Severity of Ascites Is Associated with Increased Mortality in Patients with Cirrhosis Secondary to Biliary Atresia.

BACKGROUND: Very few prior studies have investigated the presence of ascites as a prognostic factor in children with cirrhosis. To the best of our knowledge, there are no prior studies evaluating the relationship between severity of ascites and patient survival in children with biliary atresia and cirrhosis. AIMS: To evaluate the association between severity of ascites and survival of children with cirrhosis and biliary atresia. METHODS: All children with cirrhosis secondary to biliary atresia evaluated at our institution from 2000 to 2014 were included in this study. Patients were classified into four groups: NA = no ascites; A1 = grade 1 ascites; A2 = grade 2 ascites; and A3 = grade 3 ascites. The primary endpoint of the study was mortality within the first year after patient inclusion. Ninety-day mortality was also evaluated. Prognostic factors related to both endpoints also were studied. RESULTS: One-year patient survival for NA was 97.1%, versus 80.8% for A1, versus 52% for A2, versus 13.6 for A3 (p < 0.001). The presence of ascites increased mortality by 17 times. In the multivariate analysis, clinically detectable ascites (HR 3.14, 95% CI 1.14-8.60, p = 0.026), lower sodium (HR 1.15, 95% CI 1.04-1.27, p = 0.006), higher bilirubin (HR 1.06, 95% CI 1.00-1.12, p = 0.023), and higher PELD score (HR 1.05, 95% CI 1.02-1.08, p = 0.001) were all associated with decreased survival. Lower serum sodium (HR 1.20, 95% CI 1.09-1.32, p < 0.001) and higher PELD score (HR 1.03, 95% CI 1.001-1.063, p = 0.043) were associated with increased 90-day mortality. CONCLUSIONS: Clinically detectable ascites is associated with decreased 1-year survival of children with biliary atresia. These patients should be treated with caution and prioritized for liver transplantation.

Hypothermia is better than ischemic preconditioning for preventing early hepatic ischemia/reperfusion in rats.

BACKGROUND: Topical hypothermia (TH) and ischemic preconditioning (IPC) are used to decrease I/R injury. The efficacy of isolated or combined use of TH and IPC in the liver regarding inflammation and cytoprotection in early ischemia/reperfusion (I/R) injury needs to be evaluated. MATERIAL AND METHODS: Wistar rats underwent 70% liver ischemia for 90 min followed by 120 min of reperfusion. Livers of animals allocated in the sham, normothermic ischemia (NI), IPC, TH, and TH+IPC groups were collected for molecular analyses by ELISA and Western blot, aiming to compare proinflammatory, anti-inflammatory, and antioxidant profiles. RESULTS: Compared with NI, TH presented decreased tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IL-12 concentrations and increased IL-10 levels. TH animals displayed lower inducible nitric oxide synthase (iNOS) and higher endothelial nitric oxide synthase (eNOS) expressions. NAD(P)H-quinone oxidoreductase-1(NQO1) expression was also lower with TH. Isolated IPC and NI were similar regarding all these markers. TH+IPC was associated with decreased IL-12 concentration and reduced iNOS and NQO1 expressions, similarly to isolated TH. Expression of Kelch-like ECH-associated protein (Keap)-1 was increased and expression of nuclear and cytosolic nuclear erythroid 2-related factor 2 (Nrf2) was decreased with TH+IPC vs. NI. CONCLUSION: TH was the most effective method of protection against early I/R injury. Isolated IPC entailed triggering of second-line antioxidant defense enzymes. Combined TH+IPC seemed to confer no additional advantage over isolated TH in relation to the inflammatory process, but had the advantage of completely avoid second-line antioxidant defense enzymes.

Angiopoietin 1 and angiopoietin 2 are associated with medial thickening of hepatic arterial branches in biliary atresia.

BACKGROUND: Biliary atresia (BA) is an infantile disorder characterized by progressive sclerosing cholangiopathy leading to biliary obstruction. First-line treatment of BA is hepatoportoenterostomy, the prognosis of which is related to age at surgery and to histological variables such as extent of fibrosis and ductular reaction. Hepatic arterial medial thickening (MT) suggests an arteriopathy in BA pathogenesis. We evaluated the expression of angiopoietin (ANGPT)/tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2 (TIE2) system in liver samples obtained from patients with BA, correlating it with MT, variables associated with disease severity, and postoperative prognosis. METHODS: ANGPT1, ANGPT2, and TIE2 expression levels were assessed by quantitative PCR in liver samples obtained from BA patients (n = 23) at portoenterostomy and age-matched infants with intrahepatic cholestasis (IHC; n = 7). Histological variables were morphometrically assessed. RESULTS: ANGPT1 and ANGPT2 were overexpressed in BA in comparison with IHC (P = 0.024 and P = 0.029, respectively). In BA, ANGPTs expression was positively correlated with MT (ANGPT1: rs = 0.59, P = 0.013; ANGPT2: rs = 0.52, P = 0.032), not with the variables associated with disease severity. TIE2 and ANGPTs expression levels were negatively correlated (ANGPT1: rs = -0.73, P < 0.001; ANGPT2: rs = -0.54, P = 0.007). CONCLUSION: In BA, there is overexpression of both ANGPT1 and ANGPT2, which is correlated with MT but not with age at portoenterostomy or with the histological variables associated with disease severity at the time of procedure.

