Treatment of HCV Genotype 1 (G1) infection with PEG-IFN α-2b and Ribavirin (RBV): age and gender related differences in viral response and RBV action

Background and Aims: Recently, higher SVR rates in female genotype (G) 1 patients (pts) have been reported in the IDEAL study. In order to better understand the main factors associated to those results, we evaluated predictors of viral response by gender and age. Methods: Data from the German Peg-IFNα-2b/RBV observational study were retrospectively analyzed. This real-life cohort study assessed the safety and efficacy of pts treated with Peg-IFN α-2b 1.5µg/kg/wk+weight-based RBV (800–1200mg/day) for up to 48 wks at 285 sites. Pts who discontinued for non-response or for any other reasons were included in the analysis. SVR was defined as HCV-RNA undetectable 24 weeks after end of therapy. Results: Of 1890 pts treated for G1 infection, 800 pts achieved SVR (42.3%). Significantly higher SVR rates were observed in females compared to male pts (47.1% vs. 38.7%, p=0.0002). Data analysis according to age (Table) showed most prominent SVR differences up to 17% in 40 to 60 years old pts. This was caused by a marked decline of SVR rates in male pts accompanied by an increase of relapse as well as nonresponse rates. This was not related to BMI or viral load but more likely due to more pronounced fibrosis as indicated by a higher proportion of male pts with a low platelet count. The decline in hemoglobin (Hb) as a pharmacodynamic marker of RBV action was inversely related to SVR; Interestingly, Hb decline considerably changed with increased age and was significantly different between female and male pts. Logistic regression analyses demonstrated gender and age, as well as baseline HCV and platelets to be significant effects for SVR. Conclusions: In this observational study, SVR differences between female and male pts are most prominent in the group of 40–60 years old pts and could be in part related to differences in fibrosis progression. The role of age- and gender dependent differences in RBV metabolism/action for viral response remains to be elucidated in further detail.

Table 1: Age- and gender-related differences

Female (F) vs. male (M), Chi square test: ap<0.001, bp<0.01, cp<0.05, dp<0.0001; T-test: ep<0.05, fp<0.001
	Age (years) of G1 pts
		<30 N=260	≥30– <40 N=428	≥40– <50 N=573	≥50– <60 N=402	≥60 N=227
SVR,%	F	60.0	53.0	48.3	46.1	30.9
	M	49.9	46.9	34.1a	28.9a	34.1
Relapse	F	16.7	14.9	21.4	19.3	33.8
	M	15.0	14.5	28.6	35.8b	33.3
Nonresponse,%	F	19.0	25.8	32.6	33.0	39.6
	M	18.8	28.9	40.4	46.9b	37.5
BMI, mean	F	22.7	24.7	25.1	26.3	26.5
	M	23.8e	25.4	25.5	26.3	25.9
HVL,%	F	38.0	38.4	53.0	54.5	55.4
	M	46.3	50.9c	56.4	60.7	52.3
Platelets <150/nL,%	F	1.0	11.3	9.7	19.3	33.1
	M	3.1	7.2	21.1f	27.5	34.1
Hb decline >3g/dl,%	F	34.0	43.5	48.5	65.4	65.4
	M	53.9b	60.9a	66.8d	72.9	83.7d

Hepatitis C - PEG-IFN α-2b - Ribavirin - Viral response