Long-term Outcome of Risankizumab in Crohn's Disease: a Real-world GETAID Study.

BACKGROUND & AIMS: The aim of this study was to assess the long-term effectiveness and safety of risankizumab maintenance treatment in a large real-world cohort of patients with Crohn's Disease (CD). METHODS: From May 2021 to August 2023, all consecutive patients with CD treated with risankizumab in 25 GETAID centers have been retrospectively included. The primary endpoint was steroid-free clinical remission (Harvey Bradshaw Index [HBI] <5) at 52 weeks. RESULTS: Of the 174 patients included, 99%, 93%, and 96% had been previously exposed to anti-TNF, vedolizumab, and ustekinumab, respectively. All patients had received ≥3 biologics, and 108 (62%) had previous intestinal resection. Median follow-up was 13.7 months (interquartile range, 10.0-18.1 months). The rates of steroid-free clinical remission and clinical remission at week 26 were 47% (72/152) and 52% (79/152), and 46% (58/125), and 48% (60/125) at week 52, respectively. Risankizumab persistence rates were 94%, 89%, and 79% at weeks 12, 26, and 52, respectively. At the end of follow-up, 45 (45/174; 26%) patients had discontinued risankizumab (loss of response, 42%; primary failure, 37%; intolerance, 13%). Thirty-six patients (36/174; 20.9%) were hospitalized, and 22 (22/174; 12.6%) required intestinal resection. Fifty-one patients (29%) had an adverse event, including 26 (15%) serious adverse events (CD flare, n = 17). One death (myocardial infarction) and one cancer (papillary thyroid carcinoma) were observed. CONCLUSION: This is the first real-life study to report long-term outcomes in patients with refractory CD treated with risankizumab. One-half of the patients achieved steroid-free clinical remission after 1 year, and the safety profile was consistent with the literature.

Effect of Prophylactic Antibiotics on Mortality in Severe Alcohol-Related Hepatitis: A Randomized Clinical Trial.

Importance: The benefits of prophylactic antibiotics for hospitalized patients with severe alcohol-related hepatitis are unclear. Objective: To determine the efficacy of amoxicillin-clavulanate, compared with placebo, on mortality in patients hospitalized with severe alcohol-related hepatitis and treated with prednisolone. Design, Setting, and Participants: Multicenter, randomized, double-blind clinical trial among patients with biopsy-proven severe alcohol-related hepatitis (Maddrey function score ≥32 and Model for End-stage Liver Disease [MELD] score ≥21) from June 13, 2015, to May 24, 2019, in 25 centers in France and Belgium. All patients were followed up for 180 days. Final follow-up occurred on November 19, 2019. Intervention: Patients were randomly assigned (1:1 allocation) to receive prednisolone combined with amoxicillin-clavulanate (n = 145) or prednisolone combined with placebo (n = 147). Main Outcome and Measures: The primary outcome was all-cause mortality at 60 days. Secondary outcomes were all-cause mortality at 90 and 180 days; incidence of infection, incidence of hepatorenal syndrome, and proportion of participants with a MELD score less than 17 at 60 days; and proportion of patients with a Lille score less than 0.45 at 7 days. Results: Among 292 randomized patients (mean age, 52.8 [SD, 9.2] years; 80 [27.4%] women) 284 (97%) were analyzed. There was no significant difference in 60-day mortality between participants randomized to amoxicillin-clavulanate and those randomized to placebo (17.3% in the amoxicillin-clavulanate group and 21.3% in the placebo group [P = .33]; between-group difference, -4.7% [95% CI, -14.0% to 4.7%]; hazard ratio, 0.77 [95% CI, 0.45-1.31]). Infection rates at 60 days were significantly lower in the amoxicillin-clavulanate group (29.7% vs 41.5%; mean difference, -11.8% [95% CI, -23.0% to -0.7%]; subhazard ratio, 0.62; [95% CI, 0.41-0.91]; P = .02). There were no significant differences in any of the remaining 3 secondary outcomes. The most common serious adverse events were related to liver failure (25 in the amoxicillin-clavulanate group and 20 in the placebo group), infections (23 in the amoxicillin-clavulanate group and 46 in the placebo group), and gastrointestinal disorders (15 in the amoxicillin-clavulanate group and 21 in the placebo group). Conclusion and Relevance: In patients hospitalized with severe alcohol-related hepatitis, amoxicillin-clavulanate combined with prednisolone did not improve 2-month survival compared with prednisolone alone. These results do not support prophylactic antibiotics to improve survival in patients hospitalized with severe alcohol-related hepatitis. Trial Registration: ClinicalTrials.gov Identifier: NCT02281929.

