Response to interferon alfa is HBV genotype dependent: genotype A is more sensitive to interferon than genotype D

Klinik für Gastroenterologie, Hepatologie und Infektiologie, Heinrich-Heine-Universität Düsseldorf, Moorenstr 5, D-40225 Düsseldorf, Germany.
Gut (Impact Factor: 14.66). 07/2005; 54(7):1009-13. DOI: 10.1136/gut.2004.060327
Source: PubMed

ABSTRACT Current interferon alfa (IFN) treatment of chronic hepatitis B has limited efficacy. The role of hepatitis B virus (HBV) genotypes for response to IFN was investigated.
HBV genotype was determined by direct sequencing of the HBV X gene in 165 consecutive patients with chronic replicative hepatitis B treated with standard IFN. HBV genotype A or D was found in 144 cases.
Sustained response (six months after treatment) to standard IFN therapy was higher in HBV genotype A compared with HBV genotype D infected patients (49% v 26%; p<0.005). Sustained response to IFN was 46% versus 24% (p<0.03) in hepatitis B e antigen (HBeAg) positive hepatitis (n = 99) and 59% versus 29% (p<0.05) in HBeAg negative hepatitis (n = 45) for HBV genotype A compared with HBV genotype D. HBeAg status had no negative impact on IFN response. Multivariate logistic regression identified HBV genotype A and high pretreatment alanine aminotransferase levels (>2 x upper limit of normal) as independent positive predictive parameters of IFN response.
The present study indicates that HBV genotypes A and D are important and independent predictors of IFN responsiveness in chronic hepatitis B. HBV genotype adapted treatment regimens may further improve treatment efficacy in chronic hepatitis B.

