Publications by authors named "Didier Samuel"

395 Publications

State of the art treatment of HBV hepatocellular carcinoma and the role of HBsAg post liver transplantation and resection.

Liver Int 2021 Nov 30. Epub 2021 Nov 30.

Centre Hepatobiliaire, University Hospital Paul Brousse, University Paris-Saclay and Inserm-Paris Saclay Research Unit 1193, Villejuif, France.

Chronic hepatitis B virus (HBV) infection is the major aetiology of hepatocellular carcinoma (HCC). The optimal goal of therapy, hepatitis B surface antigen (HBsAg) loss and anti-HBs production, is achieved rarely and HBsAg-associated HCC risk is well recognized. Here we review the role of HBsAg in HCC, the link between HBsAg and HCC recurrence post-liver transplantation or resection, and the implications for therapy. HBV-associated carcinogenesis is a multifactorial process. The observation that HBV-related HCC can occur in the absence of cirrhosis is compatible with a direct oncogenic effect of the virus, which may occur via multiple mechanisms, including those mediated by both mutated and unmutated HBsAg. HCC recurrence in HBsAg-positive patients post-liver transplantation has been reported in 10-15% of patients and is likely to be due to expansion of residual HCC tumour cell populations containing integrated HBV DNA, which expand and independently replicate HBV, leading to the recurrence of both HCC and HBV. The direct role of HBsAg in HCC recurrence post-liver resection is less clear. Cirrhosis is the most important risk factor for HCC development, and precancerous cirrhotic liver remains after resection, with the potential to undergo malignant transformation regardless of the existence of HBV-derived oncogenic drivers. The role of HBsAg in the development of HCC and its recurrence post-surgical intervention has multiple implications for therapy and suggests a potential role for immunotherapy in the future management of HCC, in particular post-liver transplantation. Use of HBIGs that target HBsAg directly, alongside immune-oncology therapies, may be relevant in this setting.
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http://dx.doi.org/10.1111/liv.15124DOI Listing
November 2021

Impact of COVID - 19 in patients awaiting liver transplantation.

Liver Int 2021 Nov 19. Epub 2021 Nov 19.

AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France.

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http://dx.doi.org/10.1111/liv.15105DOI Listing
November 2021

Prognostic impact of surgical margins for hepatocellular carcinoma according to preoperative alpha-fetoprotein level.

HPB (Oxford) 2021 Nov 1. Epub 2021 Nov 1.

Department of Surgery, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif, 94800, France; Université Paris-Saclay, UMRS 1193, Université Paris-Saclay, Inserm, Physiopathogénèse et Traitement des Maladies Du Foie, FHU Hepatinov, 94800, Villejuif, France. Electronic address:

Background: HCC are known to have satellite nodules and microvascular invasions requiring sufficient margins. An alpha-fetoprotein (AFP) level >100 ng/mL is associated with worse pathological features in HCC. In practice, large resection margins, particularly >1 cm, are infrequently retrieved on the specimens.

Methods: 397 patients from 5 centres were included from 2012 to 2017. The primary endpoint was time-to-recurrence in relation to AFP level (> or <100 ng/ml) as well as surgical margins (> or <1 cm). The secondary endpoint was overall survival (OS).

Results: The median follow-up was 25 months. In Low AFP group, median time to recurrence (TTR) for patients with margins <1 cm was 36 months and for patients with margins ≥1 cm was 34 months (p = 0.756), and overall survival (OS) was not significantly different according to margins (p = 0.079). In High-AFP group, patients with margins <1 cm had a higher recurrence rate than patients with margins ≥1 cm (p = 0.016): median TTR for patients with margins <1 cm was 8 months whereas it was not reached for patients with margins ≥1 cm. Patients with margins <1 cm had a significantly worse OS compared to the patients with margins ≥1 cm (p = 0.043).

Conclusion: Preoperative AFP level may help determine margins to effectively treat high AFP tumours. For low-AFP tumours, margins didn't have an impact on TTR or OS.
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http://dx.doi.org/10.1016/j.hpb.2021.10.012DOI Listing
November 2021

Impact of body mass index on hepatocellular carcinoma recurrence after liver transplantation through long-term follow-up.

Hepatobiliary Surg Nutr 2021 Oct;10(5):598-609

AP-HP Hôpital Paul Brousse, Hepato-Biliary Centre, INSERM UMR 1193, Université Paris Saclay, Villejuif, France.

Background: Obesity is associated with increased oncological risk and outcomes but the evidence surrounding the effect of body mass index (BMI) on increased risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) is still questionable. The purpose of this retrospective study of a large cohort of adult patients transplanted for HCC was to investigate the effect of BMI on the incidence of HCC recurrence and outcome.

Methods: Data from 427 adult recipients transplanted for HCC between 2000 and 2017 were collected. Patients were classified at time of LT according to the World Health Organization BMI classification into 3 groups; group 1: BMI <25 (n=166), group 2: BMI 25-29.9 (n=150) and group 3: BMI ≥30 (n=111).

Results: There were no significant changes of mean BMI overtime 26.8±5.0 kg/m2 at time of LT and 28.8±23.1 at 5 years. The recurrence rates of HCC after LT in the three groups were 19%, 16% and 17% respectively. The 5, 10 and 15-year recurrence free survival (RFS) rates were respectively 68.6%, 47.3% and 40.8% in group 1, 73.3%, 66.2% and 49.5% in group 2 and 68.8%, 57.5% and 47.7% in group 3 (log rank P=0.47).

Conclusions: Recipient BMI at time of transplant and during follow-up didn't impact the incidence of HCC recurrence nor long-term patient survival, irrespective to the status of the patients and their tumor characteristic at time of LT. The present study clearly confirms that obesity should not be considered, when selecting patients with HCC to LT, as a predictive factor of recurrence.
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http://dx.doi.org/10.21037/hbsn.2020.04.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527412PMC
October 2021

PIAS1 Regulates Hepatitis C Virus-Induced Lipid Droplet Accumulation by Controlling Septin 9 and Microtubule Filament Assembly.

Pathogens 2021 Oct 15;10(10). Epub 2021 Oct 15.

Unité 1193, INSERM, F-94800 Villejuif, France.

