Hepatitis B is a common cause of chronic hepatitis. Patients may be asymptomatic or have nonspecific manifestations such as fatigue and malaise. Diagnosis is by serologic testing. Without treatment, cirrhosis often develops; risk of hepatocellular carcinoma is increased even without cirrhosis. Antiviral medications do not cure but can control the virus.
(See also Causes of Hepatitis, Overview of Chronic Hepatitis, and Acute Hepatitis B.)
Hepatitis lasting > 6 months is generally defined as chronic hepatitis, although this duration is arbitrary.
Acute hepatitis B becomes chronic in about 5 to 10% of immunocompetent patients overall. However, the younger the age that acute hepatitis B occurs, the higher the risk of developing chronic hepatitis B.
The Centers for Disease Control and Prevention (CDC) estimates that 862,000 people in the United States have chronic hepatitis B (1). Worldwide, the World Health Organization (WHO) estimates that about 257 million people have chronic hepatitis B (2).
Without treatment, chronic hepatitis B can resolve (uncommon), progress rapidly, or progress slowly to cirrhosis over decades. Resolution often begins with a transient increase in disease severity and results in seroconversion from hepatitis B e antigen (HBeAg) to antibody to hepatitis B e antigen (anti-HBe), followed by loss of hepatitis B surface antigen (HBsAg).
Chronic HBV infection even in the absence of cirrhosis increases the risk of hepatocellular carcinoma.
Coinfection with hepatitis D virus (HDV) causes the most severe form of chronic HBV infection; without treatment, cirrhosis develops in up to 70% of patients.
General references
1. Centers for Disease Control and Prevention (CDC): Hepatitis B Resources for Health Care Professionals. Accessed June 17, 2024.
2. World Health Organization (WHO): Hepatitis B. Accessed June 17, 2024.
Symptoms and Signs of Chronic Hepatitis B
Symptoms of chronic hepatitis B 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
Signs of chronic liver disease or cirrhosis (eg, splenomegaly, spider nevi, palmar erythema)
Complications of cirrhosis (eg, portal hypertension, ascites, encephalopathy)
Extrahepatic manifestations may include polyarteritis nodosa and glomerular disease.
Diagnosis of Chronic Hepatitis B
Serologic testing
Liver biopsy
The diagnosis of chronic hepatitis B is suspected in patients with any of the following:
Suggestive symptoms and signs
Incidentally noted elevations in aminotransferase levels
Previously diagnosed acute hepatitis
Diagnosis is confirmed by finding positive hepatitis B surface antigen (HBsAg) and IgG antibody to hepatitis B core (IgG anti-HBc) and negative IgM anti-HBc (see table Hepatitis B Serology) and by measuring hepatitis B virus DNA (quantitative HBV-DNA).
Hepatitis B Serology*
Marker | Acute HBV Infection | Chronic HBV Infection | Prior HBV Infection† |
|---|---|---|---|
HBsAg | + | + | − |
Anti-HBs | − | − | + ‡ |
IgM anti-HBc | + | − | − |
IgG anti-HBc | − | + | ± |
HBeAg | ± | ± | − |
Anti-HBe | − | ± | ± |
HBV-DNA | + | + | − |
* Antibody to hepatitis D virus (anti-HDV) levels should be measured if serologic tests confirm HBV and infection is severe. | |||
† Patients have had HBV infection and recovered. | |||
‡ Anti-HBs is also seen as the sole serologic marker after HBV vaccination. | |||
Anti-HBc = antibody to hepatitis B core; anti-HBe = antibody to HBeAg; anti-HBs = antibody to HBsAg; HBeAg = hepatitis B e antigen; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus. | |||
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 or if patients belong to a known at-risk population (eg, those with HIV infection, injection drug users, men who have sex with men, or immigrants from areas of high endemicity, and possibly those who are HBsAg-positive with low HBV DNA but high ALT levels), antibody to hepatitis D virus (anti-HDV) is measured.
Quantitative HBV-DNA tests (viral load) are also used before and during treatment to assess response.
Noninvasive assessment of fibrosis (FIB-4 index, ultrasonography, and elastography) is done to evaluate degree of fibrosis after chronic hepatitis B is diagnosed.
Biopsy is occasionally 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 Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance).
Other tests
Liver tests are needed if not previously done; they include serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase.
Other tests should be done to evaluate liver function and disease severity; they include serum albumin, bilirubin, platelet count, and prothrombin time/international normalized ratio (PT/INR).
Patients should also be tested for HIV and hepatitis C infection because transmission of these infections is similar.
If symptoms or signs of cryoglobulinemia develop during chronic hepatitis, cryoglobulin levels and rheumatoid factor should be measured; high levels of rheumatoid factor and low levels of complement suggest cryoglobulinemia.
Screening for complications
Patients with chronic HBV infection should be screened every 6 months for hepatocellular carcinoma with ultrasonography and serum alpha-fetoprotein measurement, although the cost-effectiveness of this practice, particularly alpha-fetoprotein measurement, is debated (1).
