Symptoms vary depending on the degree of underlying liver damage.

Many patients, particularly children, are asymptomatic. However, malaise, anorexia, and fatigue are common, sometimes with low-grade fever and nonspecific upper abdominal discomfort. Jaundice is usually absent.

Often, the first findings are

A few patients with chronic hepatitis develop manifestations of cholestasis (eg, jaundice, pruritus, pale stools, steatorrhea).

Extrahepatic manifestations may include polyarteritis nodosa and glomerular disease.

The diagnosis of chronic hepatitis B is suspected in patients with suggestive symptoms and signs, incidentally noted elevations in aminotransferase levels, or previously diagnosed acute hepatitis.

Diagnosis is confirmed by finding positive hepatitis B surface antigen (HBsAg) and IgG anti-HBc and negative IgM antibody to HBcAg (anti-HBc—see Table: Hepatitis B Serology*) and by measuring hepatitis B virus DNA (quantitative HBV-DNA).

If chronic hepatitis B is confirmed, testing for hepatitis B e antigen (HBeAg) and antibody to hepatitis B e antigen (anti-HBe) is usually done to help determine the prognosis and to guide antiviral therapy. If serologically confirmed HBV infection is severe, antibody to hepatitis D virus (anti-HDV) is measured.

Quantitative HBV-DNA tests are also used before and during treatment to assess response.

Biopsy is typically done to evaluate the extent of liver damage and to exclude other causes of liver disease. Liver biopsy is most useful in cases that do not meet clear-cut guidelines for treatment (see also the American Association for the Study of Liver Disease's practice guideline Diagnosis and Management of Autoimmune Hepatitis.).

(See also the American Association for the Study of Liver Disease’s Practice Guidelines for the Treatment of Chronic Hepatitis B.)

Antiviral treatment is indicated for patients with

The goal is to eliminate HBV-DNA (1). Treatment can occasionally cause loss of hepatitis B e antigen (HBeAg), or, even more rarely, loss of hepatitis B surface antigen (HBsAg). However, the majority of patients treated for chronic hepatitis B must be treated indefinitely; thus, treatment may be very expensive.

Stopping treatment prematurely can lead to relapse, which may be severe. However, treatment may be stopped if one of the following occurs:

Drug resistance is also a concern.

Seven antiviral drugs—entecavir, adefovir, lamivudine, interferon alfa (INF-alpha), pegylated INF-alpha (peginterferon-alpha), telbivudine, and tenofovir—are available (see Table: Comparison of Drugs Commonly Used to Treat Chronic Viral Hepatitis B).

First-line treatment is usually with

Oral antiviral drugs have few adverse effects and can be given to patients with decompensated liver disease. Combination therapy has not proved superior to monotherapy, but studies continue to examine their comparative usefulness.

If HBsAg becomes undetectable and HBeAg seroconversion occurs in patients with HBeAg-positive chronic HBV infection, these patients may be able to stop antiviral drugs. Patients with HBeAg-negative chronic HBV infection almost always need to take antiviral drugs indefinitely to maintain viral suppression; they have already developed antibodies to HBeAg, and thus the only specific criterion for stopping HBV treatment would be HBsAg that becomes undetectable.

Entecavir has a high antiviral potency, and resistance to it is uncommon; it is considered a first-line treatment for HBV infection. Entecavir is effective against adefovir-resistant strains. Dosage is 0.5 mg po once/day; however, patients who have previously taken a nucleoside analog should take 1 mg po once/day. Dose reduction is required in patients with renal insufficiency. Serious adverse effects appear to be uncommon, although safety in pregnancy has not been established.

Tenofovir has replaced adefovir (an older nucleotide analog) as a first-line treatment. Tenofovir is the most potent oral antiviral for hepatitis B; resistance to it is minimal. It has few adverse effects. Dosage is 300 mg po once/day; dosing frequency may need to be reduced if creatinine clearance is reduced.

For adefovir, dosage is 10 mg po once/day.

Interferon alfa (IFN-alpha) can be used but is no longer considered first-line treatment. Dosage is 5 million IU sc once/day or 10 million IU sc 3 times/wk for 16 to 24 wk in patients with HBeAg-positive chronic HBV infection and for 12 to 24 mo in patients with HBeAg-negative chronic HBV infection. In about 40% of patients, this regimen eliminates HBV-DNA and causes seroconversion to anti-HBe; a successful response is usually presaged by a temporary increase in aminotransferase levels. The drug must be given by injection and is often poorly tolerated. The first 1 or 2 doses cause an influenza-like syndrome. Later, fatigue, malaise, depression, bone marrow suppression, and, rarely, bacterial infections or autoimmune disorders can occur.

Contraindications to INF-alpha include the following:

In a few patients, treatment must be stopped because of intolerable adverse effects. The drug should be given cautiously or not at all to patients with ongoing substance abuse or a major psychiatric disorder.

Pegylated IFN-alpha can be used instead of IFN-alpha. Dosage is usually 180 mcg by injection once/wk for 48 wk. Adverse effects are similar to those of IFN-alpha but may be less severe.

Lamivudine (a nucleoside analog) is no longer considered first-line treatment for HBV infection because risk of resistance is higher and efficacy is lower than those of newer antiviral drugs. Dosage is 100 mg po once/day; it has few adverse effects.

Telbivudine is a newer nucleoside analog that has greater efficacy and potency than lamivudine but also has a high rate of resistance; it is not considered first-line treatment. Dosage is 600 mg po once/day.

Liver transplantation should be considered for end-stage liver disease caused by HBV. In patients with HBV infection, the long-term use of first-line oral antivirals and peritransplantation use of hepatitis B immune globulin (HBIG) has improved outcomes after liver transplantation. Survival is equal to or better than that after transplantation for other indications, and recurrences of hepatitis B are minimized.