For HBV Patients With Low Viral Load, Combo Therapy Better Than None
SAN FRANCISCO, CA—Combination treatment with peginterferon alfa-2a (peg-IFN) and adefovir or tenofovir for 48 weeks results in a loss and greater decline in HBsAg compared to no treatment in chronic hepatitis B (CHB) patients with a low viral load (LVL), reported Annikki de Niet, MD, from Academic Medical Center, Amsterdam, Netherlands, at The Liver Meeting® 2015.
Despite being the largest group of CHB patients, and despite elevated risks of cirrhosis and hepatocellular carcinoma, those with LVL are not eligible to receive antiviral treatment, Dr. de Niet noted. The researchers therefore set out to assess HBsAg loss and decline in CHB patients with LVL receiving combination treatment of peg-IFN and adefovir or tenofovir vs. no treatment.
The trial included 134 CHB patients (HBeAg-negative, HBV-DNA <20,000 IU/mL) randomized 1:1 to receive peg-IFN + adefovir (arm 1; n=46), peg-IFN + tenofovir (arm 2; n=45) or no treatment (arm 3; n=43) for 48 weeks (ITT population), and for an additional 24 weeks follow-up. HBsAg loss (AxSYM <0.05 IU/mL) and quantitative HBsAg levels were measured and compared at regular intervals.
"HBsAg loss at Week 72 only occurred in patients receiving combination treatment," the researchers reported: HBsAg loss was seen in 4 patients receiving combination therapy (2 patients from arm 1 and 2 patients from arm 2) vs. none in the untreated arm (ITT 4.4% vs. 0%, P=0.31, n.s.).
"A strong on-treatment HBsAg decline (>1.0 log IU/mL at Week 48) was observed in 17 (21%) treated patients, but in none of the untreated patients (P<0.001)," they added. "Predictors of HBsAg decline were male sex (P=0.041), higher maximum on-treatment ALT level (P=0.003), and lower Week 12 HBsAg level (P=0.002)."
In multivariate analysis, on-treatment increases in ALT and Week 12 HBsAg level remained significant predictors of HBsAg decline on treatment, the team reported.
In a per-protocol analysis, HBsAg level was found to have declined significantly by Week 48 in all study arms, the authors reported; median log-reductions for arms 1, 2 and 3, respectively, were: -0.33 (P<0.001), -0.22 (P<0.001), and -0.07 (P=0.02). "No difference in HBsAg decline was observed between treatment arms," the researchers reported. "However, HBsAg declined more in treatment arms 1 (P<0.001) and 2 (P=0.002) compared to the control arm 3."
"No increase in serious or unexpected adverse events was observed in the treatment arms as compared to the control group," the researchers noted. "Twelve patients discontinued the study during or after treatment: 5 in the Peg-IFN+ADV arm, 6 in the Peg-IFN+TDF arm, and 1 in the no-treatment arm."
"The significant decline in HBsAg in treated patients may indicate a further increase in the rate of HBsAg loss during longer follow-up," the investigators concluded.