Publications by authors named "Alexandre Louvet"

95 Publications

Reply to HEP-21-0216 "Acute Liver Injury due to Therapeutic Doses of Acetaminophen - Confounders must be ruled out!"

Hepatology 2021 Feb 27. Epub 2021 Feb 27.

Hôpital Claude Huriez, Service d'Hépato-gastroentérologie, France.

We disagree with the conclusion of Vojjala et al., which states that clinicians should pay attention to metabolic risk factors, fatty liver and concurrent drug use. The authors questioned the presence of NAFLD in our study. However, the median BMI was normal in the patients admitted with ALITD and was not different from that of patients admitted with acetaminophen overdose: 21.9 vs. 22 kg/m , p=0.5. Therefore, the prevalence of metabolic syndrome was a rare event. Moreover, previous studies have not identified any relationship between BMI and the outcome or pattern of intoxication(1). Obesity was not found to have any impact on acetaminophen toxicity in the study by Radosevich et al.(2).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.31769DOI Listing
February 2021

Letter: the improvement of sarcopenia after TIPSS might result from the survivor bias-authors' reply.

Aliment Pharmacol Ther 2021 03;53(5):677-678

Service des maladies de l'appareil digestif, Hôpital Claude Huriez, CHU Lille, Lille, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.16274DOI Listing
March 2021

Trajectory of Serum Bilirubin Predicts Spontaneous Recovery in a Real-World Cohort of Patients With Alcoholic Hepatitis.

Clin Gastroenterol Hepatol 2021 Jan 28. Epub 2021 Jan 28.

Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Background And Aims: Alcoholic hepatitis (AH) is a severe condition with poor short-term prognosis. Specific treatment with corticosteroids slightly improves short-term survival but is associated with infection and is not used in many centers. A reliable method to identify patients who will recover spontaneously will minimise the numbers of patients who experience side effects of available treatments.

Methods: We analysed the trajectory of serum bilirubin concentration over the course of hospital admissions in patients with AH to predict spontaneous survival and the need for treatment.

Results: data from 426 patients were analysed. Based on bilirubin trajectory, patients were categorized into three groups: 'fast fallers' (bilirubin <0.8 x admission value at day 7), 'static' (bilirubin of >0.9 - <1.2 x admission value) and 'rapid risers' (bilirubin of ≥1.2 x admission bilirubin). Fast fallers had significantly better 90-day survival compared to other groups (log rank p < .001), and showed no benefit of corticosteroid therapy (OR for survival at 28 days of treatment, 0.94, 95% CI 0.06 - 8.41). These findings remained even amongst patients with severe disease based on initial DF, GAHS or MELD scores.

Conclusions: We present an intuitive method of classifying patients with AH based on the trajectory of bilirubin over the first week of admission. It is complimentary to existing scores that identify candidates for corticosteroid treatment or assess response to treatment. This method identifies a group of patients with AH who recover spontaneously and can avoid corticosteroid therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2021.01.042DOI Listing
January 2021

TIPSS and reversal of sarcopenia, and TIPSS is a promising therapy for sarcopenia in cirrhosis-Authors' reply.

Aliment Pharmacol Ther 2021 01;53(1):211-212

Service des maladies de l'appareil digestif, Hôpital Claude Huriez, CHU Lille, Lille, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.16152DOI Listing
January 2021

Letter: TIPSS improves muscle mass indices in patients with cirrhosis and severe portal hypertension - authors' reply.

Aliment Pharmacol Ther 2021 01;53(1):199-200

Service des maladies de l'appareil digestif, Hôpital Claude Huriez, CHU Lille, Lille, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.16154DOI Listing
January 2021

Integrated Multiomics Reveals Glucose Use Reprogramming and Identifies a Novel Hexokinase in Alcoholic Hepatitis.

Gastroenterology 2021 Apr 10;160(5):1725-1740.e2. Epub 2020 Dec 10.

Division of Gastroenterology and Hepatology, Departments of Medicine and Nutrition, and Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, North Carolina; Department of Gastroenterology and Hepatology, Division of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address:

Background & Aims: We recently showed that alcoholic hepatitis (AH) is characterized by dedifferentiation of hepatocytes and loss of mature functions. Glucose metabolism is tightly regulated in healthy hepatocytes. We hypothesize that AH may lead to metabolic reprogramming of the liver, including dysregulation of glucose metabolism.

Methods: We performed integrated metabolomic and transcriptomic analyses of liver tissue from patients with AH or alcoholic cirrhosis or normal liver tissue from hepatic resection. Focused analyses of chromatin immunoprecipitation coupled to DNA sequencing was performed. Functional in vitro studies were performed in primary rat and human hepatocytes and HepG2 cells.

Results: Patients with AH exhibited specific changes in the levels of intermediates of glycolysis/gluconeogenesis, the tricarboxylic acid cycle, and monosaccharide and disaccharide metabolism. Integrated analysis of the transcriptome and metabolome showed the used of alternate energetic pathways, metabolite sinks and bottlenecks, and dysregulated glucose storage in patients with AH. Among genes involved in glucose metabolism, hexokinase domain containing 1 (HKDC1) was identified as the most up-regulated kinase in patients with AH. Histone active promoter and enhancer markers were increased in the HKDC1 genomic region. High HKDC1 levels were associated with the development of acute kidney injury and decreased survival. Increased HKDC1 activity contributed to the accumulation of glucose-6-P and glycogen in primary rat hepatocytes.

Conclusions: Altered metabolite levels and messenger RNA expression of metabolic enzymes suggest the existence of extensive reprogramming of glucose metabolism in AH. Increased HKDC1 expression may contribute to dysregulated glucose metabolism and represents a novel biomarker and therapeutic target for AH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2020.12.008DOI Listing
April 2021

Acute Liver Injury With Therapeutic Doses of Acetaminophen: A Prospective Study.

