Ten years have elapsed since the
identification of the viral agent (hepatitis C virus [HCV])
responsible for hepatitis C was first reported.1 This
remarkable achievement occurred after >20 years of intense effort by
investigators worldwide following the observation that at least 1 additional viral agent, other than hepatitis A and hepatitis B, was the
major cause of posttransfusion hepatitis.2
 |
BACKGROUND |
Before the discovery of HCV, the term non-A, non-B hepatitis
(NANB) was used to designate viral hepatitis for which there were no
recognized serologic or virologic markers. Because most instances of
NANB hepatitis were, in reality, hepatitis C, prospective studies and
observations conducted in the 1970s and 1980s shed much light on the
clinical features and natural history of HCV infection in adults.
However, the discovery and characterization of the viral agent was a
major leap forward and rapidly led to the development of assays to
detect anti-HCV antibodies and more recently to the application of
polymerase chain reaction assays that recognize minute amounts of
circulating HCV genome (HCV-RNA). The development of these tests have
made it possible to firmly establish a diagnosis of hepatitis C in the
clinical setting and have led to a better understanding of the salient
epidemiologic, clinical, biochemical, and histologic manifestations of
HCV infection. In addition, they provide information essential for
obtaining a more accurate assessment of the effects of both established and experimental therapeutic regimens on the course of infection. Moreover, the ability to screen potentially infectious materials, such
as blood donated for transfusion, has had an important impact in
preventing the spread of hepatitis C.
| |
THE VIRAL AGENT |
HCV is an enveloped RNA virus with a genome that consists of
~10 000 nucleotides.3 The virus is a member of the
flavivirus family, which also includes other parenterally spread
viruses, such as yellow fever and dengue. At least 6 genotypes as well as a number of subtypes have been identified.4 A
correlation seems to exist between the between the genotype and the
clinical course of infection and its responsiveness to treatment. For
example, genotype 1, which is common in the United States, seems to be the most virulent of the genotypes and more resistant to treatment. Unfortunately, HCV is a very mutagenic virus, a characteristic that
enables it to survive the immune defense mechanisms of the host. As a
result, >75% of those adults acquiring acute infection go on to
develop chronic hepatitis C with continuing HCV
infection.5,6
| |
TERMINOLOGY |
HCV infection is designated hepatitis C when it is accompanied by
biochemical and/or histologic evidence of inflammation and necrosis. By
convention, the term chronic is used when the duration of HCV infection
or hepatitis is greater than 6 months. Only a small percentage of
patients with chronic hepatitis C eventually eradicate HCV
spontaneously. Current or previous HCV infection is diagnosed by
finding anti-HCV antibodies in the serum by immunoassay, now in its
third generation of development, and confirming the presence of
anti-HCV by supplemental testing with a recombinant immunoblot assay
(RIBA). The diagnosis of acute or chronic HCV infection is made, by
convention, when serum anti-HCV positivity is detected in temporal
association with clinical or laboratory evidence of hepatitis without
other evident cause. HCV infection can also be determined with
certainty by testing for HCV-RNA but this test at present is expensive,
more difficult to perform, and is not routinely used for establishing a
diagnosis.
| |
HCV IN ADULTS |
Epidemiology
Primarily transmitted percutaneously, the major mode of spread
today is via intravenous drug abuse.7,8 The magnitude of
household, sexual, and perinatal transmission is debated but seems to
be less of a problem than with hepatitis B.9 Perinatal
transmission does occur and is particularly frequent when the pregnant
female has very high levels of HCV in the bloodstream, such as that
seen in the setting of co-infection with human immunodeficiency virus
(HIV).9,10
Prospective studies in the 1970s demonstrated that 7% to 10% of
recipients of blood obtained from volunteer donors developed posttransfusion hepatitis of whom ~90% were attributable to
HCV.2 Although routine blood donor screening for serologic
evidence of hepatitis C has greatly reduced the risk of posttransfusion hepatitis C,11 and the total number of number of new cases
estimated by the Centers for Disease Control and Prevention to occur
each year has fallen appreciably over the past decade, it is estimated
that ~4 million adults in this country are infected with
HCV.12 Indeed, the US carrier rate for HCV among otherwise
healthy adults is estimated to be on the order of 1% to 1.8%. These
alarming numbers are in large part the result of transmission
attributable to intravenous drug use and blood transfusions over the
previous decades before HCV screening and programs to curtail
parenteral exposure were introduced.
