Dataset Information

Chronic Hepatitis B Virus Infection: The Relation between Hepatitis B Antigen Expression, Telomere Length, Senescence, Inflammation and Fibrosis.

ABSTRACT: BACKGROUND:Chronic Hepatitis B virus (HBV) infection can lead to the development of chronic hepatitis, cirrhosis and hepatocellular carcinoma. We hypothesized that HBV might accelerate hepatocyte ageing and investigated the effect of HBV on hepatocyte cell cycle state and biological age. We also investigated the relation between inflammation, fibrosis and cell cycle phase. METHODS:Liver samples from patients with chronic HBV (n = 91), normal liver (n = 55) and regenerating liver (n = 15) were studied. Immunohistochemistry for cell cycle phase markers and HBV antigens was used to determine host cell cycle phase. Hepatocyte-specific telomere length was evaluated by quantitative fluorescent in-situ hybridization (Q-FISH) in conjunction with hepatocyte nuclear area and HBV antigen expression. The effects of induced cell cycle arrest and induced cellular senescence on HBV production were assessed in vitro. RESULTS:13.7% hepatocytes in chronic HBV had entered cell cycle, but expression of markers for S, G2 and M phase was low compared with regenerating liver. Hepatocyte p21 expression was increased (10.9%) in chronic HBV and correlated with liver fibrosis. Mean telomere length was reduced in chronic HBV compared to normal. However, within HBV-affected livers, hepatocytes expressing HBV antigens had longer telomeres. Telomere length declined and hepatocyte nuclear size increased as HBV core antigen (HBcAg) expression shifted from the nucleus to cytoplasm. Nuclear co-expression of HBcAg and p21 was not observed. Cell cycle arrest induced in vitro was associated with increased HBV production, in contrast to in vitro induction of cellular senescence, which had no effect. CONCLUSION:Chronic HBV infection was associated with hepatocyte G1 cell cycle arrest and accelerated hepatocyte ageing, implying that HBV induced cellular senescence. However, HBV replication was confined to biologically younger hepatocytes. Changes in the cellular location of HBcAg may be related to the onset of cellular senescence.

SUBMITTER: Tachtatzis PM

PROVIDER: S-EPMC4449162 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Chronic Hepatitis B Virus Infection: The Relation between Hepatitis B Antigen Expression, Telomere Length, Senescence, Inflammation and Fibrosis.

Tachtatzis Phaedra M PM Marshall Aileen A Arvinthan Aloysious A Verma Suman S Penrhyn-Lowe Sue S Mela Marianna M Scarpini Cinzia C Davies Susan E SE Coleman Nicholas N Alexander Graeme J M GJ

PloS one 20150529 5

<h4>Background</h4>Chronic Hepatitis B virus (HBV) infection can lead to the development of chronic hepatitis, cirrhosis and hepatocellular carcinoma. We hypothesized that HBV might accelerate hepatocyte ageing and investigated the effect of HBV on hepatocyte cell cycle state and biological age. We also investigated the relation between inflammation, fibrosis and cell cycle phase.<h4>Methods</h4>Liver samples from patients with chronic HBV (n = 91), normal liver (n = 55) and regenerating liver ( ...[more]

PMID: 26024529

Similar Datasets

Project description:IntroductionCushing's syndrome (CS) increases cardiovascular risk (CVR) and adipocytokine imbalance, associated with an increased inflammatory state. Telomere length (TL) shortening is a novel CVR marker, associated with inflammation biomarkers. We hypothesized that inflammatory state and higher CVR in CS might be related to TL shortening, as observed in premature aging.AimTo evaluate relationships between TL, CVR and inflammation markers in CS.MethodsIn a cross-sectional study, 77 patients with CS (14 males, 59 pituitary-, 17 adrenal- and 1 ectopic-origin; 21 active disease) and 77 age-, gender-, smoking-matched controls were included. Total white blood cell TL was measured by TRF-Southern technique. Clinical data and blood samples were collected (lipids, adrenal function, glucose). Adiponectin, interleukin-6 (IL6) and C-reactive protein (CRP) were available in a subgroup of patients (n=32). Correlations between TL and clinical features were examined and multiple linear regression analysis was performed to investigate potential predictors of TL.ResultsDyslipidemic CS had shorter TL than non-dyslipidemic subjects (7328±1274 vs 7957±1137 bp, p<0.05). After adjustment for age and body mass index, cured and active CS dyslipidemic patients had shorter TL than non-dyslipidemic CS (cured: 7187±1309 vs 7868±1104; active: 7203±1262 vs 8615±1056, respectively, p<0.05). Total cholesterol and triglycerides negatively correlated with TL (r-0.279 and -0.259, respectively, p<0.05), as well as CRP and IL6 (r-0.412 and -0.441, respectively, p<0.05). No difference in TL according the presence of other individual CVR factors (hypertension, diabetes mellitus, obesity) were observed in CS or in the control group. Additional TL shortening was observed in dyslipidemic obese patients who were also hypertensive, compared to those with two or less CVR factors (6956±1280 vs 7860±1180, respectively, p<0.001). Age and dyslipidemia were independent negative predictors of TL.ConclusionTL is shortened in dyslipidemic CS patients, further worse if hypertension and/or obesity coexist and is negatively correlated with increased inflammation markers. Increased lipids and a "low" grade inflammation may contribute to TL shortening and consequently to premature ageing and increased morbidity in CS.

Project description:BackgroundNon-invasive evaluation for liver fibrosis is clinically important, especially in patients with undetectable hepatitis B virus (HBV) DNA treated with nucleoside analogs.AimTo clarify the monitoring power of hepatitis B core-related antigen (HBcrAg) for hepatic histologic changes in patients with chronic hepatitis B (CHB) treated with entecavir.MethodsThis prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression, respectively, in 403 CHB patients, including 374 with entecavir for 72 weeks (291 underwent paired liver biopsy) and 29 as controls.ResultsLevel of HBcrAg correlated negatively with liver fibrosis staging (γ = -0.357, P < 0.001) in hepatitis B e antigen (HBeAg)-positive patients, and positively with liver fibrosis staging in HBeAg-negative patients. Higher HBcrAg concentration was associated with younger age, HBeAg positive status, high HBV DNA loads, high level of hepatitis B surface antigen (HBsAg) and higher necroinflammation, but not with HBV genotype. Serum concentration of HBcrAg, basal core promoter/precore (BCP/PC) mutant, quantitation of HBsAg (qHBsAg) and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression. HBV DNA was undetectable in 88.37% of patients treated with entecavir at week 72, while their level of HBcrAg was still detectable. A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement. HBcrAg concentration > 6.33 log IU/mL at baseline and logarithmic reduction > 1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement, respectively.ConclusionHBcrAg level is associated with liver fibrosis progression. HBcrAg is an excellent monitor of hepatic histological changes, especially in CHB patients treated with nucleoside analogs.

Dataset Information

Chronic Hepatitis B Virus Infection: The Relation between Hepatitis B Antigen Expression, Telomere Length, Senescence, Inflammation and Fibrosis.

Publications

Chronic Hepatitis B Virus Infection: The Relation between Hepatitis B Antigen Expression, Telomere Length, Senescence, Inflammation and Fibrosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets