INTRODUCTION — Children represent only a small proportion of the hepatitis C virus (HCV)-infected population. Nevertheless, a substantial number of children have chronic HCV infection and are at risk for complications. According to one report [1], there are approximately 115 million infected persons in the world, 11 million of whom are younger than 15 years of age. Eighty million are viremic, of whom 5 million are younger than 15 years of age. It has been estimated that the global health care costs for HCV-infected children and their families are hundreds of millions of dollars annually [2].
The major issues related to HCV in children will be reviewed here. Perinatal transmission of HCV is discussed separately. (See "Vertical transmission of hepatitis C virus".)
Treatment of HCV in adults is discussed in the following topic reviews:
●(See "Overview of the management of chronic hepatitis C virus infection".)
●(See "Treatment regimens for chronic hepatitis C virus genotype 1 infection in adults".)
●(See "Treatment regimens for chronic hepatitis C virus genotypes 2 and 3 infection in adults".)
●(See "Treatment regimens for chronic hepatitis C virus genotypes 4, 5, and 6 infection in adults".)
EPIDEMIOLOGY — In the United States, antibodies to HCV are present in approximately 0.3 percent of children under 14 years of age and 9 percent of those ages 15 through 24 years [3]. The prevalence in youth and young adults is increasing, driven by injection drug use, but is still less than in older adults [4]. A systematic review reports an overall prevalence of HCV in children of 0.87 percent, ranging from 0.34 percent in Europe to 3.02 percent in Africa [5]. The frequency of cases that are clinically identified is far lower (5 percent of the expected number), suggesting that screening for and case identification of pediatric HCV are grossly inadequate [6,7]. The proportion of children who are HCV antibody-positive who are also HCV ribonucleic acid (RNA)-positive is not known precisely; based upon studies in adults, it is estimated to be approximately 75 to 80 percent. HCV viremia was detected in 56.8 percent of children in the systematic review [5]. (See "Epidemiology and transmission of hepatitis C virus infection".)
Of concern, rates of acute HCV infection among young people appear to be increasing in the United States, particularly in suburban populations [8,9]. This pattern mirrors the epidemic of prescription opioid and subsequent heroin use in these areas. (See "Epidemiology and transmission of hepatitis C virus infection", section on 'Incidence of new infection'.)
The estimated burden of viremic HCV infection in children ages 1 to 19 years is 3.5 million people (95% CI 3.1-3.9 million) [10]. The largest numbers of infected children are in countries in Asia, the Middle East, and Africa. There have been no recent epidemiologic studies of HCV-infected children in developed countries, but the incidence of new cases has been increasing in the United States, paralleling the opioid epidemic. Since many young women infected by this route are of childbearing age, pediatric cases are expected to increase in parallel.
Perinatal transmission is by far the most common source of HCV infection in children, probably accounting for more than 1500 new cases/year in the United States, although many of these cases remain undiagnosed [11]. The incidence of HCV vertical transmission is approximately 1 to 5 percent in HCV RNA-positive mothers, with the highest risk in mothers with high HCV viral load [12,13]. The risk is further increased for mothers with untreated human immunodeficiency virus (HIV) coinfection. (See "Vertical transmission of hepatitis C virus".)
Antiretroviral therapy in HIV/HCV-coinfected women reduces the rate of vertical transmission by HCV-infected women [14]. The advent of highly effective direct-acting antiviral agents (DAAs) for HCV has the potential to further reduce the rates of HCV in children if reproductive-aged women with HCV can be identified and treated prior to conception. Screening of pregnant women for HCV is discussed separately. (See "Prenatal care: Initial assessment", section on 'Hepatitis C'.)
Other individuals acquire the infection during adolescence through high-risk behaviors such as intravenous or intranasal drug use and use of shared tattoo equipment. (See "Epidemiology and transmission of hepatitis C virus infection", section on 'Routes of transmission'.)
NATURAL HISTORY — Because HCV liver disease generally progresses slowly, serious consequences such as cirrhosis or hepatocellular carcinoma are rare during childhood. The following general observations have emerged from natural history studies in children.
Spontaneous clearance — Infections acquired during infancy (usually through perinatal transmission) are most likely to clear spontaneously, with spontaneous clearance rates ranging from 20 to 45 percent [15-22]. Those with perinatally acquired HCV have rates of clearance on the lower end of this range. By contrast, HCV acquired later in life is less likely to clear spontaneously. (See 'Factors associated with disease progression' below.)
One of the largest series with long-term follow-up in perinatally acquired HCV included 266 children who were followed for a median of 4.2 years [23]. Approximately 20 percent cleared the infection, while 80 percent had chronic infection. Clearance was less likely in children who remained polymerase chain reaction (PCR)-positive after the first year of life and those who were persistently PCR-positive during the first year of life. Most children with chronic infection were asymptomatic. Hepatomegaly was observed in 10 percent.
There is also some evidence that the risk of developing chronic infection may be lower in patients presenting with symptomatic acute HCV infection [24]. (See "Clinical manifestations, diagnosis, and treatment of acute hepatitis C virus infection in adults", section on 'Spontaneous viral clearance'.)
Advanced disease — In many patients, hepatic fibrosis scores tend to increase with age, suggesting there is slowly progressive histologic injury [25-29]. The development of advanced liver disease is uncommon until more than 30 years after infection in children [15,16]. However, progression to advanced fibrosis and cirrhosis during childhood occasionally occurs, as described in the following case series:
●In a series of 121 treatment-naive children with hepatitis C, 80 percent had some fibrosis [28]. This was usually mild, but five patients had bridging fibrosis and two had cirrhosis. The patients with advanced fibrosis tended to be older, suggesting that fibrosis increases with time. Obesity and perhaps other cofactors probably contribute to the severity of the liver disease.
●In a series of 332 children with hepatitis C and persistent viremia, six children progressed to decompensated cirrhosis; the duration of infection before cirrhosis was noted was 2 to 15 years [30]. Five of the six children were infected with genotype 1a HCV, and only one was coinfected with HIV.
●In our practice, we have seen a number of children who developed decompensated cirrhosis during adolescence. Three children with decompensated HCV-associated cirrhosis at ages 4, 6, and 11 years have also been reported by other centers [31]. In all of these children, the HCV infection was acquired perinatally.
Factors associated with disease progression — Several factors associated with disease progression have been described, although the strength of these associations is unclear. Clinical predictors for disease progression in adults are discussed in detail separately. (See "Clinical manifestations and natural history of chronic hepatitis C virus infection", section on 'Natural history'.)
Perinatal transmission — Perinatally acquired ("vertical" or "mother-to-child" transmission) HCV infection is the major route of new infections in children in developed countries. The risk of transmitting the virus from an HCV-infected woman to her infant is 1 to 5 percent, with higher rates if the mother has inadequately controlled HIV coinfection [12,13,32]. The infants who are infected commonly have elevated serum aminotransferases for a few years that often become normal [33]. Ten to 20 percent of children with perinatally acquired HCV infection clear the virus during the first two years of life [19,23]. Estimated rates of spontaneous clearance vary, probably because different standards are used to define the infected status at birth; one small series suggested spontaneous clearance rates of up to 75 percent [34]. Almost all children who remain viremic after three years of age have chronic hepatitis [19,23,35,36]. The risk factors for perinatal transmission of HCV are discussed in detail separately. (See "Vertical transmission of hepatitis C virus".)
Other — Several other factors associated with disease progression have been identified, including immunosuppression (from HIV infection or other causes), chronic alcohol ingestion, obesity, and possibly by viral factors [37,38]. (See "Clinical manifestations and natural history of chronic hepatitis C virus infection".)
SCREENING — Universal screening for childhood HCV infection is not warranted in most communities. This was suggested by a review of 1034 children seen in an urban pediatric hospital; only one child was found to be HCV-positive, although some members of the population screened had risk factors for HCV disease (7 percent of the children's mothers had a history of blood transfusion, and 1.8 percent had a history of intravenous drug use) [39].
However, selected screening is appropriate for the following groups of individuals who are at increased risk for HCV [22,40,41]. Screening uses the same approach as diagnostic testing (see 'Diagnosis' below):
●Children with clinical evidence of hepatitis, including unexplained elevation of serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), even if asymptomatic.
●Infants or children whose mothers are known to be infected with HCV or have a history of intravenous drug use, or siblings of children with vertically acquired chronic HCV, if born to the same mother.
