In this study, chronic hepatitis C infection was silent in most of the children, and there was little biochemical evidence of liver disease in these patients. Only one girl with portal hypertension and liver failure developed symptoms related to the infection. Consequently, our data suggest that HCV infection may be currently underdiagnosed in children and, moreover, that young patients could become a potential source of infection. We therefore strongly recommend that children falling in risk groups be screened for HCV infection.
Of the 37 pediatric patients in this series, seven (19%) had NOSAs. These antibodies are highly prevalent in subjects exposed to the HCV, and a positive test result for SMA, GPCA and ANA is part of the natural course of chronic HCV infection in adults and children [7
]. Lenzi et al. [13
] reported a higher prevalence of NOSAs in anti-HCV-positive adult patients than in normal controls (25 vs. 6%). Stroffolini et al. [22
] found positive NOSAs in 36.9% of 502 subjects with HCV-RNA-positive chronic hepatitis. Muratori et al. [16
] detected positive NOSAs in 16 of 47 children (34%) with chronic hepatitis C, and anti-LKM was present in 11% of the children.
Of the 37 children participating in our study who manifested past or active HCV infection, two had serum anti-LKM. This incidence is lower than that observed by Muratori et al. (11%) [16
] and Bortolotti et al. (10.3%) [4
] in children with HCV infection. A possible explanation for this finding is the higher age and longer mean duration of HCV infection in the patients included in our series in comparison to the children in the other two studies. The prevalence reported by Lenzi et al. (1.3% [13
]), Stroffolini et al. (2.25% [22
]) and Reddy et al. (0% [18
]) in adults support this hypothesis. Anti-LKM is an immunomarker of type 2 autoimmune hepatitis [2
] that tends to present at younger ages and to affect mainly children. Our data suggest that age may be a factor contributing to the presence of anti-LKM1 in children infected with HCV. Moreover, we observed that one of our non-viremic patients had persistent antibodies after the test for anti-HCV became negative.
Liver specimens from the children with hepatitis C showed mild necroinflammatory changes and a low level of fibrosis. In most patients, fibrosis was absent or low grade. Only one patient, as mentioned above, developed cirrhosis and liver failure over a period of 6 years. This leukemic patient had other additional risk factors for liver damage that may have affected this outcome. In this respect, Hoshiyama et al. [9
] observed that chronic hepatitis C is more frequent among children with hepatitis C infection following blood transfusions for malignant disease than in patients with hepatitis C following blood transfusions for open heart surgery.
We have compared our results with those obtained from other pediatric series [6
]. Table summarizes the data on fibrosis obtained from liver biopsies of 210 pediatric patients (above-mentioned studies). Fibrosis was not detected or was low grade in 200 patients (95%), and severe fibrosis or cirrhosis was detected in ten patients (5%). Minola et al. [15
] and Poynard et al. [17
] demonstrated an inverse correlation between age at HCV infection and progression to cirrhosis that suggests that chronic HCV infection in childhood induces mild changes in the liver with a low level of fibrosis and a low rate of progression. However, it has been observed that mild chronic hepatitis C can be a progressive disease in adult patients [3
] and that the long evolution of infection acquired in childhood could increase the risk of fibrosis. Thus, some children infected early in life, in whom chronic disease has a mild liver expression, might develop fibrosis in adulthood.
Hepatic fibrosis in biopsies from children with HCV infection
It is noteworthy that 6/27 of the children with HCV infection in our series had a co-infection with HGV (HGV-RNA-positive) or had a past HGV infection (anti-HGV-positive). This prevalence of HGV infection is higher than that found in healthy children (6%) in Spain [10
]. These data suggest that HCV-infected children must be considered to be a risk group for HGV infection since HCV and HGV are both parenterally transmitted. Moreover, no differences were observed in biochemical and histological findings in HCV-infected children with and without a concomitant infection with HGV, which suggests that superimposed HGV infection does not influence the course of HCV infection.
Conversely, our data do not support that HEV, which can be transmitted by a parenteral route [24
], is prevalent in children who had undergone blood transfusions (prevalence rate: 0%). However, this low value may result from the low prevalence of HEV infection in Spain (2.8%) [14