Search

Intractable pruritus secondary to bile salts retention in Progressive Familial Intrahepatic Cholestasis (PFIC) can be relieved surgically by diverting bile drainage from ileum to reduce bile salts reabsorption into entero-hepatic circulation. We are reporting on the successful biliary diversion in a child with PFIC, with the use of the appendix as a conduit to drain bile from gallbladder to the colon (cholecysto-appendicostomy). [ABSTRACT FROM AUTHOR]

Abstract: Background/Purpose: The surgical treatment for patients with progressive familial intrahepatic cholestasis (PFIC) is either liver transplantation (LTX) or partial external biliary diversion (PEBD). Both procedures achieve a good short-term outcome. However, the treatment strategy for these children remains controversial because the long-term outcome after PEBD is unknown. The aim of our study was to assess the long-term outcome and complications after PEBD in our institution. Methods: We retrospectively analyzed the characteristics of all patients with PFIC undergoing PEBD in our department from 1994 to 2008. The course of serum bile acids, pruritus, and liver enzymes was assessed in a regular follow-up. Results: Twenty-four patients underwent PEBD. Thirteen patients (54%) improved significantly, with a normalization of serum bile acids (P < .001 vs postoperatively) and lessened pruritus (P < .05 vs preoperatively) at 12 months after PEBD. None of these patients showed progression of cholestasis during a median follow-up of 9.8 years (range, 1.6-14.3 years). Partial external biliary diversion failed to normalize bile acids in 11 patients, of whom 9 required secondary LTX at a 1-year follow-up, with a median interval of 1.9 years (range, 0.5-3.8 years). All 7 patients (100%) with liver cirrhosis at the time of PEBD and 2 of 17 patients without cirrhosis (12%) required secondary LTX (P < .001). Conclusions: Clinical improvement with normalization of serum bile acids within 1 year was associated with an excellent long-term outcome in patients with PEBD. The presence of liver cirrhosis at the time of PEBD indicated an unfavorable outcome. Thus, we recommend primary LTX only in PFIC patients with liver cirrhosis. [Copyright &y& Elsevier]

Abstract: Objective: The aim of this study was to review evidence-based data addressing key clinical questions regarding parenteral nutrition–associated cholestasis (PNAC) and parenteral nutrition–associated liver disease (PNALD) in children. Data Source: Data were obtained from PubMed, Medicine databases of the English literature (up to October 2010), and the Cochrane Database of Systematic Reviews. Study Selection: The review of PNAC/PNALD has been divided into 4 areas to simplify one''s understanding of the current knowledge regarding the pathogenesis and treatment of this disease: (1) nonnutrient risk factors associated with PNAC, (2) PNAC and lipid emulsions, (3) nutritional (nonlipid) considerations in the prevention of PNAC, and (4) supplemental medications in the prevention and treatment of PNAC. Results: The data for each topic area relevant to the clinical practice of pediatric surgery were reviewed, evaluated, graded, and summarized. Conclusions: Although the conditions of PNAC and PNALD have been well recognized for more than 30 years, only a few concrete associations and treatment protocols have been established. [Copyright &y& Elsevier]

Abstract: Microvillous inclusion disease is a congenital intestinal epithelial cell disorder leading to lifelong intestinal failure. In this report, we discuss the use of a fish oil–based lipid emulsion in the treatment of 3 patients with microvillous inclusion disease who developed parenteral nutrition–associated liver disease. [Copyright &y& Elsevier]

Abstract: Background: Defects in ABCB4 have been found to cause progressive familial intrahepatic cholestasis type 3. Liver histology is important, but not specific, for diagnosis. Genotyping is conclusive. Aim: To determine the pathogenetic role of two novel ABCB4 mutations in two unrelated children from North Africa and South Asia. Methods: In both children liver histology showed extensive ductular reaction with portal and periportal fibrosis. Immunohistochemical analysis displayed absence of MDR3 protein expression at the canalicular pole. Genotype analysis was performed. Results: Genotyping revealed two novel mutations in ABCB4: the c.1783 C>T (p.R595X) mutation in exon 15 was detected in compound heterozygosity with the c.937_992 in/del in exon 9 in one case, whereas the homozygous p.R595X mutation was recognized in the second child. Conclusions: Two novel loss-of-function mutations have been identified. Progressive familial intrahepatic cholestasis type 3 has a worldwide distribution and genetic analyses are conclusive for correct diagnosis. [Copyright &y& Elsevier]