Hepatology 2020 Dec 11. Epub 2020 Dec 11.

Service des Maladies de l'appareil digestif, Hôpital Huriez, CHU de Lille, Lille, France.

Background And Aims: Because of the extensive use of this drug, further evaluation of acute liver injury (ALI) with therapeutic doses of acetaminophen (APAP; ≤6 g/d) is required. We characterize ALI with therapeutic doses of APAP and determine the host factors associated with disease severity and the predictors of outcome.

Approach And Results: All patients admitted with severe APAP-related ALI in our center were included from 2002 to 2019, either attributable to therapeutic doses or overdose. ALI with therapeutic doses (ALITD) was defined as APAP intake <6 g/d. Overall, 311 of 400 patients with APAP-related ALI had overdose and 89 had taken therapeutic doses. The host factors associated with ALITD were fasting ≥1 day (47.5% of ALITD patients vs. 26% in overdose; P = 0.001), excess drinking (93.3% vs. 48.5%; P < 0.0001), and repeated APAP use (4 vs. 1 day; P < 0.0001). Patients with ALITD were older (44 vs. 30.7 years; P < 0.0001) and had more severe liver injury. In the overall population, the independent predictors of disease severity were older age, longer duration of APAP, and excess drinking. Thirty-day survival was lower in ALITD than in overdose (87.2 ± 3.6% vs. 94.6 ± 1.3%; P = 0.02). Age and the presence of at least one of the King's College Hospital criteria were independent predictors of 30-day survival whereas the pattern of drug intoxication, excess drinking, and bilirubin were not.

Conclusions: ALI with therapeutic doses of APAP is associated with more severe liver injury than overdose. It only occurs in patients with excess drinking and/or fasting. A warning should be issued about the repeated use of nontoxic doses of APAP in patients with those risk factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.31678DOI Listing
December 2020

Consequences of TIPSS placement on the body composition of patients with cirrhosis and severe portal hypertension: a large retrospective CT-based surveillance.

Aliment Pharmacol Ther 2020 11 15;52(9):1516-1526. Epub 2020 Sep 15.

Service des maladies de l'appareil digestif, Hôpital Claude Huriez, CHU Lille, Lille, France.

Background: Body composition may be modified after improvement of portal hypertension (PHT) by transjugular intrahepatic portosystemic shunt (TIPSS) insertion.

Aims: To evaluate changes in body composition following TIPSS placement, their relationship with radiological TIPSS patency and function, and the predictive value of these parameters METHODS: We retrospectively included 179 patients with cirrhosis who underwent TIPSS placement in our centre for severe PHT from 2011 to 2017. CT scan-based surveillance was performed at baseline, 1-3 (M1-M3) and 6 months (M6).

Results: The median model for end-stage liver disease (MELD) score was 11.4 (8.8-15.1) and Child-Pugh score 8 (7-9). Only the MELD score (HR 1.14, 95% CI 1.08-1.20) and sarcopenia assessed by transversal right psoas muscle thickness at the umbilical level/height (TPMPT/height) (HR 0.86, 95% CI 0.79-0.96) were independently associated with 6-month mortality on multivariate analysis. After TIPSS insertion, TPMT/height increased from 19 mm/m (baseline) to 19.6 mm/m (M1-M3, P = 0.004) and 21.1 mm/m (M6, P < 0.0001). The improvement and its extent were dependent on the radiological patency and dysfunction of TIPSS. Subcutaneous fat surface (SCFS) increased from 183.4 to 193 cm (P < 0.0001) and 229.8 cm (P < 0.0001), respectively. We observed a decrease in visceral fat surface (VFS) between baseline and M1-M3 (163.5-140.5 cm [P < 0.0001]), but not between M1-M3 and M6 (140.5-141.2 cm [P = 0.9]). SCFS and VFS did not seem to be modified by radiological TIPSS patency and dysfunction.

Conclusions: Sarcopenia is independently associated with 6-month outcome and improves after TIPSS placement, together with an inverse evolution of subcutaneous and visceral fat. TIPSS not only treats PHT but also improves body composition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.16080DOI Listing
November 2020

A tool to predict progression of non-alcoholic fatty liver disease in severely obese patients.

Liver Int 2021 01;41(1):91-100

Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France.

Background & Aims: Severely obese patients are a growing population at risk of non-alcoholic fatty liver disease (NAFLD). Considering the increasing burden, a predictive tool of NAFLD progression would be of interest. Our objective was to provide a tool allowing general practitioners to identify and refer the patients most at risk, and specialists to estimate disease progression and adapt the therapeutic strategy.

Methods: This predictive tool is based on a Markov model simulating steatosis, fibrosis and non-alcoholic steatohepatitis (NASH) evolution. This model was developped from data of 1801 severely obese, bariatric surgery candidates, with histological assessment, integrating duration of exposure to risk factors. It is then able to predict current disease severity in the absence of assessment, and future cirrhosis risk based on current stage.

Results: The model quantifies the impact of sex, body-mass index at 20, diabetes, age of overweight onset, on progression. For example, for 40-year-old severely obese patients seen by the general practitioners: (a) non-diabetic woman overweight at 20, and (b) diabetic man overweight at 10, without disease assessment, the model predicts their current risk to have NASH or F3-F4: for (a) 5.7% and 0.6%, for (b) 16.1% and 10.0% respectively. If those patients have been diagnosed F2 by the specialist, the model predicts the 5-year cirrhosis risk: 1.8% in the absence of NASH and 6.0% in its presence for (a), 10.3% and 26.7% respectively, for (b).

Conclusions: This model provides a decision-making tool to predict the risk of liver disease that could help manage severely obese patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14650DOI Listing
January 2021

Alcoholic hepatitis: Towards an era of personalised management.

