Raoel Maan1, Adriaan J van der Meer1, Bettina E Hansen1, Jordan J Feld2, Heiner Wedemeyer3, Jean-François Dufour4, Hooman F Zangneh2, Frank Lammert5, Michael P Manns3, Stefan Zeuzem6, Harry L A Janssen7, Robert J de Knegt1, Bart J Veldt8. 1. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. 2. Toronto Centre for Liver Disease, Toronto Western & General Hospital, University Health Network, Toronto, Canada. 3. Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany. 4. Hepatology, Department of Clinical Research, University of Bern, Bern, Switzerland. 5. Department of Medicine II, Saarland University Medical Center, Homburg, Germany. 6. Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany. 7. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Toronto Centre for Liver Disease, Toronto Western & General Hospital, University Health Network, Toronto, Canada. 8. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: b.veldt@erasmusmc.nl.
Abstract
BACKGROUND & AIMS: Pegylated interferon is still the backbone of hepatitis C treatment and may cause thrombocytopenia, leading to dose reductions, early discontinuation, and eventually worse clinical outcome. We assessed associations between interferon-induced thrombocytopenia and bleeding complications, interferon dose reductions, early treatment discontinuation, as well as SVR and long-term clinical outcome. METHODS: All consecutive patients with chronic HCV infection and biopsy-proven advanced hepatic fibrosis (Ishak 4-6) who initiated interferon-based therapy between 1990 and 2003 in 5 large hepatology units in Europe and Canada were included. RESULTS: Overall, 859 treatments were administered to 546 patients. Baseline platelets (in 10(9)/L) were normal (⩾150) in 394 (46%) treatments; thrombocytopenia was moderate (75-149) in 324 (38%) and severe (<75) in 53 (6%) treatments. Thrombocytopenia-induced interferon dose reductions occurred in 3 (1%); 46 (16%), and 15 (30%) treatments respectively (p<0.001); interferon was discontinued due to thrombocytopenia in 1 (<1%), 8 (3%), and in 8 (16%) treatments respectively (p<0.001). In total, 104 bleeding events were reported during 53 treatments. Only two severe bleeding complications occurred. Multivariate analysis showed that cirrhosis and a platelet count below 50 were associated with on-treatment bleeding. Within thrombocytopenic patients, patients attaining SVR had a lower occurrence of liver failure (p<0.001), hepatocellular carcinoma (p<0.001), liver related death or liver transplantation (p<0.001), and all-cause mortality (p=0.001) compared to patients without SVR. CONCLUSIONS: Even in thrombocytopenic patients with chronic HCV infection and advanced hepatic fibrosis, on-treatment bleedings are generally mild. SVR was associated with a marked reduction in cirrhosis-related morbidity and mortality, especially in patients with baseline thrombocytopenia.
BACKGROUND & AIMS: Pegylated interferon is still the backbone of hepatitis C treatment and may cause thrombocytopenia, leading to dose reductions, early discontinuation, and eventually worse clinical outcome. We assessed associations between interferon-induced thrombocytopenia and bleeding complications, interferon dose reductions, early treatment discontinuation, as well as SVR and long-term clinical outcome. METHODS: All consecutive patients with chronic HCV infection and biopsy-proven advanced hepatic fibrosis (Ishak 4-6) who initiated interferon-based therapy between 1990 and 2003 in 5 large hepatology units in Europe and Canada were included. RESULTS: Overall, 859 treatments were administered to 546 patients. Baseline platelets (in 10(9)/L) were normal (⩾150) in 394 (46%) treatments; thrombocytopenia was moderate (75-149) in 324 (38%) and severe (<75) in 53 (6%) treatments. Thrombocytopenia-induced interferon dose reductions occurred in 3 (1%); 46 (16%), and 15 (30%) treatments respectively (p<0.001); interferon was discontinued due to thrombocytopenia in 1 (<1%), 8 (3%), and in 8 (16%) treatments respectively (p<0.001). In total, 104 bleeding events were reported during 53 treatments. Only two severe bleeding complications occurred. Multivariate analysis showed that cirrhosis and a platelet count below 50 were associated with on-treatment bleeding. Within thrombocytopenicpatients, patients attaining SVR had a lower occurrence of liver failure (p<0.001), hepatocellular carcinoma (p<0.001), liver related death or liver transplantation (p<0.001), and all-cause mortality (p=0.001) compared to patients without SVR. CONCLUSIONS: Even in thrombocytopenicpatients with chronic HCV infection and advanced hepatic fibrosis, on-treatment bleedings are generally mild. SVR was associated with a marked reduction in cirrhosis-related morbidity and mortality, especially in patients with baseline thrombocytopenia.
Authors: Raoel Maan; Adriaan J van der Meer; Willem Pieter Brouwer; Elisabeth P C Plompen; Milan J Sonneveld; Robert Roomer; Annemiek A van der Eijk; Zwier M A Groothuismink; Bettina E Hansen; Bart J Veldt; Harry L A Janssen; Andre Boonstra; Robert J de Knegt Journal: PLoS One Date: 2015-10-06 Impact factor: 3.240