Abstract: Purpose: Multidisciplinary treatment of pediatric intestinal failure has shown promising results. However, there are limited data as to the optimal time frame for referral of patients to intestinal failure programs. The aim of this study was to explore the relationship of hyperbilirubinemia at referral with patient outcomes in a multidisciplinary program. Methods: A retrospective analysis was performed of a prospectively collected database from a multidisciplinary intestinal failure program. Multivariable logistic regression adjusted for age at referral was used to model the association between the conjugated bilirubin at referral and risk of mortality. Median values with range are reported. Results: Sixty-two patients were referred from 2005 to 2009. Patients presented at age 6.4 months (0.4-261.4 months) and were followed up for 16.8 (0.3-53.0) months. Nine subjects (14.5%) died, and 12 subjects (19.4%) were listed for combined liver-intestine transplant. A 50% mortality was seen in patients referred with a conjugated bilirubin ≥7.2 mg/dL (n = 12), whereas mortality at referral bilirubin levels <7.2 mg/dL was 6%. After adjusting for age at referral, patients with a conjugated bilirubin ≥7.2 mg/dL at referral were 15.4 times more likely to die than patients who presented with lower bilirubin levels (P = .001; 95% confidence interval, 2.8-83.4). Conclusion: Within a pediatric intestinal failure program, mortality is associated with the degree of hyperbilirubinemia at time of referral. These data strongly suggest that these patients should be referred to a multidisciplinary program early in the evolution of their liver disease. [Copyright &y& Elsevier]

Abstract: Background: The purpose of the study was to determine the distribution of excreted bile during cholestatic periods and in remission in patients with progressive familial intrahepatic cholestasis (PFIC) after surgery with partial external biliary diversion (PEBD), using hepatobiliary scintigraphy. Methods: Using intravenously administered technetium Tc 99m–labeled mebrofenin, the distribution of bile during periods of biochemical cholestasis and in remission was investigated in patients with PFIC operated with PEBD. Stomal bile, urine, and feces from the patients were collected during 24 hours after administration of technetium Tc 99m–labeled mebrofenin; and the fractions of remaining radioactivity in the 3 compartments and the remaining isotopic activity in the body were quantified using scintigraphy. Results: Nine patients (4 boys and 5 girls) were studied. The median age was 13 (range, 5-24) years, and they had been operated with PEBD at a median time of 10 (range, 4-14) years before entering the study. Thirteen scintigraphic examinations were analyzed: 8 during noncholestatic remission (n = 7 patients) and 5 during cholestasis (n = 3 patients). The patients studied during remission discharged a significantly larger fraction of isotopic activity through the stoma (median, 90% vs 22%; P < .05) and a significantly lower fraction through the urine (median, 2.5% vs 15%; P < .05) compared with the patients studied during cholestasis. Conclusion: Hepatobiliary scintigraphy could detect substantial differences in the output of bile. Further studies are needed to determine whether these differences may explain the mechanism of the PEBD operation or merely are secondary to the degree of cholestasis. [Copyright &y& Elsevier]