United European Gastroenterol J 2020 11 27;8(9):995-1002. Epub 2020 Jul 27.

Service des maladies de l'appareil digestif, Université Lille Nord de France, Lille, France.

Alcoholic hepatitis should be suspected in every patient with excessive chronic alcohol consumption and recent onset of jaundice. Diagnosis of alcoholic hepatitis is based on clinical and laboratory findings, and confirmed by a liver biopsy when available. Several scores are available to assess severity and prognosis of alcoholic hepatitis. The 1-month mortality of patients with severe alcoholic hepatitis, as defined by Maddrey's discriminant function, is 20-30%. Therefore, severe alcoholic hepatitis should be treated with a 28-day course of oral prednisolone after systematic screening for infection. In this review, we discuss diagnosis of alcoholic hepatitis, the different scores to assess severity of the disease, indications for corticosteroid therapy and alternative therapeutic options for non-responders to medical therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2050640620945886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724541PMC
November 2020

Intestinal Virome in Patients With Alcoholic Hepatitis.

Hepatology 2020 12 10;72(6):2182-2196. Epub 2020 Oct 10.

Department of Medicine, University of California San Diego, La Jolla, CA.

Background And Aims: Alcoholic hepatitis (AH) is a severe manifestation of alcohol-associated liver disease (ALD) with high mortality. Although gut bacteria and fungi modulate disease severity, little is known about the effects of the viral microbiome (virome) in patients with ALD.

Approach And Results: We extracted virus-like particles from 89 patients with AH who were enrolled in a multicenter observational study, 36 with alcohol use disorder (AUD), and 17 persons without AUD (controls). Virus-like particles from fecal samples were fractionated using differential filtration techniques, and metagenomic sequencing was performed to characterize intestinal viromes. We observed an increased viral diversity in fecal samples from patients with ALD, with the most significant changes in samples from patients with AH. Escherichia-, Enterobacteria-, and Enterococcus phages were over-represented in fecal samples from patients with AH, along with significant increases in mammalian viruses such as Parvoviridae and Herpesviridae. Antibiotic treatment was associated with higher viral diversity. Specific viral taxa, such as Staphylococcus phages and Herpesviridae, were associated with increased disease severity, indicated by a higher median Model for End-Stage Liver Disease score, and associated with increased 90-day mortality.

Conclusions: In conclusion, intestinal viral taxa are altered in fecal samples from patients with AH and associated with disease severity and mortality. Our study describes an intestinal virome signature associated with AH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.31459DOI Listing
December 2020

Bariatric Surgery Provides Long-term Resolution of Nonalcoholic Steatohepatitis and Regression of Fibrosis.

Gastroenterology 2020 10 15;159(4):1290-1301.e5. Epub 2020 Jun 15.

Service des Maladies de l'Appareil Digestif et de la Nutrition, Centre Hospitalier Universitaire de Lille, Lille, France; LIRIC (Lille Inflammation Research International Center) U995, Université de Lille, Institut National de la Santé et de la Recherche Médicale, Centre Hospitalier Universitaire de Lille, Lille, France. Electronic address:

Background And Aims: Studies are needed to determine the long-term effects of bariatric surgery for patients with nonalcoholic steatohepatitis (NASH). We evaluated sequential liver samples, collected the time of bariatric surgery and 1 and 5 years later, to assess the long-term effects of bariatric surgery in patients with NASH.

Methods: We performed a prospective study of 180 severely obese patients with biopsy-proven NASH, defined by the NASH clinical research network histologic scores. The patients underwent bariatric surgery at a single center in France and were followed for 5 years. We obtained liver samples from 125 of 169 patients (76%) having reached 1 year and 64 of 94 patients (68%) having reached 5 years after surgery. The primary endpoint was the resolution of NASH without worsening of fibrosis at 5 years. Secondary end points were improvement in fibrosis (reduction of ≥1 stage) at 5 years and regression of fibrosis and NASH at 1 and 5 years.

Results: At 5 years after bariatric surgery, NASH was resolved, without worsening fibrosis, in samples from 84% of patients (n = 64; 95% confidence interval, 73.1%-92.2%). Fibrosis decreased, compared with baseline, in samples from 70.2% of patients (95% CI, 56.6%-81.6%). Fibrosis disappeared from samples from 56% of all patients (95% CI, 42.4%-69.3%) and from samples from 45.5% of patients with baseline bridging fibrosis. Persistence of NASH was associated with no decrease in fibrosis and less weight loss (reduction in body mass index of 6.3 ± 4.1 kg/m in patients with persistent NASH vs reduction of 13.4 ± 7.4 kg/m; P = .017 with resolution of NASH). Resolution of NASH was observed at 1 year after bariatric surgery in biopsies from 84% of patients, with no significant recurrence between 1 and 5 years (P = .17). Fibrosis began to decrease by 1 year after surgery and continued to decrease until 5 years (P < .001).

Conclusions: In a long-term follow-up of patients with NASH who underwent bariatric surgery, we observed resolution of NASH in liver samples from 84% of patients 5 years later. The reduction of fibrosis is progressive, beginning during the first year and continuing through 5 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2020.06.006DOI Listing
October 2020

Real life experience of mycophenolate mofetil monotherapy in liver transplant patients.

Clin Res Hepatol Gastroenterol 2021 Jan 11;45(1):101451. Epub 2020 Jun 11.

Maladies Appareil Digestif, pole médico-chirurgical, Hôpital Huriez CHU Lille, Inserm U995, Université de Lille, France. Electronic address:

Background: Mycophenolate mofetil (MMF) monotherapy following liver transplantation (LT) remains controversial due to a risk of acute rejection. The aim of this study was to report the largest multicenter experience of the use a MMF monotherapy guided by therapeutic drug monitoring using pharmacoslope modeling and Bayesian estimations of the MPA inter-dose AUC (AUC) before withdrawing calcineurin inhibitors (CNI) and to evaluate the benefit of MMF monotherapy.

