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.
occurred in approximately a fifth of study participants. Independent risk factors were
female sex, a history of depression and nadir (lowest ever) lymphocyte count.
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.”
A shortage of neutrophils, a type of white blood
cell that fights bacterial infections.
cells in the blood which can attack bacteria and fungal infections.
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 among patients taking PegIFN-alfa/ribavirin therapy ranges
between 4 and 12%.
quarter of people taking HCV therapy develop infections, but the relationship
between cytopenia and the risk of infections has not been well researched.
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 patients
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
developed in 36% of patients, and in 19% of individuals' infections were
moderate, severe or life threatening.
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
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
“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.”
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, “clinicians should be aware of the increased
infection incidence in women treated with PegIFN/RBV.”
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