Abstract: Background: The changes in liver blood flow associated with living donor liver transplantation (LDLT) in children have not yet been studied. The aim of the present study was to investigate changes in hepatic hemodynamics before and after pediatric partial liver transplantation. Methods: In 7 pediatric recipients with congenital cholestasis and native liver Child-Pugh classes B and C, portal vein flow (PVF) and hepatic arterial flow (HAF) were measured using an ultrasonic transit time flow meter before removal of the native liver and after transplantation and compared with donor left PVF and donor left HAF. Results: The mean portal contribution to total hepatic blood flow was markedly decreased in the recipient native liver compared with that in the donor (69% ± 15% vs 32% ± 15%; P = .0003) and after reperfusion changed to almost the same ratio as that in the donor liver (73% ± 18%; P < .0001). Conclusion: The extreme imbalance between PVF and HAF that is common in implanted partial liver in adult LDLT recipients was not observed in pediatric LDLT. After transplantation of an appropriately sized liver graft, the portal contribution to total liver blood flow normalized to the value for normal liver. [Copyright &y& Elsevier]

Abstract: Purpose: The aim of the study was to determine the frequency of biochemical cholestasis (direct bilirubin [DB] ≥2 mg/dL) in children with short bowel syndrome and biopsy-proven parenteral nutrition (PN)-associated liver disease and to define predictive factors for the occurrence and degree of hepatic fibrosis. Methods: After institutional review board approval, a retrospective review was conducted of patients followed by 2 multidisciplinary intestinal rehabilitation programs between January 1, 2000, and September 30, 2008. Inclusion criteria were exposure to PN (>30 days) and having undergone a liver biopsy. Liver biopsy specimens were graded from 0 to 3 based upon degree of fibrosis in the pathology report. The most recent DB within 10 days before biopsy was recorded. Results: A total of 66 children underwent 83 liver biopsy procedures. The most common diagnoses included necrotizing enterocolitis (NEC) (36.4%), gastroschisis (22.7%), and intestinal atresia (15.1%). Median age at biopsy was 6.1 months with a median duration of PN of 4.7 months. Of the patients, 70.3% had a history of exposure to parenteral ω-3 lipid emulsion. Of the liver biopsy specimens, 89% (74/83) demonstrated some degree of fibrosis (fibrosis scale 1-3), including 9.6% (8/83) with evidence of cirrhosis. 83% of biopsies without fibrosis and 55% of biopsies with fibrosis were obtained in patients without evidence of biochemical cholestasis (P = .20). Three (37%) of the 8 patients with cirrhosis on liver biopsy had no evidence of biochemical cholestasis. Univariate analysis identified only gestational age (GA) at birth as significantly associated with the degree of liver fibrosis (P = .03). A multivariate logistic regression model accounting for multiple biopsy procedures in patients revealed that GA was a predictor of fibrosis only in patients with a diagnosis other than NEC (P < .01). Conclusions: In children with short bowel syndrome, biochemical cholestasis does not reflect the presence or degree of histologically confirmed PN-associated liver fibrosis. Careful follow-up, combined with further refinement of diagnostic and hepatoprotective strategies, may be warranted in this patient population. [Copyright &y& Elsevier]

Background: One of the most common complications in infants under parenteral nutrition treatment is parenteral nutrition-associated cholestasis (PNAC). The etiology of PNAC is thought to be multifactorial. The aims of this study were to evaluate the risk factors for PNAC in our neonatal intensive care unit and determine useful predictors. Methods: This study enrolled premature infants (gestational age < 36 weeks) who were admitted to our neonatal intensive care unit and treated with parenteral nutrition infusion for at least 2 weeks between January 2004 and January 2007. Multiple possible risk factors were analyzed by a retrospective review study design. PNAC was defined as direct bilirubin greater than 1.5 mg/dL during parenteral nutrition. Results: A total of 62 premature infants with prolonged course of parenteral nutrition were eligible for this study; 11 (17.74%) of the infants developed PNAC. There were significant differences in terms of gestational age, birth body weight, duration of parenteral nutrition, septic episodes, and average energy intake during the 2nd and 3rd weeks of life between infants with cholestasis and those without cholestasis. Of these risk factors, the duration of parenteral nutrition was most significant after multivariate logistic regression analysis. Conclusion: Young gestational age, low birth body weight, more sepsis episodes, and long duration of parenteral nutrition were significant risk factors for PNAC in our study. Low energy intake during the 2nd and 3rd weeks of life is a predictor for PNAC. [Copyright &y& Elsevier]

