Pediatric Hepatitis B Workup

Updated: May 14, 2021
  • Author: Nicholas John Bennett, MBBCh, PhD, FAAP, MA(Cantab); Chief Editor: Russell W Steele, MD  more...
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Approach Considerations

All patients with chronic hepatitis B (HBV) infection should have laboratory tests to assess liver diseases (complete blood counts with platelets, hepatic panel, and prothrombin time), serologic markers of HBV replication, and tests for coinfection with HCV (anti HCV), HDV (anti HDV) in persons from countries where HDV infection is common and in those with history of injection drug use, or HIV (anti HIV) in those at risk. Test should be performed to screen for hepatocellular carcinoma–alpha fetoprotein (HCC-AFP) at baseline, and ultrasound should be performed in high-risk patients.


Liver Function 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 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.


Hepatitis B Virus Serologic Tests

HBV serologic testing can be confusing and requires multiple tests for antigens (Ag) and antibody (Ab) responses in order to accurately diagnose the stage of infection. See Hepatitis B Test.

HBV surface antigen (HBsAg) 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 HBsAg in the serum.

Hepatitis B e antigen HBeAg, HBV DNA, and DNA polymerase appear in the serum soon after HBsAg, 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-HBc. Detection of IgM HBcAb is diagnostic of acute HBV infection, but total HBcAb is not helpful since IgG antibodies to HBcAg may persist for life.

IgG anti-HBs 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 HBsAg. Anti-HBs may persist for life, conferring protection; this is the basis for current vaccination strategies using noninfectious HBsAg. Hepatitis B surface antibody (HBsAb), but not hepatitis B core antibody (HBcAb), is detected in persons who have received the hepatitis B vaccine. The coexistence of HBsAg and HBsAb has been reported in approximately 25% of individuals who are HBsAg positive.

The carrier state is defined by the presence of HBsAg in the serum for 6 months or longer after its initial detection.

The presence of HBsAg alone does not necessarily indicate replication of complete virions, and patients may be asymptomatic and without liver damage. Chronic replication of HBV virions is characterized by persistence of circulating HBsAg, HBeAg, and HBV DNA, usually with anti-HBc and, occasionally, with anti-HBs. In these patients, progressive liver damage may occur.

During convalescence, HBsAg and HBeAg are cleared, and IgG antibodies to HBsAg, HBcAg, and HBeAg develop.

Quantification of serum HBV DNA is a crucial component in the evaluation of patients with chronic HBV infection and in the assessment of the efficacy of antiviral treatment. Most HBV DNA assays used in clinical practice are based on polymerase chain reaction (PCR) amplification with lower limits of detection of 50-200 IU/mL (250-1,000 copies/mL) and a limited dynamic range, up to 4-5 log10 IU/mL.

Tests for HBV DNA in serum rarely help in identifying HBV as the cause of liver disease in patients who are HBsAg negative; knowledge of this fact is especially important in patients with fulminant hepatitis B, in whom HBsAg may have cleared by the time they seek care.


Liver Biopsy

Patients with signs of chronic disease may require a liver biopsy to assess the extent of histologic involvement and response to therapeutic protocols. Liver biopsy is useful in patients who do not meet the clear-cut criteria for starting treatment. Liver biopsy helps to assess the degree of liver damage and rule out other causes of liver disease.

Decisions on liver biopsy should take into consideration age, the new suggested upper limits of normal for ALT, HBeAg status, HBV DNA levels, and other clinical features suggestive of chronic liver disease or portal hypertension. However, liver histology can improve significantly in patients who have sustained response to antiviral therapy or spontaneous HBeAg seroconversion. Liver histology also can worsen rapidly in patients who have recurrent exacerbations or reactivations of hepatitis.


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 HBsAg using electron microscopy. Other HBV-infected hepatocytes may have sanded nuclei due to abundant HBcAg; 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.



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.