Background Patients with chronic hepatitis C virus (HCV) infection are at greater risk of develop... more Background Patients with chronic hepatitis C virus (HCV) infection are at greater risk of developing metabolic disorders. Obesity is a major risk factor for these disorders, and therefore, managing body weight is crucial. Cannabis use, which is common in these patients, has been associated with lower corpulence in various populations. However, this relationship has not yet been studied in persons with chronic HCV infection. Methods Using baseline data from the French ANRS CO22 Hepather cohort, we used binary logistic and multinomial logistic regression models to test for an inverse relationship between cannabis use (former/current) and (i) central obesity (i.e., large waist circumference) and (ii) overweight and obesity (i.e., elevated body mass index (BMI)) in patients from the cohort who had chronic HCV infection. We also tested for relationships between cannabis use and both waist circumference and BMI as continuous variables, using linear regression models. Results Among the 634...
Background & Aims In this study we aimed to analyse the impact of the aetiology of cirrhosis ... more Background & Aims In this study we aimed to analyse the impact of the aetiology of cirrhosis on the incidence, characteristics and prognosis of hepatocellular carcinoma (HCC) diagnosed during a surveillance program. Methods Individual data from a randomized trial and 2 prospective cohorts of patients with compensated histologically proven cirrhosis recruited between 2000 and 2016 were pooled. The influence of cirrhosis aetiology on survival after HCC detection was assessed using multivariable regression models. Results Among 3,533 patients (1,926 virus [VIR], 1,167 alcohol [ALC], 440 combined [MIX]), 431 were diagnosed with HCC after a median follow-up of 57.1 months. The 5-year HCC incidence was lowest in ALC (VIR 12.6%, ALC 9.1%, MIX 14.3%, p = 0.04). At the time of diagnosis, tumour burden and Child-Pugh score were comparable across aetiology groups, but early BCLC stages (0/A) were significantly less frequent in ALC (VIR 80%, ALC 37%, MIX 72%) as a result of worse ECOG performance status. However, similar access to first-line curative HCC treatment was reported across aetiology groups (p = 0.68). Median survival after HCC diagnosis was significantly reduced in ALC (VIR 39, ALC 21, MIX 34 months, p = 0.02). However, when adjusting for tumour size, ECOG and Child-Pugh score, the aetiology of the underlying cirrhosis no longer had a significant impact. Conclusion Compared to patients with virus-related cirrhosis, patients with alcohol-related compensated cirrhosis enrolled in a surveillance program have: i) the lowest 5-year HCC incidence; ii) worse overall prognosis, mostly driven by a poor general condition, despite similar access to first-line curative treatment. Lay summary It has been suggested that early detection of hepatocellular carcinoma (HCC) may be futile in patients with alcohol-related cirrhosis. By comparing outcomes in more than 3,000 patients with compensated cirrhosis included in surveillance programs, this study suggests that HCC surveillance enables early diagnosis in most patients with alcohol-related cirrhosis despite a higher competing risk of death in these patients. We also report similar access to first-line curative HCC treatment in these patients compared to those with viral cirrhosis, despite higher rates of comorbidities and impaired liver function. Following HCC detection, the later parameters were major drivers of death irrespective of the cause of cirrhosis. Registration CHC2000 (NCT00190385) and CIRRAL (NCT01213927) cohorts were registered at ClinicalTrials.gov and the full protocols are available at the following links (https://clinicaltrials.gov/ct2/show/NCT00190385) and https://clinicaltrials.gov/ct2/show/NCT01213927, respectively). The full CirVir protocol is available via the ANRS Web site (http://anrs.fr).
Late presentation for care of hepatitis C virus (HCV) infection – defined as having severe liver ... more Late presentation for care of hepatitis C virus (HCV) infection – defined as having severe liver fibrosis when first consulting a specialist for HCV care – increases morbidity and mortality. Identifying the socio‐behavioural correlates of late presentation is essential to improve HCV strategies to optimize HCV cascade of care. We investigated clinical and socio‐behavioural correlates of late presentation for care in HCV mono‐infected individuals.