Abstract: Background: Progressive familial intrahepatic cholestasis (PFIC) is a family of rare childhood diseases that was universally fatal until the development of liver transplant. In the last 20 years, the use of nontransplant surgery to treat PFIC has become the standard of care. There are various surgical techniques that have been performed. There are no reviews evaluating the outcome of these operations. Methods: A systematic search of the literature for articles evaluating the outcome of nontransplant surgical interventions in PFIC patients was performed. Data from these studies was abstracted and summarized. Results: No trials have been performed addressing nontransplant surgical interventions in PFIC patients. We analyzed 11 case series and case reports. Generally, patients had successful outcomes (81%) with cessation of progression of disease and resolution of symptoms. Treatment failures were often associated with more advanced disease. Discussion: There is no evidence to demonstrate a superiority of one type of nontransplant surgical intervention in PFIC patients. We propose the development of a registry and standardization of outcomes measurements to allow improved comparison of results. [Copyright &y& Elsevier]

Background & Aims: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and progressive bile duct fibrosis. There are limited data on pediatric PSC. Methods: We performed a retrospective chart review of 47 pediatric patients with PSC. Results: The mean age at diagnosis was 11 ± 4.9 years. Symptoms occurred before presentation in 81% of patients; inflammatory bowel disease was found in 59% and autoimmune hepatitis (overlap syndrome) in 25% of patients. Magnetic resonance cholangiography revealed both extrahepatic and intrahepatic, isolated intrahepatic, isolated extrahepatic, and no biliary involvement (small-duct PSC) in 40%, 14%, 10%, and 36%, respectively. Advanced fibrosis (stage >II) was present in 65%. Colonoscopy revealed pancolitis, rectal sparing, and normal findings in 24%, 24%, and 18%, respectively. All patients were treated with ursodeoxycholic acid (UDCA); 9 with overlap syndrome also received immunosuppressants. Fifteen patients without overlap syndrome had positive autoimmune markers and responded to UDCA monotherapy. Liver transplantation was performed in 9 patients (3 with overlap syndrome and 2 with small-duct PSC) at a median time of 7 years after diagnosis. The 10-year posttransplant survival rate was 89%. Conclusions: In one of the largest single-center studies of children with PSC, we found that most children with PSC had inflammatory bowel disease or autoimmune overlap and advanced fibrosis at diagnosis. Levels of alanine aminotransferase and γ-glutamyl transferase were highest in patients with overlap syndrome and lowest in those with small-duct PSC. Levels of serum liver enzymes normalized after therapy with UDCA, including patients with positive autoimmune markers without histologic features of autoimmune hepatitis. [Copyright &y& Elsevier]

Abstract: Purpose: The aim of the study was to investigate the effect of prophylactic cycling of parenteral nutrition (PN) on PN-induced cholestasis in patients with gastroschisis. Methods: Retrospective review of initial hospital admission charts for each patient with gastroschisis from 1996 to 2007 was performed. Results: One hundred seven patients were analyzed (36 prophylactically cycled, 71 control). Prophylactic cycling of PN was initiated at a mean age of 23 days (range, 7-89 days). Patients were followed for a total of 4255 days with 27 developing hyperbilirubinemia (cycled, 5; continuous, 22). Time to hyperbilirubinemia was longer in the prophylactically cycled group (P = .005). Cumulative incidence of hyperbilirubinemia at 25 and 50 days of PN exposure was 5.7% and 9.8% (cycled) vs 22.3% and 48.8% (continuous). At any given time, children in the continuous group were 4.76 times more likely to develop hyperbilirubinemia (95% confidence interval, 1.62-14.00). After adjusting for confounding factors, children in the continuous group were 2.86 times more likely to develop hyperbilirubinemia (95% confidence interval, 0.86-9.53), but the difference was not significant (P = .088). Conclusions: Prophylactic cyclic PN is associated with a decreased incidence and prolonged time to onset of hyperbilirubinemia. Other factors, however, significantly affect this relationship. Prospective randomized investigation is warranted to investigate for a possible causal relationship. [Copyright &y& Elsevier]