Methods: MMF daily doses were adjusted to reach the AUC target of 45μg.h/mL. Then CNI were withdrawn and patients were followed on liver test and clinical outcomes.

Main Findings: From 2000-2014, in 2 transplantation centers, 94 liver transplant recipients received MMF monotherapy 6.5±4 years after LT. The mean AUC was 45.5±16μg.h/mL. During follow-up, 4 patients experienced acute rejection (4%). During the first year, estimated glomerular filtration rate (eGFR) improved from 46.2±10.5 to 49.1±11.5mL/kg/min (P=0.025). Benefit persisted at year 5. In patients with metabolic syndrome, eGFR did not improve.

Conclusion: MMF monotherapy regimen appears usually safe and beneficial, with low risk of acute rejection and eGFR improvement. Therapeutic drug monitoring strategy seemed useful by identifying 14% of patients with low MMF exposure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2020.04.017DOI Listing
January 2021

Combined alcoholic and non-alcoholic steatohepatitis.

JHEP Rep 2020 Jun 22;2(3):100101. Epub 2020 May 22.

Service des maladies de l'appareil digestif, Hôpital Huriez, Rue Polonowski, 59037 Lille Cedex, France.

While metabolic syndrome and alcohol consumption are the two main causes of chronic liver disease, one of the two conditions is often predominant, with the other acting as a cofactor of morbimortality. It has been shown that obesity and alcohol act synergistically to increase the risk of fibrosis progression, hepatic carcinogenesis and mortality, while genetic polymorphisms can strongly influence disease progression. Based on common pathogenic pathways, there are several potential targets that could be used to treat both diseases; based on the prevalence and incidence of these diseases, new therapies and clinical trials are needed urgently.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhepr.2020.100101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267467PMC
June 2020

Transcatheter aortic valve replacement (TAVR) as bridge therapy restoring eligibility for liver transplantation in cirrhotic patients.

Am J Transplant 2020 09 8;20(9):2567-2570. Epub 2020 Jul 8.

Department of Hepatogastroenterology, CHU Lille, Lille, France.

Severe aortic stenosis is a widespread valve disease, constituting a contraindication to organ transplantation due to cardiovascular morbidity and projected mortality. Mortality after conventional surgical aortic valve replacement in cirrhotic patients depends upon the Child-Pugh class. In the past few years, transcatheter aortic valve replacement has progressively become the treatment of choice for high-risk patients with severe aortic stenosis. Here, we report the cases of 3 cirrhotic patients who became eligible for liver transplantation after successful transcatheter aortic valve replacement as bridge therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.15955DOI Listing
September 2020

IL-33/ST2 pathway regulates neutrophil migration and predicts outcome in patients with severe alcoholic hepatitis.

J Hepatol 2020 06 15;72(6):1052-1061. Epub 2020 Jan 15.

Hôpital Claude-Huriez, Service Maladies de l'Appareil Digestif, CHU Lille, Lille, France; Université de Lille/Inserm/CHU de Lille, U995 - LIRIC - Lille Inflammation Research Center, Lille, France. Electronic address:

Background & Aims: Severe alcoholic hepatitis (SAH) is associated with a high risk of infection. The IL-33/ST2 pathway is involved in sepsis control but data regarding its role in alcohol-related liver disease (ALD) are lacking. We aimed to characterize the role of IL-33/ST2 in the polymorphonuclear neutrophils (PMNs) of patients with ALD and SAH.

Methods: Serum and circulating neutrophils were collected from patients with SAH, alcoholic cirrhosis and healthy controls. We quantified IL-33/ST2 pathway activity and CXCR2 at baseline and after exposure to IL-33. We also determined the migration capacity of PMNs.

Results: The decoy receptor of IL-33 (soluble ST2 [sST2]) was increased in SAH vs. cirrhosis and controls, demonstrating the defect in this pathway during ALD. The sST2 level was associated with response to treatment, 2-month survival, infection-free survival and probability of infection in SAH. Endotoxemia was weakly correlated with sST2. GRK2, a negative regulator of CXCR2, was overexpressed in PMNs of patients with SAH and cirrhosis and was decreased by IL-33. CXCR2 levels on PMNs were lower in SAH vs. cirrhosis and controls. Treatment with IL-33 partially restored CXCR2 expression in SAH and cirrhosis. PMN migration upon IL-8 was lower in patients with SAH and cirrhosis vs. controls. Treatment with IL-33 partially restored migration in those with SAH and cirrhosis. Interestingly, the migration capacity of PMNs and the response to IL-33 were enhanced in responders to corticosteroids (Lille <0.45) compared to non-responders.

Conclusion: The IL33/ST2 pathway is defective in SAH and predicts outcome. This defect is associated with decreased CXCR2 expression on the surface of PMNs and lower migration capacity, which can be corrected by IL-33, especially in patients responding to steroids. These results suggest that IL-33 has therapeutic potential for SAH and its infectious complications.

Lay Summary: The neutrophils of patients with severe alcoholic hepatitis are associated with a defect in the IL-33/ST2 pathway. This defect is associated with lower migration capacities in neutrophils and a higher probability of getting infected. Administration of IL-33 to the neutrophils at least partly restores this defect and may be effective at reducing the risk of infection in patients with severe alcoholic hepatitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2019.12.017DOI Listing
June 2020

A Model to Identify Heavy Drinkers at High Risk for Liver Disease Progression.

Clin Gastroenterol Hepatol 2020 Sep 11;18(10):2315-2323.e6. Epub 2020 Jan 11.