●Children who are international adoptees or refugees. Most children adopted into the United States in recent years have come from countries with relatively high prevalence rates, including China, Russia, and Southeast Asia and because risk factors for infection rarely are known. (See "International adoption: Infectious disease aspects", section on 'Hepatitis C virus'.)
●Children and adolescents with HIV infection.
●Adolescents or children who are victims of a sexual assault or adolescents with a history of multiple sexual partners.
●Adolescents with a history or suspicion of illicit injection drug use. A high index of suspicion for this possibility is appropriate in the United States, given the unfolding epidemic of opioid and subsequent heroin use, especially in nonurban populations. (See 'Epidemiology' above.)
In contrast with the selective screening for adolescents, as recommended above, universal screening for HCV infection is now recommended for adults in the United States. (See "Screening and diagnosis of chronic hepatitis C virus infection", section on 'Routine one-time screening for adults'.)
Individuals with a positive HCV antibody test should be further evaluated with a HCV RNA test to confirm the diagnosis, as discussed in the next section.
DIAGNOSIS
●Children 18 months and older – The principles of diagnosis of HCV infection in children are similar to those employed in adults. Initial diagnostic evaluation for chronic HCV typically begins with an anti-HCV antibody test. A reactive or indeterminate/equivocal antibody test in a child 18 months or older should be followed by HCV RNA testing. This can be done immediately to identify those children at risk for chronic infection and link them to a follow-up schedule or can be deferred until after three years of age, when spontaneous resolution is no longer likely and treatment will be available. If HCV RNA is detected, the diagnosis of HCV infection is confirmed. These patients should be further evaluated to determine the genotype and extent of disease, then monitored for disease progression or spontaneous clearance, as discussed below. (See 'Further evaluation' below and 'Subsequent monitoring' below.)
If HCV RNA is not detected, then a reactive antibody likely represents either a past HCV infection that subsequently was cleared or a false-positive antibody test. (See "Screening and diagnosis of chronic hepatitis C virus infection", section on 'Initial testing'.)
●Infants <18 months – For infants with perinatal HCV exposure, updated recommendations now prioritize early testing to try to minimize loss to follow-up, using a two-step process:
•The first step is to test for HCV RNA during infancy (ideally between two and six months of age) [42-44]. A negative HCV RNA test at this time point can be used to reassure the family that HCV infection is very unlikely [42]. Conversely, a positive HCV RNA test in infancy suggests infection but does not necessarily predict chronic infection, because of the possibility of spontaneous viral clearance [32]. Repeated HCV RNA testing prior to 18 months of age is unnecessary.
•The second step is to test for anti-HCV antibodies at 18 months of age for all perinatally exposed infants, regardless of the results of early HCV RNA testing. Those with positive results should be tested for HCV RNA, as outlined above.
Previous recommendations for HCV evaluation in this cohort were to wait until infants are 18 months old to test for HCV infection, starting with anti-HCV antibody testing, followed by HCV RNA testing for those with positive results. Prior to 18 months, anti-HCV antibodies in infancy are not specific for infection, because a positive test could reflect passive transfer of maternal immunoglobulin G (IgG) antibodies [45]. Passively acquired maternal antibodies against HCV are cleared in 95 percent of infants by 12 months [33,46]. However, this approach is associated with significant loss to follow-up because of the prolonged time prior to testing, such that 70 to 90 percent of exposed infants were never screened for HCV after vertical exposure [47-50].
FURTHER EVALUATION — When HCV infection is diagnosed in a child, further evaluation is warranted to inform treatment decisions and to monitor for progression of liver disease.
Hepatitis C virus genotyping — With the availability of direct-acting antiviral agents (DAAs) that have activity against all known HCV genotypes, there is less need for genotype testing. Nonetheless, many public and private treatment programs require HCV genotyping for children with confirmed HCV infection prior to approving treatment. The genotype may determine duration of DAA treatment, especially if there is advanced liver disease or if previous treatment has failed. (See "Screening and diagnosis of chronic hepatitis C virus infection".)
Liver biopsy
Indications — For most pediatric patients with HCV infection, a liver biopsy is not necessary, because it does not affect treatment decisions. Treatment is now available for most pediatric patients ages six years and older, using DAAs, as discussed below (see 'Management of chronic hepatitis C virus' below). A liver biopsy is not required to establish the diagnosis of HCV infection.
