BACKGROUND & AIMS:Liver transplantation (LT) is increasingly performed in the setting of acute-on-chronic liver failure (ACLF). In this context, pre-transplant evaluation must be completed rapidly while minimizing the risk of overlooking contraindications. We aimed to describe current practices for pre-transplant assessment in patients with ACLF. METHODS:We conducted a survey across 34 European LT centers (including 16 French) and 22 French non-LT centers to assess pre-transplant evaluation practices, focusing on cardiopulmonary, addiction, oncological, and nutritional assessments. Practices were compared across three clinical scenarios: outpatients (OutPat), hospitalized decompensated patients without ACLF (Hosp), and patients with ACLF admitted to intensive care units (ACLF-ICU). In parallel, we retrospectively evaluated post-transplant outcomes in patients with cirrhosis and severe ACLF transplanted in two high-volume centers. RESULTS:Fifty-three centers (96%) responded. Cardiological stress testing was reported in 2% of ACLF-ICU patients vs. 21% of OutPat (p = 0.002) vs. 17% of Hosp patients (p = 0.008). Coronary angiography following abnormal non-invasive testing was less frequently performed in ACLF (42%) than in OutPat (76%, p = 0.0004) or Hosp patients (66%, p = 0.01). Alcohol abstinence requirements were more often decided on a case-by-case basis in patients with ACLF (62%) than in OutPat or Hosp patients. Oncological screening, including colonoscopy and ear, nose, and throat consultation, was also less frequently performed in ACLF-ICU patients. Median time from assessment initiation to listing was 7 days in ACLF-ICU vs. 45 days in OutPat and 18 days in Hosp patients (both p <0.0001). In the retrospective cohort (n = 221), patients listed after ACLF onset had a higher 1-year incidence of cardiovascular events than those listed before ACLF onset (19% vs. 9%). CONCLUSIONS:In ACLF-ICU patients, pre-transplant evaluation is markedly abbreviated, with critical gaps-particularly in cardiological assessment-highlighting the need for dedicated, evidence-based guidelines. IMPACT AND IMPLICATIONS:We sent a questionnaire to centers with an expertise in the management of patients with ACLF to assess current practices in pre-transplant evaluation in patients with ACLF admitted to an intensive care unit, as compared with patients without (outpatients and patients hospitalized in a regular ward). According to the responses from 53 centers, cardiological stress test and coronary angiography were less commonly performed as part of the pre-transplant evaluation in patients with ACLF admitted to the ICU, as well as colonoscopy and ear, nose, and throat consultation. Median timeframe from pre-LT workup initiation to listing was 7 days in patients with ACLF admitted to the ICU, which was significantly shorter than in patients without ACLF. These results suggest that pre-transplant workup is abbreviated in patients with ACLF, and might have an impact on post-transplant outcome, especially cardiovascular complications. Further dedicated studies are needed to specifically address the relation between pre-transplant workup and post-LT complications in patients with ACLF.

BACKGROUND & AIMS:Liver transplantation (LT) is indicated for liver complications related to hepatitis B virus (HBV) infection: acute liver failure (ALF), decompensated cirrhosis or hepatocellular carcinoma (HCC). The present study aimed to describe and evaluate patient survival after LT for HBV-related disease in France and identify the factors influencing survival. METHODS:The present retrospective cohort study based on medical record information included all adult patients transplanted with positive HBsAg (+/- coinfection with Hepatitis D virus (HDV)) between January 1, 2005 and December 31, 2023 in all French LT centres. RESULTS:The study population consisted of 1083 patients, the majority of whom were men (81.5%) with a median [IQR] age at LT listing of 52.8 [42.5-59.8] years. Indications for LT were HBV-related HCC (47.2%), HBV-related cirrhosis (28.5%), HDV-related cirrhosis (11.2%), HBV-related ALF (10.5%), HDV-related HCC (1.4%) and other (0.7%). Median [IQR] post-LT follow-up was 6.0 [2.2-11.1] years. Patient survival at 1, 5, 10 and 15 years after LT was 91.6%, 80.1%, 71.8% and 63.6% respectively. Multivariate analysis showed that independent significant prognostic factors were age at LT (HR: 1.030; 95CI: 1.019-1.042; p < 0.0001) and the pre-LT nucleos(t)ides analogue (NUC) regimen: in comparison to tenofovir, the use of entecavir alone (HR: 1.735; 95CI: 1.312-2.295; p < 0.0001) or another NUC or combination therapy (HR: 1.471; 95CI: 1.059-2.043; p = 0.021) were associated with decreased survival. CONCLUSIONS:Survival after LT for HBV-related liver disease is good. NUC type prior to LT seems to be associated with patient survival.

