title: On-treatment mortality predictors in chronic hepatitis B patients experiencing severe acute exacerbation: a prospective observational study.
abstract: BACKGROUND
  Severe acute exacerbation in chronic hepatitis B could lead to mortality in some patients unless timely liver transplantation is performed. The baseline bilirubin level has been reported to be an important prognostic factor for mortality. Here we conducted a prospective observational study to examine the clinical performance of this predictor.
  
  
  METHODS
  Twenty-one consecutive chronic hepatitis B patients experiencing severe acute exacerbation were treated with either telbivudine or entecavir. The clinical characteristics at baseline and week-2 were documented and correlated with mortality.
  
  
  RESULTS
  Of the 21 patients included, 9 had baseline bilirubin >10 mg/dL. Four of these 9 patients (44.4%) eventually died, whereas all other patients survived. During the initial 2-week period, the change of bilirubin was -1.2 mg/dl in the survivors, but was +8.05 mg/dl in the mortalities (P = 0.009). When this on-treatment factor was combined, 5 of the 21 patients had baseline bilirubin > 10 mg/dL plus an increase of bilirubin level at week-2. Of these 5 patients, 4 (80%) died. Thus, by combining the baseline and on-treatment bilirubin levels, a positive predictive value of 80% and a negative predictive value of 100% could be achieved. Other significant on-treatment mortality predictors (at week-2) included higher international normalized ratio of prothrombin time (2.75 vs. 1.3, P = 0.004), higher model for end-stage liver disease score (30 vs. 17, P = 0.006), lower alpha-fetoprotein level (36.3 vs. 459.6 ng/mL, P = 0.039), and more rapid deterioration of the estimated glomerular filtration rate (eGFR) (P = 0.008). Interestingly, during the course, deterioration of eGFR was statistically significant in entecavir-treated (P = 0.028), but not in telbivudine-treated patients. Additionally, the patients treated with telbivudine had significant increase in serum alpha-fetoprotein (27.9 to 191.9 ng/ml, P = 0.046) in the first 2 weeks, whereas the corresponding feature was not found in those treated with entecavir (P = 0.139).
  
  
  CONCLUSIONS
  In this prospective observational study, we discovered that the baseline and on-treatment bilirubin levels should be combined to achieve a better predictive value. Telbivudine might have a renoprotective effect in addition to its efficacy in viral suppression in patients with severe acute exacerbation.
authors.affiliation: Department of Gastroenterology-Hepatology, Liver Research Unit, Division of Hepatology, Taipei, Taiwan. chautingy@gmail.com.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Chen
authors.forename: Chao-Wei
authors.initials: CW
authors.lastname: Hsu
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Chang
authors.forename: Chau-Ting
authors.initials: CT
authors.lastname: Yeh
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D001663:Bilirubin / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D011517:Prothrombin Time; D016019:Survival Analysis; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D006513:Hepatitis B e Antigens; D000509:alpha-Fetoproteins; D000077712:Telbivudine; C413685:entecavir; D006147:Guanine; D001663:Bilirubin; D013936:Thymidine