Albumin Use in Patients With Cirrhosis in France: Results of the "ALBU-LIVE" Survey: A Case for Better EASL Guidelines Diffusion and/or Revision.

INTRODUCTION: The use of human albumin for the management of cirrhosis has increased. Recommendations have been published for therapeutic paracentesis (TP), spontaneous bacterial peritonitis (SBP), and type 1 hepatorenal syndrome (HRS). The goal of this survey was to assess the prescription practices of French hepatogastroenterologists. METHODS: All hepatogastroenterologists were contacted. The questionnaire evaluated (1) the use of albumin in validated indications and (2) the prescription of albumin for nonvalidated clinical situations. RESULTS: Responses were analyzed from 451 (50.1%) practitioners. The mean age was 40 years (range, 24 to 67 y). Physicians practiced in a university hospital (47.7%) or a general hospital (45.8%). There were 56.7% senior practitioners. Overall 99.6% of the practitioners compensated for TP. Albumin was used by 87.8% of the physicians, with a fixed dose being used by 84.6%. For SBP, 94% of the physicians used albumin concomitantly with antibiotics. The recommended protocol was followed by 56.2% of the practitioners: more often by senior university hospital practitioners than by senior general hospital practitioners (P=0.015). About 66.5% used albumin infusion for the diagnosis of HRS: used more often by senior university hospital practitioners (P=0.0006). Albumin was used concomitantly with vasopressor treatment by 84%; the dose and the duration varied considerably. About 23.5% used albumin for severe bacterial infection, 47.9% for severe hyponatremia, 43.9% for severe hypoalbuminemia, and 65.9% for hydrothorax. CONCLUSIONS: In this large French survey, albumin is only prescribed in accordance with recommendations for TP. The schedule for SBP is followed by only 56% of the practitioners. The use of albumin for HRS is not adapted to recommendations, which are not well known, suggesting that they should be more diffused.

[Autoimmune hepatitis]. / Hépatite auto-immune.

Autoimmune hepatitis is a chronic liver disease characterized by a necroinflammatory activity of the portal tract resulting from an immune response against hepatocytes. It is relatively rare and its cause is unknown. There are three types (I, II and III) associated with the presence of some autoantibodies which are not always specific. The diagnosis is based on clinical, biochemical, immunological and histological features. The preferred treatment is a combination regimen of predniso(lo)ne and azathioprine (budezonide and aziathioprine in when cirrhosis is absent). The corticosteroid must be slowly tapered down keeping the immunosuppressive agent as maintenance therapy. Drug withdrawal should only be considered whether serum transaminases and γ-globulins level are normal and after a normal or near normal liver biopsy.

Management of primary biliary cholangitis: results from a large real-life observational study in France and Belgium.

BACKGROUND AND AIMS: To assess the characteristics, care, treatment response, and outcomes of primary biliary cholangitis (PBC) patients recently followed-up by hepato-gastroenterologists in various French and Belgian healthcare settings. METHODS: This retrospective cohort study included patients with PBC who recently visited 79 hepato-gastroenterologists in France and Belgium. Data were collected at the time of diagnosis and at last visit and were compared according to biochemical response (BR) to ursodeoxycholic acid (UDCA) (BR), using Paris I-II criteria, and clinical outcomes. RESULTS: A total of 436 patients (mean age at diagnosis 57 years, 88% females, median follow-up 5.2 years) were included. Liver biopsy, transient elastography, or none of these two procedures were performed at baseline in 216 (50%), 194 (45%), and 107 (25%) patients, respectively. Late-stage disease (histological stage III or IV, or transient elastography ≥9.6 kPa, or bilirubin >17 µM and albumin <35 g/L, or platelets <150.000/µl, or unequivocal signs of portal hypertension or cirrhosis) was reported in 37% of patients. UDCA was taken by 95% of patients (27% had suboptimal dosage). Inadequate BR was observed in 37% of patients. Clinicians overestimated disease control. Liver-related complications occurred in 9% of patients. Bilirubin and albumin independently predicted inadequate BR; advanced disease stage and inadequate BR independently predicted complications. CONCLUSIONS: Recently followed-up French and Belgian patients with PBC had homogeneous management. Late stage at diagnosis and inadequate BR were reported in around 40% of patients. Disease control was frequently overestimated by clinicians. Disease stage and BR were the main prognostic factors.

