Bacterial infections in acute variceal hemorrhage despite antibiotics-a multicenter study of predictors and clinical impact.

BACKGROUND AND AIMS: Current guidelines recommend antibiotic prophylaxis in all patients presenting with cirrhosis and acute variceal hemorrhage (AVH). We aimed to evaluate the characteristics and clinical impact of "early" infections (developing within 14 days) of AVH in a real-world setting. METHODS: We analyzed retrospective data from a cohort of 371 adult patients with cirrhosis and AVH all of whom had received antibiotic prophylaxis (74% men; mean age 56 years), admitted to tertiary care hospitals in Edmonton, Alberta, Canada, and Barcelona, Spain. Sensitivity analyses were presented for culture-positive (confirmed) infections. RESULTS: The mean MELD was 16. Fifty-two percent of patients received quinolones, 45% third-generation cephalosporins and 3% other antibiotics. Fourteen percent (51/371) developed an infection within 14 days of AVH. Seventy-five percent of infections were culture positive and occurred at a mean of six days from AVH. When all infections were considered, respiratory infections were the most common (53%) followed by urinary tract infections (17%) and bacteremia (16%). Resistance patterns differed between countries. Outpatient antibiotic prophylaxis (OR 5.4) and intubation (OR 2.6) were independent predictors of bacterial infection. Bacterial infection (OR 2.6) and the MELD (OR 1.2) were independent predictors of six-week mortality. CONCLUSIONS: Early bacterial infections develop in 14% of cirrhotic patients with AVH despite antibiotic prophylaxis, and have a negative impact on six-week mortality. Intubation and outpatient antibiotic prophylaxis are associated with increased risk of early bacterial infections. Patients at risk should be followed closely with prompt infection workup and local antibiogram-based expansion of antibiotic therapy in case of clinical decline.

Laparoscopic nephroureterectomy is associated with higher risk of adverse events compared to laparoscopic radical nephrectomy.

INTRODUCTION: Laparoscopic radical nephrectomy (LRN) and laparoscopic nephroureterectomy (LNU) are similar procedures and some surgeons may believe the perioperative risks are the same. The purpose of this study is to characterize and compare complications following LRN and LNU. METHODS: A historical cohort of patients who received either LRN or LNU between 2006 and 2012 was reviewed from the National Surgical Quality Improvement Program (NSQIP) database. Patient characteristics, surgical characteristics, and perioperative outcomes up to 30 days postoperatively were abstracted. Unadjusted and adjusted associations between procedure (LRN or LNU) and any adverse event were determined. RESULTS: During the study period, 4904 patients met study inclusion criteria; 4159 (84.8%) received a LRN while 745 (15.2%) received a LNU. Overall, 651 (13.3%) patients experienced at least one postoperative complication. LNU was associated with more complications than LRN (21% and 12%, respectively, p value <0.01). The most common complications were: bleeding requiring blood transfusion (9.0% LNU vs. 6.0% LRN), urinary tract infection (4.6% LNU vs. 1.5% LRN), wound infection (1.3% LNU vs. 1.8% LRN), and unplanned intubation (2.3% LNU vs. 0.9% LRN). After adjusting for potential confounders, LNU was associated with higher risk of any complication compared to LRN (relative risk [RR] 1.41, 95% confidence interval [CI] 1.16-1.72). Other variables independently associated with an increased risk of complications included: increasing patient age (RR 1.01, 95% CI 1.01-1.02), American Society of Anesthesiologists (ASA) classification ≥3 (RR 1.34, 95% CI 1.10-1.63), higher preoperative creatinine (RR 1.11, 95% CI 1.06-1.17), >4 units of blood transfused within 72 hours before surgery (RR 1.93, 95% CI 1.29-2.86), and operative time >6 hours (RR 2.17, 95% CI 1.71-2.75). CONCLUSIONS: Postoperative complications within 30 days of surgery are common after LNU and LRN. Despite having technical similarities, LNU carries a significantly higher risk of developing short-term complications compared to LRN. This information should be considered when counseling patients prior to surgery. Notable limitations of this study included the lack of information on tumour stage and management of the distal ureter.

