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.

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.

Causes and consequences of portal vein thrombosis in 1,243 patients with cirrhosis: results of a longitudinal study.

UNLABELLED: In cirrhosis, portal vein thrombosis (PVT) could be a cause or a consequence of the progression of liver disease. We analyzed data from a prospective trial of ultrasound screening for hepatocellular carcinoma in order to identify risk factors for and the impact of PVT in patients with cirrhosis. In all, 1,243 adults with cirrhosis without PVT were enrolled from 43 liver units in France and Belgium between June 2000 and March 2006. The mean follow-up was 47 months. Doppler ultrasonography was used to check the portal vein. Progression of liver disease was defined by the development of: ascites, hepatic encephalopathy, variceal bleeding, prothrombin <45%, serum bilirubin >45 µmol/L, albumin <28 g/L, and/or creatinine >115 µmol/L. G20210A prothrombin and factor V gene mutations were assessed in sera stored at three large centers. The 5-year cumulative incidence of PVT was 10.7%. PVT was mostly partial and varied over time. The development of PVT was independently associated with baseline esophageal varices (P = 0.01) and prothrombin time (P = 0.002), but not with disease progression before PVT, or prothrombotic mutations. Disease progression was independently associated with baseline age (hazard ratio [HR] 1.55; 95% confidence interval [CI]: 1.11-2.17), body mass index (HR 1.40; 95% CI: 1.01-1.95), prothrombin time (HR 0.79; 95% CI: 0.70-0.90), serum albumin (HR 0.97; 95% CI: 0.94-0.99), and esophageal varices (HR 1.70; 95% CI: 1.21-2.38) but not with the prior development of PVT (HR 1.32; 95% CI: 0.68-2.65). CONCLUSION: In patients with cirrhosis, the development of PVT is associated with the severity of liver disease at baseline, but does not follow a recent progression of liver disease. There is no evidence that the development of PVT is responsible for further progression of liver disease.

[Vascular liver diseases]. / MALADIES VASCULAIRES DU FOIE.

Vascular liver diseases include a group of rare, even exceptional, diseases: portal vein thrombosis, obliterative portal venopathy and Budd-Chiari syndrome. Here we will discuss in detail the least rare, portal vein thrombosis, of which the main complication (when recanalization was not reached during the acute-phase) is esophageal variceal bleeding. However, a prothrombotic condition (including myeloproliferative syndrome) is often the cause of portal vein thrombosis. Thereby, in certain cases, a long-term anticoagulation is necessary despite the bleeding risk. Aside from these rare diseases, vascular and thrombotic involvement participate in the pathophysiology of cirrhosis, and anticoagulant treatment might be beneficial in some patients.

Towards elimination of chronic viral hepatitis in French Polynesia: results from a national population-based survey.

Background: In French Polynesia, hepatitis B virus (HBV) infection appears as a major risk factor for hepatocellular carcinoma (HCC), which detection rate in the Austral archipelago is among the highest in the world. Through a nationally representative cross-sectional survey of the adult population, this study aimed at assessing the prevalence of HBV, but also hepatitis C virus (HCV), and hepatitis delta virus (HDV). Methods: A total of 1942 blood samples from participants aged 18-69 years were tested for anti-HBc, anti-HBs, HBsAg, anti-HCV IgG, and HDV RNA. Complete genome sequencing of detected HBV strains was performed. Findings: Among participants, 315/1834, 582/1834, 33/1834, 0/1857, and 0/33 tested positive for anti-HBc, anti-HBs, HBsAg, anti-HCV IgG, and HDV RNA, respectively. The population prevalence of HBsAg was estimated at 1.0% (95% CI: 0.6-1.7). All HBsAg carriers were born in French Polynesia before vaccination at birth became mandatory. In multivariate analyses, identified factors associated with HBsAg carriage included: the archipelago of residence (p < 0.0001), age (p < 0.0001), and education level (p = 0.0077). HBV genotypes B, C, and F were detected. Interpretation: French Polynesia has a low endemicity level of HBV and its population may be considered at low risk for HCV and HDV infection. However, prevalence of HBsAg was found concerning in Austral (3.8%; 95% CI: 1.9-7.5) and Marquesas (6.5%; 95% CI: 3.8-11) archipelagoes. In the Austral archipelago, the presence of genotype C may account for the elevated rate of HCC. Our findings warrant more efforts to improve access to detection, prevention and care to people born before the systematic vaccination policy application, and residing in higher-risk areas, to achieve HBV elimination in French Polynesia. Funding: Research Delegation of French Polynesia.

