Individuals were evaluated month to month during the treatment period and every 3 months thereafter. and Wilson’s disease; (ii) positivity for SMA, GPC, ANA is definitely part of the natural course of chronic HCV illness, their prevalence becoming unaffected by IFN-; and (iii) IFN- should be used cautiously in the treatment of LKM-1/HCV-positive individuals. = 42), and to the Paediatric Liver Service, King’s College Hospital, London, UK (= 9). All individuals were anti-HCV+ (second generation ELISA; United Biomedical Inc., Hauppage, NY and Sanofi Pasteur, Marnes-la-Coquette, France) and HCV-RNA+ (Amplicor; Hoffmann La Roche, Basel, Switzerland). All experienced sufficient amount of stored serum, collected over a median period of 9 weeks (range 5C42 weeks), for serial analysis. None of the individuals experienced serological evidence of coinfection with hepatitis B (microparticle Asymmetric dimethylarginine enzyme immunoassay; Abbott, Chicago, IL), delta (EIA; Abbott) and HIV-1 (Access Immunoassay; Sanofi Diagnostic Pasteur). None of them experienced clinically overt autoimmune disease. Of the 51 individuals, 42 underwent percutaneous liver biopsy (Table 2). Twenty-four (57%) individuals experienced histological evidence of chronic hepatitis with slight to moderate activity, nine (21%) experienced chronic hepatitis with minimal activity and nine (21%) experienced non-specific reactive hepatitis. None of these individuals experienced histological evidence of cirrhosis. Liver biopsy was not performed in nine individuals because of absence of parental consent in three, presence of connected medical disorders in two instances (tetralogy of Fallot and seizure disorder) and persistently normal aminotransferase levels in four. In the second option, positivity for HCV RNA had been shown on at least two occasions over a follow-up period of 7, 13, 24 and 96 weeks. Clinical history suggested that HCV illness was acquired by parenteral route in 35 (69%) individuals, vertical transmission in 12 (24%), while in four (7%) the mode of illness was unknown. Table 1 Clinical and immunological features of 51 children with chronic liver disease due to HCV, 84 children with additional Asymmetric dimethylarginine chronic liver disorders and 24 healthy controls at access to the study Open in a separate window Table 2 Clinical, biochemical and histological features of children with chronic liver disease due to HCV illness at entry into the study divided according to the presence or absence of autoantibodies Open in a separate window Twenty-nine individuals received IFN- treatment three times weekly for 12 months; 19 with recombinant IFN-2b (Viraferon; Schering Plough Ltd, Kenilworth, NJ) at 5 million models/m2 and 10 with lymphoblastoid IFN- (Wellferon; Wellcome Ltd, Beckenham, UK) at 3 million models/m2. Criteria for IFN- Asymmetric dimethylarginine treatment were as follows: positivity for HCV-RNA, aminotransferase levels exceeding or the top limit of normal for at least 1 year and liver histology compatible with chronic hepatitis. Individuals were evaluated regular monthly during the treatment period and every 3 months thereafter. Response to treatment was defined as disappearance of serum HCV-RNA (virological response) or aminotransferase normalization happening during and persisting until cessation of IFN- treatment (biochemical response). Of the 84 individuals with anti-HCV? (second generation ELISA; Sanofi Pasteur) chronic liver disorders, 24 experienced chronic hepatitis B computer virus illness. All were HBV-DNA+ (dot blot assay; Abbott) and HBeAg+ (microparticle enzyme immunoassay; Abbott) for at least 6 months with features of chronic hepatitis on liver biopsy. Twenty children experienced Wilson’s disease (irregular levels of 24-h urinary copper excretion before and after penicillamine challenge ), 20 Alagille’s syndrome and 20 1-antitrypsin deficiency (AATD) (PIZZ phenotype by isoelectric focusing). These pathological settings were selected to represent a wide range of liver pathology from cholestasis (Alagille’s syndrome) to chronic hepatitis (Wilson’s disease) and progressive fibrosis (AATD). Asymmetric dimethylarginine Sera from 24 age-matched healthy children (median age 9 (2C14) years; 16 kids) were tested as settings. Autoantibody detection Serum samples from HCV+ children and pathological and healthy controls were tested for the presence of autoantibodies by a single investigator blinded to medical details. One hundred and sixty-five sequential serum samples IL15RB (median of three serum samples per patient) were available from children with chronic liver disease due to HCV illness. Amongst the 29 individuals treated with IFN-, serum samples were taken before initiation of treatment and Asymmetric dimethylarginine two additional samples were acquired during and/or after IFN- (median time 9 (5C41) weeks). The samples from untreated individuals were collected over a period of 6C24 weeks (median 10 weeks). Blood samples were taken.
Individuals were evaluated month to month during the treatment period and every 3 months thereafter