Université de Lille, INSERM, Centre Hospitalier Universitaire de Lille, U1286-INFINITE, Lille, France; Université de Paris, IAME, INSERM, Paris, France. Electronic address:

Background & Aims: Alcohol-related liver disease (ALD) causes chronic liver disease. We investigated how information on patients' drinking history and amount, stage of liver disease, and demographic feature can be used to determine risk of disease progression.

Methods: We collected data from 2334 heavy drinkers (50 g/day or more) with persistently abnormal results from liver tests who had been admitted to a hepato-gastroenterology unit in France from January 1982 through December 1997; patients with a recorded duration of alcohol abuse were assigned to the development cohort (n=1599; 75% men) or the validation cohort (n=735; 75% men), based on presence of a liver biopsy. We collected data from both cohorts on patient history and disease stage at the time of hospitalization. For the development cohort, severity of the disease was scored by the METAVIR (due to the availability of liver histology reports); in the validation cohort only the presence of liver complications was assessed. We developed a model of ALD progression and occurrence of liver complications (hepatocellular carcinoma and/or liver decompensation) in association with exposure to alcohol, age at the onset of heavy drinking, amount of alcohol intake, sex and body mass index. The model was fitted to the development cohort and then evaluated in the validation cohort. We then tested the ability of the model to predict disease progression for any patient profile (baseline evaluation). Patients with a 5-y weighted risk of liver complications greater than 5% were considered at high risk for disease progression.

Results: Model results are given for the following patient profiles: men and women, 40 y old, who started drinking at an age of 25 y, drank 150 g/day, and had a body mass index of 22 kg/m according to the disease severity at baseline evaluation. For men with baseline F0-F2 fibrosis, the model estimated the probabilities of normal liver, steatosis, or steatohepatitis at baseline to be 31.8%, 61.5% and 6.7%, respectively. The 5-y weighted risk of liver complications was 1.9%, ranging from 0.2% for men with normal liver at baseline evaluation to 10.3% for patients with steatohepatitis at baseline. For women with baseline F0-F2 fibrosis, probabilities of normal liver, steatosis, or steatohepatitis at baseline were 25.1%, 66.5% and 8.4%, respectively; the 5-y weighted risk of liver complications was 3.2%, ranging from 0.5% for women with normal liver at baseline to 14.7% for patients with steatohepatitis at baseline. Based on the model, men with F3-F4 fibrosis at baseline have a 24.5% 5-y weighted risk of complications (ranging from 20.2% to 34.5%) and women have a 30.1% 5-y weighted risk of complications (ranging from 24.7% to 41.0%).

Conclusions: We developed a Markov model that integrates data on level and duration of alcohol use to identify patients at high risk of liver disease progression. This model might be used to adapt patient care pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2019.12.041DOI Listing
September 2020

Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease.

Nature 2019 11 13;575(7783):505-511. Epub 2019 Nov 13.

Department of Medicine, University of California San Diego, La Jolla, CA, USA.

Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality. Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated liver disease. The gut microbiota promotes ethanol-induced liver disease in mice, but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin-a two-subunit exotoxin that is secreted by Enterococcus faecalis-as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis. The presence of cytolysin-positive (cytolytic) E. faecalis correlated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis. We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecalis with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-019-1742-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872939PMC
November 2019

Editorial: when cirrhosis deserves haemodialysis-rethinking strategies. Authors' reply.

Aliment Pharmacol Ther 2019 08;50(4):457-458

Hôpital Claude Huriez, Service Maladies de l'Appareil Digestif and INSERM Unité 995, Lille, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.15366DOI Listing
August 2019

Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis.

Nat Commun 2019 07 16;10(1):3126. Epub 2019 Jul 16.

Division of Gastroenterology, Hepatology and Nutrition, Pittsburgh Liver Research Center, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, 15261, USA.

Alcoholic hepatitis (AH) is a life-threatening condition characterized by profound hepatocellular dysfunction for which targeted treatments are urgently needed. Identification of molecular drivers is hampered by the lack of suitable animal models. By performing RNA sequencing in livers from patients with different phenotypes of alcohol-related liver disease (ALD), we show that development of AH is characterized by defective activity of liver-enriched transcription factors (LETFs). TGFβ1 is a key upstream transcriptome regulator in AH and induces the use of HNF4α P2 promoter in hepatocytes, which results in defective metabolic and synthetic functions. Gene polymorphisms in LETFs including HNF4α are not associated with the development of AH. In contrast, epigenetic studies show that AH livers have profound changes in DNA methylation state and chromatin remodeling, affecting HNF4α-dependent gene expression. We conclude that targeting TGFβ1 and epigenetic drivers that modulate HNF4α-dependent gene expression could be beneficial to improve hepatocellular function in patients with AH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-11004-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635373PMC
July 2019

Time to Reconsider Listing Criteria for Alcohol-Associated Liver Disease?

Liver Transpl 2019 09;25(9):1303-1304

Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lt.25597DOI Listing
September 2019

Intestinal Fungal Dysbiosis and Systemic Immune Response to Fungi in Patients With Alcoholic Hepatitis.

Hepatology 2020 02 20;71(2):522-538. Epub 2019 Aug 20.

Department of Medicine, University of California San Diego, La Jolla, CA.

