Treatment of Hepatitis C in children

Paloma Jara; Loreto Hierro

Expert Rev Gastroenterol Hepatol. 2010;4(1):51-61.

Origin of HCV Infection in Children: Mother-to-child Transmission

Hepatitis C is an asymptomatic disease in infants. The only efficient method for its detection is the investigation of children at risk. Infants of women with hepatitis C should be tested for HCV RNA on two occasions, between the ages of 2 and 6 months, and again at 18 to 24 months, along with serum anti-HCV.^[3–5] Variants to this schedule are also employed. Tests performed in umbilical cord or before 1 month of age give a high rate of false-negative and false-positive results and are not recommended.

The offspring of anti-HCV-positive mothers have anti-HCV antibodies in their blood as a result of passive transplacental transfer. These antibodies remain detectable in the infant for the first 12–15 months of life. The definition of mother-to-child transmission of HCV includes: the detection of anti-HCV antibodies in a child over 18 months of age, or the detection of HCV RNA in a child over 2 months of age, preferably confirmed in two different samples.^[3]

Children born to anti-HCV-positive and HCV RNA-positive mothers have an infection risk of 4–10%, with no differences between caesarean or vaginal delivery, or between children who are breastfed or receive infant formulas.^[3,6] Once pre- or peri-natal transmission has been discarded, cohabitation of the child with the mother entails no appreciable risk.

Excellent reviews on HCV vertical transmission are available.^[3,6,7] Some risk factors have been clearly identified, such as maternal viremia^[4,8] or maternal co-infection with HIV-1.^[3] Maternal intravenous drug use, the presence of HCV RNA in maternal peripheral blood mononuclear cells and genetic factors (HLA-DRB1*10 in children) could also facilitate transmission.^[9–11]

However, discordance exists between studies. Viral load in the mother is a rational risk factor involved in transmission to the child, but was found to be either high or not significantly different between transmitting and nontransmitting mothers.^[8,12] Other risk factors are linked to abnormal labor, as published data support facilitated transmission by a prolonged time from rupture of membranes to birth.^[6,13,14] Antiretroviral treatment of HIV-infected mothers decreases the risk of HCV transmission to levels similar to HIV-negative mothers.^[6]

Mother-to-child transmission theoretically can occur in utero, at the end of pregnancy or at delivery. Among 54 infected infants tested within 3 days of birth, 31% displayed HCV viremia, suggesting that intrauterine infection could have occurred.^[15]

There are currently no established interventions to prevent infection of the child born to an infected mother. In particular, there is no evidence to suggest that women should be offered an elective caesarean delivery or be advised to avoid breastfeeding.^[4]

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Abstract and Introduction
Origin of HCV Infection in Children: Mother-to-child Transmission
Course of HCV Infection in Children
Liver Damage in Pediatric Chronic HCV Infection
Severe Liver Disease in Children
Outcomes in Adult Age
Treatment
Conclusion
Expert Commentary
Five-year View
References
Sidebar

Table 1. Liver damage in children with chronic hepatitis C.
Study	Country	Children (n)	Age at biopsy (years)	Comorbid conditions (%)	Scoring system	Grade, activity (0–18)	Stage Ishak 0–6, Knodell 0–4	Cirrhosis	Factors associated with fibrosis progression	Ref.
Iorio et al. (2005)	Italy	64	8.2 (2–14)	None	Ishak	Median: 4.4 Range: 1–8	Median: 1.6	0	Age or duration not related to fibrosis	^[31]
Mohan et al. (2007)	USA	42	15 ± 1.8 (cohort) 8.8 ± 5 (referral)	26	Knodell	71% mild (0–8), 5% severe (>13)	88% mild (0–1)	0 initial, 14% in follow up	Age of infection shows positive correlation with fibrosis (in referral group)	^[32]
Harris et al. (2007)	UK	98	14 ± 3.5	54	Ishak	Median: 3 Range: 1–7	Median: 1 Range: 0–6	3%	Comorbid conditions, OR: 7.1 Duration of infection in children with comorbidities Female, OR: 0.31	^[33]
Jara et al. (2003)	Spain–Italy–Belgium	92	1–17	None	Ishak	Mean ± SD: 3.9 ± 2, 76% mild (0–6)	1.6 ± 1.3	1%	Age > 15 years	^[26]
Goodman et al. (2008)	PEDS-C USA	121	Mean 9.8	No	Knodell	Mean: 5.1 59% mild, 3% severe	80% some fibrosis	2%	Fibrosis scores correlated with inflammation, but not with age Overweight	^[34]

