Effect of thrombocytopenia on treatment tolerability and outcome in patients with chronic HCV infection and advanced hepatic fibrosis

Raoel Maan, AJ van der Meer, Bettina Hansen, JJ Feld, H Wedemeyer, JF Dufour, HF Zangneh, F Lammert, MP Manns, S Zeuzem, HLA Janssen, Rob de Knegt, Bart Veldt

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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. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)482-491
Number of pages10
JournalJournal of Hepatology
Volume61
Issue number3
Publication statusPublished - 2014

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