BACKGROUND Few studies have evaluated the frequency of and the reasons behind the refusal of listing liver transplantation candidates.AIM To assess the ineligibility rate for liver transplantation and its motivations....BACKGROUND Few studies have evaluated the frequency of and the reasons behind the refusal of listing liver transplantation candidates.AIM To assess the ineligibility rate for liver transplantation and its motivations.METHODS A single-center retrospective study was conducted on adult patients which entailed a formal multidisciplinary assessment for liver transplantation eligibility.The predictors for listing were evaluated using multivariable logistic regression.RESULTS In our center,314 patients underwent multidisciplinary work-up before liver transplantation enlisting over a three-year period.The most frequent reasons for transplant evaluation were decompensated cirrhosis(51.6%)and hepatocellular carcinoma(35.7%).The non-listing rate was 53.8%and the transplant rate was 34.4%for the whole cohort.Two hundred and five motivations for ineligibility were collected.The most common contraindications were psychological(9.3%),cardiovascular(6.8%),and surgical(5.9%).Inappropriate or premature referral accounted for 76(37.1%)cases.On multivariable analysis,a referral from another hospital(OR:2.113;95%CI:1.259–3.548)served as an independent predictor of non-listing.CONCLUSION A non-listing decision occurred in half of our cohort and was based on an inappropriate or premature referral in one case out of three.The referral from another hospital was taken as a strong predictor of non-listing.展开更多
Liver cirrhosis is commonly associated with nutritional alterations,reported in 20% of patients with compensated disease and over 60% of patients with decompensated cirrhosis.Nutritional disturbances are associated wi...Liver cirrhosis is commonly associated with nutritional alterations,reported in 20% of patients with compensated disease and over 60% of patients with decompensated cirrhosis.Nutritional disturbances are associated with a worse prognosis and increased risk of complication.Serum levels of branched-chain amino acids(BCAAs)are decreased in patients with liver cirrhosis.The imbalance of amino acids levels has been suggested to be associated with the development of complications,such as hepatic encephalopathy and sarcopenia,and to affect the clinical presentation and prognosis of these patients.Several studies investigated the efficacy of BCAAs supplementation as a therapeutic option in liver cirrhosis,but uncertainties remain about the real efficacy,the best route of administration,and dosage.展开更多
The intimate connection and the strict mutual cooperation between the gut and the liver realizes a functional entity called gut-liver axis.The integrity of intestinal barrier is crucial for the maintenance of liver ho...The intimate connection and the strict mutual cooperation between the gut and the liver realizes a functional entity called gut-liver axis.The integrity of intestinal barrier is crucial for the maintenance of liver homeostasis.In this mutual relationship,the liver acts as a second firewall towards potentially harmful substances translocated from the gut,and is,in turn,is implicated in the regulation of the barrier.Increasing evidence has highlighted the relevance of increased intestinal permeability and consequent bacterial translocation in the development of liver damage.In particular,in patients with non-alcoholic fatty liver disease recent hypotheses are considering intestinal permeability impairment,diet and gut dysbiosis as the primary pathogenic trigger.In advanced liver disease,intestinal permeability is enhanced by portal hypertension.The clinical consequence is an increased bacterial translocation that further worsens liver damage.Furthermore,this pathogenic mechanism is implicated in most of liver cirrhosis complications,such as spontaneous bacterial peritonitis,hepatorenal syndrome,portal vein thrombosis,hepatic encephalopathy,and hepatocellular carcinoma.After liver transplantation,the decrease in portal pressure should determine beneficial effects on the gut-liver axis,although are incompletely understood data on the modifications of the intestinal permeability and gut microbiota composition are still lacking.How the modulation of the intestinal permeability could prevent the initiation and progression of liver disease is still an uncovered area,which deserves further attention.展开更多
