Frequency of and reasons behind non-listing in adult patients referred for liver transplantation: Results from a retrospective study

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.

Branched chain amino acids in hepatic encephalopathy and sarcopenia in liver cirrhosis:Evidence and uncertainties

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.

Intestinal permeability in the pathogenesis of liver damage: From non-alcoholic fatty liver disease to liver transplantation

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.

Liver toxicity of rosuvastatin therapy

We report here a case of clinically significant liver toxicity after a brief course of rosuvastatin, which is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Whether rosuvastatin has a greater potential compared with other statins to damage the liver is unclear and the involved mechanisms are also unknown. However, rosuvastatin is taken up by hepatocytes more selectively and more efficiently than other statins, and this may reasonably represent an important variable to explain the hepatotoxic potential of rosuvastatin. Our report supports the view that a clinically significant risk of liver toxicity should be considered even when rosuvastatin is given at the range of doses used in common clinical practice.

Intestinal permeability after Mediterranean diet and low-fat diet in non-alcoholic fatty liver disease

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.

Tumor necrosis factor-α inhibitors and chronic hepatitis C:A comprehensive literature review

Tumor necrosis factor-α(TNF-α)inhibitors are known to increase reactivation of concurrent chronic hepatitis B,but their impact on the hepatitis C virus(HCV)is controversial.Some conditions of immunosuppression,such as liver transplantation,typically cause an increase in the rate of HCV evolution.Inhibition of TNF-α,a cytokine involved in the apoptotic signaling pathway of hepatocytes infected by HCV,could potentially increase viral replication.Currently available clinical data appear to contradict this hypothesis.A review of medical literature revealed that a total of 216 patients with HCV were exposed to one or more treatments with TNF-αinhibitors,with a median observation time of 1.2 years and 260 cumulative patient-years of exposure.Only three cases of drug withdrawal due to suspected HCV liver disease recrudescence were reported.Treatment with TNF-αinhibitors in patients with HCV infection appears to be safe in the short term,but there are insufficient data to assess their long-term safety.Universal screening for HCV before beginning treatment with TNF-αinhibitors is currently controversial.The presence of HCV is not a contraindication to therapy with TNF-αinhibitors,with the exception of cirrhotic patients.In cases of cirrhosis,the benefit/risk ratio should be evaluated at the individual level.Prior to treatment with TNF-αinhibitors,patients with HCV should be referred to a hepatologist to determine the necessity of hepatic disease assessment,using liver biopsy or noninvasive methods,and the potential indication for antiviral therapy.In patients with HCV infection who are treated with TNF-αinhibitors,liver function monitoring every three months is advised.

Ethanol injection is highly effective for hepatocellular carcinoma smaller than 2cm

AIM： To analyze the long-term prognosis in a cohort of western cirrhotic patients with single hepatocellular carcinoma treated with ethanol injection.METHODS： One-hundred forty-eight patients with solitan/hepatocellular carcinoma were enrolled. The tumor diameter was lower than 2 cm in 47 patients but larger in the remaining 101 patients. The impact of some pre- treatment clinical and laboratory parameters and of tu- mor recurrence on patients＇ survival was assessed.RESULTS： Among the pre-treatment parameters, only a tumor diameter of less than 2 cm was an independent prognostic factor of survival. The occurrence of new nodules in other liver segments and the neoplastic portal invasion were linked to a poorer prognosis at univariate analysis. Patients with a single hepatocellular carcinoma smaller than 2 cm showed a better 5-year cumulative survival （73.0% vs 47.9%） （P = 0.009）, 3-year local re- currence rate （29.1% vs 51.5%） （P = 0.011）, and 5-year distant intrahepatic recurrence rate （52.g% vs 62.8%） （P = 0.054） compared to patients with a larger tumor. CONCLUSION： The 5-year survival rate of patients with single hepatocellular carcinoma 〈 2 cm undergoing ethanol injection is excellent and comparable to that achieved using radiofrequency ablation.

Hepatocellular carcinoma treated by conventional transarterial chemoembolization in field-practice:Serum sodium predicts survival

AIM: To assess the prognostic role of baseline clinical, biochemical and radiological characteristics of patients with hepatocellular carcinoma (HCC) treated with the first transarterial chemoembolization (TACE) procedure.

Reverse time-dependent effect of alphafetoprotein and disease control on survival of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma

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.

Liver transplantation for intermediate hepatocellular carcinoma: An adaptive approach

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.

Two elective invasive procedures after a single avatrombopag treatment in a patient with liver cirrhosis and severe thrombocytopenia

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].