Search

Background & Aims: Utility, a major principle for allocation in the context of transplantation, is questioned in patients with acute-on chronic liver failure grade 3 (ACLF-3) who undergo liver transplantation (LT). We aimed to explore long-term outcomes of patients included in a three-centre retrospective French study published in 2017., Method: All patients with ACLF-3 (n = 73), as well as their transplanted matched controls with ACLF-2 (n = 145), 1 (n = 119) and no ACLF (n = 292), who participated in the Princeps study published in 2017 were included. We explored 5- and 10-year patient and graft survival rates, causes of death and their predictive factors., Results: Median follow-up of patients with ACLF-3 was 7.5 years. At LT, median MELD was 40. In patients with ACLF-3, 2, 1 and no ACLF, 5-year patient survival rates were 72.6% vs. 69.7% vs. 76.4% vs. 77.0%, respectively (p = 0.31). Ten-year patient survival for ACLF-3 was 56.8% and was not different to other groups (p = 0.37). Leading causes of death in patients with ACLF-3 were infections (33.3%) and cardiovascular events (23.3%). After exclusion of early death, UCLA futility risk score, age-adjusted Charlson comorbidity index and CLIF-C ACLF score were independently associated with 10-year patient survival. Long-term graft survival rates were not different across the groups. Clinical frailty scale and WHO performance status improved over time in patients alive after 5 years., Conclusion: 5- and 10-year patient and graft survival rates were not different in patients with ACLF-3 compared to matched controls. 5-year patient survival is higher than the 50%-70% threshold defining the utility of a liver graft. Efforts should focus on candidate selection based on comorbidities, as well as the prevention of infection and cardiovascular events., Impact and Implications: While short-term outcomes following liver transplantation in the most severely ill patients with cirrhosis (acute-on-chronic liver failure grade 3 [ACLF-3]) are known, long-term data are limited, raising questions about the utility of graft allocation in the context of scarce medical resources. This study provides a favourable long-term update, confirming no differences in 5- and 10-year patient and graft survival following liver transplantation in patients with ACLF-3 compared to matched patients with ACLF-2, ACLF-1, and no-ACLF. The study highlights the risk of dying from infection and cardiovascular causes in the long-term and identifies scores including comorbidity evaluation, such as the age-adjusted Charlson comorbidity index, as independently associated with long-term survival. Therefore, physicians should consider the cumulative burden of comorbidities when deciding whether to transplant these patients. Additionally, after transplantation, the study encourages mitigating infectious risk with tailored immunosuppressive regimens and tightly managing cardiovascular risk over time., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Chronic hepatitis C Virus (HCV) infection presents a global health challenge, with significant morbidity and mortality worldwide. Despite remarkable progress in treatment options, achieving elimination targets by 2030, as set by the World Health Organization, remains elusive. Our study aimed to address this gap by integrating HCV screening into a national breast cancer screening program. Between March 2022 and March 2023, a prospective cross-sectional multicenter study was conducted in four radiology centers in Montpellier, France. We proposed HCV screening to consecutive women undergoing mammography, targeting 1,500 participants aged 50-74 years. A rapid diagnostic test (RDT) for HCV antibodies (HCV Ab) was performed on capillary whole blood, with positive cases undergoing serological and RNA confirmation. Participants also completed a questionnaire on demographic data and risk factors. Acceptance rates, HCV prevalence, and linkage to care were assessed. The acceptance rate for this integrated screening approach was 82.4%. Notably, the seroprevalence of HCV was found to be 0.65%. Linkage to care was prompt, and the cascade of care demonstrated successful treatment outcomes. Importantly, the majority of detected infections were successfully resolved. These findings underscore the feasibility and acceptability of integrating HCV screening with breast cancer screening programs providing updated prevalence data and valuable insights for refining future screening strategies., (© 2024 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Background: Partial splenic embolization (PSE) has been proposed to treat the consequences of hypersplenism in the context of portal hypertension, especially thrombocytopenia. However, a high morbidity/mortality rate has made this technique unpopular. We conducted a multicenter retrospective nationwide French study to reevaluate efficacy and tolerance., Methods: All consecutive patients who underwent PSE for hypersplenism and portal hypertension in 7 tertiary liver centers between 1998 and 2023 were included., Results: The study population consisted of 91 procedures in 90 patients, with a median age of 55.5 years [range 18-83]. The main cause of portal hypertension was cirrhosis (84.6 %). The main indications for PSE were (1) an indication of medical treatment or radiological/surgical procedure in the context a severe thrombocytopenia (59.3 %), (2) a chronic hemorrhagic disorder associated with a severe thrombocytopenia (18.7 %), and (3) a chronic pain associated with a major splenomegaly (9.9 %). PSE was associated with a transjugular intrahepatic portosystemic shunt in 20 cases. Median follow-up after PSE was 41.9 months [0.5-270.5]. Platelet count increased from a median of 48.0 G/L [IQR 37.0; 60.0] to 100.0 G/L [75.0; 148]. Forty-eight patients (52.7 %) had complications after PSE; 25 cases were considered severe (including 7 deaths). A Child-Pugh B-C score (p < 0.02) was significantly associated with all complications, a history of portal vein thrombosis (p < 0.01), and the absence of prophylactic antibiotherapy (p < 0.05) with severe complications., Conclusion: Our results strongly confirm that PSE is very effective, for a long time, although a quarter of the patients experienced severe complications. Improved patient selection (exclusion of patients with portal vein thrombosis