Peg-interferon improves liver histology in patients with HBeAg-positive chronic hepatitis B: No additional benefit of combination with lamivudine

Monika van Zonneveld; Pieter E. Zondervan; Yilmaz Cakaloglu; Christopher Simon; Ulus S. Akarca; Thomas M. K. So; Hajo J. Flink; Robert A. de Man; Solko W. Schalm; Harry L. A. Janssen; H. G. M. Niesters; B. Hansen; B. C. M. Vroom; C. M. J. van Nieuwkerk; R. A. de Vries; J. Jansen; J. Drenth; S. J. van den Hazel; J. W. den Ouden-Muller; A. C. Tan; D. M. Adler; P. Michielsen; H. van Vlierberghe; F. Nevens; J. Delwaide; J. Henrion; S. Zeuzem; G. Gerken; S. Bein; U. Treichel; J. Trojan; M. P. Manns; J. Hadem; J. Niederau; M. R. Buhl; I. M. Hansen; K. Krogsgaard; J. Cianciara; J. Jablonska; J. Kozlowska; D. Prokopowicz; R. Flisiak; T. Mach; M. Buti; A. Valdes; R. Esteban; M. Rodriguez; M. Garcia Espiga; A. Andriulli; G. Stornaiulo; G. B. Gaeta; G. Montalto; F. D'Antona; G. E. Kitis; P. Xiarchos Panagiotis; N. C. Tassopoulos; G. Ersöz; S. Karayalcin; C. Yurdayin; H. Bozkaya; H. Simsek; Y. Balaban; H. Senturk; F. Tabak; Y. Lurie; J. Heathcote; S. V. Feinman; S. Greenbloom; D. A. Sulaiman; R. Guan; I. Merican

doi:https://doi.org/10.1111/j.1478-3231.2006.01257.x

Peg-interferon improves liver histology in patients with HBeAg-positive chronic hepatitis B: No additional benefit of combination with lamivudine

Monika van Zonneveld, Pieter E. Zondervan, Yilmaz Cakaloglu, Christopher Simon, Ulus S. Akarca, Thomas M. K. So, Hajo J. Flink, Robert A. de Man, Solko W. Schalm, Harry L. A. Janssen, H. G. M. Niesters, B. Hansen, B. C. M. Vroom, C. M. J. van Nieuwkerk, R. A. de Vries, J. Jansen, J. Drenth, S. J. van den Hazel, J. W. den Ouden-Muller, A. C. TanD. M. Adler, P. Michielsen, H. van Vlierberghe, F. Nevens, J. Delwaide, J. Henrion, S. Zeuzem, G. Gerken, S. Bein, U. Treichel, J. Trojan, M. P. Manns, J. Hadem, J. Niederau, M. R. Buhl, I. M. Hansen, K. Krogsgaard, J. Cianciara, J. Jablonska, J. Kozlowska, D. Prokopowicz, R. Flisiak, T. Mach, M. Buti, A. Valdes, R. Esteban, M. Rodriguez, M. Garcia Espiga, A. Andriulli, G. Stornaiulo, G. B. Gaeta, G. Montalto, F. D'Antona, G. E. Kitis, P. Xiarchos Panagiotis, N. C. Tassopoulos, G. Ersöz, S. Karayalcin, C. Yurdayin, H. Bozkaya, H. Simsek, Y. Balaban, H. Senturk, F. Tabak, Y. Lurie, J. Heathcote, S. V. Feinman, S. Greenbloom, D. A. Sulaiman, R. Guan, I. Merican

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

37 Citations (Scopus)

Abstract

Background: The effect of pegylated interferon or its combination with lamivudine on liver histology of patients with chronic hepatitis B (CHB) is unknown. In a double-blinded, randomized, multi-center study we assessed histological changes in 110 hepatitis B e-antigen (HBeAg)-positive CHB patients treated for 52 weeks with Pegylated interferon α-2b (PEG-IFN) in combination with either lamivudine or placebo. Liver biopsies were taken before and at the end of treatment. All biopsies were blinded and scored according to the Ishak system. Results: Necroinflammatory score improved (defined as a decrease of at least two points) in 25 patients (48%) of the PEG-IFN/lamivudine combination therapy group and in 31 patients (53%) of the PEG-IFN monotherapy group. The fibrosis score improved (decrease of at least 1 point) in 17 patients (33%) of the combination therapy group vs. 13 patients (22%) of the PEG-IFN monotherapy group (P=0.23). Responders (n=42), defined as serum HBeAg negative at the end of therapy, showed a larger decline in necroinflammatory score than non-responders (mean decline 2.3 and 1.2 pointsm respectively, P=0.02). Among patients receiving PEG-IFN monotherapy necroinflammation improved more frequently in responders (78% responders vs. 43% of non-responders, P=0.01) and in patients who showed normalization of ALT (76% of patients with normal ALT vs. 40% of patients with abnormal ALT, P = 0.01). Fibrosis score in the PEG-IFN monotherapy group improved more often in responders (39%) than in non-responders (15%, P=0.04). In the PEG-IFN/lamivudine combination therapy group, we found no signigficant association between virological and biochemical endpoints and histological improvement. Conclusion: Treatment with PEG-IFN therapy improves liver necroinflammation in HBeAg-positive CHB patients, particularly in responders to therapy. PEG-IFN also improves fibrosis in responders. Addition of lamivudine to PEG-IFN did not further improve the histological outcome. © 2006 Blackwell Munksgaard.

Original language	English
Pages (from-to)	399-405
Journal	Liver international
Volume	26
Issue number	4
DOIs	https://doi.org/10.1111/j.1478-3231.2006.01257.x
Publication status	Published - 2006
Externally published	Yes

Access to Document

https://doi.org/10.1111/j.1478-3231.2006.01257.x

Cite this

van Zonneveld, M., Zondervan, P. E., Cakaloglu, Y., Simon, C., Akarca, U. S., So, T. M. K., Flink, H. J., de Man, R. A., Schalm, S. W., Janssen, H. L. A., Niesters, H. G. M., Hansen, B., Vroom, B. C. M., van Nieuwkerk, C. M. J., de Vries, R. A., Jansen, J., Drenth, J., van den Hazel, S. J., den Ouden-Muller, J. W., ... Merican, I. (2006). Peg-interferon improves liver histology in patients with HBeAg-positive chronic hepatitis B: No additional benefit of combination with lamivudine. Liver international, 26(4), 399-405. https://doi.org/10.1111/j.1478-3231.2006.01257.x

@article{5db5d9a869454d379aa706422ce2c2a4,

title = "Peg-interferon improves liver histology in patients with HBeAg-positive chronic hepatitis B: No additional benefit of combination with lamivudine",

abstract = "Background: The effect of pegylated interferon or its combination with lamivudine on liver histology of patients with chronic hepatitis B (CHB) is unknown. In a double-blinded, randomized, multi-center study we assessed histological changes in 110 hepatitis B e-antigen (HBeAg)-positive CHB patients treated for 52 weeks with Pegylated interferon α-2b (PEG-IFN) in combination with either lamivudine or placebo. Liver biopsies were taken before and at the end of treatment. All biopsies were blinded and scored according to the Ishak system. Results: Necroinflammatory score improved (defined as a decrease of at least two points) in 25 patients (48%) of the PEG-IFN/lamivudine combination therapy group and in 31 patients (53%) of the PEG-IFN monotherapy group. The fibrosis score improved (decrease of at least 1 point) in 17 patients (33%) of the combination therapy group vs. 13 patients (22%) of the PEG-IFN monotherapy group (P=0.23). Responders (n=42), defined as serum HBeAg negative at the end of therapy, showed a larger decline in necroinflammatory score than non-responders (mean decline 2.3 and 1.2 pointsm respectively, P=0.02). Among patients receiving PEG-IFN monotherapy necroinflammation improved more frequently in responders (78% responders vs. 43% of non-responders, P=0.01) and in patients who showed normalization of ALT (76% of patients with normal ALT vs. 40% of patients with abnormal ALT, P = 0.01). Fibrosis score in the PEG-IFN monotherapy group improved more often in responders (39%) than in non-responders (15%, P=0.04). In the PEG-IFN/lamivudine combination therapy group, we found no signigficant association between virological and biochemical endpoints and histological improvement. Conclusion: Treatment with PEG-IFN therapy improves liver necroinflammation in HBeAg-positive CHB patients, particularly in responders to therapy. PEG-IFN also improves fibrosis in responders. Addition of lamivudine to PEG-IFN did not further improve the histological outcome. {\textcopyright} 2006 Blackwell Munksgaard.",

