title: Circulating free DNA in the progression of liver damage to hepatocellular carcinoma.
abstract: OBJECTIVE
  Circulating free DNA (cfDNA) is an extracellular DNA released in the blood by tumor apoptotic/necrotic cells. cfDNA determination has been proposed as a non-invasive and sensitive marker in the diagnosis of cancer. Our aim was to validate the quantification of cfDNA as a diagnostic and prognostic tool in hepatocellular carcinoma (HCC).
  
  
  METHODS
  cfDNA was quantified by real-time PCR amplification of the hTERT gene in 142 plasma samples obtained from 66 patients with HCC, 35 with cirrhosis (CIRR) and 41 with advanced HCV-related chronic hepatitis (CH).
  
  
  RESULTS
  cfDNA was documented in the plasma of 22 % of the CH patients, 57 % of those with CIRR and 61 % of HCC patients. Its concentration was lower in CH with respect to CIRR and HCC (p = 0.02). A cutoff value in the diagnosis of HCC was calculated by the ROC method (area under the curve 0.69, 91 % sensitivity, 43 % specificity) considering HCC versus CH/CIRR, taken together. Patients with multinodular HCC showed significantly higher levels of cfDNA (p = 0.05). A cutoff value for cfDNA was also calculated for discriminating patients with long or short survival. Survival was significantly longer in patients with cfDNA below than in those above the cutoff value (37 vs. 24 months, p = 0.03). Similar results were obtained in the subgroups of patients with viral or with HCV-only etiology, with slightly higher overall diagnostic accuracy.
  
  
  CONCLUSIONS
  The role of the quantitative analysis of cfDNA as a diagnostic test is debatable, but cfDNA levels discriminate patients with more advanced stages of disease, demonstrating a prognostic relevance in patients with HCC.
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Padova University, Padua, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Piciocchi
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Padova University, Padua, Italy.
authors.forename: Romilda
authors.initials: R
authors.lastname: Cardin
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Padova University, Padua, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vitale
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Padova University, Padua, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Vanin
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Padova University, Padua, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Giacomin
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Padova University, Padua, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Pozzan
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Padova University, Padua, Italy.
authors.forename: Gemma
authors.initials: G
authors.lastname: Maddalo
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Padova University, Padua, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Cillo
authors.affiliation: Department of Medicine, Padova University, Padua, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Guido
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Padova University, Padua, Italy. fabio.farinati@unipd.it.|Department of Surgery, Oncology and Gastroenterology, Policlinico Universitario, Via Giustiniani 2, 35128, Padua, Italy. fabio.farinati@unipd.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Farinati
keywords: Circulating free DNA; Cirrhosis; HCV-related chronic hepatitis; Hepatocellular carcinoma