Chronic hepatitis C virus (HCV) infection often leads to fibrosis and chronic hepatitis, then cirrhosis and ultimately hepatocellular carcinoma (HCC). The processes of the HVC life cycle involve intimate interactions between viral and host cell proteins and lipid metabolism. However, the molecules and mechanisms involved in this tripartite interaction remain poorly understood. Herein, we show that the infection of HCC-derived Huh7.5 cells with HCV promotes upregulation of the protein inhibitor of activated STAT1 (PIAS1). Reciprocally, PIAS1 regulated the expression of HCV core protein and HCV-induced LD accumulation and impaired HCV replication. Furthermore, PIAS1 controlled HCV-promoted septin 9 filament formation and microtubule polymerization. Subsequently, we found that PIAS1 interacted with septin 9 and controlled its assembly on filaments, which thus affected septin 9-induced lipid droplet accumulation. Taken together, these data reveal that PIAS1 regulates the accumulation of lipid droplets and offer a meaningful insight into how HCV interacts with host proteins.
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http://dx.doi.org/10.3390/pathogens10101327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537804PMC
October 2021

Mass Spectrometry-Based Proteomics Reveal Alcohol Dehydrogenase 1B as a Blood Biomarker Candidate to Monitor Acetaminophen-Induced Liver Injury.

Int J Mol Sci 2021 Oct 14;22(20). Epub 2021 Oct 14.

Univ. Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, FR2048, 38000 Grenoble, France.

Acute liver injury (ALI) is a severe disorder resulting from excessive hepatocyte cell death, and frequently caused by acetaminophen intoxication. Clinical management of ALI progression is hampered by the dearth of blood biomarkers available. In this study, a bioinformatics workflow was developed to screen omics databases and identify potential biomarkers for hepatocyte cell death. Then, discovery proteomics was harnessed to select from among these candidates those that were specifically detected in the blood of acetaminophen-induced ALI patients. Among these candidates, the isoenzyme alcohol dehydrogenase 1B (ADH1B) was massively leaked into the blood. To evaluate ADH1B, we developed a targeted proteomics assay and quantified ADH1B in serum samples collected at different times from 17 patients admitted for acetaminophen-induced ALI. Serum ADH1B concentrations increased markedly during the acute phase of the disease, and dropped to undetectable levels during recovery. In contrast to alanine aminotransferase activity, the rapid drop in circulating ADH1B concentrations was followed by an improvement in the international normalized ratio (INR) within 10-48 h, and was associated with favorable outcomes. In conclusion, the combination of omics data exploration and proteomics revealed ADH1B as a new blood biomarker candidate that could be useful for the monitoring of acetaminophen-induced ALI.
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http://dx.doi.org/10.3390/ijms222011071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540689PMC
October 2021

Donor HLA Class 1 Evolutionary Divergence Is a Major Predictor of Liver Allograft Rejection : A Retrospective Cohort Study.

Ann Intern Med 2021 10 24;174(10):1385-1394. Epub 2021 Aug 24.

Centre Hépato-Biliaire, Hôpital Paul-Brousse, Assistance Publique-Hôpitaux de Paris, Université Paris-Saclay, unité Institut National de la Santé et de la Recherche Médicale 1193, Villejuif, France (C.F., M.A., C.D., A.C., F.S., E.V., D.A., D.S.).

Background: The HLA evolutionary divergence (HED), a continuous metric quantifying the peptidic differences between 2 homologous HLA alleles, reflects the breadth of the immunopeptidome presented to T lymphocytes.

Objective: To assess the potential effect of donor or recipient HED on liver transplant rejection.

Design: Retrospective cohort study.

Setting: Liver transplant units.

Patients: 1154 adults and 113 children who had a liver transplant between 2004 and 2018.

Measurements: Liver biopsies were done 1, 2, 5, and 10 years after the transplant and in case of liver dysfunction. Donor-specific anti-HLA antibodies (DSAs) were measured in children at the time of biopsy. The HED was calculated using the physicochemical Grantham distance for class I ( or ) and class II ( or ) alleles. The influence of HED on the incidence of liver lesions was analyzed through the inverse probability weighting approach based on covariate balancing, generalized propensity scores.

Results: In adults, class I HED of the donor was associated with acute rejection (hazard ratio [HR], 1.09 [95% CI, 1.03 to 1.16]), chronic rejection (HR, 1.20 [CI, 1.10 to 1.31]), and ductopenia of 50% or more (HR, 1.33 [CI, 1.09 to 1.62]) but not with other histologic lesions. In children, class I HED of the donor was also associated with acute rejection (HR, 1.16 [CI, 1.03 to 1.30]) independent of the presence of DSAs. There was no effect of either donor class II HED or recipient class I or class II HED on the incidence of liver lesions in adults and children.

Limitation: The DSAs were measured only in children.

Conclusion: Class I HED of the donor predicts acute or chronic rejection of liver transplant. This novel and accessible prognostic marker could orientate donor selection and guide immunosuppression.

Primary Funding Source: Institut National de la Santé et de la Recherche Médicale.
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http://dx.doi.org/10.7326/M20-7957DOI Listing
October 2021

2020 position statement and recommendations of the European Liver and Intestine Transplantation Association (ELITA): management of hepatitis B virus-related infection before and after liver transplantation.

Aliment Pharmacol Ther 2021 09 19;54(5):583-605. Epub 2021 Jul 19.

Valencia, Spain.

Background: Prophylaxis of HBV recurrence is critical after liver transplantation in HBV patients. Despite new prophylactic schemes, most European LT centres persist on a conservative approach combining hepatitis B immunoglobulin (HBIG) and nucleos(t)ides analogues (NA).

Aim: This setting prompted the European Liver Intestine Transplantation Association (ELITA) to look for a consensus on the prevention of HBV recurrence.

Methods: Based on a 4-round Delphi process, ELITA investigated 16 research questions and established 50 recommendations.

