Diagnosis and management of hepatic encephalopathy: The French recommendations.

Hepatic encephalopathy (HE) is a frequent and severe complication of liver disease with poor patient outcomes. However, it is a poorly understood complication, with no consensus for diagnosis. Therefore, HE is often underdiagnosed. Differential diagnosis may be cumbersome because of non-specific symptoms, such as confusion, cognitive disorders, the aetiological factors of cirrhosis and comorbidities, which are often observed in cirrhotic patients. Therefore, an overt or covert form of HE should be systematically investigated. Advice is provided to drive patient work-up. Effective treatments are available to prevent or treat HE bouts, but the issue of single or combination therapy has not been resolved. Transjugular intrahepatic portosystemic shunt (TIPS) placement largely improved the prognosis of cirrhotic patients, but HE occurrence of HE is often a fear, even when post-TIPS HE can be avoided by a careful selection of patients and preventive treatment. HE is an indication of liver transplantation. However, its reversibility post-transplantation and the consequences of transplantation in patients with other causes of neurological disorders remain controversial, which supports the performance of an extensive work-up in expert centres for this subset of patients. The present guidelines assist clinicians in the diagnosis of the overt or covert form of HE to implement curative and preventive treatments and clarify which patients require referral to expert centres for consideration for liver transplantation. These guidelines are very clinically oriented and address different frequent clinical issues to help physicians make bedside decisions.

International survey among hepatologists and pulmonologists on the hepatic hydrothorax: plea for recommendations.

BACKGROUND: The Hepatic hydrothorax is a pleural effusion related to portal hypertension; its diagnosis and therapeutic management may be difficult. The aims of this article are which follows: To gather the practices of hepatogastroenterologists or pulmonologists practitioners regarding the diagnosis and management of the hepatic hydrothorax. METHODS: Practitioners from 13 French- speaking countries were invited to answer an online questionnaire on the hepatic hydrothorax diagnosis and its management. RESULTS: Five hundred twenty-eight practitioners (80% from France) responded to this survey. 75% were hepatogastroenterologists, 20% pulmonologists and the remaining 5% belonged to other specialities. The Hepatic hydrothorax can be located on the left lung for 64% of the responders (66% hepatogastroenterologists vs 57% pulmonologists; p = 0.25); The Hepatic hydrothorax can exist in the absence of clinical ascites for 91% of the responders (93% hepatogastroenterologists vs 88% pulmonologists; p = 0.27). An Ultrasound pleural scanning was systematically performed before a puncture for 43% of the responders (36% hepatogastroenterologists vs 70% pulmonologists; p < 0.001). A chest X-ray was performed before a puncture for 73% of the respondeurs (79% hepatogastroenterologists vs 54% pulmonologists; p < 0.001). In case of a spontaneous bacterial empyema, an albumin infusion was used by 73% hepatogastroenterologists and 20% pulmonologists (p < 0.001). A drain was used by 37% of the responders (37% hepatogastroenterologists vs 31% pulmonologists; p = 0.26).An Indwelling pleural catheter was used by 50% pulmonologists and 22% hepatogastroenterologists (p < 0.01). TIPS was recommended by 78% of the responders (85% hepatogastroenterologists vs 52% pulmonologists; p < 0.001) and a liver transplantation, by 76% of the responders (86% hepatogastroenterologists vs 44% pulmonologists; p < 0.001). CONCLUSIONS: The results of this large study provide important data on practices of French speaking hepatogastroenterologists and pulmonologists; it appears that recommendations are warranted.

Baclofen Combined With Psychosocial Care is Useful and Safe in Alcohol-Related Cirrhosis Patients: A Real-Life Multicenter Study.