Chronic alcohol consumption causes increased intestinal permeability and changes in the intestinal microbiota composition, which contribute to the development and progression of alcohol-related liver disease. In this setting, little is known about commensal fungi in the gut. We studied the intestinal mycobiota in a cohort of patients with alcoholic hepatitis, patients with alcohol use disorder, and nonalcoholic controls using fungal-specific internal transcribed spacer amplicon sequencing of fecal samples. We further measured serum anti-Saccharomyces cerevisiae antibodies (ASCA) as a systemic immune response to fungal products or fungi. Candida was the most abundant genus in the fecal mycobiota of the two alcohol groups, whereas genus Penicillium dominated the mycobiome of nonalcoholic controls. We observed a lower diversity in the alcohol groups compared with controls. Antibiotic or steroid treatment was not associated with a lower diversity. Patients with alcoholic hepatitis had significantly higher ASCA levels compared to patients with alcohol use disorder and to nonalcoholic controls. Within the alcoholic hepatitis cohort, patients with levels of at least 34 IU/mL had a significantly lower 90-day survival (59%) compared with those with ASCA levels less than 34 IU/mL (80%) with an adjusted hazard ratio of 3.13 (95% CI, 1.11-8.82; P = 0.031). Conclusion: Patients with alcohol-associated liver disease have a lower fungal diversity with an overgrowth of Candida compared with controls. Higher serum ASCA was associated with increased mortality in patients with alcoholic hepatitis. Intestinal fungi may serve as a therapeutic target to improve survival, and ASCA may be useful to predict the outcome in patients with alcoholic hepatitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.30832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925657PMC
February 2020

Therapeutic Prospects of Cannabidiol for Alcohol Use Disorder and Alcohol-Related Damages on the Liver and the Brain.

Front Pharmacol 2019 31;10:627. Epub 2019 May 31.

Service Universitaire d'Addictologie de Lyon (SUAL), Bron, France.

Cannabidiol (CBD) is a natural component of cannabis that possesses a widespread and complex immunomodulatory, antioxidant, anxiolytic, and antiepileptic properties. Much experimental data suggest that CBD could be used for various purposes in alcohol use disorder (AUD) and alcohol-related damage on the brain and the liver. To provide a rationale for using CBD to treat human subjects with AUD, based on the findings of experimental studies. Narrative review of studies pertaining to the assessment of CBD efficiency on drinking reduction, or on the improvement of any aspect of alcohol-related toxicity in AUD. Experimental studies find that CBD reduces the overall level of alcohol drinking in animal models of AUD by reducing ethanol intake, motivation for ethanol, relapse, anxiety, and impulsivity. Moreover, CBD reduces alcohol-related steatosis and fibrosis in the liver by reducing lipid accumulation, stimulating autophagy, modulating inflammation, reducing oxidative stress, and by inducing death of activated hepatic stellate cells. Finally, CBD reduces alcohol-related brain damage, preventing neuronal loss by its antioxidant and immunomodulatory properties. CBD could directly reduce alcohol drinking in subjects with AUD. Any other applications warrant human trials in this population. By reducing alcohol-related steatosis processes in the liver, and alcohol-related brain damage, CBD could improve both hepatic and neurocognitive outcomes in subjects with AUD, regardless of the individual's drinking trajectory. This might pave the way for testing new harm reduction approaches in AUD, in order to protect the organs of subjects with an ongoing AUD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2019.00627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554654PMC
May 2019

The prognostic impact of cirrhosis on patients receiving maintenance haemodialysis.

Aliment Pharmacol Ther 2019 07 14;50(1):75-83. Epub 2019 May 14.

Hôpital Claude Huriez, Services des Maladies de l'Appareil Digestif, CHRU Lille, and Unité INSERM 995, Lille, France.

Background: Further study is needed on the prognostic impact of cirrhosis on haemodialysis patients.

Aim: To evaluate cirrhosis' impact according to severity on survival and to provide therapeutic guidelines for haemodialysis cirrhotic patients.

Methods: Patients with end-stage renal failure treated with haemodialysis were included retrospectively from 01/01/2000 to 31/12/2004 and prospectively from 01/01/2005 to 31/12/2014 in our French Region. Clinical data, presence of cirrhosis and its severity were recorded at the beginning of haemodialysis. The primary endpoint was 2-year survival.

Results: Seven thousand three hundred and fifty-four patients (96%) without cirrhosis and 304 patients (4%) with cirrhosis were included. Two-year survival in noncirrhotic patients was higher than in cirrhotic patients (71.7% vs 54.4%, P < 0.0001). Patients with decompensated cirrhosis had a worse 2-year outcome (44.1%) as compared to compensated cirrhotic (62.8%, P = 0.002) and noncirrhotic patients (71.7%, P < 0.0001). Compensated and decompensated cirrhosis were independent predictive factors of 2-year mortality. In sensitivity analysis restricted to cirrhotic patients, 2-year survival of Child-Pugh A patients was higher than in Child-Pugh B and C patients (65.5% vs 27.7% vs 0%, P < 0.0001). Development of predictive models based either on severity scores (MELD and Child-Pugh) and extrahepatic comorbidities allowed correct classification of around 70% of patients in terms of mortality and may help to better stratify mortality risk in this population.

Conclusions: Cirrhosis is independently associated with mortality in haemodialysis patients. Patients with severe cirrhosis have a poor 2-year outcome. Severity of cirrhosis and presence of extrahepatic comorbidities should be considered when deciding to initiate renal replacement therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.15279DOI Listing
July 2019

Serum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease.

Dig Dis Sci 2019 07 10;64(7):1878-1892. Epub 2019 May 10.

Department of Medicine, University of California San Diego, La Jolla, CA, USA.

Background: Alcohol-related liver disease is one of the most prevalent chronic liver diseases worldwide. Mechanisms involved in the pathogenesis of alcohol-related liver disease are not well understood. Oxylipins play a crucial role in numerous biological processes and pathological conditions. Nevertheless, oxylipins are not well studied in alcohol-related liver disease.

Aims: (1) To characterize the patterns of bioactive ω-3 and ω-6 polyunsaturated fatty acid metabolites in alcohol use disorder and alcoholic hepatitis patients and (2) to identify associations of serum oxylipins with clinical parameters in patients with alcohol-related liver disease.

Methods: We performed a comprehensive liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis of serum and fecal oxylipins derived from ω-6 arachidonic acid, ω-3 eicosapentaenoic acid, and docosahexaenoic acid in a patient cohort with alcohol-related liver disease.