Unravelling the determinants of human health in French Polynesia: the MATAEA project.

Background: French Polynesia is a French overseas collectivity in the Southeast Pacific, comprising 75 inhabited islands across five archipelagoes. The human settlement of the region corresponds to the last massive migration of humans to empty territories, but its timeline is still debated. Despite their recent population history and geographical isolation, inhabitants of French Polynesia experience health issues similar to those of continental countries. Modern lifestyles and increased longevity have led to a rise in non-communicable diseases (NCDs) such as obesity, diabetes, hypertension, and cardiovascular diseases. Likewise, international trade and people mobility have caused the emergence of communicable diseases (CDs) including mosquito-borne and respiratory diseases. Additionally, chronic pathologies including acute rheumatic fever, liver diseases, and ciguatera, are highly prevalent in French Polynesia. However, data on such diseases are scarce and not representative of the geographic fragmentation of the population. Objectives: The present project aims to estimate the prevalence of several NCDs and CDs in the population of the five archipelagoes, and identify associated risk factors. Moreover, genetic analyses will contribute to determine the sequence and timings of the peopling history of French Polynesia, and identify causal links between past genetic adaptation to island environments, and present-day susceptibility to certain diseases. Methods: This cross-sectional survey is based on the random selection of 2,100 adults aged 18-69 years and residing on 18 islands from the five archipelagoes. Each participant answered a questionnaire on a wide range of topics (including demographic characteristics, lifestyle habits and medical history), underwent physical measurements (height, weight, waist circumference, arterial pressure, and skin pigmentation), and provided biological samples (blood, saliva, and stool) for biological, genetic and microbiological analyses. Conclusion: For the first time in French Polynesia, the present project allows to collect a wide range of data to explore the existence of indicators and/or risk factors for multiple pathologies of public health concern. The results will help health authorities to adapt actions and preventive measures aimed at reducing the incidence of NCDs and CDs. Moreover, the new genomic data generated in this study, combined with anthropological data, will increase our understanding of the peopling history of French Polynesia. Clinical trial registration: https://clinicaltrials.gov/, identifier: NCT06133400.

Extrahepatic portal venous system thrombosis in recurrent acute and chronic alcoholic pancreatitis is caused by local inflammation and not thrombophilia.

OBJECTIVES: Extrahepatic portal venous system thrombosis (EPVST) occurs in 13% of patients with either recurrent acute (AP) or chronic (CP) alcoholic pancreatitis. The role of thrombophilia has never been assessed in this entity. METHODS: All consecutive patients with alcoholic AP or CP were included in a prospective study. All patients underwent a computerized tomography (CT) scan of the pancreas to evaluate EPVST as well as thorough testing for thrombophilia (protein C, S, and antithrombin deficiency, factor II, factor V, and JAK2 gene mutations, homocystein, biological antiphospholipid syndrome). RESULTS: A total of 119 patients (male, n=100 (84%); smokers, n=110 (92%)) were included. EPVST was found in 41 patients (35%). The portal, superior mesenteric, or splenic veins were involved in 34%, 24%, and 93% of patients, respectively. Thrombophilia was identified in 18% (n=22), including the biological antiphospholipid syndrome, factor V Leiden mutation, and factor II G20210A gene mutation in 21 (17.6%), 2 (1.6%), and 1 patient (0.8%), respectively. On univariate analysis, the factors associated with EPVST were smoking (RR=1.6 (1.38-1.85), P=0.03), pseudocysts (RR=2.91 (1.29-6.56), P=0.008), a pseudocyst in the pancreatic tail (P=0.03), a high CT severity index for AP (P=0.007), and pancreatic parenchymal necrosis (P=0.02). The presence of hemostatic risk factors was not associated with an increased risk of EPVST. On multivariate analysis, only pseudocysts were associated with EPVST (hazard ratio: 6.402; 95% confidence interval (1.59-26.54), P=0.009). CONCLUSIONS: EPVST is found in 35% of patients with acute/chronic alcoholic pancreatitis. Local inflammation appears to be the major predisposing condition. The presence of some form of thrombophilia does not increase the risk of EPVST and should not be systematically searched for in case of EPVST.

