Hepatitis C PDF - Red Book 2018

428 HEPATITIS C potential for HBV transmission after human bites but also wi...

428 HEPATITIS C potential for HBV transmission after human bites but also will allay anxiety about trans- mission from attendees who may be HBsAg positive. Children who are HBsAg positive and who have no behavioral or medical risk fac- tors, such as unusually aggressive behavior (eg, frequent biting), generalized dermatitis, or a bleeding problem, should be admitted to child care without restrictions. Under these circumstances, the risk of HBV transmission in child care settings is negligible, and rou- tine screening for HBsAg is not warranted. Admission of HBsAg-positive children with behavioral or medical risk factors should be assessed on an individual basis by the child’s physician, in consultation with the child care staff. Effectiveness of Hepatitis B Prevention Programs. Routine hepatitis B immunization programs have resulted in significant decreases in the prevalence of chronic HBV infection among children in populations with a high incidence of HBV infection. There is an association between higher coverage with HepB vaccine and larger decreases in HBsAg prevalence. All rights reserved. May not be reproduced in any form without permission from the publisher, except fair uses permitted under U.S. or applicable copyright law. Although the long-term sequelae of chronic HBV infection usually are not recognized until adolescence and adulthood, cirrhosis and HCC occur in children. Worldwide, rou- tine infant immunization programs and introduction of immunization schedules starting within the first 24 hours of life are expected to decrease significantly the incidence of death from cirrhosis and HCC attributable to HBV infection over the next 30 to 50 years. The Centers for Disease Control and Prevention Division of Viral Hepatitis main- tains a Web site (www.cdc.gov/hepatitis) with information on hepatitis for health care professionals and the public. Hepatitis C CLINICAL MANIFESTATIONS: Signs and symptoms of hepatitis C virus (HCV) infection are indistinguishable from those of hepatitis A or hepatitis B virus infections. Acute dis- ease tends to be mild and insidious in onset, and most infections are asymptomatic. Jaun- dice occurs in less than 20% of patients with HCV infection, and abnormalities in serum alanine transaminase concentrations generally are less pronounced than in patients with hepatitis B virus infection. Persistent infection with HCV occurs in up to 80% of infected children, even in the absence of biochemical evidence of liver disease. Most children with chronic infection are asymptomatic. Although chronic HCV infection develops in ap- proximately 75% to 85% of infected adults, limited data indicate that chronic HCV infec- tion and cirrhosis occur less commonly in children, in part because of the usually indolent nature of infection in pediatric patients. Liver failure secondary to HCV infection is one of the leading indications for liver transplantation among adults in the United States. ETIOLOGY: HCV is a small, single-stranded, positive-sense RNA virus and is a member of the family Flaviviridae in the genus Hepacivirus. At least 7 HCV genotypes exist with more Copyright 2018. American Academy of Pediatrics. than 50 subtypes. Distribution of genotypes and subtypes varies by geographic location, with genotype 1a being the most common in the United States. EPIDEMIOLOGY: The incidence of acute symptomatic HCV infection in the United States was 0.8 per 100 000 in 2015 (www.cdc.gov/hepatitis/statistics/ 2015surveillance/index.htm). After asymptomatic infection and underreporting were considered, approximately 30 000 new cases were estimated to have occurred in 2014. For all age groups, the incidence of HCV infection decreased markedly in the United States since the 1990s and reached its lowest incidence in 2006–2010. However, EBSCO Publishing : eBook Academic Collection (EBSCOhost) - printed on 8/17/2021 6:24 AM via UNIV OF SOUTH ALABAMA AN: 1809323 ; Kimberlin, David W., Brady, Michael T., Jackson, Mary Anne, Long, Sarah S..; Red Book 2018 : Report of the Committee on Infectious Diseases Account: s4595122.main.emed  HEPATITIS C 429 after 2010, there was a 2.6-fold increase in reported cases of acute HCV in the United States by 2014. This increase was mostly seen in white, nonurban young people with a history of using injection drugs and opioid agonists such as oxycodone (www.cdc.gov/ hepatitis/statistics/2011surveillance/commentary.htm). A substantial burden of disease still exists in the United States because