Sex Differences in Spontaneous Degranulation Activity of Intrahepatic Natural Killer Cells during Chronic Hepatitis B: Association with Estradiol Levels

Jilkova, Zuzana Macek; Decaens, Thomas; Marlu, Alice; Marche, Hélène; Jouvin‐Marche, Evelyne; Marche, Patrice N.

doi:10.1155/2017/3214917

Cited by 13 publications

(16 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanisms underlying the effect of menopause on HBV-associated liver fibrosis remain unknown. Given the protective effects of estrogens in hepatic injury (30, 31), fibrogenesis (32, 33), and HBV infection (12, 34), we hypothesize that a state of estrogen deficiency may be associated with the progression of liver fibrosis. There are several lines of evidence to support this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Influence of Gender and Reproductive Factors on Liver Fibrosis in Patients With Chronic Hepatitis B Infection

Xiong

Yang

et al. 2019

Clinical and Translational Gastroenterology

View full text Add to dashboard Cite

INTRODUCTION:The role of reproductive factors in the development of chronic hepatitis B (CHB) remains unknown. We assessed the potential contributions of gender, menopausal status, and menarche age to liver fibrosis in CHB.METHODS:A cross-sectional prospective study included 716 women and 716 age-matched men with CHB who were not currently receiving antiviral therapy. Liver stiffness measurement using transient elastography was used to stage liver fibrosis as F0–F1 (<7.2 kPa), F ≥ 2 (7.2 kPa), F ≥ 3 (9.4 kPa), and F = 4 (12.2 kPa). Female patients were asked regarding their age at menarche and menopausal status using a questionnaire.RESULTS:Of the 716 women, 121 (16.9%) were postmenopausal, and 80 (11.2%) had advanced liver fibrosis. Multivariate logistic regression analysis showed that the postmenopausal status compared with the premenopausal status (odds ratio [OR] = 3.65–8.83; P < 0.05) and age at menarche of >14 years compared with <13 years (OR = 2.85–3.95; P < 0.05) were significantly associated with advanced fibrosis. Compared with premenopausal women, age-matched men had a higher OR for advanced fibrosis (P < 0.05). Compared with postmenopausal women, age-matched men did not show a significant difference in the degree of liver fibrosis (P > 0.05). Longitudinal data analysis showed that postmenopausal women (n = 31) were significantly less likely to undergo regression of liver fibrosis after antiviral treatment vs premenopausal women (n = 19) (26.3% vs 74.2%, respectively; P < 0.001).DISCUSSION:Menopause and late menarche aggravated liver fibrosis in untreated CHB, besides menopause delayed fibrosis regression under antiviral therapy. The protective effect of female gender against fibrosis was lost for postmenopausal women.TRANSLATIONAL IMPACT:It is important to consider menopausal status and age at menarche in establishing surveillance strategies among CHB females. Postmenopausal estrogen therapy may be considered for the prevention or treatment of liver fibrosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Influence of Gender and Reproductive Factors on Liver Fibrosis in Patients With Chronic Hepatitis B Infection

Xiong

Yang

et al. 2019

Clinical and Translational Gastroenterology

View full text Add to dashboard Cite

show abstract

“…Many studies indicated that male subjects are more susceptible to aggravation of chronic hepatitis B than female subjects because of their sex hormones [ 28 , 29 ], which might suggest strong immune response in males. In similar context, the male predominance in HBsAg-serocleared patients in the present study might suggest the potential impact of gender on HBV elimination in CHB patients in the endemic region of vertical HBV transmission.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel susceptibility loci associated with hepatitis B surface antigen seroclearance in chronic hepatitis B