Results: Prophylaxis should be driven according to 3 simplified risk groups: Low and high virological risk patients, with undetectable and detectable HBV DNA pre-LT, respectively, and special populations (HDV, HCC, poorly adherent patients). In low-risk patients, short-term (4 weeks) combination of third-generation NA+ HBIG, or third generation NA monotherapy can be considered as prophylactic options. In high-risk patients, HBIG can be discontinued once HBV DNA undetectable. Combined therapy for 1 year is advised. HBV-HCC patients should be treated according to their virological risk. In HDV/HBV patients, indefinite dual prophylaxis remains the gold standard. Full withdrawal of HBV prophylaxis following or not HBV vaccination should only be attempted in the setting of clinical trials. Organs from HBsAg+ve donors may be considered after assessment of risks, benefits, and patient consent. They should not be used if HDV is present. In poorly adherent patients, dual long-term prophylaxis is recommended. Budget impact analysis should be taken into account to drive prophylactic regimen.

Conclusions: These ELITA recommendations should stimulate a more rational and homogeneous approach to HBV prophylaxis across LT programs.
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http://dx.doi.org/10.1111/apt.16374DOI Listing
September 2021

External validation of LCR1-LCR2, a multivariable HCC risk calculator, in patients with chronic HCV.

JHEP Rep 2021 Aug 24;3(4):100298. Epub 2021 Apr 24.

Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, Paris, France.

Background & Aims: The Liver Cancer Risk test algorithm (LCR1-LCR2) is a multianalyte blood test combining proteins involved in liver cell repair (apolipoprotein-A1 and haptoglobin), known hepatocellular carcinoma (HCC) risk factors (sex, age, and gamma-glutamyl transferase), a marker of fibrosis (alpha2-macroglobulin) and alpha-fetoprotein (AFP), a specific marker of HCC. The aim was to externally validate the LCR1-LCR2 in patients with chronic HCV (CHC) treated or not with antivirals.

Methods: Pre-included patients were from the Hepather cohort, a multicentre prospective study in adult patients with CHC in France. LCR1-LCR2 was assessed retrospectively in patients with the test components and AFP, available at baseline. The co-primary study outcome was the negative predictive value (NPV) of LCR1-LCR2 for the occurrence of HCC at 5 years and for survival without HCC according to the predetermined LCR1-LCR2 cut-offs. The cut-offs were adjusted for risk covariables and for the response to HCV treatment, and were quantified using time-dependent proportional hazards models.

Results: In total, 4,903 patients, 1,026 (21.9%) with baseline cirrhosis, were included in the study. Patients were followed for a median of 5.7 (IQR 4.2-11.3) years. A total of 3,788/4,903 (77.3%) patients had a sustained virological response. There were 137 cases of HCC at 5 years and 214 at the end of follow-up. HCC occurred at 5 years in 24/3,755 patients with low-risk LCR1-LCR2 compared with 113/1,148 patients with high-risk LCR1-LCR2. The NPV was 99.4% (95% CI 99.1-99.6). Similar findings (hazard ratio, 10.8; 95% CI, 8.1-14.3; <0.001) were obtained after adjustment for exposure to antivirals, age, sex, geographical origin, HCV genotype 3, alcohol consumption, and type 2 diabetes mellitus.

Conclusions: The results showed that LCR1-LCR2 can be used to successfully identify patients with HCV at very low risk of HCC at 5 years.

Lay Summary: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide and the fastest growing cause of cancer death in many countries. We constructed and internally validated a new multianalyte blood test to assess this Liver Cancer Risk (LCR1-LCR2). This study confirmed the performance of LCR1-LCR2 in patients with chronic HCV in the national French cohort Hepather, and its ability to identify patients at a very low risk of HCC at 5 years.

Clinical Trials Registration: The study is registered at ClinicalTrials.gov (NCT01953458).
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http://dx.doi.org/10.1016/j.jhepr.2021.100298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187244PMC
August 2021

Hepatic Arteriovenous Malformation: The Search for a PTEN Mutation!

Hepatology 2021 Aug 15;74(2):1121-1123. Epub 2021 Jun 15.

Hepato-Biliary Center, Paul Brousse University Hospital, APHP, Villejuif, France.

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http://dx.doi.org/10.1002/hep.31694DOI Listing
August 2021

Liver Transplantation for Hepatocellular Carcinoma: A Real-Life Comparison of Milan Criteria and AFP Model.

Cancers (Basel) 2021 May 19;13(10). Epub 2021 May 19.

Faculty of Medicine, University Grenoble-Alpes, 38000 Grenoble, France.

Purpose: To compare the agreement for the criteria on the explant and the results of liver transplantation (LT) before and after adoption of the AFP (α-fetoprotein) model.

Methods: 523 patients consecutively listed in five French centers were reviewed to compare results of the Milan criteria period (MilanCP, = 199) (before 2013) and the AFP score period (AFPscP, = 324) (after 2013). (NCT03156582).

Results: During AFPscP, there was a significantly longer waiting time on the list (12.3 vs. 7.7 months, < 0.001) and higher rate of bridging therapies (84 vs. 75%, = 0.012) compared to the MilanCP. Dropout rate was slightly higher in the AFPscP (31 vs. 24%, = 0.073). No difference was found in the histological AFP score between groups ( = 0.838) with a global agreement in 88% of patients. Post-LT recurrence was 9.2% in MilanCP vs. 13.2% in AFPscP ( = 0.239) and predictive factors were AFP > 2 on the last imaging, downstaging policy and salvage transplantation. Post-LT survival was similar (83 vs. 87% after 2 years, = 0.100), but after propensity score analysis, the post-listing overall survival (OS) was worse in the AFPscP (HR 1.45, = 0.045).

Conclusions: Agreement for the AFP model on explant analysis (≤2) did not significantly change. AFP score > 2 was the major prognostic factor for recurrence. Graft allocation policy has a major impact on prognosis, with a post-listing OS significantly decreased, probably due to the increase in waiting time, increase in bridging therapies, downstaging policy and salvage transplantation.
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http://dx.doi.org/10.3390/cancers13102480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160826PMC
May 2021

Limitations of current liver donor allocation systems and the impact of newer indications for liver transplantation.

J Hepatol 2021 07;75 Suppl 1:S178-S190

Liver Failure Group, Institute for Liver and Digestive Health, University College London, London and European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain.