BACKGROUND In non-alcoholic fatty liver disease(NAFLD), a high-fat or high-fructose diet increases intestinal permeability and promotes derangement of the gut-liver axis.We hypothesize that, diet could be able to modu...BACKGROUND In non-alcoholic fatty liver disease(NAFLD), a high-fat or high-fructose diet increases intestinal permeability and promotes derangement of the gut-liver axis.We hypothesize that, diet could be able to modulate intestinal permeability in patients with NAFLD.AIM To detect diet-induced modification of intestinal permeability in patients with NAFLD undergoing a Mediterranean diet or a low-fat diet.METHODS The current study was a dietary intervention for non-diabetic, patients with biopsy-verified NAFLD and increased transaminases. A crossover design was employed: participants underwent 16 weeks of Mediterranean diet, 16 wk of free wash-out, and 16 weeks of low-fat diet. Both diets were hypocaloric and no consumption of supplements was allowed. All patients were followed bimonthly by a dietitian. Evaluations of clinical and metabolic parameters were completed at baseline and at the end of each dietary period. Intestinal permeability was assessed by chromium-51 ethylene diamine tetraacetate excretion testing(51 CrEDTA).RESULTS Twenty Caucasian patients, 90% male, median age 43 years, body mass index(BMI) 30.9, with biopsy-verified NAFLD were enrolled. At the end of 16 weeks of a Mediterranean diet, a significant reduction in mean body weight(-5.3 ± 4.1 kg,P = 0.003), mean waist circumference(-7.9 ± 4.9 cm, P = 0.001), and mean transaminase levels [alanine aminotransferase(ALT)-28.3 ± 11.9 IU/L, P =0.0001; aspartate aminotransferase(AST)-6.4 ± 56.3 IU/L, P = 0.01] were observed. These benefits were maintained after 16 wk of wash-out and also after16 wk of low-fat diet, without further improvements. Fourteen of the 20 patients had intestinal permeability alteration at baseline(mean percentage retention of51 Cr-EDTA = 5.4%), but no significant changes in intestinal permeability were observed at the end of the 16 wk of the Mediterranean diet or 16 wk of the low-fat diet.CONCLUSION Mediterranean diet is an effective strategy for treating overweight, visceral obesity and serum transaminase in patients with NAFLD. If the Mediterranean diet can improve intestinal permeability in patients with NAFLD, it deserves further investigation.展开更多
In recent years,the traditional concept that cirrhosis-related coagulopathy is an acquired bleeding disorder has evolved.Currently,it is known that in cirrhotic patients,the hemostatic system is rebalanced,which invol...In recent years,the traditional concept that cirrhosis-related coagulopathy is an acquired bleeding disorder has evolved.Currently,it is known that in cirrhotic patients,the hemostatic system is rebalanced,which involves coagulation factors,fibrinolysis and platelets.These alterations disrupt homeostasis,skewing it toward a procoagulant state,which can lead to thromboembolic manifestations,especially when hemodynamic and endothelial factors co-occur,such as in the portal vein system in cirrhosis.Portal vein thrombosis is a common complication of advanced liver cirrhosis that negatively affects the course of liver disease,prognosis of cirrhotic patients and success of liver transplantation.It is still debated whether portal vein thrombosis is the cause or the consequence of worsening liver function.Anticoagulant therapy is the mainstay treatment for acute symptomatic portal vein thrombosis.In chronic portal vein thrombosis,the role of anticoagulant therapy is still unclear.Traditional anticoagulants,vitamin K antagonists and low-molecular-weight heparin are standard-of-care treatments for portal vein thrombosis.In the last ten years,direct oral anticoagulants have been approved for the prophylaxis and treatment of many thromboembolicrelated diseases,but evidence on their use in cirrhotic patients is very limited.The aim of this review was to summarize the evidence about the safety and effectiveness of direct oral anticoagulants for treating portal vein thrombosis in cirrhotic patients.展开更多
AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC) and to ascertain the factors predicting the achievement of disease control(DC).METH...AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC) and to ascertain the factors predicting the achievement of disease control(DC).METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. RESULTS One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo(95%CI: 10.6-17.0). Only alphafetoprotein(AFP) serum level > 200 ng/m L and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up(HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year(HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC(OR = 0.263, 95%CI: 0.111-0.622, P = 0.002).CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients' survival confers them as useful predictive tools for treatment management and clinical decisions.展开更多
