Recent outcomes of liver transplantation for Budd-Chiari syndrome: A study of the European Liver Transplant Registry (ELTR) and affiliated centers.

BACKGROUND AND AIMS: Management of Budd-Chiari syndrome (BCS) has improved over the last decades. The main aim was to evaluate the contemporary post-liver transplant (post-LT) outcomes in Europe. APPROACH AND RESULTS: Data from all patients who underwent transplantation from 1976 to 2020 was obtained from the European Liver Transplant Registry (ELTR). Patients < 16 years, with secondary BCS or HCC were excluded. Patient survival (PS) and graft survival (GS) before and after 2000 were compared. Multivariate Cox regression analysis identified predictors of PS and GS after 2000. Supplemental data was requested from all ELTR-affiliated centers and received from 44. In all, 808 patients underwent transplantation between 2000 and 2020. One-, 5- and 10-year PS was 84%, 77%, and 68%, and GS was 79%, 70%, and 62%, respectively. Both significantly improved compared to outcomes before 2000 ( p < 0.001). Median follow-up was 50 months and retransplantation rate was 12%. Recipient age (aHR:1.04,95%CI:1.02-1.06) and MELD score (aHR:1.04,95%CI:1.01-1.06), especially above 30, were associated with worse PS, while male sex had better outcomes (aHR:0.63,95%CI:0.41-0.96). Donor age was associated with worse PS (aHR:1.01,95%CI:1.00-1.03) and GS (aHR:1.02,95%CI:1.01-1.03). In 353 patients (44%) with supplemental data, 33% had myeloproliferative neoplasm, 20% underwent TIPS pre-LT, and 85% used anticoagulation post-LT. Post-LT anticoagulation was associated with improved PS (aHR:0.29,95%CI:0.16-0.54) and GS (aHR:0.48,95%CI:0.29-0.81). Hepatic artery thrombosis and portal vein thrombosis (PVT) occurred in 9% and 7%, while recurrent BCS was rare (3%). CONCLUSIONS: LT for BCS results in excellent patient- and graft-survival. Older recipient or donor age and higher MELD are associated with poorer outcomes, while long-term anticoagulation improves both patient and graft outcomes.

New sequential combinations of non-invasive fibrosis tests provide an accurate diagnosis of advanced fibrosis in NAFLD.

BACKGROUND & AIMS: Advanced liver fibrosis is an important diagnostic target in non-alcoholic fatty liver disease (NAFLD) as it defines the subgroup of patients with impaired prognosis. The non-invasive diagnosis of advanced fibrosis is currently limited by the suboptimal positive predictive value and the grey zone (representing indeterminate diagnosis) of fibrosis tests. Here, we aimed to determine the best combination of non-invasive tests for the diagnosis of advanced fibrosis in NAFLD. METHODS: A total of 938 patients with biopsy-proven NAFLD were randomized 2:1 into derivation and validation sets. All patients underwent liver stiffness measurement with vibration controlled transient elastography (VCTE) and blood fibrosis tests (NAFLD fibrosis score, Fibrosis-4 [FIB4], Fibrotest, Hepascore, FibroMeter). FibroMeterVCTE, which combines VCTE results and FibroMeter markers in a single test, was also calculated in all patients. RESULTS: For the diagnosis of advanced fibrosis, VCTE was significantly more accurate than the blood tests (area under the receiver operating characteristic curve [AUROC]: 0.840 ±â€¯0.013, p ≤0.005). FibroMeter was the most accurate blood test (AUROC: 0.793 ±â€¯0.015, p ≤0.017). The combinatory test FibroMeterVCTE outperformed VCTE and blood tests (AUROC: 0.866 ±â€¯0.012, p ≤0.005). The sequential combination of FIB4 then FibroMeterVCTE (FIB4-FMVCTE algorithm) or VCTE then FibroMeterVCTE (VCTE-FMVCTE algorithm) provided an excellent diagnostic accuracy of 90% for advanced fibrosis, with liver biopsy only required to confirm the diagnosis in 20% of cases. The FIB4-FMVCTE and VCTE-FMVCTE algorithms were significantly more accurate than the pragmatic algorithms currently proposed. CONCLUSION: The sequential combination of fibrosis tests in the FIB4-FMVCTE and VCTE-FMVCTE algorithms provides a highly accurate solution for the diagnosis of advanced fibrosis in NAFLD. These algorithms should now be validated for the diagnosis of advanced liver fibrosis in diabetology or primary care settings. LAY SUMMARY: The evaluation of liver fibrosis is mandatory in non-alcoholic fatty liver disease (NAFLD), as advanced fibrosis identifies the subgroup of patients with impaired prognosis. FibroMeterVCTE is a new fibrosis test combining blood markers and the result of vibration controlled transient elastography (VCTE) into a single diagnostic test. Our results show that FibroMeterVCTE outperforms other blood fibrosis tests and VCTE alone for the diagnosis of advanced fibrosis in a large multi-centric cohort of 938 patients with biopsy-proven NAFLD. Sequential algorithms using a simple blood test or VCTE as a first-line procedure, then FibroMeterVCTE as a second-line test accurately classified 90% of patients.

Cytomegalovirus detection is associated with ICU admission in non-AIDS and AIDS patients with Pneumocystis jirovecii pneumonia.

