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Published in: Virology Journal 1/2019

Open Access 01-12-2019 | Hepatitis B | Research

Serum hepatitis B virus RNA levels as a predictor of HBeAg seroconversion during treatment with peginterferon alfa-2a

Authors: Wen Jia, Men Qi Zhu, Xun Qi, Ting Wang, Xiao Wen, Pei Dong Chen, Qing Qi Fan, Wen-Hong Zhang, Ji Ming Zhang

Published in: Virology Journal | Issue 1/2019

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Abstract

Background

Hepatitis B e antigen (HBeAg) seroconversion represents an endpoint of treatment of chronic hepatitis B virus (HBV) infections.

Methods

We have studied whether levels of serum hepatitis B virus ribonucleic acid (HBV RNA) during pegylated interferon alfa-2a treatment might be helpful for predicting HBeAg seroconversion. 61 HBeAg-positive chronic hepatitis B (CHB) patients treated with pegylated interferon alfa-2a alone or in combination with adefovir (10 mg/day) for 48 weeks were included in this retrospective analysis. Response was defined as HBeAg seroconversion at 24 weeks posttreatment. Receiver operating characteristic analyses were used to identify baseline and on-treatment HBV RNA levels associated with response.

Results

Twenty-two of 61 (36.1%) patients achieved a response. Baseline HBV RNA levels were lower in responders than in nonresponders (4.55 ± 1.19 and 5.90 ± 1.13 copies/mL, respectively, P = 0.001). Baseline HBV RNA cut off level (200,000 copies/mL) provided a positive predictive value (PPV) of 56.0% and a negative predictive value (NPV) of 77.8%. HBV RNA level (3000 copies/mL) at week 12 provide a PPV of 75.0% and a NPV of 82.8%. Moreover, HBeAg seroconversion rates at 24 weeks posttreatment were significantly higher in patients with HBV RNA ≤ 200,000 copies/mL at baseline and HBV RNA ≤ 3000 copies/mL at week 12 (92.9%) versus others (12.5%) (All P < 0.05).