P497 DIRECT SEQUENCING OF PROTEIN-C AND -S GENES IN PATIENTS WITH BUDD–CHIARI SYNDROME (BCS), POR... more P497 DIRECT SEQUENCING OF PROTEIN-C AND -S GENES IN PATIENTS WITH BUDD–CHIARI SYNDROME (BCS), PORTAL-VEIN THROMBOSIS (PVT) AND OBLITERATIVEPORTAL-VENOPATHY (OPV) AND SUSPICION OF INHERITED PROTEIN-C OR -S DEFICIENCY A. Plessier, L. Elkrief, P.E. Rautou, E. Deraucourt, O. Goria, K. Zekrini, L. Boudaoud, D. Valla, M. Alhenc Gelas. Department of Hepatology, Hopital Beaujon, AP-HP, University Paris-Diderot, INSERM U 773, Department of Hematology, Haemostasis and Biology, AP-HP, Hopital Beaujon, INSERM U 773 & Universite Paris-VII, Clichy, Department of Gastroenterology, Hepatology, CHU Rouen, Rouen, Hopital Beaujon, AP-HP, University Paris-Diderot, INSERM U 773, Service d’Hepatologie, Clichy, Department of Hematology, Haemostasis and Biology, AP-HP, Hopital Europeen Georges Pompidou, INSERM & Universite Paris, Paris, France E-mail: aurelie.plessier@bjn.aphp.fr Background and Aims: Protein C (PC) and S (PS) deficiencies identified in up to 30% of vascular liver disease patients, are possible risk factors for such diseases, but may alternatively be a mere consequence of liver dysfunction. To address this point, we analyzed PROC or PROS1 genes in these patients with PC or PS deficiency suspicion. Methods: Out of 150 PVT, 74 BCS, 30 OPV, currently included in the dedicated database for vascular disease, inherited PC or PS deficiency [isolated deficiency (protein C clotting activity <70% or PS activity <60% in men, <55% in women), or low level compared to other vitamin K dependent factors level] was suspected in 26 patients (10 BCS, 11 PVT, and 5 OPV) in whom direct sequencing of PROC (N =13) or PROS1 (N =14) genes was performed. Results: Mean (±SD) PC or PS activity was 50±10% and 43±8% respectively. Detrimental PROC or PROS1 heterozygous mutations were found in 38% (N=5) and 29% (N=4) patients, respectively (7 PVT and 2 OPV). No significant differences in PC or PS activity levels were observed between detrimental mutation carriers and non-carriers. Other risk factors for thrombosis (myeloproliferative disease, antiphospholipid syndrome) were present in 4 of 9 heterozygotes. Mutation carrying was associated with initial thrombosis of other splanchnic veins (100%vs18%, p < 0.001). Conclusions: Detrimental mutations of PROC and PROS1 were identified in a proportion of patients with PVT or OPV, but not BCS. Isolated low PC or PS levels in BCS patients appear to result mostly from altered liver function.
Résumé/Abstract Objectif-Ce travail visait à estimer la population exposée à l'aspirine à fa... more Résumé/Abstract Objectif-Ce travail visait à estimer la population exposée à l'aspirine à faible dose (< 330 mg/j) en France et à étudier le rôle de l'aspirine à ces doses dans la survenue d'une d'hémorragie digestive haute. Sujets et méthodes-Mille six cent deux ...
