@article{5b13e1c6c7a74b809d7f8b957c51a209,
title = "Changes in serum hepatitis B surface and e antigen, interferon-inducible protein 10, and aminotransferase levels during combination therapy of immune-tolerant chronic hepatitis B",
abstract = "Background and Aims: Treatment of immune-tolerant (IT) children and adults with combined peginterferon alfa-2a and entecavir results in a decline in serum HBeAg and HBsAg concentrations but rarely results in loss of HBeAg or sustained off-treatment response. Factors associated with declines in these viral antigens during treatment remain unexplored. Approach and Results: We investigated the pattern of virologic and biochemical response in 86 participants (59 children, 27 adults) by serial quantitative measurement of HBsAg (qHBsAg), quantitative HBeAg (qHBeAg), HBV RNA, interferon-inducible protein (IP-10), IL-18, and alanine aminotransferase (ALT). Each individual had previously been treated with 8 weeks of entecavir followed by 40 weeks of combined peginteferon and entecavir. We defined the interrelationships between these parameters and virologic response measured as nadir declines from baseline for HBeAg and HBsAg. The patterns of HBsAg and HBeAg decline were similar in pediatric and adult participants. Higher levels of IP-10 were observed during treatment in participants with greater ALT elevations and greater reductions of qHBsAg and qHBeAg. Individuals with peak ALT values exceeding three times the upper limit of normal were significantly more likely to have >1 log10 decline in both viral antigens. HBV DNA became undetectable in 21 of 86 (24%) and HBV RNA in 4 of 77 (5%) during therapy, but both markers remained negative only in those who became HBsAg negative, all of whom also had ALT elevations. Conclusions: Induction of IP-10 during peginterferon treatment in adults and children in the IT phase of chronic HBV infection is associated with ALT elevations and decline in viral antigens, suggesting a degree of interferon-inducible viral control.",
author = "{for the Hepatitis B Research Network (HBRN)} and Robert Perrillo and Lin, {Hsing Hua S.} and Schwarz, {Kathleen B.} and Philip Rosenthal and Mauricio Lisker-Melman and Chung, {Raymond T.} and Ludmila Prokunina-Olsson and Gavin Coherty and Jordan Feld and Lau, {Daryl T.Y.} and Roberts, {Lewis R.} and Hassan, {Mohamed A.} and Schwarzenberg, {Sarah Jane} and {Di Bisceglie}, {Adrian M.} and Jeffrey Teckman and Janssen, {Harry L.A.} and Wong, {David K.} and Joshua Juan and Colina Yim and Keyur Patel and Ling, {Simon C.} and Lee, {William M.} and Murakami, {Carol S.} and Son Do and Norberto Rodriguez-Baez and Han, {Steven Huy B.} and Tran, {Tram T.} and Terrault, {Norah A.} and Mandana Khalili and Cooper, {Stewart L.} and {Suk-Fong Lok}, Anna and Fontana, {Robert J.} and Naoky Tsai and Barak Younoszai and Fried, {Michael W.} and Andrew Muir and Donna Evon and Darling, {Jama M.} and Carithers, {Robert C.} and Margaret Shuhart and Kowdley, {Kris V.} and Wang, {Chia C.} and Murray, {Karen F.} and Sterling, {Richard K.} and Luketic, {Velimir A.} and Ghany, {Marc G.} and {Jake Liang}, T. and Edward Doo and Hoofnagle, {Jay H.} and Chang, {Kyong Mi} and Park, {Jang June} and Belle, {Steven H.} and Abdus Wahed and King, {Wendy C.} and David Kleiner",
