Abstract and Introduction
Abstract
Peginterferon-alpha (PegIFNa) frequently causes neutropenia, mainly due to bone marrow suppression. The aim of this study was to explore factors that are associated with infections during antiviral treatment. We analysed data from 275 chronic hepatitis C (CHC) patients with compensated liver disease who underwent 318 courses of PegIFNa and ribavirin. Neutropenia was defined as neutrophils <1000 cells/μL. Mean leucocytes count significantly decreased from baseline to treatment nadir (7081 ± 2182 vs 3293 ± 1331 cells/μL, P < 0.001), while neutropenia was observed in 32% during treatment. Thirty-one infections were observed. The incidence rate for infection was assessed at 1.46 infections per 100 person-months of therapy. The hazard rate for infection did not correlate with the neutrophils' nadir or the decrease in white blood cells. In multivariate Cox's regression analysis, cirrhosis was the only factor that was significantly associated with the occurrence of infection. Our data show that the development of bacterial infections during treatment with PegIFNa and ribavirin in patients with compensated CHC is not associated with reduction or the nadir of white cells or neutrophil counts. Baseline cirrhosis is the only factor related with infection during treatment. The common practice of dose adjustment or discontinuation of interferon should be revised; careful assessment of liver damage before therapy and close monitoring during therapy are essential in all patients receiving interferon-based regimes, to minimize the detrimental consequences of infections.
Introduction
Chronic hepatitis C (CHC) is one of the most common viral diseases worldwide and is a major cause of cirrhosis, hepatic failure and hepatocellular carcinoma. Treatment with peginterferon-alpha (PegIFNa) and ribavirin achieves sustained virological response (SVR) in 40–80% of the patients with genotypes 2, 3, 4 infection, while the addition of the first-generation direct-acting antivirals to the combination of PegIFNa and ribavirin has increased SVR to nearly 75% in the naïve patients with genotype 1. SVR is associated with a reduction in the liver-related complications and death. However, many patients could not start therapy due to contraindications, while a proportion of patients discontinued therapy due to several adverse events; therefore, treatment limitations often lead to reduced effectiveness.
Neutropenia due to bone marrow suppression is one of the most common side effects of interferon-alpha (IFNa); it has been shown that neutropenia may lead to dose reduction or discontinuation of treatment in 18% and 1%, respectively, of patients treated with PegIFNa and ribavirin combination, while triple therapy seems to increase myelotoxicity as neutrophil counts <750/μL were reported in 19–25% of patients. Guidelines and experts suggest to perform dose adjustments or complete withdrawal of therapy when absolute neutrophil count decreases below 750 and 500 cells/μL, respectively. However, the guidelines for dose reduction for neutropenia are especially based on studies in oncology patients who underwent chemotherapy, while the clinical impact of IFNa-induced neutropenia on the development of significant infection is controversial. To date, limited data are available on the clinical significance of neutropenia, the risk of infection and the factors that may be associated with severe infection during antiviral therapy for CHC.
The aims of this study were (i) to evaluate the association between the incidence of infection and white blood cells (WBC) count and (ii) to explore for factors that may be associated with the infection during antiviral treatment for CHC.