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Clinical Trial
. 2005 Nov;54(11):1604-9.
doi: 10.1136/gut.2004.062208. Epub 2005 May 29.

Flares in chronic hepatitis B patients induced by the host or the virus? Relation to treatment response during Peg-interferon {alpha}-2b therapy

H J Flink  1 , D Sprengers, B E Hansen, M van Zonneveld, R A de Man, S W Schalm, H L A Janssen; HBV 99-01 Study Group
Affiliations
Clinical Trial

Flares in chronic hepatitis B patients induced by the host or the virus? Relation to treatment response during Peg-interferon {alpha}-2b therapy

H J Flink et al. Gut. 2005 Nov.

Abstract

Background and aims: Flares are a well known phenomenon during antiviral treatment for chronic hepatitis B. Little is known about the effect of flares on response. We investigated the timing and characteristics of flares, in relation to treatment response (hepatitis B e antigen loss).

Patients: A total of 266 patients, participating in a global randomised controlled study, were assigned to 52 weeks of 100 mug pegylated (Peg)-interferon alpha-2b weekly, combined with either daily lamivudine 100 mg or placebo.

Results: Sixty seven patients (25%) exhibited 75 flares, with 38 (51%) flares in the combination therapy and 37 (49%) in the monotherapy groups. Overall, 30% of patients with and 38% of patients without a flare responded to therapy (p = 0.25). In 24 patients (36%) the flare was followed by a decrease in hepatitis B virus (HBV) DNA (host induced flare). In 25 (38%) patients the flare was preceded by an increase in HBV DNA (virus induced flare). In 17 (26%) patients the flare did not meet one of these criteria (indeterminate flare). Of patients with host induced flare, 58% responded whereas only 20% of patients with virus induced flares responded (p = 0.008). Hepatitis B surface antigen loss (n = 8) was exclusively seen in patients experiencing a host induced flare. Multivariate logistic analysis showed that host induced flares was an independent predictor of response (p = 0.043).

Conclusion: Flares are not more common in responders than in non-responders to Peg-interferon alpha-2b therapy. Virus induced flares, which occur after an increase in HBV DNA level, and most probably are indicative for increased expression of viral antigens, did not lead to treatment response. In contrast, host induced flares which were followed by a HBV DNA decrease were highly associated with treatment response.

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Figures

Figure 1
Figure 1
Proportion of response in relation to the time of the flare. Early presence of a flare increased the chance of response (p = 0.081). Probability of response is shown on the y axis.
Figure 2
Figure 2
(A) Frequency of flares according to hepatitis B virus (HBV) genotype. Among the most important genotypes in our study (HBV genotypes A, B, C and D (n = 255)), no significant difference in the frequency of flares was found. (B) Proportion of flares recorded during treatment among the flare population according to HBV genotype (n = 63). On-treatment flares predominantly occurred within genotype A. Genotype A versus genotype D, p = 0.029. (C) Flares leading to response according to genotype (n = 63). Genotype A versus genotype D, p = 0.050.
Figure 3
Figure 3
(A) Case with host induced flare. The elevation in serum alanine aminotransferase (ALT) was followed by a decrease in viral load (log hepatitis B virus (HBV) DNA). (B) Case with virus induced flare. Serum ALT elevation was preceded by a sharp increase in serum HBV DNA.
Figure 4
Figure 4
Host induced, indeterminate, and virus induced flares in relation to treatment response. Host induced versus virus induced, p = 0.008.
See this image and copyright information in PMC

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