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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., Competing Interests: Conflict-of-interest statement: Dr. Biolato has nothing to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

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., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

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., Competing Interests: Conflict-of-interest statement: Nothing to declare.

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 (51Cr-EDTA)., 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 after 16 wk of low-fat diet, without further improvements. Fourteen of the 20 patients had intestinal permeability alteration at baseline (mean percentage retention of 51Cr-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., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report.

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/mL 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., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest.

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., Methods: Patients with HCC treated with conventional TACE in a tertiary care setting from 1997 to 2008 were retrospectively reviewed. Predictors of survival were identified using the Cox proportional regression model., Results: Two hundred and seventy patients were included. Median age was 66 years, 81% were male, 58% were HCV-positive, 18% hepatitis B surface antigen-positive, 64% had a Child A status, 40% patients had a largest nodule diameter ≥ 5 cm and 32% had more than 3 tumor nodules. Median overall survival of the whole cohort was 25 mo (95%CI: 21.8-28.2) and the 1-, 2- and 3-year probability of survival was 80%, 50% and 31%, respectively. Non-tumor segmental portal vein thrombosis (HR = 1.76, 95%CI: 1.22-2.54), serum sodium (HR = 1.65, 95%CI: 1.25-2.18), diameter of largest nodule (HR = 1.59, 95%CI: 1.22-2.091), number of nodules (HR = 1.41, 95%CI: 1.06-1.88), alpha-fetoprotein (HR = 1.35, 95%CI: 1.03-1.76) and alkaline phosphatase (HR = 1.33, 95%CI: 1.01-1.74) were independent prognostic factors for overall survival on multivariate analysis., Conclusion: The inclusion of serum sodium alongside the already known prognostic factors may allow a better prognostic definition of patients with HCC as candidates for conventional TACE.

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-α inhibitors, 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-α inhibitors 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-α inhibitors is currently controversial. The presence of HCV is not a contraindication to therapy with TNF-α inhibitors, 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-α inhibitors, patients with HCV should be referred to a hepatologist to determine the necessity of hepatic disease assessment, using liver biopsy or non-invasive methods, and the potential indication for antiviral therapy. In patients with HCV infection who are treated with TNF-α inhibitors, liver function monitoring every three months is advised.

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 solitary 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 tumor 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 recurrence rate (29.1% vs 51.5%) (P = 0.011), and 5-year distant intrahepatic recurrence rate (52.9% 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.

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.