Hepatocellular carcinoma is becoming an increasing indication for liver transplantation, but selection and allocation of patients are challenging because of organ shortages. Conventional Milan criteria are the referen...Hepatocellular carcinoma is becoming an increasing indication for liver transplantation, but selection and allocation of patients are challenging because of organ shortages. Conventional Milan criteria are the reference for the selection of patients worldwide, but many expanded criteria, like University of California San Francisco criteria and up-to-7 criteria, have demonstrated that survival and recurrence results are lower than those for restricted indications. Correct staging is crucial and should include surrogate markers of biological aggressiveness(α-fetoprotein, response to loco-regional treatments). Successful down-staging can select between patients with tumor burden initially beyond transplantation criteria those with a more favorable biology, provided a 3-mo stability in meeting the transplantation criteria. Allocation rules are constantly adjusted to minimize the imbalance between the priorities of candidates with and without hepatocellular carcinoma, and take into account local donor rate and waitlist dynamics. Recently, Mazzaferro et al proposed a benefit-oriented "adaptive approach", in which the selection and allocation of patients are based on their response to non-transplantation treatments: low priority for transplantation in case of complete response, high priority in case of partial response or recurrence, and no listing in case of progression beyond transplantation criteria.展开更多
Introduction The Society for Vascular Surgery recommends treating nonruptured splenic artery aneurysms(SAAs)of>3 cm with a demonstrable increase in size or with associated symptoms[1].Percutaneous intervention with...Introduction The Society for Vascular Surgery recommends treating nonruptured splenic artery aneurysms(SAAs)of>3 cm with a demonstrable increase in size or with associated symptoms[1].Percutaneous intervention with embolization coils or covered stents has become popular due to its high technical success rates and low morbidity[2,3].展开更多
Introduction Severe thrombocytopenia(platelet count<50×10^(9)/L)occurs in 1%–2%of patients with liver cirrhosis and is associated with an increased risk of bleeding[1].In this clinical setting,there is no def...Introduction Severe thrombocytopenia(platelet count<50×10^(9)/L)occurs in 1%–2%of patients with liver cirrhosis and is associated with an increased risk of bleeding[1].In this clinical setting,there is no definite agreement on the platelet cut-off below which bleeding risk increases.However,in vitro evidence indicates that thrombin generation is preserved in patients with cirrhosis and platelet counts of>56×10^(9)/L[2].Observational studies found that severe thrombocytopenia may be predictive of post-procedure bleeding after liver biopsy,dental extractions,percutaneous ablation of liver tumors,and endoscopic polypectomy[3].展开更多
文摘BACKGROUND Few studies have evaluated the frequency of and the reasons behind the refusal of listing liver transplantation candidates.AIM To assess the ineligibility rate for liver transplantation and its motivations.METHODS A single-center retrospective study was conducted on adult patients which entailed a formal multidisciplinary assessment for liver transplantation eligibility.The predictors for listing were evaluated using multivariable logistic regression.RESULTS In our center,314 patients underwent multidisciplinary work-up before liver transplantation enlisting over a three-year period.The most frequent reasons for transplant evaluation were decompensated cirrhosis(51.6%)and hepatocellular carcinoma(35.7%).The non-listing rate was 53.8%and the transplant rate was 34.4%for the whole cohort.Two hundred and five motivations for ineligibility were collected.The most common contraindications were psychological(9.3%),cardiovascular(6.8%),and surgical(5.9%).Inappropriate or premature referral accounted for 76(37.1%)cases.On multivariable analysis,a referral from another hospital(OR:2.113;95%CI:1.259–3.548)served as an independent predictor of non-listing.CONCLUSION A non-listing decision occurred in half of our cohort and was based on an inappropriate or premature referral in one case out of three.The referral from another hospital was taken as a strong predictor of non-listing.