A liver biopsy may be appropriate for selected children and adolescents with the following characteristics:
●Those with comorbid disease, such as obesity with possible nonalcoholic fatty liver disease, HIV coinfection, or congenital heart disease with elevated right heart pressure, or children who require potentially hepatotoxic drugs (such as anticonvulsants, psychotropic medications, or chemotherapy). In such patients, a liver biopsy is appropriate if the results would influence the decision to initiate early treatment for HCV or modify treatment of the underlying disease.
●Those with suspected advanced liver disease (eg, with signs of portal hypertension, such as splenomegaly), if the results of the biopsy would influence the treatment decision, such as strategies to access a DAA-based regimen. Some DAA regimens vary by cirrhosis status, and some are contraindicated in decompensated cirrhosis. (See "Overview of the management of chronic hepatitis C virus infection", section on 'Regimen selection'.)
Histology — Histologic features of HCV infection in children are similar to those in adults. Characteristic findings include portal lymphoid aggregates or follicles, sinusoidal lymphocytes, and steatosis (picture 1 and picture 2) [26,27,51]. Although the histologic features are similar, liver disease appears to be less severe in children than in adults with similar duration of infection, HCV RNA level, and genotype [52]. Cirrhosis occasionally occurs during childhood or adolescence but is much less common than in adults (picture 3). (See 'Natural history' above.)
The best clinical predictors of disease progression in adults with chronic HCV infection are the amount of inflammation and fibrosis on liver biopsy. Other clinical factors that predict disease progression are discussed separately. (See 'Factors associated with disease progression' above and "Clinical manifestations and natural history of chronic hepatitis C virus infection", section on 'Liver histology'.)
Testing for coinfection — Individuals with HCV infection should also be screened for coinfection with hepatitis B virus (HBV) and HIV due to common modes of transmission [13]. In addition, pre-treatment assessment of the patient's HBV status is warranted because latent HBV infection may be activated when HCV is treated with certain DAA regimens, as described in case reports. (See "Overview of the management of chronic hepatitis C virus infection", section on 'Other monitoring'.)
HBV screening is performed by measuring hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and hepatitis B surface antibody (HBsAb):
●Positive results for HBsAg or HBcAb indicate coinfection with HBV, which increases the risk for progressive HCV disease and for hepatocellular carcinoma (see 'Malignancy' below). In addition, individuals with HCV/HBV coinfection are at risk for HBV reactivation during treatment with DAAs. (See 'Precautions and monitoring' below.)
●Negative results for HBsAb indicate susceptibility to HBV infection or waning antibody levels. Individuals with this result should be immunized or reimmunized against hepatitis B. (See "Hepatitis B virus immunization in adults".)
In addition, individuals with HCV infection should be screened for hepatitis A virus (HAV) antibodies and immunized if not immune. (See "Overview of hepatitis A virus infection in children".)
SUBSEQUENT MONITORING — Once the diagnosis of chronic HCV is established and the disease is fully characterized as described above, the patient should be monitored for disease progression [13].
Serum aminotransferases — Serum aminotransferase levels are not consistently related to disease severity in HCV-infected patients. In one series of children with HCV infection, one-third had normal aminotransferase levels despite substantial histopathologic evidence of inflammation [28]. However, serial measurements may be used to monitor disease activity.
For otherwise healthy, HCV-infected children who will not be treated (eg, if treatment is not appropriate or available for some reason), we monitor by physical examination and measurement of alanine aminotransferase (ALT) every 6 to 12 months. More frequent monitoring is performed in children with comorbidities, such as coinfection with HIV or those taking potentially hepatotoxic medications.
Serial testing for hepatitis C virus RNA — In general, we do not perform serial testing of HCV RNA in children with documented chronic HCV infection. This is because the HCV RNA level does not correlate with disease severity and does not influence the timing of treatment decisions.
We repeat this test under the following circumstances:
●If ALT reverts to normal for >12 months. In this case, we measure HCV RNA to determine if the child has spontaneously cleared the HCV infection. (See 'Spontaneous clearance' above.)
●If treatment is being considered (eg, if the child reaches the age at which a direct-acting antiviral agent [DAA] regimen is available). In this case, we measure HCV RNA to confirm that the child has active HCV before proceeding with treatment.
