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Objectives: Primary prophylaxis of bleeding is debated in children with gastroesophageal varices; one of the reasons is the limited number of studies concerning its efficacy and safety. We report our experience with endoscopic primary prophylaxis., Methods: From 2006 to 2019, 145 children (median age, 3.5 years; cirrhosis, n = 116) with high-risk gastroesophageal varices underwent primary prophylaxis (banding, n = 114; sclerotherapy n = 31, primarily in smaller children)., Results: We observed the eradication of varices in 93% of children after a mean of 6 months, at least one recurrence of varices in 45% after eradication, and gastrointestinal bleeding in 17% of children. Irrespective of the cause of portal hypertension, grade 3 esophageal varices, presence of gastric varices along the cardia and a lower composite score of endoscopic severity were associated with a worse probability of eradication, a longer time to eradication and a lower risk of a first recurrence and of bleeding following the procedure, respectively. Ten-year probabilities of overall survival and of bleeding-free survival were 95% and 75%, respectively., Conclusions: Endoscopic primary prophylaxis of variceal bleeding is reasonably effective and safe in children with high-risk gastroesophageal varices. Worse results are observed in children with more advanced endoscopic features. This pleads for endoscopic screening in children with portal hypertension and early detection of varices warranting primary prophylaxis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.) more...

Objective: In children with biliary atresia and portal hypertension, progression to gastroesophageal varices carrying a risk of bleeding depends on age, total serum bilirubin concentration and initial endoscopic features. We report an attempt to use these factors for early detection of high-risk varices (HRVs)., Methods: Based on different combinations of these factors, a model was set to estimate the probabilities of emergence of HRVs at various time intervals. A 10% probability was chosen to set the date of the next endoscopy in children who did not display HRVs initially. A total of 113 children without HRVs who underwent their first endoscopy before age 8 in 2013-2020 were included. A comparison was made with children seen during the period 1990-2012 when this model was not used., Results: In all, 65 of the 113 children underwent one to five additional endoscopies at dates set according to the model. The emergence of HRVs was recorded in 22 children after a mean interval of 14 months and was managed by endoscopic primary prophylaxis in all but one who underwent liver transplantation. Three other children bled before the next planned endoscopy. Compared with 175 children of the same age ranges without HRVs in the period 1990-2012, the use of the model was associated with a faster detection of HRVs with a lower number of endoscopic procedures (P  = 0.0022 and P  = 0.023, respectively)., Conclusion: The results suggest that the model reported may be a useful tool for the early detection of HRVs to allow primary prophylaxis of bleeding., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.) more...

Objectives: To describe a cohort of Wilson disease (WD) pediatric cases, and to point out the diagnostic particularities of this age group and the long-term outcome., Methods: Clinical data of 182 pediatric patients included in the French WD national registry from 01/03/1995 to 01/06/2019 were gathered., Results: Diagnosis of WD was made at a mean age of 10.7 ± 4.2 years (range 1-18 years). At diagnosis, 154 patients (84.6%) had hepatic manifestations, 19 (10.4%) had neurological manifestations, and 9 patients (4.9%) were asymptomatic. The p.His1069Gln mutation was the most frequently encountered (14% of patients).Neurological patients were diagnosed at least 1 year after they presented their first symptoms. At diagnosis, the median urinary copper excretion (UCE) was 4.2 μmol/24 hours (0.2-253). The first-line treatment was d-penicillamine (DP) for 131 (72%) patients, zinc salts for 24 (13%) patients, and Trientine for 17 (9%) patients. Liver transplantation was performed in 39 (21.4%) patients, for hepatic indications in 33 of 39 patients or for neurological deterioration in 6 of 39 patients, mean Unified Wilson's Disease Rating Scale of the latter went from 90 ± 23.1 before liver transplantation (LT) to 26.8 ± 14.1 (P < 0.01) after a mean follow-up of 4.3 ± 2.5 years. Overall survival rate at 20 years of follow-up was 98%, patient and transplant-free combined survival was 84% at 20 years., Conclusion: Diagnosis of WD can be challenging in children, particularly at the early stages of liver disease and in case of neurological presentation; hence the support of clinical scores and genetic testing is essential. Diagnosis at early stages and proper treatment ensure excellent outcomes, subject to good long-term treatment compliance. LT is a valid option for end-stage liver disease not responding to treatment and can be discussed for selected cases of neurological deterioration., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.) more...

