Malnutrition is highly prevalent in liver cirrhosis and its presence carries important prognostic implications.The clinical conditions and pathophysiological mechanisms that cause malnutrition in cirrhosis are multipl...Malnutrition is highly prevalent in liver cirrhosis and its presence carries important prognostic implications.The clinical conditions and pathophysiological mechanisms that cause malnutrition in cirrhosis are multiple and interrelated.Anorexia and liver decompensation symptoms lead to poor dietary intake;metabolic changes characterised by elevated energy expenditure,reduced glycogen storage,an accelerated starvation response and protein catabolism result in muscle and fat wasting;and,malabsorption renders the cirrhotic patient unable to fully absorb or utilise food that has been consumed.Malnutrition is therefore a considerable challenge to manage effectively,particularly as liver disease progresses.A high energy,high protein diet is recognised as standard of care,yet patients struggle to follow this recommendation and there is limited evidence to guide malnutrition interventions in cirrhosis and liver transplantation.In this review,we seek to detail the factors which contribute to poor nutritional status in liver disease,and highlight complexities far greater than“poor appetite”or“reduced oral intake”leading to malnutrition.We also discuss management strategies to optimise nutritional status in this patient group,which target the inter-related mechanisms unique to advanced liver disease.Finally,future research requirements are suggested,to develop effective treatments for one of the most common and debilitating complications afflicting cirrhotic patients.展开更多
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...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.展开更多
Upper gastrointestinal bleeding from oesophageal or gastric varices is an important medical condition in patients with portal hypertension.Despite the emergence of a number of novel endoscopic and radiologic therapies...Upper gastrointestinal bleeding from oesophageal or gastric varices is an important medical condition in patients with portal hypertension.Despite the emergence of a number of novel endoscopic and radiologic therapies for oesophagogastric varices,controversy exists regarding the indication,timing and modality of therapy.The aim of this review is to provide a concise and practical evidence-based overview of these issues.展开更多
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 i...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<0.001).Fifty-nine patients were waitlisted for emergency 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.展开更多
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 days.Uppe...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 days.Upper 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 transplantation.AIM To investigate the use of DEXA LM in predicting gender-stratified early posttransplant outcomes.METHODS Liver transplant recipients who underwent pre-transplant DEXA body composition imaging between 2002 and 2017 were included.Endpoints included posttransplant mortality and graft failure,bacterial infections,acute cellular rejection(ACR)and intensive care and total hospital length of stay.RESULTS 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 16.Median 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 only.There 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 men.In women,neither MELD nor body composition parameters were associated with post-transplant adverse outcomes or increased length of stay.Body composition parameters,MELD and age were not associated with 90-d mortality or graft failure in either gender.There were no significant predictors of early ACR.CONCLUSION Sarcopenia is an independent and potentially modifiable predictor of increased post-transplant bacterial infections and hospital length of stay in men with cirrhosis.DEXA upper limb LM provides a novel measure of muscle wasting that has prognostic value in this cohort.The lack of association in women requires further investigation.展开更多
Due to advances in modern medicine,liver transplantation has revolutionised the prognosis of many previously incurable liver diseases.This progress has largely been due to advances in immunosuppressant therapy.However...Due to advances in modern medicine,liver transplantation has revolutionised the prognosis of many previously incurable liver diseases.This progress has largely been due to advances in immunosuppressant therapy.However,despite the judicious use of immunosuppression,many liver transplant recipients still experience complications such as rejection,which necessitates diagnosis via invasive liver biopsy.There is a clear need for novel,minimally-invasive tests to optimise immunosuppression and improve patient outcomes.An emerging biomarker in this‘‘precision medicine’‘liver transplantation field is that of donorspecific cell free DNA.In 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.展开更多
BACKGROUND Management of single small hepatocellular carcinoma(HCC)is straightforward with curative outcomes achieved by locoregional therapy or resection.Liver transplantation is often considered for multiple small o...BACKGROUND Management of single small hepatocellular carcinoma(HCC)is straightforward with curative outcomes achieved by locoregional therapy or resection.Liver transplantation is often considered for multiple small or single large HCC.Management of two small HCC whether presenting synchronously or sequentially is less clear.AIM To define the outcomes of patients presenting with two small HCC.METHODS Retrospective review of HCC databases from multiple institutions of patients with either two synchronous or sequential HCC≤3 cm between January 2000 and March 2018.Primary 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 analysis.CONCLUSION TFS in patients presenting with two HCC≤3 cm is poor regardless of the timing of the second tumor.All patients presenting with two small HCC should be considered for transplantation.展开更多
