Background:
A 30-50% decrease of eutrophil count is expected in CHC patients receiving PEG-IFN plus RBV, leading to increased risk of infection. Despite potential impact on survival, available evidence on such adverse events only comes from retrospective studies or from RCTs on highly selected patients.
Aim:
To assess prospectively incidence and risk factors for infections during PEG-IFN plus RBV treatment for CHC in an outpatient setting.
Methods:
Between October 2002 and April 2004 in our centre we offered PEG-IFN α-2a (180 µg/wk) plus RBV (800-1200 mg/day) treatment to 188 consecutive outpatients with histologically-proven CHC fulfilling NIH criteria. 174 patients (age 53±11 yr, range 28-70; 63% men; 31% with cirrhosis) accepted to enter the trial. Presence of infection was serially assessed by clinical, radiologic, microbiologic criteria and graded severe if required hospitalization, bed rest, i.v. therapy or study treatment discontinuation.
Results:
After 21±12 wk (4-48), 47 patients developed 51 mild (17 upper respiratory tract, 14 genito-urinary, 11 muco-cutaneous, 9 viral) and 10 severe infections (3 pneumonia, 2 large abscess, 1 discitis, pericarditis, meningo-encephalitis, tuberculosis and sepsis). Incidence rate of all infections was 5.2% (n of cases per 100 patient-mo), cumulative incidence was 47%. The corresponding figures for severe infections were 1.1% and 14.3%. Incidence of all infections was higher in the 86 patients with eutrophil counts below sex-specific median value (1330 or 1200 cells/µL, male/female patients) on treatment wk 4 (7.2% vs 2.9%, P=0.006), in the 41 in the upper age quartile (≥64 yr) (8.8% vs 4.4%, P=0.014), with a borderline significance in women (7.3% vs 4.2%, P=0.062). Low eutrophil count on wk 4 (hazard ratio 2.63, 95%CI 1.37-5.05; P=0.019) and old age (2.21, 1.14-4.28; P=0.019) independently predicted infections at Cox regression analysis.
Conclusions:
In a “real world” setting of CHC patients, incidence of infectious adverse events to a PEG-IFN plus RBV regimen appears to be more frequent than reported so far. Cumulative incidence of severe, sometimes life-threatening infections may be as high as 14%. Careful clinical monitoring is recommended in older patients and in those with low eutrophil counts after 4-wk treatment.
