Liver Transplantation in Polish Children With α1-Antitrypsin Deficiency: A Single-Center Experience.

BACKGROUND: α1-Antitrypsin deficiency (ATD) is the most common genetic cause of liver injury in young children. Asymptomatic hepatitis is observed in most patients. However, the course of liver disease due to ATD is unpredictable, and some children develop liver cirrhosis. Liver transplantation (Ltx) dramatically improves their outcome and in some cases is required in the first years of life. The aim of the study was to evaluate the course of the disease in children with ATD treated with Ltx in a single center. METHODS: We retrospectively reviewed the clinical features (ascites, esophageal varices, esophageal bleeding) and laboratory parameters of liver function in children with ATD who were treated with Ltx. RESULTS: Twenty-two Ltxs were performed in 20 children (13 boys, 7 girls). Median age at transplantation was 12 years (range 0.5 to 17.1). Four children were transplanted in the first 2 years of life and 16 patients were over 7 years old. The indications for Ltx in younger children were progressive cholestasis with coagulopathy and ascites. In older patients, the indications were as follows: liver failure presenting with variceal bleeding in 7 patients, ascites in 5 patients, hypersplenism in all but 1 patient. In the group of children transplanted over 7 years old, the frequency of cholestasis decreased intermittently in the second year of life: 4 patients (25%) compared to 15 patients (94%) and 10 patients (63%) in the neonatal and pretransplant period, respectively. In the group of children transplanted earlier, cholestasis and hepatitis were maintained until Ltx. Of transplanted patients, 50% were malnourished at the transplantation, and 50% were followed for more than 10 years. Five-year post-transplant survival was 100% (n = 14), and 10-year survival was 90%. Two patients died as adults with biliary post-transplant complications and problems with compliance. CONCLUSIONS: Our experience suggests that transient normalization of liver parameters in some patients with ATD do not exclude the liver disease progression to cirrhosis and unfavorable outcome of liver disease in childhood. In our group of patients, median age at transplantation was high compared to other centers. The long-term prognosis in children after transplantation is very good, but early post-transplant complications and probable problems with compliance in young adults may lead to graft failure.

Liver transplantation for severe hepatic graft-versus-host disease in two children after hematopoietic stem cell transplantation.

Chronic graft-versus-host disease (GVHD) is a frequent complication of bone marrow transplantation (BMT). After the skin, the liver is the second, most frequent target of GVHD, which presenting with hyperbilirubinemia, elevated liver enzymes, and coagulopathy. Progressive destruction of small intrahepatic bile ducts causes vanishing bile duct syndrome and leads to end-stage liver disease. We report 2 successful cases of orthotopic liver transplantation performed in children with severe GVHD after hematopoietic stem cell transplantation from a matched unrelated donor (HSCT-MUD).

Good and bad prognosis of alpha-1-antitrypsin deficiency in children: when to list for liver transplantation.

Alpha1-antitrypsin deficiency (alpha1-ATD) is a genetic disorder that may predispose to chronic liver disease. The clinical manifestations and prognosis of this disorder are variable. The aim of the study was to evaluate the clinical presentation and liver tests in two groups of children with alpha1-ATD: those with a good prognosis who survived long term with their native liver, and those with a bad one, requiring liver transplantation (OLT) or dying before OLT. We studied 59 children homozygous for alpha1-ATD admitted to our hospital with cholestasis or chronic hepatitis since infancy. Patients without liver transplantation were regarded to be the good prognosis group I (n=45). In contrast the 11 children who required liver transplantation and the three who died before OLT were the bad prognosis cohort (Group II, n=14). We analyzed the laboratory parameters of cholestasis, hepatitis, and liver insufficiency in both groups. In the group with a good prognosis, eight children still suffered from cholestasis at the ages of 9 to 14 years while nine had hepatitis at the ages of 9 to 14 years. We observed a temporarily increased international normalized ratio (1.2 to 1.5) in eight subjects at the ages of 1 month to 17 years, and slight hypoalbuminemia (30 to 35 mg/dL) in nine children at the ages of 1 month to 10 years. OLT was performed in 11 children at the ages of 10 to 17 years. Our center's experience suggested that in the PiZZ patients with portal hypertension, esophageal varices, or deterioration of hepatic function, liver transplantation should not be delayed.

Effect of Lactobacillus casei DN-114001 application on the activity of fecal enzymes in children after liver transplantation.

