Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication

Adriaan J. van der Meer, Jordan J. Feld, Harald Hofer, Piero L. Almasio, Vincenza Calvaruso, Conrado M. Fernández-Rodríguez, Soo Aleman, Nathalie Ganne-Carrié, Roberta D'Ambrosio, Stanislas Pol, Maria Trapero-Marugan, Raoel Maan, Ricardo Moreno-Otero, Vincent Mallet, Rolf Hultcrantz, Ola Weiland, Karoline Rutter, Vito Di Marco, Sonia Alonso, Savino Bruno & 5 others Massimo Colombo, Robert J. de Knegt, Bart J. Veldt, Bettina E. Hansen, Harry L A Janssen

Research output: Contribution to journalArticle

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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 <45. years, 9.7% (95% CI 5.8-13.6) among patients from 45-60. years, and 12.2% (95% CI 5.3-19.1) among patients >60. years 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 8. years 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.

Original languageEnglish
Pages (from-to)485-493
JournalJournal of Hepatology
Volume66
Issue number3
DOIs
Publication statusPublished - 2017

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Hepacivirus
Fibrosis
Hepatocellular Carcinoma
Disease Progression
Chronic Hepatitis C
Virus Diseases
Liver Neoplasms
Diabetes Mellitus
Incidence
Liver Failure
Survival Analysis
Platelet Count
Early Detection of Cancer
Antiviral Agents
Liver Diseases
Cohort Studies

Keywords

  • Chronic hepatitis C
  • Cirrhosis
  • Fibrosis
  • Hepatocellular carcinoma
  • Liver failure
  • Survival analysis
  • Sustained virological response

ASJC Scopus subject areas

  • Hepatology

Cite this

van der Meer, A. J., Feld, J. J., Hofer, H., Almasio, P. L., Calvaruso, V., Fernández-Rodríguez, C. M., ... Janssen, H. L. A. (2017). Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication. Journal of Hepatology, 66(3), 485-493. https://doi.org/10.1016/j.jhep.2016.10.017

Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication. / van der Meer, Adriaan J.; Feld, Jordan J.; Hofer, Harald; Almasio, Piero L.; Calvaruso, Vincenza; Fernández-Rodríguez, Conrado M.; Aleman, Soo; Ganne-Carrié, Nathalie; D'Ambrosio, Roberta; Pol, Stanislas; Trapero-Marugan, Maria; Maan, Raoel; Moreno-Otero, Ricardo; Mallet, Vincent; Hultcrantz, Rolf; Weiland, Ola; Rutter, Karoline; Di Marco, Vito; Alonso, Sonia; Bruno, Savino; Colombo, Massimo; de Knegt, Robert J.; Veldt, Bart J.; Hansen, Bettina E.; Janssen, Harry L A.

In: Journal of Hepatology, Vol. 66, No. 3, 2017, p. 485-493.

Research output: Contribution to journalArticle

van der Meer, AJ, Feld, JJ, Hofer, H, Almasio, PL, Calvaruso, V, Fernández-Rodríguez, CM, Aleman, S, Ganne-Carrié, N, D'Ambrosio, R, Pol, S, Trapero-Marugan, M, Maan, R, Moreno-Otero, R, Mallet, V, Hultcrantz, R, Weiland, O, Rutter, K, Di Marco, V, Alonso, S, Bruno, S, Colombo, M, de Knegt, RJ, Veldt, BJ, Hansen, BE & Janssen, HLA 2017, 'Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication', Journal of Hepatology, vol. 66, no. 3, pp. 485-493. https://doi.org/10.1016/j.jhep.2016.10.017
van der Meer, Adriaan J. ; Feld, Jordan J. ; Hofer, Harald ; Almasio, Piero L. ; Calvaruso, Vincenza ; Fernández-Rodríguez, Conrado M. ; Aleman, Soo ; Ganne-Carrié, Nathalie ; D'Ambrosio, Roberta ; Pol, Stanislas ; Trapero-Marugan, Maria ; Maan, Raoel ; Moreno-Otero, Ricardo ; Mallet, Vincent ; Hultcrantz, Rolf ; Weiland, Ola ; Rutter, Karoline ; Di Marco, Vito ; Alonso, Sonia ; Bruno, Savino ; Colombo, Massimo ; de Knegt, Robert J. ; Veldt, Bart J. ; Hansen, Bettina E. ; Janssen, Harry L A. / Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication. In: Journal of Hepatology. 2017 ; Vol. 66, No. 3. pp. 485-493.
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title = "Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication",
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 <45. years, 9.7{\%} (95{\%} CI 5.8-13.6) among patients from 45-60. years, and 12.2{\%} (95{\%} CI 5.3-19.1) among patients >60. years 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 8. years 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.",
keywords = "Chronic hepatitis C, Cirrhosis, Fibrosis, Hepatocellular carcinoma, Liver failure, Survival analysis, Sustained virological response",
author = "{van der Meer}, {Adriaan J.} and Feld, {Jordan J.} and Harald Hofer and Almasio, {Piero L.} and Vincenza Calvaruso and Fern{\'a}ndez-Rodr{\'i}guez, {Conrado M.} and Soo Aleman and Nathalie Ganne-Carri{\'e} and Roberta D'Ambrosio and Stanislas Pol and Maria Trapero-Marugan and Raoel Maan and Ricardo Moreno-Otero and Vincent Mallet and Rolf Hultcrantz and Ola Weiland and Karoline Rutter and {Di Marco}, Vito and Sonia Alonso and Savino Bruno and Massimo Colombo and {de Knegt}, {Robert J.} and Veldt, {Bart J.} and Hansen, {Bettina E.} and Janssen, {Harry L A}",
year = "2017",
doi = "10.1016/j.jhep.2016.10.017",
language = "English",
volume = "66",
pages = "485--493",
journal = "Journal of Hepatology",
issn = "0168-8278",
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TY - JOUR

T1 - Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication

AU - van der Meer, Adriaan J.

AU - Feld, Jordan J.

AU - Hofer, Harald

AU - Almasio, Piero L.

AU - Calvaruso, Vincenza

AU - Fernández-Rodríguez, Conrado M.

AU - Aleman, Soo

AU - Ganne-Carrié, Nathalie

AU - D'Ambrosio, Roberta

AU - Pol, Stanislas

AU - Trapero-Marugan, Maria

AU - Maan, Raoel

AU - Moreno-Otero, Ricardo

AU - Mallet, Vincent

AU - Hultcrantz, Rolf

AU - Weiland, Ola

AU - Rutter, Karoline

AU - Di Marco, Vito

AU - Alonso, Sonia

AU - Bruno, Savino

AU - Colombo, Massimo

AU - de Knegt, Robert J.

AU - Veldt, Bart J.

AU - Hansen, Bettina E.

AU - Janssen, Harry L A

PY - 2017

Y1 - 2017

N2 - 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 <45. years, 9.7% (95% CI 5.8-13.6) among patients from 45-60. years, and 12.2% (95% CI 5.3-19.1) among patients >60. years 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 8. years 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.

AB - 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 <45. years, 9.7% (95% CI 5.8-13.6) among patients from 45-60. years, and 12.2% (95% CI 5.3-19.1) among patients >60. years 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 8. years 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.

KW - Chronic hepatitis C

KW - Cirrhosis

KW - Fibrosis

KW - Hepatocellular carcinoma

KW - Liver failure

KW - Survival analysis

KW - Sustained virological response

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