Malignancy — Chronic infection with HCV has been associated with hepatocellular carcinoma, which is rare and occurs almost exclusively in individuals with the following additional risk factors:
●Cirrhosis [53]
●Coinfection with hepatitis B virus (HBV; even in the absence of cirrhosis)
●History of childhood leukemia [53,54] or other malignancy
Monitoring children for the possibility of hepatocellular carcinoma is recommended for children with cirrhosis. In such patients, guidance suggests monitoring with liver ultrasonography and serum alpha-fetoprotein levels every six months [13]. Successful treatment of HCV in cirrhotic patients probably does not completely eliminate the risk of hepatocellular carcinoma, so we continue to monitor these patients. (See "Epidemiology and risk factors for hepatocellular carcinoma", section on 'Hepatitis C virus'.)
MANAGEMENT OF ACUTE HEPATITIS C VIRUS — Acute HCV infection is uncommonly recognized in children except in rare outbreaks [24]. Fulminant hepatitis is rare. A minority of patients clear the infection spontaneously, but the natural history in children is not known.
There are no data regarding treatment of acute HCV infection in children. However, we suggest treatment for most patients, provided that an effective regimen of direct-acting antiviral agents (DAAs) is available, following guidance for adults with acute HCV infection. (See "Clinical manifestations, diagnosis, and treatment of acute hepatitis C virus infection in adults".)
MANAGEMENT OF CHRONIC HEPATITIS C VIRUS — The treatment of chronic HCV infection has changed dramatically since the development of direct-acting antiviral agents (DAAs) and combination drug regimens. These therapies represent a major milestone in the treatment of HCV in adults, adolescents, and children as young as three years of age and are likely to be available for younger children in the near future. DAA regimens are effective, well tolerated, all oral, and interferon free. Regimen selection may vary by genotype and other patient factors, such as the presence of cirrhosis and treatment history. (See "Overview of the management of chronic hepatitis C virus infection".)
Pediatric trials — Trials of DAAs in pediatric cohorts have led to approvals by the US Food and Drug Administration (FDA) for several drugs and combinations, and some additional trials have been completed. The key trials are summarized below.
●Sofosbuvir-velpatasvir was evaluated in an open-label trial of 216 children in children ≥3 years with chronic HCV infection, most of whom had been infected through vertical transmission and were treatment-naïve (NCT03022981) [55]. The sustained virologic response (SVR) rates for all genotypes were >90 percent, and pharmacokinetics were similar to those in adults. It is important to note that most children who did not achieve SVR were either lost to follow-up or left the study after one dose of drug. This study was the basis for FDA approval for treatment of chronic HCV infection in children ≥3 years. Gastrointestinal adverse events were somewhat more common in the younger children.
●Glecaprevir-pibrentasvir was evaluated in 47 adolescents with various HCV genotypes and had an SVR rate of 100 percent with as little as eight weeks of treatment [56].
Glecaprevir-pibrentasvir was studied in children age 3 to <12 years of age with various HCV genotypes and had an SVR rate of 96 percent [57]. The subjects were given weight-based doses of glecaprevir-pibrentasvir for 8, 12, or 16 weeks. Final efficacious pediatric doses were 250 mg glecaprevir plus 100 mg pibrentasvir (in children weighing ≥30 kg to <45 kg), 200 mg glecaprevir plus 80 mg pibrentasvir (≥20 kg to <30 kg), and 150 mg glecaprevir plus 60 mg pibrentasvir (12 kg to <20 kg). No participants had virologic failures on the final dose ratio of glecaprevir 50 mg/pibrentasvir 20 mg. Most adverse events were mild, no drug-related serious adverse events occurred, and pharmacokinetic exposures were comparable with those of adults.
The above studies were the basis for the approval of glecaprevir-pibrentasvir for treatment of HCV infection in children three years and older by the FDA [58].
Both of these drug combinations are among the preferred regimens for adults with any HCV genotype, except for selected treatment-experienced patients. (See "Overview of the management of chronic hepatitis C virus infection", section on 'Antiviral therapy'.)