Diagnosis reference
1. Aghoram R, Cai P, Dickinson JA: Alpha-foetoprotein and/or liver ultrasonography for screening of hepatocellular carcinoma in patients with chronic hepatitis B. Cochrane Database Syst Rev 2012(9):CD002799, 2012. doi: 10.1002/14651858.CD002799.pub2
Treatment of Chronic Hepatitis B
Antiviral medications
Sometimes liver transplantation
(See also the American Association for the Study of Liver Diseases [AASLD] guidelines Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance.)
Antiviral treatment is indicated for patients with chronic hepatitis B and one or more of the following:
Elevated aminotransferase levels
Elevated HBV viral load
Clinical or biopsy evidence of progressive disease
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. These medications cannot cure the disease.
Stopping treatment prematurely can lead to relapse, which may be severe. However, treatment may be stopped if one of the following occurs:
HBeAg converts to antibody to HBeAg (anti-HBe).
Tests for HBsAg become negative.
First-line treatment is usually with one of the following:
Pegylated interferon alfa
Oral antivirals have few adverse effects and can be given to patients with decompensated liver disease. Lactic acidosis is a potential side effect, and lactic acid levels should be checked if there is clinical concern. Combination therapy has not proved superior to monotherapy. Patients should be tested for HIV before treatment is initiated.
If HBsAg becomes undetectable and HBeAg seroconversion occurs in patients with HBeAg-positive chronic HBV infection, these patients may be able to stop antivirals. Patients with HBeAg-negative chronic HBV infection almost always need to take antivirals 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.
Tenofovir
Dosing frequency for TDF may need to be reduced if creatinine clearance is reduced. Potential side effects include nephropathy, Fanconi syndrome, and osteomalacia. If patients are at risk of renal impairment, creatinine clearance, serum phosphate, and urine glucose and protein should be checked at least annually. Bone density studies at baseline and during treatment should be considered if patients have a history of fracture or risk factors for osteopenia.
No dose adjustments for TAF are necessary if creatinine clearance is reduced. TDF and TAF are similar in efficacy, but TAF is safer in patients when renal toxicity or bone density is a concern. Serum creatinine and phosphorus, creatinine clearance, and urine glucose and protein should be checked before initiating and during therapy.
Pegylated interferon alfa can be used instead of interferon alfa. Pegylated interferon alfa is given by injection once a week for 48 weeks. Adverse effects are similar to those of interferon alfa but may be less severe. More than 40% of patients treated with pegylated interferon alfa report fatigue, fever, myalgia, and headache. Other potential adverse effects include mood disturbances, cytopenia, and autoimmune disorders.
Contraindications to pegylated interferon alfa include the following:
Decompensated liver disease
Autoimmune hepatitis
Renal failure
Immunosuppression
Solid organ transplantation
Cytopenia
The following tests should be used to monitor patients treated with pegylated interferon alfa:
Complete blood count (monthly to every 3 months)
Thyroid-stimulating hormone (every 3 months)
Clinical monitoring for autoimmune, ischemic, neuropsychiatric, and infectious complications
Lactic acid levels if there is clinical concern
Test for HIV before initiating treatment
Nonpreferred antiviral therapies
is a nucleotide analog. Dosage is 10 mg orally once a day. It is not a preferred first-line treatment because renal failure and lactic acidosis are risks.
(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 antivirals. Dosage is 100 mg orally once a day; it has few adverse effects.
Telbivudine
Interferon alfa can be used but is no longer considered first-line treatment and has generally been replaced by pegylated interferon alfa.
Treatment reference
1. Terrault NA, Lok ASF, McMahon BJ, et al: Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 67(4):1560-1599, 2018. doi: 10.1002/hep.29800
Key Points
Acute hepatitis B becomes chronic in about 5 to 10% of patients overall; risk is highest at a young age (90% for infants, 25 to 50% for children aged 1 to 5 years, and about 5% for adults).
Symptoms vary depending on the degree of underlying liver damage.
Antiviral medications can improve liver test results and liver histology and delay progression to cirrhosis but may need to be taken indefinitely; drug resistance has become less of a concern with newer drugs.
Liver transplantation may be required in patients with decompensated cirrhosis due to hepatitis B.
More Information
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
Alpha-Foetoprotein and/or Liver Ultrasonography for Screening of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B: This study evaluates the beneficial and harmful effects of using alpha-fetoprotein, ultrasonography, or both to screen for hepatocellular carcinoma in patients with chronic hepatitis B. Accessed May 8, 2024.
American Association for the Study of Liver Disease Practice Guidelines (AASLD): A multidisciplinary panel of experts developed guidelines for diagnosing and managing various hepatic disorders using clinically relevant questions, which are answered by systematic reviews of the literature and followed by data-supported recommendations. The panel rates the quality (level) of the evidence and strength of each recommendation. Accessed May 8, 2022.
