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Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence.

Liver transplant (LT) candidates with a body mass index (BMI) over 40 kg/m2have lower access to a liver graft without clear explanation. Thus, we studied the impact of obesity on the waiting list (WL) and aimed to explore graft proposals and refusal. Data between January 2007 and December 2017 were extracted from the French prospective national database: CRISTAL. Competing risk analyses were performed to evaluate predictors of receiving LT. Competitive events were (1) death/WL removal for disease aggravation or (2) improvement. The link between grade obesity, grafts propositions, and reason for refusal was studied. 15,184 patients were analysed: 10,813 transplant, 2847 death/dropout for aggravation, 748 redirected for improvement, and 776 censored. Mortality/dropout were higher in BMI over 35 (18% vs. 14% 1 year after listing) than in other candidates. In multivariate analysis, BMI>35, age, hepatic encephalopathy, and ascites were independent predictors of death/dropout. Candidates with a BMI ≥ 35 kg/m2had reduced access to LT, without differences in graft proposals. However, grafts refusal was more frequent especially for ‘morphological incompatibility’ (14.9% vs. 12.7% p< 0.01). BMI over 35 kg/m2reduces access to LT with increased risk of dropout and mortality. Increased mortality and dropout could be due to a lower access to liver graft secondary to increased graft refusal for morphological incompatibility.

ObjectiveImmunoglobulin A vasculitis (IgAV) and nephropathy (IgAN) share common immunological mechanisms. Liver cirrhosis is well known to be associated with IgAN. Here, we aimed to describe the presentation and outcome of IgAV patients with underlying cirrhosis.MethodsWe conducted a French nationwide retrospective study of adult patients presenting with both IgAV and cirrhosis. Baseline characteristics were compared to those of the 260 patients included in the French nationwide IgAV registry (IGAVAS).ResultsTwenty patients were included, and 7 (35%) were female. The mean ± SD age was 62.7 ± 11 years. At baseline, compared with IGAVAS patients, patients with underlying cirrhosis were older (62.7 ± 11 vs 50.1 ± 18, P< 0.01) and displayed more constitutional symptoms (weight loss 25% vs 8%, P= 0.03). Patients with underlying cirrhosis were also more likely to exhibit elevated serum IgA levels (5.6 g/L vs 3.6 g/L, P= 0.02). Cirrhosis and IgAV were diagnosed simultaneously in 12 patients (60%). Cirrhosis was mainly related to alcohol intake (n = 15, 75%), followed by nonalcoholic steato-hepatitis (n = 2), chronic viral hepatitis (n = 1), hemochromatosis (n = 1), and autoimmune hepatitis (n = 1). During follow-up with a median of 17 months (IQR 12–84), 10/13 (77%) exhibited IgAV remission at Month 3. One patient presented a minor relapse. Six patients died, but no deaths were related to IgAV.ConclusionWe report the first case series of IgAV patients with underlining cirrhosis, to our knowledge, which was mainly alcohol related. The liver disease did not seem to affect baseline vasculitis characteristics. Physicians should investigate the existence of liver cirrhosis at IgAV diagnosis, especially in the context of alcohol abuse.

Introduction: Glecaprevir/pibrentasvir is approved for treating chronic hepatitis C virus (HCV) genotypes (GT) 1–6. We evaluated real-world effectiveness, safety, and patient-reported outcomes of glecaprevir/pibrentasvir in underserved patient populations, focusing on persons who use drugs infected with HCV. Methods: Data were pooled from nine countries (13 November 2017–31 January 2020). Patients had HCV GT1–6, with or without compensated cirrhosis, with or without prior HCV treatment and received glecaprevir/pibrentasvir consistent with local label at their physician’s discretion. Patients with prior direct-acting antiviral exposure were excluded from efficacy and quality-of-life analyses. The percentage of patients achieving sustained virologic response at post-treatment week 12 (SVR12) was assessed. Mean changes from baseline to SVR12 visit in 36-Item Short-Form Health Survey mental and physical component summary scores were reported. Safety was assessed in patients receiving at least one dose of glecaprevir/pibrentasvir. Results: Of 2036 patients, 1701 (83.5%) received 8-week glecaprevir/pibrentasvir. In 1684 patients with sufficient follow-up, SVR12 rates were 98.0% (1651/1684) overall, 98.1% (1432/1459) in 8-week treated patients, 97.0% (519/535) in persons who use drugs, and greater than 95% across subgroups. Mean changes from baseline in mental and physical component summary scores were 3.7 and 2.4, respectively. One glecaprevir/pibrentasvir-related serious adverse event was reported; six glecaprevir/pibrentasvir-related adverse events led to discontinuation. Conclusions: Glecaprevir/pibrentasvir was highly effective, well tolerated, and improved quality of life in HCV-infected persons who use drugs and other underserved patients. Trial Registration: These multinational post-marketing observational studies are registered with ClinicalTrials.gov, number NCT03303599.

