title: Two patterns of alanine aminotransferase increase to predict long-term viral response in chronic hepatitis B patients: virus- or host-induced?
abstract: BACKGROUND
  Serum alanine aminotransferase (ALT) increase is a well-known phenomenon during interferon treatment for chronic hepatitis B. However, little is known about these increases during nucleoside/nucleotide treatment and the effects on long-term clinical outcomes.
  
  
  METHODS
  A total of 170 treatment-naive hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients were treated with a nucleoside/nucleotide analogue for at least 2 years and followed up for 1 more year post-treatment. Clinical characteristics were detected and analysed at baseline and at every 3-month interval.
  
  
  RESULTS
  Two patterns of ALT increase, virus- and host-induced, were detected. Virus-induced increases were characterized by a rapid increase in serum ALT and HBV DNA typically after 2 years of treatment, and were more common than host-induced ALT increases (15.9% versus 6.5%; P<0.05) with a median ALT increase of 5.7-fold the upper limit of normal (ULN). Host-induced ALT increases were characterized by moderately increased ALT (median 2.5-fold ULN) with a slow decrease in HBV DNA that occurred mainly in the first year of treatment (63.6%). Most importantly, host-induced increases were associated with favourable long-term treatment outcomes in HBV DNA undetectable rate (82% versus 0%), HBeAg seroconversion (82% versus 7%) and histological improvement. Moreover, interferon-γ-expressing T-helper cells were increased in patients with host-induced ALT increases.
  
  
  CONCLUSIONS
  Two patterns of ALT increases may occur during nucleoside/nucleotide analogue treatment. Host induced ALT increases, accompanied by decreased HBV DNA, lead to better long-term clinical outcomes.
authors.affiliation: Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China. youhong30@sina.com
authors.forename: Hong
authors.initials: H
authors.lastname: You
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Wu
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Ou
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: Qianyi
authors.initials: Q
authors.lastname: Wang
authors.forename: Tianhui
authors.initials: T
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Cong
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Baoen
authors.initials: B
authors.lastname: Wang
authors.forename: Jidong
authors.initials: J
authors.lastname: Jia
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D000998:Antiviral Agents / Q000737:chemistry / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000627:therapeutic use; D063065:Organophosphonates / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011744:Pyrimidinones / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives; D016896:Treatment Outcome; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D009705:Nucleosides; D063065:Organophosphonates; D011744:Pyrimidinones; D000077712:Telbivudine; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D007371:Interferon-gamma; D000410:Alanine Transaminase; D000225:Adenine; D013936:Thymidine