Risk of variceal hemorrhage and pretransplant mortality in children with biliary atresia.

BACKGROUND AND AIMS: The natural history of gastroesophageal variceal hemorrhage (VH) in biliary atresia (BA) is not well characterized. We analyzed risk factors, incidence, and outcomes of VH in a longitudinal multicenter study. APPROACH AND RESULTS: Participants enrolled in either an incident (Prospective Database of Infants with Cholestasis [PROBE]) or prevalent (Biliary Atresia Study of Infants and Children [BASIC]) cohort of BA were included. Variceal hemorrhage (VH) was defined based on gastrointestinal bleeding in the presence of varices accompanied by endoscopic or nontransplant surgical intervention. Cumulative incidence of VH and transplant-free survival was compared based on features of portal hypertension (e.g., splenomegaly, thrombocytopenia) and clinical parameters at baseline in each cohort (PROBE: 1.5 to 4.5 months after hepatoportoenterostomy [HPE]; BASIC: at enrollment > 3 years of age). Analyses were conducted on 869 children with BA enrolled between June 2004 and December 2020 (521 in PROBE [262 (51%) with a functioning HPE] and 348 in BASIC). The overall incidence of first observed VH at 5 years was 9.4% (95% CI: 7.0-12.4) in PROBE and 8.0% (5.2-11.5) in BASIC. Features of portal hypertension, platelet count, total bilirubin, aspartate aminotransferase (AST), albumin, and AST-to-platelet ratio index at baseline were associated with an increased risk of subsequent VH in both cohorts. Transplant-free survival at 5 years was 45.1% (40.5-49.6) in PROBE and 79.2% (74.1-83.4) in BASIC. Two (2.5%) of 80 participants who had VH died, whereas 10 (12.5%) underwent transplant within 6 weeks of VH. CONCLUSIONS: The low risk of VH and associated mortality in children with BA needs to be considered in decisions related to screening for varices and primary prophylaxis of VH.

Unraveling the Relationship Between Itching, Scratch Scales, and Biomarkers in Children With Alagille Syndrome.

Pruritus is a debilitating symptom for patients with Alagille syndrome (ALGS). In a previously reported trial of maralixibat, an investigational antipruritic agent, itching was assessed using a digital diary based on twice-daily caregiver observation of itching severity (Itch Reported Outcome, ItchRO[Observer]). The goal of this study was to characterize pruritus in participants with ALGS at baseline in this trial, as assessed by the ItchRO instrument and the physician-observed clinician scratch scale (CSS), relative to biomarkers putatively associated with pruritus and health-related quality of life assessment. Thirty-seven participants with ALGS (median age of 6 years; range 1-17 years) were enrolled. No association was identified between CSS and ItchRO(Obs) (r = 0.22, P = 0.2). Neither CSS nor ItchRO were associated with serum bile acids (r = -0.08, P = 0.6 for both) or autotaxin (r = 0.22, P = 0.2; r = 0.28, P = 0.12). There was no significant association between Pediatric Quality of Life Inventory total parent scores and CSS or ItchRO (r = -0.23, P = 0.2; r = -0.16, P = 0.36). There was a significant association between ItchRO and Multidimensional Fatigue Scale and Family Impact Module total scores (Pearson correlation coefficient -0.575, P = 0.0005; 0.504, P = 0.002). In exploratory analysis, selected questions relating to fatigue and sleep disturbance (n = 12) from Pediatric Quality of Life Inventory, Multidimensional Fatigue Scale, and Family Impact Module were correlated with pruritus scores; positive associations were identified. Conclusion: Itching scores did not correlate with each other, nor with putative serum biomarkers of pruritus, and further, did not correlate with quality of life. Hypothesis-generating analyses implicate sleep disturbance and fatigue as key associations with caregiver observations of itching. This is highly relevant to the selection of surrogate endpoints for clinical trials of pruritus therapies.

Cost-effectiveness analysis of fecal microbiota transplantation for recurrent Clostridium difficile infection.