Ulipristal has recently been suspected to be hepatotoxic by the European Medicines Agency but the evidence base for hepatotoxicity is sparse. This is a brief formal report of a patient administered ulipristal for 6–8 weeks and who developed acute liver failure leading to liver transplantation. The explanted liver showed extensive hepatocyte necrosis and inflammation compatible with drug-induced liver injury and cirrhosis. The usual causes of acute hepatitis and cirrhosis were eliminated. There were no other potential causative drugs. This case suggests that ulipristal may cause acute hepatitis, with pre-existing cirrhosis probably contributing to the severity of liver injury observed in this case. Ulipristal prescribers must remain vigilant and monitor liver function in their patients.

Cytotoxic chemotherapy is generally ineffective in patients with hepatocellular carcinoma. We assessed the intravenous perfusion of doxorubicin-loaded nanoparticles in patients with hepatocellular carcinoma in whom previous sorafenib therapy had failed.

•Partial splenic embolization (PSE) has been proposed to treat the consequences of hypersplenism in the context of portal hypertension.•Retrospective data from 91 procedures from 1998 to 2023 were collected.•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).

This multicentric French study demonstrates the value of combination vasoactive therapy in liver transplantation for porto-pulmonary hypertension with good results in a well-selected cohort of liver transplantation candidates. Supplemental digital content is available in the text.

This multicenter study reports excellent results achieved with interferon-free sofosbuvir-based therapy in hepatitis C-HIV coinfected patients with recurrent hepatitis C, not different from those obtained by monoinfected recipients.

Hepatitis C virus (HCV) infection is associated with reduced patient survival following combined liver-kidney transplantation (LKT). The aim of this study was to assess the efficacy and safety of second-generation direct-acting antivirals (DAAs) in this difficult-to-treat population. The ANRS CO23 “Compassionate use of Protease Inhibitors in Viral C Liver Transplantation” (CUPILT) study is a prospective cohort including transplant recipients with recurrent HCV infection treated with DAAs. The present work focused on recipients with recurrent infection following LKT. The study population included 23 patients. All patients received at least one NS5B inhibitor (sofosbuvir) in their antiviral regimen an average of 90 months after LKT. Ninety-six percent of recipients achieved a sustained virological response (SVR) at week 12 (SVR12). In terms of tolerance, 39% of recipients presented with at least one serious adverse event. None of the patients experienced acute rejection during therapy and there were no deaths during follow-up. The glomerular filtration rate (GFR) decreased significantly from baseline to the end of therapy. However, this study did not show that the decline in GFR persisted over time or that it was directly related to DAAs. The DAA-based regimen is well tolerated with excellent results in terms of efficacy. It will become the gold standard for the treatment of recurrent HCV following LKT.