BACKGROUND: Alcohol-related cirrhosis is a frequent and difficult-to-treat disease. Despite the low hepatic metabolism of baclofen, data on its use in this subgroup are scarce. The French multicenter Observatory of patients treated with Baclofen for Alcohol DEpendence real-life cohort assessed: (a) prescription modalities of baclofen in liver units; (b) safety profile of baclofen; and (c) declared alcohol intake, biological markers of excessive alcohol intake and hepatic function at 12 months. METHODS: All consecutive patients with cirrhosis who received baclofen to reduce alcohol consumption or maintain abstinence were prospectively included. Psychosocial management was always associated. Clinical and biological data were collected every 3 months for 1 year. RESULTS: Between November 2013 and December 2016, 71 in- or outpatients were included from 10 liver units. Of the patients, 25% had ascites. After 12 months, 52 patients (73%) were still being followed, and 41 (57.7%) were still receiving baclofen at a mean dosage of 75 mg/day (r30-210). The overall declared consumption decreased from 100.2 to 14.7 g/day (P < 0.0001), and 29 patients (40.8%) reached abstinence. Significant improvement in the usual biomarkers of excessive alcohol intake (AST, GGT and MCV) and liver function (Prothrombin ratio (PTr), albumin levels) were observed. The usual side effects such as drowsiness were frequent (22%) but no serious adverse events (AEs) or overt encephalopathy related to baclofen was reported. CONCLUSION: In this 1-year follow-up series, baclofen was combined with psychosocial treatment in patients with cirrhosis and was well tolerated. This treatment was associated with a significant decrease in declared alcohol consumption as well as improvement in hepatic function.

Cirrhotic patients with portal hypertension-related bleeding and an indication for early-TIPS: a large multicentre audit with real-life results.

BACKGROUND: The Baveno VI consensus meeting concluded that an early TIPS must be considered in high-risk cirrhotic patients presenting with variceal bleeding (VB) (Child B + active bleeding at endoscopy or Child C10-13 patients). Whether this therapeutic approach is feasible in a real-life setting remains unclear. AIMS: To determine (1) the proportion of patients eligible for early-TIPS among cirrhotic patients with VB, (2) the proportion of these patients who underwent early-TIPS placement and the main reasons for discarding TIPS, and (3) the outcomes of patients who experienced early-TIPS placement in a large, national, prospective, multicentre audit including academic and non-academic centres. MATERIALS AND METHODS: All French centres recruiting gastrointestinal bleeding were invited to participate. All consecutive patients with cirrhosis and PHT-related bleeding were included. RESULTS: 964 patients were included (58 centres: 26 academic, 32 non-academic; patient characteristics: male sex, 77%; age, 59.6 ± 12.1 years; aetiologies of cirrhosis (alcoholic,viral/other, 67%/15%/18%); source of bleeding (EV/GV/other, 80/11/9%); active bleeding at endoscopy 34%; Child A 21%/B 44%/C 35%. Overall, 35% of the patients were eligible for early-TIPS, but only 6.8%, displaying less severe cirrhosis underwent early-TIPS placement. The main reason for discarding TIPS was a lack of availability. The actuarial probability of survival at one year was significantly increased in early-TIPS patients (85.7±0.07% vs 58.9±0.03%, p=0.04). The severity of liver disease was the only parameter independently associated with improved one-year survival. CONCLUSION: In this real-life study, one-third of the cirrhotic patients admitted for VB fulfilled the criteria for early-TIPS placement, whereas only 7% had access to TIPS. TIPS was restricted to patients displaying less severe cirrhosis. The severity of liver disease was the only parameter that influenced survival.

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.

The Periscreen Strip Is Highly Efficient for the Exclusion of Spontaneous Bacterial Peritonitis in Cirrhotic Outpatients.

