title: Elevated pre-treatment IL-18 level is associated with HBeAg seroconversion in HIV-HBV coinfection.
abstract: BACKGROUND
  In HBV-infected patients, hepatitis B e antigen (HBeAg) seroconversion is associated with better outcomes. Interleukin-18 (IL-18) controls hepatitis B replication in a mouse model. However, its role in treatment response in HIV-HBV-coinfected patients is unknown.
  
  
  METHODS
  We enrolled 35 treatment-naive, HBeAg-positive, HIV-HBV-coinfected patients. HBV DNA, HIV RNA, CD4+T-cell count, HBV surface antigen (HBsAg) quantification (qHBsAg), HBeAg quantification (qHBeAg) and IL-18 levels were measured prior to, at 24 and 48 weeks of HBV-active combination antiretroviral therapy (cART). Multivariate Poisson regression models with robust standard errors were used to determine factors associated with HBeAg seroconversion.
  
  
  RESULTS
  Twenty-one patients received tenofovir (TDF) + lamivudine (3TC) based cART while 14 patients received 3TC-based cART. After 48 weeks of treatment, 10 patients experienced HBeAg seroconversion. Compared with non-seroconverters, seroconverters had higher median HIV RNA (5.22 versus 4.58 log copies/ml; P=0.030), lower median qHBsAg (3.97 versus 4.76 log IU/ml; P=0.011), lower median qHBeAg (1.61 versus 3.01 log PEIU/ml; P=0.004) and marginally higher median IL-18 (2.70 versus 2.53 log pg/ml; P=0.068) prior to ART. In the multivariate regression, higher baseline IL-18 (adjusted relative risk [aRR] 2.99 per 1 log pg/ml increase; P=0.035), high HIV RNA (aRR 1.84 per 1 log copies/ml; P=0.029) and low qHBeAg (aRR 0.71 per 1 log PEIU/ml; P=0.029) were significantly associated with HBeAg seroconversion.
  
  
  CONCLUSIONS
  In HIV-HBV-coinfected patients with HBeAg positivity, higher IL-18 levels, HIV RNA load, as well as low qHBeAg prior to cART were associated with HBeAg seroconversion.
authors.affiliation: Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.|Present address: University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Yijia
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.|Clinical Immunology Center, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Huanling
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Nidan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Chloe L
authors.initials: CL
authors.lastname: Thio
authors.affiliation: Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.|Clinical Immunology Center, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Taisheng
authors.initials: T
authors.lastname: Li
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D060085:Coinfection; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000821:virology; D006509:Hepatitis B / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000821:virology; D006513:Hepatitis B e Antigens / Q000097:blood*; D006801:Humans; D020382:Interleukin-18 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral; D000069078:Seroconversion; D019562:Viral Load
chemical_list: D015415:Biomarkers; D006513:Hepatitis B e Antigens; D020382:Interleukin-18; D012367:RNA, Viral