Viral Hepatitis

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Chapter 350 Viral Hepatitis

Viral hepatitis continues to be is a major health problem in both developing and developed countries. This disorder is caused by at least 5 pathogenic hepatotropic viruses recognized to date: hepatitis A, B, C, D, and E viruses (Table 350-1). Many other viruses (and diseases) can cause hepatitis, usually as 1 component of a multisystem disease. These include herpes simplex virus (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella-zoster virus, HIV, rubella, adenoviruses, enteroviruses, parvovirus B19, and arboviruses (Table 350-2).

The hepatotropic viruses are a heterogeneous group of infectious agents that cause similar acute clinical illness. In most pediatric patients, the acute phase causes no or mild clinical disease. Morbidity is related to rare cases of acute liver failure (ALF) triggered in susceptible patients and to the chronic disease state and attendant complications that three of these viruses (hepatides B, C, and D) can cause.

Issues Common to All Forms of Viral Hepatitis

Common Biochemical Profiles in the Acute Infectious Phase

Acute liver injury caused by the hepatotropic viruses manifests in 3 main functional liver biochemical profiles. These serve as an important guide to supportive care and monitoring in the acute phase of the infection for all viruses.

As a reflection of cytopathic injury to the hepatocytes, there is a rise in serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The magnitude of enzyme elevation does not correlate with the extent of hepatocellular necrosis and has little prognostic value. There is usually slow improvement over several weeks, but AST and ALT levels lag behind the serum bilirubin level, which tends to normalize first. Rapidly falling aminotransferase levels can predict a poor outcome, particularly if their decline occurs in conjunction with a rising bilirubin level and a prolonged prothrombin time; this combination of findings usually indicates that massive hepatic injury has occurred.

Cholestasis, defined by elevated serum conjugated bilirubin levels, results from abnormal bile flow at the canalicular and cellular level due to hepatocyte damage and inflammatory mediators. Elevation of serum alkaline phosphatase (ALP), 5′-nucleotidase, γ-glutamyl transpeptidase (GGT), and urobilinogen all mark cholestasis. Improvement tends to parallel the acute hepatitis phase. Absence of cholestatic markers does not rule out progression to chronicity in HCV or HBV infections.

The most important marker of liver injury is altered synthetic function. Monitoring of synthetic function should be the main focus in clinical follow-up to define the severity of the disease. In the acute phase, the degree of liver synthetic dysfunction guides treatment and helps to establish intervention criteria. Abnormal liver synthetic function is a marker of liver failure and is an indication for prompt referral to a transplant center. Serial assessment is necessary because liver dysfunction does not progress linearly. Synthetic dysfunction is reflected by a combination of abnormal protein synthesis (prolonged prothrombin time, high international normalized ratio [INR], low serum albumin levels), metabolic disturbances (hypoglycemia, lactic acidosis, hyperammonemia), poor clearance of medications dependent on liver function, and altered sensorium with increased deep tendon reflexes (hepatic encephalopathy; Chapter 356).

Hepatitis A

Hepatitis A virus (HAV) infection is the most prevalent of the 5. This virus is also responsible for most forms of acute and benign hepatitis; although fulminant hepatic failure can occur, it is rare and occurs more often in adults than in children.

Epidemiology

HAV infection occurs throughout the world but is most prevalent in developing countries. In the United States, 30-40% of the adult population has evidence of previous HAV infection. Hepatitis A is thought to account for ∼50% of all clinically apparent acute viral hepatitis in the United States. As a result of aggressive implementation of a childhood vaccination strategy, the prevalence of symptomatic HAV cases in the United States has declined significantly. However, outbreaks in daycare centers (where the spread from young, nonicteric, infected children can occur easily) as well as multiple foodborne and waterborne outbreaks have justified the implementation of a universal vaccination program.

