BACKGROUND Survival in patients with autoimmune liver disease overlap syndromes(AILDOS)compared to those with single autoimmune liver disease is unclear.AIM To investigate the survival of patients with AILDOS and asse...BACKGROUND Survival in patients with autoimmune liver disease overlap syndromes(AILDOS)compared to those with single autoimmune liver disease is unclear.AIM To investigate the survival of patients with AILDOS and assess the accuracy of non-invasive serum models for predicting liver-related death.METHODS Patients with AILDOS were defined as either autoimmune hepatitis and primary biliary cholangitis overlap(AIH-PBC)or autoimmune hepatitis and primary sclerosing cholangitis overlap(AIH-PSC)and were identified from three tertiary centres for this cohort study.Liver-related death or transplantation(liver-related mortality)was determined using a population-based data linkage system.Prognostic scores for liver-related death were compared for accuracy[including liver outcome score(LOS),Hepascore,Mayo Score,model for end-stage liver disease(MELD)score and MELD incorporated with serum sodium(MELD-Na)score].RESULTS Twenty-two AILDOS patients were followed for a median of 3.1 years(range,0.35-7.7).Fourteen were female,the median age was 46.7 years(range,17.8 to 82.1)and median Hepascore was 1(range,0.07-1).At five years post enrolment,57%of patients remained free from liver-related mortality(74%AIH-PBC,27%AIH-PSC).There was no significant difference in survival between AIH-PBC and AIH-PSC.LOS was a significant predictor of liver-related mortality(P<0.05)in patients with AIH-PBC(n=14)but not AIH-PSC(n=8).A LOS cut-point of 6 discriminated liver-related mortality in AIH-PBC patients(P=0.012,log-rank test,100%sensitivity,77.8%specificity)(Harrell's C-statistic 0.867).The MELD score,MELD-Na score and Mayo Score were not predictive of liver-related mortality in any group.CONCLUSION Survival in the rare,AILDOS is unclear.The current study supports the LOS as a predictor of liver-related mortality in AIH-PBC patients.Further trials investigating predictors of survival in AILDOS are required.展开更多
AIM:To evaluate whether desferrioxamine decreases ischemia and perfusion injury aggravated by cold storage(CS)in a rat liver perfusion model. METHODS:Isolated rat livers were kept in CS in University of Wisconsin Solu...AIM:To evaluate whether desferrioxamine decreases ischemia and perfusion injury aggravated by cold storage(CS)in a rat liver perfusion model. METHODS:Isolated rat livers were kept in CS in University of Wisconsin Solution for 20 h at 4℃,then exposed to 25 min of warm ischemia(WI)at 37℃ followed by 2 h of warm perfusion(WP)at 37℃with oxygenated(95%oxygen and 5%carbon dioxide) Krebs-Henseleit buffer.Desferrioxamine(DFO),an iron chelator,was added at different stages of storage,ischemia and perfusion:in CS only,in WI only,in WP only, in WI and perfusion,or in all stages.Effluent samples were collected after CS and after WI.Perfusate samples and bile were collected every 30 min(0,0.5,1,1.5 and 2 h)during liver perfusion.Cellular injury was assessed by the determination of lactate dehydrogenase(LDH) and aspartate aminotransferase(AST)in the effluent and perfusate samples.Total iron was analysed in the perfusate samples.After WP,the liver was collected for the determination of liver swelling(wet to dry ratio) and liver morphological examination(hematoxylin and eosin staining). RESULTS:Increased CS time caused increased liver dysfunction during WP.After 2 h of WP,liver injury was indicated by increased release of AST(0.5 h CS:9.4± 2.2 U/g liver vs 20 h CS:45.9±10.8 U/g liver,P<0.05) and LDH(0.5 h CS:59±14 U/g liver vs 20 h CS:297 ±71 U/g liver,P<0.05).There was an associated increase in iron release into the perfusate(0.5 h CS:0.11 ±0.03μmoL/g liver vs 20 h CS:0.58±0.10μmoL/g liver,P<0.05)and reduction in bile flow(0.5 h CS: 194±12μL/g vs 20 h CS:71±8μL/g liver,P<0.05). When DFO was added during WI and WP following 20 h of CS,release of iron into the perfusate was de- creased(DFO absent 0.58±0.10μmoL/g liver vs DFO present 0.31±0.06μmoL/g liver,P<0.05),and liver function substantially improved with decreased release of AST(DFO absent 45.9±10.8 U/g liver vs DFO present 8.1±0.9 U/g liver,P<0.05)and LDH(DFO absent 297±71 U/g liver vs DFO present 56±7 U/g liver,P<0.05),and increased bile flow(DFO absent 71±8μL/g liver vs DFO present 237±36μL/g liver, P<0.05).DFO was also shown to improve liver morphology after WP.Cellular injury(the release of LDH and AST)was significantly reduced with the addition of DFO in CS medium but to a lesser extent compared to the addition of DFO in WP or WI and perfusion.There was no effect on liver swelling or bile flow when DFO was only added to the CS medium. CONCLUSION:DFO added during WI and perfusion decreased liver perfusion injury aggravated by extended CS.展开更多
