868-878页

作者： Karl Vaz Marios Efthymiou Rhys Vaughan adam g testro Hin-Boon Lew Leonardo Zorron Cheng Tao Pu Sujievvan Chandran Department of gastroenterology and Hepatology Austin HealthHeidelberg 3084VictoriaAustralia University of Melbourne Parkville 3052VictoriaAustralia Department of Radiology Austin HealthHeidelberg 3084VictoriaAustralia

Upper gastrointestinal bleeding from oesophageal or gastric varices is an important medical condition in patients with portal *** the emergence of a number of novel endoscopic and radiologic therapies for oesophagogastric varices,controversy exists regarding the indication,timing and modality of *** aim of this review is to provide a concise and practical evidence-based overview of these issues.

关键词： Upper gastrointestinal bleeding Portal hypertension gastric varices Variceal band ligation Variceal obliteration Sclerotherapy Transjugular intrahepatic portosystemic shunt Balloon-occlusion retrograde transvenous obliteration

Epidemiology and outcomes of acute liver failure in Australia

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World Journal of Hepatology 2019年第7期11卷 586-595页

作者： Penelope Hey Timothy P Hanrahan Marie Sinclair adam g testro Peter W Angus adam Peterson Stephen Warrillow Rinaldo Bellomo Marcos V Perini graham Starkey Robert M Jones Michael Fink Tess McClure Paul gow Liver Transplant Unit Austin HealthHeidelberg 3084Australia The University of Melbourne Melbourne 3052Australia Department of Intensive Care Austin HeathMelbourne 3084Australia Department of Surgery Austin HealthMelbourne 3084Australia

BACKgROUND Acute liver failure (ALF) is a life-threatening syndrome with varying aetiologies requiring complex care and multidisciplinary management. Its changing incidence, aetiology and outcomes over the last 16 years in the Australian context remain uncertain. AIM To describe the changing incidence, aetiology and outcomes of ALF in South Eastern Australia. METHODS The database of the Victorian Liver Transplant Unit was interrogated to identify all cases of ALF in adults (> 16 years) in adults hospitalised between January 2002 and December 2017. Overall, 169 patients meeting criteria for ALF were identified. Demographics, aetiology of ALF, rates of transplantation and outcomes were collected for all patients. Transplant free survival and overall survival (OS) were assessed based on survival to discharge from hospital. Results were compared to data from a historical cohort from the same unit from 1988- 2001. RESULTS Paracetamol was the most common aetiology of acute liver failure, accounting for 50% of cases, with an increased incidence compared with the historical cohort (P = 0.046). Viral hepatitis and non-paracetamol drug or toxin induced liver injury accounted for 15% and 10% of cases respectively. Transplant free survival (TFS) improved significantly compared to the historical cohort (52% vs 38%, P = 0.032). TFS was highest in paracetamol toxicity with spontaneous recovery in 72% of cases compared to 31% of non-paracetamol ALF (P gency liver transplantation. Nine of these died while waiting for an organ to become available. Forty-two patients (25%) underwent emergency liver transplantation with a 1, 3 and 5 year survival of 81%, 78% and 72% respectively. CONCLUSION Paracetamol toxicity is the most common aetiology of ALF in South-Eastern Australia with a rising incidence over 30 years. TFS has improved, however it remains low in non-paracetamol ALF.

关键词： Liver failure Acute Paracetamol Australia Victoria Liver transplant

Immune monitoring post liver transplant

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World Journal of Transplantation 2014年第1期4卷 30-39页

作者： Siddharth Sood adam g testro Liver Transplant Unit Victoria Level 8 HSB Austin Health University of Melbourne

Many of the causes of short and late morbidity following liver transplantation are associated with immunosuppression or immunosuppressive medications. Current care often involves close monitoring of liver biochemistry as well as therapeutic drug levels. However, the postoperative course following liver transplantation can often be associated with significant complications including infection and rejection, suggesting an inadequacy in current immune function monitoring. Many assays have been tested in the research setting to identify possible biomarkers that may be used to predict clinical events such as acute cellular rejection, and therefore allow modification of a patient's immunosuppressive regimen prior to a clinical event. However, these generally require significant laboratory processing and have had difficulty becoming established in common clinical use outside the research setting. One assay, Cylex ImmuK now has been food and drug administration approved but has had variable results. In this review we discuss the assays that have been used to assess monitoring of immune function after liver transplantation and consider possible future directions.