Objectives: This study analyses the prognosis of biliary atresia (BA) in France since 1986, when both Kasai operation (KOp) and liver transplantation (LT) became widely available., Methods: The charts of all patients diagnosed with BA born between 1986 and 2015 and living in France were reviewed., Results: A total of 1428 patients were included; 1340 (94%) underwent KOp. Total clearance of jaundice (total bilirubin ≤20 μmol/L) was documented in 516 patients (39%). Age at KOp (median 59 days, range 6-199) was stable over time. Survival with native liver after KOp was 41%, 35%, 26%, and 22% at 5, 10, 20, and 30 years, stable in the 4 cohorts. 25-year survival with native liver was 38%, 27%, 22%, and 19% in patients operated in the first, second, third month of life or later, respectively (P = 0.0001). Center caseloads had a significant impact on results in the 1986 to 1996 cohort only. 16%, 7%, 7%, and 8% of patients died without LT in the 4 cohorts (P = 0.0001). A total of 753 patients (55%) underwent LT. Patient survival after LT was 79% at 28 years. Five-year patient survival after LT was 76%, 91%, 88%, and 92% in cohorts 1 to 4, respectively (P < 0.0001). Actual BA patient survival (from diagnosis) was 81%. Five-year BA patient survival was 72%, 88%, 87%, and 87% in cohorts 1986 to 1996, 1997 to 2002, 2003 to 2009, and 2010 to 2015, respectively (P < 0.0001)., Conclusions: In France, 87% of patients with BA survive nowadays and 22% reach the age of 30 years without transplantation. Improvement of BA prognosis is mainly due to reduced mortality before LT and better outcomes after LT. more...

Objectives: Early diagnosis of bile acid synthesis disorders (BASDs) is important because, untreated, these conditions can be fatal. Our objectives were to screen children with cholestasis or unexplained liver disease for BASD and in those with confirmed BASD to evaluate the effectiveness of cholic acid therapy., Methods: A routine serum total bile acid measurement was performed on children with cholestasis, liver cirrhosis, and liver failure. Patients were screened for BASD by fast atom bombardment ionization-mass spectrometry (FAB-MS) analysis of urine, and molecular analysis confirmed diagnosis. Treatment response to oral cholic acid (10-15 mg/kg bw/day) was assessed from liver function tests and fat-soluble vitamin levels. FAB-MS analysis of urine was used to monitor compliance and biochemical response., Results: Between 2007 and 2016, 626 patients were evaluated; 450 with infantile cholestasis. Fifteen cases of BASD were diagnosed: 12 presented with infantile cholestasis (2.7%, 7 boys), an 8-year-old boy presented with cirrhosis, and two 18-month-old boys presented with hepatomegaly and rickets. Eleven were caused by 3β-hydroxy-Δ-C27-steroid oxidoreductase dehydrogenase deficiency, 3 from Δ-3-oxosteroid 5β-reductase deficiency, and 1 had Zellweger spectrum disorder. In all but 1, serum total bile acids were normal or low. With cholic acid therapy, 10 are alive and healthy with their native liver. Liver failure developed in 3 infants despite therapy; 2 died and 1 underwent liver transplantation., Conclusions: BASDs are rare but treatable causes of metabolic liver disease in Saudi Arabia. BASD should be considered in infants with cholestasis and low or normal serum total bile acid concentrations. more...

Objective: Inborn errors of primary bile acid (BA) synthesis are genetic cholestatic disorders leading to accumulation of atypical BA with deficiency of normal BA. Unless treated with primary BA, chronic liver disease usually progresses to cirrhosis and liver failure before adulthood. We sought to determine the prevalence of 2 common disorders, 3β-hydroxy-Δ-C27-steroid dehydrogenase (3β-HSD) and Δ-3-oxosteroid-5β-reductase (Δ-3-oxoR) deficiencies and to describe current diagnostic and treatment strategies among different European paediatric hepatology centres., Methods: A total of 52 clinical paediatric centres were approached and 39 centres in 21 countries agreed to participate in the Web-based survey. The survey comprised questions regarding general information, number of cases, diagnostic, and therapeutic management., Results: Seventeen centres located in 11 countries reported patients with inborn errors in primary BA synthesis, 22 centres never had cases diagnosed. In total, we could identify 63 patients; 55 with 3β-HSD and 8 with Δ-3-oxoR deficiency in 21 countries. The minimum estimated combined prevalence of these diseases was 1.13 cases per 10 million (0.99 and 0.14 for 3β-HSD and Δ-3-oxoR deficiencies, respectively). The surveyed colleagues indicated their main challenges to be the rarity of diseases and the lack of convenient laboratory facilities nearby., Conclusion: We have identified the largest cohort of patients with 3β-HSD or Δ-3-oxoR deficiency described so far. These diseases are likely underdiagnosed mainly due to unawareness of their existence and the lack of laboratory facilities. more...