Outcomes of upper gastrointestinal bleeding are similar between direct oral anticoagulants and vitamin K antagonists.

BACKGROUND: The increased risk of upper gastrointestinal bleeding (UGIB) related to direct oral anticoagulants (DOACs) as compared to vitamin K antagonists (VKA) remains debated. AIMS: To describe the epidemiology and outcomes of UGIB in patients treated with oral anticoagulants. METHODS: A prospective, multicentre study in French general hospitals enrolled all consecutive patients with UGIB during one year. Patients treated with oral anticoagulants were retrieved from the cohort. Main outcomes were mortality and rebleeding during the first 6 weeks and need for non-endoscopic treatment (surgery or interventional radiology). RESULTS: Among the 2498 patients included, 475 (19%) had an oral anticoagulant, mostly with VKA (267 patients [56.2%]). Baseline characteristics were similar between the groups except for renal failure and cirrhosis that were more prevalent in the VKA group. Gastroscopy was normal in 73 patients (15.3%); peptic lesions were the main cause of UGIB (n = 233, 49%). Endoscopic treatment was performed in 128 patients (26.9%), leading to bleeding resolution in 74% (n = 95). Mortality rate at 6 weeks was 12.4% (59 patients), and was higher in the VKA group compared to DOACs (16.1% vs 7.8%, P < 0.01). By multivariate analysis, only the Charlson index ≥ 5 and UGIB occurrring in in-patients were independently associated with mortality. Rebleeding (56 patients [11.8%]) and need for non-endoscopic treatment (18 patients [3.8%]) were not associated with the type of anticoagulant. CONCLUSION: DOACs do not alter outcomes of UGIB as compared to VKA. Comorbidities and associated treatment are the most important factors worsening the prognosis of UGIB.

Management of diabetes mellitus in patients with cirrhosis: An overview and joint statement.

Type 2 diabetes mellitus (T2DM) is a frequent comorbidity in patients with cirrhosis that is projected to rise in prevalence due to the worldwide burden of obesity, insulin-resistance and non-alcoholic fatty liver disease. The management of T2DM in patients with cirrhosis is complex given the requirement for accurate adaptation according to the level of liver function impairment, with lack of summary of the little evidence available in the literature. Here, we summarise the data available with respect to the epidemiology and the impact of T2DM in patients with cirrhosis, as well as those on the management of T2DM in these patients. We provide guidance for the diagnosis of T2DM and the monitoring of glycaemic control in patients with cirrhosis, and for the management of nutrition and pharmacological treatments in relation to the level of liver dysfunction.

Management of infections in patients with cirrhosis in the context of increasing therapeutic resistance: A systematic review.

Patients with cirrhosis are prone to develop bacterial infections, which consist in one of the major precursors of Acute-on-Chronic Liver Failure (ACLF) and are responsible for a high mortality rate. In recent years, the management of bacterial infections in patients with cirrhosis has become increasingly complicated due to a change in bacterial ecology associated with a higher rate of cocci gram positive bacteria in Europe and America along with the emergence of a multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria leading to a decrease in the efficacy of empirical strategies based on the administration of third-generation cephalosporins. MDR and XDR now account for about 40% of the infections worldwide, and up to 70% in India. Among them, the most common ones are extended-spectrum beta-lactamase producing (ESBL-P) bacteria, carbapenem-resistant enterobacteriaceae (CRE), Methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE). An early diagnosis associated to an empirical antibiotic adapted to the site of infection and potential bacterial resistance is now crucial in order to improve the chances of survival and contain the resistance phenomenon. Moreover, a fungal infection must always be discussed in these high-risks patients, especially in the absence of clinical improvement under appropriate antibiotic treatment. In this review, we will focus on the emerging threat of MDR and XDR organisms, as well as fungal infections, in order to better adapt the therapeutic management of cirrhotic patients with infections.

Efficacy and safety of treatment of chronic hepatitis C with sofosbuvir and ribavirin with or without peginterferon: a French prospective real-life cohort study of unselected 211 patients.

