Patients with chronic HBV have either e-antigen positive or negative disease. E-antigen negative disease is more difficult to treat and requires longer treatment duration. Chronic HBV can be treated with peg-interferon alpha-2a (Pegasys) or a nucleoside reverse transcriptase inhibitor (NRTI).4 Peg-interferon alpha-2a and the NRTIs are similar in efficacy for e-antigen positive and negative HBV; however, seroconversion of the e-antigen occurs more often at 1 year for peg-interferon alpha-2a and 2 years for NRTIs. Viral resistance does not develop to peg-interferon alpha-2a, but is associated with NRTIs.4
The most common interferon adverse effects are flu-like symptoms (fever, headache, nausea, musculoskeletal pain, myalgia, and weakness), thrombocytopenia, neutropenia, depression, alopecia, fatigue, anxiety, and insomnia. Severe adverse effects include hepatic decompensation, bone marrow suppression, gastrointestinal hemorrhage or ischemic colitis, hemorrhagic or ischemic stroke, pulmonary disease including respiratory failure, and severe psychiatric side effects (depression, suicidal ideation, and suicide attempt). There are black box warnings for caution in patients with neuropsychiatric disorders, autoimmune disease, persistent severe infections, and ischemic disorders. Contraindications to interferon therapy include hypersensitivity to the drug, autoimmune hepatitis, and decompensated cirrhosis.13-15
The NRTIs, including lamivudine (Epivir), adefovir (Hepsera), entecavir (Baraclude), telbivudine (Tyzeka), and tenofovir (Viread), inhibit HBV polymerase. Administered orally, they are well tolerated with few adverse effects. Headache and gastrointestinal problems are the most commonly reported side effects. Rare, but serious side effects include lactic acidosis, hepatomegaly with steatosis, and HBV exacerbation upon discontinuation of the NRTI (black box warning).16-20 Adefovir and tenofovir can cause nephrotoxicity; therefore serum creatinine should be monitored closely. Telbivudine may cause peripheral neuropathy and increased creatine kinase.
Lamivudine was the first NRTI used to treat chronic HBV, but it is plagued with a high incidence of viral resistance and cross-resistance. Newer NRTIs display less resistance and cross-resistance.4 Studies involving combination therapy with NRTIs have not shown improved results compared to monotherapy; therefore, combination therapy is not warranted in most patients.