AIM To evaluate the effect of long haul airplane transport of donor livers on post-transplant outcomes. METHODS A retrospective cohort study of patients who received a liver transplantation was performed in Perth, Aus...AIM To evaluate the effect of long haul airplane transport of donor livers on post-transplant outcomes. METHODS A retrospective cohort study of patients who received a liver transplantation was performed in Perth, Australia from 1992 to 2012. Donor and recipient characteristics information were extracted from Western Australian liver transplantation service database. Patients were followed up for a mean of six years. Patient and graft survival were evaluated and compared between patients who received a local donor liver and those who received an airplane transported donor liver. Predictors of survival were determined by univariate and multivariate analysis using cox regression.RESULTS One hundred and ninety-three patients received alocal donor liver and 93 patients received an airplane transported donor liver. Airplane transported livers had a significantly lower alanine transaminase(mean: 45 U/L vs 84 U/L, P = 0.035), higher donor risk index(mean: 1.88 vs 1.42, P < 0.001) and longer cold ischemic time(CIT)(mean: 10.1 h vs 6.4 h, P < 0.001). There was a weak correlation between CIT and transport distance(r2 = 0.29, P < 0.001). Mean follow up was six years and 93 patients had graft failure. Multivariate analysis found only airplane transport retained significance for graft loss(HR = 1.92, 95%CI: 1.16-3.17). One year graft survival was 0.88 for those with a local liver and was 0.71 for those with an airplane transported liver. One year graft loss was due to primary graft non-function or associated with preservation injury in 20.8% of recipients of an airplane transported liver compared with 4.6% in those with a local liver(P = 0.027). CONCLUSION Airplane transport of donor livers was independently associated with reduced graft survival following liver transplantation.展开更多
AIM To establish if serial Hepascore tests(referred to as delta Hepascore) in those with chronic hepatitis C(CHC) correlate with the increase and/or decrease in risk of liver related complications.METHODS Three hundre...AIM To establish if serial Hepascore tests(referred to as delta Hepascore) in those with chronic hepatitis C(CHC) correlate with the increase and/or decrease in risk of liver related complications.METHODS Three hundred and forty-six CHC patients who had two Hepascore tests performed were studied. During 1944 patient years follow-up 28(8.1%) reached an endpoint. The Hepascore is a serum test that provides clinically useful data regarding the stage of liver fibrosis andsubsequent clinical outcomes in chronic liver disease.RESULTS Patients with a baseline Hepascore > 0.75 had a significantly increased rate of reaching a composite endpoint consisting of hepatocellular carcinoma, liver death, and/or decompensation(P < 0.001). In those with an initial Hepascore > 0.75, a subsequent improved Hepascore showed a significantly decreased risk for the composite endpoint(P = 0.004). There were no negative outcomes in those with a stable or improved delta Hepascore. The minimum time between tests that was found to give a statically significant result was in those greater than one year(P = 0.03).CONCLUSION In conclusion, Hepascore is an accurate predictor of liver related mortality and liver related morbidity in CHC patients. Of note, we have found that there is a decreased risk of mortality and morbidity in CHC patients when the patient has an improving delta Hepascore. Repeat Hepascore tests, when performed at a minimum one-year interval, may be of value in routine clinical practice to predict liver related clinical outcomes and to guide patient management.展开更多
