BACKGROUND:Invasive aspergillosis is a rare but severe complication of liver transplantation. Incidence varies from 1·2% to 5·6% and mortality is greater than 50%. Few studies have investigated this complication. We aimed to describe cases of, and identify the factors associated with, invasive aspergillosis occurrence and mortality. METHODS:This nationwide, retrospective, matched case-control study included cases of invasive aspergillosis occurring after liver transplantation between Jan 1, 2007, and Dec 31, 2021, matched 1:1 on centre and transplantation period to control individuals without invasive aspergillosis across 15 liver transplantation centres in France. Cases were patients aged 18 years or older who presented with proven or probable invasive aspergillosis. The matched control was the next patient who received a transplant at the same transplantation centre after the case. Cases were retrospectively identified in each centre using the mycology laboratory database and the French Medicalised Information System Programme. Data were retrieved from hospital charts. The primary outcome was the identification of risk factors associated with the development of invasive aspergillosis following liver transplantation. Multivariable analysis using conditional logistic regression with a random effect for study centres was done to establish risk factors. FINDINGS:Among 14 332 liver transplantations, 196 recipients with invasive aspergillosis (62 [32%] female and 134 [68%] male) were identified and matched with 196 control individuals (54 [28%] female and 142 [73%] male). Invasive aspergillosis occurred at a median of 29 days (IQR 7-173) after liver transplantation. Risk factors for developing invasive aspergillosis were history of chronic kidney disease (adjusted odds ratio 4·13 [95% CI 2·35-7·24]), liver transplantation for acute liver disease (3·41 [1·44-8·06]), post-liver transplantation renal replacement therapy (3·82 [1·96-7·42]), and post-liver transplantation vasopressor support for longer than 24 h (2·82 [1·70-4·68]). INTERPRETATION:This study identifies three patient populations at risk of invasive aspergillosis after liver transplantation: patients with history of chronic kidney disease, those who have received a transplant for acute liver disease, and those who had a post-operative period marked by organ failure. This identification could lead to new invasive aspergillosis prophylactic strategies. FUNDING:None.

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:Anastomotic biliary complications (ABCs) after liver transplantation (LT) remain a significant source of morbidity. The influence of a surgeon's experience on the incidence of ABCs has been rarely investigated. METHODS:A retrospective review of consecutive first LTs performed by a single surgeon over 10 years was conducted. Cumulative sum analysis was used to identify the number of LTs necessary to decrease the rate of ABCs below the benchmark threshold. Multivariate logistic analysis was used to identify the risk factors for ABCs. RESULTS:This study included 365 first consecutive LTs by a single surgeon. The incidence of ABCs was 16.9%, and 90 cases were necessary to lower the rate of ABCs below the 6-month benchmark threshold (20%). A comparison of 4 clusters of 90 LTs revealed a statistically significant reduction in operative times, cold ischemia times, transfusion rates, and reoperation. However, a similar rate of ABCs was observed. Multivariate analysis identified the following independent risk factors for ABCs: early allograft dysfunction (hazard ratio [HR], 1.87 [95% CI, 1.08-3.25]; P =.025), presence of preoperative portal vein thrombosis (HR, 2.08 [95% CI, 1.20-5.63]; P =.015), need for intraoperative transfusions of >6 units of red blood cell (HR, 1.92 [95% CI, 1.04-3.54]; P =.035), and graft common bile duct of <5 mm (HR, 2.62 [95% CI, 1.34-5.13]; P =.005). Only the use of a T-tube was associated with the occurrence of late biliary fistulas (9 ABCs [14.5%]). CONCLUSION:In LT, increased experience does not improve the rate of ABCs. Factors, such as early allograft dysfunction, increased perioperative bleeding, preoperative portal vein thrombosis, and thin bile ducts, are associated with an increased rate of ABCs.

