eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease
Hepatitis B: Differential Diagnoses & Workup
Updated: May 1, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Differential Diagnoses
Autoimmune Chronic Active Hepatitis
Cytomegalovirus Infection
Hepatitis A
Hepatitis C
Herpes Simplex Virus Infection
Other Problems to Be Considered
Viral hepatitis shares certain clinical features with other viral diseases, such as Epstein Barr virus, herpes simplex, coxsackie viruses, and toxoplasmosis. These diseases elevate serum aminotransferase levels and, less commonly, serum bilirubin levels.
In addition, a complete drug history is particularly important because many drug and some anesthetic agents can produce a picture of acute hepatitis. Alcoholic hepatitis must also be considered in the differential. Acute hepatitis often is confused with acute cholecystitis, common duct stone, or ascending cholangitis.
Workup
Laboratory Studies
- Elevations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are hallmarks of acute hepatitis. Values as high as 1000-2000 IU/L are typical, with ALT values higher than AST values. In patients with hepatitis, increases in bilirubin levels often lag behind increases in aminotransferase levels. The prothrombin time is the best indicator of prognosis. Alpha-fetoprotein levels as high as 8000 ng/mL may also be seen.
- Because the symptoms of acute hepatitis B virus (HBV) infection and the laboratory indicators of hepatocellular dysfunction are indistinguishable from those of other forms of viral hepatitis, definitive diagnosis depends on serologic testing for HBV infection. Serological findings are as follows:
- HBs Ag appears before the onset of symptoms, peaks during overt disease, and then declines to undetectable levels in 3-6 months. Acute HBV infection is characterized by the presence of HBs Ag in the serum.
- HBe Ag, HBV DNA, and DNA polymerase appear in the serum soon after HBs Ag, and all signify active viral replication. Measuring HBV DNA with quantitative DNA polymerase chain reaction (PCR) is ideal for monitoring disease progression and effect of treatment.
- Immunoglobulin M (IgM) anti-HBc becomes detectable in serum shortly before the onset of symptoms, concurrent with the onset of elevation of serum aminotransferases. Over months, the IgM antibody is replaced by immunoglobulin G (IgG) anti-HB c .
- Anti-HB e is detectable shortly after the disappearance of HB e Ag, implying that the acute infection has peaked and the disease is on the wane.
- IgG anti-HB s does not rise until the acute disease is over and is usually not detectable for a few weeks to several months after the disappearance of HB s Ag. Anti-HB s may persist for life, conferring protection; this is the basis for current vaccination strategies using noninfectious HB s Ag.
- During convalescence, HB s Ag and HB e Ag are cleared, and IgG antibodies to HB s Ag, HB c Ag, and HB e Ag develop.
- Hepatitis B surface antibody (HB s Ab) is a protective antibody that neutralizes the virus, although the coexistence of HB s Ag and HB s Ab has been reported in approximately 25% of individuals who are HB s Ag positive. HB s Ab, but not hepatitis B core antibody (HB c Ab), is detected in persons who have received the hepatitis B vaccine.
- Total HB c Ab, including IgM and IgG, indicates exposure to the virus and viral replication. HB c Ab appears shortly after HB s Ag in acute disease and persists for life; therefore, HB c Ab is not a good marker for acute disease.
- Detection of IgM HB c Ab is diagnostic of acute HBV infection. The carrier state is defined by the presence of HB s Ag in the serum for 6 months or longer after its initial detection.
- The carrier state is defined by the presence of HB s Ag in serum for 6 months or longer after initial detection. The presence of HB s Ag alone does not necessarily indicate replication of complete virions, and patients may be asymptomatic and without liver damage.
- In contrast, chronic replication of HBV virions is characterized by persistence of circulating HB s Ag, HB e Ag, and HBV DNA, usually with anti-HB c and, occasionally, with anti-HB s . In these patients, progressive liver damage may occur.
