What is the Best Treatment Strategy for Hepatitis B?
Response-guided interferon therapy is the most cost-effective first-line treatment for hepatitis B e antigen (HBeAg)-positive patients, whereas nucleos(t)ide analogues are the most cost-effective first-line therapy for HBeAg-negative patients, researchers report in the February issue of Clinical Gastroenterology and Hepatology.
Pegylated interferon and nucleos(t)ide analogues are recommended first-line treatment options for patients with chronic hepatitis B. However, most patients receive nucleos(t)ide analogues because of concerns about side effects and efficacy of interferon.
Interferon therapy might be more effective for some patients, depending on their hepatitis B virus (HBV) genotype. If a response-guided approach for interferon therapy could be implemented, similar to that used for patients with hepatitis C, peginterferon therapy might be more attractive—patients who are unlikely to respond to the treatment could be spared their side effects and costs.
Angeline Oi-Shan Lo et al investigated the cost-effectiveness of response-guided interferon therapy for patients positive and negative for HBeAg (a marker of viral replication). They constructed a Markov model using Hong Kong population data and rates of disease progression and treatment response from data in the literature to compare the cost-effectiveness ratio (CER) of different treatment strategies (based on quality-adjusted life-years), compared with no treatment.
They found that for HBeAg-positive patients, stopping peginterferon therapy after 12 weeks had the lowest CER ($9501/quality-adjusted life-year) compared with no treatment. Conventional (48-week) peginterferon treatment had a CER of $9664/quality-adjusted life-year.
For HBeAg-negative patients, entecavir had the lowest CER ($34,310/quality-adjusted life-year). Entecavir was more cost effective than either peginterferon strategies for these patients (CERs of $37,423/quality-adjusted life-years for 12 weeks of peginterferon and $38,474/quality-adjusted life-years for 48 weeks of treatment).
Lo et al therefore recommend response-guided interferon as first-line therapy for HBeAg-positive patients and support the continued use of nucleos(t)ide analogues as first-line therapy for HBeAg-negative patients.
They add that the 12-week stopping rule increases the cost effectiveness of peginterferon therapy. The need for long-term antiviral therapy for HBeAg-negative patients makes entecavir the most cost-effective strategy.
In an editorial that accompanies the article, Monica A. Konerman and Anna S. Lok remind readers that all models are limited by the accuracy of estimates of disease progression. Chronic HBV infection is characterized by fluctuations in viral replication and activity, and many factors (host, virus, and environment) contribute to disease progression. They write that extrapolation of data from studies with short durations of follow-up or combining data from multiple studies that focused on different subsets of CHB patients to provide estimates of disease progression can be misleading.
Konerman and Lok add that the study is also limited by outcome variables and differences in drug costs among countries.
However, Konerman and Lok say that it is important to revive the debate over whether interferon or nucleos(t)ide analogues should be used as the first-line treatment for chronic hepatitis B. They propose peginterferon therapy with a response-guided stop rule for patients who do not have other medical contraindications—especially for patients with a high likelihood of response.
This approach would allow for a durable response in some patients, with a defined course of treatment, and spare non-responders from continued side effects of interferon. They state that prospective studies validating the stop rules in diverse populations of patients are needed to further investigate this approach.