A total of 2%–10% of patients with vascular liver disease (VLD) have paroxysmal nocturnal hemoglo... more A total of 2%–10% of patients with vascular liver disease (VLD) have paroxysmal nocturnal hemoglobinuria (PNH). Eculizumab reduces complement‐mediated haemolytic activity in PNH. This study was aimed at assessing the impact of eculizumab on VLD outcome. Retrospective cohort of PNH patients, in Valdig registry, who had VLD diagnosed between 1997 and 2019 is considered. Eculizumab was the exposure of interest. Studied outcomes were death, venous thrombosis, bleeding, arterial ischemic event, infection, and liver‐related complications. We compared survival and new thrombotic events from PNH/VLD cohort to Envie2 non‐PNH cohort. Sixty‐two patients (33 women), median age 35 years (28–48) and median follow‐up VLD diagnosis 4.7 years (1.2–9.5), were included. Clone size was 80% (70–90), median hemoglobin concentration was 10.0 g/dl (8–11), and lactate dehydrogenase (LDH) was 736 IU (482–1744). Forty‐two patients (68%) had eculizumab; median exposure time was 40.1 [9.3–72.6] months. Mortality was significantly lower in exposed versus nonexposed period: 2.6 versus 8.7 per 100 (PY), incidence rate ratio (IRR) was 0.29, 95% CI (0.1–0.9), p = .035. Thrombosis recurrence occurred less frequently during the exposure to eculizumab: 0.5 versus 2.8 per 100 PY, IRR 0.22 (0.07–0.64). Other secondary end points (i.e., bleeding, arterial ischemic lesions, infection, and liver complications) were less common during the exposure to eculizumab, although not reaching statistical significance. Six‐year thrombosis‐free survival was 70%, 95% CI [0.60–0.83] for PNH cohort and 83%, 95% CI [0.70–1.00] for non‐PNH Envie 2 patients, (p < .001). In conclusion, patients with PNH and VLD are at higher risk of recurrent thrombosis than non‐PNH patients. Eculizumab is significantly associated with a lower mortality and less thrombotic recurrence in patients with PNH and VLD.
BACKGROUND AND AIMS Non-O blood group promotes deep vein thrombosis and liver fibrosis in both ge... more BACKGROUND AND AIMS Non-O blood group promotes deep vein thrombosis and liver fibrosis in both general population and hepatitis C. We aimed to evaluate the influence of Non-O group on the outcome of Child-Pugh A cirrhotic patients. METHODS We used 2 prospective cohorts of Child-Pugh A cirrhosis due either to alcohol or viral hepatitis. Primary end point was the cumulated incidence of "Decompensation" at 3 years, defined as the occurrence of ascites , hydrothorax, encephalopathy, gastrointestinal bleeding related to portal hypertension, or bilirubin > 45 umol/l. Secondary end points were the cumulated incidences of 1) "Disease Progression" including a « decompensation» or « the occurrence of one or more parameters » among: prothrombin time (PT) < 45%, albumin < 28g/L, Child-Pugh worsening (B or C versus A or B, C versus B), hepatorenal syndrome, and hepato-pulmonary syndrome, 2) other events such as Non-Malignant Portal Vein Thrombosis, and 3) overall survival. RESULTS Patients (n= 1789; 59.9% Non-O group; 40.1% group O) were followed during a median of 65.4 months. At 3 years cumulated incidence of Decompensation was 8.3% in Non-O group and 7.2% in group O (p=0.27). Cumulated incidence of Disease Progression was 20.7% in Non-O group and 18.9% in group O (p=0.26). Cumulated incidence of non-malignant portal vein thrombosis was 2.7% in Non-O group and 2.8% in group O (p=0.05). At 3 years overall survival was 92.4% in Non-O group and 93.4% in group O (p=1). CONCLUSION Non-O group does not influence disease outcome in Child-Pugh A cirrhotic patients.
Méthodes — Les cas étaient constitués de sujets, habitant dans la région de Fécamp, séropositifs ... more Méthodes — Les cas étaient constitués de sujets, habitant dans la région de Fécamp, séropositifs pour le virus de l’hépatite C ; les témoins (2 par cas) étaient des sujets, habitant la même région, séronégatifs pour le virus de l’hépatite C ; ils étaient appariés en âge et en sexe aux cas. Les données recueillies étaient : démographiques, médicales, professionnelles, environnementales. L’analyse statistique comprenait des comparaisons par le test duv ou de Fisher et une régression logistique.
HIV‐coinfected patients experience higher incidences of non‐liver‐related cancers than HCV‐monoin... more HIV‐coinfected patients experience higher incidences of non‐liver‐related cancers than HCV‐monoinfected patients. Chronic inflammation, immunosuppression, but also higher tobacco or alcohol consumption and metabolic dysregulation could explain this higher risk. We aimed to estimate the direct, indirect and total effects of HIV coinfection on the risk of non‐liver‐related cancers in HCV participants treated with direct‐acting antivirals (DAAs).
