Diagnostic performance of FibroTest, SteatoTest and ActiTest in patients with NAFLD using the SAF score as histological reference

BACKGROUND: Blood tests of liver injury are less well validated in non‐alcoholic fatty liver disease (NAFLD) than in patients with chronic viral hepatitis. AIMS: To improve the validation of three blood tests used in NAFLD patients, FibroTest for fibrosis staging, SteatoTest for steatosis grading and ActiTest for inflammation activity grading. METHODS: We pre‐included new NAFLD patients with biopsy and blood tests from a single‐centre cohort (FibroFrance) and from the multicentre FLIP consortium. Contemporaneous biopsies were blindly assessed using the new steatosis, activity and fibrosis (SAF) score, which provides a reliable and reproducible diagnosis and grading/staging of the three elementary features of NAFLD (steatosis, inflammatory activity) and fibrosis with reduced interobserver variability. We used nonbinary‐ROC (NonBinAUROC) as the main endpoint to prevent spectrum effect and multiple testing. RESULTS: A total of 600 patients with reliable tests and biopsies were included. The mean NonBinAUROCs (95% CI) of tests were all significant (P < 0.0001): 0.878 (0.864–0.892) for FibroTest and fibrosis stages, 0.846 (0.830–0.862) for ActiTest and activity grades, and 0.822 (0.804–0.840) for SteatoTest and steatosis grades. FibroTest had a higher NonBinAUROC than BARD (0.836; 0.820–0.852; P = 0.0001), FIB4 (0.845; 0.829–0.861; P = 0.007) but not significantly different than the NAFLD score (0.866; 0.850–0.882; P = 0.26). FibroTest had a significant difference in median values between adjacent stage F2 and stage F1 contrarily to BARD, FIB4 and NAFLD scores (Bonferroni test P < 0.05). CONCLUSIONS: In patients with NAFLD, SteatoTest, ActiTest and FibroTest are non‐invasive tests that offer an alternative to biopsy, and they correlate with the simple grading/staging of the SAF scoring system across the three elementary features of NAFLD: steatosis, inflammatory activity and fibrosis

Preemptive-TIPS improves outcome in high-risk variceal bleeding : An observational study

Objective Patients admitted with acute variceal bleeding (AVB) and Child Pugh C score (CP\u2010C) or Child Pugh B plus active bleeding at endoscopy (CP\u2010B+AB) are at high risk for treatment failure, rebleeding and mortality. Preemptive TIPS (p\u2010TIPS) has been shown to improve survival in these patients but its use in clinical practice has been challenged and not routinely incorporated. The present study aimed to further validate the role of preemptive TIPS in a large number of high\u2010risk patients. Design Multicenter, international, observational study including 671 patients from 34 centers admitted for AVB and high\u2010risk of treatment failure. Patients were managed according to current guidelines and use of drugs and endoscopic therapy (D+E) or preemptive TIPS (p\u2010TIPS) was based on individual center policy. Results p\u2010TIPS in the setting of AVB is associated with a lower mortality in Child C patients compared to D+E (1 year mortality 22% vs 47% in D+E group; P=0.002). Mortality rate in CP\u2010B+AB patients was low and p\u2010TIPS did not improve it. In CP\u2010C and CP\u2010B +AB patients, p\u2010TIPS reduces treatment failure and rebleeding (1 year CIF\u2010probability of remaining free of the composite endpoint: 92% vs 74% in the D+E group; P=0.017), development of \u201cde novo\u201d or worsening of previous ascites without increasing rates of hepatic encephalopathy. Conclusion p\u2010TIPS must be the treatment of choice in CP\u2010C patients with AVB. Due to the strong benefit in preventing further bleeding and ascites, p\u2010TIPS could be a good treatment strategy for CP\u2010B+AB patients

Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study

peer reviewedBackground: 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. Methods: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. Findings: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI –∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8–27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI −0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17–0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33–2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16–0·47] and 0·21 [0·13–0·32]). Interpretation: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. Funding: The present study has been granted by the French Ministry of Health—Programme Hospitalier de Recherche Clinique 2010

Hepatic encephalopathy in aptients with cirrhosis : pathophysiology, TIPS as a risk factor, multimodal MRI for the prediction of neurological prognosis after TIPS placement