of the propensity of HCV to establish chronic infection and the high incidence of acute HCV infection through the 1980s. The prevalence of HCV infection in the general population of the United States is estimated at 1.3%, equating to an estimated 3.5 million people in the United States who have chronic HCV infection. Seroprevalence varies among populations according to risk fac- tors. The pediatric prevalence of HCV corresponding to the National Health and Nutri- tion Examination Survey (NHANES) 1999–2002 was approximately 0.1%, although the numbers of HCV infections in the younger age groups were too small for reliable esti- mates. Worldwide, the prevalence of chronic HCV infection is highest in northern Africa, the Middle East, and parts of Asia. HCV is transmitted primarily through percutaneous (parenteral) exposures to infec- tious blood that can result from injection drug use, needle stick injuries, and inadequate infection control in health-care settings. The most common risk factors for adults to ac- quire infection are injection drug use or receipt of blood products before 1992. The most common route of infection for children is maternal-fetal transmission. The current risk of HCV infection after blood transfusion in the United States is estimated to be less than 1 per 2 million units transfused because of exclusion of high-risk donors and of HCV- positive units after antibody testing as well as screening of pools of blood units by nucleic acid amplification test (NAAT). All intravenous and intramuscular Immune Globulin products available commercially in the United States undergo an inactivation procedure for HCV or are documented to be HCV RNA negative before release. Approximately 60% of acute HCV cases reported to public health authorities are in acknowledged injection drug users who have shared needles or injection paraphernalia. For reported chronic HCV cases for which age is known, 63.5% were among people older than 40 years, and almost all infected people are outside the pediatric age range. Data from recent multicenter, population-based cohort studies indicate that approxi- mately one third of young injection drug users 18 to 30 years of age are infected with HCV. People with sporadic percutaneous exposures, such as health care professionals (approximately 1% of cases), may be infected. Approximately half of the 18 000 people with hemophilia who received transfusions before adoption of heat treatment of clotting factors in 1987 are HCV-seropositive. Also, more recently appreciated has been the num- ber of infections acquired in the health care setting, especially nonhospital clinics where infection control and needle and intravenous hygienic procedures have not been prac- ticed strictly. Prevalence is high among people with frequent but smaller direct percutane- ous exposures, such as patients receiving hemodialysis (10%–20%). Sexual transmission of HCV between monogamous heterosexual partners is ex- tremely rare. HCV virus has been identified in semen. However, studies show that the risk for HCV transmission is greater for parenteral transmission than sexual transmission. The risk for HCV acquisition by sexual transmission is increased with a high number of sexual partners, group sex, and coinfection with human immunodeficiency virus (HIV). Injection drug users may have a greater number of sex partners, so the role of sexual transmission is not fully understood. Sexual transmission of HCV among people coin- fected with HIV has been described between HIV-infected men who have sex with men EBSCOhost - printed on 8/17/2021 6:24 AM via UNIV OF SOUTH ALABAMA. All use subject to https://www.ebsco.com/terms-of-use  430 HEPATITIS C or HIV-infected heterosexual women. Transmission among family contacts is uncommon but can occur from direct or inap- parent percutaneous or mucosal exposure to blood. Seroprevalence among pregnant women in the United States has been estimated at approximately 1% to 2%. The risk of perinatal transmission averages 5% to 6%, and transmission occurs only from women who are HCV RNA positive at the time of deliv- ery. The exact timing of HCV transmission from mother to infant is not established. Fac- tors that increase perinatal transmission include internal fetal monitoring, vaginal lacera- tions, and prolonged rupture of membranes (>6 hours). The method of delivery has no effect on perinatal infection risk. Serum antibody to HCV (anti-HCV) and HCV RNA have been detected in colostrum, but the risk of HCV transmission is similar in breastfed and formula-fed infants. Breastfeeding is safe as long as mother’s