BACKGROUND:A significant proportion of patients presenting a primary sclerosing cholangitis (PSC) will require liver transplantation (LT). The present study aimed to investigate graft loss and patient death in a large cohort of patients. METHODS:We conducted a nationwide multicenter retrospective study including all adult patients transplanted for PSC in France From 1985 to 2019. RESULTS:Were included 571 patients; median follow-up after LT was 89.0 months (IQR, 43.0-151.0). Patient survival at 5, 10 and 20 years after LT was 88.2%, 81.2% and 62.6%. After exclusion of patients who died during the first month after LT, 37 patients (6.6%) died during the first 2 years and the main cause was malignancies (n = 15, 40.5%, including 12 cases of recurrent cholangiocellular carcinoma). After 2 years, 90 patients (17.2%) died; the two main causes were malignancies (n = 36, 40.0%, including 13 cases of colorectal cancer) and sepsis (n = 23, 25.6%, of which 7 were related to recurrent PSC). Graft survival at 5, 10 and 20 years was 89.5%,78.7% and 62.7%. Independent factors associated with late patient death (after 2 years) were an older age at LT, a bilio-digestive anastomosis and the use of preventive UDCA; independent factors associated with late graft loss were recurrent PSC, cellular rejection, a younger age at LT, and the use of tacrolimus (protective). CONCLUSIONS:Our results emphasise that the prognosis after LT for PSC could be improved by better detection of cholangiocellular carcinoma before LT, and colorectal cancer after LT.

ABSTRACTBackgroundFamilial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease, associated with MEFV mutations. FMF patients can experience liver involvement, potentially leading to cirrhosis.ObjectivesThis study aimed to evaluate liver involvement in FMF patients at a French tertiary centre for adult FMF.MethodsWe conducted an observational study with FMF patients displaying 2 pathogenic MEFV mutations at the National Reference Center for Autoinflammatory Diseases and Inflammatory Amyloidosis (CEREMAIA) in Paris and included in the JIR cohort. MEFV heterozygous patients and those with other liver disease causes were excluded.ResultsAmong 533 FMF patients 12.4% had chronic liver abnormalities, with 30% who developed cirrhosis 54 years [36–57] in median after disease onset. Forty‐seven per cent were colchicine resistant, and 41% received interleukin‐1 inhibitors. Cirrhotic patients experienced delayed hepatopathy diagnosis, prolonged FMF diagnosis delay and late‐onset treatment initiation compared to those with only liver function test abnormalities. Colchicine resistance and interleukin‐1 inhibitor use were more common in cirrhotic patients. Body mass index and AA amyloidosis rates did not differ significantly between groups. Twenty‐one patients had undergone liver biopsies including 14 cirrhotic patients revealing steatohepatitis in 12 cases and probable steatohepatitis in 4. Other lesions, like iron overload and sinusoidal dilatation, were sporadically observed.ConclusionFMF patients are at risk of chronic liver disease. Regular liver function monitoring is crucial, particularly in case of persistent inflammation, due to the risk of progression to cirrhosis and its associated morbidity and mortality.

Background/Objectives: Multiple criteria are used worldwide to select hepatocellular carcinoma (HCC) patients with a low risk of recurrence for liver transplantation (LT). However, it remains unclear which criteria are best for the LT-involved stakeholders, particularly in accurately identifying patients at high risk of recurrence. This work aimed to identify the most accurate criteria for selecting HCC patients for LT. Methods: In June 2023, a systematic literature search was conducted in PubMed and CENTRAL to identify studies including LT selection criteria of HCC patients. Data was extracted from recurrence-free survival curves using a validated algorithm and subsequently used to calculate measures of diagnostic performance routinely used in clinical trials. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were applied. Results: Of 815 records screened, only 17 met our study inclusion parameters, embodying 14 LT selection criteria. All LT criteria achieved an adjusted positive predictive value (aPPV) over 80%, indicating the correct selection of at least 80% of low-risk HCC patients. However, the adjusted negative predictive value (aNPV) was below 50% in most cases, indicating that these criteria cannot correctly identify patients with a true high risk of recurrence. This raises major ethical concerns regarding the models’ ability to exclude patients from LT. Since a perfect model is nonexistent, we created a ranking to account for the distinct concerns of all stakeholders in LT eligibility in the context of HCC. Conclusions: These results highlight the urgent need for refined or newly developed criteria with improved specificity and NPV to select more patients amenable to LT who are currently excluded.