Results: Our results show profound alterations in the serum oxylipin profile of patients with alcohol use disorder and alcoholic hepatitis compared to nonalcoholic controls. Spearman correlation of the oxylipins with clinical parameters shows a link between different serum oxylipins and intestinal permeability, aspartate aminotransferase, bilirubin, albumin, international normalized ratio, platelet count, steatosis, fibrosis and model for end-stage liver disease score. Especially, higher level of serum 20-HETE was significantly associated with decreased albumin, increased hepatic steatosis, polymorphonuclear infiltration, and 90-day mortality.

Conclusions: Patients with alcohol-related liver disease have different oxylipin profiles. Future studies are required to confirm oxylipins as disease biomarker or to connect oxylipins to disease pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10620-019-05638-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588282PMC
July 2019

Control of replication of hepatitis B and C virus improves patient and graft survival in kidney transplantation.

J Hepatol 2019 05 14;70(5):831-838. Epub 2019 Mar 14.

CHRU de Lille, France, Service des maladies de l'appareil digestif, Université Lille 2 and Inserm U795, France. Electronic address:

Background & Aims: Before antiviral therapy, kidney transplant recipients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) had poor outcomes. Since the 90s, nucleos(t)ide analogues have been widely used in HBV-infected patients, while interferon-based therapy was rarely used in HCV-infected patients. The aim of this study was to assess the impact of HBV and HCV on patient and graft survival, according to viral replication status.

Methods: Data from January 1993 to December 2010 were extracted from the French national database CRISTAL. A total of 31,433 kidney transplant recipients were included, of whom 575, 1,060 and 29,798 had chronic hepatitis B, C, or were not infected, respectively.

Results: Ten-year survival was lower in HCV-infected (71.3%) than in HBV-infected (81.2%, p = 0.0004) or non-infected kidney transplant recipients (82.7%, p <0.0001). Ten-year kidney graft survival was lower in HCV-infected (50.6%) than in HBV-infected (62.3%, p <0.0001) or non-infected kidney transplant recipients (64.7%, p <0.0001). A random analysis of the medical records of 184 patients with HBV and 504 patients with HCV showed a control of viral replication in 94% and 35% of cases, respectively. Ten-year patient and graft survival in patients with detectable HCV RNA was lower than in their matching controls. Conversely, patients with HCV and undetectable HCV RNA had higher 10-year survival than their matched controls without significant differences in graft survival.

Conclusions: Chronic HBV infection does not impact 10-year patient and kidney graft survival thanks to control of viral replication with nucleos(t)ide analogues. In kidney transplant recipients infected with HCV, patients with detectable RNA had worse outcomes, whereas the outcomes of those with undetectable RNA were at least as good as non-infected patients. Thus, direct-acting antivirals should be systematically offered to HCV-infected patients.

Lay Summary: Previously, infections with hepatitis B or hepatitis C virus led to poor outcomes in kidney transplant recipients. However, the outcomes of kidney transplants in patients with viral suppression are as good as those for kidney transplants in non-infected patients. Antiviral therapy should be systematically proposed to hepatitis B and/or hepatitis C-infected kidney transplant recipients or candidates to prevent the deleterious hepatic and extrahepatic impact of chronic viral replication. Recent access to direct-acting antivirals in patients with hepatitis C virus and renal dysfunction provides exciting new opportunities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2018.12.036DOI Listing
May 2019

Nucleotide-binding oligomerization domain 1 (NOD1) modulates liver ischemia reperfusion through the expression adhesion molecules.

J Hepatol 2019 06 25;70(6):1159-1169. Epub 2019 Jan 25.

LIRIC - Lille Inflammation Research International Center - U995, Univ. Lille, Inserm, CHU Lille, F-59000 Lille, France. Electronic address:

Background & Aims: In liver transplantation, organ shortage leads to the use of marginal grafts that are more susceptible to ischemia-reperfusion (IR) injury. We identified nucleotide-binding oligomerization domain 1 (NOD1) as an important modulator of polymorphonuclear neutrophil (PMN)-induced liver injury, which occurs in IR. Herein, we aimed to elucidate the role of NOD1 in IR injury, particularly focusing on its effects on the endothelium and hepatocytes.

Method: Nod1 WT and KO mice were treated with NOD1 agonists and subjected to liver IR. Expression of adhesion molecules was analyzed in total liver, isolated hepatocytes and endothelial cells. Interactions between PMNs and hepatocytes were studied in an ex vivo co-culture model using electron microscopy and lactate dehydrogenase levels. We generated NOD1 antagonist-loaded nanoparticles (np ALINO).

Results: NOD1 agonist treatment increased liver injury, PMN tissue infiltration and upregulated ICAM-1 and VCAM-1 expression 20 hours after reperfusion. NOD1 agonist treatment without IR increased expression of adhesion molecules (ICAM-1, VCAM-1) in total liver and more particularly in WT hepatocytes, but not in Nod1 KO hepatocytes. This induction is dependent of p38 and ERK signaling pathways. Compared to untreated hepatocytes, a NOD1 agonist markedly increased hepatocyte lysis in co-culture with PMNs as shown by the increase of lactate dehydrogenase in supernatants. Interaction between hepatocytes and PMNs was confirmed by electron microscopy. In a mouse model of liver IR, treatment with np ALINO significantly reduced the area of necrosis, aminotransferase levels and ICAM-1 expression.

Conclusion: NOD1 regulates liver IR injury through induction of adhesion molecules and modulation of hepatocyte-PMN interactions. NOD1 antagonist-loaded nanoparticles reduced liver IR injury and provide a potential approach to prevent IR, especially in the context of liver transplantation.