文摘BACKGROUND Survival in patients with autoimmune liver disease overlap syndromes(AILDOS)compared to those with single autoimmune liver disease is unclear.AIM To investigate the survival of patients with AILDOS and assess the accuracy of non-invasive serum models for predicting liver-related death.METHODS Patients with AILDOS were defined as either autoimmune hepatitis and primary biliary cholangitis overlap(AIH-PBC)or autoimmune hepatitis and primary sclerosing cholangitis overlap(AIH-PSC)and were identified from three tertiary centres for this cohort study.Liver-related death or transplantation(liver-related mortality)was determined using a population-based data linkage system.Prognostic scores for liver-related death were compared for accuracy[including liver outcome score(LOS),Hepascore,Mayo Score,model for end-stage liver disease(MELD)score and MELD incorporated with serum sodium(MELD-Na)score].RESULTS Twenty-two AILDOS patients were followed for a median of 3.1 years(range,0.35-7.7).Fourteen were female,the median age was 46.7 years(range,17.8 to 82.1)and median Hepascore was 1(range,0.07-1).At five years post enrolment,57%of patients remained free from liver-related mortality(74%AIH-PBC,27%AIH-PSC).There was no significant difference in survival between AIH-PBC and AIH-PSC.LOS was a significant predictor of liver-related mortality(P<0.05)in patients with AIH-PBC(n=14)but not AIH-PSC(n=8).A LOS cut-point of 6 discriminated liver-related mortality in AIH-PBC patients(P=0.012,log-rank test,100%sensitivity,77.8%specificity)(Harrell's C-statistic 0.867).The MELD score,MELD-Na score and Mayo Score were not predictive of liver-related mortality in any group.CONCLUSION Survival in the rare,AILDOS is unclear.The current study supports the LOS as a predictor of liver-related mortality in AIH-PBC patients.Further trials investigating predictors of survival in AILDOS are required.
文摘AIM:To evaluate whether desferrioxamine decreases ischemia and perfusion injury aggravated by cold storage(CS)in a rat liver perfusion model. METHODS:Isolated rat livers were kept in CS in University of Wisconsin Solution for 20 h at 4℃,then exposed to 25 min of warm ischemia(WI)at 37℃ followed by 2 h of warm perfusion(WP)at 37℃with oxygenated(95%oxygen and 5%carbon dioxide) Krebs-Henseleit buffer.Desferrioxamine(DFO),an iron chelator,was added at different stages of storage,ischemia and perfusion:in CS only,in WI only,in WP only, in WI and perfusion,or in all stages.Effluent samples were collected after CS and after WI.Perfusate samples and bile were collected every 30 min(0,0.5,1,1.5 and 2 h)during liver perfusion.Cellular injury was assessed by the determination of lactate dehydrogenase(LDH) and aspartate aminotransferase(AST)in the effluent and perfusate samples.Total iron was analysed in the perfusate samples.After WP,the liver was collected for the determination of liver swelling(wet to dry ratio) and liver morphological examination(hematoxylin and eosin staining). RESULTS:Increased CS time caused increased liver dysfunction during WP.After 2 h of WP,liver injury was indicated by increased release of AST(0.5 h CS:9.4± 2.2 U/g liver vs 20 h CS:45.9±10.8 U/g liver,P<0.05) and LDH(0.5 h CS:59±14 U/g liver vs 20 h CS:297 ±71 U/g liver,P<0.05).There was an associated increase in iron release into the perfusate(0.5 h CS:0.11 ±0.03μmoL/g liver vs 20 h CS:0.58±0.10μmoL/g liver,P<0.05)and reduction in bile flow(0.5 h CS: 194±12μL/g vs 20 h CS:71±8μL/g liver,P<0.05). When DFO was added during WI and WP following 20 h of CS,release of iron into the perfusate was de- creased(DFO absent 0.58±0.10μmoL/g liver vs DFO present 0.31±0.06μmoL/g liver,P<0.05),and liver function substantially improved with decreased release of AST(DFO absent 45.9±10.8 U/g liver vs DFO present 8.1±0.9 U/g liver,P<0.05)and LDH(DFO absent 297±71 U/g liver vs DFO present 56±7 U/g liver,P<0.05),and increased bile flow(DFO absent 71±8μL/g liver vs DFO present 237±36μL/g liver, P<0.05).DFO was also shown to improve liver morphology after WP.Cellular injury(the release of LDH and AST)was significantly reduced with the addition of DFO in CS medium but to a lesser extent compared to the addition of DFO in WP or WI and perfusion.There was no effect on liver swelling or bile flow when DFO was only added to the CS medium. CONCLUSION:DFO added during WI and perfusion decreased liver perfusion injury aggravated by extended CS.