INTRODUCTION: Sofosbuvir is the first directly-acting antiviral for the treatment of hepatitis C virus. First, the regimens were combinations with sofosbuvir+ribavirin (SR) or with sofosbuvir+ribavirin and pegylated-interferon α-2a (SPR) with cure rates around 90%. The aim of this study was to report the results of these combinations in 'real-life' in France. MATERIALS AND METHODS: Main features of patients treated with SR or SPR in 24 hospitals were collected. Undetectable hepatitis C virus week 12 viral load after treatment defined sustained virological response (SVR12). Statistics were performed using StatView software for descriptive analysis and χ for the sub-groups comparisons. RESULTS: Two hundred and eleven patients were analyzed. The average age was 56.1. One hundred and seventy-one (89%) patients had a fibrosis score of at least 3. Seventy-nine patients were infected by a genotype 1 (G1). One hundred and thirteen patients were treated with SR and 95 with SPR. In naive patients: with SPR for 12 weeks, SVR12 was 93% in G1, 100% in G3 and 83% in G4. With SR for 12 weeks, SVR12 was 100% in G2 patients (6/6). The safety of these regimens was satisfactory with only two patients who had to stop P due to severe side effects. Multivariate analysis shows a higher SVR in SPR versus SR (odds ratio = 1.28; P = 0.05) and in G2 or G3 versus others (odds ratio = 1.56; P = 0.04). Moreover, Child-Pugh score B or C (P = 0.02), platelets count under 100G/l (P = 0.05) or a past event of ascites (P = 0.04) was independently associated with less SVR. CONCLUSION: This multicenter large study confirms the good results of SR for 12 weeks in G2 naive patients. Finally, a decompensated cirrhosis, a past event of ascites and a baseline low platelet count were strongly associated with poor response.

Infectious endocarditis in the case of cirrhosis: where do we stand?

Bacterial infections are common in the case of cirrhosis and represent a major cause of morbidity and mortality. The most frequent infections are spontaneous bacterial peritonitis, urinary tract infection, and pneumonia, but few data on infectious endocarditis are available. Infectious endocarditis is a rare event, and diagnosis can be made at all stages of Child-Pugh classification. In the case of cirrhosis, the clinical features and bacterial ecology are similar to that of the general population (two males/one female, preferential location on the aortic and mitral valves, history of heart disease, majority of Gram-positive bacteria), but in-hospital mortality is higher. The Child-Pugh score and a history of decompensation have been identified as independent predictive factors for in-hospital mortality and a Child-Pugh score more than C10 was associated with a higher risk of death. Less frequent use of aminoglycosides, rifampin, and cardiac surgery has been described in cirrhotic patients, probably because of potential toxicity. Nevertheless, as they are a cornerstone of therapy, prospective studies on the impact of these therapeutics are warranted to improve outcome in this population of patients.

Severe liver failure rather than cirrhosis is associated with mortality in patients with infectious endocarditis: a retrospective case-control study.

BACKGROUND: Data on infectious endocarditis (IE) in patients with liver cirrhosis (LC) are sparse. We aimed to describe the characteristics and predictors of mortality from IE in patients with LC. PATIENTS AND METHODS: Overall, 101 patients with LC and 101 controls with IE matched for sex, age, date of IE, and diabetes were retrospectively selected in 23 liver units between 2000 and 2013. RESULTS: Mean age was 60.8±10.5 and 60.6±11.5 years in LC and controls, respectively. Causes of cirrhosis (Child-Pugh A/B/C: 10.4%/41.7%/47.9%, MELD score: 17±7.8) were excess alcohol intake (79.6%), viral hepatitis (17.3%), and metabolic syndrome (14.3%). Previous history of cardiopathy was found in 24.8% of LC (prosthetic valve 8.9%) and 37.6% of controls (P=0.07). The most frequent bacteria involved were gram-positive cocci. LC had significantly fewer aminoglycosides (P=0.0007), rifamycin (P=0.03), and valve surgery (P=0.02) than controls. The proportion of patients who died following cardiac surgery was similar between the two groups (9.7% for LC vs. 8.7% for controls, P=1). In-hospital mortality for Child-Pugh C patients was significantly higher than controls (61.4 vs. 23%, P<0.001), but not for Child-Pugh A (33.3%) or B patients (25.0%). A Child-Pugh score of above C10 was the best predictor of in-hospital mortality. In LC, Child-Pugh score (odds ratio=1.5; 95% confidence interval: 1.2-2.0; P=0.002) and history of decompensation (odds ratio=3.1; 95% confidence interval: 1.1-9.0; P=0.003) were independent predictive factors for in-hospital mortality. CONCLUSION: Severe liver failure but not cirrhosis is the strongest predictive factor of mortality related to IE in LC. Use of aminosides and rifamycin should be reassessed in LC, and cardiac surgery should be considered for selected patients.

