Acute Hepatitis

Hepatitis A Virus

Worldwide, HAV is the most common cause of acute viral hepatitis. Infection primarily is spread through direct human fecal-oral contamination or by contaminated food and water. In young children, HAV infection usually is mild and often manifests with symptoms of an influenza-like illness. HAV infection is common in early childhood, especially in developing countries with poor conditions of sanitation and hygiene. Almost all children in these countries become seropositive before 5 years of age. In the US, transmission often occurs in childcare facilities, but with inclusion of hepatitis A vaccine in the childhood immunization schedule in the US, a significant decrease in rates of disease has occurred. ^, Incidence of HAV infection has been increasing between 2011 and 2017. Outbreaks in childcare facilities are first recognized usually by illnesses with jaundice in staff members or parents of attendees (see Chapter 3 ).

Hepatitis B Virus

HBV is a noncytopathic, hepatotropic member of the hepadnavirus family. Highly infectious, it is transmitted through sexual contact, infected blood and body fluids, and vertically from mother to child and represents a global public health problem. The virus causes both acute and chronic necroinflammatory liver disease, with a wide spectrum of presentation, ranging from subclinical to fulminant hepatitis in acute phase, and from an asymptomatic carrier state to persistent hepatitis to cirrhosis in chronic phase. ^,

The severity of infection is inversely related to the effectiveness of the immune system to diminish viral replication. Two main patterns of transmission occur. In endemic areas such as China, Southeast Asia, and sub-Saharan Africa, the infection usually spreads via mother-to-infant transmission. In the US, the most common routes of transmission are injection drug use, sexual contact, and nosocomial infection; no risk factor is found in approximately 30% of cases. The incidence of HBV infections in neonates is declining in countries with neonatal hepatitis B immunization programs. Most neonatal infections are not associated with clinically evident disease, but chronic infection develops in infants not treated immediately after birth with hepatitis B immune globulin and vaccine. ^, Children and adolescents are more likely to develop clinical illness if they are infected with HBV, usually acquired by close contact with an infected adult, sexual contact, or use of intravenous drugs. Viral genotypes are important predictors of clinical outcome, drug responses, and mutations. ^, Implementation of a national vaccination strategy to eliminate HBV transmission has greatly reduced the disease burden in the US, but elimination will require an effective vaccination program for several generations, including vaccination of at-risk adults. Antiviral therapy is recommended in children (ages 2 to <18 years) who are HBeAg-positive and have both elevated ALT and measurable HBV-DNA concentrations. In the US, the following agents have been approved for use in children with chronic HBV: antiviral interferon-α-2b (for children 1 year of age and older), nucleoside drugs (lamivudine, entecavir, and telbivudine) and nucleotides (tenofovir disoproxil fumarate and adefovir dipivoxil, although these no longer have a major role in HBV treatment). Lamivudine and entecavir are approved for children 2 years of age and older, and tenofovir disoproxil fumarate for children 12 years and older; telbivudine is approved for adolescents 16 years and older. ^,

Hepatitis C Virus

HCV is an enveloped single-stranded, positive-sense RNA virus of the Flaviviridae family. It causes chronic hepatitis in humans and carries an immense global health burden, affecting 170 million persons worldwide, of which 7 million adults and 100,000 children are in the US. HCV infection in young children is acquired primarily by perinatal transmission in the US, but unsafe injections and unsafe medical procedures are important causes of pediatric HCV infection in resource-poor countries. In young adults, most cases are caused by injection drug use or sexual contact with an infected partner. Rates of HCV infection among young nonurban adults have been increasing. Because of major improvements in serologic diagnosis, HCV infection now is rarely caused by blood transfusion or organ transplantation. In contrast to HAV and HBV, no effective HCV vaccine is available. The efficiency of perinatal transmission appears to be low in the general population but greatly increases if the mother is coinfected with HIV or has a high titer of HCV RNA. HCV infections usually are mild or asymptomatic in children, but in many infected children disease progresses, and fibrosis, cirrhosis, and hepatocellular cancer may develop.

The emergence of direct-acting antiviral (DAA) agents with >90% sustained viral response rate and excellent safety profile has revolutionized the therapy of chronic HCV in children. Currently DAA treatment is recommended for HCV-infected children ≥3 years of age. Treatment is tailored based on the child’s age, weight, prior exposure to treatment, degree of cirrhosis, and HCV genotype. Combination of glecaprevir/pibrentasvir is approved for adolescents aged ≥12 years to treat to treat all six genotypes of hepatitis C virus; ledipasvir/sofosbuvir is now approved for children ≥3 years of age, infected with HCV genotype 1, 4, 5, 6 and meeting certain criteria, while sofosbuvir + ribavirin is approved for children ≥3 years of age with HCV genotype 2 or 3. Newer combination agents such as sofosbuvir/velpatasvir are expected to gain approval for treatment of HCV genotype 2 or 3 in children.

Hepatitis D (Delta) Virus

HDV infection, which can occur only in conjunction with HBV infection, has been recognized as an emerging problem due to improvement in diagnostic testing and immigration from endemic countries. HDV infection is rarely described in neonates, and the importance of perinatal transmission appears to be minimal. In older infants and children, the disease is uncommon.