Conclusions

In Conclusions, serum HBV RNA levels may serve as a novel tool for prediction of HBeAg seroconversion during therapy with pegylated interferon alfa-2a in HBeAg-positive CHB patients.
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Literature
1.
go back to reference Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med. 2004;350:1118–29.CrossRef Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med. 2004;350:1118–29.CrossRef
2.
go back to reference Wright TL, Lau JY. Clinical aspects of hepatitis B virus infection. Lancet. 1993;342:1340–4.CrossRef Wright TL, Lau JY. Clinical aspects of hepatitis B virus infection. Lancet. 1993;342:1340–4.CrossRef
3.
go back to reference EASL clinical practice guidelines. Management of chronic hepatitis B virus infection. J Hepatol. 2012;57:167–85.CrossRef EASL clinical practice guidelines. Management of chronic hepatitis B virus infection. J Hepatol. 2012;57:167–85.CrossRef
4.
go back to reference Buster EH, Flink HJ, Cakaloglu Y, Simon K, Trojan J, Tabak F, So TM, Feinman SV, Mach T, Akarca US, et al. Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b. Gastroenterology. 2008;135:459–67.CrossRef Buster EH, Flink HJ, Cakaloglu Y, Simon K, Trojan J, Tabak F, So TM, Feinman SV, Mach T, Akarca US, et al. Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b. Gastroenterology. 2008;135:459–67.CrossRef
5.
go back to reference Janssen HL, van Zonneveld M, Senturk H, Zeuzem S, Akarca US, Cakaloglu Y, Simon C, So TM, Gerken G, de Man RA, et al. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet. 2005;365:123–9.CrossRef Janssen HL, van Zonneveld M, Senturk H, Zeuzem S, Akarca US, Cakaloglu Y, Simon C, So TM, Gerken G, de Man RA, et al. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet. 2005;365:123–9.CrossRef
6.
go back to reference Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G, Gane E, Fried MW, Chow WC, Paik SW, et al. Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med. 2005;352:2682–95.CrossRef Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G, Gane E, Fried MW, Chow WC, Paik SW, et al. Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med. 2005;352:2682–95.CrossRef
7.
go back to reference Liaw YF, Leung N, Kao JH, Piratvisuth T, Gane E, Han KH, Guan R, Lau GK, Locarnini S. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int. 2008;2:263–83.CrossRef Liaw YF, Leung N, Kao JH, Piratvisuth T, Gane E, Han KH, Guan R, Lau GK, Locarnini S. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int. 2008;2:263–83.CrossRef
8.
go back to reference Liaw YF, Kao JH, Piratvisuth T, Chan HL, Chien RN, Liu CJ, Gane E, Locarnini S, Lim SG, Han KH, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int. 2012;6:531–61.CrossRef Liaw YF, Kao JH, Piratvisuth T, Chan HL, Chien RN, Liu CJ, Gane E, Locarnini S, Lim SG, Han KH, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int. 2012;6:531–61.CrossRef
9.
go back to reference Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50:661–2.CrossRef Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50:661–2.CrossRef
10.
go back to reference Moucari R, Korevaar A, Lada O, Martinot-Peignoux M, Boyer N, Mackiewicz V, Dauvergne A, Cardoso AC, Asselah T, Nicolas-Chanoine MH, et al. High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: a long-term follow-up study. J Hepatol. 2009;50:1084–92.CrossRef Moucari R, Korevaar A, Lada O, Martinot-Peignoux M, Boyer N, Mackiewicz V, Dauvergne A, Cardoso AC, Asselah T, Nicolas-Chanoine MH, et al. High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: a long-term follow-up study. J Hepatol. 2009;50:1084–92.CrossRef
11.