Risk of Bacterial Infection in Patients With Cirrhosis and Acute Variceal Hemorrhage, Based on Child-Pugh Class, and Effects of Antibiotics.

BACKGROUND & AIMS: Antibiotics frequently are overused and are associated with serious adverse events in patients with cirrhosis. However, these drugs are recommended for all patients presenting with acute variceal hemorrhage (AVH). We investigated whether patients should be stratified for antibiotic prophylaxis based on Child-Pugh scores, to estimate risks of bacterial infection, rebleeding, and mortality, and whether antibiotics have equal effects on patients of all Child-Pugh classes. We performed a sensitivity analysis using model for end-stage liver disease (MELD) scores. METHODS: In a retrospective study, we analyzed data from 381 adult patients with cirrhosis and AVH (70% men; mean age, 56 y), admitted from 2000 through 2009 to 2 tertiary care hospitals in Edmonton, Alberta, Canada. We excluded patients with bacterial infection on the day of AVH. The association between antibiotic prophylaxis and outcomes was adjusted by liver disease severity and by a propensity score. RESULTS: The patients included in the study had mean MELD scores of 16, and 54% received antibiotic prophylaxis. Overall, antibiotic therapy was associated with lower risks of infection (adjusted odds ratio, 0.37; 95% confidence interval, 0.91-0.74) and mortality (adjusted odds ratio, 0.63; 95% confidence interval, 0.31-1.29). Among patients categorized as Child-Pugh class A given antibiotics, only 2% developed infections and the mortality rate was 0.4%. Among patients categorized as Child-Pugh class B given antibiotics, 6% developed infections, compared with 14% of patients who did not receive antibiotics; antibiotics did not affect mortality. Administration of antibiotics to patients categorized as Child-Pugh class C reduced infections and mortality by approximately 50%, compared with patients who did not receive antibiotics. MELD scores were not as useful as Child-Pugh class in identifying patients at risk for infection. CONCLUSIONS: Based on a retrospective analysis of patients with cirrhosis and AVH, those categorized as Child-Pugh class A had lower rates of bacterial infection and lower mortality rates in the absence of antibiotic prophylaxis than patients categorized as classes B or C. The recommendation for routine antibiotic prophylaxis for this subgroup requires further evaluation.

A MELD-based model to determine risk of mortality among patients with acute variceal bleeding.

BACKGROUND & AIMS: Patients with cirrhosis with acute variceal bleeding (AVB) have high mortality rates (15%-20%). Previously described models are seldom used to determine prognoses of these patients, partially because they have not been validated externally and because they include subjective variables, such as bleeding during endoscopy and Child-Pugh score, which are evaluated inconsistently. We aimed to improve determination of risk for patients with AVB. METHODS: We analyzed data collected from 178 patients with cirrhosis (Child-Pugh scores of A, B, and C: 15%, 57%, and 28%, respectively) and esophageal AVB who received standard therapy from 2007 through 2010. We tested the performance (discrimination and calibration) of previously described models, including the model for end-stage liver disease (MELD), and developed a new MELD calibration to predict the mortality of patients within 6 weeks of presentation with AVB. MELD-based predictions were validated in cohorts of patients from Canada (n = 240) and Spain (n = 221). RESULTS: Among study subjects, the 6-week mortality rate was 16%. MELD was the best model in terms of discrimination; it was recalibrated to predict the 6-week mortality rate with logistic regression (logit, -5.312 + 0.207 • MELD; bootstrapped R(2), 0.3295). MELD values of 19 or greater predicted 20% or greater mortality, whereas MELD scores less than 11 predicted less than 5% mortality. The model performed well for patients from Canada at all risk levels. In the Spanish validation set, in which all patients were treated with banding ligation, MELD predictions were accurate up to the 20% risk threshold. CONCLUSIONS: We developed a MELD-based model that accurately predicts mortality among patients with AVB, based on objective variables available at admission. This model could be useful to evaluate the efficacy of new therapies and stratify patients in randomized trials.

Risk factors for recurrence of autoimmune hepatitis after liver transplantation.