OBJECTIVE: Clostridium difficile infection (CDI) places a high burden on the US healthcare system. Recurrent CDI (RCDI) occurs frequently. Recently proposed guidelines from the American College of Gastroenterology (ACG) and the American Gastroenterology Association (AGA) include fecal microbiota transplantation (FMT) as a therapeutic option for RCDI. The purpose of this study was to estimate the cost-effectiveness of FMT compared with vancomycin for the treatment of RCDI in adults, specifically following guidelines proposed by the ACG and AGA. DESIGN: We constructed a decision-analytic computer simulation using inputs from the published literature to compare the standard approach using tapered vancomycin to FMT for RCDI from the third-party payer perspective. Our effectiveness measure was quality-adjusted life years (QALYs). Because simulated patients were followed for 90 days, discounting was not necessary. One-way and probabilistic sensitivity analyses were performed. RESULTS: Base-case analysis showed that FMT was less costly ($1,669 vs $3,788) and more effective (0.242 QALYs vs 0.235 QALYs) than vancomycin for RCDI. One-way sensitivity analyses showed that FMT was the dominant strategy (both less expensive and more effective) if cure rates for FMT and vancomycin were ≥70% and <91%, respectively, and if the cost of FMT was <$3,206. Probabilistic sensitivity analysis, varying all parameters simultaneously, showed that FMT was the dominant strategy over 10, 000 second-order Monte Carlo simulations. CONCLUSIONS: Our results suggest that FMT may be a cost-saving intervention in managing RCDI. Implementation of FMT for RCDI may help decrease the economic burden to the healthcare system.

Renal replacement therapy in infants and children with hepatorenal syndrome awaiting liver transplantation: a case-control study.

Limited data on short- and long-term outcomes of renal replacement therapy (RRT) in pediatric liver transplantation (LT) patients exist. We evaluated risk factors for RRT in pediatric LT recipients with hepatorenal syndrome (HRS) and described the outcomes. We performed a single-center, case-control study of LT recipients who required RRT for HRS from 1999 to 2011. Three controls who did not receive RRT were matched with each case on the basis of age, diagnosis, and LT date. We identified 8 recipients among 133 recipients of 152 LT cases [6%, 95% confidence interval = 2%-10%; mean age = 7.7 years, range = 0.5-19.8 years) who required RRT before LT for HRS. Four patients were <1 year old and weighed 5.6 to 6.6 kg. Biliary atresia was the most common LT indication. Cases had higher Model for (Pediatric) End-Stage Liver Disease scores at listing (26 versus 16, P = 0.01) and lower glomerular filtration rates (GFRs; 15 versus 102 mL/minute/1.73 m(2) , P < 0.001) at RRT initiation or LT. Ascites, gastrointestinal bleeding, and infections occurred more commonly among cases: (100% versus 54%, P = 0.03; 100% versus 46%, P = 0.01; and 88% versus 33%, P = 0.01, respectively). Cases also experienced toxic vancomycin troughs more frequently (38% versus 0%, P = 0.01) and received RRT for a median of 21 days (range = 3-355 days). The case mortality rate was 37.5% (3/8 at 1, 26, and 346 days after LT) and 0% for controls. The 4 infants required 0 to 3 dialysis catheter replacements during RRT. Cases and controls had similar median follow-ups [3.2 years (range = 1.5-7.6 years) versus 4.9 years (range = 0.2-11 years), P = 0.29]. After LT, they also had similar GFRs (83 versus 99 mL/minute/1.73 m(2) at 1 month, P = 0.19; 80 versus 107 mL/minute/1.73 m2 at 1 year, P > 0.99; and 97 versus 114 mL/minute/1.73 m2 at the most recent follow-up, P = 0.09). The case survival rates were 75% and 63% at 1 month and 1 year, respectively; 4 cases required antihypertensives and diuretics 1 month after LT, but at the last follow-up, only 1 case required antihypertensive therapy, and none required diuretics. In conclusion, pediatric patients with HRS, including infants, benefit from RRT. Although HRS decreases survival, patients with HRS who undergo LT generally recover renal function within 1 month that persists during long-term follow-up.