go back to reference van Zonneveld M, Honkoop P, Hansen BE, Niesters HG, Darwish MS, de Man RA, Schalm SW, Janssen HL. Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B. Hepatology. 2004;39:804–10.CrossRef van Zonneveld M, Honkoop P, Hansen BE, Niesters HG, Darwish MS, de Man RA, Schalm SW, Janssen HL. Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B. Hepatology. 2004;39:804–10.CrossRef
12.
go back to reference Zhou P, Yang F, Wang J, Mao R, Qi X, Huang Y, Zhang J. Improved efficacy of a pegylated interferon-alpha-2a stepwise optimization treatment strategy in the treatment of hepatitis B e antigen-positive chronic hepatitis B patients. Medicine (Baltimore). 2015;94:e730.CrossRef Zhou P, Yang F, Wang J, Mao R, Qi X, Huang Y, Zhang J. Improved efficacy of a pegylated interferon-alpha-2a stepwise optimization treatment strategy in the treatment of hepatitis B e antigen-positive chronic hepatitis B patients. Medicine (Baltimore). 2015;94:e730.CrossRef
13.
go back to reference Fried MW, Piratvisuth T, Lau GK, Marcellin P, Chow WC, Cooksley G, Luo KX, Paik SW, Liaw YF, Button P, Popescu M. HBeAg and hepatitis B virus DNA as outcome predictors during therapy with peginterferon alfa-2a for HBeAg-positive chronic hepatitis B. Hepatology. 2008;47:428–34.CrossRef Fried MW, Piratvisuth T, Lau GK, Marcellin P, Chow WC, Cooksley G, Luo KX, Paik SW, Liaw YF, Button P, Popescu M. HBeAg and hepatitis B virus DNA as outcome predictors during therapy with peginterferon alfa-2a for HBeAg-positive chronic hepatitis B. Hepatology. 2008;47:428–34.CrossRef
14.
go back to reference Marcellin P, Wursthorn K, Wedemeyer H, Chuang WL, Lau G, Avila C, Peng CY, Gane E, Lim SG, Fainboim H, et al. Telbivudine plus pegylated interferon alfa-2a in a randomized study in chronic hepatitis B is associated with an unexpected high rate of peripheral neuropathy. J Hepatol. 2015;62:41–7.CrossRef Marcellin P, Wursthorn K, Wedemeyer H, Chuang WL, Lau G, Avila C, Peng CY, Gane E, Lim SG, Fainboim H, et al. Telbivudine plus pegylated interferon alfa-2a in a randomized study in chronic hepatitis B is associated with an unexpected high rate of peripheral neuropathy. J Hepatol. 2015;62:41–7.CrossRef
15.
go back to reference Xie Q, Zhou H, Bai X, Wu S, Chen JJ, Sheng J, Xie Y, Chen C, Chan HL, Zhao M. A randomized, open-label clinical study of combined pegylated interferon alfa-2a (40KD) and entecavir treatment for hepatitis B "e" antigen-positive chronic hepatitis B. Clin Infect Dis. 2014;59:1714–23.CrossRef Xie Q, Zhou H, Bai X, Wu S, Chen JJ, Sheng J, Xie Y, Chen C, Chan HL, Zhao M. A randomized, open-label clinical study of combined pegylated interferon alfa-2a (40KD) and entecavir treatment for hepatitis B "e" antigen-positive chronic hepatitis B. Clin Infect Dis. 2014;59:1714–23.CrossRef
16.
go back to reference Marcellin P, Bonino F, Yurdaydin C, Hadziyannis S, Moucari R, Kapprell HP, Rothe V, Popescu M, Brunetto MR. Hepatitis B surface antigen levels: association with 5-year response to peginterferon alfa-2a in hepatitis B e-antigen-negative patients. Hepatol Int. 2013;7:88–97.CrossRef Marcellin P, Bonino F, Yurdaydin C, Hadziyannis S, Moucari R, Kapprell HP, Rothe V, Popescu M, Brunetto MR. Hepatitis B surface antigen levels: association with 5-year response to peginterferon alfa-2a in hepatitis B e-antigen-negative patients. Hepatol Int. 2013;7:88–97.CrossRef
17.
go back to reference Sonneveld MJ, Hansen BE, Piratvisuth T, Jia JD, Zeuzem S, Gane E, Liaw YF, Xie Q, Heathcote EJ, Chan HL, Janssen HL. Response-guided peginterferon therapy in hepatitis B e antigen-positive chronic hepatitis B using serum hepatitis B surface antigen levels. Hepatology. 2013;58:872–80.CrossRef Sonneveld MJ, Hansen BE, Piratvisuth T, Jia JD, Zeuzem S, Gane E, Liaw YF, Xie Q, Heathcote EJ, Chan HL, Janssen HL. Response-guided peginterferon therapy in hepatitis B e antigen-positive chronic hepatitis B using serum hepatitis B surface antigen levels. Hepatology. 2013;58:872–80.CrossRef
