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.

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.

Renal dysfunction associated with telaprevir-containing triple therapy for chronic hepatitis C: is early prediction possible?

INTRODUCTION: Renal dysfunction has recently been described as a potential complication of tritherapy with telaprevir (TVR) in patients with chronic hepatitis C. This study aimed to identify predictive factors for and consequences of TVR-associated renal dysfunction. PATIENTS AND METHODS: A retrospective-prospective study was carried out in 96 patients with chronic hepatitis C, genotype 1, treated with TVR-based tritherapy in 2012-2013, in whom regular serum creatinine measurements were performed during the first 12 weeks of treatment. The patients received standard doses of peginterferon, ribavirin and TVR (2250 mg/day). The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula. RESULTS: eGFR decreased significantly from baseline at weeks 4, 8 and 12, the mean maximum decrease being 22.0±23.6 ml/min, with a significant correlation between baseline and minimum eGFR (r=0.58, P<10), stronger between week 2 and minimum eGFR in the subgroup of 62 patients in whom creatinine measurement was performed at week 2. Thirteen patients had an eGFR below 60 ml/min during treatment. Age and baseline eGFR were independent predictors of eGFR below 60 ml/min in the entire population, and only week 2 eGFR when available. The decrease in haemoglobin was significantly correlated with the decrease in eGFR. Age, baseline haemoglobin and the maximum variation in eGFR were independent predictors for minimum haemoglobin. The patients with decreased eGFR had more severe anaemia, and received more blood transfusions and erythropoietin. Renal dysfunction regressed in all patients after stopping TVR. CONCLUSION: The reversible decrease in eGFR in patients receiving TVR-containing tritherapy can be predicted early, possibly allowing measures aimed at preventing anaemia.

Severe sinusoidal lesions: a serious and overlooked complication of oxaliplatin-containing chemotherapy?

The main toxicity of Oxaliplatin, a major drug in the treatment of metastatic colorectal carcinoma, is neurologic. Severe sinusoidal lesions of the liver have been recently described in patients receiving pre-operative (neoadjuvant) oxaliplatin-containing chemotherapy, but their clinical relevance is unknown. Four patients with metastatic colon cancer receiving oxaliplatin, 5 fluorouracil and elvorin, developped a progressive increase in gammaglutamyl transpeptidase and alkaline phosphatase, contrasting with tumour regression established by CT-scan and decrease in serum carcinoembryonic antigen concentrations. Histological examination of liver biopsies showed sinusoidal dilatation in all cases, with perisinusoidal fibrosis and centrilobular vein lesions in 3, peliosis in 1 (in a patient receiving oxaliplatine by intraarterial hepatic route), and nodular regenerative hyperplasia in 1. The patient with peliosis developped ascites, and died from hepatic failure, despite withdrawal of the drug. The patient with nodular regenerative hyperplasia developped jaundice, ascites and severe infection following a right hepatectomy. In the three surviving patients, liver function tests improved after the withdrawal of oxaliplatin, and, in one, deteriorated again after reintroduction of the drug. The prevalence of liver sinusoid lesions induced by oxaliplatin-containing chemotherapeutic regimens is probably underestimated. Careful monitoring of gamma-glutamyl transpeptidase and alkaline phosphatase is mandatory in treated patients, especially in those receiving adjuvant therapy, in whom significant sequelae could occur despite initially asymptomatic lesions.

The underestimated role of opiates in patients with suspected sphincter of Oddi dysfunction after cholecystectomy.

AIMS: Pain recurrence after cholecystectomy is often attributed to sphincter of Oddi dysfunction, whose diagnostic criteria and treatments remain uncertain. We performed a retrospective study to assess the possible precipitating role of opiate ingestion in this setting. METHODS: The retrospective study of the files of 147 consecutive patients investigated for post-cholecystectomy syndrome by endoscopic ultrasonography and/or endoscopic retrograde cholangiography yielded 37 cases of suspected biliary-type sphincter of Oddi dysfunction. RESULTS: Thirteen patients (30%) with suspected sphincter of Oddi dysfunction had taken opiate-containing drugs 15 minutes to two hours (median 1 hr) before the onset of pain ("Opiate group"). When compared with the 23 patients having not taken opiates ("Non Opiate Group"), they were significantly younger (47 vs. 60 yrs), had a narrower common bile duct (5.0 vs. 7.7 mm), but had similar biochemical abnormalities and belonged to the same Milwaukee's classes, mainly class II. None of the patients in the "Opiate group" were submitted to retrograde cholangiography or endoscopic sphincterotomy vs. 52% and 39%, respectively of the patients of the "Non-Opiate Group". After a mean follow-up of 3.5 years, there were three recurrences of biliary-type pain (1 choledochal stone, and 2 suspected sphincter of Oddi dysfunction) in the "Opiate Group", and 2 (1 choledochal stone, 1 after codeine intake) in the "Non-Opiate Group". CONCLUSIONS: Opiate intake is a frequent cause of suspicion of sphincter of Oddi dysfunction after cholecystectomy, especially in young patients with a narrow common bile duct. A careful history taking is essential to avoid unnecessary and potentially harmful procedures.