Objectives: Angiogenic defects secondary to gene mutations of JAG1 and NOTCH2, causing arterial anomalies in Alagille syndrome (AGS), are well described in the literature. The study analyzes the frequency of abdominal arterial anomalies in children with AGS with an emphasis on outcomes following liver transplantation (LT)., Methods: Between 1988 and 2013, 242 children with AGS were treated at our institution. We performed a retrospective analysis of 55 who underwent LT during the study period. Preoperative abdominal arterial findings, operative reports, arterial reconstruction technique, and early as well as late complications following LT were reviewed specifically focusing on arterial thrombosis., Results: Twenty-five patients had preoperative imaging available for analysis. Twelve of these patients showed celiac trunk stenosis (48.0%), 2, a superior mesenteric artery stenosis (8.0%) and one a stenosis of both renal arteries. Twenty patients (36.3%) underwent standard hepatic reconstruction using the native recipient hepatic artery. Thirty-five patients (63.7%) underwent aortic conduit reconstruction (ACR) from the infrarenal aorta using donor arterial conduits. Hepatic artery thrombosis occurred in 9 patients (16.3%). This number was higher in the standard arterial anastomosis group 7/20 (35.0%) than in those with ACR 2/35 (5.7%, P = 0.0079)., Conclusions: In this series, children with AGS pretransplant have a high prevalence of abdominal arterial anomalies. Preoperative abdominal vascular imaging makes it possible to anticipate whether or not a classical arterial revascularization can be performed or whether an ACR is required. more...

Objectives: Pruritus is a severe symptom accompanying chronic cholestasis. It can be debilitating and difficult to control. In children, first-line treatments are ursodeoxycholic acid and rifampicin. Refractory pruritus may require invasive therapies including liver transplantation. Clinical trials based on small samples of adult patients suggest that serotonin reuptake inhibitors can improve pruritus in cholestatic or uremic disease. We performed a prospective, multicenter study to assess efficiency and safety of the serotonin reuptake inhibitor sertraline in treating children with refractory cholestatic pruritus., Methods: Twenty children experiencing refractory cholestatic pruritus related to Alagille syndrome or progressive familial intrahepatic cholestasis were included from 4 centers between 2007 and 2014, and treated with sertraline at a starting dose of 1 mg · kg · day and thereafter individually adapted up to 4 mg · kg · day. Before and after 3 months with therapy, pruritus was assessed using a visual itching scale graded on 10 points, a skin scratch marks score and a sleeping impairment score., Results: Sertraline was prescribed at a median daily dose of 2.2 mg · kg · day. After 3 months, pruritus improved in 14 out of 20 treated patients, and the median itching score decreased significantly from 8/10 (5-10) to 5/10 (2-10). Likewise, skin scratch marks and sleep quality improved in 9 of these 14 patients. Nonsevere adverse events were reported in 6 children, leading to treatment discontinuation in 3., Conclusion: Our data suggest that sertraline may constitute a useful drug in the management of refractory cholestatic pruritus in children. more...

Objectives: D-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe to provide an orally bioavailable source of vitamin E in children with cholestasis. The aim was to analyze the safety/efficacy of Vedrop in a large group of children with chronic cholestasis., Methods: Two hundred seventy-four children receiving Vedrop for vitamin E deficiency or for its prophylaxis were included from 7 European centers. Median age at treatment onset was 2 months and median follow-up was 11 months. Vedrop was prescribed at a daily dose of 0.34 mL/kg (25 IU/kg) of body weight. Three methods were used to determine a sufficient serum vitamin E status: vitamin E, vitamin E/(total cholesterol), vitamin E/(total cholesterol + triglycerides)., Results: Before Vedrop therapy, 51% of children had proven vitamin E deficiency, 30% had normal vitamin E status and 19% had an unknown vitamin E status. During the first months of treatment, vitamin E status was restored in the majority of children with insufficient levels at baseline (89% had a normal status at 6 months). All children with a normal baseline vitamin E status had a normal vitamin E status at 6 months. Among children with an unknown vitamin E status at baseline, 93% had a normal vitamin E status at 6 months. A sufficient vitamin E status was observed in 80% of children with significant cholestasis (serum total bilirubin >34.2 μmol/L). No serious adverse reaction was reported., Conclusions: Vedrop seems a safe and effective oral formulation of vitamin E that restores and/or maintains sufficient serum vitamin E level in the majority of children with cholestasis, avoiding the need for intramuscular vitamin E injections. more...