18.
go back to reference Sarri G, Westby M, Bermingham S, Hill-Cawthorne G, Thomas H. Diagnosis and management of chronic hepatitis B in children, young people, and adults: summary of NICE guidance. BMJ. 2013;346:f3893.CrossRef Sarri G, Westby M, Bermingham S, Hill-Cawthorne G, Thomas H. Diagnosis and management of chronic hepatitis B in children, young people, and adults: summary of NICE guidance. BMJ. 2013;346:f3893.CrossRef
19.
go back to reference Rijckborst V, Hansen BE, Ferenci P, Brunetto MR, Tabak F, Cakaloglu Y, Lanza AG, Messina V, Iannacone C, Massetto B, et al. Validation of a stopping rule at week 12 using HBsAg and HBV DNA for HBeAg-negative patients treated with peginterferon alfa-2a. J Hepatol. 2012;56:1006–11.CrossRef Rijckborst V, Hansen BE, Ferenci P, Brunetto MR, Tabak F, Cakaloglu Y, Lanza AG, Messina V, Iannacone C, Massetto B, et al. Validation of a stopping rule at week 12 using HBsAg and HBV DNA for HBeAg-negative patients treated with peginterferon alfa-2a. J Hepatol. 2012;56:1006–11.CrossRef
20.
go back to reference Huang YW, Chayama K, Tsuge M, Takahashi S, Hatakeyama T, Abe H, Hu JT, Liu CJ, Lai MY, Chen DS, et al. Differential effects of interferon and lamivudine on serum HBV RNA inhibition in patients with chronic hepatitis B. Antivir Ther. 2010;15:177–84.CrossRef Huang YW, Chayama K, Tsuge M, Takahashi S, Hatakeyama T, Abe H, Hu JT, Liu CJ, Lai MY, Chen DS, et al. Differential effects of interferon and lamivudine on serum HBV RNA inhibition in patients with chronic hepatitis B. Antivir Ther. 2010;15:177–84.CrossRef
21.
go back to reference van Bommel F, Bartens A, Mysickova A, Hofmann J, Kruger DH, Berg T, Edelmann A. Serum hepatitis B virus RNA levels as an early predictor of hepatitis B envelope antigen seroconversion during treatment with polymerase inhibitors. Hepatology. 2015;61:66–76.CrossRef van Bommel F, Bartens A, Mysickova A, Hofmann J, Kruger DH, Berg T, Edelmann A. Serum hepatitis B virus RNA levels as an early predictor of hepatitis B envelope antigen seroconversion during treatment with polymerase inhibitors. Hepatology. 2015;61:66–76.CrossRef
22.
go back to reference Tsuge M, Murakami E, Imamura M, Abe H, Miki D, Hiraga N, Takahashi S, Ochi H, Nelson HC, Ginba H, et al. Serum HBV RNA and HBeAg are useful markers for the safe discontinuation of nucleotide analogue treatments in chronic hepatitis B patients. J Gastroenterol. 2013;48:1188–204.CrossRef Tsuge M, Murakami E, Imamura M, Abe H, Miki D, Hiraga N, Takahashi S, Ochi H, Nelson HC, Ginba H, et al. Serum HBV RNA and HBeAg are useful markers for the safe discontinuation of nucleotide analogue treatments in chronic hepatitis B patients. J Gastroenterol. 2013;48:1188–204.CrossRef
23.
go back to reference Jansen L, Kootstra NA, van Dort KA, Takkenberg RB, Reesink HW, Zaaijer HL. Hepatitis B virus Pregenomic RNA is present in Virions in plasma and is associated with a response to Pegylated interferon alfa-2a and Nucleos(t)ide analogues. J Infect Dis. 2016;213:224–32.CrossRef Jansen L, Kootstra NA, van Dort KA, Takkenberg RB, Reesink HW, Zaaijer HL. Hepatitis B virus Pregenomic RNA is present in Virions in plasma and is associated with a response to Pegylated interferon alfa-2a and Nucleos(t)ide analogues. J Infect Dis. 2016;213:224–32.CrossRef
24.
go back to reference Pan CQ, Zhang JX. Natural history and clinical consequences of hepatitis B virus infection. Int J Med Sci. 2005;2:36–40.CrossRef Pan CQ, Zhang JX. Natural history and clinical consequences of hepatitis B virus infection. Int J Med Sci. 2005;2:36–40.CrossRef
25.
go back to reference Schadler S, Hildt E. HBV life cycle: entry and morphogenesis. Viruses. 2009;1:185–209.CrossRef Schadler S, Hildt E. HBV life cycle: entry and morphogenesis. Viruses. 2009;1:185–209.CrossRef