INTRODUCTION:Primary sclerosing cholangitis (PSC) may recur after liver transplantation (LT). We aimed to evaluate the incidence of recurrent PSC (rPSC), its characteristics, and risk factors, in a large cohort with long-term follow-up. METHODS:We conducted a nationwide multicenter retrospective study in France, including all adult patients transplanted for PSC from March 1985 to March 2019. Clinical, biological, and histological data were collected. Risk factors for rPSC were identified using a multivariate Cox-regression model. RESULTS:Five hundred seventy-one patients were included (389 males, 68.1%) with a median age at LT of 42.0 (interquartile range [IQR] 32.0-52.8). Median follow-up after LT was 7.4 years (IQR 3.6-12.6). Overall, rPSC occurred in 25.9% of patients; actuarial risk of developing rPSC at 5, 15, and 25 years was 15.6%, 37.9%, and 52.6%, respectively. The median time to rPSC was 4.9 years (IQR 2.3-8.9). The factors independently associated with rPSC were the presence of IBD (hazard ratio [HR] 1.97, 95% confidence interval [CI] 1.24-3.14), maintenance treatment with corticosteroids (HR 1.76, 95% CI 1.17-2.66), and younger age at LT (HR 1.02 per 1-year increase, 95% CI 1.01-1.03). Type of biliary anastomosis or preventive treatment with ursodeoxycholic acid had no impact on the incidence of rPSC. DISCUSSION:Our results from a large cohort with long-term follow-up strongly confirm that rPSC after LT is frequent. The only modifiable factor associated with rPSC was maintenance treatment with corticosteroids, which could therefore be discontinued in the absence of a specific extrahepatic indication.

There is an increasing recognition of the need for a specialized hepatohematology program in countries with a high prevalence of sickle cell disease. This program would be tailored specifically for patients with sickle cell disease, addressing the unique challenges they face, including the management of liver and biliary complications, and hematological issues associated with their condition. By integrating hepatology and hematology expertise, we can improve knowledge of liver SCD-related diseases, and patient outcomes, enhance care coordination, and provide comprehensive management strategies for this vulnerable population. While the primary focus of this program is on SCD-related liver disease, there may be opportunities shortly to expand its scope to include patients with various hematological liver diseases.

Background:Adult solid organ transplant recipients (SOTRs) have decreased responsiveness to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination and higher incidence of infection, but there are few data on the serological response in pediatric SOTR. The aim of this study was to determine serological response to SARS-CoV-2 vaccination in pediatric liver (LT) and kidney transplant (KT) recipients and compare it with adult SOTR. Methods:A European, prospective, multicenter study was performed. Samples were taken at 7 and 32 wk following COVID-19 vaccination and serological endpoints were measured by ELISA. Results:A total of 42 pediatric (16 post-LT and 26 post-KT) and 117 adult (all post-LT) were included. All pediatric participants and 94% adult participants received mRNA vaccines. Paediatric SOTR patients had significantly higher anti-Spike IgG levels than adult participants at week 7 (114 220.7 [59 285.92-220 058.55] versus 8756.7 [5643.69-13 586.71], P < 0.0001) and week 32 (46 113.2 [10 992.91-193 436.14] versus 8207.0 [3561.20-18 913.43], P = 0.0032). No significant difference in week 7 anti-Spike IgG response was found between pediatric LT and KT (129 434.4 [51 888.64-322 869.69] versus 105 304.5 [39 910.20-277 849.50], P = 0.9854). No differences were seen between children and adults in the rate of decline of anti-Spike IgG between weeks 7 and 32 (P = 0.8000). Male sex and hemolytic-uremic syndrome or postischemic kidney disease were associated with lower anti-Spike IgG levels at week 7 in pediatric SOTR. Conclusions:Paediatric SOTR demonstrate greater SARS-CoV-2 vaccine responses than comparable adult SOTR patients. These data support efficacy and safety of SARS-CoV-2 vaccination in child SOTR and may alleviate vaccine hesitancy in this patient group.

Background: Selective internal radiation therapy (SIRT) is recommended as a downstaging (DS) strategy for solitary unresectable HCC <8 cm. The aim of this study was to report the results of acquired experience in a tertiary center for all unresectable HCCs. Methods: We conducted a retrospective, observational study using data collected from consecutive patients undergoing SIRT between October 2013 and June 2020. DS was considered achieved when a curative treatment could be proposed 6 months after SIRT. Results: One hundred twenty-seven patients were included (male = 90%, 64 +/- 11 y), of whom 112 (n = 88%) had cirrhosis. HCC was classified as BCLC stage C in 64 patients (50%), with a median diameter of 61 mm, an infiltrative pattern in 51 patients (40%), and portal vein invasion in 62 (49%) patients. Fifty patients (39%) achieved DS 6 months following SIRT, with 29 of them (23%) undergoing curative treatment in a median time of 4.3 months: 17 (13%) were transplanted, 11 (85%) had liver resection, and 1 patient had a radiofrequency ablation. The median overall survival of patients with or without DS was 51 versus 10 months, respectively (p < 0.001). In patients who achieved DS, progression-free survival was higher in patients who underwent surgery: 47 versus 11 months (p < 0.001). Four variables were independently associated with DS: age (OR: 0.96, 95% CI: [0.92, 0.99]; p = 0.032), baseline alpha-fetoprotein (OR: 1.00, 95% CI: [1.00, 1.00]; p = 0.034), HCC distribution (OR: 0.3, 95% CI: [0.11, 0.75]; p = 0.012), and ALBI grade (OR: 0.34. 95% CI: [0.14, 0.80]; p = 0.014). Conclusions: These results suggest that SIRT in patients with unresectable HCC could be an effective treatment: DS was achieved for around 39% of the patients and more than half of these then underwent curative treatment.