Hepatitis C virus(HCV) infection is associated with reduced patient survival following combined liver‐kidney transplantation (LKT). The aim of this study was to assess the efficacy and safety of second‐generation direct‐acting antivirals (DAAs) in this difficult‐to‐treat population. The ANRS CO23 “Compassionate use of Protease Inhibitors in Viral C Liver Transplantation” (CUPILT)study is a prospective cohort including transplant recipients with recurrent HCVinfection treated with DAAs. The present work focused on recipients with recurrent infection following LKT. The study population included 23 patients. All patients received at least one NS5B inhibitor (sofosbuvir) in their antiviral regimen an average of 90 months after LKT. Ninety‐six percent of recipients achieved a sustained virological response (SVR)at week 12 (SVR12). In terms of tolerance, 39% of recipients presented with at least one serious adverse event. None of the patients experienced acute rejection during therapy and there were no deaths during follow‐up. The glomerular filtration rate (GFR) decreased significantly from baseline to the end of therapy. However, this study did not show that the decline in GFRpersisted over time or that it was directly related to DAAs. The DAA‐based regimen is well tolerated with excellent results in terms of efficacy. It will become the gold standard for the treatment of recurrent HCVfollowing LKT. In liver–kidney recipients with recurrent hepatitis C chronic infection, treatment with second‐generation direct active antivirals for 12 or 24 weeks is safe and well tolerated, and results in a sustained virological response rate of 95.7% in patients.

The last thirty years have been very prosperous in the field of liver transplantation (LT), with great advances in organ conservation, surgical techniques, peri-operative management and long-term immunosuppression, resulting in improved patient and graft survival rates as well as quality of life. However, substance addiction after LT, namely alcohol and tobacco, results in short term morbidity together with medium and long-term mortality. The main consequences can be vascular (increased risk of hepatic artery thrombosis in smokers), hepatic (recurrent alcoholic cirrhosis in alcohol relapsers) and oncological (increased risk of malignancy in patients consuming tobacco and/or alcohol after LT). This issue has thus drawn attention in the field of LT research. The management of these two at-risk behaviors addictions need the implication of hepatologists and addiction specialists, before and after LT. This review will summarize our current knowledge in alcohol use and cigarette smoking in the setting of LT, give practical tools for identification of high risk patients and treatment options.

In this French multicentre, open-label study, we analyzed the efficacy, safety and patient-reported outcomes of a boceprevir-based triple therapy in HCV genotype 1 cirrhotic patients awaiting liver transplantation (LT).

Alcohol relapses after liver transplantation (LT) constitute a critical issue. Because there is no widely accepted definition of LT, its prevalence varies from 7 to 95% across studies. Only a severe relapse, the frequency of which is estimated to be 11 to 26%, decreases life expectancy after 5 years of LTand requires specific care. To improve the early identification of alcohol consumption among transplanted patients, liver transplant teams may be helped by input from an addiction team. Nevertheless, added benefit of involvement by addiction specialists in treating posttransplant patients has not been demonstrated. Thus, the aim of this study was to compare the evaluation of the alcohol consumption after LTperformed routinely during the transplant consultation or obtained from a specific addiction consultation. This was a prospective single‐site study. Patients were seen consecutively by their hepatologist and by an addiction specialist, and they completed the Alcohol Use Disorders Identification Test–Consumption (AUDIT‐C). Thus, the patient's alcohol status was assessed using 3 different sources of information: the hepatologist's interview, the AUDIT‐C score, and the addiction specialist visit. One hundred forty‐one patients were consecutively evaluated. Alcohol consumption was identified by the hepatologist in 31 patients (21.9%), in 52 (36.8%) using the AUDIT‐Cquestionnaire, and in 58 (41.1%) by the addiction specialist. The 31 patients concerned reported an average of 6.5 alcohol units/wk to the transplant physician, a number which was significantly greater (p= 0.001) by 8.6 units/wk when they were interviewed by the addiction specialist. This study highlights the clinical utility of a systematic addiction consultation among liver transplant patients, irrespective of the reason for transplantation. Alcohol relapses after liver transplantation constitutes a critical issue. The aim of the study was to compare the evaluation of the alcohol consumption after LTusing three different sources: the hepatologist interview, the AUDIT, and the addiction specialist visit. Alcohol consumption was identified in 31 of 141 patients by the hepatologist, in 52 using the AUDIT, and in 58 by the addiction specialist. This study highlights the interest of a systematic addiction consultation among liver transplant patients.