Le TIPS (Transjugular Intrahepatic Portosystemic Shunts) est le traitement de référence au cours de l'hémorragie digestive par rupture de varices, ou dans le traitement de l'ascite réfractaire chez les patients atteitns de cirrhose. Il peut entraîner une encéphalopathie hépatique (EH), dans 35% des cas environ. L'imagerie par résonnance magnétique (IRM) cérébrale est l'examen de référence pour le diagnostic et le pronostic des maladies neurologiques. L'IRM multimodale combine la spectroscopie, l'imagerie par tenseur de diffusion, et l'IRM fonctionnelle de repos. La combinaison de ces différentes techniques a un intérêt pour le pronostic neurologique après traumatisme crânien ou arrêt cardio-respiratoire. Dans la première partie de ce travail, nous ferons une revue de la littérature sur l'EH en 2017. Nous décrirons les bénéfices du TIPS dans la prise en charge des complications de la cirrhose telles que l'hémorragie digestive et l'ascite, et aussi la probabilité de développer une EH après TIPS. La deuxième partie de ce travail sera consacrée à l'IRM cérébrale mutimodale. Nous en expliquerons les principes généraux, puis nous décrirons les données publiées dans la cirrhose. Enfin, nous présenterons les résultats obtenus en IRM cérébrale multimodale chez des patients candidats à la pose d'un TIPS. Nous décrirons en particulier qu'il existe des facteurs prédictifs de développement d'une EH après TIPS. En effet, la fraction d'anisotropie est plus basse dans notre série avant TIPS chez les aptients qui vont développer une EH après TIPS. Ainsi, le tenseur de diffusion pourrait aider à discrimier les patients qui sont les plus à risque de développer une EH.TIPS placement is required for the management of variceal bleeding or ascites in cirrhosis. However, hepatic encephalopathy (HE) may occur in 35% of patients after TIPS placement. Magnetic resonance imaging (MRI) is the best exam for the diagnosis and the prognosis of several neurological diseases. Multimodal MRI combines spectroscopy, diffusion tensor imaging and resting state. It has been proven to help for neurological prognostic in comatose patients after traumatic brain injury or cardiac arrest. In this manuscript, we will explain HE pathophysiology and management of HE in 2017. We will also describe results obtained with TIPS placement in patients with variceal bleeding. The second part of the manuscript will be dedicated to multimodal MRI: we will clarify each technique and what has been published in the setting of cirrhosis. Last, we will explain our results obtained in patients who are candidate for non urgent TIPS placement and will suggest that a low fractional anisotropy before TIPS may help to identify patients that are at risk of developing HE after TIPS

Encéphalopathie hépatique chez les patiens atteints de cirrhose : le TIPS comme facteur de risque, apport de l'IRM multitmodale

TIPS placement is required for the management of variceal bleeding or ascites in cirrhosis. However, hepatic encephalopathy (HE) may occur in 35% of patients after TIPS placement. Magnetic resonance imaging (MRI) is the best exam for the diagnosis and the prognosis of several neurological diseases. Multimodal MRI combines spectroscopy, diffusion tensor imaging and resting state. It has been proven to help for neurological prognostic in comatose patients after traumatic brain injury or cardiac arrest. In this manuscript, we will explain HE pathophysiology and management of HE in 2017. We will also describe results obtained with TIPS placement in patients with variceal bleeding. The second part of the manuscript will be dedicated to multimodal MRI: we will clarify each technique and what has been published in the setting of cirrhosis. Last, we will explain our results obtained in patients who are candidate for non urgent TIPS placement and will suggest that a low fractional anisotropy before TIPS may help to identify patients that are at risk of developing HE after TIPS.Le TIPS (Transjugular Intrahepatic Portosystemic Shunts) est le traitement de référence au cours de l'hémorragie digestive par rupture de varices, ou dans le traitement de l'ascite réfractaire chez les patients atteitns de cirrhose. Il peut entraîner une encéphalopathie hépatique (EH), dans 35% des cas environ. L'imagerie par résonnance magnétique (IRM) cérébrale est l'examen de référence pour le diagnostic et le pronostic des maladies neurologiques. L'IRM multimodale combine la spectroscopie, l'imagerie par tenseur de diffusion, et l'IRM fonctionnelle de repos. La combinaison de ces différentes techniques a un intérêt pour le pronostic neurologique après traumatisme crânien ou arrêt cardio-respiratoire. Dans la première partie de ce travail, nous ferons une revue de la littérature sur l'EH en 2017. Nous décrirons les bénéfices du TIPS dans la prise en charge des complications de la cirrhose telles que l'hémorragie digestive et l'ascite, et aussi la probabilité de développer une EH après TIPS. La deuxième partie de ce travail sera consacrée à l'IRM cérébrale mutimodale. Nous en expliquerons les principes généraux, puis nous décrirons les données publiées dans la cirrhose. Enfin, nous présenterons les résultats obtenus en IRM cérébrale multimodale chez des patients candidats à la pose d'un TIPS. Nous décrirons en particulier qu'il existe des facteurs prédictifs de développement d'une EH après TIPS. En effet, la fraction d'anisotropie est plus basse dans notre série avant TIPS chez les aptients qui vont développer une EH après TIPS. Ainsi, le tenseur de diffusion pourrait aider à discrimier les patients qui sont les plus à risque de développer une EH

