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

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.

• Authors: Raoel Maan, Adriaan J van der Meer, Bettina E Hansen, Jordan J Feld, Heiner Wedemeyer, Jean-François Dufour, Hooman F Zangneh, Frank Lammert, Michael P Manns, Stefan Zeuzem, Harry L A Janssen, Robert J de Knegt, Bart J Veldt
• Journal: Journal of hepatology (J Hepatol) Vol. 61 Issue 3 Pg. 482-91 (Sep 2014) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 24780302 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• Interferon-alpha
• Recombinant Proteins
• Polyethylene Glycols
• peginterferon alfa-2a

Topics

• Adult
• Antiviral Agents (adverse effects, pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Female
• Hemorrhage (epidemiology)
• Hepacivirus (physiology)
• Hepatitis C, Chronic (drug therapy)
• Humans
• Incidence
• Interferon-alpha (adverse effects, pharmacology, therapeutic use)
• Liver Cirrhosis (drug therapy)
• Male
• Middle Aged
• Multivariate Analysis
• Polyethylene Glycols (adverse effects, pharmacology, therapeutic use)
• Recombinant Proteins (adverse effects, pharmacology, therapeutic use)
• Retrospective Studies
• Severity of Illness Index
• Thrombocytopenia (chemically induced, complications)
• Treatment Outcome
• Virus Replication (drug effects)
• Withholding Treatment