Management of alcohol-related liver disease: the French Association for the Study of the Liver and the French Alcohol Society clinical guidelines.

Excessive alcohol consumption is the leading cause of liver diseases in Western countries, especially in France. Alcohol-related liver disease (ARLD) is an extremely broad context and there remains much to accomplish in terms of identifying patients, improving prognosis and treatment, and standardising practices. The French Association for the Study of the Liver wished to organise guidelines together with the French Alcohol Society in order to summarise the best evidence available about several key clinical points in ARLD. These guidelines have been elaborated based on the level of evidence available in the literature and each recommendation has been analysed, discussed and voted by the panel of experts. They describe how patients with ARLD should be managed nowadays and discuss the main unsettled issues in the field.

Diagnostic Delay Is Associated with a Greater Risk of Early Surgery in a French Cohort of Crohn's Disease Patients.

AIM: To investigate whether a diagnostic delay is associated with a poor outcome in Crohn's disease (CD). METHODS: Medical and socioeconomic characteristics as well as medications and need for surgery of consecutive CD adults patients followed in three referral centers were prospectively recorded using an electronic database (Focus_MICI®). A long diagnostic delay was defined by the upper quartile. We compared patients with long diagnostic delay to those with earlier diagnosis regarding the time to: (1) first intestinal surgery, (2) first use of immunosuppressants (IMSs), and (3) first use of anti-tumor necrosis factor (anti-TNF) therapy using the Kaplan-Meier test and the log-rank test. RESULTS: A total of 497 patients with CD (53.6 % women) were analyzed. Median diagnostic delay was 5 months (IQR 25-75 %: 2-13 months). Median follow-up was 9 years (IQR 4-16.2), and 148 (29.8 %) patients had major surgery. There were no significant differences between patients with late and early diagnosis regarding age at diagnosis, disease phenotype, need for IMS therapy, and need for anti-TNF therapy. Time to first major surgery was shorter in patients with late diagnosis (p = 0.05). CONCLUSION: In this large multicenter prospective cohort of French CD patients, a long diagnostic delay (>13 months) increased the risk of early surgery. No associated factors could be identified in this study.

Effect of albumin in cirrhotic patients with infection other than spontaneous bacterial peritonitis. A randomized trial.

BACKGROUND & AIMS: Albumin infusion improves renal function and survival in cirrhotic patients with spontaneous bacterial peritonitis (SBP) but its efficacy in other types of infections remains unknown. We investigated this issue through a multicenter randomized controlled trial. METHODS: A total of 193 cirrhotic patients with a Child-Pugh score greater than 8 and sepsis unrelated to SBP were randomly assigned to receive antibiotics plus albumin (1.5 g/kg on day 1 and 1g/kg on day 3; albumin group [ALB]: n=96) or antibiotics alone (control group [CG]: n=97). The primary endpoint was the 3-month renal failure rate (increase in creatinine ⩾50% to reach a final value ⩾133 µmol/L). The secondary endpoint was 3-month survival rate. RESULTS: Forty-seven (24.6%) patients died (ALB: n=27 vs. CG: n=20; 3-month survival: 70.2% vs. 78.3%; p=0.16). Albumin infusion delayed the occurrence of renal failure (mean time to onset, ALB: 29.0 ± 21.8 vs. 11.7 ± 9.1 days, p=0.018) but the 3-month renal failure rate was similar (ALB: 14.3% vs. CG: 13.5%; p=0.88). By multivariate analysis, MELD score (p<0.0001), pneumonia (p=0.0041), hyponatremia (p=0.031) and occurrence of renal failure (p<0.0001) were predictors of death. Of note, pulmonary edema developed in 8/96 (8.3%) patients in the albumin group of whom two died, one on the day and the other on day 33 following albumin infusion. CONCLUSIONS: In cirrhotic patients with infections other than SBP, albumin infusion delayed onset of renal failure but did not improve renal function or survival at 3 months. Infusion of large amounts of albumin should be cautiously administered in the sickest cirrhotic patients.

Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: a randomized clinical trial.

IMPORTANCE: Prednisolone or pentoxifylline is recommended for severe alcoholic hepatitis, a life-threatening disease. The benefit of their combination is unknown. OBJECTIVE: To determine whether the addition of pentoxifylline to prednisolone is more effective than prednisolone alone. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, double-blind clinical trial conducted between December 2007 and March 2010 in 1 Belgian and 23 French hospitals of 270 patients aged 18 to 70 years who were heavy drinkers with severe biopsy-proven alcoholic hepatitis, as indicated by recent onset of jaundice in the prior 3 months and a Maddrey score of at least 32. Duration of follow-up was 6 months. The last included patient completed the study in October 2010. None of the patients were lost to follow-up for the main outcome. INTERVENTION: Patients were randomly assigned to receive either a combination of 40 mg of prednisolone once a day and 400 mg of pentoxifylline 3 times a day (n=133) for 28 days, or 40 mg of prednisolone and matching placebo (n=137) for 28 days. MAIN OUTCOMES AND MEASURES: Six-month survival, with secondary end points of development of hepatorenal syndrome and response to therapy based on the Lille model, which defines treatment nonresponders after 7 days of initiation of treatment. RESULTS: In intention-to-treat analysis, 6-month survival was not different in the pentoxifylline-prednisolone and placebo-prednisolone groups (69.9% [95% CI, 62.1%-77.7%] vs 69.2% [95% CI; 61.4%-76.9%], P = .91), corresponding to 40 vs 42 deaths, respectively. In multivariable analysis, only the Lille model and the Model for End-Stage Liver Disease score were independently associated with 6-month survival. At 7 days, response to therapy assessed by the Lille model was not significantly different between the 2 groups (Lille model score, 0.41 [95% CI, 0.36-0.46] vs 0.40 [95% CI, 0.35-0.45], P = .80). The probability of being a responder was not different in both groups (62.6% [95% CI, 53.9%-71.3%] vs 61.9% [95% CI, 53.7%-70.3%], P = .91). The cumulative incidence of hepatorenal syndrome at 6 months was not significantly different in the pentoxifylline-prednisolone and the placebo-prednisolone groups (8.4% [95% CI, 4.8%-14.8%] vs 15.3% [95% CI, 10.3%-22.7%], P = .07). CONCLUSION AND RELEVANCE: In patients with alcoholic hepatitis, 4-week treatment with pentoxifylline and prednisolone, compared with prednisolone alone, did not result in improved 6-month survival. The study may have been underpowered to detect a significant difference in incidence of hepatorenal syndrome, which was less frequent in the group receiving pentoxifylline. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01214226.

Hepatitis E Virus Infection in Patients with Chronic Inflammatory Bowel Disease Treated with Immunosuppressive Therapy.

BACKGROUND: Medical treatment of inflammatory bowel disease (IBD) has evolved significantly, and treatment with immunomodulators is recommended. These medications may alter the patient's immune response and increase the risk of opportunistic infections. Our aim was to evaluate the prevalence and the incidence of acute or chronic HEV infection in IBD patients under immunomodulatory treatment. PATIENTS AND METHODS: We conducted a retrospective, multicenter, observational study between 2017 and 2018. IBD outpatients hospitalized for the infusion of immunomodulators were included in 16 French centers. During their daily hospitalization, blood samples were drawn for HEV serology (IgM and IgG) and HEV RNA detection. RESULTS: A total of 488 patients were included, of which 327 (67%) patients had Crohn's disease and 161 (33%) ulcerative colitis. HEV IgM was detected in 3 patients, but HEV RNA was undetectable in all patients. The HEV IgG seroprevalence rate was 14.2%. IgG-positive patients were older at sampling (p = 0.01) and IBD diagnosis (p = 0.03), had higher seafood consumption (p = 0.01) and higher doses of azathioprine (p = 0.03). Ileal and upper digestive tract involvement was more frequent in IgG-positive patients (p = 0.009), and ileocolic involvement was more frequent in IgG-negative patients (p = 0.01). Under multivariate analysis, age > 50 years [OR: 2.21 (1.26, to 3.85), p = 0.004] was associated with previous HEV infection. CONCLUSION: Systematic screening for HEV infection is not needed among IBD patients on immunomodulatory medications. However, in the event of abnormal liver test findings, HEV should be part of the classic diagnostic assessment.