Background Patients with chronic hepatitis C virus (HCV) infection are at greater risk of develop... more Background Patients with chronic hepatitis C virus (HCV) infection are at greater risk of developing metabolic disorders. Obesity is a major risk factor for these disorders, and therefore, managing body weight is crucial. Cannabis use, which is common in these patients, has been associated with lower corpulence in various populations. However, this relationship has not yet been studied in persons with chronic HCV infection. Methods Using baseline data from the French ANRS CO22 Hepather cohort, we used binary logistic and multinomial logistic regression models to test for an inverse relationship between cannabis use (former/current) and (i) central obesity (i.e., large waist circumference) and (ii) overweight and obesity (i.e., elevated body mass index (BMI)) in patients from the cohort who had chronic HCV infection. We also tested for relationships between cannabis use and both waist circumference and BMI as continuous variables, using linear regression models. Results Among the 634...
Background & Aims In this study we aimed to analyse the impact of the aetiology of cirrhosis ... more Background & Aims In this study we aimed to analyse the impact of the aetiology of cirrhosis on the incidence, characteristics and prognosis of hepatocellular carcinoma (HCC) diagnosed during a surveillance program. Methods Individual data from a randomized trial and 2 prospective cohorts of patients with compensated histologically proven cirrhosis recruited between 2000 and 2016 were pooled. The influence of cirrhosis aetiology on survival after HCC detection was assessed using multivariable regression models. Results Among 3,533 patients (1,926 virus [VIR], 1,167 alcohol [ALC], 440 combined [MIX]), 431 were diagnosed with HCC after a median follow-up of 57.1 months. The 5-year HCC incidence was lowest in ALC (VIR 12.6%, ALC 9.1%, MIX 14.3%, p = 0.04). At the time of diagnosis, tumour burden and Child-Pugh score were comparable across aetiology groups, but early BCLC stages (0/A) were significantly less frequent in ALC (VIR 80%, ALC 37%, MIX 72%) as a result of worse ECOG performance status. However, similar access to first-line curative HCC treatment was reported across aetiology groups (p = 0.68). Median survival after HCC diagnosis was significantly reduced in ALC (VIR 39, ALC 21, MIX 34 months, p = 0.02). However, when adjusting for tumour size, ECOG and Child-Pugh score, the aetiology of the underlying cirrhosis no longer had a significant impact. Conclusion Compared to patients with virus-related cirrhosis, patients with alcohol-related compensated cirrhosis enrolled in a surveillance program have: i) the lowest 5-year HCC incidence; ii) worse overall prognosis, mostly driven by a poor general condition, despite similar access to first-line curative treatment. Lay summary It has been suggested that early detection of hepatocellular carcinoma (HCC) may be futile in patients with alcohol-related cirrhosis. By comparing outcomes in more than 3,000 patients with compensated cirrhosis included in surveillance programs, this study suggests that HCC surveillance enables early diagnosis in most patients with alcohol-related cirrhosis despite a higher competing risk of death in these patients. We also report similar access to first-line curative HCC treatment in these patients compared to those with viral cirrhosis, despite higher rates of comorbidities and impaired liver function. Following HCC detection, the later parameters were major drivers of death irrespective of the cause of cirrhosis. Registration CHC2000 (NCT00190385) and CIRRAL (NCT01213927) cohorts were registered at ClinicalTrials.gov and the full protocols are available at the following links (https://clinicaltrials.gov/ct2/show/NCT00190385) and https://clinicaltrials.gov/ct2/show/NCT01213927, respectively). The full CirVir protocol is available via the ANRS Web site (http://anrs.fr).
Late presentation for care of hepatitis C virus (HCV) infection – defined as having severe liver ... more Late presentation for care of hepatitis C virus (HCV) infection – defined as having severe liver fibrosis when first consulting a specialist for HCV care – increases morbidity and mortality. Identifying the socio‐behavioural correlates of late presentation is essential to improve HCV strategies to optimize HCV cascade of care. We investigated clinical and socio‐behavioural correlates of late presentation for care in HCV mono‐infected individuals.