nipples are not cracked or bleeding. When nipples are cracked or bleeding, mothers should stop breastfeeding and pump and discard their milk, and resume breastfeeding when the nipples have healed. Maternal coinfection with (untreated) HIV has been associated with increased risk of perinatal transmission of HCV, with transmission rates between 10% and 20%; trans- mission depends in part on the concentration of HCV RNA in the mother’s blood. All people with HCV RNA in their blood are considered to be infectious. The incubation period for HCV infection averages 6 to 7 weeks, with a range of 2 weeks to 6 months. The time from exposure to development of viremia generally is 1 to 2 weeks. DIAGNOSTIC TESTS 1: The 2 types of tests available for laboratory diagnosis of HCV in- fections are immunoglobulin (Ig) G antibody enzyme immunoassays (EIA) or chemilumi- nescent immunoassays (CIA) for HCV and NAATs to detect HCV RNA. The diagnosis of HCV infection usually is made by serologic testing. Third-generation immunoassays cleared by the US Food and Drug Administration (FDA) are at least 97% sensitive and more than 99% specific. For some assays, a positive result is considered initially reactive, and repeat testing in duplicate is required. Final results are reported as reactive when at least 2 replicates are positive. Some of the newer assays with high performance allow for reporting of initial possible results without repeat testing. In June 2010, the FDA ap- proved for use in people 15 years and older the OraQuick rapid blood test, which uses a test strip that produces a blue line within 20 minutes if anti-HCV antibodies are present. False-negative results early in the course of acute infection can result from any of the HCV serologic tests because of the prolonged interval between exposure and onset of ill- ness and seroconversion. In a clinical setting where acute HCV infection is considered likely and the initial immunoassay result is negative, repeat testing with a third-generation immunoassay or NAAT should be performed. Within 15 weeks after exposure and within 5 to 6 weeks after onset of hepatitis, 80% of patients will have positive test results for se- rum anti-HCV antibody. Among infants born to anti-HCV–positive mothers, passively acquired maternal antibody may persist for up to 18 months. FDA-licensed diagnostic NAATs for qualitative detection of HCV RNA are available commercially and recommended in the 2013 Centers for Disease Control and Prevention (CDC) HCV testing algorithm as follow-up for patients with a positive HCV serologic test result. HCV RNA can be detected in serum or plasma within 1 to 2 weeks after exposure 1 Centers for Disease Control and Prevention. Testing for HCV Infection: an update of guidance for clinicians and laboratorians. MMWR Morb Mortal Wkly Rep. 2013;62(18):362–365 EBSCOhost - printed on 8/17/2021 6:24 AM via UNIV OF SOUTH ALABAMA. All use subject to https://www.ebsco.com/terms-of-use  HEPATITIS C 431 to the virus and weeks before onset of liver enzyme abnormalities or appearance of anti- HCV antibody. Assays for detection of HCV RNA are used commonly in clinical prac- tice to: (1) detect HCV infection after needlestick or transfusion and before seroconver- sion; (2) identify anti-HCV–positive patients with active infection who are viremic; (3) identify infection in infants early in life (ie, perinatal transmission) when maternal anti- body interferes with ability to detect antibody produced by the infant; and (4) monitor patients receiving antiviral therapy. However, false-positive and false-negative results of NAATs can occur from improper handling, storage, and contamination of test specimens. Viral RNA may be detected intermittently in acute infection (ie, in the first 6 or 12 months following infection); thus, a single negative assay result is not conclusive if per- formed during this acute infection period. Highly sensitive quantitative assays for measur- ing the concentration of HCV RNA have largely replaced qualitative assays. Quantitative RNA and genotyping assays of HCV are useful for determination of drug treatment regi- mens and duration of treatment. HCV genotyping has become extremely important in determining which direct-acting antiviral agents should be used in individual patients. Because perinatally HCV-infected infants have a low risk of HCV acquisition, they usually do not exhibit symptoms for years, and there currently are no antiviral therapies available in the first 2 years of life, assessment of HCV infection may rely on serologic testing at 18 months of age. Prior to serologic