author = "{van Zonneveld}, Monika and Zondervan, {Pieter E.} and Yilmaz Cakaloglu and Christopher Simon and Akarca, {Ulus S.} and So, {Thomas M. K.} and Flink, {Hajo J.} and {de Man}, {Robert A.} and Schalm, {Solko W.} and Janssen, {Harry L. A.} and Niesters, {H. G. M.} and B. Hansen and Vroom, {B. C. M.} and {van Nieuwkerk}, {C. M. J.} and {de Vries}, {R. A.} and J. Jansen and J. Drenth and {van den Hazel}, {S. J.} and {den Ouden-Muller}, {J. W.} and Tan, {A. C.} and Adler, {D. M.} and P. Michielsen and {van Vlierberghe}, H. and F. Nevens and J. Delwaide and J. Henrion and S. Zeuzem and G. Gerken and S. Bein and U. Treichel and J. Trojan and Manns, {M. P.} and J. Hadem and J. Niederau and Buhl, {M. R.} and Hansen, {I. M.} and K. Krogsgaard and J. Cianciara and J. Jablonska and J. Kozlowska and D. Prokopowicz and R. Flisiak and T. Mach and M. Buti and A. Valdes and R. Esteban and M. Rodriguez and {Garcia Espiga}, M. and A. Andriulli and G. Stornaiulo and Gaeta, {G. B.} and G. Montalto and F. D'Antona and Kitis, {G. E.} and {Xiarchos Panagiotis}, P. and Tassopoulos, {N. C.} and G. Ers{\"o}z and S. Karayalcin and C. Yurdayin and H. Bozkaya and H. Simsek and Y. Balaban and H. Senturk and F. Tabak and Y. Lurie and J. Heathcote and Feinman, {S. V.} and S. Greenbloom and Sulaiman, {D. A.} and R. Guan and I. Merican",

