HBV: the same than HCV?

Transcription

1 HBV: the same than HCV? Maurizia Rossana Brunetto UO Epatologia - Azienda Ospedaliero Universitaria Pisana Centro Riferimento Regionale - Diagnosi e trattamento delle epatopatie croniche e del tumore di fegato

2 A personalized approach to the management of chronic hepatitis C in women requires a careful evaluation of liver disease stage and activity according to age, co-factors of liver disease and personal needs

3 Impact of Gender, Viral transmission and Aging in the prevalence of HBsAg Tsay P-W, Chang Gung Med J 2009 Gender differences in prevalence of HBsAg and anti-hcv in individuals receiving a general check-up in Taiwan. The prevalence of HBsAg was higher in men than in women (p<0.001) especially for those younger than 60 years.

4 Gender and HBV infection The long term serological course of asymptomatic HBV carriers and development of HCC Alward WL, J Infect Dis 1985 In a cohort of 150 asymptomatic carriers during a mean f.u. 6.1 years, both HBeAg/anti-HBe seroconversion and HBsAg clearance occurred more frequently in female than male ( p <0.01 and 0.02 respectively) Incidence and determinants of spontaneous seroclearance of HBeAg and DNA in patients with CHB Yang H-I, Clin Gastroent. and Hepatol 2012 In a cohort of 1289 HBV carriers, 439 of whom HBeAg positive, the factors influencing HBeAg/anti-HBe seroconversion were female sex (p=0.002), genotype B (p<0.001), pre-core 1896 (p=0.043), baseline ALT and HBV- DNA. Female sex, on the contrary, did not influence the HBV-DNA clearance

5 Gender and HBV infection HBeAg to anti-hbe seroconversion occurs at higher rates in females as compared to males Predictors associated with a nonresponse to HBV vaccination include male sex, older age, obesity and immunocompromising chronic diseases Estradiol induces the production of IFNγ in lymphocytes Estradiol augments an antigen-specific primary antibody response in PBMC

6 Chronic HBV infection profile in a single center cohort UO Epatologia - Pisa 516 chronic HBV carriers 163 females 353 males (31.6%) (68.4%) Brunetto MR, Roma y Mean age 51.2 y p=n.s 7.4% HBeAg pos/anti-hbe 15.1% p=0.021 Liver disease No/Yes 49.7%/50.3% 34%/66.8% p= % HCC 6.2% p=0.05

7 Chronic HBV infection profile in a single center cohort UO Epatologia - Pisa 511 chronic HBV carriers 161 females 350 males (31.6%) Inactive Carriers (68.4%) 56 (39.7%) (60.2%) Active Carriers HBV-DNA <20000 IU/ml 23 (41.8%) 32 (58.2%) 55 Active Carriers 57 (29.1%) 139 (70.9%) HBV-DNA >20000 IU/ml 196 Cirrhosis (21%) 94 (79%) Chi , p =0.003 Brunetto MR, Roma 2012

8 Presence/absence of Chronic Hepatitis B by gender and age N. of patients Age (by decades) Brunetto MR, Roma 2012

9 Prevalence of Cirrhosis by age Age years Prevalence Variation Eemales Males Prevalence Variation <30 0/8 0/ /31 (3.2%) 3/56 (5.4%) /43 (7.0%) 8/72 (11.1%) /38 (7.9%) 25/96 (26.0%) 4.5 x /27 (37%) 38/75 (50.7%) 1.3 x /16 (50%) 20/28 (71.4%) 2.5 x 2 x 1.4 x Brunetto MR, Roma 2012

10 Male to female ratio between 2 age groups of HBV related HCC 901 Japanese patients 32.8% P< % Tanaka Y et al, J Hepatol 2006

11 HCC incidence is 5 to 7-fold higher in males than females Androgens Higher activities of androgen axis correlate with a higher risk of HCC HBx protein enhances the transcriptional activity of the androgen receptor in an androgen concentration dependent manner Wu J-F et al, Gastroenterology 2010 Androgen and its receptor enhance HBV replication in transgenic mice Tian Y et al, J Virol 2012 Estrogens Estrogens can repress transcription of HBV genes by up-regulating ER-α which interacts with and alters the binding of HNF-4 α to the HBV enhancer 1 This could account for lower viral load and reduced incidence of HCC in women Wang S-H et al, Gastroenterology 2012

12 than a man? Better to be a woman

13 Hepatology Unit University Hospital - Pisa, Italy Antonella Cristofani Simonetta Ferretti (part-time) Simona Giannetti Teresa Crisponi (part-time) Isabella Rossi (Chief) Nurses Pietro Ciccorossi Barbara Coco Piero Colombatto Filippo Oliveri Veronica Romagnoli Carlotta Rastelli Beatrice Cherubini Medical Doctors Administrative Personel Arianna Del Chicca Biologists Daniela Cavallone Francesco Moriconi Angela Stabile Bio-Physics Luigi Civitano Ranieri Bizzarri Ferruccio Bonino Gatroenterology Chair Pisa University