Risk of infections during interferon-based treatment 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; Lammert, Frank; Manns, Michael P; Zeuzem, Stefan; Janssen, Harry L A; de Knegt, Robert J; Veldt, Bart J (2015). Risk of infections during interferon-based treatment in patients with chronic HCV infection and advanced hepatic fibrosis. Journal of gastroenterology and hepatology, 30(6), pp. 1057-1064. Wiley-Blackwell Publishing Asia 10.1111/jgh.12929

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BACKGROUND & AIMS

Pegylated interferon-based treatment is still the backbone of current hepatitis C therapy and is associated with bone marrow suppression and an increased risk of infections. The aim of this retrospective cohort study was to assess the risk of infections during interferon-based treatment among patients with chronic HCV infection and advanced hepatic fibrosis and its relation to treatment-induced neutropenia.

METHODS

This cohort study included all consecutive patients with chronic HCV infection and biopsy-proven bridging fibrosis or cirrhosis (Ishak 4-6) who started treatment between 1990 and 2003 in five large hepatology units in Europe and Canada. Neutrophil counts between 500/μL-749/μL and below 500/μL were considered as moderate and severe neutropenia, respectively.

RESULTS

This study included 723 interferon-based treatments, administered to 490 patients. In total, 113 infections were reported during 88 (12%) treatments, of which 24 (21%) were considered severe. Only one patient was found to have moderate neutropenia and three patients were found to have severe neutropenia at the visit before the infection. Three hundred and twelve (99.7%) visits with moderate neutropenia and 44 (93.6%) visits with severe neutropenia were not followed by an infection. Multivariable analysis showed that cirrhosis (OR 2.85, 95%CI 1.38-5.90, p=0.005) and severe neutropenia at the previous visit (OR 5.42, 95%CI 1.34-22.0, p=0.018) were associated with the occurrence of infection, while moderate neutropenia was not. Among a subgroup of patients treated with PegIFN, severe neutropenia was not significantly associated (OR 1.63, 95%CI 0.19-14.2, p=0.660).

CONCLUSIONS

In this large cohort of patients with bridging fibrosis and cirrhosis, infections during interferon-based therapy were generally mild. Severe interferon-induced neutropenia rarely occurred, but was associated with on-treatment infection. Moderate neutropenia was not associated with infection, suggesting that current dose reduction guidelines might be too strict.

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