year = "2006",

doi = "https://doi.org/10.1111/j.1478-3231.2006.01257.x",

language = "English",

volume = "26",

pages = "399--405",

journal = "Liver international",

issn = "1478-3223",

publisher = "Wiley-Blackwell",

number = "4",

}

van Zonneveld, M, Zondervan, PE, Cakaloglu, Y, Simon, C, Akarca, US, So, TMK, Flink, HJ, de Man, RA, Schalm, SW, Janssen, HLA, Niesters, HGM, Hansen, B, Vroom, BCM, van Nieuwkerk, CMJ, de Vries, RA, Jansen, J , Drenth, J, van den Hazel, SJ, den Ouden-Muller, JW, Tan, AC, Adler, DM, Michielsen, P, van Vlierberghe, H, Nevens, F, Delwaide, J, Henrion, J, Zeuzem, S, Gerken, G, Bein, S, Treichel, U, Trojan, J, Manns, MP, Hadem, J, Niederau, J, Buhl, MR, Hansen, IM, Krogsgaard, K, Cianciara, J, Jablonska, J, Kozlowska, J, Prokopowicz, D, Flisiak, R, Mach, T, Buti, M, Valdes, A, Esteban, R, Rodriguez, M, Garcia Espiga, M, Andriulli, A, Stornaiulo, G, Gaeta, GB, Montalto, G, D'Antona, F, Kitis, GE, Xiarchos Panagiotis, P, Tassopoulos, NC, Ersöz, G, Karayalcin, S, Yurdayin, C, Bozkaya, H, Simsek, H, Balaban, Y, Senturk, H, Tabak, F, Lurie, Y, Heathcote, J, Feinman, SV, Greenbloom, S, Sulaiman, DA, Guan, R & Merican, I 2006, 'Peg-interferon improves liver histology in patients with HBeAg-positive chronic hepatitis B: No additional benefit of combination with lamivudine', Liver international, vol. 26, no. 4, pp. 399-405. https://doi.org/10.1111/j.1478-3231.2006.01257.x

TY - JOUR

T1 - Peg-interferon improves liver histology in patients with HBeAg-positive chronic hepatitis B

T2 - No additional benefit of combination with lamivudine

AU - van Zonneveld, Monika

AU - Zondervan, Pieter E.

AU - Cakaloglu, Yilmaz

AU - Simon, Christopher

AU - Akarca, Ulus S.

AU - So, Thomas M. K.

AU - Flink, Hajo J.

AU - de Man, Robert A.

AU - Schalm, Solko W.

AU - Janssen, Harry L. A.

AU - Niesters, H. G. M.

AU - Hansen, B.

AU - Vroom, B. C. M.

AU - van Nieuwkerk, C. M. J.

AU - de Vries, R. A.

AU - Jansen, J.

AU - Drenth, J.

AU - van den Hazel, S. J.

AU - den Ouden-Muller, J. W.

AU - Tan, A. C.

AU - Adler, D. M.

AU - Michielsen, P.

AU - van Vlierberghe, H.

AU - Nevens, F.

AU - Delwaide, J.

AU - Henrion, J.

AU - Zeuzem, S.

AU - Gerken, G.

AU - Bein, S.

AU - Treichel, U.

AU - Trojan, J.

AU - Manns, M. P.

AU - Hadem, J.

AU - Niederau, J.

AU - Buhl, M. R.

AU - Hansen, I. M.

AU - Krogsgaard, K.

AU - Cianciara, J.

AU - Jablonska, J.

AU - Kozlowska, J.

AU - Prokopowicz, D.

AU - Flisiak, R.

AU - Mach, T.

AU - Buti, M.

AU - Valdes, A.

AU - Esteban, R.

AU - Rodriguez, M.

AU - Garcia Espiga, M.

AU - Andriulli, A.

AU - Stornaiulo, G.

AU - Gaeta, G. B.

AU - Montalto, G.

AU - D'Antona, F.

AU - Kitis, G. E.

AU - Xiarchos Panagiotis, P.

AU - Tassopoulos, N. C.

AU - Ersöz, G.

AU - Karayalcin, S.

AU - Yurdayin, C.

AU - Bozkaya, H.

AU - Simsek, H.

AU - Balaban, Y.

AU - Senturk, H.

AU - Tabak, F.

AU - Lurie, Y.

AU - Heathcote, J.

AU - Feinman, S. V.

AU - Greenbloom, S.

AU - Sulaiman, D. A.

AU - Guan, R.

AU - Merican, I.

