Natural History and Management of Hepatitis C: Does Sex Play a Role?

Baden, Rachel; Rockstroh, Jürgen K.; Buti, Marı́a

doi:10.1093/infdis/jiu057

Cited by 109 publications

(102 citation statements)

References 36 publications

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“…Women are more likely to eradicate hepatitis C virus than men after they are exposed to initial infection. However, postmenopausal women exhibit increased rates of fibrosis compared with those of reproductive age because they have lost the protective effects of oestrogen (Baden et al, 2014). The evident increase in oestrogen levels in pregnant women, especially in the third trimester, facilitates HEV infection; by contrast, HEV replication reduces ER expression.…”

Section: Discussionmentioning

confidence: 99%

Pregnancy serum facilitates hepatitis E virus replication in vitro

Yang

et al. 2015

Journal of General Virology

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Hepatitis E virus (HEV) infection causes high mortality in pregnant women. However, the pathogenic mechanisms of HEV infection in pregnant women remain unknown. In this study, the roles of pregnancy serum in HEV infection were investigated using an efficient cell culture system. HEV infection was exacerbated by supplementing with pregnancy serum, especially theat in third trimester of pregnancy. Oestrogen receptors (ER-a and ER-b) were activated in cells supplemented with pregnancy serum and were significantly inhibited during HEV infection. Type I IFN, especially IFN-b, showed delayed upregulation in HEV-infected cells supplemented with the serum in the third trimester of pregnancy, which indicated that delayed IFN-b expression may facilitate viral replication. Results suggested that pregnancy serum accelerated HEV replication by suppressing oestrogen receptors and type I IFN in the early stage of infection.

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Section: Discussionmentioning

confidence: 99%

Pregnancy serum facilitates hepatitis E virus replication in vitro

Yang

et al. 2015

Journal of General Virology

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“…HCV infection usually disproportionately affects men more than women 43 . Apetite hormone ghrelin is reduced in chronic hepatitis C patients 44 .…”

Section: Discussionmentioning

confidence: 99%

“…Because both male and female mice have a similar degree of reduced food intake, greater reduction of body weight in males may not be caused by gender-specific loss of apetite. Women are more likely to clear the virus spontaneously and have slower rates of liver disease progression than men if they become chronically infected 43 . Overall, both genders of mice showed similar rates of persistent infection, but liver pathology progresses slightly faster, if any, in males (Supplementary information, Table S9).…”

Section: Discussionmentioning

confidence: 99%

Persistent hepatitis C virus infections and hepatopathological manifestations in immune-competent humanized mice

et al. 2014

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The majority of hepatitis C virus (HCV) infection develops chronic infection, which causes steatosis, cirrhosis and hepatocellular carcinoma. However, understanding HCV chronicity and pathogenesis is hampered by its narrow host range, mostly restricted to human and chimpanzee. Recent endeavour to infect a variety of humanized mice has not been able to achieve persistent HCV infection unless the essential innate immune responsive genes are knocked out. Nevertheless, such immune-compromised humanized mice still lacked HCV infection-induced hepatopathogenesis. Here we report that transgenic mice in ICR background harboring both human CD81 and occludin genes (C/OTg) are permissive to HCV infection at a chronicity rate comparable to humans. In this mouse model, HCV accomplishes its replication cycle, leading to sustained viremia and infectivity for more than 12 months post infection with expected fibrotic and cirrhotic progression. Host factors favorable for HCV replication, and inadequate innate immune-response may contribute to the persistence. Lastly, NS3/4 protease inhibitor telaprevir can effectively inhibit de novo RNA synthesis and acute HCV infection of C/OTg mice. Thus, chronic HCV infection with complete replication cycle and hepatopathologic manifestations is recapitulated, for the first time, in immune-competent mice. This model will open a new venue to study the mechanisms of chronic hepatitis C and develop better treatments.

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“…The natural history of HCV infection varies by sex, with increased viral clearance and slower progression of liver disease in women compared with men, possibly resulting from a protective effect of estrogen on the liver. [14][15][16] Sex may also modify the response to ART among HIV-infected individuals. While some studies have found no association of sex with response to ART, [17][18][19] others have suggested that women have superior virologic, immunologic, and clinical outcomes compared with men.…”

Section: Introductionmentioning

confidence: 99%

Differences in Response to Antiretroviral Therapy by Sex and Hepatitis C Infection Status

Marcus

Leyden

Chao

et al. 2015

AIDS Patient Care and STDs

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Hepatitis C virus (HCV) co-infection and biological sex may each affect response to antiretroviral therapy (ART), yet no studies have examined HIV-associated outcomes by both HCV status and sex. We conducted a cohort study of HIV-infected adults initiating ART in Kaiser Permanente California during 1996-2011. We used piecewise linear regression to assess CD4 changes by sex and HCV status over 5 years. We used Cox regression to estimate hazard ratios (HR) by sex and HCV status for HIV RNA <500 copies/mL over 1 year, and for AIDS and death over the follow-up period. Among 12,865 subjects, there were 154 HIV/HCV-co-infected women, 1000 HIV/HCV-co-infected men, 1088 HIV-mono-infected women, and 10,623 HIV-mono-infected men. CD4 increases were slower in the first year for HIV/HCV-co-infected women (75 cells/μL) and men (70 cells/μL) compared with HIV-mono-infected women (145 cells/μL) and men (120 cells/μL; p<0.001). After 5 years, women had higher CD4 than men in both HIV-mono-infected (598 vs. 562 cells/μL, p=0.003) and HIV/HCV-co-infected individuals (567 vs. 509 cells/μL, p=0.003). Regardless of sex, HIV/HCV co-infection was associated with 40% higher mortality [95% confidence interval (CI): 1.2-1.6] compared with HIV mono-infection, but was not associated with AIDS (HR 1.1, 95% CI: 0.9-1.3) or achieving HIV RNA <500 copies/mL (HR 1.0, 95% CI: 0.9-1.1). HIV/HCV-co-infected men and women have slower CD4 recovery after starting ART and have increased mortality compared with HIV-mono-infected men and women. HCV should be aggressively treated in HIV/HCV-co-infected adults, regardless of sex.

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Natural History and Management of Hepatitis C: Does Sex Play a Role?

Cited by 109 publications

References 36 publications

Pregnancy serum facilitates hepatitis E virus replication in vitro

Pregnancy serum facilitates hepatitis E virus replication in vitro

Persistent hepatitis C virus infections and hepatopathological manifestations in immune-competent humanized mice

Differences in Response to Antiretroviral Therapy by Sex and Hepatitis C Infection Status

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