title: Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication.
abstract: The risk of hepatocellular carcinoma (HCC) is reduced but not eradicated among patients with hepatitis C virus (HCV)-induced advanced hepatic fibrosis who attained sustained viral response (SVR). We aimed to assess the risk of cirrhosis-related complications in this specific group of patients.
  
  
  
  Data from previously reported Western cohort studies including patients with chronic HCV infection and bridging fibrosis or cirrhosis who attained SVR were pooled for survival analyses on the individual patient level. The primary endpoint was HCC and the secondary endpoint was clinical disease progression, defined as liver failure, HCC or death.
  
  
  
  Included were 1000 patients with SVR. Median age was 52.7 (IQR 45.1-59.7) years, 676 (68%) were male and 842 (85%) had cirrhosis. Median follow-up was 5.7 (IQR 2.9-8.0) years. Fifty-one patients developed HCC and 101 had clinical disease progression. The cumulative 8-year HCC incidence was 1.8 (95% CI 0.0-4.3) among patients with bridging fibrosis and 8.7% (95% CI 6.0-11.4) among those with cirrhosis (p=0.058). Within the cirrhosis group, the 8-year HCC incidence was 2.6% (95% CI 0.0-5.5) among patients <45years, 9.7% (95% CI 5.8-13.6) among patients from 45-60years, and 12.2% (95% CI 5.3-19.1) among patients >60years of age at start of therapy (p=0.006). Multivariable Cox analyses indicated that higher age, lower platelet count and diabetes mellitus were independently associated with development of HCC. After 8years 4.2% (95% CI 0.1-8.3) of patients with bridging fibrosis and 15.8% (95% CI 12.3-19.3) of patients with cirrhosis experienced clinical disease progression (p=0.007).
  
  
  
  Patients with HCV-induced cirrhosis and SVR showed an annual risk of approximately 1% for HCC and 2% for clinical disease progression. Therefore, to prevent HCC surveillance, chronic HCV infection should preferably be treated before cirrhosis has developed.
  
  
  
  Patients with cirrhosis who were able to eradicate their chronic HCV infection remain at substantial risk of primary liver cancer. The risk of liver cancer increases with higher age, laboratory makers suggesting more severe liver disease, and presence of diabetes mellitus. Also after successful antiviral therapy patients with HCV-induced cirrhosis should thus remain included in follow-up for early detection of liver cancer.
authors: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: a.vandermeer@erasmusmc.nl.
authors: Adriaan J
authors: AJ
authors: van der Meer
authors: The Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada.
authors: Jordan J
authors: JJ
authors: Feld
authors: Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
authors: Harald
authors: H
authors: Hofer
authors: Gastrointestinal & Liver Unit, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
authors: Piero L
authors: PL
authors: Almasio
authors: Gastrointestinal & Liver Unit, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
authors: Vincenza
authors: V
authors: Calvaruso
authors: Unit of Gastroenterology and Liver Diseases, University Hospital Fundación Alcorcón, Madrid, Spain.
authors: Conrado M
authors: CM
authors: Fernández-Rodríguez
authors: Departments of Gastroenterology and Hepatology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors: Soo
authors: S
authors: Aleman
authors: Unité d'Hépatologie, APHP Hôspital Jean Verdier, Université Paris 13, Inserm UMR 1162, France.
authors: Nathalie
authors: N
authors: Ganne-Carrié
authors: A.M. and A. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors: Roberta
authors: R
authors: D'Ambrosio
authors: Unité d'Hépatologie, APHP Hôpital Cochin, Université Paris Descartes, Inserm U1016, Paris, France.
authors: Stanislas
authors: S
authors: Pol
authors: Gastroenterology-Hepatology Department, University Hospital La Princesa and Princesa Research Institute, Autonomous University of Madrid, Madrid, Spain.
authors: Maria
authors: M
authors: Trapero-Marugan
authors: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors: Raoel
authors: R
authors: Maan
authors: Gastroenterology-Hepatology Department, University Hospital La Princesa and Princesa Research Institute, Autonomous University of Madrid, Madrid, Spain.
authors: Ricardo
authors: R
authors: Moreno-Otero
authors: Unité d'Hépatologie, APHP Hôpital Cochin, Université Paris Descartes, Inserm U1016, Paris, France.
authors: Vincent
authors: V
authors: Mallet
authors: Departments of Gastroenterology and Hepatology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden.
authors: Rolf
authors: R
authors: Hultcrantz
authors: Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors: Ola
authors: O
authors: Weiland
authors: Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
authors: Karoline
authors: K
authors: Rutter
authors: Gastrointestinal & Liver Unit, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
authors: Vito
authors: V
authors: Di Marco
authors: Unit of Gastroenterology and Liver Diseases, University Hospital Fundación Alcorcón, Madrid, Spain.
authors: Sonia
authors: S
authors: Alonso
authors: Department of Internal Medicine, Humanitas University and IRCCS Istituto Clinico Humanitas, Rozzano (Milan), Italy.
authors: Savino
authors: S
authors: Bruno
authors: A.M. and A. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors: Massimo
authors: M
authors: Colombo
authors: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors: Robert J
authors: RJ
authors: de Knegt
authors: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors: Bart J
authors: BJ
authors: Veldt
authors: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors: Bettina E
authors: BE
authors: Hansen
authors: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; The Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada.
authors: Harry L A
authors: HLA
authors: Janssen
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000150:complications*; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D000072230:Sustained Virologic Response
keywords: Chronic hepatitis C; Cirrhosis; Fibrosis; Hepatocellular carcinoma; Liver failure; Survival analysis; Sustained virological response