To evaluate the safety and efficacy of Vitamin E in children with chronic hepatitis B.
We randomly assigned patients with chronic hepatitis B, positive for hepatitis B e antigen (HBeAg), to receive ...either Vitamin E or placebo once daily for 6 mo in a 3:1 ratio and double-blind manner. The primary end point was HBeAg seroconversion, defined as the loss of HBeAg, undetectable levels of serum hepatitis B virus DNA, and the appearance of antibodies against HBeAg 12 mo after therapy.
At baseline visit, 49 patients had normal and 43 had increased serum aminotransferase levels. Twenty-nine patients did not respond to previous treatment with interferon-alpha or lamivudine. Seventy-six children completed the study; 16 were non-compliant (n = 7), lost to follow-up (n = 7), or started another antiviral treatment (n = 3). Intention-to-treat analysis showed HBeAg seroconversion in 16 children (23.2%) treated with Vitamin E and two (8.7%) in the placebo group (P = 0.13). Vitamin E was well tolerated.
There is only a tendency that Vitamin E may promote HBeAg seroconversion. Therefore larger studies are needed to clarify the role of antioxidants in the therapy of chronic hepatitis B.
Studies in adults characterized the role of the pregnane X receptor (PXR) in the pathophysiology of inflammatory bowel disease (IBD) with conflicting results; pediatric studies are still lacking.
...Genotyping for the -25385C/T polymorphism of the PXR gene in 187 white children with IBD and 185 controls. Determination of colonic PXR expression in selected patients with IBD.
Minor allele frequency was seen in 35.6% patients with IBD and 40.5% controls (P = 0.174), although no significant differences were seen between the genotypes (P = 0.366). PXR was underexpressed in colonic tissue of 7 out of 11 Crohn disease and in 4 out of 5 patients with ulcerative colitis.
We could not confirm an association of the -25385C/T polymorphism in pediatric patients with IBD.
Molecular Adsorbents Recirculating System (MARS)-mini has recently been approved and applied in children with hepatic failure. However, its indication, efficacy and capability to induce liver ...regeneration remain unclear. The aim of our pilot study in children was to analyse the impact of MARS on markers of detoxification and regeneration.
In children with fulminant Wilson's disease and bridged with MARSmini for liver transplantation, we analyzed toxic metabolites (bile acids, bilirubin, lactate, ammonia, tryptophan and copper), regulators of the inflammatory cascade nitrate, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), methionine, cystine and hyaluronic acid and hepatic growth factors hepatocyte growth factor (HGF), epidermal growth factor (EGF), transforming growth factor-beta1 (TGF-beta1), cortisol, corticosteroid-binding globulin (CBG), insulin-like growth factor-1 (IGF-1), angiogenin, vascular endothelial growth factor (VEGF), IL-6 and TNF-alpha from blood, albumin circuit and haemodialysate from four applications.
In all four applications, transfer of toxic metabolites (6/6) and inflammatory mediators (6/6), but also of hepatic growth factors (9/10), into the albumin circuit of MARS was consistently detected. Corresponding blood levels were decreased for 3/6 metabolites, 3/6 inflammatory mediators and 1/10 growth factors and increased for 1/10 growth factors. Bridging for liver transplantation was successful with MARS.
In our prospective study, substantial extraction of albumin-bound and water-soluble candidate substances was detected with variable effect on respective blood levels. Notably, essential factors inducing liver regeneration were simultaneously removed. These data provide a basis for evaluation of liver restoration and efficacy of liver support in children with liver failure to devise a collaborative, multicentre trial.
In 1995, a new flavivirus, GBV-C/HGV was identified. Little information is available on the clinical manifestations and epidemiology of GBV-C/HGV infection. We investigated the risk of ...mother-to-infant transmission in a group of GBV-C/HGV RNA positive women and followed up the GBV-C/HGV infected babies.
Twenty-eight anti-HCV positive women, of whom 25 have been intravenous drug users, and their children were included in the study. RNA was extracted from serum, reverse transcribed and amplified with primers from the NS5 region of GBV-C/HGV and 5'-UTR of HCV in a nested polymerase chain reaction. Amplified DNA fragments were gel purified and sequenced; the sequences obtained were subjected to a phylogenetic analysis.