Liver transplantation represents a life-saving treatment for patients with decompensated cirrhosis, a severe condition associated with a high risk of waiting list mortality. When decompensation occurs rapidly in the presence of extrahepatic organ failures, the condition is called acute-on-chronic liver failure, which is associated with an even higher risk of death, though liver transplantation can also markedly improve survival in affected patients. However, there are still gaps in our understanding of how to optimise prioritisation and organ allocation, as well as survival among patients with acute-on-chronic liver failure (both before and after transplant). Moreover, it is urgent to address inequalities in access to liver transplantation in patients with severe alcoholic hepatitis and non-alcoholic steatohepatitis. Several controversies still exist regarding gender and regional disparities, as well as the use of suboptimal donor grafts. In this review, we aim to provide a critical perspective on the role of liver transplantation in patients with decompensated cirrhosis and address areas of ongoing uncertainty.
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http://dx.doi.org/10.1016/j.jhep.2021.01.007DOI Listing
July 2021

High trough levels of everolimus combined to sorafenib improve patients survival after hepatocellular carcinoma recurrence in liver transplant recipients.

Transpl Int 2021 07 7;34(7):1293-1305. Epub 2021 Jun 7.

AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris- Saclay, Villejuif, France.

Recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) occurs in 10%-20% of patients transplanted for HCC. The treatment of HCC recurrence after LT remains a challenge. Consecutive patients who underwent LT for HCC between 2005 and 2015 at our center were recruited. Characteristics of patients with recurrence, modalities of treatment and outcome were collected retrospectively. Patient survival was analyzed according to HCC recurrence therapeutic strategy. Among 306 transplanted patients, 43 patients (14.1%) developed recurrence with a median survival time after recurrence of 10.9 months (95%CI: 6.6-18.6). Survival of patients treated with Sorafenib (SOR) and everolimus (EVL) (n = 19) was significantly better than that of the group treated with other strategies (n = 24) (P = 0.001). Multivariable analysis demonstrated that SOR plus EVL therapy and absence of dissemination at diagnosis of recurrence were independent predictive factors of prolonged survival after recurrence. Among the patients who treated with EVL, survival of patients with controlled EVL blood trough levels ≥5 ng/ml was significantly better compared to those with EVL trough levels <5 ng/ml (P = 0.021). Combination therapy of sorafenib and everolimus was an independent predictor for better survival after HCC recurrence. Patients with controlled everolimus trough level ≥5 ng/ml might get the best survival benefit.
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http://dx.doi.org/10.1111/tri.13897DOI Listing
July 2021

Mild increases in plasma creatinine after intermediate to high-risk abdominal surgery are associated with long-term renal injury.

BMC Anesthesiol 2021 04 30;21(1):135. Epub 2021 Apr 30.

Department of Anesthesiology, Brugmann Hospital, Université Libre de Bruxelles, 4, Place A. Van Gehuchten, 1020 Bruxelles, Bruxelles, Belgium.

Background: The potential relationship between a mild acute kidney injury (AKI) observed in the immediate postoperative period after major surgery and its effect on long term renal function remains poorly defined. According to the "Kidney Disease: Improving Global Outcomes" (KDIGO) classification, a mild injury corresponds to a KIDIGO stage 1, characterized by an increase in creatinine of at least 0.3 mg/dl within a 48-h window or 1.5 to 1.9 times the baseline level within the first week post-surgery. We tested the hypothesis that patients who underwent intermediate-to high-risk abdominal surgery and developed mild AKI in the following days would be at an increased risk of long-term renal injury compared to patients with no postoperative AKI.

Methods: All consecutive adult patients with a plasma creatinine value ≤1.5 mg/dl who underwent intermediate-to high-risk abdominal surgery between 2014 and 2019 and who had at least three recorded creatinine measurements (before surgery, during the first seven postoperative days, and at long-term follow up [6 months-2 years]) were included. AKI was defined using a "modified" (without urine output criteria) KDIGO classification as mild (stage 1 characterised by an increase in creatinine of > 0.3 mg/dl within 48-h or 1.5-1.9 times baseline) or moderate-to-severe (stage 2-3 characterised by increase in creatinine 2 to 3 times baseline or to ≥4.0 mg/dl). The exposure (postoperative kidney injury) and outcome (long-term renal injury) were defined and staged according to the same KDIGO initiative criteria. Development of long-term renal injury was compared in patients with and without postoperative AKI.

Results: Among the 815 patients included, 109 (13%) had postoperative AKI (81 mild and 28 moderate-to-severe). The median long-term follow-up was 360, 354 and 353 days for the three groups respectively (P = 0.2). Patients who developed mild AKI had a higher risk of long-term renal injury than those who did not (odds ratio 3.1 [95%CI 1.7-5.5]; p < 0.001). In multivariable analysis, mild postoperative AKI was independently associated with an increased risk of developing long-term renal injury (adjusted odds ratio 4.5 [95%CI 1.8-11.4]; p = 0.002).

Conclusions: Mild AKI after intermediate-to high-risk abdominal surgery is associated with a higher risk of long-term renal injury 1 y after surgery.
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http://dx.doi.org/10.1186/s12871-021-01353-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086102PMC
April 2021

Diffuse Versus Localized Caroli Disease: A Comparative MRCP Study.

AJR Am J Roentgenol 2021 06 21;216(6):1530-1538. Epub 2021 Apr 21.

Université Paris Diderot, Paris, France.

The purpose of this multicenter retrospective study was to assess the MRCP features of Caroli disease (CD). Sixty-six patients were identified from 2000 to 2019. The inclusion criteria were diagnosis of diffuse or localized CD mentioned in an imaging report, presence of intrahepatic bile duct (IHBD) dilatation, and having undergone an MRCP examination. The exclusion criteria included presence of obstructive proximal biliary stricture and having undergone hepatobiliary surgery other than cholecystectomy. Histopathology records were available for 53 of the 66 (80%) patients. Diffuse and localized diseases were compared by chi-square and tests and Kaplan-Meier model. Forty-five patients had diffuse bilobar CD ((five pediatric patients [three girls and two boys] with a mean [± SD] age of 8 ± 5 years [range, 1-15 years] and 40 adult patients [26 men and 14 women] with a mean age of 35 ± 11 years [range, 20-62 years]) and 21 patients had localized disease (12 men and 9 women; mean age, 54 ± 14 years). Congenital hepatic fibrosis was found only in patients with diffuse CD (35/45 [78%]), as was a "central dot" sign (15/35 [43%]). IHBD dilatation with both saccular and fusiform features was found in 43 (96%) and the peripheral "funnel-shaped" sign in 41 (91%) of the 45 patients with diffuse CD but in none of the patients with localized disease ( < .001). Intrahepatic biliary calculi were found in all patients with localized disease but in only 16 of the 45 (36%) patients with diffuse CD ( < .001). Left liver atrophy was found in 18 of the 21 (86%) patients with localized disease and in none of the patients with diffuse CD ( < .001). The overall survival rate among patients with diffuse CD was significantly lower than that among patients with localized disease ( = .03). Diffuse IHBD dilatation with both saccular and fusiform features associated with the peripheral funnel-shaped sign can be used for the diagnosis of CD on MRCP. Localized IHBD dilatation seems to be mainly related to primary intrahepatic lithiasis.
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http://dx.doi.org/10.2214/AJR.20.23522DOI Listing
June 2021

Risk factors of de novo malignancies after liver transplantation: a French national study on 11004 adult patients.