Obliterative portal venopathy: portal hypertension is not always present at diagnosis.

BACKGROUND & AIMS: Previous studies on obliterative portal venopathy (OPV) have been biased due to the selection of patients with non-cirrhotic portal hypertension. The aim of this study was to clarify the characteristics of OVP diagnosed by liver biopsy. METHODS: Fifty-nine consecutive patients with OPV were retrospectively selected on strict histological criteria. Clinical, laboratory, portal vein patency, and associated disorders potentially involving vascular alterations were analyzed. The occurrence of complications was recorded during follow-up. RESULTS: Mean age at diagnosis was 38.5±15 years old. Initial presentation was portal hypertension (64% of patients) and/or extrahepatic portal vein thrombosis (EHPVT) (22%) or isolated abnormal laboratory tests (20%). Associated diseases found at diagnosis were: prothrombotic disorders (30% of patients) and immune-mediated disorders (17%); 53% of patients had no causal factor (idiopathic OPV). During follow-up (median 8.6 years, range 1-23 years), features of portal hypertension worsened in 46% of patients; EHPVT and portal hypertension were finally found in 44% and 88% of patients. Anti-coagulation and beta-blockers were administered in 47% and 59% of patients, respectively. Severe complications (liver transplantation and/or death) occurred in 11 (19%) patients, 8 had idiopathic OPV. Patients with prothrombotic disorders received earlier anticoagulation therapy; all survived without transplantation. CONCLUSIONS: A confident diagnosis of OPV can be done by biopsy and is conceivable in patients under 40 years without clinically significant portal hypertension. Poor outcome was noted in 19% of patients, most of them affected with idiopathic OPV. Patients with prothrombotic disorders received early anticoagulation and appeared to have a better outcome despite a high proportion of EHPVT.

Pentoxifylline does not decrease short-term mortality but does reduce complications in patients with advanced cirrhosis.

BACKGROUND & AIMS: Pentoxifylline, an inhibitor of tumor necrosis factor-alpha, is given to patients with liver diseases, but its effects in patients with advanced cirrhosis are unknown. We performed a randomized, placebo-controlled, double-blind trial of its effects in patients with cirrhosis. METHODS: A total of 335 patients with cirrhosis (Child-Pugh class C) were assigned to groups given either pentoxifylline (400 mg, orally, 3 times daily; n = 164) or placebo (n = 171) for 6 months. The primary end point was mortality at 2 months. Secondary end points were mortality at 6 months and development of liver-related complications. RESULTS: By 2 months, 28 patients in the pentoxifylline group (16.5%) and 31 in the placebo group (18.2%) had died (P = .84). At 6 months, 50 patients in the pentoxifylline group (30.0%) and 54 in the placebo group (31.5%) had died (P = .75). The proportions of patients without complications (eg, bacterial infection, renal insufficiency, hepatic encephalopathy, or gastrointestinal hemorrhage) were higher in the pentoxifylline group than in the placebo group at 2 months (78.6% vs 63.4%; P = .006) and 6 months (66.8% vs 49.7%; P = .002). The probability of survival without complications was higher in the pentoxifylline group than in the placebo group at 2 and 6 months (P = .04). In multivariate analysis, the factors associated with death were age, the Model for End-Stage Liver Disease score, and presence of early-stage carcinoma. Treatment with pentoxifylline was the only factor associated with liver-related complications. CONCLUSIONS: Although pentoxifylline does not decrease short-term mortality in patients with advanced cirrhosis, it does reduce the risk of complications.

Acute portal vein thrombosis unrelated to cirrhosis: a prospective multicenter follow-up study.

UNLABELLED: Current recommendations for early anticoagulation in acute portal vein thrombosis unrelated to cirrhosis or malignancy are based on limited evidence. The aim of this study was to prospectively assess the risk factors, outcome, and prognosis in patients managed according to these recommendations. We enrolled 102 patients with acute thrombosis of the portal vein, or its left or right branch. Laboratory investigations for prothrombotic factors were centralized. Thrombus extension and recanalization were assessed by expert radiologists. A local risk factor was identified in 21% of patients, and one or several general prothrombotic conditions in 52%. Anticoagulation was given to 95 patients. After a median of 234 days, the portal vein and its left or right branch were patent in 39% of anticoagulated patients (versus 13% initially), the splenic vein in 80% (versus 57% initially), and the superior mesenteric vein in 73% (versus 42% initially). Failure to recanalize the portal vein was independently related to the presence of ascites (hazard ratio 3.8, 95% confidence interval 1.3-11.1) and an occluded splenic vein (hazard ratio 3.5, 95% confidence interval 1.4-8.9). Gastrointestinal bleeding and intestinal infarction occurred in nine and two patients, respectively. Two patients died from causes unrelated to thrombosis or anticoagulation therapy. CONCLUSION: Recanalization occurs in one-third of patients receiving early anticoagulation for acute portal vein thrombosis, whereas thrombus extension, intestinal infarction, severe bleeding, and death are rare. Alternative therapy should be considered when ascites and splenic vein obstruction are present.

