TY - JOUR
T1 - Levels of Antibodies to Hepatitis B Core Antigen Are Associated With Liver Inflammation and Response to Peginterferon in Patients With Chronic Hepatitis B
AU - Brakenhoff, Sylvia M.
AU - de Knegt, Robert J.
AU - Oliveira, Jeffrey
AU - van der Eijk, Annemiek A.
AU - van Vuuren, Anneke J.
AU - Hansen, Bettina E.
AU - Janssen, Harry L.A.
AU - de Man, Robert A.
AU - Boonstra, André
AU - Sonneveld, Milan J.
N1 - Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - BACKGROUND: Emerging evidence suggests a pivotal role for B-cell responses in the natural history of chronic hepatitis B. Serum levels of antibodies to hepatitis B core antigen (anti-HBc) vary across infection stages, but their role in predicting response to antiviral therapy is uncertain. METHODS: Anti-HBc levels were assessed before peginterferon (PEG-IFN) therapy in patients with chronic hepatitis B who either started de novo PEG-IFN (n = 299; 195 hepatitis B e antigen [HBeAg] positive) or started PEG-IFN as add-on to an existing nucleo(s)tide analogue backbone (n = 91; all HBeAg-positive). Associations were explored between anti-HBc and (1) serum biomarkers, (2) liver histological findings, and (3) treatment response. RESULTS: We studied 390 patients. The hepatitis B virus (HBV) genotype were A, B, C, and D in 24%, 9%, 16%, and 49%, respectively; 72% of patients were Caucasian. Among currently untreated HBeAg-positive patients, anti-HBc was correlated with HBV DNA, hepatitis B core-related antigen (HBcrAg), hepatitis B surface antigen (HBsAg), and HBV RNA, but not with alanine aminotransferase (ALT). Higher anti-HBc was associated with more severe histological inflammatory activity (P < .001), irrespective of HBeAg status. After de novo PEG-IFN, higher anti-HBc levels were associated with HBeAg loss, sustained response, HBsAg decline, and HBsAg clearance (P < .050). Among patients treated with add-on PEG-IFN, higher anti-HBc was associated with HBeAg loss (P = .01). CONCLUSIONS: Serum anti-HBc levels correlate with histological inflammatory activity. Higher anti-HBc levels were associated with favorable treatment outcomes. These findings suggest that anti-HBc could be used to select patients most likely to respond to immunomodulatory therapy. CLINICAL TRIALS REGISTRATION: NCT00114361, NCT00146705, NCT00877760, and NCT01532843.
AB - BACKGROUND: Emerging evidence suggests a pivotal role for B-cell responses in the natural history of chronic hepatitis B. Serum levels of antibodies to hepatitis B core antigen (anti-HBc) vary across infection stages, but their role in predicting response to antiviral therapy is uncertain. METHODS: Anti-HBc levels were assessed before peginterferon (PEG-IFN) therapy in patients with chronic hepatitis B who either started de novo PEG-IFN (n = 299; 195 hepatitis B e antigen [HBeAg] positive) or started PEG-IFN as add-on to an existing nucleo(s)tide analogue backbone (n = 91; all HBeAg-positive). Associations were explored between anti-HBc and (1) serum biomarkers, (2) liver histological findings, and (3) treatment response. RESULTS: We studied 390 patients. The hepatitis B virus (HBV) genotype were A, B, C, and D in 24%, 9%, 16%, and 49%, respectively; 72% of patients were Caucasian. Among currently untreated HBeAg-positive patients, anti-HBc was correlated with HBV DNA, hepatitis B core-related antigen (HBcrAg), hepatitis B surface antigen (HBsAg), and HBV RNA, but not with alanine aminotransferase (ALT). Higher anti-HBc was associated with more severe histological inflammatory activity (P < .001), irrespective of HBeAg status. After de novo PEG-IFN, higher anti-HBc levels were associated with HBeAg loss, sustained response, HBsAg decline, and HBsAg clearance (P < .050). Among patients treated with add-on PEG-IFN, higher anti-HBc was associated with HBeAg loss (P = .01). CONCLUSIONS: Serum anti-HBc levels correlate with histological inflammatory activity. Higher anti-HBc levels were associated with favorable treatment outcomes. These findings suggest that anti-HBc could be used to select patients most likely to respond to immunomodulatory therapy. CLINICAL TRIALS REGISTRATION: NCT00114361, NCT00146705, NCT00877760, and NCT01532843.
UR - http://www.scopus.com/inward/record.url?scp=85145022658&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiac210
DO - 10.1093/infdis/jiac210
M3 - Article
C2 - 35599306
AN - SCOPUS:85145022658
SN - 0022-1899
VL - 227
SP - 113
EP - 122
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 1
ER -