Treatment decisions and regimens — The decision to treat for HCV in children depends upon the child's age, genotype, and regulatory approvals for each age group. Our approach, based on the limited studies in pediatric patients and related drug approvals in United States, is consistent with guidance from the American Association for the Study of Liver Diseases and Infectious Diseases Society of America [41]. The approach will continue to evolve with further studies in pediatric populations.
Children <3 years — For children younger than three years of age with HCV infection, we suggest deferring treatment (algorithm 1) [41]. HCV infection may spontaneously resolve in these young children or they will become eligible for DAA treatment by waiting until after their third birthday (see 'Children ≥3 years' below). Deferring treatment for even several years is often appropriate because most pediatric patients have mild HCV liver disease that progresses slowly. These patients should be monitored with serial measurements of serum aminotransferases; some patients should also be monitored for development of malignancy, as discussed above. (See 'Subsequent monitoring' above.)
Children ≥3 years
●Choice of medication – For children ≥3 years and adolescents, several options are approved in the United States (algorithm 1) and can be used for all HCV genotypes:
•Sofosbuvir-velpatasvir is given for 12 weeks, using weight-based dosing outlined in the LexiComp monograph. An exception is the rare child with decompensated cirrhosis, who may need combination therapy with ribavirin.
•Glecaprevir-pibrentasvir is given for eight weeks for treatment-naïve patients, using weight-based dosing as outlined in the LexiComp monograph. Longer courses are indicated for patients previously treated with other regimens for HCV. The combination of glecaprevir-pibrentasvir can interfere with the metabolism of other medications. (See "Direct-acting antivirals for the treatment of hepatitis C virus infection", section on 'Glecaprevir-pibrentasvir'.)
The choice among these regimens may be dictated by the payor, but all of the above regimens have comparable and excellent efficacy and safety.
For the rare patient who experiences relapse of HCV infection or who does not respond to pan-genotype regimens, sofosbuvir-velpatasvir-voxilaprevir can be offered. This regimen is FDA-approved for patients >18 years old and has demonstrated efficacy in adolescents who are both treatment-naïve and those who experienced DAA treatment failure [59].
●Options outside of the United States – In some global settings, the combination of sofosbuvir and daclatasvir has been used to treat children as young as eight years old with chronic HCV infection. Reports of real-world safety and efficacy demonstrate that this is a highly effective regimen in children [60]. The experience in adults is discussed separately. (See "Treatment regimens for chronic hepatitis C virus genotypes 2 and 3 infection in adults", section on 'Daclatasvir plus sofosbuvir'.)
If an effective DAA regimen is not available to the patient (eg, in countries in which these drugs are not approved for this age group), it is reasonable to defer treatment for at least a few years until a DAA regimen becomes available. Deferring treatment for several years is often appropriate because most pediatric patients have mild HCV liver disease that progresses slowly. These patients should have regular follow-up and monitoring of aminotransferases, as described above (see 'Subsequent monitoring' above). However, it is important to avoid pregnancy until after successful treatment is completed to avoid the risk of perinatal transmission of HCV. If ribavirin is included in the regimen, pregnancy must be avoided both during and after treatment to avoid teratogenicity. (See "Vertical transmission of hepatitis C virus" and 'Precautions and monitoring' below.)
Alternate DAA regimens also may be available outside of the United States. DAA regimens for adults are described separately. (See "Overview of the management of chronic hepatitis C virus infection", section on 'Regimen selection'.)
Special considerations may apply to the rare adolescent who has tried and failed a previous course of treatment (either interferon-based or a DAA regimen), those with advanced cirrhosis, or those with hepatitis B virus (HBV) or HIV coinfection. Although there is little information available about treatment of such patients during adolescence, it would be reasonable to consider the regimens that are recommended for adults with the same characteristics. HIV coinfection is one reason to prioritize a patient for HCV antiviral therapy because of more rapid progression to advanced liver disease in the setting of HIV. Patients with HBV coinfection are at risk for HBV reactivation during treatment with DAAs. (See "Overview of the management of chronic hepatitis C virus infection", section on 'Regimen selection'.)
●Administration to young children – For young children who have difficulty swallowing pills, pellet or granule formulations are available. Young children may not find the small granules palatable or be able to swallow them without chewing, so it may be prudent to defer treatment until the medication can be reliably administered.
