Patterns of hepatitis B surface antigen decline and HBV DNA suppression in Asian treatment-experienced chronic hepatitis B patients after three years of tenofovir treatment
Wai-Kay Seto a,
Kevin Liu a,
Danny Ka-Ho Wong a, b,
James Fung a, b,
Fung-Yu Huang a,
Ivan Fan-Ngai Hung a,
Ching-Lung Lai a, b,
Man-Fung Yuen a, b, Corresponding author contact information, E-mail the corresponding author
a Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hong Kong
b State Key Laboratory for Liver Research, the University of Hong Kong, Queen Mary Hospital, Hong Kong
Abstract
Background
Patterns of serum hepatitis B surface antigen (HBsAg) decline during nucleos(t)ide analogue (NA) therapy have not been well-investigated.
Methods
We determined the cumulative serologic, virologic and biochemical outcomes of 142 Asian CHB patients, with at least 6 months exposure to other NAs, receiving tenofovir with or without lamivudine for up to 3 years. Liver biochemistry, serum HBV DNA and HBsAg levels were determined at baseline, 6 months and yearly from years 1 to 3.
Results
142, 123 (86.6%) and 70 (49.3%) CHB patients were followed up for 1, 2, and 3 years respectively. Two phases of HBsAg decline were observed. Patients with baseline HBsAg ⩾3 log IU/mL, when compared to patients with baseline HBsAg <3 log IU/mL, had a greater median rate of HBsAg reduction through 3 years of treatment (0.155 and 0.039 log IU/mL/year respectively, p<0.001). Among patients with 3 years of follow-up, there was a significantly greater median rate of HBsAg reduction during the first year when compared to the second and third years (0.220, 0.136 and 0.081 log IU/mL/year respectively, p<0.001). HBeAg status, HBV genotype and concomitant lamivudine therapy were not important determinants of HBsAg kinetics (all p>0.05). The 3-year cumulative virologic suppression rate was 93.3%, with no cases of resistance detected.
Conclusion
Serum HBsAg levels in NA-experienced patients receiving tenofovir demonstrated a variable pattern of decline, with slower rates of reduction noted in patients with lower baseline HBsAg levels, and could explain the rarity of HBsAg seroclearance during NA therapy. (ClinicalTrials.gov Identifier NCT01728935). 作者: StephenW 时间: 2013-6-23 18:54
ClinicalTrials.gov Identifier NCT01728935)
Tenofovir in Asian Chronic Hepatitis B Patients
Purpose
Tenofovir (TDF) has been demonstrated to have potency antiviral against the hepatitis B virus (HBV) in various multiple-centre trials, with no cases of resistance encountered. However, its efficacy and resistance profile in the Asian population, which constitute the majority of chronic hepatitis B (CHB) patients, is unknown. Compared to other nucleoside analogues, TDF has been associated with relatively high rates of hepatitis B surface antigen (HBsAg) seroclearance. It would be interested to see if this could be reproduced. The investigators plan to report the serologic and virologic results of our 140 nucleoside analogue-experienced patients who were commenced on TDF.
Detailed Description:
Recent multi-center trials have shown tenofovir disoprovil fumarate (TDF) demonstrating potent antiviral efficacy in both nucleoside-naive and -experienced chronic hepatitis B (CHB) patients. At present, there has been no identifiable amino acid substitutions associated with resistance to TDF.
Since TDF and adefovir (ADV), another licensed drug for CHB, belong to same molecular group, acyclic phosphonate, there had been various studies investigating the efficacy of TDF in ADV-resistant patients. The efficacy of tenofovir in this group of patients is conflicting. While several studies have shown TDF achieving similar viral suppression when compared to CHB patients without ADV-resistance , another study found that patients with the signature ADV mutations of rtA181V/T and /or rtN236T responded suboptimally to TDF. For all published studies, the number of patients with documented genotypic resistance to adefovir is actually small (n = 17-40), and therefore, further studies in this area are required.
Another interesting point to note was the relatively high rate of hepatitis B surface antigen (HBsAg) seroclearance found in patients taking TDF. The cumulative rate of HBsAg seroclearance up in hepatitis B e antigen (HBeAg)-positive was 10% after 4 years . However, the same study did not find any HBeAg-negative patients achieving HBsAg seroclearance. In addition, studies on TDF were mainly performed in Caucasian patients, the majority being genotypes A and D. A preliminary study performed in Asian patients, predominantly genotypes B and C, did not discover any cases of HBsAg seroclearance . Given the majority of the CHB population is found in Asia, further studies are needed to clarify if HBsAg seroclearance by nucleoside / nucleotide analogues is potentially achievable using TDF.
Enrollment: 141
Study Start Date: April 2008
Estimated Study Completion Date: March 2013
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure) 作者: StephenW 时间: 2013-6-23 19:02