- The major clinical role of serum HBV DNA assays is the assessment of the candidacy of patients with chronic HBV infection for antiviral therapy and their response to it. Tests for HBV DNA in serum rarely help in identifying HBV as the cause of liver disease in patients who are HB s Ag-negative; knowledge of this fact is especially important in patients with fulminant hepatitis B in whom HB s Ag may have cleared by the time they seek care.
Procedures
- Patients with signs of chronic disease may require a liver biopsy to assess the extent of histologic involvement and response to therapeutic protocols.
Histologic Findings
Morphologic changes in acute and chronic viral hepatitis are shared among the hepatotropic viruses and can be mimicked by drug reactions. HBV infection may generate ground-glass hepatocytes, with a finely granular, eosinophilic cytoplasm depicted as spheres and tubules of HB s Ag using electron microscopy. Other HBV-infected hepatocytes may have sanded nuclei due to abundant HB c Ag; this finding indicates active viral replication.
With acute hepatitis, hepatocyte injury takes the form of diffuse swelling (balloon degeneration). Cholestasis is an inconstant finding. Two patterns of hepatocyte cell death are observed: cytolysis (cell rupture) and apoptosis (cell shrinkage). In severe cases, confluent necrosis of hepatocytes may lead to bridging necrosis. Inflammation is a prominent feature of acute hepatitis. Kupffer cells undergo hypertrophy and hyperplasia. Usually, the portal tracts are infiltrated with a mixture of inflammatory cells.
Histologic features of chronic hepatitis range from exceedingly mild to severe. In the mildest forms, significant inflammation is limited to the portal tracts. Liver architecture is usually well preserved, but smoldering hepatocyte necrosis throughout the lobule may occur in all forms of chronic hepatitis. Continued interface hepatitis and bridging necrosis are harbingers of progressive liver damage. Deposition of fibrous tissue is the hallmark of irreversible liver damage. Continued loss of hepatocytes and fibrosis results in cirrhosis, with fibrous septae and hepatocyte regenerative nodules. This pattern of cirrhosis is characterized by irregularly sized nodules separated by variable, but mostly broad, scars. Historically, this pattern of cirrhosis has been termed postnecrotic cirrhosis. The term postnecrotic cirrhosis has been applied to all forms of cirrhosis in which the liver shows large, irregular-sized nodules with broad scars, regardless of etiology.
Staging
In current practice, including a statement regarding the severity of inflammatory activity (grade) and fibrosis (stage) in the liver biopsy pathology report is recommended in patients with chronic hepatitis. Disease activity and histological response to treatment are usually defined based on a scoring system for the grade and stage of chronic hepatitis.
More on Hepatitis B |
| Overview: Hepatitis B |
 Differential Diagnoses & Workup: Hepatitis B |
| Treatment & Medication: Hepatitis B |
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References
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Lai CL, Ratziu V, Yuen MF, Poynard T. Viral hepatitis B. Lancet. Dec 20 2003;362(9401):2089-94. [Medline].
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Further Reading
Keywords
hepatitis B, hepatitis B virus, HBV, infectious hepatitis, hepatitis B infection, acute liver disease, chronic liver disease, fulminant hepatic failure, viral hepatitis, viral hepatitis type B, cirrhosis, hepatocellular carcinoma, urticarial rashes, arthralgia, arthritis, Gianotti-Crosti syndrome, papular acrodermatitis, necrotizing vasculitis, hypocomplementemic glomerulonephritis, Essential mixed cryoglobulinemia, pulmonary hemorrhage, vasculitis, acute pericarditis, polyserositis, Henoch-Schönlein purpura, anorexia, nausea, malaise, vomiting, arthralgias, myalgias, headache, photophobia, pharyngitis, coryza, jaundice, dark urine, abdominal pain, splenomegaly, cervical adenopathy, spider angioma, encephalopathy, fetor hepaticus, coagulopathy, renal failure, adult respiratory distress syndrome, pancreatitis, myocarditis, atypical pneumonia, aplastic anemia, transverse myelitis, peripheral neuropathy
