title: Early Predictors of Long-term Outcomes of HCV-negative Liver Transplant Recipients Having Survived the First Postoperative Year.
abstract: BACKGROUND
  The non-improvement in >1-year post-liver transplant (LT) survival and diminishing importance of hepatitis C (HCV) with modern antivirals justify identification of early factors predictive of long-term outcome post-LT in HCV-negative recipients.
  
  
  METHODS
  This nationwide study included all 631 HCV-negative adult patients transplanted in Finland 1982-2013 with at least 1-year graft survival (6311 person-year follow-up). We tested 37 variables, including immunosuppression, for their association with >1-year combined graft loss/mortality, late rejection, cancer, or infections.
  
  
  RESULTS
  Significant multivariate predictors of graft loss/mortality were male gender (HR 2.40, P = 0.001), pretransplant hepatocellular (HR 2.92, P = 0.001) or biliary cancer (HR 12.7, P < 0.001), glomerular filtration rate (HR 0.89, P = 0.002), hypertension (HR 0.44, P < 0.001), early posttransplant infections (HR 1.52-1.67, P = 0.007-0.03), and alkaline phosphatase (ALP) (HR 1.05, P < 0.001). Elevated ALP at 1 year, affecting 30% of patients, predicted both graft loss and rejection, independent of immunologic stability, etiology, and immunosuppression type. Area under the curve of ALP in predicting graft loss from rejection was 0.81 (95% CI 0.71-0.90) and 0.85 (95% CI 0.72-0.98, P = 0.001) among patients under 50. Among immunologically stable patients who underwent transplantation after 2000, antimetabolite use at 1 year was associated with improved survival (P = 0.04), specifically in the subgroup with native-liver hepatocellular or biliary cancer (P = 0.02).
  
  
  CONCLUSIONS
  Easily measurable, widely available, and noninvasive factors known at 1 year post-LT can help stratify patients according to their long-term risk of death or graft loss, and thus facilitate a personalization of long-term follow-up. ALP deserves routine monitoring, and the cause for an elevated ALP should be sought.
authors.affiliation: 1 Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland. 2 Clinic of Gastroenterology, Helsinki University Hospital, Helsinki University, Finland.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Åberg
authors.forename: Arno
authors.initials: A
authors.lastname: Nordin
authors.forename: Leena
authors.initials: L
authors.lastname: Toivonen
authors.forename: Helena
authors.initials: H
authors.lastname: Isoniemi
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003141:Communicable Diseases / Q000209:etiology; D015897:Comorbidity; D003661:Decision Support Techniques; D005260:Female; D005387:Finland; D006084:Graft Rejection / Q000209:etiology; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000209:etiology; D016016:Proportional Hazards Models; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D017741:Survivors; D013997:Time Factors; D066027:Transplant Recipients; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D000469:Alkaline Phosphatase