Low-phospholipid-associated cholelithiasis syndrome: Prevalence, clinical features, and comorbidities.

BACKGROUND & AIMS: Low-phospholipid-associated cholelithiasis (LPAC) syndrome, a rare genetic form of intrahepatic cholelithiasis in adults, is still poorly understood. We report the results of the largest-ever case-control study of patients with LPAC syndrome aiming to assess the prevalence, clinical features, and comorbidities of the disease. METHODS: We included all LPAC cases diagnosed between 2001 and 2016 in 11 French centres. Controls consisted of all patients who underwent a cholecystectomy for common gallstone disease in a single non-academic centre over 1 year. A logistic regression analysis was used to identify the clinical features associated with LPAC syndrome across several patient strata with increasing levels of diagnostic confidence. The ratio between the incident cases of LPAC syndrome and the total number of cholecystectomies for gallstones was used to assess the relative prevalence of the disease. RESULTS: In this study, 308 cases and 206 controls were included. LPAC syndrome accounted for 0.5-1.9% of all patients admitted with symptomatic gallstone disease. Age at first symptoms <40 years, absence of overweight, persistence of symptoms after cholecystectomy, intrahepatic micro- or macrolithiasis, common bile duct (CBD) lithiasis, and no history of cholecystitis were independently associated with LPAC diagnosis. ATP-binding cassette subfamily B member 4 (ABCB4) variants, present in 46% of cases, were associated with CBD lithiasis, chronic elevation of gamma-glutamyltransferase (GGT), and personal or family history of hepato-biliary cancer. CONCLUSIONS: In this case-control study, LPAC syndrome accounted for approximately 1% of symptomatic cholelithiasis in adults. In addition to pre-established diagnostic criteria, normal weight, CBD lithiasis, and no history of cholecystitis were significantly associated with the syndrome. ABCB4 gene variations in patients with LPAC were associated with CBD lithiasis, chronic cholestasis, and a personal or family history of hepato-biliary cancer. LAY SUMMARY: In the largest case-control study ever conducted in patients with LPAC syndrome, a rare genetic form of intrahepatic cholelithiasis in young adults, LPAC syndrome was found in approximately 1% of all patients admitted to the hospital for symptomatic gallstones and, in addition to the pre-established characteristics of the syndrome (age at first symptoms <40 years, recurrence of symptoms after cholecystectomy, and/or imaging evidence of intrahepatic microlithiasis), was associated with lower BMI, higher prevalence of common bile duct stones, and lower incidence of acute cholecystitis. ABCB4 gene variants, which were detected in about half of cases, were associated with common bile duct stones and a personal or family history of hepato-biliary cancer.

The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases.

Myeloproliferative diseases (MPDs) represent the commonest cause of splanchnic vein thrombosis (SVT), including Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT), but their diagnosis is hampered by changes secondary to portal hypertension, while their influence in the outcome of SVT remains unclear. We assessed the diagnostic and prognostic value of JAK2 and MPL515 mutations in 241 SVT patients (104 BCS, 137 PVT). JAK2V617F was found in 45% of BCS and 34% of PVT, while JAK2 exon 12 and MPL515 mutations were not detected. JAK2V617F was found in 96.5% of patients with bone marrow (BM) changes specific for MPD and endogenous erythoid colonies, but also in 58% of those with only one feature and in 7% of those with neither feature. Stratifying MPD diagnosis first on JAK2V617F detection would have avoided BM investigations in 40% of the patients. In BCS, presence of MPD carried significantly poorer baseline prognostic features, required hepatic decompression procedures earlier, but had no impact on 5-year survival. Our results suggest that JAK2V617F testing should replace BM investigations as initial test for MPD in patients with SVT. Underlying MPD is associated with severe forms of BCS, but current therapy appears to offset deleterious effects of MPD on the medium-term outcome.