Clin Res Hepatol Gastroenterol 2021 Jul 11;45(4):101514. Epub 2021 Mar 11.

Hôpital Jean Minjoz, Service d'Hépatologie et Soins Intensifs Digestifs, Besançon, France.

Background: After liver transplantation (LT),de novo malignancies are one of the leading causes of late mortality. The aim of the present retrospective study was to identify the risk factors of de novo malignancies in a large cohort of LT recipients in France, using Fine and Gray competing risks regression analysis.

Methods: The study population consisted in 11004 adults transplanted between 2000 and 2013, who had no history of pre-transplant malignancy, except primary liver tumor. A Cox model adapted to the identification of prognostic factors (competitive risks) was used.

Results: From the entire cohort, one (or more)de novo malignancy was reported in 1480 L T recipients (13.45%). The probability to develop a de novo malignancy after LT was 2.07% at 1 year, 13.30% at 5 years, and 28.01% at 10 years. Of the known reported malignancies, the most common malignancies were hematological malignancy (22.36%), non-melanoma skin cancer (19.53%) and lung cancer (12.36%). According to Fine and Gray competing risks regression multivariate analysis, were significant risk factors for post-LT de novo malignancy: recipient age (Subdistribution Hazard Ratio (SHR) = 1.03 95%CI 1.03-1.04), male gender (SHR = 1.45 95%CI 1.27-1.67), non-living donor (SHR = 1.67 95%CI 1.14-2.38), a first LT (SHR = 1.35 95%CI 1.09-1.69) and the type of initial liver disease (alcohol-related liver disease (SHR = 1.63 95%CI 1.22-2.17), primary sclerosing cholangitis (SHR = 1.98 95%CI 1.34-2.91), and primary liver tumor (SHR = 1.88 95%CI 1.41-2.54)). Initial immunosuppressive regimen had no significant impact.

Conclusion: The present study confirms that LT recipient characteristics are associated with the risk ofde novo malignancy and this underlines the need for personalized screening in order to improve survival.
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http://dx.doi.org/10.1016/j.clinre.2020.07.019DOI Listing
July 2021

Early liver transplantation for corticosteroid non-responders with acute severe autoimmune hepatitis: The SURFASA score.

J Hepatol 2021 06 24;74(6):1325-1334. Epub 2021 Jan 24.

CHRU Lille, Hôpital Claude Huriez, Service des Maladies de l'Appareil Digestif, Lille, France.

Background & Aims: In acute severe autoimmune hepatitis (AS-AIH), the optimal timing for liver transplantation (LT) remains controversial. The objectives of this study were to determine early predictive factors for a non-response to corticosteroids and to propose a score to identify patients in whom LT is urgently indicated.

Methods: This was a retrospective, multicenter study (2009-2016). A diagnosis of AS-AIH was based on: i) Definite or probable AIH based on the simplified IAIHG score; ii) international normalized ratio (INR) ≥1.5 and/or bilirubin >200 μmol/L; iii) No previous history of AIH; iv) Histologically proven AIH. A treatment response was defined as LT-free survival at 90 days. The evolution of variables from corticosteroid initiation (day-D0) to D3 was estimated from: Δ%3 = (D3-D0)/D0.

Results: A total of 128 patients were included, with a median age of 52 (39-62) years; 72% were female. Overall survival reached 88%. One hundred and fifteen (90%) patients received corticosteroids, with a LT-free survival rate of 66% at 90 days. Under multivariate analysis, D0-INR (odds ratio [OR] 6.85; 95% CI 2.23-21.06; p <0.001), Δ%3-INR ≥0.1% (OR 6.97; 95% CI 1.59-30.46; p <0.01) and Δ%3-bilirubin ≥-8% (OR 5.14; 95% CI 1.09-24.28; p <0.04) were predictive of a non-response. The SURFASA score: -6.80+1.92∗(D0-INR)+1.94∗(Δ%3-INR)+1.64∗(Δ%3-bilirubin), created by combining these variables, was highly predictive of LT or death (AUC = 0.93) (88% specificity; 84% sensitivity) with a cut-off point of <-0.9. Below this cut-off, the chance of responding was 75%. With a score higher than 1.75, the risk of dying or being transplanted was between 85% and 100%.

Conclusion: In patients with AS-AIH, INR at the introduction of corticosteroids and the evolution of INR and bilirubin are predictive of LT or death. Within 3 days of initiating corticosteroids, the SURFASA score can identify non-responders who require a referral for LT. This score needs to be validated in a prospective cohort.

Lay Summary: The management of patients with acute severe autoimmune hepatitis is highly challenging, particularly regarding their early referral for liver transplantation. We found that international normalized ratio at the initiation of corticosteroid therapy and the evolution of international normalized ratio and bilirubin values after 3 days of therapy were highly predictive of liver transplantation or death. We are thus proposing a score that combines these variables and identifies patients in whom liver transplantation is urgently required.
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http://dx.doi.org/10.1016/j.jhep.2020.12.033DOI Listing
June 2021

Systemic inflammation and liver cirrhosis complications: Driving or secondary event? How to square the circle?

Authors:
Didier Samuel

J Hepatol 2021 03 18;74(3):508-510. Epub 2021 Jan 18.

AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France; Univ Paris-Saclay, UMR-S 1193, Université Paris-Saclay, Villejuif, F-94800, France; Inserm, Unité 1193, Université Paris-Saclay, Villejuif, F-94800, France; Hepatinov, Villejuif, F-94800, France. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2021.01.001DOI Listing
March 2021

Cyclin-dependent kinase inhibitors p21 and p27 function as critical regulators of liver regeneration following 90% hepatectomy in the rat.

World J Hepatol 2020 Dec;12(12):1198-1210

INSERM, U1193, Paul-Brousse University Hospital, Hepatobiliary Centre, Villejuif 94800, France.

Background: Liver reduction is the main curative treatment for primary liver cancer, but its use remains limited as liver regeneration requires a minimum of 30% functional parenchyma.

Aim: To study the dynamics of the liver regeneration process and consequent behavior of cell cycle regulators in rats after extended hepatectomy (90%) and postoperative glucose infusions.

Methods: Post-hepatectomy liver failure was triggered in 84 Wistar rats by reducing their liver mass by 90%. The animals received a post-operative glucose infusion and were randomly assigned to two groups: One to investigate the survival rate and the other for biochemical analyses. Animals that underwent laparotomy or 70% hepatectomy were used as controls. Blood and liver samples were collected on postoperative days 1 to 7. Liver morphology, function, and regeneration were studied with histology, immunohistochemistry, and western blotting.

Results: Postoperative mortality after major resection reached 20% and 55% in the first 24 h and 48 h, respectively, with an overall total of 70% 7 d after surgery. No apparent signs of apoptotic cell death were detected in the extended hepatectomy rat livers, but hepatocytes displaying a clear cytoplasm and an accumulation of hyaline material testified to changes affecting their functional activities. Liver regeneration started properly, as early events initiating cell proliferation occurred within the first 3 h, and the G1 to S transition was detected in less than 12 h. However, a rise in p27 (Kip1) followed by p21 (Waf1/Cip1) cell cycle inhibitor levels led to a delayed S phase progression and mitosis. Overall, liver regeneration in rats with a 90% hepatectomy was delayed by 24 h and associated with a delayed onset and lower peak magnitude of hepatocellular deoxyribonucleic acid synthesis.

Conclusion: This work highlights the critical importance of the cyclin/cyclin-dependent kinase inhibitors of the Cip/Kip family in regulating the liver regeneration timeline following extended hepatectomy.
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http://dx.doi.org/10.4254/wjh.v12.i12.1198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772727PMC
December 2020

De novo hepatocellular carcinoma in a non-cirrhotic allograft 27 years after liver transplantation: A case report.

Am J Transplant 2021 05 23;21(5):1953-1958. Epub 2021 Jan 23.

Centre Hépato-Biliaire, AP-HP Hôpital Paul Brousse, Inserm UMR-S 1193, Université Paris-Saclay, Villejuif, France.

Hepatocellular carcinoma recurrence after liver transplantation is a well-known complication but the development of de novo hepatocellular carcinoma in non-cirrhotic allograft with no previous history of hepatic malignancy either in the donor or the recipient is extremely rare. A 33-year-old man underwent deceased donor liver transplantation due to HBV-HDV cirrhosis in 1991. The donor was healthy, with negative viral serology. Pretransplant assessment and explant liver pathology revealed no tumor. He developed an 8 cm mediastinal thymus cancer in 2014, a chronic myeloid leukemia in 2015 and a 16 mm renal cell carcinoma in 2017. After 27 years, in 2018, his routine follow-up sonography showed incidentally a 37 mm hepatic nodule in segment VII which revealed after percutaneous liver guided biopsy a hepatocellular carcinoma. As no extra hepatic metastasis was noted, segmentectomy was done. The pathological report confirmed a moderately differentiated hepatocellular carcinoma nodule of 50 mm diameter with absence of microvascular invasion and the non-tumoral liver showed histological features of NASH (SAF score: S1A2F3, NAS score: A3F3 and LAFSc:5) with absence of HBsAg and HBcAg. This case emphasizes the importance of long-term close surveillance by imaging of the graft even in the absence of viral recurrence and graft cirrhosis.
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http://dx.doi.org/10.1111/ajt.16476DOI Listing
May 2021

Predicting the risk of post-hepatectomy portal hypertension using a digital twin: A clinical proof of concept.

J Hepatol 2021 03 16;74(3):661-669. Epub 2020 Nov 16.

INRIA, Centre de Recherche de Paris, 2 rue Simone Iff, Paris 75012, France.

Background & Aims: Despite improvements in medical and surgical techniques, post-hepatectomy liver failure (PHLF) remains the leading cause of postoperative death. High postoperative portal vein pressure (P) and portocaval gradient (PCG), which cannot be predicted by current tools, are the most important determinants of PHLF. Therefore, we aimed to evaluate a digital twin to predict the risk of postoperative portal hypertension (PHT).

Methods: We prospectively included 47 patients undergoing major hepatectomy. A mathematical (0D) model of the entire blood circulation was assessed and automatically calibrated from patient characteristics. Hepatic flows were obtained from preoperative flow MRI (n = 9), intraoperative flowmetry (n = 16), or estimated from cardiac output (n = 47). Resection was then simulated in these 3 groups and the computed P and PCG were compared to intraoperative data.

Results: Simulated post-hepatectomy pressures did not differ between the 3 groups, comparing well with collected data (no significant differences). In the entire cohort, the correlation between measured and simulated P values was good (r = 0.66, no adjustment to intraoperative events) or excellent (r = 0.75) after adjustment, as well as for PCG (respectively r = 0.59 and r = 0.80). The difference between simulated and measured post-hepatectomy PCG was ≤3 mmHg in 96% of cases. Four patients suffered from lethal PHLF for whom the model satisfactorily predicted their postoperative pressures.

Conclusions: We demonstrated that a 0D model could correctly anticipate postoperative PHT, even using estimated hepatic flow rates as input data. If this major conceptual step is confirmed, this algorithm could change our practice toward more tailor-made procedures, while ensuring satisfactory outcomes.

Lay Summary: Post-hepatectomy portal hypertension is a major cause of liver failure and death, but no tool is available to accurately anticipate this potentially lethal complication for a given patient. Herein, we propose using a mathematical model to predict the portocaval gradient at the end of liver resection. We tested this model on a cohort of 47 patients undergoing major hepatectomy and demonstrated that it could modify current surgical decision-making algorithms.
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http://dx.doi.org/10.1016/j.jhep.2020.10.036DOI Listing
March 2021

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors.

