Seminal fluid ribavirin level and functional semen parameters in patients with chronic hepatitis C on antiviral combination therapy.
OBJECTIVE
Due to the possible teratogenic effect of ribavirin, effective contraception is mandatory during antiviral therapy in patients with chronic hepatitis C (CHC). The aim of this study was to evaluate seminal parameters and ribavirin and HCV-RNA concentrations in seminal fluid and serum prior to and during antiviral treatment.


METHODS
Fifteen male patients (age: 42+/-9 (years+/-SD)) with CHC treated with pegylated interferon-alpha-2a and ribavirin were investigated. Seminal fluid (sperm concentration, motility, and morphology) was analysed morphologically. HCV-RNA and ribavirin concentration were determined by quantitative PCR and HPLC, respectively. Examinations were carried out at baseline, week 4, and week 12.


RESULTS
Ribavirin concentration was higher in seminal fluid than in serum (week 4: 5.2+/-2.5 vs. 2.1+/-0.3; week 12: 4.4+/-1.8 vs. 2.0+/-0.3 (microg/ml, mean+/-SD; p<0.001)). Semen abnormalities were common at baseline (asthenoteratozoospermia: n=6; asthenozoospermia: n=3; teratozoospermia: n=3). Sperm density (BL: 67+/-33x10(6)/ml; week 4: 42+/-25 (p<0.05); week 12: 49+/-33 (n.s.)), percentage of sperm with progressive motility (BL: 40+/-26%; week 4: 27+/-25; week 12: 31+/-20 (n.s.)), and percentage of sperm with normal morphology (BL: 25+/-15; week 4: 20+/-11; week 12: 16+/-9; p<0.05 for both) further decreased during antiviral therapy. HCV-RNA was detectable in the seminal fluid of only two patients prior to antiviral therapy and was undetectable in all patients during combination therapy.


CONCLUSIONS
Semen abnormalities were common in CHC patients, with further impairment during antiviral therapy. Ribavirin concentration was elevated twofold in seminal fluid compared to serum levels, which reinforces the need for contraception during antiviral combination therapy.
Hofer
Harald
H
Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Waehringerguertel 18-20, Vienna, Austria. harald.hofer@meduniwien.ac.at
Donnerer
Josef
J
Sator
Kathrin
K
Staufer
Katharina
K
Scherzer
Thomas-Matthias
TM
Dejaco
Clemens
C
Sator
Michael
M
Kessler
Harald
H
Ferenci
Peter
P
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D053627:Asthenozoospermia / Q000139:chemically induced* / Q000473:pathology; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009845:Oligospermia / Q000139:chemically induced / Q000473:pathology; D012367:RNA, Viral / Q000378:metabolism; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012661:Semen / Q000378:metabolism / Q000821:virology; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects* / Q000473:pathology
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin