Liver-related complications before and after successful treatment of chronic hepatitis C virus infection in people with inherited bleeding disorders

Cas J Isfordink; Karel J van Erpecum; Kathelijn Fischer; Paul R van der Valk; Lize F D van Vulpen; Roger E G Schutgens; Joop E Arends; Evelien P Mauser-Bunschoten

doi:10.1111/hae.14668

Liver-related complications before and after successful treatment of chronic hepatitis C virus infection in people with inherited bleeding disorders

Haemophilia. 2023 Jan;29(1):106-114. doi: 10.1111/hae.14668. Epub 2022 Oct 2.

Authors

Cas J Isfordink^{1

2}, Karel J van Erpecum², Kathelijn Fischer¹, Paul R van der Valk¹, Lize F D van Vulpen¹, Roger E G Schutgens¹, Joop E Arends³, Evelien P Mauser-Bunschoten¹

Affiliations

¹ Van Creveldkliniek, Department of Benign Hematology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
² Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
³ Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Abstract

Introduction: With availability of direct-acting antivirals (DAA), most persons with inherited bleeding disorders are currently cured of hepatitis C virus (HCV) infection. The risk of liver-related complications following HCV cure has not been reported for this population.

Aim: Reporting liver-related complications during long-term chronic HCV infection and following sustained virological response (SVR) in this population.

Methods: Retrospective follow-up of a prospective single-centre cohort of HCV antibody-positive persons with inherited bleeding disorders. Primary endpoint was liver-related complications [hepatocellular carcinoma (HCC), decompensated cirrhosis, bleeding gastroesophageal varices]. Liver-related complications were reported separately during chronic HCV and following SVR, stratified for interferon-based and DAA-based SVR.

Results: In total 309/381 (81%) HCV antibody-positive individuals developed chronic HCV infection. Median follow-up was 44 years [interquartile range (IQR): 34-50]. Liver-related complications occurred in 36/309 (12%) of individuals with chronic HCV infection after median 31 years of chronic infection. Of 199 individuals with SVR, 97 were cured with interferon-based regimens and 102 with DAA after median infection durations of 29 and 45 years, respectively. At end of follow-up, respectively, 21% and 42% had advanced fibrosis or cirrhosis. Post-SVR, seven (4%) individuals had a liver-related complication, mainly HCC (n = 4). Incidence of liver-related complications per 100 patient-years post-SVR follow-up was .2 for interferon-cured and 1.0 for DAA-cured individuals (p = .01).

Conclusion: Successful HCV treatment does not eliminate the risk of liver-related complications in persons with inherited bleeding disorders. Due to higher baseline risk, incidence was higher after DAA than interferon-based SVR. We advise continuing HCC surveillance post-SVR in all with advanced fibrosis or cirrhosis.

Keywords: antiviral agents; cirrhosis; haemophilia; hepatocellular carcinoma; viral hepatitis.

MeSH terms

Antiviral Agents / therapeutic use
Carcinoma, Hepatocellular* / complications
Hepacivirus / genetics
Hepatitis C* / complications
Hepatitis C, Chronic* / complications
Hepatitis C, Chronic* / drug therapy
Humans
Interferons / therapeutic use
Liver Cirrhosis / complications
Liver Neoplasms* / complications
Liver Neoplasms* / epidemiology
Prospective Studies
Retrospective Studies

Substances

Antiviral Agents
Interferons