Cost-effectiveness — Although DAA regimens are generally costly, they are considered cost-effective because they can help prevent complicated HCV liver disease throughout the lifespan. As an example, one analysis estimated that treating 10, 000 individuals during childhood would prevent 330 cases of cirrhosis, 18 cases of hepatocellular carcinoma, and 48 liver-related deaths during adulthood [61].
Precautions and monitoring — Before initiating DAA treatment, HBV coinfection should be excluded by measuring hepatitis B core antibody (HBcAb). This is because reactivation of HBV has been reported in adults with HCV/HBV coinfection who were undergoing DAA treatment. (See "Overview of the management of chronic hepatitis C virus infection", section on 'Other monitoring' and 'Malignancy' above.)
Ribavirin is teratogenic and is contraindicated during pregnancy and in male sexual partners of pregnant women. Therefore, for females of childbearing age, pregnancy testing and assessment of contraception use should be performed before, during, and for nine months after ribavirin treatment [62]. Both males and females who are sexually active should use two forms of effective contraception during ribavirin treatment. Effective contraception should be continued after completing treatment for nine months for female patients, or six months for male patients. Ribavirin will not be needed in pediatric HCV treatment once pangenotypic regimens are approved for children as young as three years of age. (See "Treatment regimens for chronic hepatitis C virus genotypes 2 and 3 infection in adults", section on 'Selection of treatment regimen'.)
Monitoring for viremia and drug toxicity during antiviral therapy is discussed separately. (See "Overview of the management of chronic hepatitis C virus infection", section on 'Monitoring during antiviral therapy'.)
Follow-up after antiviral therapy — Virologic response to treatment should be assessed by checking the viral load at 12 weeks after completing therapy. Patients with bridging fibrosis or cirrhosis require ongoing monitoring for complications. (See "Overview of the management of chronic hepatitis C virus infection", section on 'Follow-up after antiviral therapy'.)
COUNSELING
Prevention of transmission — Patients with active HCV and their families should be counseled about the specific routes of HCV transmission (perinatal transmission and via infected blood) and given advice to reduce the risk of transmission to other individuals (table 1). Key information includes:
●HCV is not spread within households, school, or daycare settings, and children with HCV should not be excluded [13,63,64]. Because HCV is transmitted by blood, it may be prudent to avoid sharing razors, toothbrushes, nail clippers, and other implements that may be contaminated with blood of an infected individual. Although HCV can be detected in low levels in saliva [65], the risk of transmission through saliva (eg, via kissing) appears to be minimal. The risk of transmission through a human bite also is probably minimal; it has been the subject of only a few anecdotal case reports [66]. It is not necessary to avoid sharing eating utensils, drinking glasses, or towels.
●For older children and adolescents with HCV, counseling focuses mostly on avoiding high-risk behaviors. Self-tattooing and self-piercing with shared needles are common practices and should be discouraged. Similarly, the risk of transmission is increased with the use of intravenous drugs and/or intranasal cocaine because of sharing of potentially contaminated equipment. They should understand that the risk of sexual transmission of HCV is low, but that barrier methods further reduce the risk and are recommended for patients with multiple partners, sexually transmitted disease, or HIV coinfection [13,67]. Sex with multiple partners is a risk factor for HCV infection but may not be directly responsible for transmission. (See "Epidemiology and transmission of hepatitis C virus infection", section on 'Sexual transmission'.)
●Successful treatment of HCV infection eliminates the risk of transmission to others. In particular, mother-to-child transmission of HCV does not occur if the mother has been successfully treated and is not viremic [68]. Therefore, women with HCV should be treated prior to conception. Both female and males treated with a ribavirin-containing regimen and who are sexually active should use reliable contraception during treatment; effective contraception should be continued after completing treatment for nine months for female patients, or six months for male patients [62]. (See "Vertical transmission of hepatitis C virus", section on 'Screening and prevention'.)
Minimizing risk for disease progression — The following general measures are recommended for patients with chronic HCV [41]:
●Patients should avoid alcohol consumption. Alcohol promotes the progression of chronic HCV. (See "Hepatitis C and alcohol".)
●Patients should be immunized against hepatitis A and hepatitis B, if not already immune. They should also receive standard immunizations that are applicable to an otherwise healthy population. (See "Immunizations for patients with chronic liver disease" and "Standard immunizations for children and adolescents: Overview", section on 'Infants and children'.)
