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Management of Viral Hepatitis in Children
the short term ranges from 20 to 40%, and is highest in children with study in children two to 18 years of age is being planned. Tenofovir
elevated transaminases and horizontal transmission.
14
The role of disoproxil fumarate is a nucleotide analogue that is similar to adefovir but
prednisone priming is unproven, but it may increase the spontaneous more effective.
25
A randomised, placebo-controlled, multicentre study in
remission rate and reduce time to seroconversion.
15
adolescents has just begun. Entecavir, a carbocyclic analogue, inhibits HBV
replication at three different steps: the priming of HBV DNA polymerase,
Interferon has many unpleasant side effects. Fever and ‘flu-like’ symptoms reverse transcription and synthesis of HBV-DNA. It is more potent than
and bone marrow suppression are common at the beginning of treatment. lamivudine in suppressing wild-type HBV, but less effective in adults
Autoimmune thyroid disease, alopecia and severe depression are also with lamivudine resistance. Viral resistance is rare. An open-label,
reported, as is growth retardation. It is not recommended in children with multicentre trial is under way in children.
26
The European Medicines Agency
decompensated liver disease, epilepsy, pancytopenia and severe renal, (EMEA) is considering guidelines for therapy for viral hepatitis in children and
cardiac or autoimmune disease. Pegylated interferon (PEG-IFN), in which the will be planning future therapy, so treatment outcomes may improve.
attachment of a polyethylene glycol (PEG) moiety increases the half-life, has
not yet been approved for HBV treatment in children, but is more effective Hepatitis C
than interferon in adults. Injections can be given once weekly rather than The hepatitis C virus (HCV) is a flavivirus that was cloned in 1989.
27
It is an
three times each week.
16
RNA virus with a high degree of heterogeneity, leading to the rapid
accumulation of mutations. This genetic diversity allows the virus to avoid
Lamivudine immune surveillance, leading to chronic infection and difficulty in producing
Lamivudine is a pyrimidine nucleoside analogue that prevents replication of an effective vaccine.
28
There are six major genotypes with different subtypes
HBV in infected hepatocytes. It is incorporated into viral DNA, leading to and a distinct geographical distribution. Diagnostic assays for HCV are now
chain termination, and competitively inhibits viral reverse transcriptase. It well established. The most useful screening test is the detection of anti-HCV
leads to a rapid reduction in HBV DNA within two weeks of starting IgG in serum using an enzyme immunoassay (EIA), but the detection of
treatment. A double-blind, placebo-controlled trial of 286 children with HCV RNA is necessary to determine infectivity and response to therapy.
chronic HBV was effective in 23% of children after 52 weeks compared with Initially, most children were infected with HCV parenterally from blood
13% in the placebo group.
17
Although longer treatment increased products or transplanted organs, but now the main source of infection is
seroconversion rates, the main limitation of lamivudine treatment was the peri-natal transmission from intravenous drug abusers or recent migrants.
29
relapse rate following cessation of therapy and the development of Transmission of infection is more likely in mothers with high titres of HCV
resistance with the development of tyrosine-methionine-aspartate-aspartate RNA and with those who are HIV-positive,
30,31
with transmission rates
(YMDD) mutant variants of HBV.
18
varying from 2 to 12% depending on maternal infectivity. Hepatitis C
antibody is passively transmitted, and so all infants will have HCV antibodies
Adefovir Dipivoxil for up to 13–18 months.
32
Measurement of HCV RNA, which is unreliable
Adefovir dipivoxil is a purine analogue that inhibits viral replication by before three months of age, is necessary to detect active infection.
32
binding to DNA polymerase. It may also augment natural killer cell activity Breastfeeding is safe in mothers with low titres of HCV RNA.
33
and endogenous interferon activity. Furthermore, HBV strains resistant to
lamivudine are susceptible to adefovir.
19
A recent randomised controlled trial Natural History of Hepatitis C
in 173 children demonstrated that adefovir (in doses up to 10mg) reduced The natural history, prognosis and clinical significance of chronic hepatitis C
HBV DNA most effectively in children over 12 years of age (23%) compared are unpredictable. Data from adult studies indicate that it is a chronic
with younger children. Seroconversion rates were 20% in children below 12 disease, with approximately 50% of patients developing progressive
years of age, but there was no significant difference compared with liver disease and 20% developing cirrhosis 20–30 years after infection.
placebo.
20
Viral resistance did not occur, but there is increased resistance to Hepatitis C is also a risk factor for the development of hepatocellular cancer.
adefovir in patients who were previously resistant to lamivudine.
21
Adefovir Although there is considerable variation in disease outcome, chronic liver
is not first-line therapy in young children unless for compassionate use. disease is more likely with genotype 1B.
1
Natural seroconversion is between
20 and 40% in children infected by blood products
34,35
compared with only
Combination Therapy 10% of vertically infected infants.
36
Acute HCV is uncommon in childhood,
37
In adults, PEG-IFN 180mcg weekly plus lamivudine 100mg daily for 48 and most chronically infected children are asymptomatic, with normal
weeks led to an improvement in viral suppression but no difference in growth and development. There is little biochemical evidence of liver
seroconversion rates.
16
There are a few studies of PEG-IFN in children with disease, but the majority will have chronic hepatic inflammation with a
HBV with or without lamivudine, but the results are inconclusive.
22
minority progressing to fibrosis or cirrhosis in childhood, particularly those
with multiple transfusions, previous chemotherapy or an underlying disease
Liver Transplantation such as thalassaemia.
38
Liver transplantation is indicated for children with acute or chronic liver
failure. The recurrence of HBV is unusual following transplantation for acute Management of Chronic Hepatitis C Virus Infection
fulminant hepatitis but common following transplantation for chronic HBV As for HBV, children with chronic HCV should be referred to specialised
unless prevented with oral lamivudine plus HBV immune globulin.
23
centres for information, counselling and family support. Annual
review for children includes HCV serology to detect natural
Future Therapy for Hepatitis B in Children seroconversion, evidence of progressive liver disease and consideration
Telbivudine is an L-nucleoside analogue that is more effective than for antiviral treatment. Selection for treatment is based on the
lamivudine in adults (26 compared with 23%) but has a high rate of viral combination of persistent infection for more than six months and
resistance and is not recommended as monotherapy.
24
A pharmacokinetic evidence of histological disease.
EUROPEAN PAEDIATRICS 63
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