et al. 2018

View full text Add to dashboard Cite

Background/AimsThe seroclearance of hepatitis B virus (HBV) surface antigen (HBsAg) is regarded as a functional cure of chronic hepatitis B (CHB) although it occurs rarely. Recently, several genome-wide association studies (GWASs) revealed various genetic alterations related to the clinical course of HBV infection. However, all of these studies focused on the progression of HBV infection to chronicity and had limited application because of the heterogeneity of HBV genotypes. In the present study, we aimed to determine susceptibility genetic markers for seroclearance of HBsAg in CHB patients with a homogenous viral genotype.MethodsOne hundred patients with CHB who had experienced HBsAg seroclearance before 60 years of age and another 100 with CHB showing high serum levels of HBsAg even after 60 years of age were enrolled. Extreme-phenotype GWAS was conducted using blood samples of participants.ResultsWe identified three single nucleotide polymorphisms, rs7944135 (P = 4.17 × 10−6, odds ratio [OR] = 4.16, 95% confidence interval [CI] = 2.27–7.63) at 11q12.1, rs171941 (P = 3.52×10−6, OR = 3.69, 95% CI = 2.13–6.42) at 5q14.1, and rs6462008 (P = 3.40×10−6, OR = 0.34, 95% CI = 0.22–0.54) at 7p15.2 as novel susceptibility loci associated with HBsAg seroclearance in patients with CHB. The flanking genes at these loci including MPEG1, DTX4, MTX3, and HOXA13 were suggested to have functional significance. In addition, through functional analysis, CXCL13 was also presumed to be related.ConclusionsTo the best of our knowledge, this study is the first GWAS regarding the seroclearance of HBsAg in CHB patients. We identify new susceptibility loci for cure of CHB, providing new insights into its pathophysiology.

show abstract

“…Cells were recovered from liver tissue by mechanical disruption as described previously [ 29 ] and whole blood samples were used in case of blood analyses. Cells without any stimulation were immune-stained for flow cytometric analysis.…”

Section: Methodsmentioning

confidence: 99%

Combination of AKT inhibitor ARQ 092 and sorafenib potentiates inhibition of tumor progression in cirrhotic rat model of hepatocellular carcinoma

et al. 2018

Self Cite

View full text Add to dashboard Cite

Copyright: Macek Jilkova et al. This is an open-access article distributed under the terms of the Creative Commons AttributionLicense 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACTThe prognosis of patients with advanced hepatocellular carcinoma (HCC) is very poor. The AKT pathway is activated in almost half of HCC cases and in addition, long term exposure to conventional drug treatment of HCC, sorafenib, often results in overactivation of AKT, leading to HCC resistance. Therefore, it is important to assess the safety and the efficacy of selective allosteric AKT inhibitor ARQ 092 (Miransertib) in combination with sorafenib.Here, we demonstrated in vitro that the combination of ARQ 092 with sorafenib synergistically suppressed proliferation, promoted apoptosis, and reduced migration. To test the effect of the combination in vivo, rats with diethylnitrosamine-induced cirrhosis and fully developed HCC were randomized and treated with vehicle, sorafenib, ARQ 092 or the combination of ARQ 092 with sorafenib; (n=7/group) for 6 weeks. Tumor progression, size of tumors and the mean tumor number were significantly reduced by the combination treatment compared to the control or single treatments. This effect was associated with a significant increase in apoptotic response and reduction in proliferation and angiogenesis. Sirius red staining showed a decrease in liver fibrosis. Moreover, treatments improved immune response in blood and in tumor microenvironment.Thus, the combination of ARQ 092 with sorafenib potentiates inhibition of tumor progression and gives the possibility of therapeutic improvement for patients with advanced HCC.

show abstract

Sex Differences in Spontaneous Degranulation Activity of Intrahepatic Natural Killer Cells during Chronic Hepatitis B: Association with Estradiol Levels

Cited by 13 publications

References 30 publications

Influence of Gender and Reproductive Factors on Liver Fibrosis in Patients With Chronic Hepatitis B Infection

Influence of Gender and Reproductive Factors on Liver Fibrosis in Patients With Chronic Hepatitis B Infection

Identification of novel susceptibility loci associated with hepatitis B surface antigen seroclearance in chronic hepatitis B

Combination of AKT inhibitor ARQ 092 and sorafenib potentiates inhibition of tumor progression in cirrhotic rat model of hepatocellular carcinoma

Contact Info

Product

Resources

About