BACKGROUND Liver transplantation(LT)is a potentially curative therapy for patients with hepatocellular carcinoma(HCC).HCC-recurrence following LT is associated with reduced survival.There is increasing interest in che...BACKGROUND Liver transplantation(LT)is a potentially curative therapy for patients with hepatocellular carcinoma(HCC).HCC-recurrence following LT is associated with reduced survival.There is increasing interest in chemoprophylaxis to improve HCC-related outcomes post-LT.AIM To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC,and patient outcomes following LT.METHODS This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022,from a single Australian centre.Drug 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 analysis.Outcome measures were the composite-endpoint of HCC-recurrence and all-cause mortality,HCC-recurrence and HCC-related mortality.Sensitivity analysis was performed to account for immortality time bias and statin dosing.RESULTS Three hundred and five patients were included in this study,with 253(82.95%)males with a median age of 58.90 years.Aetiologies 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%)metformin.During 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 mortality.Statin,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)respectively.Statin dosing was not associated with statist-ically significant differences in HCC-related outcomes.CONCLUSION Statin,metformin or aspirin use was not associated with improved HCC-related outcomes post-LT,in a largely historical cohort of Australian patients with a low proportion of NAFLD.Further prospective,multicentre studies are required to clarify any potential benefit of these drugs to improve HCC-related outcomes.展开更多
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 th...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.展开更多
Mycophenolate mofetil(MMF) is an important medication used for maintenance immunosuppression in solid organ transplants. A common gastrointestinal(GI) side effect of MMF is enterocolitis, which has been associated wit...Mycophenolate mofetil(MMF) is an important medication used for maintenance immunosuppression in solid organ transplants. A common gastrointestinal(GI) side effect of MMF is enterocolitis, which has been associated with multiple histological features. There is little data in the literature describing the histological effects of MMF in small intestinal transplant(SIT) recipients. We present a case of MMF toxicity in a SIT recipient, with histological changes in the donor ileum mimicking persistent acute cellular rejection(ACR). Concurrent biopsies of the patient's native colon showed similar changes to those from the donor small bowel, suggesting a non-graft specific process, raising suspicion for MMF toxicity. The MMF was discontinued and complete resolution of these changes occurred over three weeks. MMF toxicity should therefore be considered as a differential diagnosis for ACR and graftversus-host disease in SITs.展开更多
基金This study was approved by the Austin Health Human Ethics Research Committee(No.HREC/87459/Austin-2022).
文摘BACKGROUND Liver transplantation(LT)is a potentially curative therapy for patients with hepatocellular carcinoma(HCC).HCC-recurrence following LT is associated with reduced survival.There is increasing interest in chemoprophylaxis to improve HCC-related outcomes post-LT.AIM To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC,and patient outcomes following LT.METHODS This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022,from a single Australian centre.Drug 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 analysis.Outcome measures were the composite-endpoint of HCC-recurrence and all-cause mortality,HCC-recurrence and HCC-related mortality.Sensitivity analysis was performed to account for immortality time bias and statin dosing.RESULTS Three hundred and five patients were included in this study,with 253(82.95%)males with a median age of 58.90 years.Aetiologies 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%)metformin.During 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 mortality.Statin,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)respectively.Statin dosing was not associated with statist-ically significant differences in HCC-related outcomes.CONCLUSION Statin,metformin or aspirin use was not associated with improved HCC-related outcomes post-LT,in a largely historical cohort of Australian patients with a low proportion of NAFLD.Further prospective,multicentre studies are required to clarify any potential benefit of these drugs to improve HCC-related outcomes.
文摘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.
文摘Mycophenolate mofetil(MMF) is an important medication used for maintenance immunosuppression in solid organ transplants. A common gastrointestinal(GI) side effect of MMF is enterocolitis, which has been associated with multiple histological features. There is little data in the literature describing the histological effects of MMF in small intestinal transplant(SIT) recipients. We present a case of MMF toxicity in a SIT recipient, with histological changes in the donor ileum mimicking persistent acute cellular rejection(ACR). Concurrent biopsies of the patient's native colon showed similar changes to those from the donor small bowel, suggesting a non-graft specific process, raising suspicion for MMF toxicity. The MMF was discontinued and complete resolution of these changes occurred over three weeks. MMF toxicity should therefore be considered as a differential diagnosis for ACR and graftversus-host disease in SITs.