Objective: Pruritus is a common symptom of cholestatic liver disorders. The present study aimed at evaluating autotaxin (ATX), a lysophospholipase recently identified as potential cause for cholestatic pruritus, in pediatric cholestatic diseases presenting with or without itching., Methods: A cohort of 45 children consisting of 14 patients experiencing itching (Alagille syndrome [n = 10], complete extrahepatic biliary atresia [n = 2], neonatal sclerosing cholangitis (n = 1), progressive familial intrahepatic cholestasis type 2 [n = 1]), 9 patients with bile acid synthesis defects (3β-hydroxy-C27-steroid-oxidoreductase [n = 7] and Δ-3-oxosteroid-5β-reductase deficiency [n = 2]), and 22 healthy children were studied. Serum ATX activity and total serum bile salt were determined enzymatically, ATX protein content was semiquantified by Western blotting. Using real-time polymerase chain reaction, ATX mRNA expression was studied in HepG2 cells treated with farnesoid-X-receptor agonists or vehicle., Results: Serum ATX activity was increased in pruritic children with Alagille and other cholestatic syndromes (mean ± standard deviation: 16.1 ± 4.3 nmol · mL · min) compared with children with nonpruritic cholestatic diseases with bile acid synthesis defects (10.4 ± 4.7 nmol · mL · min; P < 0.01) and healthy controls (7.6 ± 2.3 nmol · mL · min; P < 0.001). ATX protein levels closely correlated with serum ATX activity. Serum ATX activity and total serum bile salt showed a linear correlation with itch intensity (r = 0.66, P < 0.001 and r = 0.80, P < 0.001, respectively). No correlation was observed between ATX activity and bilirubin. ATX mRNA expression in HepG2 cells was not induced by farnesoid-X-receptor ligands., Conclusions: Serum ATX activity correlated with itch intensity in children with cholestatic diseases. Bile salts did not increase ATX expression in vitro. ATX inhibitors may be useful antipruritic agents in pediatric cholestatic disorders. more...

Objective: Portopulmonary hypertension (POPH) is a known complication of cirrhosis in adults, but there is little information on its incidence and outcome in children with liver disease. We report 14 patients with POPH and present a synthesis of the medical literature., Methods: Diagnosis of POPH in the 14 patients was based on right-sided heart catheterization displaying mean pulmonary artery pressure (mPAP) >25 mmHg, indexed pulmonary vascular resistances >3 Wood units · m, and pulmonary wedge pressure <15 mmHg. A literature review added 84 patients., Results: In our unit, POPH was found in 0.5% of the children with portal hypertension, 0.9% of the children with end-stage liver disease awaiting transplantation, and 3 children with congenital portosystemic shunts (CPSSs). Analysis of 98 reported patients, including the 14 presented here, showed the cause of liver disease to be chronic liver disease or portal cavernoma in 76 instances (34 with a history of surgical portosystemic shunt) and CPSS in 22 instances. There was a precession with proven hypoxemia caused by hepatopulmonary syndrome in 6 patients. Median survival was 3 months in 56 untreated patients. An 80% 5-year probability of survival in 42 patients was treated by CPSS closure, pulmonary vasodilators, and/or liver transplantation. Mean pretransplant mPAP was 34 and 49 mmHg in transplant survivors and nonsurvivors, respectively., Conclusions: POPH is a rare but extremely severe complication of childhood liver disease. Portosystemic shunts, whether congenital or acquired, likely play an important causative role. Early diagnosis is crucial and requires systematic screening by echocardiography in children at risk. more...