and decompensated cirrhosis) and systematic prophylactic antibiotherapy could reduce morbidity and early mortality in the future., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background and Aim: Germline mutations of telomere-related genes (TRG) induce multiorgan dysfunction, and liver-specific manifestations have not been clearly outlined. We aimed to describe TRG mutations-associated liver diseases., Approach and Results: Retrospective multicenter analysis of liver disease (transaminases > 30 IU/L and/or abnormal liver imaging) in patients with TRG mutations. Main measurements were characteristics, outcomes, and risk factors of liver disease in a TRG mutations cohort. The prevalence of liver disease was compared to a community-based control group (n = 1190) stratified for age and matched 1:3 for known risk factors of liver disease. Among 132 patients with TRG mutations, 95 (72%) had liver disease, with associated lung, blood, skin, rheumatological, and ophthalmological TRG diseases in 82%, 77%, 55%, 39%, and 30% of cases, respectively. Liver biopsy was performed in 52/95 patients, identifying porto-sinusoidal vascular disease in 48% and advanced fibrosis/cirrhosis in 15%. After a follow-up of 21 months (12-54), ascites, hepato-pulmonary syndrome, variceal bleeding, and HCC occurred in 14%, 13%, 13%, and 2% of cases, respectively. Five-year liver transplantation-free survival was 69%. A FIB-4 score ≥ 3·25 and ≥1 risk factor for cirrhosis were associated with poor liver transplantation-free survival. Liver disease was more frequent in patients with TRG mutations than in the paired control group [80/396, (20%)], OR 12.9 (CI 95%: 7.8-21.3, p < 0.001)., Conclusions: TRG mutations significantly increase the risk of developing liver disease. Although symptoms may be mild, they may be associated with severe disease. Porto-sinusoidal vascular disease and cirrhosis were the most frequent lesions, suggesting that the mechanism of action is multifactorial., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background and Aims: In patients with noncirrhotic chronic extrahepatic portal vein obstruction (EHPVO), data on the morbimortality of abdominal surgery are scarce., Approach and Results: We retrospectively analyzed the charts of 76 patients (78 interventions) with EHPVO undergoing abdominal surgery within the Vascular Disease Interest Group network. Fourteen percent of the patients had ≥1 major bleeding (unrelated to portal hypertension) and 21% had ≥1 Dindo-Clavien grade ≥3 postoperative complications within 1 month after surgery. Fifteen percent had ≥1 portal hypertension-related complication within 3 months after surgery. Three patients died within 12 months after surgery. An unfavorable outcome (ie, ≥1 abovementioned complication or death) occurred in 37% of the patients and was associated with a history of ascites and with nonwall, noncholecystectomy surgical intervention: 17% of the patients with none of these features had an unfavorable outcome, versus 48% and 100% when one or both features were present, respectively. We then compared 63/76 patients with EHPVO with 126 matched (2:1) control patients without EHPVO but with similar surgical interventions. As compared with control patients, the incidence of major bleeding ( p <0.001) and portal hypertension-related complication ( p <0.001) was significantly higher in patients with EHPVO, but not that of grade ≥3 postoperative complications nor of death. The incidence of unfavorable postoperative outcomes was significantly higher in patients with EHPVO than in those without (33% vs. 18%, p =0.01)., Conclusions: Patients with EHPVO are at high risk of major perioperative or postoperative bleeding and postoperative complications, especially in those with ascites or undergoing surgery other than wall surgery or cholecystectomy., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Nirmatrelvir/ritonavir is a promising option for preventing severe COVID-19 in solid organ transplant recipients with SARS-CoV-2 infection. However, concerns have arisen regarding potential drug interactions with calcineurin inhibitors (CNI). This two-phase multicentre retrospective study, involving 113 patients on tacrolimus and 13 on cyclosporine A, aimed to assess the feasibility and outcomes of recommendations issued by The French societies of transplantation (SFT) and pharmacology (SFPT) for CNI management in this context. The study first evaluated adherence to recommendations, CNI exposure, and clinical outcomes. Notably, 96.5% of patients on tacrolimus adhered to the recommendations, maintaining stable tacrolimus trough concentrations (C 0 ) during nirmatrelvir/ritonavir treatment. After reintroduction, most patients experienced increased C 0 , with 42.9% surpassing 15 ng/mL, including three patients exceeding 40 ng/mL. Similar trends were observed in cyclosporine A patients, with no COVID-19-related hospitalizations. Moreover, data from 22 patients were used to refine the reintroduction strategy. Modelling analyses suggested reintroducing tacrolimus at 50% of the initial dose on day 8, and then at 100% from day 9 as the optimal approach. In conclusion, the current strategy effectively maintains consistent tacrolimus exposure during nirmatrelvir/ritonavir treatment, and a stepwise reintroduction of tacrolimus may be better suited to the low CYP3A recovery., Competing Interests: AD reports consultancy fees from Alnylam and Merck outside the submitted work. CM reports research grants (paid to institution), financial support for participation in congresses, and expertise fees from Chiesi and Astellas. StB received lecture fees from Astellas. BG reports financial support for participation in congresses from Chiesi and Gilead, speaker for Gilead, outside the submitted work. LC received lecture fees from Astellas, Chiesi, Novartis, Sandoz, Ostuka, GSK, and Biotest, and participated in advisory boards for Biotest, Hansa, and Novartis. LE received fees from Astellas, Chiesi, and Sandoz. FL received research grants (paid to institution) from Astellas, Sandoz, and Chiesi and fees to attend meetings from Viiv, MSD, Janssen-Cilag, Pfizer, and Gilead. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Boland, Devresse, Monchaud, Briol, Belaiche, Giguet, Couzi, Thaunat, Esposito, Meszaros, Roussoulieres, Haufroid, Le Meur and Lemaitre.)