Chronic Hepatitis B

A Treatment Update

Vincent Wong, MD; Henry Chan, MD


Semin Liver Dis. 2013;33(2):122-129. 

In This Article

Peginterferon versus Nucleos(T)Ide Analogs

Worldwide, seven drugs have been registered for the treatment of chronic hepatitis B. These include two interferons (conventional interferon and peginterferon alfa-2a) and five oral NAs (lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxilfumarate). Rather than stating which mode of treatment is the best, the relative merits and limitations of individual agents should be examined.

The main advantage of conventional interferon and peginterferon is their finite course of treatment and high durability. Among patients who have achieved HBeAg seroconversion after conventional interferon or peginterferon treatment, 80% continue to have sustained HBeAg seroconversion 5 to 10 years later.[5,7] However, interferon requires subcutaneous injections and is associated with numerous side effects such as flu-like symptoms, bone marrow suppression, thyroid dysfunction, and mood disorders. Dose reduction and premature treatment cessation are often necessary to manage the side effects. Besides, interferon may aggravate liver decompensation in patients with advanced disease or very high ALT level.

In contrast, NAs are given conveniently via oral route and carry few side effects. However, because NAs do not have direct immunomodulatory actions, the treatment effect is less durable. Virological relapse after treatment cessation occurs in 30 to 40% of patients with HBeAg-positive disease achieving HBeAg seroconversion and in around 50% of patients with HBeAg-negative disease even after a prolonged period of HBV DNA suppression.[8–10] As a result, the majority of patients require long-term treatment. This is particularly problematic for weaker agents because of their propensity to induce drug resistance.

Because of these differences, the choice of antiviral agents should be a joint decision between the patient and the hepatologist. Interferon is often preferred in young patients who do not want long-term treatment, particularly if family planning is an issue. In contrast, NAs are an attractive option for older patients and those with advanced disease because of better tolerance.

It should be highlighted that different therapeutic end points should be adopted when different agents are used. When NAs are used, the immediate goal is complete on-treatment virological response—undetectable HBV DNA. In contrast, few patients treated with interferon can have persistently undetectable HBV DNA after treatment decision. This, however, should not be taken as evidence of interferon's inferiority. In epidemiological studies, patients with HBV DNA below 2000 IU/mL have similar incidence of HCC to those with undetectable HBV DNA.[11] Besides, current observation suggests that interferon is probably as effective as NAs in preventing adverse clinical outcomes.[2] This implies that complete viral suppression may not be essential. The main reason for maintaining undetectable HBV DNA in NA-treated patients is to prevent drug resistance.