Clinical Manifestations
The vast literature that has rapidly accumulated in the past
decade has primarily concentrated on the manifestations of hepatitis C
in adults, about which a good deal is now known. Most adults with acute
hepatitis C are asymptomatic. The same is true of individuals with
chronic hepatitis C who typically have an indolent infection with low
level serum transaminase elevations, often interspersed with periods in
which these enzyme values are normal. Symptoms, when they occur, are
usually mild and constitutional, such as easy fatigability and
anorexia. As a result, many individuals are not aware that they are
infected. In the majority of instances, chronic hepatitis C does not
seem to progress. However, over a period of ~20 years, 10% to 20%
of patients develop cirrhosis of the liver.13,14 Deaths
caused by resultant hepatic failure or by the development of
hepatocellular carcinoma are well-recognized sequelae, virtually always
in the setting of cirrhosis. Factors that are associated with
progression include alcoholism, immunodeficiency, older age at onset,
viral genotype type I, and higher levels of circulating HCV. Chronic
hepatitis C is the leading indication for liver transplantation at the
present time and will remain so over the next 2 decades unless a highly effective means to eradicate chronic HCV infection is found.
Treatment
Progress in developing an effective treatment for chronic
hepatitis C has lagged behind other advances in the field, but recent developments suggest a more promising future. Interferon-
has been
used to treat adult patients with evidence of active disease manifested
by persistently elevated serum transaminases, detectable HCV-RNA, and a
liver biopsy indicating significant fibrosis or moderate-to-severe
inflammation and necrosis. Clinical, biochemical, and histologic
responses occur in 40% to 50% of treated patients but sustained
remission rates are only in the order of 10% to 15% with this
regimen.15 Recently, higher rates of remission and
apparent cure rates in the order of 25% to 50% among chronically infected adults have been reported after the use of combination therapy
with interferon- with ribavirin, another anti-viral
agent.16 Although this regimen is not ideal in that it
takes 6 to 12 months to complete, is expensive, and is accompanied by
frequent side-effects, patients who have failed interferon alone also
have responded to combined therapy.17 Reports of children
who have received interferon therapy are now appearing in the
literature.18-21 These studies demonstrated that
interferon can induce a remission and is generally well tolerated by
the few children treated to date, but the rate of a sustained remission
has been quite variable from study to study. There are no published
reports describing the long-term outcome of children treated with
interferon or the effects of interferon plus ribavirin on children with
chronic hepatitis C. A number of other therapeutic agents are now under evaluation with the objective of making available more effective, less
costly, and better tolerated regimens to arrest and cure chronic HCV
infection.
| |
POSTTRANSFUSION HCV INFECTION IN INFANTS AND CHILDREN |
Epidemiology
Field surveys of healthy children and adolescents have shown a low
rate of HCV infection, ranging from 0% to .9%.22-25 However, there is evidence demonstrating that parenteral transmission of HCV among children caused by transfusion of blood and blood products
may have been a frequent complication before the introduction of
mandatory anti-HCV donor screening. In studies that have traced transfused patients whose donors were later found to be
anti-HCV-positive after the serologic test became available, children
have represented 10% to 20% of the recipients who acquired
posttransfusion hepatitis C.26 Chang et al27
followed 88 children at risk for HCV infection, 71 of whom had received
blood before 1992, when donor screening was initiated. Evidence of
subsequent HCV infection was found in 10 (11%) of the entire group and
10% of those who had been transfused. The substantial risk of
transmission before anti-HCV donor screening is also evident in studies
of children requiring multiple blood products, such as for treatment of
sickle cell anemia, thalassemia, and hemophilia. Anti-HCV antibody prevalence rates of 40% to 95% have been found in patients
polytransfused with unscreened blood or pooled
cryoprecipitate.28-30 As with adults, the introduction of
mandatory anti-HCV donor screening also has had a favorable impact on
children who are transfused. Evidence of this comes from the studies of
Matsuoka et al31 who compared the risk of children
acquiring hepatitis C from blood for open heart surgery before and
after units positive for anti-HCV-positive were excluded. Among 161 Japanese children transfused before anti-HCV screening, 22 (14%)
developed posttransfusion HCV infection. In contrast, no cases occurred
after donors were screened for anti-HCV antibodies. The impact of donor
screening also is well documented by a very recent report from Germany
that examined the risk of posttransfusion hepatitis C and long-term
outcome of children who were transfused at a mean age of 2.8 years in
relation to open heart surgery.32 A total of 14.6% of
children transfused before donor anti-HCV screening were found to have
serologic evidence of hepatitis C infection compared with no cases
among 120 children undergoing cardiac surgery after 1992, when donor
screening was implemented in Germany. Although there are isolated
reports of posttransfusion hepatitis C among children who have received
blood subsequent to donor screening, such events are now very rare
indeed.33
The reduction in posttransfusion hepatitis C represents a major public
health achievement. Using statistical sampling methods, it has been
estimated that in the United States the risk of acquiring HCV per
transfused unit was 45/10 000 in 1985 (the year before blood was
screened for non-specific, surrogate markers, alanine aminotransferase
[ALT], and anti-hepatitis B core [anti-HBc], and
19/10 000 from 1986-1990 (when blood was screened for these surrogate
markers).11 If one roughly estimates 15 000 000 transfused units of blood and blood components per year from
1980-1990, there would be nearly 500 000 cases of
transfusion-transmitted HCV in that decade alone. It is not possible to
precisely determine the number of such transfusions that would have
been administered to children, although our data are consistent with
published estimates of 10% to 20%.26 At our facility in
1998, there were a total of 42 303 patient transfusion events
10 205
of these were in patients 16 years old or less and 1110 of these were
in neonates, 4 months old or less (unpublished observations).