PY - 2006

Y1 - 2006

N2 - Background: The effect of pegylated interferon or its combination with lamivudine on liver histology of patients with chronic hepatitis B (CHB) is unknown. In a double-blinded, randomized, multi-center study we assessed histological changes in 110 hepatitis B e-antigen (HBeAg)-positive CHB patients treated for 52 weeks with Pegylated interferon α-2b (PEG-IFN) in combination with either lamivudine or placebo. Liver biopsies were taken before and at the end of treatment. All biopsies were blinded and scored according to the Ishak system. Results: Necroinflammatory score improved (defined as a decrease of at least two points) in 25 patients (48%) of the PEG-IFN/lamivudine combination therapy group and in 31 patients (53%) of the PEG-IFN monotherapy group. The fibrosis score improved (decrease of at least 1 point) in 17 patients (33%) of the combination therapy group vs. 13 patients (22%) of the PEG-IFN monotherapy group (P=0.23). Responders (n=42), defined as serum HBeAg negative at the end of therapy, showed a larger decline in necroinflammatory score than non-responders (mean decline 2.3 and 1.2 pointsm respectively, P=0.02). Among patients receiving PEG-IFN monotherapy necroinflammation improved more frequently in responders (78% responders vs. 43% of non-responders, P=0.01) and in patients who showed normalization of ALT (76% of patients with normal ALT vs. 40% of patients with abnormal ALT, P = 0.01). Fibrosis score in the PEG-IFN monotherapy group improved more often in responders (39%) than in non-responders (15%, P=0.04). In the PEG-IFN/lamivudine combination therapy group, we found no signigficant association between virological and biochemical endpoints and histological improvement. Conclusion: Treatment with PEG-IFN therapy improves liver necroinflammation in HBeAg-positive CHB patients, particularly in responders to therapy. PEG-IFN also improves fibrosis in responders. Addition of lamivudine to PEG-IFN did not further improve the histological outcome. © 2006 Blackwell Munksgaard.

AB - Background: The effect of pegylated interferon or its combination with lamivudine on liver histology of patients with chronic hepatitis B (CHB) is unknown. In a double-blinded, randomized, multi-center study we assessed histological changes in 110 hepatitis B e-antigen (HBeAg)-positive CHB patients treated for 52 weeks with Pegylated interferon α-2b (PEG-IFN) in combination with either lamivudine or placebo. Liver biopsies were taken before and at the end of treatment. All biopsies were blinded and scored according to the Ishak system. Results: Necroinflammatory score improved (defined as a decrease of at least two points) in 25 patients (48%) of the PEG-IFN/lamivudine combination therapy group and in 31 patients (53%) of the PEG-IFN monotherapy group. The fibrosis score improved (decrease of at least 1 point) in 17 patients (33%) of the combination therapy group vs. 13 patients (22%) of the PEG-IFN monotherapy group (P=0.23). Responders (n=42), defined as serum HBeAg negative at the end of therapy, showed a larger decline in necroinflammatory score than non-responders (mean decline 2.3 and 1.2 pointsm respectively, P=0.02). Among patients receiving PEG-IFN monotherapy necroinflammation improved more frequently in responders (78% responders vs. 43% of non-responders, P=0.01) and in patients who showed normalization of ALT (76% of patients with normal ALT vs. 40% of patients with abnormal ALT, P = 0.01). Fibrosis score in the PEG-IFN monotherapy group improved more often in responders (39%) than in non-responders (15%, P=0.04). In the PEG-IFN/lamivudine combination therapy group, we found no signigficant association between virological and biochemical endpoints and histological improvement. Conclusion: Treatment with PEG-IFN therapy improves liver necroinflammation in HBeAg-positive CHB patients, particularly in responders to therapy. PEG-IFN also improves fibrosis in responders. Addition of lamivudine to PEG-IFN did not further improve the histological outcome. © 2006 Blackwell Munksgaard.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=33645730480&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/16629642

U2 - https://doi.org/10.1111/j.1478-3231.2006.01257.x

DO - https://doi.org/10.1111/j.1478-3231.2006.01257.x

M3 - Article

C2 - 16629642

SN - 1478-3223

VL - 26

SP - 399

EP - 405

JO - Liver international

JF - Liver international

IS - 4

ER -

Peg-interferon improves liver histology in patients with HBeAg-positive chronic hepatitis B: No additional benefit of combination with lamivudine

Abstract

Access to Document

Other files and links

Cite this