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Primary sclerosing cholangitis is a cholestatic disease with a low prevalence in Italy. Indications for liver transplantation and the time of listing are not stated. We performed a national survey to investigate the listing criteria, comorbidities, and outcomes. In April 2022, we surveyed liver transplantation in primary sclerosing cholangitis nationwide for the last 15 years. From 2007 to 2021, 445 patients were included on waiting lists, and 411 had undergone liver transplants. The median age at transplantation was 46 years (males 63.9%); 262 patients (59%) presented an inflammatory bowel disease. Transplants increased over the years, from 1.8 % in 2007 to 3.0 % in 2021. Cholangitis (51%) and hepatic decompensation (45%) were the main indications for listing. The disease recurred in 81 patients (20%). Patient survival after the first transplant was 94 %, 86% and 84% at one, five, and ten years. Twenty-four died in the first year (50% surgical complications, 25% infections); 33 between one to five years (36% recurrence, 21% cholangiocarcinoma recurrence) and nine after five years (56% de novo cancer, 44% recurrence). Primary sclerosing cholangitis has been an increasing indication for transplantation in Italy. Cholangitis and decompensation were the main indications for listing. Recurrence and cancer were the leading causes of death. [ABSTRACT FROM AUTHOR]

Coagulation in cirrhosis involves a complex imbalance between procoagulant and anticoagulant factors due to liver dysfunction. This results in a delicate hemostatic equilibrium that increases the risk of both bleeding and thrombosis. To analyze the occurrence of thromboembolic events in a prospective series of patients with liver cirrhosis, and to assess patients' characteristics. We prospectively enrolled 188 patients with cirrhosis admitted to our gastrointestinal ward (December 2021-December 2022). We evaluated general and liver disease-related characteristics as well as the incidence of venous thromboembolism (VTE), and death during the first year following hospital admission. Median age was 63 years, and 72.9% were males. The primary cause of hospitalization was acute decompensation (n=101, 53.7%), followed by hepatocellular carcinoma (n=34, 18.1%) or liver-related elective diagnostic-therapeutic procedures (28, 14.9%). Twenty-five (13.3%) patients were admitted due to non-liver related events. The median length of hospitalization was 9 days (IQR 5-14). Most of patients had decompensated cirrhosis (Child-Pugh B: 41.5%; Child-Pugh C: 26.6%), with median MELD-Na=14, and clinically significant portal-hypertension (CSPH) in 148 (78.7%). Sixty-two (32.9%) patients had hepatocellular carcinoma. Thirty-one patients (16.5%) were on anticoagulants. During a 1-year follow-up, three (1.6%) patients experienced VTE while 26 (13.8%) patients had variceal bleeding. Overall mortality was 42.0% (n=79). Padua and Improve-VTE risk scores, MELD-Na, Child-Pugh class, and presence of CSPH were no different between patients with or without VTE. A competitive-risk model focused on experiencing VTE and risk of death and bleeding as competing events showed no significant association between VTE and use of anticoagulant, Charlson comorbidity index, CSPH, male gender, HCC, length of hospitalization and Improve-VTE, Padua and MELD-Na scores. VTE is a rare event in patients with cirrhosis, occurring in only 1.6% of prospectively evaluated population, and no significant association between VTE and various risk factors was identified. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are commonly prescribed for gastroesophageal reflux disease (GERD) or prophylaxis of non-steroidal anti-inflammatory drugs and aspirin-induced gastric damage. However, their prolonged use in cirrhotic patients has been linked to complications like spontaneous bacterial peritonitis (SBP) and hepatic encephalopathy (EE). To evaluate the appropriateness of PPI therapy in patients with cirrhosis. We reviewed medical records of 209 cirrhotic patients admitted to our gastrointestinal ward (December 2021-December 2022). Demographics, clinical characteristics, PPI use indications, and incidence of EE and SBP were assessed. The median age was 69 years, and 74.4% were males. Main reasons for hospitalization were hepatocellular carcinoma (n=63, 28.7%), elective diagnostic-therapeutic procedures (n=63, 28.7%), non-liver-related events (n=54, 24.7%), and acute decompensation (n=39, 17.7%). Etiology of liver disease was alcohol in 91 patients (41.6%), virus-related in 77 (35.1%), and metabolic-associated in 30 (13.7%). The median MELD-Na score was 10 (8-14). At admission, 145 patients (66.2%) were on PPIs: of these, 42 patients (29.0%) had confirmed GERD, 12 (8.3%) had esophagitis ≥grade B, and 27 (18.6%) were on aspirin with bleeding risk-factors. Overall, inappropriate PPI use was observed in 74 patients (44.1%). Patients on PPIs were older, with higher MELD-Na and creatinine, and lower hemoglobin and Na compared to those not on PPIs (p<0.05). Multivariate analysis showed that PPI use was independently associated with older age (OR 1.03, IC95% 1.01-1.07) and lower hemoglobin (OR 0.82, IC95% 0.70-0.97). During a median follow-up of 18 months, the incidence of EE and SBP did not differ between PPI users and non-users. A significant proportion of patients with cirrhosis is inappropriately prescribed PPIs. Although this did not correlate with major liver-related events in the short term, proper PPI prescription education is crucial to prevent potential long-term consequences. [ABSTRACT FROM AUTHOR]

