 Author information
1Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
2Institute for Medical Statistics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University Vienna, Vienna, Austria.
3Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
4Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
5Internal Medicine IV, Ordensklinikum Linz Barmherzige Schwestern, Linz, Austria.
6Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy.
7Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
8Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
9Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
10Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
11Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
12Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
13Internal Medicine IV, Ordensklinikum Linz Barmherzige Schwestern, Linz, Austria.
14Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy.
15Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
16Department of Gastroenterology and Hepatology, Klinikum Ottakring, Vienna, Austria.
17Department of Gastroenterology and Hepatology, Klinikum Ottakring, Vienna, Austria.
18Department of Gastroenterology and Hepatology, Klinikum Ottakring, Vienna, Austria.
19Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto De Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
20Liver Unit, Hospital Universitario 12 De Octubre, Madrid, Spain.
21Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
22Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto De Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Universidad Complutense de Madrid, Madrid, Spain; Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
23Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain.
24Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
25Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain.
26Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
27Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
28Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
29Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
30Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. Electronic address: mattias.mandorfer@meduniwien.ac.at.
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Abstract
BACKGROUND&AIMS: Hepatocellular carcinoma (HCC) is a main cause of morbidity and mortality in patients with advanced chronic liver disease (ACLD) due to chronic hepatitis C and who have achieved sustained virologic response (SVR). We elaborated risk stratification algorithms for de-novo-HCC-development after SVR and validated them in an independent cohort.
METHODS: Derivation cohort: 527 patients with pre-treatment ACLD and SVR to interferon-free therapy were evaluated for de-novo-HCC-development. Among others, alpha-fetoprotein (AFP) and non-invasive surrogates of portal hypertension including liver stiffness measurement (LSM) were assessed pre-/post-treatment. Validation cohort: 1500 patients with compensated ACLD (cACLD) from other European centers.
RESULTS: During a median follow-up (FU) of 41 months, 22/475 cACLD (4.6%) (1.45/100patient-years)vs.12/52 decompensated patients (23.1%, 7.00/100patient-years, p<0.001) developed de-novo-HCC. Since decompensated patients were at substantial HCC-risk, we focused on cACLD for all further analyses. In cACLD, post-treatment-values showed a higher discriminative ability for patients with/without de-novo-HCC-development during FU than pre-treatment-values or absolute/relative changes. Models based on post-treatment AFP≥4.6ngxmL-3points, alcohol consumption (males:>30g/d/females:>20g/d)-2points (optional), age≥59year-2points, LSM≥19.0kPa-1point, and albumin<42gxL-1point, accurately predicted de-novo-HCC-development (bootstrapped Harrel's C with and without considering alcohol:0.893 and 0.836). Importantly, these parameters also provided independent prognostic information in competing risk analysis and accurately stratified patients into low-(0-3points; ≈2/3 of patients) and high-risk (≥4points; ≈1/3) groups in the derivation (algorithm with alcohol consumption; 4-year HCC-risk:0%vs.16.5%) and validation (3.3%/17.5%) cohorts. An alternative approach based on age/alcohol (optional)/FU-LSM/FU-albumin (i.e., without FU-AFP) also showed a robust performance.
CONCLUSIONS: Simple algorithms based on post-treatment age/albumin/LSM, and optionally, AFP and alcohol, accurately stratified de-novo-HCC-risk in cACLD patients with SVR. Approximately 2/3 were identified as having an HCC-risk <1%/y in both the derivation and validation cohort, thereby clearly falling below the cost-effectiveness threshold for HCC-surveillance.
LAY SUMMARY: Simple algorithms based on age, alcohol consumption, results of blood tests (albumin and α-fetoprotein), as well as liver stiffness measurement after the end of hepatitis C treatment identify a large proportion (approximately 2/3) of patients with advanced but still asymptomatic liver disease who are at very low risk (<1%/year) of liver cancer development, and thus, might not need to undergo 6-monthly liver ultrasound.
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