JHEP Rep 2020 Dec 11;2(6):100170. Epub 2020 Aug 11.

AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, INSERM Unit 1193, Univ Paris-Sud, Université Paris-Saclay, FHU Hépatinov, Villejuif, F-94800, France.

Immune checkpoint inhibitors (ICIs) improve clinical outcomes in patients suffering from different types of cancer. Liver toxicity is one of the immune-related adverse events associated with immunotherapy; although not common, its management is challenging as it is extremely heterogeneous in terms of presentation and severity. Differences in the development and evolution of ICI-related toxicity in healthy or cirrhotic livers have not yet been elucidated. Assessing causality is key to diagnosing ICI-induced liver toxicity; liver biopsies can assist not only in the differential diagnosis but also in assessing the severity of histological liver damage. The current classification of severity overestimates the grade of liver injury and needs to be revised to reflect the views of hepatologists. Spontaneous improvements in ICI-related liver toxicity have been reported, so corticosteroid therapy should probably be individualised not systematic. The reintroduction of ICIs in a patient with previous immune-mediated hepatitis may be possible, but the risk/benefit ratio should be considered, as the risk factors for hepatitis recurrence are currently unclear. The management of these patients, requiring a balance between efficacy, toxicity and specific treatments, necessitates multidisciplinary collaboration. The incidence of immune-related liver toxicity will continue to rise based on the increasing use of ICIs for most cancers, mandating improved understanding and management of this complication.
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http://dx.doi.org/10.1016/j.jhepr.2020.100170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648167PMC
December 2020

Long term results of liver transplantation for alpha-1 antitrypsin deficiency.

Dig Liver Dis 2021 May 1;53(5):606-611. Epub 2020 Nov 1.

Hospices Civils de Lyon, Hôpital Edouard Herriot, Fédération des spécialités digestives, Lyon, France; Université de Lyon, Lyon, France. Electronic address:

Introduction: Liver transplantation (LT) is the therapeutic option for end-stage liver disease associated with alpha1 antitrypsin (A1AT) deficiency. The aim of the present retrospective study was to report on long-term outcomes following LT for A1AT deficiency.

Methods: The medical records of 90 pediatric and adult patients transplanted between 1982 and 2017 in France and Geneva (Switzerland) were reviewed.

Results: The study population consisted of 32 adults and 58 children; median age at transplant was 13.0 years (range: 0.2-65.1), and 65 were male (72.2%). Eighty-two patients (94.8% of children and 84.4% of adults) had the PI*ZZ genotype/phenotype and eight patients (8.9%) had the Pi*SZ genotype/phenotype. Eighty-four patients (93.3%) were transplanted for end-stage liver disease and six (all Pi*ZZ adults) for HCC. Median follow-up after LT was 13.6 years (0.1-31.7). The overall cumulative patient survival rates post-transplant were 97.8% at 1 year, and 95.5%, 95.5%, 92.0%, 89.1% at 5, 10, 15, 20 years respectively. The overall cumulative graft survival rates were 92.2% at 1 year, and 89.9%, 89.9%, 84.4%, 81.5% at 5, 10, 15 and 20 years, respectively.

Conclusions: In a representative cohort of patients having presented with end-stage-liver disease or HCC secondary to A1AT, liver transplantation offered very good patient and graft survival rates.
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http://dx.doi.org/10.1016/j.dld.2020.10.016DOI Listing
May 2021

Temporal Trends and Outcomes in Liver Transplantation for Recipients With HIV Infection in Europe and United States.

Transplantation 2020 10;104(10):2078-2086

Keck School of Medicine, University of Southern California, Los Angeles, CA.

Background: We evaluated trends and outcomes of liver transplantation (LT) recipients with/without HIV infection.

Methods: LT recipients between 2008 and 2015 from the United Network for Organ Sharing and Organ Procurement and Transplantation Network and European Liver Transplant Registry were included. Trends and characteristics related to survival among LT recipients with HIV infection were determined.

Results: Among 73 206 LT patients, 658 (0.9%) were HIV-infected. The proportion of LT HIV-infected did not change over time (P-trend = 0.16). Hepatitis C virus (HCV) as indication for LT decreased significantly for HIV-infected and HIV-uninfected patients (P-trends = 0.008 and <0.001). Three-year cumulative graft survival in LT recipients with and without HIV infection was 64.4% and 77.3%, respectively (P < 0.001), with improvements over time for both, but with HIV-infected patients having greater improvements (P-trends = 0.02 and 0.03). Adjusted risk of graft loss was 41% higher in HIV-infected versus HIV-uninfected (adjusted hazard ratio [aHR], 1.41; P < 0.001). Among HIV-infected, model of end-stage liver disease (aHR, 1.04; P < 0.001), body mass index <21 kg/m (aHR, 1.61; P = 0.006), and HCV (aHR, 1.83; P < 0.001) were associated with graft loss, whereas more recent period of LT 2012-2015 (aHR, 0.58; P = 0.001) and donor with anoxic cause of death (aHR, 0.51; P = 0.007) were associated with lower risk of graft loss.

Conclusions: Patients with HIV infection account for only 1% of LTs in United States and Europe, with fewer LT for HCV disease over time. A static rate of LT among HIV-infected patients may reflect improvements in cirrhosis management and/or persistent barriers to LT. Graft and patient survival among HIV-infected LT recipients have shown improvement over time.
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http://dx.doi.org/10.1097/TP.0000000000003107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919403PMC
October 2020

Early Versus Late Hepatocellular Carcinoma Recurrence After Transplantation: Predictive Factors, Patterns, and Long-term Outcome.

Transplantation 2021 08;105(8):1778-1790

AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris-Saclay, Villejuif, France.

Background: Hepatocellular carcinoma (HCC) is currently the first indication of liver transplantation (LT) in Europe and Asia-Pacific region and the third in the United States. HCC recurrence is the main complication affecting short- and medium-term outcomes after LT.

