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Hepatitis B: A strategy for evaluation and management

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ABSTRACTIn hepatitis B virus (HBV) infection, a single approach to treatment cannot be applied to all patients. Acute, adult-acquired HBV infection rarely requires treatment, whereas treatment for chronic infection should be based on the patient’s clinical situation and test results. The ideal agent for treating hepatitis B does not exist, and trade-offs are the essence of agent selection. In last month’s Journal (Cleve Clin J Med 2008; 75:881–889), we outlined the natural history and diagnosis of chronic HBV infection; in this article we outline its management.

KEY POINTS

  • Patients with HBV infection should be screened for hepatocellular carcinoma, especially if they have cirrhosis.
  • Nucleoside and nucleotide analogue reverse transcriptase inhibitors are easy to use and therefore are usually the first-line therapy. Problems with these agents are that the optimal treatment duration is not known, and that drug resistance can emerge.
  • Patients with advanced liver disease or hepatocellular carcinoma should be referred promptly for possible liver transplantation.
  • Candidates for immunosuppressant therapy or cytotoxic chemotherapy should be screened for HBV, as this therapy can cause a potentially fatal flare of HBV.
  • People at risk should be vaccinated; many have not been.


 

References

Hepatitis b virus (HBV) infection is sometimes challenging to manage because the disease has several stages and many clinical scenarios. HBV-infected patients are a very heterogeneous group, and we cannot apply a single management approach to all.

An understanding of the natural history of HBV infection and its diagnosis, which we reviewed in last month’s issue of this Journal1, is critical to understanding how to manage HBV infection.

In this article, we will review the principles of HBV management in adults, including those on immunosuppressant therapy and pregnant women, and guidelines for HBV vaccination.

WORKUP FOR HBV INFECTION

Once the diagnosis of HBV infection is made,1 a full management strategy should be formulated, as outlined below.

History

When and how did the patient acquire HBV? This information is important to know when making treatment decisions. For example, most acute, adult-onset cases (eg, acquired recently via sexual contact or parenteral drug abuse) resolve spontaneously within a few months, whereas most chronic cases (defined as being positive for HBV surface antigen for more than 6 months) were acquired at birth or in early childhood. Therefore, we should try to determine if the patient’s mother, siblings, household contacts, and sexual partners are positive for HBV surface antigen or have risk factors for HBV infection1; those without infection or immunity to HBV should be vaccinated.

People at risk of HBV infection include:

  • Parenteral drug users
  • People with multiple sexual partners
  • Household contacts and sexual partners of people positive for HBV surface antigen
  • Infants born to HBV-infected mothers
  • Patients and staff in custodial institutions for the developmentally disabled
  • Recipients of certain plasma-derived products (including patients with congenital coagulation defects)
  • Hemodialysis patients
  • Health and public-safety workers who have contact with blood
  • People born in areas where HBV is endemic, and their children.1

Does the patient have risk factors for other infections? Especially look for risk factors for human immunodeficiency virus (HIV) infection (eg, intravenous drug users and men having sex with men) and hepatitis D virus (intravenous drug users and patients from countries where hepatitis D virus infection is common, particularly Eastern Europe, Mediterranean countries, and the Amazon basin).

Does the patient have other modifiable risk factors for progressive liver disease, particularly alcohol abuse and obesity?

Does the patient have symptoms or signs of cirrhosis or hepatocellular carcinoma? Symptoms and signs that involve multiple systems could be extrahepatic manifestations of HBV infection, such as polyarteritis nodosa, which causes abdominal pain, arthralgia, hypertension, and asymmetric polyneuropathy.

Baseline laboratory evaluation

At baseline we should obtain a complete blood count, blood urea nitrogen level, serum creatinine level, liver profile, prothrombin time, urinalysis, and HBV serologic markers. In addition, HBV DNA can be detected in the serum at levels as low as 60 IU/mL, and it should be measured in the initial evaluation to establish a baseline before starting antiviral therapy in patients with chronic HBV infection and subsequently to monitor the response.

All patients with chronic HBV infection should also be tested for serologic markers of hepatitis A and hepatitis C; patients at risk of HIV and hepatitis D should also be tested for these diseases.

Not all patients need liver biopsy

Liver biopsy is the most accurate tool for staging the degree of HBV-related hepatic fibrosis in patients who have no obvious clinical manifestations of cirrhosis.

Not all patients with HBV infection need a biopsy, however. In patients with acute HBV infection, liver biopsy has no benefit except if concomitant pathology (eg, iron overload, nonalcoholic steatohepatitis, or alcoholic steatohepatitis) is suspected. In patients with chronic hepatitis B, liver biopsy is helpful when the viral load alone does not provide sufficient guidance for treatment, eg, when the viral load is less than 2 × 104 IU/mL in a patient positive for hepatitis e antigen or less than 2 × 103 IU/mL in a patient negative for hepatitis e antigen. (The presence of e antigen is a marker of HBV replication and infectivity.1) Biopsy should also be considered in those who have been infected a long time (eg, more than 10 years), because they may have occult cirrhosis, and if they do they may need to undergo antiviral treatment, endoscopy to look for varices, and surveillance for liver cancer.

In some situations it is easy to decide whether antiviral therapy is indicated without resorting to liver biopsy.

We would treat:

  • A patient positive for HBV e antigen for more than 6 months, whose HBV DNA level is higher than 2 × 104 IU/mL and whose alanine aminotransferase (ALT) level is high
  • A patient with HBV for more than 6 months who is negative for e antigen and who has an HBV DNA level higher than 2 × 103 IU/mL and elevated ALT
  • A patient with compensated HBV cirrhosis and an HBV DNA level higher than 2 × 103 IU/mL
  • A patient with HBV cirrhosis with decompensation and any detectable HBV DNA.

We would not treat:

  • An HBV carrier with a normal ALT level and an HBV DNA level that is lower than 2 × 104 IU/mL or undetectable.

If a patient does not fit into one of these categories but has HBV DNA, a liver biopsy showing significant necroinflammation or fibrosis would be an indication for treatment.

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