eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Hepatitis B

Author: Poonam Sharma, MD, Assistant Professor, Department of Pathology, Creighton University Medical Center and Veterans Affairs Medical Center; Director of Pathology Course, School of Pharmacy and Health Professions, Creighton University Medical Center
Coauthor(s): Meera Varman, MD, Assistant Professor, Department of Pediatrics, Section of Pediatric Infectious Diseases, Creighton University School of Medicine; Alexander T Kessler, MD, Consulting Staff, Northside Medical Specialties, LLC; Athena P Kourtis, MD, PhD, Assistant Professor, Department of Pediatrics, Divisions of Infectious Diseases and Epidemiology, Emory University School of Medicine
Contributor Information and Disclosures

Updated: May 1, 2008

Introduction

Background

The hepatitis B virus (HBV), discovered in 1966, infects more than 350 million people worldwide.¹ Hepatitis B can cause acute and chronic liver disease. The clinical presentation ranges from subclinical hepatitis to symptomatic hepatitis and, in rare instances, fulminant hepatitis. Long-term complications of hepatitis B include cirrhosis and hepatocellular carcinoma.² Perinatal or childhood infection is associated with few or no symptoms but has a high risk of becoming chronic. A limited number of medications can be used to effectively treat chronic hepatitis B; a safe and effective vaccine is available to prevent hepatitis B infection caused by HBV.³

Pathophysiology

HBV is a double-stranded DNA virus of the Hepadnaviridae family. HBV is a hepatotropic virus that replicates in the liver and causes hepatic dysfunction. HBV is transmitted by percutaneous or permucosal exposure to infectious body fluids, by sexual contact with an infected person, and by perinatal transmission from an infected mother to her infant. Persons with chronic HBV infection are predisposed to chronic liver disease and have a greater than 200-fold increased risk of hepatocellular carcinoma.

Fulminant hepatic failure occurs in approximately 0.1-0.5% of patients and is believed to be caused by massive immune-mediated lysis of infected hepatocytes. Various extrahepatic manifestations (eg, urticarial rashes, arthralgia, arthritis) are associated with acute clinical and subclinical HBV infection, as well as multiple immune-complex disorders such as Gianotti-Crosti syndrome (papular acrodermatitis), necrotizing vasculitis, and hypocomplementemic glomerulonephritis. HBV is associated with 20% of membranous nephropathy cases in children. Essential mixed cryoglobulinemia, pulmonary hemorrhage related to vasculitis, acute pericarditis, polyserositis, and Henoch-Schönlein purpura have been reported in association with HBV infection.

Frequency

United States

The Centers for Disease Control and Prevention report an estimated 150,000 new infections each year in the United States.⁴ More than 10,000 affected individuals require hospitalization, and 250 die of fulminant disease. In addition, 22,000 women with HBV infection give birth each year. The prevalence of chronic HBV infection in the United States is 0.35%. Although the reported incidence of acute hepatitis B increased by 37% from 1979-1985, the incidence has since 1986 declined to 1979 levels.

International

Infection with HBV is a serious health problem in many parts of the world. HBV infects more than 350 million people worldwide. Approximately 5% of the world's population has chronic HBV infection and it is the leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma worldwide. An estimated 500,000-1,000,000 persons die annually from HBV-related liver disease.

The distribution of hepatitis B infection widely varies throughout the world. In some regions, over 10% of the population is positive for hepatitis surface antigen (HB _s Ag), which indicates active infection. Countries are classified as having low endemic rates (<2% of the population has the antibody to HB _s Ag), intermediate endemic rates (2-8% positive for HB _s Ag), or high endemic rates (>8% positive for HB _s Ag).

In areas with high prevalence, such as southeast Asia, China, and Africa, more than half the population is infected at some time in their lives; approximately 10% are chronic carriers of the virus, which is the result of either neonatal transmission (vertical) or transmission from one individual to another (horizontal). Areas with low levels of endemicity include North America, Western Europe, and Australia, where only a minority of people come into contact with the virus (as a result of horizontal transmission among young adults).

The virus is present in all body fluids, except stool. Blood and body fluids are the primary vehicles of transmission; the virus may also spread by contact with body secretions, such as saliva, sweat, tears, breast milk, semen, and pathologic effusions. Most HBV infections in developed countries result from sexual activity, injection-drug use, or occupational exposure. Several well-characterized groups in the United States have an increased risk of infection, including those who use injection drugs, homosexual men, persons who have heterosexual contact with multiple partners, household contacts of persons with chronic infection, persons with hemophilia, patients on hemodialysis and the staff that tends to them, and persons with occupational exposure to blood and infectious body fluids.