Background:The impact of acute-on-chronic liver failure (ACLF), a deadly form of decompensated cirrhosis characterized by the presence of organ failures, has not been well characterized, largely due to the lack of a code for ACLF in the International Classification of Diseases (ICD). We used ICD codes for extrahepatic organ failure to assess the burden of cirrhosis with extrahepatic organ failures (EHOFs) on European health care systems.Methods:The authors have searched national healthcare system databases from Germany for the period 2005-2020 and matched the data with that from France, Italy, and Denmark for admissions between 2017 and 2020, specifically for cases with an ICD diagnosis of cirrhosis combined with kidney, brain, respiratory, or circulatory failure.Results:During the 4-year period, 1,599,680 hospital admissions for cirrhosis, which included 329,093 (20.6%) admissions with at least 1 EHOF, were recorded across the 4 countries. The most frequent failing organs were kidneys (52.9%) and respiration (41.2%). The annual number of admissions for cirrhosis decreased over time (from 414,093 to 375,112), whereas the percentage of admissions with EHOF rose from 19.9% to 21.5%. Overall, the in-hospital mortality rate of patients with a diagnosis of EHOF was high (29.2%), markedly exceeding the mortality of those with a diagnosis of cirrhosis (7.9%). The proportion of estimated total healthcare claims of all hospital admissions of EHOF from cirrhosis was 44.9%.Conclusions:This study reveals that the burden of cirrhosis with EHOF was high in the 4 European countries, with a substantial impact on patient mortality. Crucially, these findings underscore the significant economic strain placed on healthcare systems by EHOF in cirrhosis patients. This should motivate all stakeholders to take action aiming at reducing this burden.

INTRODUCTION:There is considerable debate over the indication of liver transplantation (LT) for critically ill patients with cirrhosis, in part due to their potentially poor post-LT prognosis. We analyzed the epidemiology and outcome of LT for critically ill patients with cirrhosis over 4 time periods of 4 years. METHODS:We included adult patients who underwent liver transplant alone between 2005 and 2020 using the United Network for Organ Sharing registry database. We defined critically ill patients with cirrhosis as being in the intensive care unit with 1 or more of the following characteristics at the time of LT: (i) grade III/IV hepatic encephalopathy, (ii) mechanical ventilation, (iii) dialysis, and (iv) vasopressors. RESULTS:A total of 85,594 LT recipients were included, 5,827 (6.8%) of whom were classified as being critically ill with cirrhosis at the time of LT. The number and percentage of critically ill LT recipients with cirrhosis increased over the study period: 819 (4.3%) in 2005-2008 vs 2,067 (7.9%) in 2017-2020, P < 0.001. There was a 17% absolute increase in 1-year survival after LT: 72.5% in 2005-2008 vs 89.5% in 2017-2020, P < 0.001. The 1-year post-LT survival gap between critically ill and noncritically ill patients with cirrhosis narrowed over the study period: 16.7 percentage points in 2005-2008 vs 4.6 percentage points in 2017-2020. The year of LT was independently associated with lower 1-year post-LT mortality (hazard ratio 0.92, 95% confidence interval 0.91-0.93, P < 0.001). DISCUSSION:The absolute number and relative percentage of LT recipients who were critically ill increased over time, as did 1-year post-LT survival. Meanwhile, the gap in survival between this group of patients and noncritically ill patients with cirrhosis decreased but persisted. Cautious access to selected LT candidates who are critically ill may be warranted, provided the gap in survival with noncritically ill patients remains as small as possible.

Background & Aims: Inflammatory biomarkers are increasingly used as outcome predictors in the field of oncology and liver transplantation for HCC, but no study has shown the prognostic value of IL6 after LT. The goal of this study was to evaluate the predictive value of IL-6 on histopathological features of HCC on explant, its predictive value on recurrence risk and its additional value to other scores and inflammatory markers at the time of transplantation.Methods: From 2009 to 2019, all adults transplanted with a first liver graft and diagnosed with HCC on the explant analysis were retrospectively included (n = 229). Only patients who had a pre-LT IL6 level determination were analysed in this study (n = 204).Results: High IL-6 level at transplantation was associated with a significantly higher risk of vascular invasion (15% vs 6%; p = 0.023), microsatellitosis (11% vs 3%; p = 0.013), lower rate of histological response both in terms of complete response (2% vs 14%, p = 0.004) and of necrosis (p = 0.010).Patients with pre-LT IL-6 level > 15 ng/ml had a lower overall and cancer-specific survival (p = 0.013). Recurrence-free survival was lower in patients with IL-6 > 15 ng/ml with a 3-year recurrence-free survival of 88% versus 78% (p = 0.034). IL6 levels were significantly higher in patients with early recurrence compared to patients without (p = 0.002) or with late recurrence (p = 0.044).Conclusions: IL6 level at transplantation is an independent predictor of pejorative histological features of HCC and is associated to the risk of recurrence.