One year of baclofen in 100 patients with or without cirrhosis: a French real-life experience.

BACKGROUND: Several studies have suggested the efficacy of baclofen in reducing alcohol consumption, leading to a temporary recommendation for use in France. AIM: Our aim was to report our experience in using baclofen in alcohol-dependant patients with or without liver cirrhosis. PATIENTS AND METHODS: Consecutive patients from two liver and alcohol units were recruited over a 3-year period and received increasing doses of baclofen associated with social, psychological, and medical care. RESULTS: One hundred patients were treated, of whom 65 were cirrhotic. After 1 year, 86 patients were still being followed up. At a mean dosage of 40 mg/day (extremes: 30-210), the median daily alcohol consumption reduced from 80 to 0 g/day (P<0.001). Twenty patients drank a small amount of alcohol of up to 30 g/day and 44 patients were completely abstinent. These declarative results were associated with a significant improvement in alcohol-related biological markers in this 'low-consumption' group of 64 patients: the median γ-glutamyl transferase decreased from 3.9 to 2.0 UNL (P<0.001), the mean aspartate transaminase decreased from 2.6 to 1.2 UNL (P<0.001), and the mean corpuscular volume decreased from 101 to 93 µm (P<0.001). In cirrhotic patients, bilirubinemia decreased significantly from 22 to 11 µmol/l (P=0.026), prothrombin time increased from 68 to 77% (P<0.001), and albuminemia increased from 34.1 to 37.4 g/l (P<0.001). Twenty patients reported grades 1-2 adverse events. No liver or renal function deterioration occurred in cirrhotic patients. CONCLUSION: In our cohort, baclofen associated with a global care was very well tolerated even in cirrhotic patients. The marked reduction in alcohol consumption in 64 patients translated into a significant improvement in biological markers and in liver function tests. Baclofen could be very useful, especially in cases of severe alcoholic liver disease.

[Hepatic hydrothorax]. / Hydrothorax hépatique.

Hydrothorax liver is defined by the presence of pleural effusion greater than 500mL secondary to portal hypertension in cirrhotic patients. Poor tolerance of hepatic hydrothorax makes the therapeutic management of these fragile patients and is associated with iatrogenic complications. The mechanism of hydrothorax formation cirrhosis is due to a unidirectional transfer of the abdominal ascites through the diaphragmatic gaps (that were identified macroscopically and microscopically) in the pleural cavity. The treatment of hepatic hydrothorax is determined by the possibility or not of liver transplantation. In some patients, anastomosis portocaval transjugular (TIPS) may however be sufficient.

[Hepatopulmonary syndrome]. / Le syndrome hépato-pulmonaire.

Hepatopulmonary syndrome (HPS) is defined by the association of portal hypertension, increased alveolar-arterial oxygen gradient and intrapulmonary vascular dilations. Pathophysiological mechanisms of hypoxemia are characterized by ventilation-perfusion mismatch, oxygen diffusion limitation between alveolus and the centre of the dilated capillary, and right-to-left shunting. An excess of vasodilator molecules (like nitric monoxide) and proangiogenic factors (like VEGF) play an important role in the occurrence of HPS. Symptoms of HPS are not specific and dominated by a progressive dyspnea in upright position. Pulse oximetry is a simple non-invasive screening test but only detect the most severe forms of HPS. Medical treatment is disappointing and only liver transplantation may lead to resolution of HPS. Survival following liver transplantation is promising when hypoxemia is not severely decreased.

Chronic hepatitis C: treat or wait? A prospective study on reasons for treatment or nontreatment in the era of first-generation protease inhibitors.

