title: Relationship between virological response and FIB-4 index in chronic hepatitis B patients with entecavir therapy.
abstract: OBJECTIVE
  To investigate whether long-term low-level hepatitis B virus (HBV) DNA influences dynamic changes of the FIB-4 index in chronic hepatitis B (CHB) patients receiving entecavir (ETV) therapy with partial virological responses.
  
  
  METHODS
  We retrospectively analyzed 231 nucleos(t)ide (NA) naïve CHB patients from our previous study (NCT01926288) who received continuous ETV or ETV maleate therapy for three years. The patients were divided into partial virological response (PVR) and complete virological response (CVR) groups according to serum HBV DNA levels at week 48. Seventy-six patients underwent biopsies at baseline and at 48 wk. The performance of the FIB-4 index and area under the receiver operating characteristic (AUROC) curve for predicting fibrosis were determined for the patients undergoing biopsy. The primary objective of the study was to compare the cumulative probabilities of virological responses between the two groups during the treatment period. The secondary outcome was to observe dynamic changes of the FIB-4 index between CVR patients and PVR patients.
  
  
  RESULTS
  For hepatitis B e antigen (HBeAg)-positive patients (n = 178), the cumulative probability of achieving undetectable levels at week 144 was 95% and 69% for CVR and PVR patients, respectively (P < 0.001). In the Cox proportional hazards model, a lower pretreatment serum HBV DNA level was an independent factor predicting maintained viral suppression. The cumulative probability of achieving undetectable levels of HBV DNA for HBeAg-negative patients (n = 53) did not differ between the two groups. The FIB-4 index efficiently identified fibrosis, with an AUROC of 0.80 (95%CI: 0.69-0.89). For HBeAg-positive patients, the FIB-4 index was higher in CVR patients than in PVR patients at baseline (1.89 ± 1.43 vs 1.18 ± 0.69, P < 0.001). There was no significant difference in the reduction of the FIB-4 index between the CVR and PVR groups from weeks 48 to 144 (-0.11 ± 0.47 vs -0.13 ± 0.49, P = 0.71). At week 144, the FIB-4 index levels were similar between the two groups (1.24 ± 0.87 vs 1.02 ± 0.73, P = 0.06). After multivariate logistic regression analysis, a lower baseline serum HBV DNA level was associated with improvement of liver fibrosis. In HBeAg-negative patients, the FIB-4 index did not differ between the two groups.
  
  
  CONCLUSIONS
  The cumulative probabilities of HBV DNA responses showed significant differences between CVR and PVR HBeAg-positive CHB patients undergoing entecavir treatment for 144 wk. However, long-term low-level HBV DNA did not deteriorate the FIB-4 index, which was used to evaluate liver fibrosis, at the end of three years.
authors.affiliation: Ni Li, Jing-Hang Xu, Min Yu, Sa Wang, Chong-Wen Si, Yan-Yan Yu, Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Li
authors.affiliation: Ni Li, Jing-Hang Xu, Min Yu, Sa Wang, Chong-Wen Si, Yan-Yan Yu, Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China.
authors.forename: Jing-Hang
authors.initials: JH
authors.lastname: Xu
authors.affiliation: Ni Li, Jing-Hang Xu, Min Yu, Sa Wang, Chong-Wen Si, Yan-Yan Yu, Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.affiliation: Ni Li, Jing-Hang Xu, Min Yu, Sa Wang, Chong-Wen Si, Yan-Yan Yu, Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China.
authors.forename: Sa
authors.initials: S
authors.lastname: Wang
authors.affiliation: Ni Li, Jing-Hang Xu, Min Yu, Sa Wang, Chong-Wen Si, Yan-Yan Yu, Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China.
authors.forename: Chong-Wen
authors.initials: CW
authors.lastname: Si
authors.affiliation: Ni Li, Jing-Hang Xu, Min Yu, Sa Wang, Chong-Wen Si, Yan-Yan Yu, Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Yu
mesh_terms: D000328:Adult; D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D004796:Clinical Enzyme Tests; D004279:DNA, Viral / Q000097:blood; D003661:Decision Support Techniques; D005260:Female; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015999:Multivariate Analysis; D010976:Platelet Count; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012372:ROC Curve; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; C413685:entecavir; D006147:Guanine; D000410:Alanine Transaminase
keywords: Chronic hepatitis B; Entecavir; FIB-4 index; Hepatitis B virus DNA; Liver fibrosis; Partial virological response