Oméprazole à dose standard ou à forte dose en intraveineux à la seringue électrique dans l ulcère gastro-duodénal hémorragique (une étude rétrospective)

L'objectif de cette étude est de comparer l'efficacité de 2 doses d'oméprazole dans l'ulcère gastro-duodénal (UGD) hémorragique. Pour cela, nous avons revu les dossiers de tous les patients consécutifs admis entre 1997 et 2004 pour UGD hémorragique ayant bénéficié d'un traitement endoscopique efficace. Nous avons distingué 2 périodes : avant janvier 2001, oméprazole à doses standard (40 mg/jour IV jusqu'à reprise de l'alimentation, puis 40 mg per os une semaine) ; après janvier 2001, oméprazole à fortes doses (80 mg en bolus, puis 8 mg/h en perfusion continue 72 h, puis 40 mg per os une semaine). Pendant les 2 périodes, tous les patients avaient ensuite été traités par oméprazole per os 20 mg/jour 3 semaines. Nous avons inclus 114 patients (période 1, n=45 ; période 2, n=69). Le traitement par oméprazole IVSE diminuait significativement la survenue d'une évolution défavorable (27% contre 12%, p=0.04), et d'une récidive hémorragique (24% contre 7%, p=0.01), la mortalité secondaire à un choc hémorragique (11% contre 0%, p<0.001), et le recours à la chirurgie de sauvetage (9% contre 1%, p=0.05). Dans cette étude rétrospective, l'oméprazole IVSE à forte dose diminue le taux de récidive hémorragique, le recours à la chirurgie de sauvetage, et la mortalité secondaire à un choc hémorragique en cas d'UGD hémorragique, par rapport à l'oméprazole à doses standard.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Portal hypertension and hepatocellular carcinoma: des liaisons dangereuses …

International audienceIntroduction: Portal hypertension (PHT) and Hepatocellular carcinoma (HCC) are major complication of cirrhosis which significantly contribute to morbidity and mortality. In this review, we aim to describe the consequences of both angiogenesis and inflammation in the pathogenesis of PHT and HCC, but also the difficulty to propose adapted treatment when PHT and HCC coexist in the same patients.Methods: Studies for review in this article were retrieved from the PubMed database using literature published in English until March 2021.Results: PHT occurs secondary to an increase of intrahepatic vascular resistances, the opening of portosystemic collateral vessels and the formation of neovessels, related to vascular endothelial growth factor (VEGF). Recently, bacterial translocation-mediated inflammation was also identified as a major contributor to PHT. Interestingly, VEGF and chronic inflammation also contribute to HCC occurrence. As PHT and HCC often coexist in the same patient, management of PHT and its related complications as well as HCC treatment appear more complex. Indeed, PHT-related complications such as significant ascites may hamper the access to HCC treatment and the presence of HCC is also independently associated with poor prognosis in patients with acute variceal bleeding related to PHT. Due to their respective mechanism of action, the combination of Atezolizumab and Bevacizumab for advanced HCC may impact the level of PHT and its related complications and to date, no real-life data are available. Finally, appropriate evaluation and treatment of PHT remains a major issue in order to improve the outcome of HCC patients

PERSISTENT ACLF: CHARACTERISTICS OF THE PATIENTS IN THE PHASE IIb HEP 102-DHELIVER STUDY

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Unsolved Questions in Salvage TIPSS: Practical Modalities for Placement, Alternative Therapeutics, and Long-Term Outcomes

Salvage transjugular intrahepatic portosystemic shunt (TIPSS) has proven its efficacy to treat refractory variceal bleeding for patients with cirrhosis. However, this procedure is associated with very poor outcomes. As it is used as a last resort to treat a severe complication of cirrhosis, it seems essential to improve our practice, with the aim of optimizing management of those patients. Somehow, many questions are still unsolved: which stents should be used? Should a concomitant embolization be systematically considered? Is there any alternative therapeutic in case of recurrent bleeding despite TIPSS? What are the long-term outcomes on survival, liver transplantation, and hepatic encephalopathy after salvage TIPSS? Is this procedure futile in some patients? Is prognosis with salvage TIPSS nowadays as bad as earlier, despite the improvement of prophylaxis for variceal bleeding? The aim of this review is to summarize those data and to identify the lacking ones to guide further research on salvage TIPSS