Morphological analysis and assessment of HCV-RNA and ribavirin concentration in seminal fluid of chronic hepatitis C patients undergoing antiviral combination therapy

Background and Aim: Combination therapy with peginterferon and ribavirin is the treatment of choice for patients with chronic hepatitis C. Due to the possible teratogenic effect of ribavirin effective contraception is mandatory during antiviral therapy. Aim of the study was to evaluate seminal parameters, ribavirin and HCVRNA concentration in seminal fluid and serum prior to and during antiviral treatment.

Patients and Methods: 10 male patients (mean age: 43+9 (years+SD) with CHC were investigated. HCV genotype distribution was HCV-1 (n=5), HCV-2 (n=1), HCV-3 (n=1), HCV-4 (n=3). Seminal fluid (sperm concentration, motility and morphology) was analyzed morphologically. HCV-RNA and ribavirin concentration (serum and seminal fluid (diluted 1:10)) were determined by quantitative PCR (TaqMan®, Roche Austria; LOD: 10 IU/mL) and HPLC, respectively. Examinations were carried out at baseline, at week 4 and at week 12 of antiviral therapy with peginterferonalpha/ribavirin.

Results: HCV RNA was detectable in the seminal fluid of only one patient prior to antiviral therapy and was undetectable in all patients after 4 and 12 weeks of combination therapy. Ribavirin concentration was substantially higher in the seminal fluid (week 4: 4.7±1.9! g/ml, [mean±SD]; week 12: 4.3±0.4) than in serum (week 4: 2.2±0.3 [p=0.01]; week 12: 1.9±0.3 [p=0.02]). Morphological semen abnormalities were common at baseline (asthenoteratozoospermia: n=4, asthenozoospermia: n=1, teratozoospermia: n=3). Sperm density (BL: 70±31×106/ml, Week 4: 50±32, week 12: 59±43 [n.s.]), percentage of sperms with progressive motility (BL: 45±25%, Week 4: 30+28, week 8: 30+23 [n.s.]), and percentage of sperms with normal morphology (BL: 21±14%, Week 4: 19±11, week 8: 11±6 [n.s.]) tended to further decrease during antiviral therapy.

Conclusion: HCV RNA is detectable in seminal fluid only in a low proportion of CHC patients. In contrast, pre-treatment semen abnormalities with reduced percentage of spermatozoa with normal progressive motility and normal morphology are common in patients with chronic HCV infection with further impairment during antiviral therapy. Ribavirin concentration is twofold elevated in seminal fluid compared to serum levels, which reinforces the need of contraception during antiviral combination therapy.