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Article ; Online: Emerging Diagnostic Tools to Decide When to Discontinue Nucleos(t)ide Analogues in Chronic Hepatitis B

Margarita Papatheodoridi / George Papatheodoridis

Cells, Vol 9, Iss 2, p

2020 Volume 493

Abstract: The aim of this review is to outline emerging biomarkers that can serve as diagnostic tools to identify non-cirrhotic chronic hepatitis B (CHB) patients who could safely discontinue nucleos(t)ide analogues (NAs) before HBsAg loss. Regarding possible ... ...

Abstract	The aim of this review is to outline emerging biomarkers that can serve as diagnostic tools to identify non-cirrhotic chronic hepatitis B (CHB) patients who could safely discontinue nucleos(t)ide analogues (NAs) before HBsAg loss. Regarding possible predictors of post-NAs outcomes, a number of studies have evaluated numerous factors, which can be categorised in markers of hepatitis B virus (HBV) activity, markers of host immune response and markers of other patient characteristics. In clinical practice, the most important question for patients who discontinue NAs is to differentiate those who will benefit by achieving HBsAg loss or at least by remaining in remission and those who will relapse requiring retreatment. Most of the discontinuation studies so far came from Asian and only few from European populations and examined the rates and predictors of post-NA virological and/or combined relapses or HBsAg loss. To date, there is still controversy about predictors of post-NA relapses, while only HBsAg serum levels at NA discontinuation seem to be the most robust predictive marker of the probability of subsequent off-treatment HBsAg seroclearance. Newer viral markers such as HBV RNA and hepatitis B core-related antigen seem promising, but further research is required.
Keywords	discontinuation ; nucleos(t)ide analogues ; hepatitis b ; hbsag ; hbcrag ; relapse ; retreatment ; remission ; hbsag loss ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Hepatitis B Virus DNA Integration, Chronic Infections and Hepatocellular Carcinoma

Maria Bousali / George Papatheodoridis / Dimitrios Paraskevis / Timokratis Karamitros

Microorganisms, Vol 9, Iss 1787, p

2021 Volume 1787

Abstract: Hepatitis B Virus (HBV) is an Old World virus with a high mutation rate, which puts its origins in Africa alongside the origins of Homo sapiens, and is a member of the Hepadnaviridae family that is characterized by a unique viral replication cycle. It ... ...

Abstract	Hepatitis B Virus (HBV) is an Old World virus with a high mutation rate, which puts its origins in Africa alongside the origins of Homo sapiens, and is a member of the Hepadnaviridae family that is characterized by a unique viral replication cycle. It targets human hepatocytes and can lead to chronic HBV infection either after acute infection via horizontal transmission usually during infancy or childhood or via maternal–fetal transmission. HBV has been found in ~85% of HBV-related Hepatocellular Carcinomas (HCC), and it can integrate the whole or part of its genome into the host genomic DNA. The molecular mechanisms involved in the HBV DNA integration is not yet clear; thus, multiple models have been described with respect to either the relaxed-circular DNA (rcDNA) or the double-stranded linear DNA (dslDNA) of HBV. Various genes have been found to be affected by HBV DNA integration, including cell-proliferation-related genes, oncogenes and long non-coding RNA genes (lincRNAs). The present review summarizes the advances in the research of HBV DNA integration, focusing on the evolutionary and molecular side of the integration events along with the arising clinical aspects in the light of WHO’s commitment to eliminate HBV and viral hepatitis by 2030.
Keywords	hepatitis B virus ; HBV ; viral integration ; pathogen-host interactions ; insertional mutagenesis ; chronic hepatitis ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Significance of Circulating Cell-Free DNA Biomarkers in HBeAg-Negative Chronic Hepatitis B Virus Infection and Their Changes after Treatment Initiation

Nikolaos D. Karakousis / Lampros Chrysavgis / Alkistis Papatheodoridi / Aigli-Ioanna Legaki / Panagiotis Lembessis / Evangelos Cholongitas / Antonios Chatzigeorgiou / George Papatheodoridis

Pathogens, Vol 12, Iss 394, p

2023 Volume 394

Abstract: Background: Chronic hepatitis B virus (HBV) infection is a common chronic liver disease that is closely associated with increased morbidity and mortality. Circulating cell-free DNA (cf-DNA) and global DNA methylation, expressed as circulating levels of 5- ...

