Epidemiological profile of 806 Italian children with hepatitis C virus infection over a 15-year period

Background/Aims

To evaluate the epidemiological profile of Italian children with hepatitis C virus (HCV) infection over a 15-year period.

Methods

Fifteen tertiary care centers, belonging to a national Observatory established in 1998, retrospectively/prospectively recruited 806 consecutive HCV-infected, otherwise healthy, children seen from 1990 to 2004.

Results

Seven hundred and sixty four were Italian and 42 from foreign countries. Newly-diagnosed cases declined from 332 in 1995–1999 to 196 in 2000–2004, while the proportion of foreign children rose from 3% to 13%. Transfusion-transmitted infection disappeared after 1992. Maternal infection (with drug abuse in 63% of cases in the North) has become the most important mode of HCV diffusion throughout Italy and the exclusive source for all children infected in 2000–2004. The prevalence of HCV genotypes 3 and 4 increased and that of genotype 1b decreased significantly (p < 0.02). Male/female ratio was significantly (p < 0.001) lower among vertically infected (0.6) than in transfused children (1.3).

Conclusions

The number of children with newly-diagnosed HCV infection is declining in Italy and most post-transfusion cases are now young adults. Thus foreign children could significantly contribute to the reservoir of pediatric infection in years to come. New infections result from maternal transmission and seem to privilege females and genotypes 3 and 4.

Introduction

Infection with hepatitis C virus (HCV) is a worldwide health problem [1]. In Italy the prevalence of HCV antibodies (anti-HCV) in the general population averages 3% with a considerable variability between Northern and Southern regions. After the disappearance of post-transfusion hepatitis [2], intravenous drug abuse and high-risk sexual behavior are maintaining the reservoir of infection in adults and groups of adolescents [3], [4], [5], [6]. HCV infection is uncommon in children, because vertical transmission, which is responsible for most “new infections” in the Western World, has an efficiency of only about 5% [7], [8], [9], [10], [11], [12]. In the early Nineties the estimated prevalence of pediatric infection in Italy was 0.3% [13], and multicenter studies were clearly needed to evaluate the epidemiological and clinical aspects of infection in this setting. A national Observatory for HCV infection and Hepatitis C in Italian children was consequently created in 1998 to take a retrospective–prospective census of HCV-infected children referred to tertiary care centers [14]. The analysis of data retrospectively collected from 1990 to 1998 confirmed the almost complete disappearance of post-transfusion hepatitis and a concomitant increase in the proportion of vertically-infected children. Maternal drug abuse was a prominent source of infection in Northern Italy, whereas transfusions and mothers with covert exposure were likely to be responsible for the majority of cases in the South. On the other hand, the map of HCV genotypes recently investigated in a sizable proportion of the same population [15] showed a declining prevalence of genotypes 1b and 2 and an increasing number of cases with types 3 and 4. Taken together these data suggest that rapid changes in the epidemiology of HCV infection may be underway among children in Italy. To evaluate the extent of these changes, which could influence the future burden of HCV infection, we investigated the epidemiological profile of a large cohort of anti-HCV positive children over a 15-year period. The specific purpose of this prospective/retrospective study was to answer the following questions:

• Is the number of HCV infected children decreasing over the years?

• Did the map of putative exposure to HCV change during the survey?

• Are these changes correlated with the HCV genotype distribution?

• Are the putative changes related to the children’s geographic origin?

In addition, since maternal-infant transmission has become a major mode of HCV acquisition in the pediatric setting, we have investigated the time trends of related events such as: (a) maternal drug abuse, which is thought to promote transmission, and HIV coinfection which is known to facilitate the contagion; (b) mode of delivery and feeding which reflects the efficacy of counseling.