P497 DIRECT SEQUENCING OF PROTEIN-C AND -S GENES IN PATIENTS WITH BUDD–CHIARI SYNDROME (BCS), POR... more P497 DIRECT SEQUENCING OF PROTEIN-C AND -S GENES IN PATIENTS WITH BUDD–CHIARI SYNDROME (BCS), PORTAL-VEIN THROMBOSIS (PVT) AND OBLITERATIVEPORTAL-VENOPATHY (OPV) AND SUSPICION OF INHERITED PROTEIN-C OR -S DEFICIENCY A. Plessier, L. Elkrief, P.E. Rautou, E. Deraucourt, O. Goria, K. Zekrini, L. Boudaoud, D. Valla, M. Alhenc Gelas. Department of Hepatology, Hopital Beaujon, AP-HP, University Paris-Diderot, INSERM U 773, Department of Hematology, Haemostasis and Biology, AP-HP, Hopital Beaujon, INSERM U 773 & Universite Paris-VII, Clichy, Department of Gastroenterology, Hepatology, CHU Rouen, Rouen, Hopital Beaujon, AP-HP, University Paris-Diderot, INSERM U 773, Service d’Hepatologie, Clichy, Department of Hematology, Haemostasis and Biology, AP-HP, Hopital Europeen Georges Pompidou, INSERM & Universite Paris, Paris, France E-mail: aurelie.plessier@bjn.aphp.fr Background and Aims: Protein C (PC) and S (PS) deficiencies identified in up to 30% of vascular liver disease patients, are possible risk factors for such diseases, but may alternatively be a mere consequence of liver dysfunction. To address this point, we analyzed PROC or PROS1 genes in these patients with PC or PS deficiency suspicion. Methods: Out of 150 PVT, 74 BCS, 30 OPV, currently included in the dedicated database for vascular disease, inherited PC or PS deficiency [isolated deficiency (protein C clotting activity <70% or PS activity <60% in men, <55% in women), or low level compared to other vitamin K dependent factors level] was suspected in 26 patients (10 BCS, 11 PVT, and 5 OPV) in whom direct sequencing of PROC (N =13) or PROS1 (N =14) genes was performed. Results: Mean (±SD) PC or PS activity was 50±10% and 43±8% respectively. Detrimental PROC or PROS1 heterozygous mutations were found in 38% (N=5) and 29% (N=4) patients, respectively (7 PVT and 2 OPV). No significant differences in PC or PS activity levels were observed between detrimental mutation carriers and non-carriers. Other risk factors for thrombosis (myeloproliferative disease, antiphospholipid syndrome) were present in 4 of 9 heterozygotes. Mutation carrying was associated with initial thrombosis of other splanchnic veins (100%vs18%, p < 0.001). Conclusions: Detrimental mutations of PROC and PROS1 were identified in a proportion of patients with PVT or OPV, but not BCS. Isolated low PC or PS levels in BCS patients appear to result mostly from altered liver function.
Résumé/Abstract Objectif-Ce travail visait à estimer la population exposée à l'aspirine à fa... more Résumé/Abstract Objectif-Ce travail visait à estimer la population exposée à l'aspirine à faible dose (< 330 mg/j) en France et à étudier le rôle de l'aspirine à ces doses dans la survenue d'une d'hémorragie digestive haute. Sujets et méthodes-Mille six cent deux ...