A French observational, longitudinal, prospective study assesses patient adherence of once-daily tacrolimus in kidney and liver transplant recipients. Conversion to once-daily tacrolimus improves adherence rate more than 20% of patients and worsens in less than 10% of patients.

In this randomized multicenter open-label trial in liver transplant recipients, the authors show that a therapeutic protocol with mycophenolic acid AUC dose adjusted MMF in combination with tacrolimus allows early discontinuation of corticosteroid (at day 1) resulting in lower 1-year posttransplantation diabetes without increasing the incidence of acute rejection.

Alcohol-related liver disease is the second most frequent indication for liver transplantation (LT), yet as many as 90% to 95% of patients with alcohol-related end-stage liver disease are never formally evaluated for LT. Furthermore, despite its significance as a cause of chronic liver disease and indication for LT, it has received little attention in recent years for several reasons, including the good posttransplant short-term results, and the lack of specific “drugs” used for this disease. A writing group, endorsed by the International Liver Transplant Society, was convened to write guidelines on Liver Transplantation for Alcoholic Liver Disease to summarize current knowledge and provide answers to controversial and delicate ethical as well as clinical problems. We report here a short version of the guidelines (long version available at www.ilts.org) with the final recommendations graded for level of evidence. The writing group membership is expected to remain active for 5 years, reviewing the guideline annually, and updating the online version when appropriate.The ILTS guidelines for liver transplantation for alcoholic liver disease are set forth in this publication. Considerations include the candidate population and the challenges regarding both the assessment of sobriety before and the maintenance of quality of life after transplantation. The authors identify special considerations, including immunosuppression in this setting and the special considerations regarding patients with acute alcoholic hepatitis.

•Fibrosing cholestatic hepatitis is a rare and very severe form of HCV recurrence after liver transplantation.•Prognosis of HCV recurrence after liver transplantation has been dramatically modified because of direct antivirals.•Histological outcome of 17 patients has been studied.•Fibrosis stage worsened in the majority of patients with fibrosing cholestatic hepatitis despite HCV cure.

Nous rapportons une nouvelle forme clinique de lymphangiectasies cutanées superficielles acquises (LCSA) survenant au cours de la décompensation oedémato-ascitique de cirrhose hépatique (CH).

In a large prospective randomized open-label international trial, liver transplant recipients for HCC were randomized to receive non-mTOR-inhibitor-based-treatment or mTOR-inhibitor-based-treatment. Results indicate overall sirolimus does not improve long-term recurrence-free survival beyond 5 years while a benefit was seen in low-risk patients. Supplemental digital content is available in the text.

La transplantation hépatique (TH) est le seul traitement curatif de la cirrhose terminale et du cancer du foie non résécable.

A new particle-enhanced turbidimetric immunoassay, Quantitative Microsphere System (QMS) everolimus, was evaluated using an Indiko analyzer (Thermo Fisher Scientific).

Recurrent hepatitis C after liver transplantation (LT) is associated with rapid fibrosis progression. The aim of this study was to evaluate the cumulative risk for severe fibrosis and the factors influencing it.

Background:Rare cases of acute hepatitis have been reported following injection, overdose, and even during the use of buprenorphine (BPN) at therapeutic doses, especially in carriers of hepatitis C virus (HCV). Objectives:To report a case of acute hepatitis and renal failure related to intranasal BPN misuse in a HCV-negative patient and to analyze cases reported to the French postmarketing surveillance system (PMSS) of drugs and in the literature. Methods: All cases of hepatitis related to BPN reported to PMSS between January 1996 and December 2012 were analyzed. Results:A 42-year-old man with a history of intranasal BPN misuse (8 mg/d) for at least 10 years was admitted for flu-like symptoms and abdominal pain. At admission, the patient consumed alcohol, cannabis, and tobacco. Acute hepatitis and acute renal failure were diagnosed . Clinical signs and biological parameters resolved within 26 days. An objective causality assessment revealed that an adverse drug reaction (ADR) was possible. In the French PMSS database, 41 cases of suspected BPN-induced hepatitis are reported. In 36.6% of cases, BPN was misused by the intravenous route. In the literature, 16 cases of acute hepatitis related to BPN with or without renal failure are reported. In all cases, patients were HCV carriers. The primary mechanism of BPN-induced hepatitis is a mitochondrial dysfunction, exacerbated by cofactors (HCV, alcohol, and medications). Conclusion:Intranasal misuse of BPN is increasingly frequent. We report here the first documented case of acute hepatitis and renal failure related to intranasal BPN misuse in a patient negative for HCV infection.