文摘Liver cirrhosis is commonly associated with nutritional alterations,reported in 20% of patients with compensated disease and over 60% of patients with decompensated cirrhosis.Nutritional disturbances are associated with a worse prognosis and increased risk of complication.Serum levels of branched-chain amino acids(BCAAs)are decreased in patients with liver cirrhosis.The imbalance of amino acids levels has been suggested to be associated with the development of complications,such as hepatic encephalopathy and sarcopenia,and to affect the clinical presentation and prognosis of these patients.Several studies investigated the efficacy of BCAAs supplementation as a therapeutic option in liver cirrhosis,but uncertainties remain about the real efficacy,the best route of administration,and dosage.
文摘The intimate connection and the strict mutual cooperation between the gut and the liver realizes a functional entity called gut-liver axis.The integrity of intestinal barrier is crucial for the maintenance of liver homeostasis.In this mutual relationship,the liver acts as a second firewall towards potentially harmful substances translocated from the gut,and is,in turn,is implicated in the regulation of the barrier.Increasing evidence has highlighted the relevance of increased intestinal permeability and consequent bacterial translocation in the development of liver damage.In particular,in patients with non-alcoholic fatty liver disease recent hypotheses are considering intestinal permeability impairment,diet and gut dysbiosis as the primary pathogenic trigger.In advanced liver disease,intestinal permeability is enhanced by portal hypertension.The clinical consequence is an increased bacterial translocation that further worsens liver damage.Furthermore,this pathogenic mechanism is implicated in most of liver cirrhosis complications,such as spontaneous bacterial peritonitis,hepatorenal syndrome,portal vein thrombosis,hepatic encephalopathy,and hepatocellular carcinoma.After liver transplantation,the decrease in portal pressure should determine beneficial effects on the gut-liver axis,although are incompletely understood data on the modifications of the intestinal permeability and gut microbiota composition are still lacking.How the modulation of the intestinal permeability could prevent the initiation and progression of liver disease is still an uncovered area,which deserves further attention.
基金the Italian Ministry of Education,University and Research(MIUR),scientific research programs of relevant national interest year 2010-2011,No.2010C4JJWB
文摘BACKGROUND In non-alcoholic fatty liver disease(NAFLD), a high-fat or high-fructose diet increases intestinal permeability and promotes derangement of the gut-liver axis.We hypothesize that, diet could be able to modulate intestinal permeability in patients with NAFLD.AIM To detect diet-induced modification of intestinal permeability in patients with NAFLD undergoing a Mediterranean diet or a low-fat diet.METHODS The current study was a dietary intervention for non-diabetic, patients with biopsy-verified NAFLD and increased transaminases. A crossover design was employed: participants underwent 16 weeks of Mediterranean diet, 16 wk of free wash-out, and 16 weeks of low-fat diet. Both diets were hypocaloric and no consumption of supplements was allowed. All patients were followed bimonthly by a dietitian. Evaluations of clinical and metabolic parameters were completed at baseline and at the end of each dietary period. Intestinal permeability was assessed by chromium-51 ethylene diamine tetraacetate excretion testing(51 CrEDTA).RESULTS Twenty Caucasian patients, 90% male, median age 43 years, body mass index(BMI) 30.9, with biopsy-verified NAFLD were enrolled. At the end of 16 weeks of a Mediterranean diet, a significant reduction in mean body weight(-5.3 ± 4.1 kg,P = 0.003), mean waist circumference(-7.9 ± 4.9 cm, P = 0.001), and mean transaminase levels [alanine aminotransferase(ALT)-28.3 ± 11.9 IU/L, P =0.0001; aspartate aminotransferase(AST)-6.4 ± 56.3 IU/L, P = 0.01] were observed. These benefits were maintained after 16 wk of wash-out and also after16 wk of low-fat diet, without further improvements. Fourteen of the 20 patients had intestinal permeability alteration at baseline(mean percentage retention of51 Cr-EDTA = 5.4%), but no significant changes in intestinal permeability were observed at the end of the 16 wk of the Mediterranean diet or 16 wk of the low-fat diet.CONCLUSION Mediterranean diet is an effective strategy for treating overweight, visceral obesity and serum transaminase in patients with NAFLD. If the Mediterranean diet can improve intestinal permeability in patients with NAFLD, it deserves further investigation.