Effectiveness and safety of risankizumab induction therapy for 100 patients with Crohn's disease: A GETAID multicentre cohort study.

BACKGROUND: Phase III trials have demonstrated the efficacy of risankizumab in moderate-to-severe Crohn's disease (CD), but no real-world data are currently available. We aimed to assess the short-term effectiveness and safety of risankizumab in patients with CD. METHODS: From May 2021 to May 2022, all patients with refractory luminal CD treated with risankizumab in 22 French GETAID centres were retrospectively included. The primary endpoint was steroid-free clinical remission at week 12 (Harvey-Bradshaw [HB] score <5). Secondary endpoints included clinical response (≥3-point decrease of HB score and/or (HB) score <5), biochemical remission (CRP ≤ 5 mg/L), need for CD-related surgery and adverse events. RESULTS: Among the 100 patients included, all have been previously exposed to anti-TNF agents, 94 to vedolizumab, 98 to ustekinumab (all exposed to at least three biologics) and 61 had a previous intestinal resection. All but three (97%) received a 600 mg risankizumab intravenous induction at weeks 0-4-8. At week 12, steroid-free clinical remission was observed in 45.8% of patients, clinical remission in 58% and clinical response in 78.5%. In subgroup analysis restricted to patients with objective signs of inflammation at baseline (n = 79), steroid-free clinical remission at week 12 was observed in 39.2% of patients. Biochemical remission was observed in 50% of patients. Six patients discontinued risankizumab before the week 12 visit due to lack of efficacy. CD-related hospitalisation was needed in six patients, and three underwent intestinal resection. In multivariable analysis, only a history of ustekinumab loss of response (vs primary failure) (odds ratio (OR), 2.80; 95% CI: 1.07-7.82; p = 0.041) was significantly associated with clinical remission at week 12. Twenty adverse events (AE) occurred in 20 patients including 7 serious AE corresponding to 6 CD exacerbation and one severe hypertension. CONCLUSION: In a cohort of highly refractory patients with luminal CD and multiple prior drug failures including ustekinumab, risankizumab induction provided a clinical response in about 3 out of 4 patients and steroid-free clinical remission in about half of patients.

Real-world evidence of quality of life improvement in patients with distal ulcerative colitis treated by mesalazine: the Quartz study.

BACKGROUND: Distal ulcerative colitis (UC) is responsible for distressing symptoms and reduces quality of life (QoL). Oral and topical formulations of 5-amino-salicylic acid are the first line therapy for mild to moderate distal UC. OBJECTIVE: Our aim was to evaluate the impact of mesalazine treatment for mild to moderate ulcerative proctitis and proctosigmoiditis on patient QoL. METHODS: Ninety-three patients with mild to moderate ulcerative proctitis and proctosigmoiditis, initiating a treatment with Pentasa, were prospectively included. The primary endpoint was the change from baseline to W8 in patient health-related QoL (HRQoL) as measured by the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) total score. RESULTS: More than 80% of patients were prescribed with a rectal formulation, either alone (47.9%) or with an oral formulation (35.1%), and 17.0% of patients were prescribed oral formulation alone. Mean SIBDQ score was improved at W8 in patients affected with mild and moderate disease ( P < 0.001 versus baseline in both groups, as well as in patients who achieved clinical remission ( P < 0.001). Patients who achieved clinical remission at W8 reached a mean change of +6.7 (±7.1), whereas those who did not achieve clinical remission had a mean change of +1.1 (±8.9). Seventy-five per cent of patients had an improvement of their disability index at W8. Fecal incontinence was also improved at W8. CONCLUSION: HRQoL measuring with the SIBDQ is proportionally related to disease activity in patients with distal UC treated with mesalazine.