Immunosuppressive and antibacterial regimens in children after liver transplantation create a gut microflora imbalance that can be indirectly measured by the activity of fecal enzymes. The aim of this study was to specify the influence of diet supplementation with probiotic Lactobacillus casei DN on the activity of beta-glucuronidase, beta-glucosidase, and urease. Twenty-five children after liver transplantation (13 girls, 12 boys) ages 3 to 17 years were enrolled in the study. Two months after bacteria application the levels of all 3 enzymes decreased, reaching statistical significance for beta-glucuronidase and beta-glucosidase. Complete rebound in enzyme activity was observed months after the end of probiotic supplementation. We concluded that Lactobacillus casei DN-114001 consumption decreased fecal enzyme activity, a beneficial effect limited to the period of bacteria intake.

Prevention of de novo hepatitis B virus infection by vaccination and high hepatitis B surface antibodies level in children receiving hepatitis B virus core antibody-positive living related donor liver: case reports.

Transmission of hepatitis B virus (HBV) infection from donors negative for hepatitis B surface antigen (HBsAg) but positive for antibody to hepatitis B core antigen (anti-HBc) have been reported. The aim of our study was to evaluate the outcomes of recipients who received liver grafts from living related donors with serological evidence of previous exposure to hepatitis B virus (HBsAg-negative/anti-HBc-positive) after recipient vaccination against HBV before and after liver transplantation.

Lipid, carbohydrate metabolism, and antioxidant status in children after liver transplantation.

Organ transplantation is a risk factor for atherogenesis that may be related to immunosuppressive therapy. Increased free radical generation may even aggravate atherogenesis. The aim of the study was to assess lipid metabolism in relation to risk factors for atherogenesis as well as carbohydrate metabolism and antioxidant status among children after liver transplantation. We studied 35 children at 3 to 5 years after liver transplant in whom the following parameters were assessed: total cholesterol; triglyceride; high-density lipoprotein cholesterol; low-density lipoprotein cholesterol (LDL-C); very low-density lipoprotein cholesterol; apolipoproteins B, AI, E, lipoprotein (a); vitamin E; glutathione; glucose; insulin; and glutathione peroxidase activity. Three subgroups of patients were assessed according to the immunosuppressive therapy: cyclosporine (CsA), tacrolimus (Tac), or mycophenolate mofetil (MMF) in combination with low-dose CsA or Tac. We observed differences among the subgroups only in total cholesterol (CsA: 131.6 to 285.6; Tac: 144.0 to 181.61; MMF: 132.1 to 181.2) and LDL-C (CsA: 79.4 to 126.9; Tac: 42.2 to 118.8; MMF: 74.2 to 117.3). Lipid metabolism was not significantly disturbed among children after liver transplantation, an observation that does not point to a high risk of atherogenesis. CsA seems to have the strongest untoward effect on cholesterol metabolism. Decreased GSH concentration after liver transplantation may be related to slightly impaired liver function, but GPx activity and vitamin E concentrations remained normal.

Beneficial effect of liver transplantation on bone mineral density in small infants with cholestasis.

Reports of bone mineral density in children after liver transplantation are few. Eleven cholestatic children were analyzed before and 6 months after liver transplantation. No changes in serum levels of calcium, alkaline phosphates, or 25OHD were observed before versus after LTx. The serum levels of phosphorus and 1-25(OH)2D3 as well as total bone mass density and Cole index were significantly increased after liver transplantation.

Autoimmune hepatitis in transplanted liver.

Liver transplantation is recognized as the appropriate treatment for end-stage liver disease. Four patients undergoing liver transplantation for classical end-stage liver disease developed de novo autoimmune hepatitis (AIH) in the graft. Recurrence of AIH after orthotopic liver transplantation and after reduction in immunosuppressive treatment is reported in one other patient. Markedly elevated serum transaminases were observed, together with an elevated serum IgG and/or globulin fraction and histological feature typical of AIH on liver biopsy.

Absence of teratogenicity of sirolimus used during early pregnancy in a liver transplant recipient.

We describe the case of successful delivery in a 21-year-old woman who became pregnant 3 years after liver transplantation and who received sirolimus during the first 6 weeks of gestation. Sirolimus was discontinued when ultrasonography revealed a pregnancy, she was switched to tacrolimus and prednisone was continued. The course of pregnancy was uneventful; there were no signs or symptoms of graft rejection. Due to fetal intrauterine threatening asphyxia the pregnancy was concluded by cesarean section in the 39th gestational week, delivering a healthy, 2950 g, Apgar 10, female infant.

