SUMMARYHCV infection and interferon-alpha (IFN-a) therapy have been associated with autoimmunity. To assess whether chronic liver disease (CLD) due to HCV infection or its treatment with IFN-a cause autoimmune manifestations, the prevalence of tissue autoantibodies in 51 children with chronic HCV infection and 84 with other CLD was analysed by standard techniques. Sixty-five percent of patients with chronic HCV infection, 66% with chronic hepatitis B infection and 60% with Wilson's disease were positive for at least one autoantibody. In the 51 subjects with chronic HCV infection (29 treated with IFN-a, 22 untreated), tested on 165 occasions over a median of 9 months (range 5-42 months), autoantibodies to nuclei (ANA), smooth muscle (SMA), gastric parietal cell (GPC) and/or liver kidney microsomal type 1 (LKM-1) were similarly prevalent in treated and untreated patients (90% versus 68%, P ¼ 0·12). Positivity for SMA was present in 67%, GPC in 32%, ANA in 10%, LKM-1 in 8% of cases. Treatment with IFN-a had to be suspended due to transaminase elevation in one SMA-positive, one ANA-positive but in three of four LKM-1-positive patients. Our results show that: (i) autoantibodies are common in viral-induced hepatitis and Wilson's disease; (ii) positivity for SMA, GPC, ANA is part of the natural course of chronic HCV infection, their prevalence being unaffected by IFN-a; and (iii) IFN-a should be used cautiously in the treatment of LKM-1/HCV-positive patients.

Children have a low risk of developing severe IFN-induced side effects. Adverse reactions and worsening of health-related quality of life were tolerable and did not seem to be a limiting factor for IFN therapy in young candidates.

SUMMARYAutoantibodies to smooth muscle (SMA) and nuclear components (ANA) arise in the natural course of chronic infection with hepatitis C virus. In view of the growing evidence for 'molecular mimicry' as a mechanism of autoimmunity we investigated whether cross-reactive immune reactions between host smooth muscle/nuclear components and HCV antigens may contribute to the formation of SMA and ANA in chronic HCV infection. Computer-assisted protein database search methods were used to identify three smooth muscle (smoothelin 698 -717 , myosin 1035 -1054 , vimentin 69 -88 ) and three nuclear (matrin 722 -741 , histone H2A 11-30 , replication protein A 133-152 ) host antigens with the highest local sequence similarity to the HCV polyprotein and 20-mer peptides corresponding to these regions were constructed. Sera from 51 children with chronic HCV infection [median age: 8 (2-16); 27 boys], 26 SMA positive and five ANA positive, were tested for reactivity to the synthesized HCV peptides and their human homologues by enzyme linked immunosorbent assay (ELISA). Sera from patients with HBV infection and chronic liver disease of different aetiologies were used as controls. 'Double reactivity' to HCV peptides and smooth muscle/nuclear homologues was associated strongly with HCV infection ( P < 0·001 for both). Humoral cross-reactivity was established as the basis for double recognition by competition ELISA. Doublereactivity to smooth muscle and HCV peptide antigens correlated with SMA positivity by indirect immunofluouresence ( P = 0·05). Of 15 patients double-reactive to myosin 1035 -1054 and its HCV homologue, 13 recognized whole myosin by immunoblot. These results suggest that ANA and SMA in chronic HCV infection may arise, at least in part, as a consequence of cross-reactive immune responses to HCV and host smooth muscle/nuclear antigens.

Interferon is becoming the standard treatment in adults for chronic hepatitis C. Twenty one children with histologically proved chronic hepatitis C (10 boys, range 2 5-13 years), who were otherwise healthy, were enrolled in a randomised controlled study to test their response to interferon alfa. Eleven children were treated with lymphoblastoid interferon alfa (3 million units/M2) for 12 months; 10 children received no treatment. All had raised transaminases and positive antihepatitis C virus (HCV) antibodies and HCV-RNA.Alanine aminotransferase (ALT) serum levels became normal in five (45%) treated patients after a mean of three weeks (range 1-6 weeks) and no relapse had occurred by the end of follow up (30th month). Only one (10%) untreated patient had normal ALT serum levels from the 11th until the 30th month. Disappearance of serum HCV-RNA, persisting throughout the follow up period, was observed in the six children (five treated) whose ALT became normal. Biopsy specimens in treated patients showed a significant improvement in Knodell's score (median (SD) basal 9-0 (2.2); final 2-0 (0.4)).Interferon treatment was well tolerated in all. This study confirms the efficacy of interferon in children with chronic hepatitis C, not only by restoring normal ALT serum levels, but also viral clearance and histological amelioration of liver inflammation. Contrary to reports in adults no biochemical and virological relapses occurred in responder children. (Arch Dis Child 1996; 74: 152-156)

No abstract

No abstract

No abstract

No abstract