26.
go back to reference Kock J, Theilmann L, Galle P, Schlicht HJ. Hepatitis B virus nucleic acids associated with human peripheral blood mononuclear cells do not originate from replicating virus. Hepatology. 1996;23:405–13.PubMed Kock J, Theilmann L, Galle P, Schlicht HJ. Hepatitis B virus nucleic acids associated with human peripheral blood mononuclear cells do not originate from replicating virus. Hepatology. 1996;23:405–13.PubMed
27.
go back to reference Su Q, Wang SF, Chang TE, Breitkreutz R, Hennig H, Takegoshi K, Edler L, Schroder CH. Circulating hepatitis B virus nucleic acids in chronic infection : representation of differently polyadenylated viral transcripts during progression to nonreplicative stages. Clin Cancer Res. 2001;7:2005–15.PubMed Su Q, Wang SF, Chang TE, Breitkreutz R, Hennig H, Takegoshi K, Edler L, Schroder CH. Circulating hepatitis B virus nucleic acids in chronic infection : representation of differently polyadenylated viral transcripts during progression to nonreplicative stages. Clin Cancer Res. 2001;7:2005–15.PubMed
28.
go back to reference Rokuhara A, Matsumoto A, Tanaka E, Umemura T, Yoshizawa K, Kimura T, Maki N, Kiyosawa K. Hepatitis B virus RNA is measurable in serum and can be a new marker for monitoring lamivudine therapy. J Gastroenterol. 2006;41:785–90.CrossRef Rokuhara A, Matsumoto A, Tanaka E, Umemura T, Yoshizawa K, Kimura T, Maki N, Kiyosawa K. Hepatitis B virus RNA is measurable in serum and can be a new marker for monitoring lamivudine therapy. J Gastroenterol. 2006;41:785–90.CrossRef
29.
go back to reference van Bommel F, van Bommel A, Krauel A, Wat C, Pavlovic V, Yang L, Deichsel D, Berg T, Bohm S. Serum HBV RNA as a predictor of Peginterferon alfa-2a response in patients with HBeAg-positive chronic hepatitis B. J Infect Dis. 2018;218:1066–74.CrossRef van Bommel F, van Bommel A, Krauel A, Wat C, Pavlovic V, Yang L, Deichsel D, Berg T, Bohm S. Serum HBV RNA as a predictor of Peginterferon alfa-2a response in patients with HBeAg-positive chronic hepatitis B. J Infect Dis. 2018;218:1066–74.CrossRef
30.
go back to reference Piratvisuth T, Marcellin P, Popescu M, Kapprell HP, Rothe V, Lu ZM. Hepatitis B surface antigen: association with sustained response to peginterferon alfa-2a in hepatitis B e antigen-positive patients. Hepatol Int. 2013;7:429–36.CrossRef Piratvisuth T, Marcellin P, Popescu M, Kapprell HP, Rothe V, Lu ZM. Hepatitis B surface antigen: association with sustained response to peginterferon alfa-2a in hepatitis B e antigen-positive patients. Hepatol Int. 2013;7:429–36.CrossRef
31.
go back to reference Wang YC, Yang SS, Su CW, Wang YJ, Lee KC, Huo TI, Lin HC, Huang YH. Predictors of response to pegylated interferon in chronic hepatitis B: a real-world hospital-based analysis. Sci Rep. 2016;6:29605.CrossRef Wang YC, Yang SS, Su CW, Wang YJ, Lee KC, Huo TI, Lin HC, Huang YH. Predictors of response to pegylated interferon in chronic hepatitis B: a real-world hospital-based analysis. Sci Rep. 2016;6:29605.CrossRef
32.
go back to reference Sonneveld MJ, Rijckborst V, Boucher CA, Hansen BE, Janssen HL. Prediction of sustained response to peginterferon alfa-2b for hepatitis B e antigen-positive chronic hepatitis B using on-treatment hepatitis B surface antigen decline. Hepatology. 2010;52:1251–7.CrossRef Sonneveld MJ, Rijckborst V, Boucher CA, Hansen BE, Janssen HL. Prediction of sustained response to peginterferon alfa-2b for hepatitis B e antigen-positive chronic hepatitis B using on-treatment hepatitis B surface antigen decline. Hepatology. 2010;52:1251–7.CrossRef
33.
