Peginterferon plus ribavirin is standard therapy for adults with chronic hepatitis C. As no data are available for children, the aim of the study was to evaluate the efficacy and tolerability of peginterferon alfa-2b in combination with ribavirin in chronically infected children. Genotypes, alanine aminotransferase levels, and different routes of viral transmission were considered. In an open-labeled, uncontrolled pilot study, 62 children and adolescents (range, 2-17 years) were treated with subcutaneous peginterferon alfa-2b at a dose of 1.5 g/kg body weight once per week plus oral ribavirin (15 mg/kg ؋ day) for 48 weeks. Sixty-one patients completed the study. Twenty-three children discontinued therapy after 6 months according to study protocol. P eginterferon alfa and ribavirin is established as standard treatment in adults with chronic hepatitis C (HCV). International studies have yielded sustained viral response rates (SVR) between 44% and 75% according to the genotype. 1,2 Whereas interferon alfa-2b and ribavirin has been approved for individuals between 3 and 18 years of age in the United States, the indication for therapy in children and adolescents is still debated in many countries. One reason may be that ribavirin has teratogenic or embryocidal effects in animals. The risk of ribavirin as a carcinogen in humans has not been established. For more than 20 years, the substance has been used in infants for other indications, such as respiratory syncytial virus infection.The usage of peginterferon has improved response rates in adults by approximately 10% compared with a treatment regimen with interferon-alfa and ribavirin. Moreover, dosing of peginterferon once per week is another considerable advantage. No treatment study with peginterferon-alfa and ribavirin in children and adolescents with chronic HCV has been published so far.Chronic HCV in childhood features particular issues regarding mode of infection, immunological competence, and inflammatory activity. Vertical infection is the most important route of viral transmission. 3 These children are infected at a phase of high immune tolerance. A considerable number of young individuals display normal aminotransferases, reflecting a low inflammatory activity. Despite a relatively low disease progression during the first 15 to 20 years of life, severe liver disease occasionally occurs during childhood. In vertically infected patients, long-term spontaneous clearance of chronic HCV is low, SVR, sustained viral response; HCV RNA, hepatitis C virus ribonucleic acid; ALT, alanine aminotransferase. From the

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Recently, an Ile93Met substitution has been identified in the ubiquitin carboxy-terminal hydrolase L1 (UCHL1) gene in a single German PD family with autosomal dominant inheritance. To determine whether mutations in the UCHL1 gene are causative for Parkinson's disease (PD) a detailed mutation analysis was performed in a large sample of German sporadic and familial PD patients. We found no disease-causing mutation in the coding region of the UCHL1 gene. Direct sequencing revealed six intronic polymorphisms in the UCHL1 gene. Analysis of an S18Y polymorphism in exon 3 of the UCHL1 gene in sporadic PD patients and controls showed carriers of allele 2 (tyrosine) significantly less frequent in patients with a reduced risk of 0.57 (CI = 0.36-0.88; p = 0.012, p(c) = 0.047, chi2 = 6.31). Our study shows that sequence variations in the coding region of UCHL1 are a rare event. A protective effect of a certain UCHL1 variant in the pathogenesis of sporadic PD is suggested, underlining the relevance of UCHL1 in neurodegeneration.

Background & Aims NK1.1+ TCRαβint CD1-restricted T (NKT) cells are a unique subset of T lymphocytes that are thought to have an immunoregulatory role in a wide range of diseases. Most mouse NKT cells express a T-cell receptor that contains an invariant Vα14Jα18 chain and recognizes antigenic glycolipids presented in association with MHC class Ib (CD1d) molecules. These invariant NKT cells (iNKT) have been implicated in cholestatic liver injury. Methods We examined the role of iNKT cells in liver injury associated with biliary obstruction in mice with ligations of the common bile duct. Results The number of activated iNKT cells increased markedly in the livers of mice following bile duct-ligation (BDL). Plasma alanine aminotransferase (ALT) levels, an indicator of liver injury, were significantly higher in iNKT cell–deficient (Jα18−/−) mice, compared to wild-type mice, following BDL. Photoimage analysis of histologic sections confirmed that more damage was present in the livers of in Jα18−/−mice; liver damage correlated with increases in keratinocyte-derived chemokine (KC) and macrophage inflammatory protein-2 (MIP-2) production as well as neutrophil sequestration. Liver injury was significantly reduced in Jα18−/−mice treated with anti-KC and anti-MIP-2 or rendered neutrophil-deficient before BDL. Similarly, Jα18−/−mice that were injected with iNKT cells before BDL exhibited significant decreases in neutrophil accumulation and liver damage. Conclusion These data document the role of iNKT cells in suppressing the neutrophil proinflammatory response and neutrophil-dependent cholestatic liver damage.