Adriaan J van der Meer1, Jordan J Feld2, Harald Hofer3, Piero L Almasio4, Vincenza Calvaruso4, Conrado M Fernández-Rodríguez5, Soo Aleman6, Nathalie Ganne-Carrié7, Roberta D'Ambrosio8, Stanislas Pol9, Maria Trapero-Marugan10, Raoel Maan11, Ricardo Moreno-Otero10, Vincent Mallet9, Rolf Hultcrantz12, Ola Weiland13, Karoline Rutter3, Vito Di Marco4, Sonia Alonso5, Savino Bruno14, Massimo Colombo8, Robert J de Knegt11, Bart J Veldt11, Bettina E Hansen11, Harry L A Janssen15. 1. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: a.vandermeer@erasmusmc.nl. 2. The Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada. 3. Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria. 4. Gastrointestinal & Liver Unit, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy. 5. Unit of Gastroenterology and Liver Diseases, University Hospital Fundación Alcorcón, Madrid, Spain. 6. Departments of Gastroenterology and Hepatology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden. 7. Unité d'Hépatologie, APHP Hôspital Jean Verdier, Université Paris 13, Inserm UMR 1162, France. 8. 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. 9. Unité d'Hépatologie, APHP Hôpital Cochin, Université Paris Descartes, Inserm U1016, Paris, France. 10. Gastroenterology-Hepatology Department, University Hospital La Princesa and Princesa Research Institute, Autonomous University of Madrid, Madrid, Spain. 11. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. 12. Departments of Gastroenterology and Hepatology, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden. 13. Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden. 14. Department of Internal Medicine, Humanitas University and IRCCS Istituto Clinico Humanitas, Rozzano (Milan), Italy. 15. 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.
Abstract
BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. LAY SUMMARY: 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.
BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: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. LAY SUMMARY: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: M-L Plissonnier; T Lahlali; M Raab; M Michelet; C Romero-López; M Rivoire; K Strebhardt; D Durantel; M Levrero; P Mehlen; F Zoulim; R Parent Journal: Oncogene Date: 2017-08-07 Impact factor: 9.867
Authors: Lauren E Ball; Bernice Agana; Susana Comte-Walters; Don C Rockey; Henry Masur; Shyam Kottilil; Eric G Meissner Journal: J Viral Hepat Date: 2021-08-19 Impact factor: 3.728