OR: Odds ratio; PEDS-C: PEG-interferon with or without ribavirin in children with chronic hepatitis C trial; SD: Standard deviation.

Table 2. Efficacy of combined treatment in children.
Study	Treatment schedule	Children (n)	SVR overall (%)	SVR genotype 1	SVR genotype 2&3	SVR parenteral	SVR vertical	SVR		Ref.
Study	Treatment schedule	Children (n)	SVR overall (%)	SVR genotype 1	SVR genotype 2&3	SVR parenteral	SVR vertical	Age <12 years	Age >12 years	Ref.
Wirth et al. (2002)	IFN-α-2b 3–5 MU/m² three-times weekly + RBV 15 mg/kg/day	41	61	18/34 (52.9%)	7/7 (100%)	9/16 (56%)	14/21 (66%)			^[51]
Gonzalez-Peralta et al. (2005)	IFN-α-2b 3 MU/m² three-times weekly + RBV 15 mg/kg/day	118	46	33/92 (36%)	21/25 (84%)			43/75 (57%)	11/43 (26%)	^[52]
Wirth et al. (2005)	PEG- IFN-α-2b 1.5 µg/kg/week + RBV 15 mg/kg/day	61	59	22/46 (47.8%)	13/13 (100%)	19/27 (70.4%)	12/25 (48%)			^[62]
Jara et al. (2008)	IFN-α-2b 1 µg/kg/week + RBV 15 mg/kg/day	30	50	12/26 (46%)	3/3 (100%)	7/9 (78%)	8/21 (38%)	9/20 (45%)	6/10 (60%)	^[61]
P02538 study (2008)	IFN-α-2b 60 µg/kg/week + RBV 15 mg/kg/day	107	64	53%	93%					^[58]
PEDS-C trial (2008)	IFN-α-2a 180 µg/1.73 m²/week + RBV 15 mg/kg/day	55	53	47%	Non-1: 80%					^[60]

PEDS-C: PEG-interferon with or without ribavirin in children with chronic hepatitis C trial; RBV: Ribavirin; SVR: Sustained virologic response.

Table 3. Adverse events of combined treatment in children.
Study	Treatment schedule	Children (n)	Discontinuation due to AE	Reduced IFN due to AE (%)	Number of severe AE	Severe AE (n)	Permanent AE (n)	Ref.
Wirth et al. (2002)	IFN-α-2b 3–5 MU/m² three-times weekly + RBV 15 mg/kg/day	41	1 (2.4%)	0	4	Anemia: 1 Hypothyroidism: 3	0	^[51]
Gonzalez-Peralta et al. (2005)	IFN-α-2b 3 MU/m² three-times weekly + RBV 15 mg/kg/day	118	8 (7%)	31	6	Suicide attempt: 1 Suicide ideation: 1 Depression: 1 Hypothyroidism: 2 Hypothyroidism + diabetes: 1	1 hypothyroidism + diabetes	^[52]
Wirth et al. (2005)	PEG- IFN-α-2b 1.5 µg/kg/week + RBV 15 mg/kg/day	61	1 (1.6%)	5	7	Injection site reaction: 1 Hypothyroidism: 5 Diabetes: 1	1 diabetes	^[62]
Jara et al. (2008)	PEG-IFN-α-2b 1 µg/kg/week + RBV 15 mg/kg/day	30	3 (10%)	23	3	High fever: 1 Hyperthyroidism: 2	0	^[61]

AE: Adverse event; RBV: Ribavirin.

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