go back to reference EASL 2017 Clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol 2017, 67:370–398. EASL 2017 Clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol 2017, 67:370–398.
34.
go back to reference Kimura T, Rokuhara A, Sakamoto Y, Yagi S, Tanaka E, Kiyosawa K, Maki N. Sensitive enzyme immunoassay for hepatitis B virus core-related antigens and their correlation to virus load. J Clin Microbiol. 2002;40:439–45.CrossRef Kimura T, Rokuhara A, Sakamoto Y, Yagi S, Tanaka E, Kiyosawa K, Maki N. Sensitive enzyme immunoassay for hepatitis B virus core-related antigens and their correlation to virus load. J Clin Microbiol. 2002;40:439–45.CrossRef
35.
go back to reference Rokuhara A, Tanaka E, Matsumoto A, Kimura T, Yamaura T, Orii K, Sun X, Yagi S, Maki N, Kiyosawa K. Clinical evaluation of a new enzyme immunoassay for hepatitis B virus core-related antigen; a marker distinct from viral DNA for monitoring lamivudine treatment. J Viral Hepat. 2003;10:324–30.CrossRef Rokuhara A, Tanaka E, Matsumoto A, Kimura T, Yamaura T, Orii K, Sun X, Yagi S, Maki N, Kiyosawa K. Clinical evaluation of a new enzyme immunoassay for hepatitis B virus core-related antigen; a marker distinct from viral DNA for monitoring lamivudine treatment. J Viral Hepat. 2003;10:324–30.CrossRef
36.
go back to reference Tanaka E, Matsumoto A, Suzuki F, Kobayashi M, Mizokami M, Tanaka Y, Okanoue T, Minami M, Chayama K, Imamura M, et al. Measurement of hepatitis B virus core-related antigen is valuable for identifying patients who are at low risk of lamivudine resistance. Liver Int. 2006;26:90–6.CrossRef Tanaka E, Matsumoto A, Suzuki F, Kobayashi M, Mizokami M, Tanaka Y, Okanoue T, Minami M, Chayama K, Imamura M, et al. Measurement of hepatitis B virus core-related antigen is valuable for identifying patients who are at low risk of lamivudine resistance. Liver Int. 2006;26:90–6.CrossRef
37.
go back to reference Werle-Lapostolle B, Bowden S, Locarnini S, Wursthorn K, Petersen J, Lau G, Trepo C, Marcellin P, Goodman Z, Delaney WT, et al. Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy. Gastroenterology. 2004;126:1750–8.CrossRef Werle-Lapostolle B, Bowden S, Locarnini S, Wursthorn K, Petersen J, Lau G, Trepo C, Marcellin P, Goodman Z, Delaney WT, et al. Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy. Gastroenterology. 2004;126:1750–8.CrossRef
38.
go back to reference Chan HL, Wong VW, Tse AM, Tse CH, Chim AM, Chan HY, Wong GL, Sung JJ. Serum hepatitis B surface antigen quantitation can reflect hepatitis B virus in the liver and predict treatment response. Clin Gastroenterol Hepatol. 2007;5:1462–8.CrossRef Chan HL, Wong VW, Tse AM, Tse CH, Chim AM, Chan HY, Wong GL, Sung JJ. Serum hepatitis B surface antigen quantitation can reflect hepatitis B virus in the liver and predict treatment response. Clin Gastroenterol Hepatol. 2007;5:1462–8.CrossRef
39.
go back to reference Volz T, Lutgehetmann M, Wachtler P, Jacob A, Quaas A, Murray JM, Dandri M, Petersen J. Impaired intrahepatic hepatitis B virus productivity contributes to low viremia in most HBeAg-negative patients. Gastroenterology. 2007;133:843–52.CrossRef Volz T, Lutgehetmann M, Wachtler P, Jacob A, Quaas A, Murray JM, Dandri M, Petersen J. Impaired intrahepatic hepatitis B virus productivity contributes to low viremia in most HBeAg-negative patients. Gastroenterology. 2007;133:843–52.CrossRef
40.
go back to reference Zoulim F. Assessment of treatment efficacy in HBV infection and disease. J Hepatol. 2006;44:S95–9.CrossRef Zoulim F. Assessment of treatment efficacy in HBV infection and disease. J Hepatol. 2006;44:S95–9.CrossRef
41.
go back to reference Peters M. Actions of cytokines on the immune response and viral interactions: an overview. Hepatology. 1996;23:909–16.CrossRef Peters M. Actions of cytokines on the immune response and viral interactions: an overview. Hepatology. 1996;23:909–16.CrossRef
