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HBsAg loss in patients treated with peginterferon alfa-2a and adefovir is associated with SLC16A9 gene variation and lower plasma carnitine levels. / Jansen, Louis; de Niet, Annikki; Stelma, Femke et al.

In: Journal of hepatology, Vol. 61, No. 4, 2014, p. 730-737.

Research output: Contribution to journal › Article › Academic › peer-review

Harvard

Jansen, L, de Niet, A, Stelma, F, van Iperen, EPA, van Dort, KA, Tempelmans Plat-Sinnige, MJ, Takkenberg, RB, Chin, DJ, Zwinderman, AHK, Lopatin, U, Kootstra, NA & Reesink, HW 2014, 'HBsAg loss in patients treated with peginterferon alfa-2a and adefovir is associated with SLC16A9 gene variation and lower plasma carnitine levels', Journal of hepatology, vol. 61, no. 4, pp. 730-737. https://doi.org/10.1016/j.jhep.2014.05.004

APA

Jansen, L., de Niet, A., Stelma, F., van Iperen, E. P. A., van Dort, K. A., Tempelmans Plat-Sinnige, M. J., Takkenberg, R. B., Chin, D. J., Zwinderman, A. H. K., Lopatin, U., Kootstra, N. A., & Reesink, H. W. (2014). HBsAg loss in patients treated with peginterferon alfa-2a and adefovir is associated with SLC16A9 gene variation and lower plasma carnitine levels. Journal of hepatology, 61(4), 730-737. https://doi.org/10.1016/j.jhep.2014.05.004

Vancouver

Jansen L, de Niet A, Stelma F, van Iperen EPA, van Dort KA, Tempelmans Plat-Sinnige MJ et al. HBsAg loss in patients treated with peginterferon alfa-2a and adefovir is associated with SLC16A9 gene variation and lower plasma carnitine levels. Journal of hepatology. 2014;61(4):730-737. doi: 10.1016/j.jhep.2014.05.004

Author

Jansen, Louis ; de Niet, Annikki ; Stelma, Femke et al. / HBsAg loss in patients treated with peginterferon alfa-2a and adefovir is associated with SLC16A9 gene variation and lower plasma carnitine levels. In: Journal of hepatology. 2014 ; Vol. 61, No. 4. pp. 730-737.

BibTeX

@article{4c4f7a5a208a4cdbbfbae0a0ab9a36e6,
title = "HBsAg loss in patients treated with peginterferon alfa-2a and adefovir is associated with SLC16A9 gene variation and lower plasma carnitine levels",
abstract = "Achievement of HBsAg loss remains the hallmark of chronic hepatitis B treatment. In order to identify host factors contributing to treatment-induced HBsAg loss, we performed a genome-wide screen of single nucleotide polymorphisms (SNPs) and studied its immunological consequence. Chronic hepatitis B patients (40 HBeAg-positive and 44 HBeAg-negative) treated with peginterferon alfa-2a and adefovir were genotyped for 999,091 SNPs, which were associated with HBsAg loss at week 96 (n = 9). Plasma carnitine levels were measured by tandem-mass spectrometry, and the effect of carnitine on the proliferative capacity of hepatitis B virus (HBV)-specific and non-specific CD8 T cells was studied in vitro. One polymorphism, rs12356193 located in the SLC16A9 gene, was genome-wide significantly associated with HBsAg loss at week 96 (p = 1.84 × 10(-8)). The previously reported association of rs12356193 with lower carnitine levels was confirmed in our cohort, and baseline carnitine levels were lower in patients with HBsAg loss compared to patients with HBsAg persistence (p = 0.02). Furthermore, we demonstrated that carnitine suppressed HBV-specific CD8 T cell proliferation. In chronic hepatitis B patients treated with peginterferon and adefovir, we identified strong associations of SLC16A9 gene variation and carnitine levels with HBsAg loss. Our results further suggest that a lower baseline plasma carnitine level increases the proliferative capacity of CD8 T cells, making patients more susceptible to the immunological effect of this treatment. These novel findings may provide new insight into factors involved in treatment-induced HBsAg loss, and play a role in the prediction of treatment outcome",
author = "Louis Jansen and {de Niet}, Annikki and Femke Stelma and {van Iperen}, {Erik P. A.} and {van Dort}, {Karel A.} and {Tempelmans Plat-Sinnige}, {Marjan J.} and Takkenberg, {R. Bart} and Chin, {Daniel J.} and Zwinderman, {A. H. Koos} and Uri Lopatin and Kootstra, {Neeltje A.} and Reesink, {Hendrik W.}",
year = "2014",
doi = "10.1016/j.jhep.2014.05.004",
language = "English",
volume = "61",
pages = "730--737",
journal = "Journal of hepatology",
issn = "0168-8278",
publisher = "Elsevier",
number = "4",

}

RIS

TY - JOUR

T1 - HBsAg loss in patients treated with peginterferon alfa-2a and adefovir is associated with SLC16A9 gene variation and lower plasma carnitine levels

AU - Jansen, Louis

AU - de Niet, Annikki

AU - Stelma, Femke

AU - van Iperen, Erik P. A.