OBJECTIVES: We aimed to assess the performance of a new strip (Periscreen) for the rapid diagnosis of spontaneous bacterial peritonitis (SBP). METHODS: Ascitic fluid (AF) of cirrhotic patients hospitalized between March 2014 and August 2015 was independently tested by two readers using the new strip, which has four colorimetric graduations (negative, trace, small, and large). SBP was diagnosed on neutrophils in ascites>250/mm3. Ascites not related to portal hypertension were excluded. RESULTS: Overall, 649 patients from 21 French centers were included and 1,402 AF (803 AF samples from 315 outpatients and 599 samples from 334 inpatients) were assessed. Eighty-four AF samples (17 AF in 9 outpatients and 67 AF in 31 inpatients) were diagnosed as SBP. The prevalence of SBP was 6% (2.1% in outpatients vs. 11.2% in inpatients; P<0.001) and 7.2% in patients with symptoms suggestive of SBP (3% in outpatients vs. 11.3% in inpatients; P<0.001). The κ value for inter-reader agreement was 0.81 (95% confidence interval: 0.77-0.84) when using the "trace" threshold. Considering discordant results (n=131) as positive to interpret the diagnostic performance of the strip at the "trace" threshold, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 91.7, 57.1, 12.0, and 99.1%, respectively. At this "trace" threshold, sensitivity and NPV were both 100% in outpatients, and 89.5 and 97.9% in inpatients, respectively. At the "small" threshold, sensitivity, specificity, PPV and NPV were 81.0, 85.9, 25.9 and 98.7%, respectively. CONCLUSIONS: The Periscreen strip is a rapid and highly efficient tool for excluding SBP in the outpatient setting.

Effectiveness and Safety of Tenofovir Disoproxil Fumarate in Chronic Hepatitis B: A 3-Year, Prospective, Real-World Study in France.

BACKGROUND AND AIMS: Tenofovir disoproxil fumarate (TDF) demonstrated potent and sustainable antiviral efficacy and a good safety profile in patients with chronic hepatitis B (CHB) in controlled clinical trials. Real-world data are important to confirm effectiveness and safety data in patient populations encountered in routine clinical practice. METHODS: This non-interventional, prospective, 36-month study included treatment-naïve and treatment-experienced patients with CHB initiating their first TDF regimen (monotherapy or combination therapy) in routine clinical practice in France. Clinical, virologic, biochemical, compliance, and safety data were collected. RESULTS: Data from 440 consecutive patients from 58 centers were analyzed. The majority of the cohort was male (71 %), hepatitis B "e" antigen-negative (HBeAg-) (74 %), and treatment-experienced (56 %); 11 % were aged ≥65 years; and comorbidities were reported in 39 %. After 12 months, 92 % of the overall cohort achieved virologic response (HBV DNA <69 IU/mL) which was maintained to 36 months (96 %); virologic response was achieved by >90 % of patients irrespective of HBeAg status, age, or prior treatment history. At 36 months, 77 % of patients had normal alanine aminotransferase levels. Fourteen patients lost hepatis B surface (HBs) antigen, and seven seroconverted to anti-HBs. TDF was well tolerated over the 36-month study, including in 14 women who became pregnant during the study. Median estimated glomerular filtration rate did not change markedly from baseline irrespective of prior treatment history. CONCLUSIONS: TDF demonstrated potent virologic and biochemical responses across a broad range of patients reflective of routine clinical practice. The safety profile was consistent with results from pivotal trials.

[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.

Hepatitis B Delta: assessment of the knowledge and practices of hepato-gastroenterologists practicing in non-academic settings in France.

BACKGROUND: Data on the management of Hepatitis B-Delta (HB-D) by hepatogastroenterologists (HGs) practicing in nonacademic hospitals or private practices are unknown in France. OBJECTIVE: We aimed to evaluate the knowledge and practices of HGs practicing in nonacademic settings regarding HB-D. METHODS: A Google form document was sent to those HGs from May to September 2021. RESULTS: A total of 130 HGs (mean age, 45 years) have participated in this survey. Among HBsAg-positive patients, Delta infection was sought in only 89% of cases. Liver fibrosis was assessed using FibroScan in 77% of the cases and by liver biopsy in 81% of the cases. A treatment was proposed for patients with >F2 liver fibrosis in 49% of the cases regardless of transaminase levels and for all the patients by 39% of HGs. Responding HGs proposed a treatment using pegylated interferon in 50% of cases, bulevirtide in 45% of cases and a combination of pegylated interferon and bulevirtide in 40.5% of cases. Among the criteria to evaluate the treatment efficacy, a decrease or a normalization of transaminases was retained by 89% of responding HGs, a reduction of liver fibrosis score for 70% of them, an undetectable delta RNA and HBsAg for 55% of them and a 2 log 10 decline in delta viremia for 62% of the cases. CONCLUSION: Hepatitis Delta screening was not systematically performed in HBsAg-positive patients despite the probable awareness and knowledge of the few responders who were able to prescribe treatments of hepatitis delta.

