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Long-term outcome of hepatitis C in children
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Hepatology Correspondence
Volume 39, Issue 5, May 2004
Flavia Bortolotti 1, Maria Guido 2, Lucia Zancan 3, Nadia Gussetti 4
1 Medicina Clinica e Sperimentale, University of Padova, Padova, Italy
2 Pathology Department, University of Padova, Padova, Italy
3 Pediatric Department, University of Padova, Padova, Italy
4 Department of Infectious Diseases, Padova Hospital, Padova, Italy
Letter
Long-Term Outcome of Hepatitis C in Children
To the Editor:
We have read with interest the paper by Casiraghi et al.[1] concluding that hepatitis C virus (HCV) infection acquired early in life (through blood transfusions) shows mild features and a slow progression during the first 35 years after exposure. Similar results came from previous retrospective studies in adults transfused early in life for cardiac surgery or for leukemia.
Chronic HCV infection is generally associated with mild liver disease during the first two decades of life in both transfused and perinatally infected children. Nevertheless, recent data in the literature and our own experience suggest the need for caution regarding the prognosis of HCV infection acquired in childhood. Regarding the short-term prognosis, cases of severe hepatitis and cirrhosis can be seen throughout childhood and adolescence in children without underlying diseases. About 7% to 10% of Italian children with chronic hepatitis C develop liver-kidney microsomal autoantibodies, and we could observe that liver disease is more severe and progressive in these patients than in a comparable population of HCV-infected children without serological markers of autoimmunity.[2] Also, we have recently seen 3 children who had developed compensated cirrhosis in the first decade of life, apparently in the absence of known comorbid conditions and autoimmunity. All 3 were male, with alanine aminotransferase levels greater than twice the normal throughout observation, and with history of maternal drug abuse. Only one mother was coinfected with human immunodeficiency virus (HIV). Birnbaum et al.[3] reported 3 similar cases, ages 4-11 years, but with decompensated cirrhosis and with evidence of HIV coinfection in 2 of 3 mothers (abuse was not disclosed). Maternal HIV/HCV coinfection and maternal drug abuse are independent risk factors for vertical HCV transmission; drug abuse seems to favor HCV infection of maternal peripheral blood mononuclear cells, which in turn would transmit the infection from mother to offspring.[4] Whether these early events may have relevance on the outcome of infection and disease remains to be elucidated. Nevertheless we are closely following HIV-seronegative children with high alanine aminotransferase levels and history of maternal abuse and/or HIV coinfection.
Regarding medium/long-term prognosis, it appears that older adolescents and young adults have higher rates of liver fibrosis than do younger children, independent of comorbid conditions, and we have recently shown increasing rates of fibrosis in serial biopsies of children on long-term follow-up.[5] Casiraghi et al.[1] show that virus replication is maintained for decades in their patients; thus progression of liver disease could occur at any time, especially considering that exposure to cofactors of liver damage increases in youth and adulthood.
Following these considerations, we hope that the apparently benign profile of pediatric HCV infection will not discourage or delay research in the therapy of this disease, taking into account that children have a long life expectancy, and that an efficient and well-tolerated treatment regimen would be cost-effective.
References
1 Casiraghi MA, De Pascale M, Romanò L, Biffi R, Assi A, Binelli G, et al. Long-term outcome (35 years) of hepatitis C after acquisition of infection through mini transfusions of blood given at birth. HEPATOLOGY 2004; 39: 90-96.
2 Bortolotti F, Muratori L, Jara P, Hierro L, Verucchi G, Giacchino R, et al. Hepatitis C virus infection associated with liver-kidney microsomal antibody type 1 (LKM1) autoantibodies in children. J Pediatr 2003; 142: 185-190.
3 Birnbaum AH, Shneider BL, Moy L. Hepatitis C in children. N Engl J Med 2000; 342: 290-291.
4 Resti M, Azzari C, Moriondo M, Betti L, Sforzi I, Novembre E, et al. Injection drug use facilitates hepatitis C virus infection of peripheral blood mononuclear cells. Clin Infect Dis 2002; 35: 236-239.
5 Guido M, Bortolotti F, Leandro G, Jara P, Hierro L, Larrauri X, et al. Fibrosis in chronic hepatitis C acquired in infancy: is it only a matter of time? Am J Gastroenterol 2003; 98: 660-663.
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