文摘AIM To evaluate the effect of long haul airplane transport of donor livers on post-transplant outcomes. METHODS A retrospective cohort study of patients who received a liver transplantation was performed in Perth, Australia from 1992 to 2012. Donor and recipient characteristics information were extracted from Western Australian liver transplantation service database. Patients were followed up for a mean of six years. Patient and graft survival were evaluated and compared between patients who received a local donor liver and those who received an airplane transported donor liver. Predictors of survival were determined by univariate and multivariate analysis using cox regression.RESULTS One hundred and ninety-three patients received alocal donor liver and 93 patients received an airplane transported donor liver. Airplane transported livers had a significantly lower alanine transaminase(mean: 45 U/L vs 84 U/L, P = 0.035), higher donor risk index(mean: 1.88 vs 1.42, P < 0.001) and longer cold ischemic time(CIT)(mean: 10.1 h vs 6.4 h, P < 0.001). There was a weak correlation between CIT and transport distance(r2 = 0.29, P < 0.001). Mean follow up was six years and 93 patients had graft failure. Multivariate analysis found only airplane transport retained significance for graft loss(HR = 1.92, 95%CI: 1.16-3.17). One year graft survival was 0.88 for those with a local liver and was 0.71 for those with an airplane transported liver. One year graft loss was due to primary graft non-function or associated with preservation injury in 20.8% of recipients of an airplane transported liver compared with 4.6% in those with a local liver(P = 0.027). CONCLUSION Airplane transport of donor livers was independently associated with reduced graft survival following liver transplantation.
文摘AIM To establish if serial Hepascore tests(referred to as delta Hepascore) in those with chronic hepatitis C(CHC) correlate with the increase and/or decrease in risk of liver related complications.METHODS Three hundred and forty-six CHC patients who had two Hepascore tests performed were studied. During 1944 patient years follow-up 28(8.1%) reached an endpoint. The Hepascore is a serum test that provides clinically useful data regarding the stage of liver fibrosis andsubsequent clinical outcomes in chronic liver disease.RESULTS Patients with a baseline Hepascore > 0.75 had a significantly increased rate of reaching a composite endpoint consisting of hepatocellular carcinoma, liver death, and/or decompensation(P < 0.001). In those with an initial Hepascore > 0.75, a subsequent improved Hepascore showed a significantly decreased risk for the composite endpoint(P = 0.004). There were no negative outcomes in those with a stable or improved delta Hepascore. The minimum time between tests that was found to give a statically significant result was in those greater than one year(P = 0.03).CONCLUSION In conclusion, Hepascore is an accurate predictor of liver related mortality and liver related morbidity in CHC patients. Of note, we have found that there is a decreased risk of mortality and morbidity in CHC patients when the patient has an improving delta Hepascore. Repeat Hepascore tests, when performed at a minimum one-year interval, may be of value in routine clinical practice to predict liver related clinical outcomes and to guide patient management.