title: Nucleos(t)ide analogue treatment reduces apoptotic activity in patients with chronic hepatitis B.
abstract: BACKGROUND
  Reduction of necroinflammatory activity is a major goal of antiviral therapy of patients with chronic hepatitis B. Serum ALT does not detect all forms of cell death.
  
  
  OBJECTIVE
  To analyze dynamics of novel serum cell death markers for apoptosis and necrosis in association with virologic response to nucleos(t)ide (Nuc) analogue treatment.
  
  
  METHODS
  Quantification of the M30-apoptosis neoepitope and the cytokeratin-18 (M65-necrosis) serum levels before and during treatment of patients with chronic hepatitis B with Nuc (n = 26).
  
  
  RESULTS
  Before treatment, M30-apoptotic activity was significantly correlated with M65-necrosis and fibrosis but not with serum ALT. During therapy with Nucs, cell death parameters M30-apoptosis, M65-necrosis, and ALT declined in association with virologic response. The most frequent cell death pattern was simultaneous decline of ALT and M30-apoptosis which occurred more frequently in patients with HBs-Antigen decline than in patients with HBs-Antigen increase during treatment (87.5% vs. 40.0%; p = 0.024). ALT decline in association with increase of M30 apoptosis was frequent in patients with HBs-Antigen increase during treatment (36.3%) but was not observed in patients with HBs-Antigen decline during treatment.
  
  
  CONCLUSIONS
  Decline of cell death parameters in association with decline of HBV-DNA and HBs-Antigen indicates a reduction in overall cell death activity during Nuc treatment supporting the concept that response to Nuc therapy reduces necroinflammatory activity and progression of liver disease.
authors: Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, Haus 11, 60590 Frankfurt, Germany.
authors: Harald
authors: H
authors: Farnik
authors: Christian Markus
authors: CM
authors: Lange
authors: Wolf Peter
authors: WP
authors: Hofmann
authors: Annemarie
authors: A
authors: Berger
authors: Regina
authors: R
authors: Allwinn
authors: Martin-Walter
authors: MW
authors: Welker
authors: Jörg
authors: J
authors: Trojan
authors: Christoph
authors: C
authors: Sarrazin
authors: Eva
authors: E
authors: Herrmann
authors: Stefan
authors: S
authors: Zeuzem
authors: Bernd
authors: B
authors: Kronenberger
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D018450:Disease Progression; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000187:drug effects / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D053538:Keratin-18 / Q000097:blood*; D008297:Male; D009336:Necrosis; D009705:Nucleosides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D009711:Nucleotides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D053538:Keratin-18; D009705:Nucleosides; D009711:Nucleotides; D000410:Alanine Transaminase