Interferon-alpha therapy for chronic hepatitis B: Early response related to pre-treatment changes in viral replication

Abstract

Chronic hepatitis B patients with low pre-treatment HBeAg (and HBV-DNA) levels are more likely to respond to interferon-alpha therapy. In retrospect, this low level of HBeAg may have been reached just before the start of therapy. Pre-treatment changes in HBeAg levels were studied in 121 patients undergoing interferon-alpha 2B therapy. HBeAg was monitored by the AxSYM HBe 2.0 Quantitative (Abbott Laboratories) and HBV-DNA by liquid hybridisation (Abbott Laboratories). At the end of treatment (week 16) 24 patients had responded (HBeAg and HBV-DNA below the level of detection). Response was significantly (P = 0.007) related to a decrease in HBeAg level before the start of therapy. Eight of the 24 (33%) responding patients exhibited a > 50% decrease in HBeAg level just before the start of therapy compared to 7 of the 97 (7%) non-responding patients. The geometric mean titre of HBeAg decreased significantly (P < 0.005; 8-week period before start) among responding patients (271 ( 98 PEI U/ml) in contrast to non-responding patients (737 ( 724 PEI U/ml). Planning the start of interferon treatment just after a spontaneous decrease in HBV replication may increase the response rate for interferon-alpha therapy.

The Complex Role of HBeAg and Its Precursors in the Pathway to Hepatocellular Carcinoma

“…Alpha interferon (IFN-α) is used clinically to treat CHB patients; however, only approximately one-third of patients respond to IFN-α treatment [108]. Patients with low HBeAg levels prior to treatment are more likely to respond to IFN-α therapy, and HBeAg negative patients with core promoter mutations respond better to IFN-α therapy than HBeAg positive patients [109,110], suggesting that HBeAg or its intracellular precursors may interfere with the IFN signalling representing a viral strategy to persist in the host through induction of immune tolerance.…”