Abstract: No appropriate pharmaceutical therapy has been established for dyslipidemia with cholestasis in progressive familial intrahepatic cholestasis (PFIC)–1. We evaluated the efficacy of bezafibrate in PFIC-1. We monitored the clinical presentation and lipoprotein metabolism of 3 patients, aged 3, 4, and 8 years, with FIC1 deficiency, manifesting PFIC-1, over 12 months of bezafibrate therapy. Pruritus was substantially alleviated in the 3 patients after initiation of bezafibrate. Cholestasis was alleviated in 2 of them. Serum high-density lipoprotein cholesterol and low-density lipoprotein cholesterol increased 1.6- to 2.0-fold and 1.1- to 1.2-fold, respectively; but the values remained low and normal, respectively. Serum lipoprotein X, which was at normal levels before treatment, was elevated to levels above the upper limit of the reference range. High serum triglyceride levels decreased by 15% to 30%, to normal levels, after treatment initiation. The activities of lipoprotein lipase and hepatic triglyceride lipase were increased, but those of high-density lipoprotein regulators remained unchanged. Liver expression of multidrug resistance protein–3, which regulates lipoprotein X synthesis, was enhanced by bezafibrate therapy. Bezafibrate treatment favorably affected pruritus, dyslipidemia, and cholestasis in PFIC-1. [Copyright &y& Elsevier]

Prolonged neonatal jaundice when accompanied with cholestasis needs prompt diagnosis and treatment. Increasing awareness and advent of new diagnostic modalities have helped in identifying a cause for cholestasis now in most babies. Early treatment has far reaching implications in conditions such as EHBA and certain metabolic disorders. A standardized approach to investigations and early management can help in identifying several such disorders causing neonatal cholestasis and help save valuable lives. [Copyright &y& Elsevier]

Abstract: Conjugated hyperbilirubinemia can be a pointer towards an obvious liver pathology or occult systemic pathology. A careful meticulous approach with a combination of clinical and laboratory tests are necessary for the diagnosis and timely management. [Copyright &y& Elsevier]

Background & Aims: Cirrhotic liver diseases are associated with abnormalities in cardiac geometry and function in adults (cirrhotic cardiomyopathy) but rarely explored in cirrhotic infants or children. We proposed that features of cirrhotic cardiomyopathy are present in infants with cirrhosis due to biliary atresia (BA) as early as the time of evaluation for liver transplant and will correlate with mortality and postoperative morbidity. Methods: Two-dimensional echocardiography (2DE) of infants with BA (n = 40; median age, 8 months), listed for transplantation at the Texas Children''s Hospital from 2004 to 2010, were reviewed and compared with age- and sex-matched infants without cardiac or liver disease (controls). Length of stay and correlation with 2DE results were assessed. Results: Compared with controls, children with BA had significant increases in multiple 2DE parameters, notably left ventricle wall thickness (23% increase), left ventricular (LV) mass indexed to body surface area (51% increase), and LV shortening fraction (8% increase). Overall, features of cirrhotic cardiomyopathy were observed in most infants (29/40; 72%); 17 had hyperdynamic contractility, and 24 had altered LV geometry. After liver transplantation (33), infants with abnormal 2DE results had longer stays in the intensive care unit (median, 6 vs 4 days) and the hospital (21 vs 11 days) compared with infants who had normal 2DE reports. On univariate analysis, the length of hospital stay correlated with LV mass index. Conclusions: Cardiomyopathy is a prevalent condition in infants with end-stage cirrhotic liver disease due to BA (>70%). This underrecognized condition likely contributes to the prolongation of posttransplant hospitalization. [Copyright &y& Elsevier]