AU - van Dort, Karel A.

AU - Tempelmans Plat-Sinnige, Marjan J.

AU - Takkenberg, R. Bart

AU - Chin, Daniel J.

AU - Zwinderman, A. H. Koos

AU - Lopatin, Uri

AU - Kootstra, Neeltje A.

AU - Reesink, Hendrik W.

PY - 2014

Y1 - 2014

N2 - Achievement of HBsAg loss remains the hallmark of chronic hepatitis B treatment. In order to identify host factors contributing to treatment-induced HBsAg loss, we performed a genome-wide screen of single nucleotide polymorphisms (SNPs) and studied its immunological consequence. Chronic hepatitis B patients (40 HBeAg-positive and 44 HBeAg-negative) treated with peginterferon alfa-2a and adefovir were genotyped for 999,091 SNPs, which were associated with HBsAg loss at week 96 (n = 9). Plasma carnitine levels were measured by tandem-mass spectrometry, and the effect of carnitine on the proliferative capacity of hepatitis B virus (HBV)-specific and non-specific CD8 T cells was studied in vitro. One polymorphism, rs12356193 located in the SLC16A9 gene, was genome-wide significantly associated with HBsAg loss at week 96 (p = 1.84 × 10(-8)). The previously reported association of rs12356193 with lower carnitine levels was confirmed in our cohort, and baseline carnitine levels were lower in patients with HBsAg loss compared to patients with HBsAg persistence (p = 0.02). Furthermore, we demonstrated that carnitine suppressed HBV-specific CD8 T cell proliferation. In chronic hepatitis B patients treated with peginterferon and adefovir, we identified strong associations of SLC16A9 gene variation and carnitine levels with HBsAg loss. Our results further suggest that a lower baseline plasma carnitine level increases the proliferative capacity of CD8 T cells, making patients more susceptible to the immunological effect of this treatment. These novel findings may provide new insight into factors involved in treatment-induced HBsAg loss, and play a role in the prediction of treatment outcome

AB - Achievement of HBsAg loss remains the hallmark of chronic hepatitis B treatment. In order to identify host factors contributing to treatment-induced HBsAg loss, we performed a genome-wide screen of single nucleotide polymorphisms (SNPs) and studied its immunological consequence. Chronic hepatitis B patients (40 HBeAg-positive and 44 HBeAg-negative) treated with peginterferon alfa-2a and adefovir were genotyped for 999,091 SNPs, which were associated with HBsAg loss at week 96 (n = 9). Plasma carnitine levels were measured by tandem-mass spectrometry, and the effect of carnitine on the proliferative capacity of hepatitis B virus (HBV)-specific and non-specific CD8 T cells was studied in vitro. One polymorphism, rs12356193 located in the SLC16A9 gene, was genome-wide significantly associated with HBsAg loss at week 96 (p = 1.84 × 10(-8)). The previously reported association of rs12356193 with lower carnitine levels was confirmed in our cohort, and baseline carnitine levels were lower in patients with HBsAg loss compared to patients with HBsAg persistence (p = 0.02). Furthermore, we demonstrated that carnitine suppressed HBV-specific CD8 T cell proliferation. In chronic hepatitis B patients treated with peginterferon and adefovir, we identified strong associations of SLC16A9 gene variation and carnitine levels with HBsAg loss. Our results further suggest that a lower baseline plasma carnitine level increases the proliferative capacity of CD8 T cells, making patients more susceptible to the immunological effect of this treatment. These novel findings may provide new insight into factors involved in treatment-induced HBsAg loss, and play a role in the prediction of treatment outcome

U2 - 10.1016/j.jhep.2014.05.004

DO - 10.1016/j.jhep.2014.05.004

M3 - Article

C2 - 24824278

VL - 61

SP - 730

EP - 737

JO - Journal of hepatology

JF - Journal of hepatology

SN - 0168-8278

IS - 4

ER -

ID: 2407209