Reduction of naive CD4/CD45RA+ T cells in children with biliary atresia before and after liver transplantation.

The aim of this study was to examine whether liver transplantation reverses the abnormal distribution of lymphocyte subsets previously observed in biliary atresia children, namely a selective decrease in the naive CD4/CD45RA+ T cell subset and an increase in the B and natural killer cell subpopulations. Eight biliary atresia children aged 1.08 to 6 years were studied before and 1 year after LTx for comparison with 15 age-matched healthy controls. The posttransplant immunosuppressive regimens included prednisone [0.1 mg/kg] and tacrolimus (level range: a 10-12 microg/dL). The percentage, absolute cell number, and receptor density were assessed by the use of double color flow cytometry (EPICS-XL MCL fluorocytometer). Biliary atresia patients were compared after LTx with subjects before LTx, essentially showing no statistically significant changes in lymphocyte subsets. We conclude that LTx of biliary atresia children does not reverse the abnormal lymphocyte subset distribution present before transplantation. Hence, these changes may reflect either their independence from the liver status or may result from immunosuppressive treatment that contributes to defective CD4+ T cell regeneration reflected by a deficiency in CD4/CD45RA+ naive T cells.

Rapamycin in children after liver transplantation.

Experience with sirolimus (SRL) in pediatric liver transplantation (LTx) is limited. The aim of the study was to present our experience with SRL in this setting. During the last 2 years we administered SRL to 9 LTx: children in 3 due to chronic rejection and 6 due to impaired renal function. SRL was started at 2 months to 2.5 years after LTx. Target trough levels for tacrolimus for patients with chronic rejection was 8 to 10 ng/mL and SRL 10 to 12 ng/mL; for patients with impaired renal function, 4 to 6 ng/mL and 8 to 10 ng/mL respectively. For patients on only SRL and steroids the target level was 12 to 20 ng/mL. Our observation on SRL varied from 3 to 21 months, including liver function, renal function, and side effects. All patients are alive. In 3 patients with chronic rejection (ChR), follow-up biopsies showed no signs of ChR; they all normalized liver biochemistry. Independent of indication all improved their renal function. Follow-up GFR in 5 patients showed significant improvement in all. All patients showed elevated serum cholesterol values. SRL was discontinued in 3 patients due to elevation of liver enzymes in 1, persistently high serum cholesterol in 1, and repeated bouts of opportunistic infection in 1. Addition of SRL with reduced doses of tacrolimus or switching to SRL alone significantly improves renal function.

Switching cyclosporine blood concentration monitoring from C0 to C2 in children late after liver transplantation.

BACKGROUND: Measurement of cyclospoprine (CsA) blood levels at 2 hours after oral administration (C(2)) has been proposed as a better measurement of trough level (C(0)) due to reduced intrapatient variability, acute rejection rate and renal toxicity. The aim of the present study was to assess whether there was any advantage to conversion from C(0) to C(2) CsA blood level monitoring in children late after liver transplantation. We reviewed the data from 44 children more than 1 year after liver transplantation. We measured the daily dose of CsA and the C(0) level before switching versus the daily dose and C(2) level at 6 months after conversion, in addition to the alanine aminotransferase (ALT) activity, creatinine blood concentration, and episodes of acute rejection. RESULTS: Conversion from C(0) to C(2) monitoring was not associated with a significant change in mean daily dose of CsA, mean concentration of creatinine, ALT activity or occurrence of rejection episodes. CONCLUSION: Switching from C(0) to C(2) monitoring did not seem to proffer any benefits for children late after liver transplantation.

Hepatobiliary scanning in the diagnosis of biliary atresia.

Early diagnosis is vital in the neonatal cholestasis. The aim of this study was to assess the usefulness of hepatobiliary scanning in the diagnosis of biliary atresia. 33 hepatobiliary scannings performed in 30 children with cholestasis over the last two years were analysed. The mean age at the diagnosis was 6.6 weeks. The investigation was carried out with Multispect camera using intravenous infusion of 99mTc-MBrIDA. In 23 patients there was no passage of the radiolabelled substance into the intestinal tract. In 18 patients biliary atresia was diagnosed. One patient with a clinical suspicion of Alagille syndrome had two scannings performed at the interval of two weeks. In 1 child a common biliary tract cyst with total obstruction of extrahepatic biliary tree was diagnosed. In 18 children with biliary atresia the diagnosis was confirmed during the operation and Kasai procedure was performed. In 2 children the second scanning showed bile drainage. In 3 children intrahepatic cholestasis was diagnosed in addition to the bile passage failure. Hepatobiliary scanning in the diagnosis of neonatal cholestasis was characterised by high sensitivity (100%) but lower specificity (75%). In difficult cases the final diagnosis should be made on a basis of complex clinical, biochemical and radiological techniques and, if necessary, it should be verified by intraoperative cholangiography.