HAV is highly contagious. Transmission is almost always by person-to-person contact through the fecal-oral route. Perinatal transmission occurs rarely. No other form of transmission is recognized. HAV infection during pregnancy or at the time of delivery does not appear to result in increased complications of pregnancy or clinical disease in the newborn. In the USA, increased risk of infection is found in contacts with infected persons, child-care centers, and household contacts. Infection has also been associated with contact with contaminated food or water and after travel to endemic areas. Common source foodborne and waterborne outbreaks have occurred, including several due to contaminated shellfish, frozen berries, and raw vegetables; no known source is found in about half of the cases. The mean incubation period for HAV is ∼3 wk. Fecal excretion of the virus starts late in the incubation period, reaches its peak just before the onset of symptoms, and resolves by 2 wk after the onset of jaundice in older subjects. The duration of viral excretion is prolonged in infants. The patient is therefore contagious before clinical symptoms are apparent and remains so until viral shedding ceases.

Diagnosis

Acute HAV infection is diagnosed by detecting antibodies to HAV, specifically, anti-HAV (IgM) by radioimmunoassay or, rarely, by identifying viral particles in stool. A viral polymerase chain reaction (PCR) assay is available for research use (Table 350-3). Anti-HAV is detectable when the symptoms are clinically apparent, and it remains positive for 4-6 mo after the acute infection. A neutralizing anti-HAV (IgG) is usually detected within 8 wk of symptom onset and is measured as part of a total anti-HAV in the serum. Anti-HAV (IgG) confers long-term protection.

Table 350-3 DIAGNOSTIC BLOOD TESTS:

SEROLOGY AND VIRAL PCR

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Rises in serum levels of ALT, AST, bilirubin, ALP, 5′-nucleotidase, and GGT are almost universally found and do not help to differentiate the cause of hepatitis.

Prevention

Patients infected with HAV are contagious for 2 wk before and ~7 days after the onset of jaundice and should be excluded from school, child care, or work during this period. Careful handwashing is necessary, particularly after changing diapers and before preparing or serving food. In hospital settings, contact and standard precautions are recommended for 1 wk after onset of symptoms.

Immunoglobulin

Indications for intramuscular administration of immunoglobulin (IG) (0.02 mL/kg) include pre-exposure and postexposure prophylaxis (Table 350-4).

Table 350-4 HEPATITIS A VIRUS PROPHYLAXIS

PRE-EXPOSURE PROPHYLAXIS (TRAVELERS TO ENDEMIC REGIONS)
Age Exposure Dose
<1 yr of age Expected <3 mo Ig 0.02 mL/kg
Expected 3-5 mo Ig 0.06 mL/kg
Expected long term Ig 0.06 mL/kg at departure and every 5 mo thereafter
≥1 yr of age Healthy host HAV vaccine
Immunocompromised host, or one with chronic liver disease or chronic health problems HAV vaccine and Ig 0.02 mL/kg
POSTEXPOSURE PROPHYLAXIS*
Exposure Recommendations
≤2 wk since exposure < 1 y of age: IG 0.02 mL/kg
Immunocompromised host, or host with chronic liver disease or chronic health problems: IG 0.02 mL/kg and HAV vaccine
>1 yr and healthy host: HAV vaccine, IG remains optional
Sporadic non-household or close contact exposure: prophylaxis not indicated*
>2 wk since exposure None

Ig, immunoglobulin.

* Decision for prophylaxis in non-household contacts should be tailored to individual exposure and risk.

IG is recommended for pre-exposure prophylaxis for susceptible travelers to countries where HAV is endemic, and it provides effective protection for up to 3 mo. HAV vaccine given any time before travel is preferred for pre-exposure prophylaxis in healthy persons, but IG ensures an appropriate prophylaxis in children <1 yr of age, patients allergic to a vaccine component, or those who elect not to receive the vaccine. If travel is planned in <2 wk, older patients, immunocompromised hosts, and those with chronic liver disease or other medical conditions should receive both IG and the HAV vaccine.

IG as prophylaxis in postexposure situations should be used as soon as possible (not effective >2 wk after exposure). It is exclusively used for children <12 mo of age, immunocompromised hosts, those with chronic liver disease or in whom vaccine is contraindicated; IG is preferably used in patients > 40 yr of age. IG is optional in healthy persons 12 mo-40 yr, in whom HAV vaccine is preferred. An alternative approach is to immunize previously unvaccinated patients who are ≥12 mo at the age-appropriate vaccine dosage as soon as possible. IG is not routinely recommended for sporadic nonhousehold exposure (e.g., protection of hospital personnel or schoolmates).