title: The albumin-bilirubin grade improves hepatic reserve estimation post-sorafenib failure: implications for drug development.
abstract: Drug development in hepatocellular carcinoma (HCC) is limited by disease heterogeneity, with hepatic reserve being a major source of variation in survival outcomes. The albumin-bilirubin (ALBI) grade is a validated index of liver function in patients with HCC.
  
  
  
  To test the accuracy of the ALBI grade in predicting post-sorafenib overall survival (PSOS) in patients who permanently discontinued treatment.
  
  
  
  From a prospectively maintained international database of 447 consecutive referrals, we derived 386 eligible patients treated with sorafenib within Barcelona Clinic Liver Cancer C stage (62%), 75% of whom were of Child class A at initiation. Clinical variables at sorafenib discontinuation were analysed for their impact on post-sorafenib overall survival using uni- and multivariable analyses.
  
  
  
  Median post-sorafenib overall survival of the 386 eligible patients was 3.4 months and median sorafenib duration was 2.9 months, with commonest causes of cessation being disease progression (68%) and toxicity (24%). At discontinuation, 92 patients (24%) progressed to terminal stage, due to worsening Child class to C in 40 (10%). Median post-sorafenib overall survival in patients eligible for second-line therapies (n = 294) was 17.5, 7.5 and 1.9 months according respectively to ALBI grade 1, 2 and 3 (P < 0.001).
  
  
  
  The ALBI grade at sorafenib discontinuation identifies a subset of patients with prolonged stability of hepatic reserve and superior survival. This may allow improved patient selection for second-line therapies in advanced HCC.
authors.affiliation: Department of Surgery & Cancer, Hammersmith Campus of Imperial College London, London, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Pinato
authors.affiliation: Department of Surgery & Cancer, Hammersmith Campus of Imperial College London, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Yen
authors.affiliation: Department of Medicine II, University Hospital Freiburg, Freiburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Bettinger
authors.affiliation: Department of Surgery & Cancer, Hammersmith Campus of Imperial College London, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Ramaswami
authors.affiliation: Department of Gastroenterology and Hepatology, Kindai University School of Medicine, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Arizumi
authors.affiliation: Department of Surgery & Cancer, Hammersmith Campus of Imperial College London, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Ward
authors.affiliation: Department of Translational Medicine, Università degli Studi del Piemonte Orientale "A. Avogadro", Novara, Italy.|Interdisciplinary Research Center of Autoimmune Diseases, Università degli Studi del Piemonte Orientale "A. Avogadro", Novara, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pirisi
authors.affiliation: Department of Translational Medicine, Università degli Studi del Piemonte Orientale "A. Avogadro", Novara, Italy.
authors.forename: M E
authors.initials: ME
authors.lastname: Burlone
authors.affiliation: Department of Medicine II, University Hospital Freiburg, Freiburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Thimme
authors.affiliation: Department of Gastroenterology and Hepatology, Kindai University School of Medicine, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kudo
authors.affiliation: Department of Surgery & Cancer, Hammersmith Campus of Imperial College London, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Sharma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001663:Bilirubin / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D016208:Databases, Factual; D018450:Disease Progression; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018579:Patient Selection; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D011446:Prospective Studies; D000077157:Sorafenib
chemical_list: D000418:Albumins; D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D001663:Bilirubin