Transmission of GBV-C/HGV occurred in 10 (56%) of 18 infants born to GBV-C/HGV positive mothers; all these women were drug abusers. Only one (5%) of 19 babies whose mothers were HCV RNA positive by polymerase chain reaction, was infected with HCV during the follow up. High sequence homology in the NS5 region of GBV-C/HGV isolates in 10 mother-child pairs suggested mother-to-infant transmission. All 10 babies remained GBV-C/HGV RNA positive during follow up (2-12 months). None of the GBV-C/HGV infected infants became icteric or demonstrated any clinical or biochemical signs of liver disease.
Mother-to-infant transmission of GBV-C/HGV may be high, at least in HCV-infected, drug-addicted women. In GBV-C/HGV RNA positive infants the rate of GBV-C/HGV persistent infection is high, but the infection is not accompanied by any symptoms of liver disease.
Auxiliary liver transplantation offers an alternative method to conventional transplantation in acute liver failure. It is especially challenging for children because lifelong immunosuppression may ...be avoided. However, experience with this procedure is rare and there is controversy about whether to place the graft orthotopically or heterotopically.
We present the case of a 3-year-old boy with acute liver failure due to non-ABC hepatitis complicated by aplastic anemia who underwent auxiliary liver transplantation. Segments 2 and 3 of the graft were implanted heterotopically in the right lower abdomen.
Good liver function was immediately restored. Aplastic anemia resolved 3 weeks after transplantation. Immunosuppressive therapy was discontinued after 14 months, and the graft was left to atrophy. Thirty-nine months after transplantation the boy is alive and well with normal liver function tests and normal blood cell counts.
Heterotopic auxiliary liver transplantation allowed recovery of the native liver in a child with acute liver failure and aplastic anemia due to non-ABC hepatitis.
Hereditary hemorrhagic telangiectasia (HHT) and familial juvenile polyposis (EJP) are two rare autosomal dominant disorders, Genetic heterogeneity has been shown for HHT and is likely for FJP as ...well. This paper describes the coexistence of both diseases in a girl and her father in addition to twelve members of five families and two sporadic cases reported in the literature. This implies a new phenotype which may be important in elucidating the underlying genetics in HHT and FJP. Clinical diagnosis of one disease should induce screening for symptoms of the other.
In three children with chronic liver disease of different aetiology without obvious hepatic encephalopathy, bilateral and symmetrical hyperintensity of the globus pallidus in T1-weighted images was ...found on cranial MRI. Reversibility was shown in one child with autoimmune hepatitis after normalisation of liver function tests under immunosuppressive therapy.
As central nervous system involvement in liver disease is only partially understood, brain imaging by MRI offers a potential additional tool to further elucidate the incidence and time course of previously undetected brain alterations.
The main problem of children with HBeAg positive hepatitis B and associated hepatitis D is progression to liver cirrhosis with decompensation of liver function and need for liver replacement therapy ...within 15-20 years after infection. To determine whether interferon-alpha (IFN-alpha) therapy has a positive effect on HBV replication and inflammatory activity, we evaluated clinical and serological data of 8 children treated with IFN-alpha and 6 historic control patients without treatment. 4 of the nontreated patients seroconverted from HBeAg to anti-HBe between 7 to 17 years after initial diagnosis and showed decreased inflammatory activity in the liver. In the treatment group, the rate of seroconversion to anti-HBe (3 early, 2 late seroconverters) corresponded well to former trial results obtained in patients exclusively infected by HBV. Serum aminotransferase levels decreased or normalized in seroconverted children. In chronic HBV infection with associated hepatitis D (HDV) infection--compared to the spontaneous course of the disease--IFN-alpha therapy reduced inflammatory activity by earlier seroconversion to anti-HBe in responding patients. Moreover, viral replication and infectivity of hepatitis B was markedly reduced, but no effect on replication of HDV could be documented. Although long-term effects cannot be exactly estimated, at present IFN-alpha remains the only available treatment for HBeAg and anti-HDV positive children and seems to be of benefit for responding patients.
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