Objectives: Biliary atresia carries a risk of bleeding because of portal hypertension. Our goal was to define the factors associated with the emergence of endoscopic signs carrying a high risk of bleeding in children who did not display these signs at the first upper gastrointestinal endoscopy., Methods: From 1989 to 2013, a total of 225 children with low-risk signs at the first endoscopic examination underwent ≥2 upper gastrointestinal endoscopic examinations. The emergence of high-risk gastroesophageal varices was observed in 76 children in the 10 years following the first endoscopic examination. A survival study using the occurrence of high-risk varices as an event was performed to identify factors related to the emergence of these varices and to describe the probability of their emergence in 2 groups of children ages older than 18 months and 18 months or younger at the time of the first endoscopy., Results: High total serum bilirubin concentration, young age, and high number/grade of esophageal varices at the first endoscopy were significantly related to the emergence of high-risk varices. The probability of the emergence of high-risk signs was higher and these signs appeared faster in infants 12 months of age or younger and/or when the first endoscopic examination displayed >1 grade 1 or grade 2 varices. Progression to high-risk varices was also related to bilirubinemia in children older than 18 months at the first endoscopy., Conclusions: The results allow defining a program of repeat endoscopies to detect high-risk varices and to discuss endoscopic primary prophylaxis of bleeding or hasten liver transplantation when these signs are found. more...

A diagnosis of acute lymphoblastic or myeloblastic leukemia was made in 6 children ages 4 to 14 years who presented with a clinicobiochemical picture of acute hepatitis without liver failure. Standard chemotherapy, including 1 week pretreatment with steroids in children with lymphoblastic leukemia, allowed complete remission of the leukemia and normalization of serum liver tests. more...

Multiple respiratory chain deficiencies represent a common cause of mitochondrial diseases and often result in hepatic failure. There is no gold-standard test for diagnosing mitochondrial disease, and the current diagnosis relies on establishing a consistent pattern of evidence from clinical data, neuroimaging, tissue biopsy, and biochemical investigations. In some patients, the mitochondrial respiratory chain defect (MRCD) diagnosis is confirmed by genetic investigations. In most cases, genetic investigations are not informative and a number of cases remain unexplained.Here, we report on two children presenting with liver disease in whom first investigations suggested MRCD, due to decreased liver respiratory chain activities and decreased mitochondrial DNA copy number. However, sequencing of the genes known to be associated with mitochondrial DNA instability did not identify any pathogenic mutations. Further investigations including exome analysis, biliary bile salt analysis, and/or BSEP immunostaining detected a defect in the bile salt export pump (BSEP). Diagnosis of progressive familial intrahepatic cholestasis type 2 (PFIC2), a hereditary disorder in bile formation due to BSEP deficiency was confirmed by ABCB11 gene sequencing. Deleterious mutations were identified in both patients: one harboring compound heterozygous mutations (p.Arg470*/c.1308+2T>A) and the other homozygous nonsense mutation (p.Tyr354*). This report increases awareness of a possible secondary mitochondrial respiratory chain defect in the liver tissue associated with other underlying causes such as PFIC2. more...

Combined respiratory chain defect is a common feature in mitochondrial liver disease during early infancy. Mitochondrial DNA depletions, induced by mutations of the nuclear genes POLG, DGUOK, and MPV17, are the major causes of these combined deficiencies. More recently, mutations in TRMU gene encoding the mitochondrial tRNA-specific 2-thiouridylase were found in infantile hepatopathy related to mitochondrial translation defect. It is characterized by a combined defect of respiratory chain complexes without mitochondrial DNA depletion.We report here clinical, biochemical, and genetic findings from three unrelated children presenting with hepatopathy associated with hyperlactatemia and respiratory chain defect due to bi-allelic mutations in TRMU gene. Two patients recovered spontaneously in a few months, whereas the other one died of acute liver failure. Spontaneous remission is a rare feature in mitochondrial liver diseases, and early identification of TRMU mutations could impact on clinical management. Our results extend the small number of TRMU mutations reported in mitochondrial liver disorders and allowed accumulating data for genotype-phenotype correlation. more...

