The Characteristics of Diverticular Disease in Caribbean Population: A Control Group Study.

Background: Diverticulosis is not well characterized in the Caribbeans. Our aim was to compare the anatomical presentation of colonic diverticulosis in African Caribbeans (group AC) versus Europeans (group E) and severity. Methods: We conducted a prospective controlled study involving 274 patients admitted for lower gastrointestinal haemorrhage (LGIH) in France (center 1: Guadeloupe; center 2: La Roche-sur-Yon); 179 cases with diverticular haemorrhage, including 129 in group AC and 40 in group E. Exploration of the colon included a detailed assessment of diverticula using a dedicated endoscopic grid. Results: AC and E had similar characteristics in terms of age, gender, previous history of LGIH, body mass index, dietary habits, and medications, but AC had significantly poorer hemodynamic parameters at admission and required more blood transfusions (66.7% vs. 42.5%; p=0.01) during hospitalization. Out of the 169 patients included in the study, a complete exploration of the colon was achieved in 81% (N = 137) (AC, n = 106; E, n = 31), and revealed right-side diverticulosis in AC (in 90.6%, included into a pancolonic form in 73.6% vs. 35.5%; p=0.0002) and left-side diverticulosis in E (in 96.8%, isolated form in 58.1% vs. 9.4%, p=0.0002). These data were confirmed by a sensitivity analysis using an endoscopic grid in 92 patients, achieving a higher frequency and larger size of diverticula in AC. Conclusion: Our study has shown that diverticulosis was pancolonic in AC and more frequently associated with more severe haemorrhage than the left-sided diverticulosis of Europeans. This anatomical presentation may be driven by the genetic background more than the environment and diet.

Subclinical proximal tubulopathy in hepatitis B: The roles of nucleot(s)ide analogue treatment and the hepatitis B virus.

BACKGROUND: The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity, such as estimated glomerular filtration rate (eGFR) and phosphatemia, are late markers of proximal tubulopathy. Multiple early markers are available, but no consensus exists on their use. AIM: To determine the 24 mo prevalence of subclinical proximal tubulopathy (SPT), as defined with early biomarkers, in treated vs untreated hepatitis B virus (HBV)-monoinfected patients. METHODS: A prospective, non-randomized, multicenter study of HBV-monoinfected patients with a low number of renal comorbidities was conducted. The patients were separated into three groups: Naïve, starting entecavir (ETV) treatment, or starting tenofovir disoproxil (TDF) treatment. Data on the early markers of SPT, the eGFR and phosphatemia, were collected quarterly. SPT was defined as a maximal tubular reabsorption of phosphate/eGFR below 0.8 mmoL/L and/or uric acid fractional excretion above 10%. The prevalence and cumulative incidence of SPT at month 24 (M24) were calculated. Quantitative data were analyzed using analyses of variance or Kruskal-Wallis tests, whereas chi-squared or Fisher's exact tests were used to analyze qualitative data. Multivariate analyses were used to adjust for any potential confounding factors. RESULTS: Of the 196 patients analyzed, 138 (84 naïve, 28 starting ETV, and 26 starting TDF) had no SPT at inclusion. At M24, the prevalence of SPT was not statistically different between naïve and either treated group (21.1% vs 30.7%, P < 0.42 and 50.0% vs 30.7%, P = 0.32 for ETV and TDF, respectively); no patient had an eGFR lower than 50 mL/min/1.73 m² or phosphatemia less than 0.48 mmoL/L. In the multivariate analysis, no explanatory variables were identified after adjustment. The cumulative incidence of SPT over 24 mo (25.5%, 13.3%, and 52.9% in the naïve, ETV, and TDF groups, respectively) tended to be higher in the TDF group vs the naïve group (hazard ratio: 2.283, P = 0.05). SPT-free survival at M24 was 57.6%, 68.8%, and 23.5% for the naïve, ETV, and TDF groups, respectively. The median survival time without SPT, evaluated only in the TDF group, was 5.9 mo. CONCLUSION: The prevalence and incidence of SPT was higher in TDF-treated patients compared to naïve patients. SPT in the naïve population suggests that HBV can induce renal tubular toxicity.

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.

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.

Risk of pancreatic adenocarcinoma in patients with hereditary pancreatitis: a national exhaustive series.

BACKGROUND AND AIMS: An increased risk of pancreatic adenocarcinoma (PA) in patients with hereditary pancreatitis (HP) was previously demonstrated in two multinational studies. The PA frequency in this setting is however unknown due to lack of exhaustive case collection. The aims of this study were to evaluate the standardized incidence ratio (SIR) of PA in an exhaustive national series of patients with HP and to search for risk factors. METHODS: All French genetic laboratories (response rate 100%), pediatricians, and gastroenterologists (response rate 84%) were contacted. INCLUSION CRITERIA: mutation in the PRSS1 gene or recurrent, acute, or chronic pancreatitis, with no precipitating factors in two first-degree relatives or >or=3 second-degree relatives in >or=2 generations. Diagnosis of PA was based on histological records. RESULTS: Seventy-eight families and 200 patients were included (181 alive, 6,673 person-years, median number of generations 3, men 53%, alcoholism 5%, and smoking 34%). PRSS1 mutations were searched for in 96% of the patients and were detected in 68% (maternal inheritance 54%, R122H 78%, N29I 12%, and others 10%). Ten PA were diagnosed (median age 55 yr). SIR of PA for the whole population, men, and women were 87 (95% CI 42-113), 69 (25-150), and 142 (38-225), respectively, with no influence of genetic mutation. At ages 50 and 75 yr, the cumulated risk of PA was 11% and 49% for men and 8% and 55% for women, respectively. Smoking and diabetes mellitus were the main associated risk factors. CONCLUSION: Patients with HP have a marked relative and absolute increased risk of PA as compared to the general population, especially in smokers. There is no correlation with the type of PRSS1 mutation.