Nonalcoholic fatty liver disease: opinions, population served, and management from a sample of French hepato(gastroentero)logists (PERSEPT study).

OBJECTIVE: The three-fold objective of this study was to describe the opinions, the population served, and tools used for the management of nonalcoholic fatty liver disease (NAFLD) by French hepato(gastro)enterologists (HGEs). METHODS: Seventy-five French HGEs working in hospitals or in private practice, who regularly managed patients with NAFLD, completed three questionnaires: one about their opinions about disease management, one on the 10 first patients with NAFLD they saw in February 2020, and the third about the first five patients meeting the 2016 European Association for the Study of the Liver criteria for specialist referral. RESULTS: Management of NAFLD was seen as challenging, complex, time-consuming, and frustrating. Available treatments were considered to be unsatisfactory by most participants. In the whole population studied (671 patients), 41% were obese, 50% overweight, 49% had type 2 diabetes, 61% dyslipidemia, 51% arterial hypertension, 57% nonalcoholic steato-hepatitis (NASH), 37% advanced fibrosis, and 19% cirrhosis. In the subgroup of 313 patients needing specialist referral, the use of liver biopsy was low (30%) and decreasing, whereas vibration-controlled transient elastometry was high (66%) and increasing; blood fibrosis tests were rarely used. NASH was usually diagnosed without liver biopsy. Nutritional counseling was provided to 3/4 patients, physical activity counseling in 1/5. A personalized therapeutic project was defined in less than one-third of patients. Ursodeoxycholic acid and vitamin E were used in a minority of patients. CONCLUSION: The management of NAFLD is not considered satisfactory by French HGE who care for a relatively severe population. Noninvasive assessment of fibrosis and multidisciplinary management should be improved.

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.

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.

Effects of Age on Treatment of Chronic Hepatitis C with Direct Acting Antivirals.

INTRODUCTION AND AIM: Data on the efficacy and tolerance of interferon-free treatment in chronic hepatitis C (CHC) in elderly patients are limited in phase II-III trials. MATERIAL AND METHODS: A prospective cohort of adult patients with CHC treated in French general hospitals. RESULTS: Data from 1,123 patients, distributed into four age groups, were analyzed. Of these, 278 were > 64 years old (fourth quartile) and 133 were > 73 years old (tenth decile). Elderly patients weighed less, were more frequently treatment-experienced women infected with genotype 1b or 2, while they less frequently had genotype 3 or HIV coinfection, but had more frequent comorbidities and drug consumption. Half of the patients had cirrhosis, whatever their ages. The main treatment regimens were sofosbuvir/ledipasvir (37.8%), sofosbuvir/daclatasvir (31.8%), sofosbuvir/simeprevir (16.9%), sofosbuvir/ribavirin (7.8%); ribavirin was given to 24% of patients. The overall sustained virological response (SVR) rate was 91.0 % (95% CI: 89.292.5%) with no difference according to age. Logistic regression of the independent predictors of SVR were albumin, hepatocellular carcinoma and treatment regimen, but not age. The rate of severe adverse events (66 in 59/1062 [5.6%] patients) tended to be greater in patients older than 64 years of age (21/261,8.1%), but the only independent predictors of SAE by logistic regression were cirrhosis and baseline hemoglobin. Patient-reported overall tolerance was excellent in all age groups, and patient-reported fatigue decreased during and after treatment, independent of age. CONCLUSIONS: The high efficacy and tolerance of interferon-free regimens is confirmed in elderly patients in real-life conditions.

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.

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.

Hepatocellular carcinoma is diagnosed at a later stage in alcoholic patients: Results of a prospective, nationwide study.

BACKGROUND: Recent data suggest that alcohol-related hepatocellular carcinoma (HCC) is diagnosed at a later stage. The aim of this study was to compare HCC characteristics and outcomes in an alcohol-related group (group A) and a non-alcohol-related group (group NA). METHODS: A total of 1207 patients with newly diagnosed HCC were prospectively included between May 2008 and October 2009. Patients with multiple causes (alcohol plus another cause) were excluded. Patients were followed every year for 5 years. Recorded variables, including etiologies were tested as prognostic factors of survival in a multivariate Cox model after adjustments for a lead-time bias. RESULTS: In all, 894 patients were analyzed: 582 (65.1%) were in group A, and 312 (34.9%) were in group NA. Alcohol-related HCC was more likely to be diffuse and detected in patients with a worse performance status and worse liver function. After adjustments for a lead-time bias, the median overall survival (OS) was 9.7 and 5.7 months in groups NA and A, respectively (P = .0002), and 5.8 and 5.0 months in alcohol-abstinent and alcohol non-abstinent groups, respectively (P = .09). The prognostic role of alcohol disappeared when survival was assessed at each Barcelona Clinic Liver Cancer (BCLC) stage. Patients with HCC detected during a cirrhosis follow-up program (n = 199 [22.3% of the whole cohort]) had increased lead time-adjusted median OS in comparison with patients with HCC diagnosed incidentally (11.7 vs 5.4 months; P < .0001). CONCLUSIONS: In comparison with patients with non-alcohol-related HCC, patients with alcohol-related HCC have reduced OS, mainly because of worse liver function and tumor characteristics at diagnosis, as attested by similar survival within each BCLC stage. Cancer 2018;124:1964-72. © 2018 American Cancer Society.