Lay Summary: Nucleotide-binding oligomerization domain 1 (NOD1) is as an important modulator of polymorphonuclear neutrophil (PMN)-induced liver injury, which occurs in ischemia-reperfusion. Here, we show that the NOD1 pathway targets liver adhesion molecule expression on the endothelium and on hepatocytes through p38 and ERK signaling pathways. The early increase of adhesion molecule expression after reperfusion emphasizes the importance of adhesion molecules in liver injury. In this study we generated nanoparticles loaded with NOD1 antagonist. These nanoparticles reduced liver necrosis by reducing PMN liver infiltration and adhesion molecule expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2019.01.019DOI Listing
June 2019

Effects of Long-term Norfloxacin Therapy in Patients With Advanced Cirrhosis.

Gastroenterology 2018 12 23;155(6):1816-1827.e9. Epub 2018 Aug 23.

Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Département Hospitalo-Universitaire UNITY, Service d'Hépatologie, Clichy, France.

Background & Aims: There is debate over the effects of long-term oral fluoroquinolone therapy in patients with advanced cirrhosis. We performed a randomized controlled trial to evaluate the effects of long-term treatment with the fluoroquinolone norfloxacin on survival of patients with cirrhosis.

Methods: We performed a double-blind trial of 291 patients with Child-Pugh class C cirrhosis who had not received recent fluoroquinolone therapy. The study was performed at 18 clinical sites in France from April 2010 through November 2014. Patients were randomly assigned to groups given 400 mg norfloxacin (n = 144) or placebo (n = 147) once daily for 6 months. Patients were evaluated monthly for the first 6 months and at 9 months and 12 months thereafter. The primary outcome was 6-month mortality, estimated by the Kaplan-Meier method, censoring spontaneous bacterial peritonitis, liver transplantation, or loss during follow-up.

Results: The Kaplan-Meier estimate for 6-month mortality was 14.8% for patients receiving norfloxacin and 19.7% for patients receiving placebo (P = .21). In competing risk analysis that took liver transplantation into account, the cumulative incidence of death at 6 months was significantly lower in the norfloxacin group than in the placebo group (subdistribution hazard ratio, 0.59; 95% confidence interval, 0.35-0.99). The subdistribution hazard ratio for death at 6 months with norfloxacin vs placebo was 0.35 (95% confidence interval, 0.13-0.93) in patients with ascites fluid protein concentrations <15 g/L and 1.39 (95% confidence interval, 0.42-4.57) in patients with ascites fluid protein concentrations ≥15 g/L. Norfloxacin significantly decreased the incidence of any and Gram-negative bacterial infections without increasing infections caused by Clostridium difficile or multiresistant bacteria.

Conclusions: In a randomized controlled trial of patients with advanced cirrhosis without recent fluoroquinolone therapy, norfloxacin did not reduce 6-month mortality, estimated by the Kaplan-Meier method. Norfloxacin, however, appears to increase survival of patients with low ascites fluid protein concentrations. ClinicalTrials.gov ID: NCT01037959.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2018.08.026DOI Listing
December 2018

Estimate of hepatocellular carcinoma incidence in patients with alcoholic cirrhosis.

J Hepatol 2018 12 6;69(6):1274-1283. Epub 2018 Aug 6.

SBIM, APHP, Hôpital Saint-Louis, Paris, Inserm, UMR-1153, ECSTRA Team, Paris, France.

Background & Aims: More than 90% of cases of hepatocellular carcinoma (HCC) occur in patients with cirrhosis, of which alcohol is a major cause. The CIRRAL cohort aimed to assess the burden of complications in patients with alcoholic cirrhosis, particularly the occurrence of HCC.

Methods: Patients with biopsy-proven compensated alcoholic cirrhosis were included then prospectively followed. The main endpoint was the incidence of HCC. Secondary outcomes were incidence of hepatic focal lesions, overall survival (OS), liver-related mortality and event-free survival (EFS).

Results: From October 2010 to April 2016, 652 patients were included in 22 French and Belgian centers. During follow-up (median 29 months), HCC was diagnosed in 43 patients. With the limitation derived from the uncertainty of consecutive patients' inclusion and from a sizable proportion of dropouts (153/652), the incidence of HCC was 2.9 per 100 patient-years, and one- and two-year cumulative incidences of 1.8% and 5.2%, respectively. Although HCC fulfilled the Milan criteria in 33 cases (77%), only 24 patients (56%) underwent curative treatment. An explorative prognostic analysis showed that age, male gender, baseline alpha-fetoprotein, bilirubin and prothrombin were significantly associated with the risk of HCC occurrence. Among 73 deaths, 61 had a recorded cause and 27 were directly attributable to liver disease. At two years, OS, EFS and cumulative incidences of liver-related deaths were 93% (95% CI 90.5-95.4), 80.3% (95% CI 76.9-83.9), and 3.2% (95% CI 1.6-4.8) respectively.

Conclusion: This large prospective cohort incompletely representative of the whole population with alcoholic cirrhosis showed: a) an annual incidence of HCC of up to 2.9 per 100 patient-years, suggesting that surveillance might be cost effective in these patients; b) a high proportion of HCC detected within the Milan criteria, but only one-half of detected HCC cases were referred for curative treatments; c) a two-year mortality rate of up to 7%.

Lay Summary: Cirrhosis is a risk factor for primary liver cancer, leading to recommendations for periodic screening. However, for alcohol-related liver disease the rational of periodic screening for hepatocellular carcinoma (HCC) is controversial, as registry and databased studies have suggested a low incidence of HCC in these patients and highly competitive mortality rates. In this study, a large cohort of patients with biopsy-proven alcoholic cirrhosis prospectively screened for HCC demonstrated a high annual incidence of HCC (2.9%) and a high percentage of small cancers theoretically eligible for curative treatment. This suggests that patients with liver disease related to alcohol should not be ruled out of screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2018.07.022DOI Listing
December 2018