A French national survey on the use of antibiotic prophylaxis in cirrhotic patients.

BACKGROUND: Guidelines recommend antibiotic prophylaxis (AP) in well-selected groups of cirrhotic patients, but the impact of these recommendations has not been assessed in France. AIM: To evaluate AP prescription tendencies for gastrointestinal bleeding, and primary and secondary prophylaxis of spontaneous bacterial peritonitis (SBP). METHODS: Practitioners (n = 1,159) working in general hospitals (GH) or in university hospitals (UH) received a self-administered questionnaire. RESULTS: Three hundred and eighty-nine (33.6%; GH 35% and UH 30.4%) practitioners responded. AP was prescribed by 97.7%, 72.3% and 94.8% of practitioners, without significant differences between UH and GH, respectively, for gastrointestinal bleeding (quinolones 48.2%, third-generation cephalosporins 27.7% and amoxicillin-clavulanic acid 22.2%), primary (quinolones 97.2%) and secondary prophylaxis of SBP (quinolones 99%). For gastrointestinal bleeding, ofloxacin (47.6%) and norfloxacin (37.4%) were the main quinolones prescribed, and ceftriaxone (77%) was the main third-generation cephalosporin prescribed. The principal reasons for prescribing AP were a decrease in bacterial infection (88.9% for gastrointestinal bleeding, 91.3% for primary and 94.3% for secondary prophylaxis of SBP), a recommendation by a consensus conference (83%, 38% and 74.4% respectively) and an improvement in survival (72.8%, 41.3% and 57.7% respectively). Only 31.7% of practitioners (39.6% for UH vs. 28.6% for GH; P = 0.038) believed that AP may reduce the risk of bleeding recurrence. Reported side effects (28%) of AP mainly concerned the risk of quinolone resistance (62% of cases). CONCLUSION: Antibiotic prophylaxis is well-recognized by French practitioners, but its routine use depends on the expertise of practitioners. Quinolones remain the main antibiotic class prescribed irrespective of the type of prophylaxis.

A survey of patterns of practice and perception of NAFLD in a large sample of practicing gastroenterologists in France.

BACKGROUND & AIMS: Most studies on non-alcoholic fatty liver disease (NAFLD) originate from tertiary care centers with an academic interest. How this emerging entity is accepted and managed by a wider body of gastroenterologists is unknown, despite significant implications for the diagnosis of at-risk subjects and the utilization of healthcare resources. METHODS: We conducted a survey among 352 French, board-certified gastroenterologists from a large variety of practices to understand the clinical burden, perceived severity, and management patterns of NAFLD. RESULTS: Half of participants saw >30 new cases (equal to HCV) of NAFLD and 40% >5 new cases of NASH-cirrhosis yearly. Only 20% of patients were referred by endocrinologists; conversely, gastroenterologists overwhelmingly referred NAFLD patients for assessment of metabolic co-morbidities. In patients with metabolic risk factors, a majority of physicians considered the diagnosis of NAFLD, even if other liver diseases co-existed. The diagnosis heavily relies on aminotransferases, hence patients with normal ALT are usually not diagnosed. Liver biopsy is performed for fibrosis staging but not for the diagnosis/grading of steatohepatitis, and mainly decided based on non-invasive fibrosis procedures. Pharmacological treatment is used despite a lack of clear evidence of efficacy. Physicians monitor patients themselves, usually twice a year. CONCLUSIONS: NAFLD is recognized and accepted as a disease in itself with potentially severe outcomes. Most at-risk patients are currently missed because of non-referral by endocrinologists and no exploration of those with normal aminotransferases. The medical need for the diagnosis and treatment of NAFLD is real in the community of gastroenterologists at large.

Fibroscan® and Shear Wave correlated well in hepatic fibrosis evaluation of patients with chronic liver diseases "in real life situation".

