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

Maan, Raoel; van der Meer, Adriaan J; Hansen, Bettina E; Feld, Jordan J; Wedemeyer, Heiner; Dufour, Jean-François; Zangneh, Hooman F; Lammert, Frank; Manns, Michael P; Zeuzem, Stefan; Janssen, Harry L A; de Knegt, Robert J; Veldt, Bart J (2014). Effect of thrombocytopenia on treatment tolerability and outcome in patients with chronic HCV infection and advanced hepatic fibrosis. Journal of hepatology, 61(3), pp. 482-491. Elsevier 10.1016/j.jhep.2014.04.021

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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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology

UniBE Contributor:

Dufour, Jean-François


600 Technology > 610 Medicine & health








Lilian Karin Smith-Wirth

Date Deposited:

20 Apr 2015 11:32

Last Modified:

06 Nov 2015 09:40

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Antiviral treatment; Bleeding; Chronic hepatitis c; Complications; Interferon; Side effects





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