OBJECTIVES: Cytomegalovirus (CMV) is frequently detected in lung and/or blood samples of patients with Pneumocystis jirovecii pneumonia (PJP), although this co-detection is not precisely understood. We aimed to determine whether PJP was more severe in case of CMV detection. METHODS: We retrospectively included all patients with a diagnosis of PJP between 2009 and 2020 in our centre and with a measure of CMV viral load in blood and/or bronchoalveolar lavage (BAL). PJP severity was assessed by the requirement for intensive care unit (ICU) admission. RESULTS: The median age of the 249 patients was 63 [IQR: 53-73] years. The main conditions were haematological malignancies (44.2%), solid organ transplantations (16.5%), and solid organ cancers (8.8%). Overall, 36.5% patients were admitted to ICU. CMV was detected in BAL in 57/227 patients; the 37 patients with viral load ≥3 log copies/mL were more frequently admitted to ICU (78.4% vs 28.4%, p<0.001). CMV was also detected in blood in 57/194 patients; the 48 patients with viral load ≥3 log copies/mL were more frequently admitted to ICU (68.7% vs 29.4%, p<0.001). ICU admission rate was found to increase with each log of BAL CMV viral load and each log of blood CMV viral load. CONCLUSIONS: PJP is more severe in the case of concomitant CMV detection. This may reflect either the deleterious role of CMV itself, which may require antiviral therapy, or the fact that patients with CMV reactivation are even more immunocompromised.

SARS-CoV-2 anti-spike antibodies after a fourth dose of COVID-19 vaccine in adult solid-organ transplant recipients.

BACKGROUND: A fourth dose of SARS-CoV-2 vaccine is recommended in solid-organ transplant (SOT) recipients, but the immunogenicity is poorly known. METHODS: We conducted a retrospective, observational, monocentric study between the 1st January 2021 and 31st March 2022 of the anti-Spike antibody titers after one to four doses of vaccine in SOT. RESULTS: 825 SOT were included. Median age at first vaccine injection was 61.2 (IQR 50.9-69.3) years; 66.7 % were male; 63.4 % had received four vaccine doses. The proportion of participants with a strong humoral response (>260 BAU/mL) increased with the number of vaccine doses: 10.6 % after the 1st dose (D1), 35.1 % after the 2nd (D2), 48.5 % after the 3rd (D3), and 65.1 % after the 4th (D4) (p < 0.001). Among the tested patients, the proportion with a detectable humoral response was significantly higher after D4 than after D3 (47 % vs 22 %, p = 0.01). Liver transplant recipients had more frequently a strong humoral response after D2, D3 and D4 (OR = 5.3, 3.7 and 6.6 respectively when compared with other organ transplant recipients, p < 0.001). In kidney transplant recipients, belatacept-containing regimen was associated with a lower rate of detectable humoral (9 % vs 40 %, p = 0.025) after D3, but there was no statistical difference after D4. CONCLUSION: A fourth dose should be proposed to SOT recipients who did not developed an immune response after 3 doses. Kidney transplant recipients receiving belatacept have a poorer, although frequently detectable response.

Patients Treated for HCV Infection and Listed for Liver Transplantation in a French Multicenter Study: What Happens at Five Years?

BACKGROUND: Direct-acting antiviral (DAA) agents for the treatment of hepatitis C virus (HCV) infection have been proven safe and effective in cirrhotic patients awaiting liver transplantation (LT). However, in the long term, data remain minimal regarding the clinical impact of viral eradication on patients listed for decompensated cirrhosis or hepatocellular carcinoma (HCC). We aimed to elucidate the clinical outcomes of patients regarding delisting and the evolution of HCC during the long-term follow-up. METHODS: An observational, multicenter, retrospective analysis was carried out on prospectively collected data from HCV-positive patients treated with an interferon-free regimen while awaiting LT in 18 French hospitals. RESULTS: A total of 179 patients were included in the study. The indication for LT was HCC in 104 (58.1%) patients and cirrhosis in 75 (41.9%) patients. The sustained virological response was 84.4% and the treatment was well tolerated. At five years, among 75 patients with cirrhosis treated for HCV, 19 (25.3%) were delisted following improvement after treatment. Predictive factors for delisting highlighted an absence of ascites, MELD score ≤ 15, and Child-Pugh score ≤ 7. No patients with refractory ascites were delisted. Among patients with HCC, 82 (78.9%) were transplanted. The drop-out rate was low (6.7%) and few recurrences of HCC after LT were observed. CONCLUSIONS: DAAs are safe and effective in patients awaiting LT for cirrhosis or HCC. A quarter of patients with cirrhosis can be delisted because of clinical improvement. Predictive factors for delisting, as a result of improvement, may assist prescribers, before initiating HCV infection therapy in the long-term perspective.

Increased Intrahepatic Expression of Immune Checkpoint Molecules in Autoimmune Liver Disease.

Immune checkpoint molecules (ICM) are critical in maintaining immunologic homeostasis and participate in preventing or promoting autoimmune disease development. Exploring a large panel of intrahepatic inhibitory and stimulatory ICM is necessary for drawing a general picture of the immune alterations in autoimmune hepatitis (AIH). Here, we performed a multiparametric analysis of ICM, including PD-1, TIM3, LAG3, CTLA-4, OX40 and 4-1BB, and we determined their expression on intrahepatic lymphocyte subsets in untreated and in treated patients with AIH in comparison to normal liver tissue. AIH patient-derived liver tissue revealed the overexpression of ICM, mainly PD-1 and 4-1BB, as well as the strong correlation between PD-1+ CD8+ T-cell abundance and severity of AIH (alanine transaminase and aspartate transaminase levels). Our results show that the ICM play an important role in the loss of immune homeostasis in the liver, providing an attractive approach to investigate their role as targets for effective therapeutic interventions.