A low lymphocyte count is associated with an increased risk of infections during hepatitis C virus (HCV) treatment that includes pegylated interferon and ribavirin, according to the results of a large observational study published in the online edition of Clinical Infectious Diseases.
Moderate-to-severe infections occurred in approximately a fifth of study participants. Independent risk factors were female sex, a history of depression and nadir (lowest-ever) lymphocyte count.
“These findings have important implications for the management of patients during HCV treatment that includes PegIFN-alfa [pegylated interferon-alfa],” comment the authors. “Our data suggest that lymphocytopenia may be an important marker of increased risk of moderate, severe, or life threatening infections.”
PegIFN-alfa and ribavirin are the backbone of HCV therapy. Known side-effects of interferon include cytopenias – a reduction in the number of blood cells. The incidence of severe neutropenia (a lack of a type of white blood cell) among patients taking PegIFN-alfa/ribavirin therapy ranges between 4 and 12%.
Approximately a quarter of people taking HCV therapy develop infections, but the relationship between cytopenia and the risk of infections has not been well researched.
Investigators from the IDEAL (Individualized Dosing Efficacy vs Flat Dosing to Assess Optimal Pegylated Interferon Therapy) study designed an observational study involving 3070 people. The incidence of mild, moderate, severe and life-threatening infections was monitored and their risk factors assessed.
The adult participants were all HCV-treatment naive at baseline (had not taken HCV treatment before) and had compensated liver disease. Blood chemistry was monitored every two to six weeks during the 48-week course of HCV therapy, which consisted of PegIFN-alfa-2a/b with weight-based ribavirin. Dose reductions were required when neutrophils fell to below 0.75x109/l and treatment was discontinued in instances of a decline in neutrophils below 0.5x109/l.
Infections developed in 36% of participants, and in 19% of individuals' infections were moderate, severe or life threatening.
Approximately a fifth (21%) of patients had at least one neutrophil count below 0.75x109/l, only 8% of individuals experienced a sustained fall in neutrophils below this level. Twelve patients (0.4%) had severe or life-threatening infections and moderate-to-severe neutropenia. Absolute lymphocyte count fell to below 0.5x109/l in 107 patients, including 34 patients who also had nadir neutrophil counts below 0.75x109/l.
Several risk factors were independently associated with an increased risk of infections of moderate or greater severity. These included female sex (AOR = 1.61; 95% CI, 1.33-1.97), a history of depression (AOR = 0.68; 95% CI, 0.55-0.83) and nadir on-treatment lymphocyte count (AOR = 0.48; 95% CI, 0.37-0.68); all p < 0.001. Nadir neutrophil count was not associated with risk of moderate, severe or life-threatening infections.
“We identified a strong relationship between treatment-induced lymphocytopenia and incident infection,” comment the investigators. “Our findings suggest that clinicians should monitor ALC [absolute lymphocyte count] (in addition to ANC [absolute neutrophil count]) carefully during treatment….another question worthy of study is whether increased monitoring of patients at higher risk of infection, such as those with cirrhosis, is warranted.”
The relationship between sex and the risk of infection was independent of lymphocyte count. Although acknowledging further research into this finding is warranted, the authors nevertheless recommend that “clinicians should be aware of the increased infection incidence in women treated with PegIFN/RBV”.
The investigators conclude that physicians should carefully monitor both lymphocyte and neutrophil counts in patients treated with PegIFN/ribavirin. Dose reductions should be considered for patients who experience a fall in lymphocyte count below 0.5x109/l.
Melia MT et al. Infections during peginterferon/ribavirin therapy are associated with magnitude of decline in absolute lymphocyte count: results of the IDEAL study. Clin Infect Dis, published online ahead of print, 2014.