note = "Funding Information: Dr. Cloherty owns stock in and is employed by Abbott. Dr. Feld advises and received grants from Abbvie, Eiger, Enanta, Gilead, and Janssen. He advises Arbutus, Antios, GSK, and Vir. Dr. Lisker‐Melman is on the speakers{\textquoteright} bureau for Abbvie. Dr. Rosenthal consults for and received grants from Albireo, Arrowhead, Gilead, Mirum, Takeda/Vertex, and Travere. He consults for Ambys, Audentes, BioMarin, Dicerna, Encoded, and MedinCell. He received grants from Abbvie and Merck. Dr. Chung received grants from Gilead, Abbvie, Merck, BMS, Boehringer, Roche, and GSK. Dr. Schwarz consults for and received grants from Gilead. She advises Sarepta. She received grants from Albireo. Funding Information: The HBRN was funded as a Cooperative Agreement between the NIDDK to the following investigators: Lewis R. Roberts, MB, ChB, PhD (U01-DK082843), Anna Suk-Fong Lok, MD (U01-DK082863), Steven H. Belle, PhD, MScHyg (U01-DK082864), Kyong-Mi Chang, MD (U01-DK082866), Michael W. Fried, MD (U01-DK082867), Adrian M. Di Bisceglie, MD (U01-DK082871), William M. Lee, MD (U01-DK082872), Harry L. A. Janssen, MD, PhD (U01-DK082874), Daryl T-Y Lau, MD, MPH (U01-DK082919), Richard K. Sterling, MD, MSc (U01-DK082923), Steven-Huy B. Han, MD (U01-DK082927), Robert C. Carithers, MD (U01-DK082943), Mandana Khalili, MD (U01-DK082944), Kathleen B Schwarz (U01-DK082916), an interagency agreement with NIDDK: Lilia M. Ganova-Raeva, PhD (A-DK-3002-001) and support from the intramural program, NIDDK, NIH: Marc G. Ghany, MD. Additional funding to support this study was provided to Kyong-Mi Chang, MD, the Immunology Center, (NIH/NIDDK Center of Molecular Studies in Digestive and Liver Diseases P30DK50306, NIH Public Health Service Research Grant M01-RR00040), Richard K. Sterling, MD, MSc (UL1TR000058, NCATS (National Center for Advancing Translational Sciences, NIH), Norah A. Terrault, MD, MPH (CTSA Grant Number UL1TR000004), Michael W. Fried, MD (CTSA Grant Number UL1TR001111), Kathleen B. Schwarz, MD (CTSA Grant Number UL1 TR000423), and Anna Suk-Fong Lok (CTSA Grant Number UL1RR024986, U54TR001959.) Entecavir was provided by Bristol Myers Squibb and peginterferon was provided by Genentech, Inc. through respective Clinical Trial Agreements with the NIDDK. Additional support was provided by Roche Molecular Systems, Inc. through a Cooperative Research and Development Agreement with the NIDDK Funding Information: The HBRN was funded as a Cooperative Agreement between the NIDDK to the following investigators: Lewis R. Roberts, MB, ChB, PhD (U01‐DK082843), Anna Suk‐Fong Lok, MD (U01‐DK082863), Steven H. Belle, PhD, MScHyg (U01‐DK082864), Kyong‐Mi Chang, MD (U01‐DK082866), Michael W. Fried, MD (U01‐DK082867), Adrian M. Di Bisceglie, MD (U01‐DK082871), William M. Lee, MD (U01‐DK082872), Harry L. A. Janssen, MD, PhD (U01‐DK082874), Daryl T‐Y Lau, MD, MPH (U01‐DK082919), Richard K. Sterling, MD, MSc (U01‐DK082923), Steven‐Huy B. Han, MD (U01‐DK082927), Robert C. Carithers, MD (U01‐DK082943), Mandana Khalili, MD (U01‐DK082944), Kathleen B Schwarz (U01‐DK082916), an interagency agreement with NIDDK: Lilia M. Ganova‐Raeva, PhD (A‐DK‐3002‐001) and support from the intramural program, NIDDK, NIH: Marc G. Ghany, MD. Additional funding to support this study was provided to Kyong‐Mi Chang, MD, the Immunology Center, (NIH/NIDDK Center of Molecular Studies in Digestive and Liver Diseases P30DK50306, NIH Public Health Service Research Grant M01‐RR00040), Richard K. Sterling, MD, MSc (UL1TR000058, NCATS (National Center for Advancing Translational Sciences, NIH), Norah A. Terrault, MD, MPH (CTSA Grant Number UL1TR000004), Michael W. Fried, MD (CTSA Grant Number UL1TR001111), Kathleen B. Schwarz, MD (CTSA Grant Number UL1 TR000423), and Anna Suk‐Fong Lok (CTSA Grant Number UL1RR024986, U54TR001959.) Entecavir was provided by Bristol Myers Squibb and peginterferon was provided by Genentech, Inc. through respective Clinical Trial Agreements with the NIDDK. Additional support was provided by Roche Molecular Systems, Inc. through a Cooperative Research and Development Agreement with the NIDDK Publisher Copyright: {\textcopyright} 2022 American Association for the Study of Liver Diseases.",
year = "2022",
month = sep,
doi = "10.1002/hep.32400",
language = "English",
volume = "76",
pages = "775--787",
journal = "Hepatology",
issn = "0270-9139",
number = "3",
}