A total of 2%–10% of patients with vascular liver disease (VLD) have paroxysmal nocturnal hemoglo... more A total of 2%–10% of patients with vascular liver disease (VLD) have paroxysmal nocturnal hemoglobinuria (PNH). Eculizumab reduces complement‐mediated haemolytic activity in PNH. This study was aimed at assessing the impact of eculizumab on VLD outcome. Retrospective cohort of PNH patients, in Valdig registry, who had VLD diagnosed between 1997 and 2019 is considered. Eculizumab was the exposure of interest. Studied outcomes were death, venous thrombosis, bleeding, arterial ischemic event, infection, and liver‐related complications. We compared survival and new thrombotic events from PNH/VLD cohort to Envie2 non‐PNH cohort. Sixty‐two patients (33 women), median age 35 years (28–48) and median follow‐up VLD diagnosis 4.7 years (1.2–9.5), were included. Clone size was 80% (70–90), median hemoglobin concentration was 10.0 g/dl (8–11), and lactate dehydrogenase (LDH) was 736 IU (482–1744). Forty‐two patients (68%) had eculizumab; median exposure time was 40.1 [9.3–72.6] months. Mortality was significantly lower in exposed versus nonexposed period: 2.6 versus 8.7 per 100 (PY), incidence rate ratio (IRR) was 0.29, 95% CI (0.1–0.9), p = .035. Thrombosis recurrence occurred less frequently during the exposure to eculizumab: 0.5 versus 2.8 per 100 PY, IRR 0.22 (0.07–0.64). Other secondary end points (i.e., bleeding, arterial ischemic lesions, infection, and liver complications) were less common during the exposure to eculizumab, although not reaching statistical significance. Six‐year thrombosis‐free survival was 70%, 95% CI [0.60–0.83] for PNH cohort and 83%, 95% CI [0.70–1.00] for non‐PNH Envie 2 patients, (p < .001). In conclusion, patients with PNH and VLD are at higher risk of recurrent thrombosis than non‐PNH patients. Eculizumab is significantly associated with a lower mortality and less thrombotic recurrence in patients with PNH and VLD.
BACKGROUND AND AIMS Non-O blood group promotes deep vein thrombosis and liver fibrosis in both ge... more BACKGROUND AND AIMS Non-O blood group promotes deep vein thrombosis and liver fibrosis in both general population and hepatitis C. We aimed to evaluate the influence of Non-O group on the outcome of Child-Pugh A cirrhotic patients. METHODS We used 2 prospective cohorts of Child-Pugh A cirrhosis due either to alcohol or viral hepatitis. Primary end point was the cumulated incidence of "Decompensation" at 3 years, defined as the occurrence of ascites , hydrothorax, encephalopathy, gastrointestinal bleeding related to portal hypertension, or bilirubin > 45 umol/l. Secondary end points were the cumulated incidences of 1) "Disease Progression" including a « decompensation» or « the occurrence of one or more parameters » among: prothrombin time (PT) < 45%, albumin < 28g/L, Child-Pugh worsening (B or C versus A or B, C versus B), hepatorenal syndrome, and hepato-pulmonary syndrome, 2) other events such as Non-Malignant Portal Vein Thrombosis, and 3) overall survival. RESULTS Patients (n= 1789; 59.9% Non-O group; 40.1% group O) were followed during a median of 65.4 months. At 3 years cumulated incidence of Decompensation was 8.3% in Non-O group and 7.2% in group O (p=0.27). Cumulated incidence of Disease Progression was 20.7% in Non-O group and 18.9% in group O (p=0.26). Cumulated incidence of non-malignant portal vein thrombosis was 2.7% in Non-O group and 2.8% in group O (p=0.05). At 3 years overall survival was 92.4% in Non-O group and 93.4% in group O (p=1). CONCLUSION Non-O group does not influence disease outcome in Child-Pugh A cirrhotic patients.
Méthodes — Les cas étaient constitués de sujets, habitant dans la région de Fécamp, séropositifs ... more Méthodes — Les cas étaient constitués de sujets, habitant dans la région de Fécamp, séropositifs pour le virus de l’hépatite C ; les témoins (2 par cas) étaient des sujets, habitant la même région, séronégatifs pour le virus de l’hépatite C ; ils étaient appariés en âge et en sexe aux cas. Les données recueillies étaient : démographiques, médicales, professionnelles, environnementales. L’analyse statistique comprenait des comparaisons par le test duv ou de Fisher et une régression logistique.
HIV‐coinfected patients experience higher incidences of non‐liver‐related cancers than HCV‐monoin... more HIV‐coinfected patients experience higher incidences of non‐liver‐related cancers than HCV‐monoinfected patients. Chronic inflammation, immunosuppression, but also higher tobacco or alcohol consumption and metabolic dysregulation could explain this higher risk. We aimed to estimate the direct, indirect and total effects of HIV coinfection on the risk of non‐liver‐related cancers in HCV participants treated with direct‐acting antivirals (DAAs).
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