Discontinuation of hepatitis B (HBV) immune globulin (HBIG) after liver transplantation (LT) for HBV-related cirrhosis with and without hepatocellular carcinoma (HCC) represents a challenging option. The adherence to this option in real-life practice is unknown. In a contemporary cohort of patients transplanted for HBV, with and without HCC, we aimed to; 1) assess the rate of HBV recurrence (HBV-R); 2) evaluate risk factors for HBV-R; 3) evaluate the association between HBV-R and HCC recurrence (HCC-R) and patient survival. This is a multicentric, retrospective study designed by the "Permanent Transplant Commission" of the Italian Association for the Study of the Liver. All recipients who underwent LT for HBV cirrhosis were included. Exclusion criteria were: LT prior to January 1, 2010; age <18 years old; combined transplantation; HIV coinfection; duration of follow-up after LT <12 months. HBV-R was defined by positivity of HBV-DNA and/or HBsAg. Uni and multivariate linear regression analysis were used to identify predictors of HBV/HCC-R. 1115 patients were included. Indications for LT were HCC (51%), decompensated cirrhosis (41.2%), acute on chronic liver failure (ACLF) (3.4%), and acute liver failure (ALF) (4.2%). Life-long HBIG + nuclos(t)ide analogues (NA) was the most common used prophylaxis (94.4%). Overall rate of HBV-R was 2.2% (median time after LT: 7 months). Patients under life-long HBIG + NA had lower rates of HBV-R than those in whom HBIG were withdrawn and those who received NA alone (1.4% vs. 10.7% vs. 13.6%; respectively, p<0.001). HBV-R was associated with a lower survival after LT (p=0.008). In patients transplanted for HCC (n=535), the rate of HBV-R was 2.8% and of HCC-R was 10.3% (median time from LT: 17 months). Rate of HBV-R was higher in patients with vs. without HCC-R (14.6% vs. 1.2%; p<0.001). Multivariate analysis showed that HBV-R was the only parameter independently associated with HCC-R (HR: 20; CI95% 5-86; p<0.001). HCC-R was associated with a significantly reduced survival after LT (5-year survival 36% vs. 94%; p<0.001). Life-long HBIG + NA is the most commonly used scheme for HBV-R prophylaxis after LT in Italy, leading to a low risk of HBV-recurrence. In LT recipients, HBV recurrence is associated with an increased risk of death. In patients transplanted for HCC, HBV-R is independently associated with HCC recurrence. Therefore, discontinuation of HBIG in these patients should be considered only in the setting of clinical trials [ABSTRACT FROM AUTHOR]

