Hepatitis B: A strategy for evaluation and management
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.
SCREEN BEFORE CHEMOTHERAPY OR IMMUNOSUPPRESSIVE THERAPY
When patients who are positive for HBV surface antigen undergo immunosuppressive therapy or cancer chemotherapy, from 20% to 50% develop reactivated HBV infection with high HBV viral loads. Even patients who have resolved hepatitis B (ie, negative for HBV surface antigen and positive for surface antibody) may experience hepatitis B reactivation, with serious consequences. Hepatic decompensation and death have been reported during and after chemotherapy, especially in patients with cirrhosis.9 Therefore, patients at risk of HBV infection should be screened for it before starting these therapies.4 Furthermore, perhaps all patients about to undergo anticancer therapies that include anti-B-cell or anti-T-cell therapies or hematopoietic stem cell transplantation should be screened.9
Recent data indicate that many oncologists have not been screening for HBV.10 Hence, more effort is needed to make this important testing routine in this setting.
The initial tests in these patients should be liver chemistry tests, HBV surface antigen, HBV surface antibody, and HBV core antibody. In those who test positive for surface antigen, one should test for e antigen, e antibody, and HBV DNA.
Patients with indications for anti-HBV therapy (Table 1) should receive antiviral therapy. Otherwise, those positive for surface antigen should start taking anti-HBV medication at the start of chemotherapy or immunosuppressive therapy and should continue taking it until 6 months after the chemotherapy or immunosuppressive therapy is finished.4 Some experts also recommend starting anti-HBV therapy 7 days before the chemotherapy or immunosuppressive therapy and continuing it for 1 year afterward.10 Those with HBV DNA levels higher than 2 × 103 IU/mL should continue HBV therapy until they reach the same treatment end points as for immunocompetent patients as outlined above.4
Because we have little information on patients who are negative for surface antigen and who have antibodies against surface antigen and core antigen, we cannot make an unequivocal recommendation for anti-HBV therapy in this group.11 Rather, these patients should be monitored during immunosuppressive treatment, preferably with liver chemistry tests and HBV DNA titers, and antiviral drugs should be given as a deferred therapy upon evidence of HBV reactivation.9 Few cases of fatal hepatic failure in patients with this serologic pattern receiving rituximab (Rituxan) have been reported.12–14
With their small risk of drug resistance and rapid onset of action, entecavir or tenofovir may be the preferred anti-HBV therapy in patients undergoing immunosuppression or chemotherapy, especially in those requiring prolonged immunosuppressive therapy (longer than 12 months). In those requiring shorter courses, lamivudine or telbivudine is a possible alternative.4
OUTCOMES OF LIVER TRANSPLANTATION HAVE IMPROVED IN HBV PATIENTS
The early results of liver transplantation for HBV were discouraging because many patients developed rapidly progressive recurrent disease (fibrosing cholestatic hepatitis) and died within 12 to 18 months after the operation.15 However, patients with HBV are now treated perioperatively with lamivudine or adefovir combined with prolonged administration of hepatitis B immune globulin, and their survival now exceeds that of patients who receive transplants for many other conditions.16
Like patients with cirrhosis due to other causes, those with HBV-related cirrhosis who have any of the following should be referred for liver transplantation evaluation16:
- A Child-Turcotte-Pugh score of 7 or higher (Table 5).
- A major complication of cirrhosis such as ascites, variceal bleeding, hepatocellular carcinoma, or hepatic encephalopathy.
PREVENTING VERTICAL TRANSMISSION
The major problem in young women with chronic HBV infection is the risk of vertical (mother-to-infant) transmission at delivery. The risk varies, depending on the viral load and e antigen status of the mother at the time of delivery; if she is positive for e antigen, the risk of HBV infection in the newborn is 70% to 90% by the age of 6 months if the newborn does not receive postexposure immunoprophylaxis; if the mother is positive for surface antigen but negative for e antigen, the risk of chronic infection is less than 10%, even without postexposure immunoprophylaxis.17
All women should be tested for HBV surface antigen early in pregnancy each time they become pregnant. If a patient tests negative early in pregnancy but continues behaviors that put her at risk of HBV infection (eg, having multiple sexual partners, having had a sex partner positive for surface antigen, using injection drugs, or contracting any sexually transmitted disease), she should be retested at the time of admission to the hospital for delivery.17 This also includes women who were not screened prenatally and those with clinical hepatitis.
Vaccine and immune globulin for the infant
If the mother is positive for HBV surface antigen, the infant should receive single-antigen HBV vaccine and hepatitis B immune globulin within 12 hours of birth, given at different injection sites.17 The second dose of vaccine should be given at age 1 to 2 months and the third at age 6 months (but not before age 24 weeks). The response to vaccination should be ascertained by testing for surface antigen and surface antibody after completion of the vaccine series, at age 9 to 18 months.
Maternal HBV infection does not contraindicate breastfeeding, as studies suggest that breastfeeding by a mother positive for surface antigen does not increase the infant’s risk of acquiring HBV infection.18
Which HBV therapy for a pregnant woman?
Some evidence supports antiviral therapy with nucleoside/nucleotide analogues in pregnant women who have viral loads of 106 IU/mL or higher. Lamivudine is safe in pregnancy and, together with immunization of the infant, reduces HBV transmission. Interferon-based therapy is contraindicated in pregnant women (and in women who may want to become pregnant) because of interferon’s antiproliferative effects. Nucleoside/nucleotide analogues classified as category B (eg, lamivudine, telbivudine, and tenofovir) could be used when the benefit of treating the pregnant mother outweighs the risk to the mother or fetus,2 although the possible effects of tenofovir on bone density argue against its use during pregnancy or breastfeeding.19