Th2 signals induce epithelial injury in mice and are compatible with the biliary atresia phenotype.

Biliary atresia (BA) is a destructive cholangiopathy of childhood in which Th1 immunity has been mechanistically linked to the bile duct inflammation and obstruction that culminate in liver injury. Based on reports of decreased Th1 cytokines in some patients and the development of BA in mice lacking CD4+ T cells, we hypothesized that Th1-independent mechanisms can also activate effector cells and induce BA. Here, we tested this hypothesis using Stat1-/- mice, which lack the ability to mount Th1 immune responses. Infection of Stat1-/- mice with rhesus rotavirus type A (RRV) on postnatal day 1 induced a prominent Th2 response, duct epithelial injury and obstruction within 7 days, and atresia shortly thereafter. A high degree of phosphorylation of the Th2 transcription factor Stat6 was observed; however, concurrent inactivation of Stat1 and Stat6 in mice did not prevent BA after RRV infection. In contrast, depletion of macrophages or combined loss of Il13 and Stat1 reduced tissue infiltration by lymphocytes and myeloid cells, maintained epithelial integrity, and prevented duct obstruction. In concordance with our mouse model, humans at the time of BA diagnosis exhibited differential hepatic expression of Th2 genes and serum Th2 cytokines. These findings demonstrate compatibility between Th2 commitment and the pathogenesis of BA, and suggest that patient subgrouping in future clinical trials should account for differences in Th2 status.

Positive deviance: a program for sustained improvement in hand hygiene compliance.

BACKGROUND: There is a paucity of data evaluating whether positive deviance (PD) can sustain improvement in hand hygiene compliance. METHODS: An observational study comparing the effect of PD on compliance with hand hygiene was conducted in two 20-bed step-down units (SDUs) at a private tertiary care hospital. In a 3-month baseline period (April-June 2008), hand hygiene counts were performed by electronic handwashing counters. Between July 1, 2008, and November 30, 2009, (East SDU) and between September 30, 2008, and December 2009 (West SDU), PD was applied in both units. RESULTS: There was more than a 2-fold difference in the number of alcohol gel aliquots dispensed per month from April 2008 (before PD) to November 2009 (last month in PD) in the East SDU. There was also a 2-fold difference in the number of alcohol gel aliquots dispensed per month from September 2008 (before PD) to December 2009 (last month in PD) in the West SDU. The difference in the rate of health care‒associated infections (HAIs) between the baseline period and 2009 was statistically significant in the East SDU (5.8 vs 2.8 per 1,000 device-days; P = .008) and in the West SDU (3.7 vs 1.7 per 1,000 device-days; P = .023). CONCLUSIONS: PD was responsible for a sustained improvement in hand hygiene in the inpatient setting and was associated with a decrease in the incidence of device-associated HAIs.

Positive deviance: a new strategy for improving hand hygiene compliance.

OBJECTIVE: To evaluate the effectiveness of a positive deviance strategy for the improvement of hand hygiene compliance in 2 adult step-down units. DESIGN: A 9-month, controlled trial comparing the effect of positive deviance on compliance with hand hygiene. SETTING: Two 20-bed step-down units at a tertiary care private hospital. METHODS: The first phase of our study was a 3-month baseline period (from April to June 2008) in which hand hygiene episodes were counted by use of electronic handwashing counters. From July to September 2008 (ie, the second phase), a positive deviance strategy was implemented in the east unit; the west unit was the control unit. During the period from October to December 2008 (ie, the third phase), positive deviance was applied in both units. RESULTS: During the first phase, there was no statistically significant difference between the 2 step-down units in the number of episodes of hand hygiene per 1,000 patient-days or in the incidence density of healthcare-associated infections (HAIs) per 1,000 patient-days. During the second phase, there were 62,000 hand hygiene episodes per 1,000 patient-days in the east unit and 33,570 hand hygiene episodes per 1,000 patient-days in the west unit (P < .01 ). The incidence density of HAIs per 1,000 patient-days was 6.5 in the east unit and 12.7 in the west unit (p = .04). During the third phase, there was no statistically significant difference in hand hygiene episodes per 1,000 patient-days (P = .16) or in incidence density of HAIs per 1,000 patient-days. CONCLUSION: A positive deviance strategy yielded a significant improvement in hand hygiene, which was associated with a decrease in the overall incidence of HAIs.