Factors that Predict Response to Pegylated Interferon in HBeAg Positive Chronic Hepatitis B Patients

		SUMMARY: HBV genotype, HBV DNA (viral load), and alanine aminotransferase (ALT) level are predictors of sustained response to pegylated interferon for treatment of chronic hepatitis B, according to study results reported in the December 2009 issue of Gastroenterology.

By Liz Highleyman

Chronic hepatitis B virus (HBV) infection is treated with either directly-targeted antiviral agents -- such as lamivudine (Epivir-HBV), adefovir (Hepsera), entecavir (Baraclude), or tenofovir (Viread) -- or with conventional or pegylated interferon alfa, which works by stimulating the body's immune response against the virus.

Hepatitis B Virus

However, pegylated interferon produces a sustained response in only a minority of patients and causes considerable side effects, the study authors noted. Therefore, it would be useful to be able to predict in advance who is likely to respond.

The investigators analyzed data from 2 large international trials of hepatitis B "e" antigen (HBeAg) positive chronic hepatitis B patients to determine which ones were most likely to respond to pegylated interferon.

The study included 542 participants treated with 180 mcg/week pegylated interferon alpha-2a (Pegasys) for 48 weeks, and 266 patients treated with 100 mcg/week pegylated interferon alpha-2b (PegIntron) for 52 weeks. A total of 87 participants were excluded for various reasons, leaving 721 patients in the final analysis.

Sustained response was defined as HBeAg loss and HBV DNA < 2.0 x 10(4) IU/mL at 6 months after treatment. Logistic regression analysis was used to identify predictors of sustained response.

Results

	The following factors were significant predictors of sustained response:
	HBV genotype; High ALT level (>2 x upper limit of normal); Low HBV DNA level (< 2.0 x 10(8) IU/mL), Female sex; Older age; Lack of previous interferon therapy (i.e., treatment-nave).
	The strongest predictors were high ALT in genotype B patients, and low HBV DNA in genotype C patients.
	Genotype A patients with high ALT and/or low HBV DNA had > 30% predicted probability of sustained response.
	Genotype D patients, however, had a low probability of sustained response regardless of ALT or HBV DNA levels.

"The best candidates for a sustained response to [pegylated interferon alfa] were genotype A patients with high levels of ALT or low levels of HBV DNA and genotype B and C patients that have both high levels of ALT and low HBV DNA," the investigators concluded. "Genotype D patients have a low chance of sustained response."

With the licensing of pegylated interferon alfa-2a and 5 nucleoside/nucleotide analogs for the treatment of chronic hepatitis B, "the choice of antiviral therapy has become more important and more complex at the same time," the study authors elaborated in their discussion. "Because both treatment with interferon-based therapy and [nucleoside/nucleotide analog] therapy have proven effective and can improve long-term outcome, the pros and cons of these drugs as well as patient-specific characteristics should be taken into consideration."

All major practice guidelines have advocated interferon-based therapy as potential first-line treatment for both HBeAg positive and HBeAg negative patients, since sustained response and hepatitis B surface antigen (HBsAg) loss seem to occur more often with interferon than with directly targeted antiviral agents, they noted. However, the use of pegylated interferon currently accounts for no more than 10% of all prescriptions for chronic hepatitis B treatment.

"The relatively low use of [pegylated interferon] may be explained by its significant side effects and need for administration by injection. Furthermore, recommendations on the use of [pegylated interferon] in specific subsets of patients who are most likely to have a sustained response and HBsAg seroconversion were lacking," the researchers continued. "When we are able to identify patients with a high likelihood of response to [pegylated interferon], the proportion of patients achieving sustained response after treatment with this drug probably can be increased."

Department of Gastroenterology & Hepatology, Department of Epidemiology & Biostatistics, and Department of Public Health, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands; Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, China; Department of Medicine, Songklanakarin Hospital, Songkla, Thailand; Medizinische Klinik I, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.

1/05/10

Reference
E Buster, BE Hansen, GK Lau, and others. Factors that Predict Response of Patients with Hepatitis B e Antigen-Positive Chronic Hepatitis B to Peginterferon-alpha. Gastroenterology 137(6): 2002-2009 (Abstract). December 2009.