Treatment of Hepatitis C in children

Paloma Jara; Loreto Hierro

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

Outcomes in Adult Age

An assessment of the characteristics of liver disease in adults who acquired HCV infection in childhood is available for certain populations of patients. Overall, patients who acquired HCV by parenteral routes predominate, and many were affected by transient or persistent conditions that may influence outcome. A report on 11 patients infected at birth by the same blood donor found, by the age of 35 years, nine cases with no fibrosis or mild fibrosis and one each with discrete (Ishak 3) or marked (Ishak 4) fibrosis.^[40] Similar findings were obtained in children who acquired HCV infection after cardiac surgery, and in a series of leukemia survivors.^[21]

Since there are no prospective studies on the course of the infection from infancy to adulthood, the data provided by studies in adult patients are of interest. In these studies, infections beginning before 40 years of age presented a severe liver disease rate of only 2–8% after 20 years, while infections developing after age 40 years yielded a 20% cirrhosis rate after 20 years. The estimation of the percentage of patients that develop severe disease in the course of a lifetime varies according to the different studies. In the period of 20 years after first infection, 20% of the patients seen in referral centers developed cirrhosis, although in the case of patients identified through screening of the general population or blood donors, only 4–7% were found to have cirrhosis.^[41]

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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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