The Impact of Mode of Acquisition on Biological Markers of Paediatric Hepatitis C Virus Infection

K. England; C. Thorne; H. Harris; M. Ramsay; M.-L. Newell

Disclosures

J Viral Hepat. 2011;18(8):533-541. 

In This Article

Results

Data on 395 HCV-infected children were available and included 269 vertically infected and 126 parenterally infected children. Seventy-six (60%) parenterally infected children had a known date of infection, and the median age at infection for this group was 19 months of age. Follow-up in vertically infected children was more intensive; and the larger number of median follow-up visits is likely a reflection of the different study protocols.[2,12]

The male to female sex ratio in the vertically infected children was approximately 1:2, reflecting the increased likelihood of vertical HCV infection in girls compared with boys, while the male to female sex ratio in the parenterally infected children was approximately 2:1, P < 0.001 (Table 1).[17] HCV genotype was recorded for 115/269 (43%) vertically and 50/126 (40%) parenterally infected children. No significant differences were found in HCV genotype profiles by mode of acquisition when looking at each genotype individually or genotype 1 in comparison with any other genotype (Table 1).

Ten vertically infected children and 39 parenterally infected children received anti-HCV therapy during follow-up. Nine (90%) vertically infected children received IFN-alpha with the remaining child receiving IFN-alpha with Ribavirin. Eighteen (46%) parenterally infected children received IFN-alpha, 12 (30%) IFN-alpha with Ribavirin and nine (23%) Pegylated IFN-alpha with Ribavirin. Parenterally infected children were significantly more likely to have received HCV treatment than vertically infected children (Table 1), and the median age at the start of treatment was 11 years (range 1.9–17.3 years) and 5.7 years (range 2.3–11.7 years), respectively. A lower proportion of children with genotype 1 achieved a SVR [18.2% (2/11)] than children with any other genotype [50% (4/8)], but this difference was not statistically significant, Fisher's exact P-value = 0.319.

Parenterally HCV-infected children with a known date of infection began follow-up at an earlier age than those with no known infection date (median age at infection 10.5 and 14 years, respectively, P < 0.001) and had a longer duration of follow-up (median number of follow-up visits 3 and 2, respectively, P < 0.001) but otherwise did not differ in terms of their gender, HCV genotype or treatment profiles.

Clinical Signs and Symptoms of Hepatitis C Virus Infection

Parenterally infected children were significantly more likely than vertically infected children to have hepatomegaly reported at least once during follow-up [25/126 (19.8%) and 27/269 (10.0%) respectively (χ2 = 7.215, P = 0.007)]. Liver biopsy was carried out on a total of 27/269 (10.0%) vertically and 73/126 (57.9%) parenterally infected children. Similar proportions of vertically and parenterally infected children showed signs of chronic hepatitis, 82% and 67%, respectively (χ2 = 1.973, P > 0.10).

Hepatitis C Virus RNA PCR

Qualitative HCV RNA PCR was performed on 262 (of 269) vertically infected and 116 (of 126) parenterally infected children, of whom 250 and 68, respectively, had at least two PCR results recorded overall. A higher proportion of parenterally infected children had PCR results which were all positive than vertically infected children [34/68 (50.0%) and 101/250 (40.4%), respectively], but this difference did not reach statistical significance [χ2 = 2.017, P = 0.156]. Nearly 60% of both vertically and parenterally infected children were consistently viraemic (75% or more HCV RNA positive byPCR); 145/250 (58.0%) and 37/68 (54.4%), respectively [χ2 = 0.281, P = 0.596]. Clearance of HCV viraemia was seen in similar proportions of vertically (30%, 74/250) and parenterally infected children (34%, 23/68), z = −0.633, P = 0.527.

Logistic regression identified factors associated with being consistently HCV viraemic in 300 children (232 vertically and 68 parenterally infected) who had information available on all the variables (Table 2). The odds of being consistently HCV viraemic were significantly associated with a 10 times increase in the odds of having consistently elevated ALT z-scores (Table 2). Although not significantly so, being female, parenterally infected or receiving anti-HCV therapy reduced the odds of being consistently HCV viraemic. In contrast, ever having evidence of hepatomegaly increased the odds of being consistently HCV viraemic but again, not significantly so.

Univariable logistic regression was carried out on the subset of 125 children with genotype information available separately; the odds of being consistently viraemic was higher in children with HCV genotype 1 vs any other genotype, but this association just failed to reach statistical significance (unadjusted OR = 1.94, 95% CI 0.92–4.08, P = 0.082).

ALT Levels

A total of 1404 ALT observations were recorded (range 2–1213 IU/L) from 218 vertically and 91 parenterally infected children. At least one elevated ALT level was recorded from 137 (62.8%) vertically and 53 (58.2%) parenterally infected children (χ2 = 0.574, P > 0.10). In reference to a standard population of HCV-uninfected children born to HCV-infected mothers, the mean ALT z-score for vertically infected children was 2.049 (SD 2.059) and for parenterally infected children was 1.541 [(SD 1.783), t = 2.949, P = 0.03 (Fig. 1)]. The mean ALT z-score in 247 children infected before 12 months of age (2.033, SD 2.033) was also significantly higher than the mean ALT z-score in the 24 children infected after 12 months of age [(1.387 SD 1.652), t = 1.887, P = 0.030]. Among 53 parenterally infected children, there was no difference by age at infection in terms of mean ALT z-score; 1.64 (SD 1.37) in those infected before 12 months of age and 1.63 (SD 1.66) in those infected after 12 months of age (t = 0.010, P = 0.992).

Figure 1.

ALT z-score over time since infection in vertically and parenterally infected children.

Fifty-one children had consistently elevated ALT z-scores (defined as having 75% or more ALT z-scores 2 SD or above in those children with 2 or more ALT results recorded); 43/204 (21.1%) vertically and 8/39 (20.5%) parenterally infected children. Children who had ever had evidence of hepatomegaly were over three times as likely to have consistently elevated ALT z-scores in multivariable logistic regression and those who were consistently HCV viraemic were over 12 times as likely to also have consistently elevated ALT z-scores (Table 3).

In univariable logistic regression only including the 122 children with ALT z-score and genotype information, the odds of having consistently elevated ALT levels were higher in children with HCV genotype 1 vs other genotypes but this association just failed to reach statistical significance (unadjusted OR 2.23, P = 0.072).

Fifteen children were consistently HCV viraemic, had consistently elevated ALT z-scores and evidence of from a total of 295 children with no missing information on any of these variables. The proportion of children with two or more of these three markers of infection was similar in parenterally (15/84, 17.9%) and vertically infected children and also similar in those infected before 12 months of age and after 12 months of age (Table 4). Similar proportions of those parenterally infected before and after 12 months of age were found to have two or more markers of infection. Similar proportions of children receiving anti-HCV and those receiving none had two or more markers of infection, and there was no significant difference between the number of children with genotype 1 who had two or more markers of infection and those with any other genotype (Table 4).

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