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Low testosterone persists after HCV clearance

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February 11, 2019

Low levels of free testosterone are common among men with chronic hepatitis C infection following SVR and persist after HCV clearance, according to findings from a prospective, longitudinal cohort study.

“Previous research has shown that low total testosterone (TT), low free testosterone (FT), and elevated sex hormone-binding globulin (SHBG) are extrahepatic manifestations

of chronic HCV when compared with healthy controls,” Chloe S. Chaudhury, MD, post-baccalaureate research fellow at the National Institute of Allergy and Infectious Diseases, and colleagues wrote. “There is now a need for studies to examine the effect of HCV and HCV viral clearance on long-term testosterone levels and hypogonadal status.”

To evaluate testosterone levels and the prevalence of low testosterone in men with HCV, Chaudhury and colleagues enrolled 327 patients with chronic HCV infection, including 150 who were coinfected with HIV. They also evaluated a subset of 85 men who had recorded testosterone levels pre-HCV treatment and after SVR. The median follow-up duration was 36 months.

Chaudhury and colleagues observed higher TT and SHBG among men with active HCV at baseline compared with men who achieved SVR. However, there was no change in FT between the groups.

Participants with SVR were more likely to have low TT compared with those with active HCV (P = .002), whereas 50% of participants with active HCV and 42% of participants with SVR reported low FT.

The researchers also longitudinally evaluated data from patients with pre- and post-HCV treatment and clearance for changes after SVR and found that TT and SHBG decreased significantly (P < .0001), but FT remained unchanged. Moreover, low FT persisted after SVR, with 58% experiencing low FT pretreatment and 54% after SVR (P = .72).

According to the study, significant independent predictors of change in FT following SVR included HIV status and change in aspartate aminotransferase-to-platelet ratio.

Chaudhury and colleagues suggested that testosterone deficiency during active HCV infection may be masked because of elevated SHBG levels. Although the levels of SHBG improve following an SVR, low FT was still common and persisted after HCV was cleared, they explained.

“The persistence of hypogonadism following successful viral treatment demonstrates the need for enhanced awareness and potential screening in the growing number of HCV-treated patients,” Chaudhury and colleagues concluded. “Additional research is required to establish the mechanism responsible for hypogonadism in both patients with chronic HCV infection and in patients post-SVR and to develop strategies to optimize the recognition and management of testosterone deficiency in this setting.” – by Marley Ghizzone

Disclosures: Chaudhury reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

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Andrew H. Talal, MD, MPH

The authors investigated the relationships between low testosterone and HCV infection, HIV/HCV coinfection and after SVR. The study consisted of 327 men with HCV, 150 with HIV/HCV coinfection and a subset of 85 men with TT and FT levels, as well as SHBG obtained before HCV treatment and after SVR. The investigators sought to assess whether HIV/HCV coinfection compounds the issue of hypogonadism in HCV infection.

They found that active HCV infection was characterized by higher TT and increased levels of SHBG compared with subjects who achieved SVR. Increases in FT after SVR were associated with HIV and improvements in fibrosis. When defined by the level of FT, 50% of participants remained hypogonadal after SVR.

Previous research has shown that low testosterone levels are associated with HCV. This study illustrates that approximately 50% of HCV-infected individuals who achieve SVR remain hypogonadal. Additionally, it also highlights important gonadal function differences between HIV/HCV coinfected and HCV monoinfected patients. Only the coinfected patients illustrated an inverse relationship between FT levels and changes in fibrosis, ie, FT levels increased as fibrosis regressed as assessed using a noninvasive fibrosis assessment. Thus, SHBG and FT measurements, in addition to TT levels, should be collected to provide a more comprehensive understanding of these relationships.

The study highlights the important relationships between common viral infections and male hypogonadism. A more complete picture of these relationships could be obtained by also measuring other hormones important for testosterone production, including luteinizing hormone, follicle-stimulating hormone, prolactin, estradiol and estrone levels. Additionally, given the circadian rhythm of testosterone production with peak morning release, future prospective studies should endeavor to collect testosterone uniformly. The long-term effects of male hypogonadism, especially differences between HCV monoinfected and HIV/HCV coinfected patients, and potential therapeutic approaches deserve additional attention.

Andrew H. Talal, MD, MPH

Professor of medicine
The State University of New York at Buffalo

Disclosure: Talal reports numerous ties to industry.