Autoimmune hepatitis has been reported to recur after liver transplantation. The aim of our study was to evaluate the risk factors associated with recurrence of autoimmune hepatitis. Forty-six patients that underwent liver transplantation because of end-stage liver disease secondary to autoimmune hepatitis were studied. Recurrence of autoimmune hepatitis was diagnosed in 11 of the 46 (24%) patients, and the overall 5-year probability of recurrence was 18%. By univariate Cox analysis, the features before liver transplantation associated with a higher risk of recurrence were concomitant autoimmune disease [hazard ratio (HR), 3.74; 95% confidence interval (CI), 1.05-13.36; P = 0.04], high aspartate aminotransferase (HR, 1.09; 95% CI, 1.03-1.14; P = 0.002), high alanine aminotransferase (HR, 1.09; 95% CI, 1.03-1.20; P = 0.003), and high immunoglobulin G (IgG; HR, 1.25; 95% CI, 1.11-1.41; P = 0.0003). Moreover, patients with recurrence had a higher frequency of moderate to severe inflammatory activity (HR, 5.3; 95% CI, 1.55-18.79; P = 0.008) and plasma cell infiltration in the liver explant (HR, 5.8; 95% CI, 1.52-22.43; P = 0.01). In the multivariate Cox analysis, only the presence of moderate to severe inflammation (HR, 6.9; 95% CI, 1.76-26.96; P = 0.006) and high IgG levels before liver transplantation (HR, 7.5; 95% CI, 1.45-38.45; P = 0.02) were independently associated with the risk of autoimmune hepatitis recurrence. In conclusion, patients with concomitant autoimmune disease, high aspartate aminotransferase, alanine aminotransferase, and IgG before the transplant, or moderate to severe inflammatory activity or plasma cell infiltration in the liver explant have a higher risk of recurrent disease. These findings suggest that recurrence of autoimmune hepatitis may reflect incomplete suppression of disease activity prior to liver transplantation.

Urgent vs. non-urgent endoscopy in stable acute variceal bleeding.

OBJECTIVES: The optimal timing of endoscopy with acute variceal bleeding (AVB) is unknown. The aim of this study was to evaluate the association between the timing of endoscopy and outcomes of stable AVB patients. METHODS: Patients admitted at two tertiary-care centers with hemodynamically stable AVB from 1997 to 2006 were evaluated retrospectively. The primary outcome was mortality. Other recorded outcomes included stigmata at endoscopy, hemostasis, blood transfusions, rebleeding, renal function, hospitalization length, infection, transjugular intrahepatic portosystemic shunt use, and balloon tamponade use. Logistic regression analysis was used to assess the association of time to endoscopy with mortality. Outcome comparisons were also performed for three different urgency times (< or = vs. > 4 h, < or = vs. > 8 h, and < or = vs. > 12 h). RESULTS: There were 210 patients with stable AVB, accounting for 52% of the total number of AVB patients. The mean (+/- s.d.) age was 55 (+/- 12) years. The mean presenting systolic blood pressure and heart rate were 121 (+/- 16) mm Hg and 98 (+/- 20) bpm, respectively. Esophageal varices accounted for 91% (n = 191) of variceal bleeding. The mean time to endoscopy was 12 (+/- 12) h. The overall hemostasis rate after endoscopy was 97% (n = 203). The mortality rate was 9.5% (n = 20). There was no significant association of time to endoscopy with mortality (odds ratio, OR, 1.0; 95% confidence interval, CI, 0.92-1.08; P = 0.91). Significant independent predictors for mortality were lower albumin (OR, 0.82; 95% CI, 0.73-0.93; P = 0.001), infection during admission (OR, 8.9; 95% CI, 2.5-31.6; P < 0.001), and higher model end-stage liver disease (MELD) (OR, 1.17; 95% CI, 1.06-1.29; P = 0.002). There was no difference in outcomes with different urgency times. CONCLUSIONS: For patients who present with hemodynamically stable variceal bleeding, hemostasis after endoscopy is high, and the time to endoscopy does not appear to be associated with mortality.