Scintiscanning in diagnostics of hepatopulmonary syndrome in children.

BACKGROUND: Arterial blood oxygenation disturbances accompanying liver cirrhosis are referred to as hepatopulmonary syndrome (HPS). HPS develops due to the formation of intrapulmonary arteriovenous shunts and dilatation of the vascular bed. The aim of the study was to assess the incidence of arteriovenous shunts in children with hepatic cirrhosis and HPS suspected on the basis of clinical signs, qualified for liver transplantation. MATERIAL AND METHODS: The study was carried out in a group of 21 children aged from 1.2 to 17.7 years (mean age 8.4); 8 girls and 13 boys. The patients were diagnosed as follows: biliary cirrhosis due to extrahepatic bile duct impatency--12, post-inflammatory liver cirrhosis due to infection with HVB--2, autoimmune hepatitis--2, fibrosis of the liver--2, alpha 1-antitrypsin deficiency--1, progressive familial intrahepatic cholestasis--1, cystic fibrosis--1. The presence of arteriovenous anastomoses in the lungs was detected by scintiscanning utilizing microspheres (albumin macroaggregates). Under physiologic conditions, technetium-labeled microspheres injected i.v. are accumulated in pulmonary capillaries. Radioactivity detected in other organs (kidneys, brain) indicates the presence of pathologic shunts omitting the alveoli. A percentage ratio of radioactivity detected in the brain to that present in the lungs serves as the index of blood flow through the anastomosis (SI--shunt index). According to Grimon, the mean SI value for healthy children amounts to 0.43%, the values ranging from 1% to 2% are regarded as borderline ones, and those above 2% allow unequivocal diagnosis of HPS. RESULTS: The SI values obtained in the study ranged from 0.06 to 51%. In 7 patients SI exceeded 1%, reaching 1.23% in one, and over 3% in the remaining 6 patients. No correlations were found either between SI value and the etiology of cirrhosis, or between the index and clinical condition of the patient assessed according to Child-Pugh scale. CONCLUSIONS: 1. Scintiscanning revealed the presence of arteriovenous shunts in the lungs of 6/21 (28.6%) investigated patients. 2. No correlation was found between the severity of HPS and the etiology and stage of the underlying disease.

[Esophageal achalasia in children (analysis of five cases)]. / Achlazja przelyku u dzieci (analiza pieciu przypadków).

Oesophageal achalasia is a disease of middle age and is only exceptionally observed in children. Five patients aged from 6.5 to 14 years were treated for this achalasia. Routine therapeutic method was repeated pneumatic dilatation of the cardia with a Rider-Moeller dilator. In all, 33 such procedures were carried out without complications. Very good results were obtained in 2 cases already after 3 dilatation procedures. The remaining 3 cases required surgical intervention: in 2 of them esophagomyotomy with antireflux operation was done with a very good result in one case and a good result in another case. The child not treated surgically (lack of parental consent) has still most signs of achalasia with body weight below the 3 centile and with recurrent respiratory infections. The follow-up is from 5 to 66 months.

Campylobacter pylori in upper digestive tract diseases in children.

Results of studies on the frequency of the occurrence of the bacteria, Campylobacter pylori, in the mucous membrane of the gastric antrum are presented in this paper. The study was carried out on 61 children treated for chronic abdominal pain. The diagnosis was established on the basis of flexible endoscopy and histology of antral biopsies. The presence of Campylobacter pylori was determined using the CLO-test. The positive CLO-test was obtained in 87.5% of children with gastritis, in 75% of children with duodenal ulcer and in only 17% of children from control group (p less than 0.001). Four-week therapy with De Nol eradicated Campylobacter pylori in 60% of treated children, and reduced infection in the next 25%. These bacteria seem to play an important role in the pathogenesis of chronic gastritis and peptic ulcer disease.