Mortality/Morbidity

Of the 5000 persons in the United States who die each year from HBV-related conditions, 300 die from fulminant hepatitis, 3000-4000 die from cirrhosis, and 600-1000 die from primary hepatocellular carcinoma.

Race

The prevalence of HBV infection is higher among black populations than among white populations. According to the CDC, approximately 20% of new reported cases each year in the United States occur in African Americans.

Sex

Exacerbations of chronic HBV infection are observed more often in men than in women. Although the reason for this sex difference is not clear, the higher frequency of exacerbations in men may account, in part, for the higher incidence of HBV-related cirrhosis and hepatocellular carcinoma among men.

Age

Most acute HBV infections in the United States occur among young adults, although about one third of patients acquire chronic infections through perinatal and early childhood exposures. The prevalence increases with age. The age at infection primarily determines the rate of progression from acute infection to chronic infection, which is approximately 90% in the perinatal period, 20-50% in children aged 1-5 years, and less than 5% in adults.

Clinical

History

The incubation period for hepatitis B virus (HBV) infection ranges from 6 weeks to 6 months, and the clinical manifestations depend on the age at infection, the level of HBV replication, and the host's immune status. Perinatally infected infants generally have no clinical signs or symptoms, and infection produces typical illness in only 5-15% of children aged 1-5 years. Older children and adults are symptomatic in 33-50% of infections.

Clinicopathologic syndromes

• Acute asymptomatic infection with recovery: Serologic evidence only
• Acute hepatitis with resolution: Anicteric or icteric
• Chronic hepatitis, with or without progression to cirrhosis
• Fulminant hepatitis with massive liver necrosis
• Coinfection with hepatitis D virus (hepatitis delta virus)

Physical

Acute hepatitis

Clinical signs and symptoms of acute HBV infection include anorexia, nausea, malaise, vomiting, arthralgias, myalgias, headache, photophobia, pharyngitis, cough, coryza, jaundice, dark urine, clay-colored or light stools, and abdominal pain.

Upon physical examination, with the onset of clinical jaundice, the liver becomes enlarged and tender, and the patient may have right upper quadrant pain and discomfort. Splenomegaly and cervical adenopathy are present in 10-20% of patients with acute hepatitis. A few spider angiomas may appear during the icteric phase and disappear during convalescence, although angiomas are rare.

Chronic hepatitis

Chronic hepatitis is symptomatic, and affected individuals have biochemical or serologic evidence of continuing or relapsing hepatic disease for longer than 6 months, with histologically documented liver inflammation. The clinical features vary. The common symptoms include fatigue, loss of appetite, and occasional bouts of mild jaundice.

Fulminant hepatitis occurs in 1-2% of persons with acute disease and has a case:fatality ratio of 63-93%. It may present as jaundice, encephalopathy, and fetor hepaticus. Life-threatening extrahepatic complications include coagulopathy, renal failure, adult respiratory distress syndrome, electrolyte and acid-base disturbances, and sepsis. Without liver transplantation, the overall mortality ranges from 25-90%.

Consider hepatitis D virus infection if a patient who is a carrier of chronic hepatitis B presents with recurrent acute hepatitis or sudden fulminant hepatitis.

Causes

Virology

HBV, a DNA virus in the Hepadnaviridae family, causes hepatitis B. The virus is responsible for 40% of hepatitis cases in the United States. Seven major genotypes of HBV are recognized, with different geographic distributions. The genotypes are thought to affect disease progression, but their role in response to treatment is not as clear as in hepatitis C. The genome of HBV is a partially double-stranded, circular DNA molecule of 3200 nucleotides that encodes the following:

• The precore/core region of a nucleocapsid core protein (hepatitis B core antigen [HB _c Ag]) and a precore protein (hepatitis B e antigen [HB _e Ag]: HB _c Ag is retained in the infected hepatocyte; HB _e Ag is secreted into blood and is essential for the establishment of persistent infection.
• Envelope glycoprotein (ie, HB _s Ag), which may be produced and secreted into the blood in massive amounts: Blood HBsAg is immunogenic and can be visualized as spheres or tubules.
• A DNA polymerase with reverse transcriptase activity: Genomic replication takes place through an intermediate RNA known as pregenomic RNA. In this process, mutant viral genomes are frequently generated.
• HBV-X protein: This acts as a transcriptional transactivator for many viral and host genes through interaction with various transcription factors. HBV-X is required for viral infectivity and may have a role in the causation of hepatocellular carcinoma by regulating p53 degradation and expression.

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