Background Danoprevir (RG7227) is an inhibitor of the HCV NS3/4A protease. In two Phase Ib studies of treatment-naive patients with chronic HCV genotype 1 infection, danoprevir administration for 14 days was associated with HCV RNA median reduction reaching 3.8 log10in monotherapy and 5.7 log10in combination therapy with pegylated interferon (PEG-IFN)-a2a (40 KD) plus ribavirin (RBV). After the protocol-defined phase, patients were free to continue with PEG-IFN/RBV. Sustained virological response (SVR) was evaluated in patients who continued treatment with PEG-IFN/RBV.Methods Retrospective analysis of the patients who received a 14-day monotherapy regimen with danoprevir (100 or 200 mg every 8 or 12 h), or 14-day triple therapy with danoprevir (100, 200 or 300 mg every 8 h, or 400, 600 or 900 mg every 12 h) with PEG-IFN-a2a (40 KD; 180 mg/ week subcutaneously) and RBV (1,000–1,200 mg/day) followed by PEG-IFN-a2a (40 KD; 180 µg/week subcutaneously) and RBV (1,000–1,200 mg/day) for 46 weeks (triple therapy group) for a total of 48 weeks (monotherapy group).Results Data were collected from 15 patients with danoprevir monotherapy and 24 patients with danoprevir-based triple therapy. Virological results are expressed using an intention-to-treat principle. Premature treatment discontinuation occurred in five patients. Rapid virological response (RVR; week 4) rate was 50% and 69.6% and SVR rate was 60% and 70.8% in the mono-therapy and triple therapy groups, respectively. RVR was highly predictive of SVR (>90%; HCV RNA<15 IU/ml).Conclusions The addition of danoprevir for 14 days to PEG-IFN/RBV treatment results in a high SVR rate in HCV genotype 1 treatment-naive patients.

Calcineurin inhibitor-induced renal dysfunction is a major problem in liver transplantation. Interleukin-2 receptor antagonist induction followed by delayed tacrolimus (Tac) administration may minimize the renal insult without compromising immunoprotection.

Objective To report 2 cases of acute hepatitis related to intravenous administration of buprenorphine in hepatitis C–infected patients.Case Summary Two patients, aged 33 and 50 years, respectively, who were hepatitis C virus (HCV) carriers were treated with sublingual buprenorphine 8 mg/day for addiction. Several years after initiation of buprenorphine, they were hospitalized because of clinical hepatitis with jaundice that developed after intravenous injection of buprenorphine. Serum alanine aminotransferase rose to 100 times the upper limit of normal (ULN) in the first patient and to 21 times the ULN in the second. As cofactors, the first patient had consumed alcohol, and the second patient took aspirin 600 mg in addition to the injection of buprenorphine 20 mg 4 days before the onset of jaundice. After stopping the intravenous injections, both patients continued sublingual buprenorphine therapy, with no relapse of hepatitis. Interestingly, in these 2 patients, buprenorphine-induced hepatitis was followed by the disappearance of HCV RNA.Discussion Most cases of hepatotoxicity related to buprenorphine have occurred in hepatitis C–infected patients. The main mechanism for buprenorphine-induced hepatitis is a mitochondrial defect, exacerbated by cofactors with additional potential to induce mitochondria dysfunction (eg, HCV, alcohol, concomitant medications). According to the Naranjo probability scale, buprenorphine was found to be the probable cause of acute hepatitis in both patients. In addition, we assessed the relationship between intravenous buprenorphine and acute hepatitis using 2 scales for causality assessment of hepatotoxicity (the Council for International Organizations of Medical Sciences scale and the Maria & Victorino scale). The diagnosis of intravenous buprenorphine-induced hepatitis was classified as probable in both cases. In addition, these 2 cases illustrate that acute hepatitis in a carrier of chronic HCV may occasionally facilitate the clearance of virus.Conclusions Although buprenorphine is well tolerated when used at recommended sublingual doses, patients should be informed about the risk of acute hepatitis with misuse of the drug by the intravenous route. These cases illustrate that, in carriers of chronic HCV, acute hepatitis may modify the host's immunotolerance and facilitate clearance of the virus.

Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication of organ transplantation that leads to death in more than 50 of cases. The aim of this work was to identify specific risk factors for lymphoproliferative disorders after liver transplantation in adults.

The persistence and migration of donor leukocytes has been well established, but cellular kinetics immediately after revascularization and the potential relevance of these different lymphocyte populations to spontaneous tolerance remain unclear. During the early hours of revascularization, there is a transitory “congestion” of the liver graft, which is evidence of an early phase that we have termed “first cellular contact.”

Background/Aims:Bacterial infections, specially Staphylococcus aureus (S. aureus)septicemia, remain a leading cause of death following liver transplantation. It has been demonstrated that nasal carriage of S. aureusis associated with invasive infections in patients undergoing hemodialysis and could be decreased by use of antibiotic nasal ointment. However, in cirrhotic patients, the frequency of nasal carriage is unknown. The aims of this study were to determine the prevalence of S. aureusnasal carriage in cirrhotic patients and to assess nosocomial contamination.

Drug-induced hepatitis is uncommon and generally unpredictable. Hepatotoxicity may be related to the drug itself, or to chemically reactive metabolites which can bind covalently to hepatic macromolecules and may lead to either idiosyncratic, toxic hepatitis or to immunoallergic hepatitis. There is now evidence indicating that genetic variations in systems of biotransformation or detoxication may modulate either the toxic or sensitizing effects of some drugs. Thus, the genetic deficiency in a particular hepatic cytochrome P 450 isozyme (CYP 2D6) is involved in perhexiline liver injury. The deficiency in CYP 2C19 might also contribute to Atrium hepatotoxicity. Slow acetylation related to N-acetyltransferase 2 deficiency contributes to sulfonamide hepatitis. The genetic deficiency in glutathione synthetase may increase the susceptibility to several drugs including acetaminophen. A constitutional deficiency in another cell defense mechanism, still not characterized, seems to increase significantly the risk of hepatotoxicity with halothane, phenytoin, carbamazepine, phenobarbital, sulfamides and amineptine.

•After liver transplantation (LT), de novomalignancies are one of the leading causes of late mortality.•Risk factors of de novomalignancies in a large cohort of LT recipients (n=11004) are described using Fine and Gray competing risks regression analysis.•The overall incidence of de novo malignancies was 13.45%.•Were significant risk factors for de novomalignancy: recipient age, male gender, non-living donor, a first LT and the type of initial liver disease.•Initial immunosuppressive regimen had no significant impact.

•Our blinded analysis of HCC recurrence following “curative” treatment:•Argues against the “curative” efficacy of the first treatment of HCC in one third of patients.•Evidences that DAA therapy has no significant impact on the severity or progression of HCC recurrence.•Evidences that DAA therapy does not impact overall survival and could be considered in cirrhotic patients with prior history of HCC.

Abstract: Nocardiosis is a life-threatening infection, particularly among immunocompromised patients, which usually affects lungs, skin and central nervous system. We report a case of disseminated nocardiosis revealed by suppurative thyroiditis in a liver-kidney transplant recipient with poor nutritional status at the time of infection. Nocardia Asteroides was isolated from fine-needle aspiration material of the thyroid abscess. Clinical manifestations resolved after surgical drainage of the thyroid abscess, prolonged antibiotherapy and diminution of immunosuppressive regimen. Clinicians should be aware of this entity, as Nocardia Asteroides may need more than 5 days of culture to be isolated.