Staying up to date on managing hepatitis B
You’re a key player in identifying patients with this debilitating chronic infection. Here’s the latest thinking on assessment and therapy strategies.
In light of recent developments in the assessment and treatment of infection with the hepatitis B virus (HBV), the American Association for the Study of Liver Diseases has issued new practice guidelines, updating earlier versions published in 2001 and 2004.
“This is a fast-moving field,” says Anna S.F. Lok, MD, professor of internal medicine and director of clinical hepatology at the University of Michigan in Ann Arbor and an author of the guidelines. The new document reflects significant developments that have both sharpened assessment and improved the efficacy of treatment.
Primary-care clinicians play a key role in identifying individuals with chronic hepatitis B infection, who are at risk for liver injury, cirrhosis, and hepatocellular carcinoma and may transmit the disease to others. “Clinicians need to know who should be screened, what tests to use, and how to act on the results of those tests,” Dr. Lok says.
One substantial at-risk group includes individuals born in areas where the prevalence of infection with HBV is high (>8%) or intermediate (2%-7%): Asia, Africa, the South Pacific Islands, the Middle East, the European Mediterranean, Eastern Europe and the former Soviet Union, as well as Argentina and much of Central America and the Caribbean.
Others who should be screened include users and past users of injected drugs, men who have or have had sex with men, individuals infected with hepatitis C or HIV, patients undergoing renal dialysis, and household and sexual contacts of those who are infected with HBV. All pregnant women should be tested as well.
The essential screening tests, according to the guidelines, are immunoassays for hepatitis B surface antigen (HBsAg) and antibody (anti-HBs). Those who test positive for HBsAg will require further evaluation, which should include assays of hepatitis B e antigen (HBeAg), anti-HBe, and HBV DNA, in addition to a standard panel of liver enzymes. HBeAg approximates how actively the virus is replicating, while the DNA test provides a more accurate quantitative assessment. Improvements in DNA assays and their wider use represent an important advance of recent years, Dr. Lok says.
The results of these tests, perhaps augmented by other laboratory studies and ultrasound, help clinicians gauge the risk of progression to liver disease and guide therapy decisions.
Counseling and prevention
To prevent HBV transmission, the guidelines recommend that HBsAg-positive individuals not share razors or toothbrushes and not donate blood, organs, or sperm. Caution patients to cover open cuts and clean blood spills with detergent or bleach. Carriers should advise their sexual contacts to be vaccinated against HBV and themselves use barrier protection during intercourse with nonvaccinated partners.
Household members of HBsAg-positive individuals should be tested; vaccination is recommended for those who are negative for HBsAg and anti-HBs. Individuals who remain at risk should be tested one to two months later for response to vaccination, and another course of vaccination offered to nonresponders. Chronic hemodialysis patients, even if they respond to vaccination, should be retested yearly. (Detailed recommendations are outlined in a CDC and Advisory Committee on Immunization Practices guideline [www.cdc.gov/mmwr/preview/mmwrhtml/rr5416a1.htm?s_cid=rr5416a1_e and www.cdc.gov/mmwr/preview/mmwrhtml/rr5516a1.htm], both accessed April 5, 2008.)
While other dietary and lifestyle modifications have not been shown to affect the progression of liver disease, individuals with chronic hepatitis B should be counseled to avoid or limit alcohol consumption.
HBsAg-positive individuals should also be educated about the importance of extended—usually lifelong—monitoring. Whether to treat an individual with chronic HBV or test further is usually decided on the basis of indices of viral replication and liver injury—HBeAg, HBV DNA, and alanine aminotransferase (ALT) in particular. But you should be mindful that hepatitis B is a dynamic condition: “There may be a very low level of the virus now, but you don’t know what it will be like two months from now,” Dr. Lok says. “This is why everyone with chronic HBV infection requires long-term monitoring.”
Clinicians who see a lot of hepatitis B patients in their practice might monitor patients themselves, providing referral to a hepatologist when active treatment appears to be necessary. But others should refer patients at the time that they test positive for HBsAg, Dr. Lok says.
In either case, clinicians should understand the rationale and logistics of monitoring. For patients who are HBeAg-positive and have HBV DNA levels indicative of active replication, the decision on whether to treat depends on ALT levels, with liver biopsy to resolve ambiguous cases. The degree of ALT elevation and DNA findings determine how frequently to retest those who are not candidates for immediate treatment. The algorithm for HBeAg-negative patients is similar, except that treatment is recommended for lower HBV DNA levels (Figure 1).
Other factors that may affect decisions on the timing of treatment include the patient’s age, clinical evidence of cirrhosis, and family history of hepatocellular carcinoma.
Screening for hepatocellular carcinoma Individuals with chronic HBV infection are at increased risk of hepatocellular carcinoma (HCC). While HCC is often curable when detected early, only one third of cases are diagnosed at an early stage. The guidelines recommend screening every 6-12 months for many carriers, including Asian men older than 40 and women older than 50, Africans older than 20, and anyone over 40 with periodically or persistently elevated ALT or HBV DNA. Patients with cirrhosis or a family history of HCC should also be screened.
Superior sensitivity, specificity, and diagnostic accuracy make ultrasound the screening modality of choice. The guidelines recommend an a-fetoprotein determination as an alternative when ultrasound is unavailable or too costly or to back up ultrasound.
Treatment aims to suppress viral replication over the long term in order to reduce liver injury and the risk of progression to cirrhosis and HCC. It cannot eradicate the virus altogether, which is why once initiated, treatment is usually maintained for years, if not for life.
“We have better, more efficacious treatments than previously,” Dr. Lok says. “Clinicians need to know that there are multiple options and that some of the newer drugs are better-tolerated. Suppression of HBV replication has been shown to improve liver histology and to reduce progression to liver failure and HCC. Clinicians should also be aware of shortcomings, such as the limited safety records of newer medications, as well as issues of drug resistance, side effects, and cost.”
The guidelines note that there are six approved treatments for hepatitis B: two injectable formulations of interferon and four oral antiviral medications. Patients need to be monitored during treatment for response, side effects, and drug resistance. The choice of initial treatment depends on a balance between relative efficacy, side effects, rate of drug resistance, costs, anticipated duration of treatment, and patient preference; this often complex process is addressed at length in the guidelines.
The American Association for the Study of Liver Diseases practice guidelines for chronic hepatitis B were published in Hepatology. 2007;45:507-539 and are online at www.aasld.org/eweb/docs/practiceguidelines/ chronichepBcorrection.pdf (accessed April 5, 2008).