Pregnancy in women with known and treated Budd-Chiari syndrome: maternal and fetal outcomes.

BACKGROUND/AIMS: Budd-Chiari syndrome (BCS) mainly affects women of childbearing age. We aimed to clarify whether pregnancy, a thrombotic risk factor, should be contraindicated in patients with known and treated BCS. METHODS: A retrospective study of pregnancy in women with known and treated BCS. RESULTS: Sixteen women had 24 pregnancies. Nine women had undergone surgical or radiological treatment. Anticoagulation was administered during 17 pregnancies. Seven fetuses were lost before gestation week 20. Deliveries occurred between week 20 and 31 in two patients, week 32 and 36 in eleven and after week 37 in four. There was one stillbirth, but 16 infants did well. Factor II gene mutation was a factor for a poor outcome of pregnancies. In two patients, symptomatic thrombosis recurred during pregnancy or postpartum. All patients were alive after a median follow-up of 34 months after the last delivery. Bleeding at delivery, although non-lethal, occurred only on anticoagulation therapy. CONCLUSIONS: When known and treated BCS is well controlled, pregnancy should not be contraindicated as maternal outcome, and fetal outcome beyond gestation week 20, are good. The risk-benefit ratio of anticoagulant therapy needs to be further clarified. Patients should be fully informed of the persistent risks of such pregnancies.

Pancreatic portal cavernoma in patients with cavernous transformation of the portal vein: MR findings.

The purpose of the article was to prospectively evaluate the MR findings of pancreatic portal cavernoma in a consecutive series of patients with cavernous transformation of the portal vein. This study was approved by the review board of our institution, and informed consent was obtained. The clinical and biological data and the MR imaging for 20 patients (11 female, 9 male; median age, 49 years) with cavernous transformation of the portal vein and no evidence of previous pancreatic disease were reviewed. The presence of pancreatic portal cavernoma (defined as intra- and/or peripancreatic portal cavernoma), morphological changes in the pancreas, biliary and ductal pancreatic abnormalities, and extension of the portal venous thrombosis were qualitatively assessed. Fifteen patients (75%) had pancreatic portal cavernoma with collateral formation in the pancreas and/or collaterals around the pancreas seen on dynamic contrast-enhanced MR sequences: three patients had both intra- and peripancreatic portal cavernoma, six had intrapancreatic portal cavernoma alone and six had peripancreatic portal cavernoma only. The presence of intra- or peripancreatic portal cavernoma was significantly associated with extension of the thrombosis to the splenic and superior mesenteric veins (p = 0.05). Morphological changes in the pancreas, heterogeneity on T2-weighted sequences and main ductal pancreatic abnormalities were seen in two, four and two patients, respectively. All these patients had intrapancreatic portal cavernoma. Bile duct dilatation was observed in 13 (65%) patients: among them three had extrahepatic dilatation only and these three patients had associated intrapancreatic portal cavernoma. In patients with cavernous transformation of the portal vein, intra- or peripancreatic portal cavernoma is common. In conclusion, intra- or peripancreatic portal cavernoma was only observed in patients with extension of the thrombosis to the splenic vein and/or the superior mesenteric vein.

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.

Increased incidence of Campylobacter enteritis and their quinolone resistance between 2010 and 2015: Results of a French national observatory conducted in 21 general hospitals (CHG).

INTRODUCTION: In Europe, the number of cases of Campylobacter enteritis and their quinolone resistance is increasing. The aims of this work were to evaluate: (1) the hospital epidemiology of bacterial enteritis between 2010 and 2015. (2) The proportion of Campylobacter and Salmonella enteritis. (3) Resistance to quinolones in adult and paediatric populations. (4) To investigate possible regional epidemiological and bacteriological disparities. PATIENTS AND METHODS: This is a multicentric study carried out in 21 general hospitals (CHG) representing 14 French regions with a prospective collection of the results of coprocultures from 2010 to 2015 in adult and paediatric populations (children < 15 years old not exposed to quinolones). The epidemiological and bacteriological data were collected from software laboratory for positive stool cultures for Campylobacter and Salmonella. The results were compared year by year and by a period of 2 years. RESULTS: In adults, Campylobacter enteritis was each year significantly more frequent than Salmonella (P < 0.001), with a significant increase from 2010 to 2015 (P < 0.05). In children, there was also a significant and stable predominance of Campylobacter enteritis over the study period (P = 0.002). The quinolone resistance of Campylobacter was greater than 50% on the whole territory, with no North-South difference over the three periods studied. It increased significantly from 2012 to 2015 in adults (48% to 55%, P < 0.05) and in children (54% to 61%, P = 0.04). CONCLUSION: Our results confirm the increase in the prevalence of Campylobacter enteritis compared to Salmonella between 2010 and 2015. The quinolone resistance of Campylobacter is greater than 50% on the whole territory, stable between 2010 and 2015 in adults and significantly increased in children.