BACKGROUND: A new noninvasive medical device based on ultrasound elastography such as the Shear Wave Elastography (SWE) was designed in order to measure the liver hardness. The purpose of this work was to evaluate the correlation of the results of the liver elasticity measurements obtained by Fibroscan® (FS) and SWE for patients with chronic liver diseases. METHODS: Between January and October 2017, the patients who were followed during this period of time underwent noninvasive assessments of liver fibrosis by SWE in the intercostal spaces during abdominal ultrasound procedures and/or FS. The correlation between FS and SWE was estimated and tested at a 0.05 significance level. RESULTS: Four hundred and seventy-six patients were included in this study. The main etiologies of chronic liver disease were non alcoholic fatty disease (NAFLD), chronic viral hepatitis B (HBV) and chronic viral hepatitis C (HCV). All patients underwent a SWE and 167 among them underwent a FS procedure. The patients who were followed revealed a median FS measurement of 5.80 kpa (Q25 = 4.90 kPa; Q75 = 8 kPa) and a median SWE measurement of 7.00 kPa (Q25 = 6.10 kPa; Q75 = 8.10 kPa). We could observe a significant correlation between the FS and SWE measurements (0.49; P = .001) in the total cohort. The average absolute difference between the measurements of these 2 methods was of 2.54 kPa (sd = 3.39). There was no significant correlation for patients with NAFLD no matter whether they presented with signs of suspected non alcoholic steatohepatitis (NASH) or not (R = 0.20; P = .108). All patients intending to perform the examination were able to undergo the SWE, allowing 33.3% of the patients who failed the FS to have a noninvasive evaluation of their fibrosis. CONCLUSION: The SWE technique proved to be as efficient as the FS one for the evaluation of the liver fibrosis in real life situation.

From congestive hepatopathy to hepatocellular carcinoma, how can we improve patient management?

Heart failure and liver disease often coexist because of systemic disorders and diseases that affect both organs as well as complex cardio-hepatic interactions. Heart failure can cause acute or chronic liver injury due to ischaemia and passive venous congestion, respectively. Congestive hepatopathy is frequently observed in patients with congenital heart disease and after the Fontan procedure, but also in older patients with chronic heart failure. As congestive hepatopathy can evolve into cirrhosis and hepatocellular carcinoma, screening for liver injury should be performed in patients with chronic cardiac diseases and after Fontan surgery. Fibrosis starts in the centro-lobular zone and will extend progressively to the portal area. Chronic liver injury can be reversible if heart function improves. However, in the case of terminal heart failure, uncontrolled by medical resources or by assistive device support, the combination of heart and liver transplants must be discussed in patients with chronic advanced liver fibrosis. In this review of the literature, we will focus on congestive hepatopathy and its complications, such as liver fibrosis and hepatocellular carcinoma, with the aim of improving the management and surveillance of patients experiencing these complications.

Lessons from "real life experience" of rifaximin use in the management of recurrent hepatic encephalopathy.

BACKGROUND: Hepatic encephalopathy (HE) is a major complication of cirrhosis with independent prognostic significance. The current management of HE is mainly based on lactulose. Rifaximin has been shown to decrease the risk of HE recurrence in patients with episodic forms. HE can also be persistent. However, there is no drug support recommendation for rifaximin use in this setting. AIM: To assess the effectiveness of rifaximin in the management of recurrent episodes of HE and recurrent acute exacerbations on persistent HE, in "real life conditions". METHODS: In this retrospective study, using a within-subjects design, we collected data of patients treated with rifaximin for HE in two liver diseases centers, during the six-month period before and during the six-month period after the initiation of rifaximin. The primary effectiveness endpoint was the total number of HE events involving hospitalization. RESULTS: Rifaximin was introduced for prevention of recurrent HE episodes in 29 out of 62 patients with normal mental status between episodes and for prevention of recurrent acute exacerbations on persistent HE in 33 out of 62 patients. In the "prevention of recurrent HE episodes" group, fewer HE events (0.79 vs 1.78; P = 0.013) were reported during the period of time when rifaximin was used. In the "prevention of recurrent acute exacerbations on persistent HE" group, there was no significant difference in the number of HE-events (1.48 vs 1.77; P = 0.582). CONCLUSION: In this real-life experience, the effectiveness of rifaximin was confirmed in the prevention of HE episodes recurrence but was not proved in the prevention of acute exacerbations recurrence on persistent HE.