The safety and efficacy of atezolizumab/bevacizumab in patients with hepatocellular carcinoma (HCC) and impaired liver function is not completely defined. To address safety and efficacy of atezolizumab/bevacizumab in Child-Pugh class B patients reviewing the published data and analysing them by meta-analysis. Safety and efficacy of atezolizumab/becavizumab in patients with HCC and Child-Pugh B cirrhosis were compared to the respective figures in Child-Pugh A patients. Overall, 8 retrospective, non-randomized, cohort studies were identified, including a total of 1,071 class A and 225 class B patients. Adverse events grade ≥3 were observed in 11.8% and 26.8% of class A and B patients, respectively (P=0.0001; Odds Ratio 0.43, confidence interval 0.21–0.90; P=0.02). Median overall survival was 16.8±2.0 and 6.8±3.2 months in class A and B patients, respectively (mean difference 9.06 months, 7.01–11.1, P<0.0001). Progression Free Survival at both 6- (4.90±2.08 vs 4.75±2.08 months; P=0.0004) and 12-month (8.83±2.32 vs 7.26±2.33 months; P=0.002) was lower in class B patients. A trend towards higher Objective Response Rate (ORR) (25.6% vs 18.1%, P=0.070) and a significantly greater probability of obtaining an ORR was observed in class A patients (Odds Ratio 1.79, 1.12–2.86, P=0.02). Disease Control Rate (DCR) was observed in 78.4% of class A and in 66.9% of class B patients (P=0.102), although class A had significantly higher probability of DCR than class B patients (Odds Ratio 1.73, 1.17–2.56; P=0.006). Oncological efficacy of atezolizumab/bevacizumab is moderate in Child-Pugh class B patients, and the shorter survival figures associated with a greater likelihood of experiencing treatment-related adverse events observed in these patients compared to patients with less impaired liver function suggest caution and individualization of treatment. Comparative studies with best supportive care may provide further evidence supporting treatment in these patients. [ABSTRACT FROM AUTHOR]

Primary Sclerosing Cholangitis (PSC) is a rare condition with low incidence in countries of the Mediterranean Basin, such as Italy; the timing for listing and the indication for liver transplantation (LT) are not entirely stated. To investigate the Italian trend in indication, timing, and outcome for PSC LT. In April 2022, we conducted a nationwide survey of LT in PSC over the last 15 years. 85% of Italian LT Centers took part in the project. Clinical features, indications and outcomes were evaluated. From January 2007 to December 2021, 445 PSC patients have been included in the Italian LT waiting-lists, and 411 underwent LT. The median age at LT was 46 years (18-73), with a high prevalence of males (n=287, 70%). Over 15 years, the number of transplants for PSC increased from 20 to 42 per year, reaching 3.0% of all indications in 2021. Recurring cholangitis and hepatic decompensation were the main indications for listing. The dropout rate from the waiting-list was 6% (26/445), cholangiocarcinoma (CCA) not eligible for LT and being too sick were the leading causes. 71% of the LT Centers utilized induction therapy with Basiliximab. Tacrolimus+MMF was the combined therapy of choice. Overall post-LT mortality was 15% (66/441): 24 patients died in the first year (50% due to surgical complications and 25% infections); 33 patients died between 1 to 5 years (36% PSC recurrence, 21% occult CCA-recurrence) and 9 patients after 5 years (56% cancer, 44% PSC recurrence). Likewise other Countries, PSC has been an increasing indication for LT in Italy. The dropout rate from LT waiting-list was relatively low, and CCA not eligible for transplantation or being too sick for surgery were the leading causes. 5-year post-LT survival was 87%, being PSC-recurrence or neoplastic disease the main causes of death. [ABSTRACT FROM AUTHOR]

Abstract: Background: In the Western world, hepatocellular carcinoma seldom develops in patients without cirrhosis, and reports describing the characteristics of non-cirrhotic patients with hepatocellular carcinoma are rather infrequent. Methods: We evaluated the main clinical characteristics, treatment options, and survival of patients with hepatocellular carcinoma developed in non-cirrhotic liver among the 3027 consecutive cases of hepatocellular carcinoma accrued in the Italian Liver Cancer database during the last 20 years. Results: We identified 52 patients with hepatocellular carcinoma in non-cirrhotic livers (1.7% of all hepatocellular carcinomas), 42 with (80.8%) and 10 without (19.2%) chronic liver disease. In patients without chronic liver disease, median tumour diameter was greater compared to patients with chronic liver disease (7.8 versus 4.0cm, P =0.046). Curative treatment was feasible in 20 patients (38.5%). Median overall survival was 26 months and 5-year survival rate was 23.7%. Detection of hepatocellular carcinoma outside surveillance (P =0.036), advanced hepatocellular carcinoma stage (P <0.0001), and non-curative treatment (P =0.007) were associated with worse prognosis, but tumour stage was the only independent predictor of survival. Conclusions: In Italy, less than 2% of hepatocellular carcinomas develop in a non-cirrhotic liver, and almost never in a normal liver. These patients frequently present with advanced tumours, have low eligibility rates for curative treatment, and have a dismal prognosis despite their preserved liver function. [Copyright &y& Elsevier]