BACKGROUND AND AIMS: In many countries, current treatment for patients with chronic hepatitis C involves a combination of peginterferon and ribavirin, associated with a protease inhibitor for hepatitis C virus genotype 1. More recent and efficient less toxic antiviral treatments are now available for some patients. Thus, the decision to treat or to wait is challenging. The aims of this study were to: (a) estimate the proportion of treated patients, (b) evaluate the reasons for this decision, and (c) examine the patients' points-of-view in treatment decision. METHODS: This was a prospective study conducted at three French referral centers between March and June 2013. Epidemiological and virological data, reasons for treatment or nontreatment, and data on the doctors' and patients' choices were collected. RESULTS: A total of 255 patients were analyzed. Only 52.6% of patients with fibrosis of 2 or higher were treated. Treatment uptake was reduced in the following groups: previously treated patients, those with poor tolerance during prior treatment, those with heavy alcohol consumption, and those with hepatocellular carcinoma. Of the cirrhotic patients, 55% were not treated: 51.1% had a contraindication, 22.2% had a previous nonresponse. When treatment was refused by the patient, fear of side effects and professional problems were the most frequently cited reasons (90 and 40%, respectively). CONCLUSION: Patients were treated primarily according to consensus guidelines. However, only 45% of cirrhotic patients were treated. In 7.6% of the cases, the patient refused therapy. This study enabled us to measure the importance of patient choice in medical decision-making. Well-informed patients expected not only more efficient but also well-tolerated therapy.

Characteristics and clinical course of primary sclerosing cholangitis in France: a prospective cohort study.

BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) is a rare disease, and large-scale report of PSC in France is lacking. We initiated a prospective multisite observational study. METHODS: One hundred and fifty PSC patients (90 with associated inflammatory bowel disease) were included. At entry, 11 patients had a diagnosis of hepatobiliary or colon malignancy (cholangiocarcinoma: n = 5, hepatocellular carcinoma: n = 2, gallbladder carcinoma: n = 1 and colorectal cancer: n = 4). One hundred and forty-one patients (94%) were treated with ursodeoxycholic acid (UDCA) (median dose: 13.1 mg/kg/day), including 118 with UDCA started before inclusion. RESULTS: During follow-up [3.9 (0.1-7.2) years], colorectal cancer was diagnosed in four patients and biliary carcinoma in two (incidences: 0.76 and 0.38 for 100 patient-years, respectively). Kaplan-Meier transplant-free survival at 4 years was 79%. Main causes of death (n = 10) were cancer (n = 5, including three colorectal cancers and two cholangiocarcinoma) or liver failure (n = 4). Indications for transplantation (n = 25) were end-stage liver disease (n = 16), biliary cancer (known or suspected) (n = 5), recurrent acute cholangitis (n = 3) or pruritus (n = 1). Independent predictive factors of death or transplantation were alkaline phosphatase at least 3 upper limit of normal values, platelets less than or equal to 150000/mm3 and bilirubin at least 23 micromol/l. Observed and predicted survivals were similar. CONCLUSION: PSC in France shares common features with other series and is almost universally treated with UDCA. Under standard-dose UDCA, PSC remains a rather severe disease. However, the low incidence of cholangiocarcinoma is compatible with a potential chemoprotective effect of UDCA against biliary neoplasia development.

Treatment of chronic hepatitis C in sickle cell disease and thalassaemic patients with interferon and ribavirin.

BACKGROUND/AIM: Hepatic complications are a major cause of death in patients with congenital anaemia and chronic hepatitis C. Ribavirin is usually contraindicated in patients with haemolytic anaemia. This pilot study evaluated the efficacy and safety of antiviral treatment in patients with sickle cell disease (SCD) or beta-thalassaemia major (TM). METHODS: Eleven consecutive SCD and TM patients were included. Interferon monotherapy was administrated in the two first thalassaemic patients. Other patients received combination therapy with full dose of pegylated interferon 2b and increasing doses of ribavirin, starting with a low dose of ribavirin (400 mg/day). RESULTS: Hepatitis C virus genotypes were 1 or 4 in nine cases. A sustained virological response achieved in five of 11 patients despite unfavourable factors to response (genotypes, nonresponders to an earlier treatment). Haemoglobin level at the end of treatment was higher than baseline levels in five of six SCD patients. No SCD patient needed a transfusion during and after treatment period, neither presented vasoocclusive crisis. The mean increase in transfusion requirements was 32.5% in the thalassaemic group. CONCLUSION: A sustained virological response can be obtained in SCD and TM patients. No earlier study of excellent haematological tolerance among SCD patients under ribavirin has been reported to date. The results of this study suggest that full dose ribavirin could be used from the start of treatment in SCD patients.