文摘Malnutrition is highly prevalent in liver cirrhosis and its presence carries important prognostic implications.The clinical conditions and pathophysiological mechanisms that cause malnutrition in cirrhosis are multiple and interrelated.Anorexia and liver decompensation symptoms lead to poor dietary intake;metabolic changes characterised by elevated energy expenditure,reduced glycogen storage,an accelerated starvation response and protein catabolism result in muscle and fat wasting;and,malabsorption renders the cirrhotic patient unable to fully absorb or utilise food that has been consumed.Malnutrition is therefore a considerable challenge to manage effectively,particularly as liver disease progresses.A high energy,high protein diet is recognised as standard of care,yet patients struggle to follow this recommendation and there is limited evidence to guide malnutrition interventions in cirrhosis and liver transplantation.In this review,we seek to detail the factors which contribute to poor nutritional status in liver disease,and highlight complexities far greater than“poor appetite”or“reduced oral intake”leading to malnutrition.We also discuss management strategies to optimise nutritional status in this patient group,which target the inter-related mechanisms unique to advanced liver disease.Finally,future research requirements are suggested,to develop effective treatments for one of the most common and debilitating complications afflicting cirrhotic patients.
文摘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.
文摘Upper gastrointestinal bleeding from oesophageal or gastric varices is an important medical condition in patients with portal hypertension.Despite the emergence of a number of novel endoscopic and radiologic therapies for oesophagogastric varices,controversy exists regarding the indication,timing and modality of therapy.The aim of this review is to provide a concise and practical evidence-based overview of these issues.
文摘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<0.001).Fifty-nine patients were waitlisted for emergency 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.
文摘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 days.Upper 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 transplantation.AIM To investigate the use of DEXA LM in predicting gender-stratified early posttransplant outcomes.METHODS Liver transplant recipients who underwent pre-transplant DEXA body composition imaging between 2002 and 2017 were included.Endpoints included posttransplant mortality and graft failure,bacterial infections,acute cellular rejection(ACR)and intensive care and total hospital length of stay.RESULTS 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 16.Median 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 only.There 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 men.In women,neither MELD nor body composition parameters were associated with post-transplant adverse outcomes or increased length of stay.Body composition parameters,MELD and age were not associated with 90-d mortality or graft failure in either gender.There were no significant predictors of early ACR.CONCLUSION Sarcopenia is an independent and potentially modifiable predictor of increased post-transplant bacterial infections and hospital length of stay in men with cirrhosis.DEXA upper limb LM provides a novel measure of muscle wasting that has prognostic value in this cohort.The lack of association in women requires further investigation.
基金The University of Melbourne,Parkville 3000,VIC,Australia。
文摘Due to advances in modern medicine,liver transplantation has revolutionised the prognosis of many previously incurable liver diseases.This progress has largely been due to advances in immunosuppressant therapy.However,despite the judicious use of immunosuppression,many liver transplant recipients still experience complications such as rejection,which necessitates diagnosis via invasive liver biopsy.There is a clear need for novel,minimally-invasive tests to optimise immunosuppression and improve patient outcomes.An emerging biomarker in this‘‘precision medicine’‘liver transplantation field is that of donorspecific cell free DNA.In 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.
文摘BACKGROUND Management of single small hepatocellular carcinoma(HCC)is straightforward with curative outcomes achieved by locoregional therapy or resection.Liver transplantation is often considered for multiple small or single large HCC.Management of two small HCC whether presenting synchronously or sequentially is less clear.AIM To define the outcomes of patients presenting with two small HCC.METHODS Retrospective review of HCC databases from multiple institutions of patients with either two synchronous or sequential HCC≤3 cm between January 2000 and March 2018.Primary 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 analysis.CONCLUSION TFS in patients presenting with two HCC≤3 cm is poor regardless of the timing of the second tumor.All patients presenting with two small HCC should be considered for transplantation.