Safety of P28GST, a Protein Derived from a Schistosome Helminth Parasite, in Patients with Crohn's Disease: A Pilot Study (ACROHNEM).

Despite the development of novel therapies, inflammatory bowel diseases remain an innovative treatment challenge. Helminth therapy is a new promising approach, and a key issue is the identification of helminth-derived anti-inflammatory mediators. P28 glutathione-S-transferase (P28GST), a protein derived from schistosomes, a trematode parasitic helminth, was shown to reduce intestinal inflammation in experimental colitis by down-regulating the Th1/Th17 response. In this multicenter, open-label, pilot Phase 2a study, we evaluated the safety of P28GST administered to patients with mild Crohn's disease (CD). We enrolled 10 patients with a baseline Crohn's disease activity index (CDAI) value <220. Eight patients received two to three subcutaneous injections of recombinant P28GST with adjuvant. This three-month treatment was followed by a nine-month monitoring period. The primary endpoints were the monthly rate and seriousness of adverse events (AEs). Secondary endpoints were clinical recurrence, assessed with the CDAI as well as the levels of immunologic and inflammatory blood and tissue markers. The most common AEs were local or regional events at the injection site and gastrointestinal disorders. At three months after the first injection, CDAI scores and blood calprotectin levels decreased in parallel. These results indicate that P28GST showed promise as a safe and new therapeutic option for treating CD.

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.

Favorable prognosis of upper-gastrointestinal bleeding in 1041 older patients: results of a prospective multicenter study.

BACKGROUND & AIMS: Upper-gastrointestinal bleeding (UGIB) in the elderly is associated with high morbidity and mortality. The aims of this study were to determine the prognostic factors of UGIB in a large cohort of elders. METHODS: From March 2005 to February 2006, we conducted a prospective multicenter study in 53 French hospitals that consecutively enrolled 3287 patients for UGIB. A total of 1041 patients (47.8% women) were older than 74 years. Their epidemiologic characteristics and prognosis were compared with the 2246 younger patients (26.8% women). RESULTS: Elders more frequently took drugs causing UGIB: 65% versus 32% for younger patients (P < 10(-6)). Peptic ulcers, erosive gastritis, and esophagitis accounted for 63.6% of UGIB causes in elders versus 39.7% in younger patients (P < 10(-4)). Conversely, esogastric varices and gastropathy were responsible for 11% of UGIB in elders versus 44% in younger patients (P < 10(-6)). The rebleeding rate, morbidity, and in-hospital mortality were not statistically different between elders and younger patients: 11.8% versus 9.7% (P = .07), 22.6% versus 21.6% (P = .5), and 8.9% versus 8.2% (P = .5), respectively. Transfusion requirements, need for surgery, and length of stay were significantly different between elders and younger patients: 73% versus 57.5% (P < 10(-6)), 4% versus 2.5% (P < .02), 10.6 +/- 15.6 versus 8.5 +/- 12.4 days (P < 10(-6)), respectively. Whatever the etiology (peptic lesions or portal hypertension) in-hospital mortality was the same: 6.5% versus 7.3% and 10.9% versus 11.3%, respectively. CONCLUSIONS: Elders can do as well as younger patients with acute UGIB. Although the reasons are not completely clear, they may be related to differences in treatment.

Crohn's disease treatment practices in France in1999-2013: A prospective survey in non-academic hospitals.