●Acetaminophen is not contraindicated for children with HCV infection, because there is no evidence that its use promotes disease progression in patients with HCV and normal liver function. However, it is appropriate to remind patients to use no more than the recommended dose and that each course of treatment should be as brief as possible. Patients with advanced liver disease (HCV or other) should avoid nonsteroidal antiinflammatory drugs such as ibuprofen.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pediatric liver disease" and "Society guideline links: Hepatitis C virus infection".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topic (see "Patient education: Hepatitis C (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Epidemiology and natural history – The prevalence of hepatitis C virus (HCV) infection is lower in children than in adults. Perinatal transmission is by far the most common source of infection in children, although there is a reemergence of acquired HCV infection in adolescents and young adults in the United States, mirroring the epidemic of prescription opioid and subsequent heroin use. (See 'Epidemiology' above and "Vertical transmission of hepatitis C virus".)
●Natural history – HCV generally progresses slowly in children, although there are exceptions. Infections acquired during infancy often clear spontaneously, with spontaneous clearance rates ranging from 20 to 45 percent. (See 'Natural history' above.)
●Screening – Testing for HCV is recommended in several risk groups, including:
•Children of mothers known to be infected with HCV or with a history of intravenous drug use.
•Adolescents with HIV or a history or suspicion of possible intravenous drug use. A high index of suspicion for this possibility is appropriate in the United States, given the unfolding epidemic of opioid and subsequent heroin use.
•Children who are international adoptees or refugees. (See 'Screening' above.)
●Diagnostic testing – Diagnostic evaluation of HCV infection in children begins with an anti-HCV antibody test after 18 months of age. Those with a negative antibody test do not have infection. Those with a positive test should undergo HCV RNA testing, which confirms infection if positive. Infants who have vertical exposure to HCV should be screened with an HCV RNA test, which can be done as early as two months of age, but confirmatory testing at 18 months is still required. (See 'Diagnosis' above.)
●Treatment – The development of direct-acting antiviral agents (DAAs) represents a major milestone in the treatment of HCV in adults and is transforming practice in children as new regimens are studied and approved for children. These agents permit effective, well-tolerated, all-oral, interferon-free regimens for most patients. Effective DAA regimens are now available to children ≥3 years, with indications depending on HCV genotype. (See 'Management of chronic hepatitis C virus' above and "Overview of the management of chronic hepatitis C virus infection".)
•Selection of regimen – The timing and choice of treatment for chronic HCV infection depends upon the child's age, genotype, and access to an effective DAA regimen (algorithm 1):
-For children <3 years of age, treatment should be deferred until at least the child's third birthday. Deferring treatment for several years or more is appropriate because a proportion of cases will resolve spontaneously by age three years, most pediatric patients have mild HCV liver disease that progresses slowly, and the DAA regimens were not evaluated in children younger than three years of age. (See 'Children <3 years' above.)
-For children ≥3 years of age who have access to an effective DAA regimen, we recommend treatment rather than deferring treatment (Grade 1B). Options for effective DAA regimens include sofosbuvir-velpatasvir and glecaprevir-pibrentasvir (any genotype) or sofosbuvir-ledipasvir (for genotypes 1, 4, 5, or 6). The rare pediatric patient with cirrhosis, HIV, or hepatitis B virus (HBV) coinfection requires special considerations for regimen selection and duration. (See 'Children ≥3 years' above.)
-For patients who do not have access to an effective DAA regimen or those too young to reliably take the medication, it is reasonable to defer treatment for several years or more because most pediatric HCV liver disease progresses slowly. (See 'Children ≥3 years' above.)
•Pretreatment precautions – Coinfection with HBV should be excluded prior to initiating treatment with a DAA regimen, and pregnancy should be excluded prior to treatment with ribavirin. (See 'Precautions and monitoring' above.)
●Counseling – Patients with HCV and their families should be counseled about the specific routes of HCV transmission (perinatal transmission and via infected blood) and given advice to reduce the risk of transmission to other individuals (table 1). HCV is not spread within households, school, or daycare settings. Patients should avoid alcohol consumption. (See 'Prevention of transmission' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Maureen M Jonas, MD, who contributed to earlier versions of this topic review.