42.
go back to reference Thimme R, Wieland S, Steiger C, Ghrayeb J, Reimann KA, Purcell RH, Chisari FV. CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection. J Virol. 2003;77:68–76.CrossRef Thimme R, Wieland S, Steiger C, Ghrayeb J, Reimann KA, Purcell RH, Chisari FV. CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection. J Virol. 2003;77:68–76.CrossRef
43.
go back to reference Wang J, Du M, Huang H, Chen R, Niu J, Jiang J, Zhuang H, Lu F. Reply to: "serum HBV pgRNA as a clinical marker for cccDNA activity": Consistent loss of serum HBV RNA might predict the "para-functional cure" of chronic hepatitis B. J Hepatol. 2017;66:462–3.CrossRef Wang J, Du M, Huang H, Chen R, Niu J, Jiang J, Zhuang H, Lu F. Reply to: "serum HBV pgRNA as a clinical marker for cccDNA activity": Consistent loss of serum HBV RNA might predict the "para-functional cure" of chronic hepatitis B. J Hepatol. 2017;66:462–3.CrossRef
44.
go back to reference Giersch K, Allweiss L, Volz T, Dandri M, Lutgehetmann M. Serum HBV pgRNA as a clinical marker for cccDNA activity. J Hepatol. 2017;66:460–2.CrossRef Giersch K, Allweiss L, Volz T, Dandri M, Lutgehetmann M. Serum HBV pgRNA as a clinical marker for cccDNA activity. J Hepatol. 2017;66:460–2.CrossRef
45.
go back to reference Liao H, Liu Y, Li X, Wang J, Chen X, Zou J, Li Q, Liu L, Wang J, Huang B, et al. Monitoring of serum HBV RNA, HBcrAg, HBsAg and anti-HBc levels in patients during long-term nucleoside/nucleotide analogue therapy. Antivir Ther. 2018. Liao H, Liu Y, Li X, Wang J, Chen X, Zou J, Li Q, Liu L, Wang J, Huang B, et al. Monitoring of serum HBV RNA, HBcrAg, HBsAg and anti-HBc levels in patients during long-term nucleoside/nucleotide analogue therapy. Antivir Ther. 2018.
46.
go back to reference Huang YW, Takahashi S, Tsuge M, Chen CL, Wang TC, Abe H, Hu JT, Chen DS, Yang SS, Chayama K, Kao JH. On-treatment low serum HBV RNA level predicts initial virological response in chronic hepatitis B patients receiving nucleoside analogue therapy. Antivir Ther. 2015;20:369–75.CrossRef Huang YW, Takahashi S, Tsuge M, Chen CL, Wang TC, Abe H, Hu JT, Chen DS, Yang SS, Chayama K, Kao JH. On-treatment low serum HBV RNA level predicts initial virological response in chronic hepatitis B patients receiving nucleoside analogue therapy. Antivir Ther. 2015;20:369–75.CrossRef
47.
go back to reference Wang J, Shen T, Huang X, Kumar GR, Chen X, Zeng Z, Zhang R, Chen R, Li T, Zhang T, et al. Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound. J Hepatol. 2016;65:700–10.CrossRef Wang J, Shen T, Huang X, Kumar GR, Chen X, Zeng Z, Zhang R, Chen R, Li T, Zhang T, et al. Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound. J Hepatol. 2016;65:700–10.CrossRef
48.
go back to reference Hatakeyama T, Noguchi C, Hiraga N, Mori N, Tsuge M, Imamura M, Takahashi S, Kawakami Y, Fujimoto Y, Ochi H, et al. Serum HBV RNA is a predictor of early emergence of the YMDD mutant in patients treated with lamivudine. Hepatology. 2007;45:1179–86.CrossRef Hatakeyama T, Noguchi C, Hiraga N, Mori N, Tsuge M, Imamura M, Takahashi S, Kawakami Y, Fujimoto Y, Ochi H, et al. Serum HBV RNA is a predictor of early emergence of the YMDD mutant in patients treated with lamivudine. Hepatology. 2007;45:1179–86.CrossRef
Metadata
Title
Serum hepatitis B virus RNA levels as a predictor of HBeAg seroconversion during treatment with peginterferon alfa-2a
Authors
Wen Jia
Men Qi Zhu
Xun Qi
Ting Wang
Xiao Wen
Pei Dong Chen
Qing Qi Fan
Wen-Hong Zhang
Ji Ming Zhang
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2019
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-019-1152-6

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Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.