Chronic hepatitis C infection and sex hormone levels: effect of disease severity and recombinant interferon-alpha therapy.
BACKGROUND
We aimed to investigate the associations between androgen status and markers of liver disease severity and to determine the effect of interferon-alpha (IFN-alpha) treatment on sex hormone levels in the context of hepatitis C infection.


METHODS
We audited liver biopsy and sex hormone data from 35 men with chronic hepatitis C and a separate group of 11 men with hepatitis C who received IFN-alpha treatment at Fremantle Hospital.


RESULTS
We found that men with low fibrosis scores (0-2) on the modified Knodell histological activity index were more likely to have lower sex hormone-binding globulin (SHBG) levels (38.2 +/- 13.2 vs 66.6 +/- 43.3 nmol/L, P < 0.001) and higher free testosterone levels (380.4 +/- 102.0 vs 255.9 +/-83.0 pmol/L, P = 0.01) than those with higher fibrosis scores (3-6). SHBG directly correlated with fibrosis scores (r = 0.37, P = 0.032). Free testosterone levels inversely correlated with liver fibrosis scores (r = -0.43, P = 0.011). A transient reduction in total testosterone of 5.7 +/- 4.2 nmol/L (P = 0.014) occurred within the first 6 months of IFN-alpha therapy although free testosterone was unaffected.


CONCLUSIONS
More severe liver disease was associated with lower free testosterone and higher SHBG. IFN-alpha therapy reduced total testosterone but not to hypogonadal levels, with no decline in free testosterone. These data suggest that liver disease in hepatitis C infection modulates androgen status indirectly via increased SHBG. Screening for androgen deficiency in the context of hepatitis C infection should selectively target men with more severe liver disease or documented higher grade fibrosis.
Nguyen
H V
HV
Department of Endocrinology, Fremantle Hospital, Fremantle, WA, Australia.
Mollison
L C
LC
Taylor
T W
TW
Chubb
S A P
SA
Yeap
B B
BB
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000728:Androgens / Q000097:blood*; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004958:Estradiol / Q000097:blood; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology / Q000473:pathology; D008297:Male; D011994:Recombinant Proteins; D012709:Serum Albumin / Q000032:analysis; D012720:Severity of Illness Index; D012738:Sex Hormone-Binding Globulin / Q000032:analysis / Q000187:drug effects*; D013739:Testosterone / Q000097:blood*
D000728:Androgens; D000998:Antiviral Agents; D007370:Interferon Type I; D011994:Recombinant Proteins; D012709:Serum Albumin; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D000410:Alanine Transaminase