关键词： Immune function monitoring Review Biomarkers Liver transplantation

Clinical outcomes of patients with two small hepatocellular carcinomas

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World Journal of Hepatology 2021年第10期13卷 1439-1449页

作者： Anh Duy Pham Karl Vaz Zaid S Ardalan Marie Sinclair Ross Apostolov Sarah gardner Ammar Majeed gauri Mishra Ning Mao Kam Kurvi Patwala Numan Kutaiba Niranjan Arachchi Sally Bell Anouk T Dev John S Lubel Amanda J Nicoll Siddharth Sood William Kemp Stuart K Roberts Michael Fink adam g testro Peter W Angus Paul J gow The Victorian Liver Transplant Unit Austin HealthHeidelberg 3084VictoriaAustralia Department of gastroenterology Alfred HealthMelbourne 3000VictoriaAustralia The Melbourne Liver group Melbourne 3000VictoriaAustralia The University of Melbourne Parkville 3010VictoriaAustralia Central Clinical School Monash UniversityMelbourne 3004VictoriaAustralia Department of gastroenterology and Hepatology Monash HealthClayton 3168VictoriaAustralia Department of Radiology Austin HealthHeidelberg 3084VictoriaAustralia Department of Radiology Eastern HealthBox Hill 3128VictoriaAustralia Department of gastroenterology Western HealthFootscray 3011VictoriaAustralia Department of gastroenterology Eastern HealthBox Hill 3128VictoriaAustralia Department of gastroenterology Royal Melbourne HospitalParkville 3050VictoriaAustralia

BACKgROUND Management of single small hepatocellular carcinoma(HCC)is straightforward with curative outcomes achieved by locoregional therapy or *** transplantation is often considered for multiple small or single large *** of two small HCC whether presenting synchronously or sequentially is less *** To define the outcomes of patients presenting with two small *** Retrospective review of HCC databases from multiple institutions of patients with either two synchronous or sequential HCC≤3 cm between January 2000 and March *** outcomes were overall survival(OS)and transplant-free survival(TFS).RESULTS 104 patients were identified(male n=89).Median age was 63 years(interquartile range 58-67.75)and the most common aetiology of liver disease was hepatitis C(40.4%).59(56.7%)had synchronous HCC and 45(43.3%)had sequential.36 patients died(34.6%)and 25 were transplanted(24.0%).1,3 and 5-year OS was 93.0%,66.1% and 62.3% and 5-year post-transplant survival was 95.8%.1,3 and 5-year TFS was 82.1%,45.85% and 37.8%.When synchronous and sequential groups were compared,OS(1,3 and 5 year synchronous 91.3%,63.8%,61.1%,sequential 95.3%,69.5%,64.6%,P=0.41)was similar but TFS was higher in the sequential group(1,3 and 5 year synchronous 68.5%,37.3% and 29.7%,sequential 93.2%,56.6%,48.5%,P=0.02)though this difference did not remain during multivariate *** TFS in patients presenting with two HCC≤3 cm is poor regardless of the timing of the second *** patients presenting with two small HCC should be considered for transplantation.

关键词： Hepatocellular carcinoma Liver cancer Prognosis Transplantation Transplant-free survival

Statin, aspirin and metformin use and risk of hepatocellular carcinoma related outcomes following liver transplantation: A retrospective study

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World Journal of Transplantation 2024年第3期14卷 120-131页

作者： William Chung Kevin Wong Noel Ravindranayagam Lauren Tang Josephine grace Darren Wong Danny Con Marie Sinclair Avik Majumdar Numan Kutaiba Samuel Hui Paul gow Vijayaragavan Muralidharan Alexander Dobrovic adam testro Department of gastroenterology Austin HealthHeidelberg 3084VictoriaAustralia Victorian Liver Transplant Unit Austin HealthHeidelberg 3084VictoriaAustralia Department of Radiology Austin HealthHeidelberg 3084VictoriaAustralia Department of gastroenterology Monash HealthClayton 3168VictoriaAustralia Department of Surgery University of MelbourneAustin HealthHeidelberg 3048VictoriaAustralia Department of Surgery Beacon LaboratoryAustin PrecinctThe University of MelbourneAustin HospitalHeidelberg 3048VictoriaAustralia

BACKgROUND Liver transplantation(LT)is a potentially curative therapy for patients with hepatocellular carcinoma(HCC).HCC-recurrence following LT is associated with reduced *** is increasing interest in chemoprophylaxis to improve HCC-related outcomes *** To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC,and patient outcomes following *** This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022,from a single Australian *** use was defined as statin,aspirin or metformin therapy for≥29 days,within 24 months post-LT.A cox proportional-hazards model with time-dependent covariates was used for survival *** measures were the composite-endpoint of HCC-recurrence and all-cause mortality,HCC-recurrence and HCC-related *** analysis was performed to account for immortality time bias and statin *** Three hundred and five patients were included in this study,with 253(82.95%)males with a median age of 58.90 *** of liver disease were 150(49.18%)hepatitis C,73(23.93%)hepatitis B(HBV)and 33(10.82%)non-alcoholic fatty liver disease(NAFLD).56(18.36%)took statins,51(16.72%)aspirin and 50(16.39%)*** a median follow-up time of 59.90 months,34(11.15%)developed HCC-recurrence,48(15.74%)died,17(5.57%)from HCC-related ***,aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality[hazard ratio(HR):1.16,95%CI:0.58-2.30;HR:1.21,95%CI:0.28-5.27;HR:0.61,95%CI:0.27-1.36],HCC-recurrence(HR:0.52,95%CI:0.20-1.35;HR:0.51,95%CI:0.14-1.93;HR 1.00,95%CI:0.37-2.72),or HCC-related mortality(HR:0.32,95%CI:0.033-3.09;HR:0.71,95%CI:0.14-3.73;HR:1.57,95%CI:0.61-4.04)*** dosing was not associated with statist-ically significant differences in HCC-related ***