Chronic hepatitis E virus infection in a cirrhotic patient: A case report.

RATIONALE: Acute hepatitis E virus (HEV) infections are usually self-limiting in immunocompetent patients. HEV persistence has been described only in immunosuppressed patients such as solid-organ transplant recipients, patients with hematological diseases, or patients with human immunodeficiency virus (HIV) infection. PATIENT CONCERNS: A 61-year-old patient was admitted in hospital for jaundice and asthenia. DIAGNOSES: The patient had underlying cirrhosis and developed a chronic HEV infection. INTERVENTION: Ribavirin therapy was initiated. OUTCOMES: Ribavirin therapy for 12 months allowed the clearance of the virus and HEV viral load remained undetectable thereafter. This patient had taken no immunosuppressive drugs, was not suffering from any autoimmune disease and was not infected with HIV. We studied the patient's anti-HEV immune response months after the viral clearance. His peripheral blood mononuclear cells (PBMC) were stimulated in vitro by HEV peptides. The patient had a mild T lymphopenia, but polyclonal stimulation of PBMC showed a robust T cell response. The response of his anti-HEV specific interferon-γ producing T cells was low. LESSONS: Other studies are now needed to identify the population with a chronic evolution of HEV infection despite no apparent immunodepression.

Nonmalignant portal vein thrombosis in adults.

Portal vein thrombosis (PVT) consists of two different entities: acute PVT and chronic PVT. Acute PVT usually presents as abdominal pain. When the thrombus extends to the mesenteric venous arches, intestinal infarction can occur. Chronic PVT is usually recognized after a fortuitous diagnosis of hypersplenism or portal hypertension, or when there are biliary symptoms related to portal cholangiopathy. Local risk factors for PVT, such as an abdominal inflammatory focus, can be identified in 30% of patients with acute PVT; 70% of patients with acute and chronic PVT have a general risk factor for PVT, most commonly myeloproliferative disease. Early initiation of anticoagulation therapy for acute PVT is associated with complete and partial success in 50% and 40% of patients, respectively. A minimum of 6 months' anticoagulation therapy is recommended for the treatment of acute PVT. For patients with either form of PVT, permanent anticoagulation therapy should be considered if they have a permanent risk factor. In patients with large varices, beta-adrenergic blockade or endoscopic therapy seems to prevent bleeding as a result of portal hypertension, even in patients on anticoagulation therapy. In patients with jaundice or recurrent biliary symptoms caused by cholangiopathy, insertion of a biliary endoprosthesis is the first treatment option. Overall, the long-term outcome for patients with PVT is good, but is jeopardized by cholangiopathy and transformation of underlying myeloproliferative disease into myelofibrosis or acute leukemia.

Fatal cardiomyopathy associated with pegylated interferon/ribavirin in a patient with chronic hepatitis C.

We report the case of a 45-year-old man with HCV treated with pegylated interferon-alpha/ribavirin, in whom fatal cardiomyopathy occurred. Cardiomyopathy is a rare complication of high dose of standard interferon but has never been reported with pegylated interferon. The relationship between pegylated interferon-alpha/ribavirin and the development of cardiomyopathy is highly probable for the following reasons: (1) a cardiologist consultation with specific investigations had been performed before treatment excluding a pre-existing cardiomyopathy; (2) symptoms of advanced dilated cardiomyopathy appeared immediately after the end of treatment; (3) other causes of cardiomyopathy have been ruled out. In all except one of the 21 reported cases with standard interferon, cardiomyopathy was reversible. In our patient, fatal cardiomyopathy occurred with a usual dose of pegylated interferon-alpha. Clinicians should be aware of this potential complication when evaluating the ratio benefit/risk of treatment in patients with chronic hepatitis C infection.