Objectives: Liver hemangiomas are vascular tumors, which occur in the first months of life and carry risks of initial complications, but are considered to be benign histologically and to regress with time. Histologic studies suggest that a subtype, type 2 hemangioendothelioma, is akin to angiosarcoma and may have a severe long-term prognosis. We report 5 girls with type 2 hemangioendothelioma of the liver., Methods and Results: Three children initially presented with classical infantile multinodular hemangioma, including cardiac and pulmonary complications and regression of tumors at age 1½ to 2½ years. All 3 experienced tumor relapse at ages 2½ to 3, leading to death at ages 2½ to 5. Tumor histology showed type 2 hemangioendothelioma. The other 2 children presented with liver tumors at ages 2 and 3 years. In 1, initial biopsy of a single tumor showed benign type 1 hemangioendothelioma, but surgical resection was followed by relapse in the remaining liver, lung metastases, and death. Whole tumor histology showed both type 1 and 2 lesions. In the other child, tumor biopsy showed type 2 lesions. She underwent liver transplantation and is alive without tumor recurrence 3 years later., Conclusions: Careful follow-up is necessary to detect late recurrence in infants with multinodular liver hemangiomas. Vascular liver tumors occurring after infancy are likely to be malignant. The high risk of relapse in the remaining liver suggests that if no metastases are detected, liver transplantation is preferable to surgical tumor resection in both situations. more...

Background and Objective: Congenital portosystemic shunts are rare vascular malformations that lead to severe complications. Their management is controversial. The aim of this study was to propose a clear definition of the risks and management of congenital portosystemic shunts in children according to our experience and a review of the literature., Patients and Methods: Twenty-two children with a complicated congenital portosystemic shunt were studied in our institution. When necessary, management included portal pressure measurement and portal vein angiography during an occlusion test and closure of the shunt by surgical and/or endovascular methods., Results: Five neonates with intrahepatic shunts presented with cholestasis that resolved spontaneously, and 17 older children presented with liver tumors (13) and/or hepatopulmonary syndrome (2), pulmonary artery hypertension (3), portosystemic encephalopathy (3), heart failure (1), and glomerulonephritis (1). The portosystemic shunt was extrahepatic (11) or intrahepatic (6). Portosystemic shunts were closed by endovascular methods in 5 children and surgically in 10, 4 of whom had portal pressure during occlusion above 35 mmHg and extremely hypoplastic or undetectable portal veins requiring banding of the fistula before closure. Shunt closure resulted in restoration of intrahepatic portal flow in all, with complete or partial regression of benign liver masses, and regression or stabilization of pulmonary, cardiac, neurological, and renal complications., Conclusions: Congenital portosystemic shunt carries risks of severe complications in children. Closure of a shunt persisting after age 2 years should be considered preventively. Intrahepatic portal flux restoration can be expected, even when intrahepatic portal veins are extremely hypoplastic or undetectable. more...

The present report describes AIRE gene analysis in 25 children with autoimmune hepatitis type I or II. The heterozygous transversion c.961C > G (p.Ser278Arg) located in exon 7 was identified in 4 patients with autoimmune hepatitis type I, and mostly in those presenting with a positive family history for autoimmune diseases. In this subgroup of patients, the allelic frequency of this polymorphic variant was at least 3-fold higher than in healthy controls. These results suggest that heterozygous AIRE gene mutation may represent a genetic predisposition to childhood autoimmune hepatitis type I. more...

Objectives: To investigate the effect of ursodeoxycholic acid (UDCA) in children with liver disease associated with ZZ alpha1-antitrypsin (AAT) deficiency., Patients and Methods: A total of 42 affected children received UDCA (30 mg x kg x day(-1)) and underwent clinical and biochemical follow-up at least yearly., Results: In group 1, 22 children whose mean initial gamma-glutamyl-transpeptidase (GGT) was 7.4 x N normalized serum liver test results after a mean treatment of 2.6 years. In 16 of these children, UDCA was discontinued. Relapse was observed in 11 children, and liver test results returned to normal after UDCA resumption. In the other 5 children, liver test results remained normal during a mean period of 2.5 years. In group 2, 11 children (mean initial GGT 12.8 x N) had improved liver test results after a mean treatment of 2.3 years. In group 3, 9 children (mean initial GGT 33.8 x N) had no liver test result improvement and evolution toward cirrhosis, requiring liver transplantation in 7. Most of the children in group 1 had normal results of clinical examination after UDCA treatment, versus none in group 3 (P < or = 0.00001). Initial GGT (P < or = 0.002) and total bilirubin (P < or = 0.05) levels were significantly lower in group 1 than in group 3. Combined initial values of GGT < or =5.5 x N and total bilirubin < or =66 micromol/L were associated with normalization of liver test results in 90% of children., Conclusions: UDCA may significantly improve clinical status and liver test results in some children with liver disease associated with ZZ AAT deficiency. No beneficial effect of UDCA was shown in children with the most severe liver involvement. Initial levels of GGT and total bilirubin may be of prognostic value for therapy effectiveness. more...