title: Long-term progression of viral load and serum markers of fibrosis among treated and untreated patients with chronic hepatitis B.
abstract: OBJECTIVE
  Antiviral therapy for patients with hepatitis B (HBV) infection is generally deferred for "immune inactive" patients, although longitudinal changes in viral load and liver fibrosis remain understudied in this population. Likewise, in treated patients, the temporal relationship between changes in viral load and liver fibrosis is not well characterized. Using data from the chronic hepatitis cohort study, the study investigated viral load and the Fibrosis-4 index (FIB4, a serum-based marker of liver fibrosis) trajectories in both untreated and treated HBV patients.
  
  
  METHODS
  We applied a bivariate, piecewise, linear spline, mixed-effects modeling approach to data from 766 HBV patients (342 untreated, 424 treated). Treatment selection bias was adjusted using propensity scores. Multiple sensitivity analyses were used to confirm results in untreated patients.
  
  
  RESULTS
  Among all untreated patients, FIB4 began to increase by 0.9% per month (11% per year; P < 0.05) at 28 months post-index date, suggesting fibrosis progression. Significant FIB4 progression was also observed in a subgroup analysis of "immune inactive" untreated patients. In treated patients, viral load declined 31.8% per month (P < 0.05) for the first 5 months after treatment initiation, and 1.4-1.7% per month (P < 0.05) thereafter. At 5 months after treatment initiation, FIB4 began to decline 0.5% per month (P < 0.05), stabilizing at 28 months.
  
  
  CONCLUSIONS
  Among untreated HBV patients, FIB4 gradually increases over time, suggesting fibrosis progression, even in those patients designated as immune inactive. In treated patients, antiviral therapy results in a rapid decline in viral load followed by a delayed decline in markers of liver fibrosis.
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, Michigan, USA.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Gordon
authors.affiliation: Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Michigan, USA.
authors.forename: Loralee B
authors.initials: LB
authors.lastname: Rupp
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA.
authors.forename: Talan
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA.
authors.forename: Sheri
authors.initials: S
authors.lastname: Trudeau
authors.affiliation: Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Holmberg
authors.affiliation: Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Moorman
authors.affiliation: Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Spradling
authors.affiliation: Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Eyasu H
authors.initials: EH
authors.lastname: Teshale
authors.affiliation: Center for Health Research, Geisinger Health System, Danville, Pennsylvania, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Boscarino
authors.affiliation: Center for Health Research, Kaiser Permanente-Hawai'i, Waipahu, Hawaii, USA.
authors.forename: Yihe G
authors.initials: YG
authors.lastname: Daida
authors.affiliation: Center for Health Research, Kaiser Permanente-Northwest, Portland, Oregon, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Schmidt
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005355:Fibrosis; D019694:Hepatitis B, Chronic / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers
keywords: FIB4; HBV; chronic hepatitis cohort study (CHeCS); growth curve modeling; join-point modeling