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    • "The present study of CHB genotype D patients showed a higher SVR of 57.1% than previously reported, as based on the earlier, less stringent definition of SVR (HBV DNA <20,000 copies ml−1). Erhardt et al. [10] reported that HBV genotype A is associated with a significantly higher SVR to IFN than HBV genotype D and showed better SVR rates than genotype C, B, or E. They also reported SVR to IFN was 59 versus 29% in HBeAg-negative genotype A compared with genotype D, respectively. In the same study, no statistically significant difference was reported in SVR between HBeAg-positive and -negative patients [37 vs. 40% = nonsignificant (NS)]. "
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    ABSTRACT: Peginterferon (PEG-IFN) α-2a has been shown to induce a sustained virologic response (SVR) in 20-30% of "hepatitis B e antigen (HBeAg)"-negative patients. To determine the safety and efficacy of PEG-IFN α-2a in HBeAg-negative, genotype D-naive patients and to analyze the predictors of response. This prospective, multicenter, open-label, nonrandomized trial was conducted at four hospitals. A total of 35 consecutive HBeAg-negative naive genotype D patients received PEG-IFN α-2a for 48 weeks. Based on a cutoff of hepatitis B virus (HBV) DNA <400 copies ml(-1), an early virologic response (EVR) at week 12, end of treatment virologic response (ETVR) at week 48, and SVR at week 72 were achieved by 3 (9%), 9 (26%), and 8 patients (23%), respectively. The EVR rate improved to 43%, ETVR to 49%, and SVR to 57%, when a HBV DNA cutoff level of <20,000 copies ml(-1) was used. Pretreatment HBsAg level was not a predictor for SVR on univariate analysis, but correlated with decline in HBV DNA levels at weeks 48 and 72. On multivariate logistic regression analysis, low body weight, high alanine aminotransferase (ALT), low HBV DNA, and low triglyceride levels were identified as baseline predictors of SVR. HBeAg-negative genotype D-naive patients treated with PEG-IFN α-2a achieved SVR in 23 (HBV <400 copies ml(-1)) and 57% (HBV <20,000 copies ml(-1)) of patients, a better response than previously reported that might be related to the absence of drug resistance in these naive patients. Pretreatment predictors of SVR were low body weight, high ALT, low HBV DNA, and low triglycerides.
    Hepatology International 10/2012; 6(4):718-726. DOI:10.1007/s12072-011-9319-2 · 1.78 Impact Factor
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    • "It has been shown that genotypes C and D are associated with more serious liver injuries and with a higher incidence of HCC than genotypes A and B [42-44]. In addition, genotype C and D have a much lower rate in response to interferon therapy than those infected with A or B genotypes [40,45]. Moreover, subtle differences in frequency and type of lamivudine resistant variants occur in genotype A and D infectious [15]. "
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    ABSTRACT: Hepatitis B virus (HBV) infection is one of the main human health problem and causes a large-scale of patients chronic infection worldwide.. As the replication of HBV depends on its host cell system, codon usage pattern for the viral gene might be susceptible to two main selections, namely mutation pressure and translation selection. In this case, a deeper investigation between HBV evolution and host adaptive response might assist control this disease. Relative synonymous codon usage (RSCU) values for the whole HBV coding sequence were studied by Principal component analysis (PCA). The characteristics of the synonymous codon usage patterns, nucleotide contents and the comparison between ENC values of the whole HBV coding sequence indicated that the interaction between virus mutation pressure and host translation selection exists in the processes of HBV evolution. The synonymous codon usage pattern of HBV is a mixture of coincidence and antagonism to that of host cell. But the difference of genetic characteristic of HBV failed to be observed to its different epidemic areas or subtypes, suggesting that geographic factor is limited to influence the evolution of this virus, while genetic characteristic based on HBV genotypes could be divided into three groups, namely (i) genotyps A and E, (ii) genotype B, (iii) genotypes C, D and G. Codon usage patterns from PCA for identification of evolutionary trends in HBV provide an alternative approach to understand the evolution of HBV. Further more, a combined selection of mutation pressure with translation selection on codon usage might shed a light on understanding the evolutionary trends of HBV genotypes.
    Virology Journal 12/2011; 8(1):544. DOI:10.1186/1743-422X-8-544 · 2.18 Impact Factor
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    • "Recent studies have suggested that HBV genotype affects the therapeutic response to both IFN and nucleos(t)ide analogue-based agents [23,24]. In brief, the incidence of sustained ALT normalization and HBeAg seroconversion 6-12 months after the cessation of interferon treatment is significantly higher in patients with HBV-A and -B than in those with HBV-C or -D [25,26]. In Asian HBeAg-positive patients, those with HBV-B are susceptible to both standard and pegylated IFN, and those with HBV-C are more likely to respond favorably to pegylated IFN than to standard IFN [27-31]. "
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    ABSTRACT: Although safe and effective vaccines for hepatitis B virus (HBV) have been available for nearly three decades, this virus kills at least 600,000 people annually worldwide and remains the leading global cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Because the HBV reverse transcriptase lacks a proofreading function, many HBV genotypes, subgenotypes, mutants, and recombinants exist. At least 10 HBV genotypes (HBV-A through J) with distinct geographic distributions have been identified; by definition, their complete genomic sequences diverge by more than 8%. HBV genotype is increasingly becoming recognized as an important factor in the progression and clinical outcome of HBV-induced disease. Infections by HBV-C or -D are significantly more likely to lead to cirrhosis and hepatocellular carcinoma than are infections by HBV-A or -B. Additionally, the hepatitis B e antigen seroconversion response to standard or pegylated interferon is more favorable in patients with HBV-A or -B than in those with HBV-C or -D. However, therapeutic responses to nucleos(t)ide analogues are generally comparable among HBV genotypes. In conclusion, genotyping of HBV is useful in identifying chronic hepatitis B patients who are at increased risk of disease progression, thereby enabling physicians to optimize antiviral therapy for these patients.
    The Korean Journal of Internal Medicine 09/2011; 26(3):255-61. DOI:10.3904/kjim.2011.26.3.255 · 1.43 Impact Factor
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