testing, liver enzyme testing can be per- formed at approximately 6-month intervals to detect the rare perinatally HCV-infected infant who has significant liver injury prior to 18 months of age. In situations in which there may be concerns about the ability to maintain contact with perinatally HCV- exposed infant until 18 months of age, if the family is not willing to wait until 18 months of age to determine the child’s HCV infection status, or if antiviral therapy becomes avail- able to younger infants, quantitative RNA tests can be performed as early as 1 to 2 months of age. If the initial quantitative HCV RNA result is negative, serologic testing should be performed at 18 months of age. TREATMENT: Patients with a diagnosis of HCV infection should be referred to a pediatric infectious disease specialist or gastroenterologist for clinical monitoring and consideration of enrollment into clinical trials of direct-acting oral hepatitis C antiviral therapy when available. Traditional interferon and ribavirin-based therapies are expensive, can have significant adverse reactions, and yield variable virologic response rates. A number of highly effective interferon-free direct-acting antiviral drug regimens have been FDA approved for adults and are the current standard of care therapy for HCV in adults. These drugs are all oral, usually taken once daily, rarely associated with serious adverse effects, and most important, almost always curative (ie, sustained virologic response). Because this is a rapidly changing field, the American Association for the Study of Liver Disease and the Infectious Diseases Society of America are continually updating recommended antiviral drug treatment (www.hcvguidelines.org). At present, the 3 direct-acting, all-oral combination drug therapy recommended for HCV genotypes 1a and 1b (>75% of all HCV in the United States) and genotype 4 (ap- proximately 2%) include: ledipasvir and sofosubuvir (Harvoni [Gilead Sciences, Foster City, CA); ombitasvir, dasabuvir, and paritaprevir, with or without ribavirin (Viekira Pak [AbbVie, North Chicago, IL]); and grazoprevir and elbasvir (Zepatier [Merck & Co Inc, Whitehouse Station, NJ]). For people with (compensated) cirrhosis or who have failed previous antiviral therapy, treatment duration may vary from 12 to 24 weeks, depending EBSCOhost - printed on 8/17/2021 6:24 AM via UNIV OF SOUTH ALABAMA. All use subject to https://www.ebsco.com/terms-of-use  432 HEPATITIS C on the treatment regimen used and the patient’s previous receipt of HCV antiviral ther- apy. For adults with genotypes 2 (about 12% of all HCV patients) or 3 (7%), current ther- apy is sofosbuvir plus either ribavirin or daclatasvir for 12 to 24 weeks. Together, these regimens offer hope for cure without significant adverse effects for a large population of adult and, ultimately, pediatric patients with HCV infection. At the current time, several of the all-oral anti-HCV regimens are being evaluated in clinical tri- als for use in children. A once-daily ledipasvir (90 mg)–sofosbuvir (400 mg) combination given for 12 weeks was well tolerated and resulted in 98% sustained viral response (cure) among 100 adolescent children 12 to 17 years of age with chronic hepatitis C caused by genotype 1. On April 7, 2017, sofosbuvir (Sovaldi) and ledipasvir and sofosbuvir (Har- voni) were approved by the FDA to treat hepatitis C virus in children 12 to 17 years of age. Management of Chronic HCV Infection. Because of the very high rate of severe hepatitis in pa- tients with HCV-associated chronic liver disease, all patients with chronic HCV infection should be immunized against hepatitis A and hepatitis B. With advancing age, chronic HCV infection increases the risk of liver-related morbidity and mortality, including cir- rhosis and primary hepatocellular carcinoma. Among children, progression of liver dis- ease appears to be accelerated when comorbid conditions, including HIV, childhood can- cer, iron overload, or thalassemia, are present. Pediatricians should be alert to concomi- tant infections, alcohol abuse, and concomitant use of prescription and nonprescription drugs, such as acetaminophen, some antiretroviral agents (such as stavudine), and herbal medications, in patients with HCV infection that may worsen liver disease. Children with chronic infection should be followed closely, including sequential monitoring of serum al- anine transaminase concentrations, because of the potential for chronic liver disease. The North American Society of Pediatric Gastroenterology, Hepatology and Nutrition pub- lished guidelines for children with HCV infection in 2012. 