Clinical Features
Information about the clinical manifestations of HCV infection in
the pediatric age group is more limited than in adults but is gradually
increasing. There is some evidence to suggest that the clinical
manifestations of hepatitis C in children are milder than in
adults.34,35 Most infants and children who acquire acute
hepatitis C are asymptomatic or have only mild symptoms. Jaundice is
unusual and fulminant hepatitis in the setting of transfusion or
perinatal spread is rare.
Chronic HCV Infection
Assuming the proportion of blood products given to those of
pediatric age a decade ago is similar to the present, a substantial number of transfusions at risk for hepatitis C transmission were administered to children and neonates before initiation of serologic screening for the viral agent.
Consequently, it is very important to define the natural history of
infection in infants and children. Unfortunately, only a few studies
have focused on examining the outcome of hepatitis C beginning in
childhood and, therefore, only a small number of infected children have
been evaluated thus far. In addition, the duration of follow-up in all
but 1 of these studies32 has been short compared with the
slow rate of progressive infection seen in adults, when it occurs. As a
result, an incomplete picture currently exists and conclusions based on
the information now available may turn out to be incorrect. The most
reliable data about chronicity come from investigations, which have
used HCV-RNA to detect the presence of the virus in the blood stream.
Because anti-HCV antibodies may persist in the circulation for years
after recovery, HCV-RNA analysis is a means of distinguishing those children who have ongoing infection, which is clinically and
biochemically silent from those who no longer are infected. The study
conducted in Japan by Matsuoka et al31 of children who
received blood transfusions during open heart surgery used HCV-RNA
analysis. Among 22 children who had evidence of posttransfusion HCV
infection, 10 (45%) were found to have circulating HCV-RNA during a
follow-up period of 4 years. Chang et al,27 noted
previously, prospectively followed 88 children at risk for hepatitis C
infection because of frequent transfusion or perinatal exposure to an
infected mother. Ten of the 88 children (11%) developed HCV infection, including 7 of the 71 (10%) who had been transfused. HCV-RNA was found
in 6 of the 10 (60%) during the 3 years the patients were followed,
including 4 of the 7 with exposure from transfusions. In the report by
Vogt and colleagues32 of German children who developed
hepatitis C infection after transfusion given in relation to cardiac
surgery, 55% of the 67 patients who acquired hepatitis C had
circulating HCV-RNA when studied after a follow-up period of ~20
years. These studies suggest that 40% to 60% of children who acquire
acute HCV from blood transfusion have evidence of chronic HCV infection
when reassessed after an interval of 3 or more years. This rate is
lower than adults but is based on the study of far fewer individuals
and, therefore, interpretation must be tempered with caution.
| |
NATURAL HISTORY OF HCV IN THE PEDIATRIC AGE GROUP |
Information about the consequence of chronic HCV infection in
children is even more limited than in adults. Reports before the
discovery of HCV emphasized the mild nature of chronic NANB hepatitis
and apparent lack of progression.36-37 Because of the
clinically silent nature and low grade biochemical changes that
characterize chronic hepatitis C in the vast majority of instances, the
histopathological findings on liver biopsy are of particular value in
determining the course of infection.