关键词： Liver transplantation Hepatocellular carcinoma Transplant oncology Statins HMg-Co-A reductase Aspirin Metformin Mammalian target of rapamycin

Liver decompensation after rapid weight loss from semaglutide in a patient with non-alcoholic steatohepatitis -associated cirrhosis

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World Journal of gastroenterology 2023年第47期29卷 6165-6167页

作者： Matthew Peverelle Jonathan Ng James Peverelle Ryan D.Hirsch adam testro Liver transplant unit Austin HealthMelbourne 3084Australia Liver transplant unit Austin HealthHeidelberg 3084VictoriaAustralia

There is rapidly increasing uptake of gLP-1 (glucagon-like peptide-1) agonistssuch as semaglutide worldwide for weight loss and management of non-alcoholicsteatohepatitis (NASH). remains a paucity of safety data in the vulnerable NASHcirrhotic population. We report herein the first documented case of liver decompensationand need for liver transplant waitlisting in a patient with NASHcirrhosistreated with semaglutide. Rapid weight loss led to the development ofascites and hepatic encephalopathy and an increase in the patients Model forEndstage Liver Disease-Na (MELD-Na) score from 11 to 22. Aggressive nutritionalsupplementation was commenced and the semaglutide was stopped. Overthe following months she regained her weight and her liver recompensated andher MELD-Na decreased to 13, allowing her to be delisted from the transplantwaitlist. This case serves as a cautionary tale to clinicians using semaglutide in thecirrhotic population and highlights the need for more safety data in this patientgroup.

关键词： Semaglutide Non-alcoholic steatohepatitis Cirrhosis Non-alcoholic steatohepatitis cirrhosis glucagon-like peptide 1 agonists Weight loss

Immune function biomarker QuantiFERON-monitor is associated with infection risk in cirrhotic patients

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World Journal of Hepatology 2016年第35期8卷 1569-1575页

作者： Siddharth Sood Lijia Yu Kumar Visvanathan Peter William Angus Paul John gow adam gareth testro Department of gastroenterology and Hepatology University of Melbourne Royal Melbourne Hospital Liver Transplant Unit Victoria University of Melbourne Innate Immune Laboratory University of Melbourne St Vincent’s Hospital

AIMTo investigate whether a novel immune function biomarker QuantiFERON-Monitor (QFM) can identify cirrhotic patients at greatest risk of infection. METHODSAdult cirrhotic patients on the liver transplant waiting list were recruited for this observational cohort study from a tertiary liver transplant referral unit. The immune function biomarker, QFM was performed using the same method as the widely available Quantiferon-gold assay, and measures output in interferon gamma in IU/mL after dual stimulation of the innate and adaptive immune systems. Ninety-one cirrhotic patients were recruited, with 47 (52%) transplanted on the day of their QFM. The remaining 44 (48%) were monitored for infections until transplant, death, or census date of 1st February 2014. RESULTSCirrhotic patients express a median QFM significantly lower than healthy controls (94.5 IU/mL vs 423 IU/mL), demonstrating that they are severely immunosuppressed. Several factors including model for end stage liver disease, presence of hepatocellular carcinoma, bilirubin, international normalized ratio and haemoglobin were associated with QFM on univariate analysis. Disease aetiology did not appear to impact QFM. On multivariate analysis, only Child-Pugh score and urea were significantly associated with a patient’s immune function as objectively measured by QFM. In the 44 patients who were not transplanted immediately after their blood test and could be monitored for subsequent infection risk, 13 (29.5%) experienced a pre-transplant infection a median 20 d (range 2-182) post-test. QFM P = 0.01) for infection. A very low QFM P = 0.003) with death in three patients who died while awaiting transplantation (HR = 56.6). CONCLUSIONQFM is lower in cirrhotics, allowing objective determinations of an individual’s unique level of immune dysfunction. Low QFM was associated with increased susceptibility to infection.

关键词： Infection Biomarker Immune dysfunction Immune function Immunosuppression Liver Immune system Cirrhosis Mortality