Methods: A total of 433 consecutive adult recipients transplanted for HCC between 2000 and 2017 (mean age: 57.8 ± 8.5 y; 83.8% were males) with a mean follow-up of 74.6 ± 58.6 months were included. Patients had to meet Milan criteria and, since 2014, alpha-fetoprotein score to be listed. Patients with HCC recurrence were classified into early (≤2 y) and late recurrence (>2 y) and were retrospectively reviewed.

Results: Patients who developed recurrence (75 patients, 17%) had more tumors outside Milan and University of California San Francisco criteria, high alpha-fetoprotein score, and microvascular invasion at pathology. Early recurrence developed in 46 patients (61.3%); the overall 5- and 10-year survival rates of these patients from time of LT were 6.7% and 0%, which were significantly lower than those with late recurrence 64.0% and 27.1%, respectively (P < 0.001). The median survival times from the diagnosis of HCC recurrence were 15 and 17 months, respectively, in the 2 groups (P < 0.001). Multivariable Cox regression analysis identified alcoholic cirrhosis as etiology of the underlying liver disease (hazard ratio [HR] = 3.074; P = 0.007), bilobar tumor at time of LT (HR = 2.001; P = 0.037), and a tumor size (>50 mm) in the explant (HR = 1.277; P = 0.045) as independent predictors of early recurrence.

Conclusions: Improving the prediction of early HCC recurrence could optimize patient selection for LT, potential adjuvant therapy with new targeted drugs and hence, improve long-term survival.
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http://dx.doi.org/10.1097/TP.0000000000003434DOI Listing
August 2021

Time to Conversion to an Everolimus-Based Regimen: Renal Outcomes in Liver Transplant Recipients From the EVEROLIVER Registry.

Liver Transpl 2020 11 12;26(11):1465-1476. Epub 2020 Oct 12.

Unité de Transplantation Hépatique, Hôpital Edouard Herriot, Lyon, France.

Longterm use of a calcineurin inhibitor (CNI)-based regimen is one of the major reasons for chronic renal failure in liver transplantation recipients (LTRs). The Everolimus Liver registry (EVEROLIVER) evaluated renal function in LTRs who were converted to everolimus (EVR). This observational registry included all LTRs receiving EVR across 9 centers from France. Data are being collected in an electronic database over 10 years (12 visits/patient) to evaluate efficacy, renal function (estimated glomerular filtration rate [eGFR]), and safety of EVR use in clinical practice, and the current analysis is reporting up to 60 months of findings. Until September 2017, 1045 patients received EVR after a mean time of 3.6 ± 5.1 years. CNI withdrawal was feasible in 57.7% of patients as of month 60. Mean eGFR improved in patients with baseline eGFR <60 mL/minute/1.73 m and was maintained in those with baseline eGFR ≥60 mL/minute/1.73 m . Among patients with chronic kidney disease (CKD; baseline eGFR <60 mL/minute/1.73 m ), 55% converted to EVR within 3 months (early conversion) and 39.4% converted between 4 and 12 months after transplantation (mid-conversion) experienced improvement in eGFR (≥60 mL/minute/1.73 m ) at month 36. Only 20.9% and 17.4% among those converted beyond 12 months (late conversion) experienced improvement respectively at month 36 and 60. A logistic regression analysis in patients with CKD stage ≥3 demonstrated that late conversion, age, and female sex were associated with nonimprovement of eGFR (≥60 mL/minute/1.73 m ). Data from this real-life use of EVR indicate that renal function was maintained from the preconversion period until month 36 even in patients with advanced CKD. However, early rather than late conversion appears to be a safe approach to preserve longterm renal function in LTRs.
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http://dx.doi.org/10.1002/lt.25879DOI Listing
November 2020

Impact of negative air pressure in ICU rooms on the risk of pulmonary aspergillosis in COVID-19 patients.

Crit Care 2020 09 1;24(1):538. Epub 2020 Sep 1.

Liver Intensive Care Unit, Centre Hépato-Biliaire, AP-HP, Hôpital Paul-Brousse, Université Paris-Saclay, Inserm U1193, 12 Avenue Paul Vaillant Couturier, F-94804, Villejuif, France.

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http://dx.doi.org/10.1186/s13054-020-03221-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458783PMC
September 2020

Liver Resection for Early Hepatocellular Carcinoma: Preoperative Predictors of Non Transplantable Recurrence and Implications for Treatment Allocation.

Ann Surg 2020 11;272(5):820-826

Hepatobiliary Center Paul Brousse Hospital, APHP-Université Paris Saclay, Villejuif, France.

Background And Aims: LR and LT are the standard curative options for early HCC. LT provides best long-term survival but is limited by organ shortage. LR, readily available, is hampered by high recurrence rates. Salvage liver transplantation is an efficient treatment of recurrences within criteria. The aim of the study was to identify preoperative predictors of non transplantable recurrence (NTR) to improve patient selection for upfront LR or LT at initial diagnosis.

Study Design: Consecutive LR for transplantable HCC between 2000 and 2015 were studied. A prediction model for NTR based on preoperative variables was developed using sub-distribution hazard ratio after multiple imputation and internal validation by bootstrapping. Model performance was evaluated by the concordance index after correction for optimism.

Results: A total of 148 patients were included. Five-year overall survival and recurrence free survival were 73.6% and 29.3%, respectively (median follow-up 45.8 months). Recurrence rate was 54.8%. NTR rate was 38.2%. Preoperative model for NTR identified >1 nodule [sub-distribution hazard ratio 2.35 95% confidence interval (CI) 1.35-4.09], AFP >100 ng/mL (2.14 95% CI 1.17-3.93), and F4 fibrosis (1.93 95% CI 1.03-3.62). The apparent concordance index of the model was 0.664 after correction for optimism. In the presence of 0, 1, and ≥2 factors, NTR rates were 2.6%, 22.7%, and 40.9%, respectively. The number of prognostic factors was significantly associated with the pattern of recurrence (P = 0.001) and 5-year recurrence free survival (P < 0.001).

Conclusions: Cirrhosis, >1 nodule, and AFP >100 ng/mL were identified as preoperative predictors of NTR. In the presence of 2 factors or more upfront transplantation should be probably preferred to resection in regard of organ availability. Other patients are good candidates for LR and salvage liver transplantation should be encouraged in eligible patients with recurrence.
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http://dx.doi.org/10.1097/SLA.0000000000004259DOI Listing
November 2020
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