Liver biopsies of children have demonstrated the same histologic
patterns that are found in adults,27,31,37,38 although
several reports have emphasized that the pathologic changes among
pediatric aged individuals are milder.31,32,35 A
longitudinal study by Bortolotti et al39 of 77 consecutively observed European children and adolescents with chronic
hepatitis C provides pertinent information on this matter. During a
follow-up period of 6 years, ~80% remained asymptomatic and both
growth and pubertal development were normal. However, nearly 90% of
the children had elevated serum ALT levels. Liver biopsy in the main showed mild or inactive liver disease. However, cirrhosis was found in
2 of the 77 (2.6%) patients in this group. Both children were found to
have autoantibodies, which raised the possibility that autoimmune liver
disease may have been a contributing factor. These observations led the
authors to conclude that even in the face of persistent liver damage,
severe hepatitis and cirrhosis are infrequent complications of chronic
HCV infection in childhood and adolescence. A report by Badizadegan et
al40 provides a detailed analysis of the histologic
changes of the liver caused by chronic hepatitis C among 40 children
studied in Boston. Eligible children were 18 years old or younger at
the time of evaluation (mean age: 11.4 years) and the mean duration of
infection before biopsy was 6.8 years. Infection was attributed to
blood products in 26 of the patients, representing the major source of
exposure. The investigators found that although necrosis and
inflammation was mild, fibrosis was present in 78% of the patients and
was significant in 58%. Cirrhosis was found in 8% of the patients. The degree of fibrosis correlated with the age and the duration of the
infection, and led the authors to conclude that "chronic hepatitis C
in childhood is not benign, and in some instances, may lead to
significant subsequent morbidity." A correlation between the extent
of fibrosis and the age of the of the child and the duration of
infection also was observed by Guido and colleagues38 who
examined 80 Italian children with chronic hepatitis C without other
medical conditions. The very recent publication of Vogt et
al,32 cited previously, describes the assessment of the
14.6% of German children who developed posttransfusion hepatitis C at
a mean age of 2.8 years as a result of transfusion given in relation to
cardiac surgery. After an interval of ~20 years, among the 67 (14.6%) who were found to be anti-HCV-positive, 37 (55%) had
detectable HCV-RNA in their blood. Thus, 45% of the individuals had
eliminated their infection spontaneously. Seventeen of the 37 who were
viremic (HCV-RNA-positive) underwent liver biopsy. Minimal lymphocytic
infiltration of portal triads without evidence of fibrosis or necrosis
was present in 14 patients. Periportal fibrosis was found in 2 patients, but both also had severe congestive heart failure. A third
patient had cirrhosis but this individual also was infected with
hepatitis B. Of note, there was no statistically significant difference
in biochemical tests, such as the serum transaminases, between those
who were HCV-RNA-positive and those who had cleared the virus.
Moreover, genotype 1, the most virulent HCV genotype, predominated in
their series. These observations led the authors to conclude that
children chronically infected with hepatitis C have a more benign
clinical course than individuals who acquire HCV infection initially as
adults. However, it should be noted that only 17 of the 37 infected
children were biopsied.
Based on currently available information, it would seem that chronic
hepatitis C is clinically milder in children compared with adults and
progresses less often and perhaps more slowly when it occurs. Cirrhosis
in those initially infected in childhood is a very infrequent sequela
in the absence of associated conditions, at least during the initial 3 to 20 years after infection. The extent to which other factors, such as
an underlying disease, iron overload from hemolysis, or the development
of autoimmune liver disease, contribute to the development of cirrhosis
is unknown at present. Long-term follow-up of additional children with
chronic hepatitis C is needed to determine the actual risk of
progression, the rate of progression when it occurs, and whether other
factors are important determinants.
| |
POSTTRANSFUSION HCV INFECTION IN NEONATES |
Neonates comprise a substantial proportion of pediatric aged
individuals who are transfused and yet relatively little is known about
their risks of developing posttransfusion hepatitis C and its outcome.