1 Evidence-based, consensus recommendations from the Infectious Diseases Society of America, the American Associ- ation for the Study of Liver Diseases, and the International Antiviral Society–USA for screening, treatment, and management of patients with HCV can be found online (www.HCVguidelines.org). ISOLATION OF THE HOSPITALIZED PATIENT: Standard precautions are recommended. CONTROL MEASURES: Care of Exposed People. Immunoprophylaxis. On the basis of lack of clinical efficacy in humans and data from an- imal studies, use of Immune Globulin for postexposure prophylaxis against HCV infec- tion is not recommended. Furthermore, potential donors of immune globulin are screened for antibody to HCV and excluded from donation if positive, so Immune Glob- ulin preparations are devoid of anti-HCV antibody. Breastfeeding. Mothers infected with HCV should be advised that transmission of HCV by breastfeeding has not been documented. According to guidelines of the American Acad- emy of Pediatrics and the CDC, maternal HCV infection is not a contraindication to breastfeeding. Mothers who are HCV infected and choose to breastfeed should interrupt 1Mack CL, Gonzalez-Peralta RP, Gupta N, et al; North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. NASPGHAN practice guidelines: diagnosis and management of hepatitis C infec- tion in infants, children, and adolescents. J Pediatr Gastroenterol Nutr. 2012;54(6):838–855 EBSCOhost - printed on 8/17/2021 6:24 AM via UNIV OF SOUTH ALABAMA. All use subject to https://www.ebsco.com/terms-of-use  HEPATITIS C 433 breastfeeding temporarily if their nipples are bleeding or cracked and can consider ex- pressing and discarding their milk until the nipples are healed. Once the nipples no longer are cracked or bleeding, HCV-infected mothers may fully resume breastfeeding. Child Care. Exclusion of children with HCV infection from out-of-home child care is not indicated. Serologic Testing for HCV Infection. People Who Have Risk Factors for HCV Infection. HCV testing is recommended for anyone at increased risk for HCV infection and other populations, including 1–3: People born from 1945 through 1965; People who have ever injected illegal drugs, including those who injected only once many years ago; Recipients of clotting factor concentrates made before 1987; Recipients of blood transfusions or solid organ transplants before July 1992; Patients who have ever received long-term hemodialysis treatment; People with known exposures to HCV, such as ♦ Health care workers after needlesticks involving HCV-positive blood; ♦ Recipients of blood or organs from a donor who later tested HCV-positive; All people with HIV infection; Patients with signs or symptoms of liver disease (eg, abnormal liver enzyme test re- sults); Children born to HCV-positive mothers (to avoid detecting maternal antibody, these children should not be tested serologically before 18 months of age); Incarcerated people; and People who use intranasal illicit drugs or received tattoos from unregulated settings. Pregnant Women. Routine serologic testing of pregnant women for HCV infection is not currently recommended. Children Born to Women With HCV Infection. Children born to women previously identified to be HCV infected should be tested for HCV infection, because 5% to 6% of these children will acquire the infection. Transmission depends, in part, on the concentration of HCV RNA in the mother’s blood, and if the mother does not have detectable HCV RNA at the time of delivery, then the likelihood of transmission to the infant is very low. The duration of passively acquired maternal antibody in infants can be as long as 18 months. There- fore, testing for anti-HCV antibodies should not be performed until after 18 months of age. If earlier diagnosis is desired, a NAAT to detect HCV RNA may be performed at or after the infant’s first well-child visit at 1 to 2 months of age. Adoptees. See Medical Evaluation for Infectious Diseases for Internationally Adopted, Refugee, and Immigrant Children (p 175) for specific situations when serologic testing is warranted. 1Centers for Disease Control and Prevention. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945–1965. MMWR Recomm Rep. 2012;61(RR–4):1–32 2 Centers for Disease Control and Prevention. Guidelines for prevention and treatment of opportunistic infec- tions in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009;58(RR–4):1–207 3https://aidsinfo.nih.gov/guidelines EBSCOhost - printed on 8/17/2021 6:24 AM via UNIV OF SOUTH ALABAMA. All use subject to https://www.ebsco.com/terms-of-use