Spontaneous Clearance of Childhood Hepatitis C Virus Infection
Spontaneous Clearance of Childhood Hepatitis C Virus Infection
To describe the spontaneous clearance rate of childhood hepatitis C virus (HCV) infection, to determine whether route of transmission affects the clearance rate and to identify other predictors of clearance. Children with chronic hepatitis C were identified between 1990 and 2001. The rate of spontaneous clearance (defined as ≥2 positive anti-HCV antibody test but negative HCV RNA) was calculated using survival analysis. Univariate and multivariate predictor variables [route of transmission, age at infection, age at last follow-up, alanine aminotransferase (ALT) and gender] for clearance were evaluated. Of 157 patients, 28% of children cleared infection (34 transfusional and 10 nontransfusional cases). The 123 transfusional cases were older at time of infection and at follow-up, compared with the 34 nontransfusional cases. Younger age at follow-up (p < 0.0001) and normal ALT levels (p < 0.0001) favoured clearance. Among cases of neonatal infection, 25% demonstrated spontaneous clearance by 7.3 years. The rate of spontaneous clearance of childhood HCV infection was comparable between transfusional and nontransfusional cases. If clearance occurs, it tends to occur early in infection, at a younger age.
Hepatitis C virus (HCV) infection may lead to chronic hepatitis, cirrhosis and hepatocellular carcinoma. Yet most children with HCV infection are asymptomatic and have mild histological findings. Thus for children, spontaneous clearance of HCV infection is more relevant than histological progression of disease. Studies that focus on the observed rate of spontaneous clearance have reported rates ranging from 21% to 67%. However, all but one of these studies report the crude clearance rate without adjusting for varying duration of patient follow-up, rather than a clearance rate which takes into account different follow-up periods among patients. By characterizing the timing of spontaneous clearance in childhood, we can identify the infected children who are unlikely to clear and thus warrant consideration for treatment.
Hepatitis C virus transmission results from the transfusion of contaminated blood products, injection from contaminated needles (such as through i.v. drug use or occupational exposure), from vertical (mother-to-infant) exposure, or sexual routes. In children, cases of hepatitis C can be classified as transfusional or nontransfusional (acquired through mother-to-infant transmission or other exposure). Whether the route of transmission is an informative prognostic factor for HCV disease remains controversial. Several adult studies have indicated that transfusion-associated hepatitis C (TAC) is histologically more severe than hepatitis C from intravenous drug use. Furthermore, TAC was more likely than nontransfusion-associated hepatitis C (non-TAC) to result in liver failure. Others have found that route of transmission has no correlation with disease outcome. Childhood chronic hepatitis C provides a unique opportunity to evaluate the prognostic value of route of transmission in this disease. It is less susceptible to the confounding effects of prolonged duration of infection, alcohol consumption, high-risk sexual behaviour and i.v. drug use.
We report the time-dependent rate and timing of spontaneous clearance of HCV infection in a large cohort of children.
To describe the spontaneous clearance rate of childhood hepatitis C virus (HCV) infection, to determine whether route of transmission affects the clearance rate and to identify other predictors of clearance. Children with chronic hepatitis C were identified between 1990 and 2001. The rate of spontaneous clearance (defined as ≥2 positive anti-HCV antibody test but negative HCV RNA) was calculated using survival analysis. Univariate and multivariate predictor variables [route of transmission, age at infection, age at last follow-up, alanine aminotransferase (ALT) and gender] for clearance were evaluated. Of 157 patients, 28% of children cleared infection (34 transfusional and 10 nontransfusional cases). The 123 transfusional cases were older at time of infection and at follow-up, compared with the 34 nontransfusional cases. Younger age at follow-up (p < 0.0001) and normal ALT levels (p < 0.0001) favoured clearance. Among cases of neonatal infection, 25% demonstrated spontaneous clearance by 7.3 years. The rate of spontaneous clearance of childhood HCV infection was comparable between transfusional and nontransfusional cases. If clearance occurs, it tends to occur early in infection, at a younger age.
Hepatitis C virus (HCV) infection may lead to chronic hepatitis, cirrhosis and hepatocellular carcinoma. Yet most children with HCV infection are asymptomatic and have mild histological findings. Thus for children, spontaneous clearance of HCV infection is more relevant than histological progression of disease. Studies that focus on the observed rate of spontaneous clearance have reported rates ranging from 21% to 67%. However, all but one of these studies report the crude clearance rate without adjusting for varying duration of patient follow-up, rather than a clearance rate which takes into account different follow-up periods among patients. By characterizing the timing of spontaneous clearance in childhood, we can identify the infected children who are unlikely to clear and thus warrant consideration for treatment.
Hepatitis C virus transmission results from the transfusion of contaminated blood products, injection from contaminated needles (such as through i.v. drug use or occupational exposure), from vertical (mother-to-infant) exposure, or sexual routes. In children, cases of hepatitis C can be classified as transfusional or nontransfusional (acquired through mother-to-infant transmission or other exposure). Whether the route of transmission is an informative prognostic factor for HCV disease remains controversial. Several adult studies have indicated that transfusion-associated hepatitis C (TAC) is histologically more severe than hepatitis C from intravenous drug use. Furthermore, TAC was more likely than nontransfusion-associated hepatitis C (non-TAC) to result in liver failure. Others have found that route of transmission has no correlation with disease outcome. Childhood chronic hepatitis C provides a unique opportunity to evaluate the prognostic value of route of transmission in this disease. It is less susceptible to the confounding effects of prolonged duration of infection, alcohol consumption, high-risk sexual behaviour and i.v. drug use.
We report the time-dependent rate and timing of spontaneous clearance of HCV infection in a large cohort of children.
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