That which has been reported gives a conflicting picture. Two studies
suggest that hepatitis C, at least chronic HCV infection among
transfused neonates, is uncommon. Preiksaitis et al41
conducted a retrospective analysis of 109 neonates transfused between
1983 and 1985. Serum from 84 of the patients obtained at least 10 weeks
after transfusion (mean: 16.6 weeks) were later tested for anti-HCV by
third generation immunoassay and none were found to be positive. It
should be noted that this study was originally designed to examine the
occurrence of cytomegalovirus infection in this population rather than
HCV. Because anti-HCV seroconversion may not occur for >3 months after
the onset of infection, the time of follow-up in this study was less
than desirable. Keller and Wirth42 reported the HCV
infection rate of 262 children who received multiple units (5-927
mg/kg birth weight) of blood as neonates. At a mean age of 3.5 years, 14 (5.3%) were anti-HCV reactive and an additional 2 were
suspected on clinical grounds. Only 3 (1%) of the patients were
anti-HCV-positive when reassessed 6.5 years later and all had normal
liver enzymes. However, this study used a first-generation assay test
system for detection, which is less sensitive than assays that are
currently in use, and HCV-RNA testing was not performed. As a result,
the study may have underestimated (or overestimated) the actual number
of neonates who developed chronic HCV infection. Nonetheless, these observations suggest that infection even if present was not accompanied by biochemical changes. In contrast to these 2 reports, other studies
indicate that acute HCV infection consequent to transfusion during the
neonatal period was common before donor anti-HCV screening and that
chronic infection did occur as a consequence. In the European study of
77 children with chronic hepatitis C cited earlier, 46 (60%) had been
transfused during the neonatal period, representing the most common
identified exposure among the children studied.38 O'Riordan and colleagues43 investigated newborns
transfused between 1980 and 1991 who had received blood products,
primarily anti-D globulin, which were later found to be infected with
HCV. They identified a total of 24 infants transfused at a mean age of
12 days and were able to trace 21 of the children. Of the 20 children
with complete transfusion records, 12 (60%) were found to be
anti-HCV-positive and 7 (35%) had detectable HCV-RNA indicative of
chronic HCV infection when assessed at a mean age of 6.3 years. Nelson
and Jonas44 determined the prevalence of anti-HCV among 83 of 187 neonates who were treated with extracorporeal membrane
oxygenation therapy from 1986 to 1992. Records that were still
available indicated possible exposure to an average of 31 donors per
child. Among the 50 neonates given blood before anti-HCV donor
screening, 6 (12%) were found to be positive. This compared with a
rate of 3% among the 33 patients transfused at a later time only with
blood that had been prescreened for anti-HCV. This calculates to a
minimum RIBA confirmed infection rate of 4.8%. Among the 7 patients
found to be anti-HCV reactive, 4 still had elevated ALT levels
consistent with chronic hepatitis C on follow-up. Three had liver
biopsies at 2 to 5 years old, which demonstrated mild-to-moderate
fibrosis and necroinflammatory activity of varying degrees. These
findings led the authors to conclude that pediatricians must be alert
to the occurrence of chronic hepatitis C in children exposed to the
viral agent as neonates.
Taken together, the available information indicates that neonates given
blood before donor anti-HCV screening were at substantial risk for
posttransfusion hepatitis C and may constitute a sizeable proportion of
those with chronic HCV infection who were infected during childhood.
Infection in neonates seems to be clinically silent and biochemical
abnormalities may be minimal or absent. However, its long-term course
in transfused neonates is at present unknown. More data are very much
needed. We are currently conducting a 20-year follow-up of young adults
who were transfused as very low birth weight neonates that might
provide additional information in this regard.
As a result of its silent nature, chronic hepatitis C will likely be
missed by the pediatrician unless it is suspected on historical grounds
because of a history of premature delivery or a medical problem for
which transfusion with a blood product may have been indicated (or if
there is a history of maternal high-risk factors for acquiring HCV).
Children and their parents may be unaware that transfusions were given
during the neonatal period and this information may be difficult to
obtain from old records. These factors were important determinants in
initiating the lookback process, recently mandated by the Food and Drug
Administration (FDA).
| |
THE LOOKBACK PROCESS |
The lookback process, first implemented by organized blood banking
and later mandated by the FDA for donor HIV testing, has as its
objective the identification of recipients of blood that may be
contaminated with infectious agents.45,46 There are 2 types of lookback, targeted and general. Targeted lookback consists of
tracing back, from a specific donor positive for a
transfusion-transmitted agent, previous blood components provided by
this donor and transfused to patients at a time when the donor was
either test negative or not yet tested for the particular transmissible
agent. General lookback consists of varying degrees of broad-based
education programs directed to the patient, the public, and physicians
through media coverage, public service announcements, written
materials, and meetings. It is designed to inform an audience about the
risks of transfusion and thereby achieve voluntary participation, based
on risk, in a blood-testing program. A lookback program has 2 broad
practical purposes. It is first and foremost a public health
initiative, designed to detect and prevent the spread of transmissible
diseases from largely unsuspecting and often asymptomatic individuals.
