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Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care

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World Journal of Hepatology 2024年第4期16卷 650-660页

作者： Dorothy Liu Mark M Youssef josephine A grace Marie Sinclair Department of Gastroenterology Austin HealthMelbourne 3084VictoriaAustralia Victorian Liver Transplant Unit Austin HealthMelbourne 3084VictoriaAustralia Department of Medicine University of MelbourneMelbourne 3084VictoriaAustralia

BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant *** immunosuppression has been shown to contribute to post-transplant malignancy(PTM)*** is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of *** inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(MPA),the active metabolite of mycophenolate mofetil,may limit tumour *** transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this ***,there is limited clinical data on this subject in both LT and other solid organ transplant *** To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ *** A literature search was conducted using MEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August *** terms,synonyms and explosion of MeSH terms,Boolean operators and truncations were also utilised in the *** lists of retrieved articles were also reviewed to identify any additional *** duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in ***-text articles were assessed for eligibility based on pre-specified inclusion and exclusion *** A total of 6 studies were included in this *** studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol us

关键词： Immunosuppression Solid organ transplantation Liver transplantation Carcinogenicity Tacrolimus Mycophenolate

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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

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Hepatocellular carcinoma surveillance and quantile regression for determinants of underutilisation in at-risk Australian patients

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World Journal of Gastrointestinal Oncology 2021年第12期13卷 2149-2160页

作者： Elizabeth SL Low Ross Apostolov Darren Wong Sandra Lin Numan Kutaiba josephine A grace Marie Sinclair Department of Gastroenterology and Liver Transplant Unit Austin HealthHeidelberg 3084VictoriaAustralia Department of Medicine University of MelbourneMelbourne 3000VictoriaAustralia Department of Radiology Monash HealthClayton 3168VictoriaAustralia Department of Radiology Austin HealthHeidelberg 3084VictoriaAustralia

BACKGROUND While clinical guidelines recommend hepatocellular carcinoma(HCC)surveillance for at-risk individuals,reported surveillance rates in the United States and Europe remain disappointingly *** To quantify HCC surveillance in an Australian cohort,and assess for factors associated with surveillance *** All patients undergoing HCC surveillance liver ultrasounds between January 1,2018 to June 30,2018 at a tertiary hospital in Melbourne,Australia,were followed until July 31,2020,or when surveillance was no longer *** primary outcome was the percentage of time up-to-date with HCC surveillance(PTUDS).Quantile regression was performed to determine the impact of factors associated with HCC surveillance *** Among 775 at-risk patients followed up for a median of 27.5 months,the median PTUDS was 84.2%(IQR:66.3%-96.3%).85.0%of patients were followed up by specialist *** those receiving specialist care,quantile regression demonstrated differential associations at various quantile levels of PTUDS for several *** age at the 25th quantile(estimate 0.002 per percent,P=0.03),and cirrhotic status at the 75th quantile(estimate 0.021,P=0.017),were significantly associated with greater percentage of time *** ethnicity(estimate-0.089,P=0.048)and a culturally and linguistically diverse(CALD)background(estimate-0.063,P=0.01)were significantly associated with lower PTUDS at the 50th quantile,and again for CALD at the 75th quantile(estimate-0.026,P=0.045).CONCLUSION While median PTUDS in this Australian cohort study was 84.2%,awareness of the impact of specific factors across PTUDS quantiles can aid targeted interventions towards improved HCC surveillance.

关键词： Liver cirrhosis Hepatitis,viral,human Carcinoma,hepatocellular Liver neoplasms Early detection of cancer Population surveillance

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Therapeutic potential of targeting the renin angiotensin system in portal hypertension

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World Journal of Gastrointestinal Pathophysiology 2013年第1期4卷 1-11页

作者： Chandana B Herath josephine A grace Peter W Angus Department of Medicine University of MelbourneAustin HealthHeidelberg Victoria 3084Australia Department of Gastroenterology Austin HealthHeidelbergVictoria 3084Australia

Portal hypertension is responsible for the bulk of the morbidity and mortality in patients with *** therapy to reduce portal pressure involves targeting two vascular *** first approach is to reduce intra hepatic vascular tone induced by the activity of powerful vasocontrictors such as angiotensin Ⅱ,endothelin-1 and the sympathetic system and mediated via contraction of perisinusoidal myofibroblasts and pervascular smooth muscle *** second approach is to reduce mesenteric and portal blood ***-selective b-blockers are widely used and have been shown to prolong patient survival and reduce oesophageal variceal bleeding in advanced *** many patients are unable to tolerate these drugs and they are ineffective in a significant proportion of *** there are no other drug therapies that have proven efficacy in the treatment of portal hypertension and prevention of variceal *** review briefly outlines current therapeutic approaches to themanagement of portal hypertension,and the evidence supporting the role of the renin angiotensin system(RAS) and the use of RAS blockers in this *** will also outline recent advances in RAS research that could lead to the development of new treatments focusing in particular on the recently discovered "alternate axis" of the RAS.

关键词： Angiotensin-(1-7) Portal hypertension Intrahepatic resistance Mesenteric vasodilatation Variceal bleeding Non-selective b-blockers Renin angiotensin system Mas receptor Angiotensin receptor Cirrhosis

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