文摘In recent years,the traditional concept that cirrhosis-related coagulopathy is an acquired bleeding disorder has evolved.Currently,it is known that in cirrhotic patients,the hemostatic system is rebalanced,which involves coagulation factors,fibrinolysis and platelets.These alterations disrupt homeostasis,skewing it toward a procoagulant state,which can lead to thromboembolic manifestations,especially when hemodynamic and endothelial factors co-occur,such as in the portal vein system in cirrhosis.Portal vein thrombosis is a common complication of advanced liver cirrhosis that negatively affects the course of liver disease,prognosis of cirrhotic patients and success of liver transplantation.It is still debated whether portal vein thrombosis is the cause or the consequence of worsening liver function.Anticoagulant therapy is the mainstay treatment for acute symptomatic portal vein thrombosis.In chronic portal vein thrombosis,the role of anticoagulant therapy is still unclear.Traditional anticoagulants,vitamin K antagonists and low-molecular-weight heparin are standard-of-care treatments for portal vein thrombosis.In the last ten years,direct oral anticoagulants have been approved for the prophylaxis and treatment of many thromboembolicrelated diseases,but evidence on their use in cirrhotic patients is very limited.The aim of this review was to summarize the evidence about the safety and effectiveness of direct oral anticoagulants for treating portal vein thrombosis in cirrhotic patients.
文摘AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC) and to ascertain the factors predicting the achievement of disease control(DC).METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. RESULTS One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo(95%CI: 10.6-17.0). Only alphafetoprotein(AFP) serum level > 200 ng/m L and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up(HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year(HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC(OR = 0.263, 95%CI: 0.111-0.622, P = 0.002).CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients' survival confers them as useful predictive tools for treatment management and clinical decisions.
文摘Hepatocellular carcinoma is becoming an increasing indication for liver transplantation, but selection and allocation of patients are challenging because of organ shortages. Conventional Milan criteria are the reference for the selection of patients worldwide, but many expanded criteria, like University of California San Francisco criteria and up-to-7 criteria, have demonstrated that survival and recurrence results are lower than those for restricted indications. Correct staging is crucial and should include surrogate markers of biological aggressiveness(α-fetoprotein, response to loco-regional treatments). Successful down-staging can select between patients with tumor burden initially beyond transplantation criteria those with a more favorable biology, provided a 3-mo stability in meeting the transplantation criteria. Allocation rules are constantly adjusted to minimize the imbalance between the priorities of candidates with and without hepatocellular carcinoma, and take into account local donor rate and waitlist dynamics. Recently, Mazzaferro et al proposed a benefit-oriented "adaptive approach", in which the selection and allocation of patients are based on their response to non-transplantation treatments: low priority for transplantation in case of complete response, high priority in case of partial response or recurrence, and no listing in case of progression beyond transplantation criteria.
文摘Introduction The Society for Vascular Surgery recommends treating nonruptured splenic artery aneurysms(SAAs)of>3 cm with a demonstrable increase in size or with associated symptoms[1].Percutaneous intervention with embolization coils or covered stents has become popular due to its high technical success rates and low morbidity[2,3].
文摘Introduction Severe thrombocytopenia(platelet count<50×10^(9)/L)occurs in 1%–2%of patients with liver cirrhosis and is associated with an increased risk of bleeding[1].In this clinical setting,there is no definite agreement on the platelet cut-off below which bleeding risk increases.However,in vitro evidence indicates that thrombin generation is preserved in patients with cirrhosis and platelet counts of>56×10^(9)/L[2].Observational studies found that severe thrombocytopenia may be predictive of post-procedure bleeding after liver biopsy,dental extractions,percutaneous ablation of liver tumors,and endoscopic polypectomy[3].