Secondly, it is a means of identifying individuals with a specific
infection early in their course, who might be amenable to lifestyle
changes and/or treatment modalities.46 Because lookback
efforts for transfusion-associated HIV have had mixed results in
identifying infected transfusion recipients, there was minimal
enthusiasm for mandating similar efforts for HCV.45
Nonetheless, in September 1998, the FDA issued a policy requiring blood
collection facilities to notify hospitals of all previous donations
obtained from a donor who on the most recent donation since May 1990, tested positive for HCV and who either: 1) previously tested negative
for HCV or 2) donated before testing was implemented in May 1990. Initially, the FDA mandated that recipient tracking be required to
extend back at least 10 years to a cutoff date of January 1, 1988.47 More recently, the FDA has recommended that
recipient tracking continue back indefinitely "to the extent that
electronic or other readily retrievable records
exist."48 Because notification of transfusion recipients
is not required until September 30, 2001 and because only donors who
later return and test HCV-positive will trigger a lookback, at this
time, there are many thousands of recipients who are unaware of the
fact that they may have been infected with HCV. This is especially
relevant to the many young women who received blood as neonates 20 or
more years ago and who are now approaching childbearing age and could be a source of secondary infection to their offspring. In addition to
the FDA-mandated, targeted lookback approach, the Centers for Disease
Control and Prevention has recommended a general lookback educational
approach that focuses primarily on health care providers to ascertain a
patient history of transfusion therapy from their patients with
follow-up HCV testing as indicated.
Preliminary data from Canada are available on the efficacy of a general
HCV lookback in a pediatric population. Heddle and coworkers49 sent notification letters to 1546 patients, 16 years old and younger, who received blood transfusions between February
1978 and November 1985 in an effort to discern the efficiency of the
notification process, awareness of transfusion history, and interest in
follow-up testing. Not surprisingly, one third of the notification
letters were returned undelivered, and nearly one third were unaware of
their transfusion status. However, nearly 90% of those successfully
contacted indicated a willingness to undergo HCV serology testing. In
another general lookback study in a Canadian pediatric population,
Roberts and coworkers50 conducted a lookback study in 1995 of people transfused between December 1985 and May 1990. They
identified 146 HCV-positive transfusion recipients for a minimum
prevalence of new infection of 1.4%. In the lookback effort to assess
individuals who had been treated with extracorporeal membrane
oxygenation as neonates cited earlier, only 44% of the 187 who were
still alive were traced and tested.44 These studies
indicate that targeted lookback can identify some at-risk individuals
who were previously unaware of their HCV infection and that some, but
not all, will seek appropriate follow-up.
Many children with chronic hematologic disorders requiring transfusion
therapy have already been tested for hepatitis C. However, children,
particularly neonates, transfused immediately or shortly after birth
and not requiring ongoing transfusion support, may be unaware of their
previous transfusion history and risk status for hepatitis
C.26 It is important to target such individuals for
hepatitis C testing. At present, only individuals who were born on or
after January 1, 1988 will be preferentially identified by the current
targeted donor lookback process because hospitals may or may not
receive notifications of transfusions from potentially infected donors
before this time. We urge that hospitals, neonatologists, and
pediatricians become partners in this lookback process by reviewing
their files to identify at-risk patients transfused as neonates or as
children, so they (or their parents) can be contacted to offer
hepatitis C testing. Those identified should be encouraged to be tested
for the presence of anti-HCV, and positive test results should be
further analyzed with a RIBA supplemental test for confirmation.
Consideration should also be given to testing those whose antibody
positivity has been RIBA confirmed, by polymerase chain assay for
circulating HCV-RNA to determine whether they continue to be infected.
Children who have continuing HCV infection will require on-going
follow-up for this condition, and encouragement to maintain a lifestyle
that minimizes the risk of progression of their infection. In
particular, excessive alcohol use and needle sharing should be
avoided.51 It also is very important that they be
vaccinated to prevent against coinfection with the hepatitis A and the
hepatitis B viruses.10 Serious and even life-threatening
fulminant hepatitis has been described in individuals with chronic
hepatitis C who become superinfected with acute hepatitis
A.52
A major challenge to those in the field is to better define the natural
history of hepatitis C in children. This is particularly true for those
who were initially infected as neonates because so little is known
currently about the course of hepatitis C in this population. As more
effective therapeutic regimens with fewer side-effects become
available, such studies will help provide the guidelines so very much
needed to direct the course of management of what may be a substantial
number of young HCV-infected individuals.
,
, 
Top
Background
References