AIMS: To describe the characteristics of patients with Crohn's disease (CD) in non-academic hospitals in France and to evaluate how therapeutic practices changed between 1999 and 2013. METHODS: During 2 weeks in September 2013, we solicited disease and treatment information for CD patients seen by gastroenterologists in 57 French non-academic hospitals. In four groups of patients defined according to the date of CD diagnosis (<1999, 1999-2003, 2004-2008, and 2009-2013), the use of immunosuppressor (IS) and anti-TNF treatments during the first 5 years following diagnosis of CD was compared using the Kaplan-Meier method. RESULTS: 739 consecutive CD patients (median age at diagnosis 25.4 years) were included in the survey. CD location was ileal for 31%, colonic for 21%, and ileocolonic for 45%. CD phenotypes were non-penetrating/non-stricturing (58.7%), stricturing (26.9%), and penetrating (12.7%), with perianal lesions in 26.1%. The proportions of patients who began IS or anti-TNF treatment within 5 years of diagnosis increased significantly from 18% and 0%, respectively, in <1999 (n=170) to 52% and 23% in 1999-2003 (n=120), 66% and 70% in 2004-2008 (n=155), and 75% and 100% in 2009-2013 (n=294; P<0.0001). CONCLUSIONS: In this French non-academic hospital cohort of CD patients, the proportions of patients being treated with anti-TNF or IS therapy in the first 5 years after diagnosis both increased sharply since 1999.

Evolution in clinical presentation of inflammatory bowel disease over time at diagnosis: a multicenter cohort study.

INTRODUCTION: Delayed diagnosis of inflammatory bowel disease (IBD) has become a major issue, particularly in terms of the presence of nonspecific and heterogeneous clinical signs. This study aimed to identify changes over time in the epidemiological characteristics and clinical presentation of IBD in a French cohort. PATIENTS AND METHODS: Sociodemographic data from patients at three French hospitals (age, sex, country of origin, smoking habits) and characteristics of IBD [diagnostic delay, phenotype, location, first symptoms, first test suggesting diagnosis (endoscopy, imaging examination)] were collected in a computerized database (Focus_MICI). Four diagnostic time periods were assessed: <2000, 2000-2004, 2005-2009, and >2009. RESULTS: Among the 926 patients analyzed, 638 (<2000, n=181; 2000-2004, n=104; 2005-2009, n=147; >2009, n=206) had Crohn's disease (CD) and 288 (<2000, n=54; 2000-2004, n=39; 2005-2009, n=80; >2009, n=115) had ulcerative colitis (UC). For CD, statistically significant differences over time were observed for (a) the first revealing disease symptom [more frequent abdominal pain vs. chronic diarrhea (P<0.001)], (b) first investigation suggestive of diagnosis [more frequent computed tomography vs. colonoscopy (P<0.001)], and (c) CD behavior [more frequent inflammatory vs. stricturing/penetrating forms (P<0.001)]. No significant differences over time were observed for UC variables. CONCLUSION: In this large multicenter cohort study clinical diagnostic presentation of CD has changed over time. By contrast, there were no changes in the UC clinical presentation.

Low incidence of spontaneous bacterial peritonitis in asymptomatic cirrhotic outpatients.

AIM: To compare the incidence of spontaneous bacterial peritonitis in cirrhotic outpatients and inpatients undergoing therapeutic paracentesis METHODS: From January 1 to May 31, 2004, 1041 patients from 70 different hospitals underwent 2123 therapeutic abdominal paracentesis (AP) performed as a outpatient procedure in 355 and as inpatient procedure in 686 cases respectively. The following parameters were compared prospectively between outpatients and inpatients: spontaneous bacterial peritonitis (SBP) prevalence, age, gender, cause of cirrhosis, symptoms, score and grade according to Child-Pugh classification, cirrhosis complications, antibiotics treatment, serum creatinine, platelet count and ascitic protein concentration. RESULTS: SBP was observed in 91 patients. In the whole population the SBP prevalence was 8.7% (95%CI: 7.2-10.6) it was 11.7% (95%CI: 9.5-14.3) in inpatients and 3.1% (95%CI: 1.7-5.5) in outpatients (P < 0.00001). SBP prevalence was 8.3% (95%CI: 4.3-15.6) in symptomatic outpatients vs 1.2% (95%CI: 0.4-3.4) in asymptomatic outpatients (P < 0.002). Patients undergoing outpatient AP were significantly different from those undergoing inpatient AP; they were older (61.1 ± 11.1 years vs 59.4 ± 11.7 years; P = 0.028), cause of cirrhosis was less often alcohol (83 .7 vs 88.2%; P < 0.001), Child-Pugh score was lower (8.9 vs 10.1; P < 0.001) and more often B than C (63.7% vs 38%; P < 0.001). In addition, in outpatients the platelet count was higher (161 ± 93 Giga/L vs 143 ± 89 Giga/L; P = 0.003), serum total bilirubin concentration was lower (38.2 ± 60.7 µmol/L vs 96.3 ± 143.3 µmol/L; P < 0.0001), and ascitic protein concentration higher (17.9 ± 10.7 g/L vs 14.5 ± 10.9 g/L; P < 0.001) than in inpatients. CONCLUSION: In asymptomatic cirrhotic outpatients, the incidence of spontaneous bacterial peritonitis is low thus exploratory paracentesis could be avoided in these patients without significant risk.