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.

Hepatitis C treatment with all-oral direct-acting antivirals: Effectiveness and tolerance in a multicenter, prospective, observational study from French general hospitals (APROVVIE, ANGH).

BACKGROUND AND AIMS: According to clinical trials, the treatment of patients with chronic hepatitis C (CHC) with second-generation direct acting antiviral agents (DAAs) is highly efficient and well tolerated. The goal of this study was to investigate the effectiveness and safety of various combinations of these drugs during their first 2 years of use in the real-world practice of French general hospitals. METHODS: Data from patients treated with all-oral DAAs in 24 French non-academic hospital centers from March 1, 2014 to January 1, 2016, were prospectively recorded. The sustained virological response 12-24 weeks after treatment (SVR 12-24) was estimated and severe adverse events (SAE) were evaluated and their predictive factors were determined using logistic regression. RESULTS: Data from 1123 patients were analyzed. The population was 69% genotype (G) 1, 13% G3, 11.5% G4, 5% G2, 49% with cirrhosis and 55% treatment-experienced. The treatment regimens were sofosbuvir/ledipasvir (38%), sofosbuvir/daclatasvir (32%), sofosbuvir/simeprevir (17%), ombitasvir+paritaprevir+ritonavir (5%) (with dasabuvir 3.5%), and sofosbuvir/ribavirin (8%). Ribavirin was given to 24% of patients. The SVR 12-24 was 91.0% (95% CI: 89.2-92.5%). Sofosbuvir-ribavirin was less effective than other regimens. The independent predictors of SVR 12-24 by logistic regression were body weight, albumin, previous hepatocellular carcinoma and treatment regimen (sofosbuvir/ribavirin vs. others). Sixty-four severe adverse events (SAE) were observed in 59 [5.6%] patients, and were independently predicted by cirrhosis and baseline hemoglobin. Serum creatinine increased during treatment (mean 8.5%, [P<10-5]), satisfying criteria for acute kidney injury in 62 patients (7.3%). Patient-reported overall tolerance was excellent, and patient-reported fatigue decreased during and after treatment. CONCLUSIONS: Second generation DAAs combinations are as effective and well tolerated in a « real-world ¼ population as in clinical trials. Further studies are needed on renal tolerance.

Prevalence of hepatitis C infection and risk factors in hospitalized diabetic patients: results of a cross-sectional study.

OBJECTIVES: Although there may exist a nosocomial risk of hepatitis C virus (HCV) infection in patients with type 1 or type 2 diabetes, this risk has not been fully investigated thus far and its magnitude is unknown. The aim of this multicenter cross-sectional study was to evaluate the prevalence of, and risk factors for, hepatitis C infection in consecutive hospitalized patients with diabetes and to assess the nosocomial risk and magnitude of HCV infection in these patients. PATIENTS AND METHODS: Consecutive hospitalized patients with diabetes seen in 11 French hepatogastroenterology and diabetology departments were studied. The prevalence of anti-HCV antibodies was compared with that observed in healthy blood donors and individuals seen during routine medical checkup. Diabetic patients with anti-HCV antibodies were compared with patients without anti-HCV antibodies for assessment of risk factors. RESULTS: In total 1561 patients were studied. Independent risk factors for HCV infection were assessed through multivariate analysis. Thirty-three patients (2.11%) had anti-HCV antibodies and 21 (63.70%) had HCV identified risk factors. The prevalence of HCV infection was higher in patients with diabetes than in blood donors (0.08%) or healthy controls (0.20%) (P<0.001). Multivariate analysis identified four independent risk factors for HCV infection: blood transfusion before 1991 [odds ratio (OR)=2.88, P=0.033], intravenous drug use (OR=21.37, P=0.012), treatment in a hepatogastroenterology center (OR=4.17, P=0.002) and a high number (>2) of previous admissions since the onset of diabetes (OR=2.52, P=0.039). CONCLUSION: A nosocomial source of HCV infection in hospitalized diabetic patients is suggested by the increased risk of HCV infection associated with the number of hospitalizations. This may account for at least 36% of cases of HCV infection.

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.