Effect of thrombocytopenia on treatment tolerability and outcome in patients with chronic HCV infection and advanced hepatic fibrosis.
OBJECTIVE
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.
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Raoel
R
Maan
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Adriaan J
AJ
van der Meer
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Bettina E
BE
Hansen
Toronto Centre for Liver Disease, Toronto Western & General Hospital, University Health Network, Toronto, Canada.
Jordan J
JJ
Feld
Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany.
Heiner
H
Wedemeyer
Hepatology, Department of Clinical Research, University of Bern, Bern, Switzerland.
Jean-François
JF
Dufour
Toronto Centre for Liver Disease, Toronto Western & General Hospital, University Health Network, Toronto, Canada.
Hooman F
HF
Zangneh
Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
Frank
F
Lammert
Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany.
Michael P
MP
Manns
Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Stefan
S
Zeuzem
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.
Harry L A
HL
Janssen
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Robert J
RJ
de Knegt
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: b.veldt@erasmusmc.nl.
Bart J
BJ
Veldt
D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology; D016174:Hepacivirus / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D016898:Interferon-alpha / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013921:Thrombocytopenia / Q000139:chemically induced / Q000150:complications*; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects; D028761:Withholding Treatment
D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a
Antiviral treatment; Bleeding; Chronic hepatitis c; Complications; Interferon; Side effects