Diagnostic accuracy of the Multistix 8 SG reagent strip in diagnosis of spontaneous bacterial peritonitis.

UNLABELLED: Recent studies have shown that the diagnosis of spontaneous bacterial peritonitis (SBP) can be rapidly obtained using leukocyte esterase reagent strips. However, published studies were restricted to one or two centers, and the number of patients with SBP was thus limited. The aims of the current prospective multicenter study were: (1) to assess the diagnostic accuracy of the Multistix 8SG urine test for the diagnosis of SBP; and (2) to assess the prevalence of SBP. From January to May 2004, 2 reactive strips were tested independently in inpatients with cirrhosis and in outpatients undergoing paracentesis. Cultures of ascitic fluid were performed at the bedside using aerobic and anaerobic blood culture bottles. Two thousand one hundred twenty-three paracenteses were performed in 1,041 patients from 70 centers. One hundred seventeen samples, obtained from 91 patients, had ascites polymorphonuclear cell (PMN) counts>or=250/microl (range, 250-34,000), among which 56 were associated with positive ascitic fluid cultures. The prevalence of SBP was 5.5% in the whole population, 9% in inpatients, and 1.3% in outpatients (P<0.0001). The prevalence of SBP was 0.57% in asymptomatic outpatients versus 2.4% in symptomatic outpatients (P=0.04). Using a threshold of 2+ for positivity of the reagent strip, sensitivity was 45.3% for the diagnosis of SBP, specificity was 99.2%, positive predictive value was 77.9%, and negative predictive value was 96.9%. CONCLUSION: This study confirms the low prevalence of SBP in asymptomatic outpatients according to a priori defined criteria, and indicates an absence of diagnostic efficacy for this specific strip test.

Cirrhosis and bleeding: the need for very early management.

BACKGROUND/AIMS: Retrospective studies suggest that the prognosis of patients with cirrhosis and variceal hemorrhage has improved in more recent decades. In a prospective cohort study in which the choice of prophylactic therapy was left to each practitioner, we followed cirrhotic patients with medium/large varices to determine factors predictive of bleeding and death. METHODS: Three hundred fourteen patients with grades 2 or 3 esophageal varices (Child A and B/C: 218 and 96) were enrolled. One hundred seventy-three patients had no previous history of variceal bleeding. Only 245 patients (100% of patients with prior variceal hemorrhage, 61% of patients without prior hemorrhage) were receiving some form of prophylactic therapy. The median follow-up was 18 months. RESULTS: There were 76 bleeding events and 14 related deaths (18%); nine of these deaths occurred within 24 h of bleeding onset (two at home, two during hospital transfer, and five in hospital, a mean of 2.5 h after onset; six involved Child C patients). Twenty-five deaths were not due to bleeding but were closely related to cirrhosis. In a Cox model, the presence of tense ascites (relative risk 3.4, 95% confidence interval, CI 2.5-5.9) and a prior history of hemorrhage (relative risk 4.4, 95% CI 2.6-7.5) were independent predictors of variceal hemorrhage. In patients without a prior history of bleeding, bleeding risk was higher with more prolonged prothrombin time and lower when patients were receiving propranolol. CONCLUSIONS: Despite the advent of effective drugs and endoscopic therapy for variceal bleeding, about a quarter of deaths occur very early after bleeding onset, confirming the need for rapid specific management.