We appreciate the letter of Bortolotti et al. and the update on their results regarding the prognosis of hepatitis C virus (HCV) infection acquired in childhood, either through transfusion or by the vertical/perinatal route. We agree that hepatitis C is not always an innocuous disease in childhood, and that cirrhosis and extensive fibrosis may occur in some children even in the absence of comorbidities.1, 2 The authors indicate that liver disease may be more severe and progressive in children with liver/kidney microsomal antibody type 1 autoantibodies compared to those without serological markers of autoimmunity.3 In addition, they suggest that maternal coinfection with human immunodeficiency virus and HCV, as well as maternal drug use, both independent risk factors for vertical transmission,4 might have a role in worsening the outcome of HCV infection acquired perinatally. Our data concern the long-term outcome (35 years) of HCV infection in a unique cohort of individuals who acquired HCV through mini blood transfusions derived from an HCV-infected donor.5 All recipients were infected with the same virus genotype (1b), at the same time (shortly after birth) and with the same volume of infectious blood (21–30 mL), and were specifically traced through the clinical files of the hospital in which they were born. None of our HCV-infected individuals were liver/kidney microsomal antibody type 1 -positive and none had comorbid conditions such as hepatitis B virus or human immunodeficiency infection, or alcohol intake (>50 g per day). Moreover, none of the individuals enrolled in this study were aware of having been transfused and infected during the first weeks of life, and only one (who was a drug user) had additional risk factors for HCV infection. Therefore, it would seem that the differences in the outcome of HCV infection acquired in childhood, observed in our and other studies, may be due to differences in the population examined. Taking into account the above findings, one could expect subgroups of children (i.e., those born to HCV-carrier mothers who are coinfected with human immunodeficiency virus and/or are drug users, and those with autoimmune abnormalities) who are at increased risk of developing severe liver disease and even cirrhosis early in life. However, the role of these determinants in heralding a more aggressive outcome in HCV-positive children requires further investigation. Finally, we fully agree with our colleagues that the apparent benign course of HCV infection seen in most children does not imply that treatment should be delayed or even unwarranted in childhood, and that the research of novel, well-tolerated, and effective therapeutic strategies should remain a priority. Alessandro Zanetti*, Maria Antonietta Casiraghi , * Institute of Virology, University of Milan, Milan, Italy, Liver Unit—Department of Medicine, Hospital of Legnano, Milan, Italy.