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.

Middle-term mortality and re-bleeding after initial diverticular bleeding: A nationwide study of 365 mostly elderly French patients.

BACKGROUND AND AIMS: The aim of this study was to determine the mortality and re-bleeding rates, and the risk factors involved, in a cohort of patients with previous diverticular bleeding (DB). METHODS: In 2007, data on 2462 patients with lower gastrointestinal (GI) bleeding were collected prospectively at several French hospitals. We studied the follow-up of patients with DB retrospectively. The following data were collected: age, mortality rates and re-bleeding rates, drug intake, surgery and comorbidities. RESULTS: Data on 365 patients, including 181 women (mean age 83.6 ± 9.8 years) were available. The median follow-up time was 3.9 years (IQR 25-75: 1.7-5.4). Of these, 148 patients died (40.5%). Among the 70 patients (19.2%) who had at least one re-bleeding episode, nine died and three underwent surgical procedures. Anticoagulation and antiplatelet therapy was discontinued in 70 cases (19.2%). The independent risk factors contributing to mortality were age > 80 years (HR = 3.18 (2.1-4.9); p < 0.001) and a Charlson comorbidity score > 2 (1.91 (1.31-2.79); p = 0.003). Discontinuation of therapy was not significantly associated with a risk of death due to cardiovascular events. No risk factors responsible for re-bleeding were identified, such as antiplatelet and anticoagulant therapy in particular. CONCLUSIONS: In this cohort, the rates of mortality and DB re-bleeding after a median follow-up time of 3.9 years were 19.2% and 40.5%, respectively. The majority of the deaths recorded were not due to re-bleeding.

Over 90% of cases of Microscopic Colitis can be diagnosed by performing a short colonoscopy.

AIMS: To determinate the topographical distribution of key diagnostic histological features of lymphocytic colitis (LC) and collagenous colitis (CC) and to establish what correlations may exist between the histological findings and the causes and severity of MC. PATIENTS AND METHODS: Patients with MC were included in a prospective multicentre French study from September 2010 to October 2012. MC was diagnosed by performing total colonoscopy with multiple biopsies of the rectum and colon collected in separate jars and analyzed separately for each site (descending and sigmoid colon, transverse colon, ascending colon). CC was defined as a subepithelial collagen layer>10µm thick and LC as an intraepithelial lymphocyte (IEL) count>20 lymphocytes per 100 epithelial cells without any associated thickening of the subepithelial collagen. RESULTS: Ninety-five patients, 69 with LC 26 and with CC, were included in the analysis. The sensitivity of the biopsies for diagnosing MC was maximum in the transverse colon and minimum in the rectum. Rectal and left colonic biopsies resulted in the diagnosis of CC and CL in 93% and 94% of cases, respectively. All the remaining cases of MC were diagnosed by performing additional biopsies beyond the splenic flexure. In patients with LC, a higher rate of IELs was associated with the absence of abdominal pain (P=0.01) and a shorter duration of diarrhea (P=0.001). In patients with CC, a lower level of collagen thickness in the basement membrane was associated with the presence of an autoimmune disease (P=0.02). CONCLUSION: More than 90% of cases of microscopic colitis were diagnosed in this study by performing rectal and left colonic biopsies.

Treatment of autochthonous acute hepatitis E with short-term ribavirin: a multicenter retrospective study.

BACKGROUND & AIMS: Hepatitis E virus (HEV) genotypes 3 and 4 cause sporadic cases of infection in developed countries. Being elderly and having an underlying liver disease are the main risk factors for death in this population. Chronic infection has been described in immunocompromised patients. Ribavirin is now the antiviral treatment of choice in solid-organ-transplant recipients with chronic HEV infection. We hypothesized that early short-term treatment of acute HEV infection may be useful for patients with risk factors or undergoing chemotherapy. METHODS: Between July 2010 and January 2014, 21 patients diagnosed with acute HEV infection were treated with ribavirin, at 600-800 mg/day for up to 3 months. All serum samples were positive for HEV RNA. RESULTS: Nine patients were treated for severe hepatitis. Six patients were aged >70 years. Four patients were receiving an immunosuppressive therapy for an autoimmune disease and two patients were undergoing chemotherapy for a malignancy. Two patients received a fixed-dose regimen. For all other patients, ribavirin was stopped when HEV became undetectable in the serum. The median duration of ribavirin treatment was 26 days. Two patients developed severe anaemia. Two patients with encephalopathy died. One patient relapsed transiently. All patients were cleared of HEV and regained normalized liver-enzyme levels. Immunosuppressive treatment and chemotherapy could be resumed. CONCLUSIONS: Treatment of acute HEV infection using ribavirin seems safe and effective. Short-term treatment tailored to viraemia may be the best regimen for this indication.