Abstract	Background: Chronic hepatitis B virus (HBV) infection is a common chronic liver disease that is closely associated with increased morbidity and mortality. Circulating cell-free DNA (cf-DNA) and global DNA methylation, expressed as circulating levels of 5-methyl-2′-deoxycytidine, are increasingly used to monitor chronic inflammatory diseases of several etiologies. This study attempts to investigate the serum levels of circulating cf-DNA and 5-methyl-2′-deoxycytidine in HBeAg-negative patients with chronic infection (carriers) and chronic hepatitis B (CHB), as well as their changes after treatment initiation in CHB. Methods: Serum samples from a total of 61 HBeAg-negative patients (30 carriers and 31 CHB patients) were included in order to quantify the levels of circulating cf-DNA and 5-methyl-2′-deoxycytidine. In addition, serum samples from 17 CHB patients in complete virological and biochemical remission after initiation of treatment with a nucleos(t)ide analogue were included. Results: Circulating cf-DNA concentration was significantly increased after the initiation of treatment (15 vs. 10 ng/mL, p = 0.022). There was a trend in higher mean levels of circulating 5-methyl-2′-deoxycytidine in carriers compared to CHB patients (211.02 vs. 175.66 ng/mL, p = 0.089), as well as a trend in increasing 5-methyl-2′-deoxycytidine levels after treatment initiation in CHB patients compared to pre-treatment levels (215 vs. 173 ng/mL, p = 0.079). Conclusions: Both circulating levels of cf-DNA and 5-methyl-2′-deoxycytidine might be useful biomarkers in order to monitor liver disease activity and response to antiviral treatment in HBeAg-negative chronic HBV patients, but further studies are essential in order to validate these intriguing findings.
Keywords	hepatitis B ; cell-free DNA ; 5-methyl-2′-deoxycytidine ; global DNA methylation ; Medicine ; R
Subject code	610
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Significance of Circulating Cell-Free DNA Species in Non-Alcoholic Fatty Liver Disease

Lampros Chrysavgis / Alkistis Papatheodoridi / Evangelos Cholongitas / Michael Koutsilieris / George Papatheodoridis / Antonios Chatzigeorgiou

International Journal of Molecular Sciences, Vol 22, Iss 8849, p

2021 Volume 8849

Abstract: The pathogenetic mechanisms involved in the progression of non-alcoholic fatty liver disease (NAFLD) have not been completely elucidated, while the significance of circulating cell-free DNA (cf-DNA) species has been rarely evaluated in NAFLD. Herein, we ... ...

Abstract	The pathogenetic mechanisms involved in the progression of non-alcoholic fatty liver disease (NAFLD) have not been completely elucidated, while the significance of circulating cell-free DNA (cf-DNA) species has been rarely evaluated in NAFLD. Herein, we assessed the serum levels of cf-DNA species in NAFLD patients and investigated their potential associations with patients’ characteristics and severity of liver disease. Forty-nine adult patients with NAFLD of any stage were included in this cohort study. Cf-DNA was isolated from patients’ sera and the levels of several distinct cf-DNA species including total cf-DNA, gene-coding cf-DNA, Alu repeat sequences, mitochondrial DNA copies and 5-methyl-2′-deoxycytidine were determined. Cirrhotic compared to non-cirrhotic patients had significantly lower serum levels of cf-DNA and RNAse P coding DNA as well as higher expression of 5-methyl-2′-deoxycytidine. After adjustment for the significant clinico-epidemiological factors, lower serum levels of cf-DNA or RNAse P were independently associated with the presence of cirrhosis. Serum levels of total and gene-coding DNA are associated with the presence of cirrhosis in NAFLD patients regardless of clinical or epidemiological parameters and may therefore be used as a screening tool for NAFLD progression.
Keywords	non-alcoholic fatty liver disease (NAFLD) ; cell-free DNA (cf-DNA) ; genomic DNA ; liver cirrhosis ; liquid biopsy ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610 ; 612
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Preoperative Evaluation of Coronary Artery Disease in Liver Transplant Candidates

Maria Bonou / Sophie Mavrogeni / Chris J. Kapelios / Marina Skouloudi / Constantina Aggeli / Evangelos Cholongitas / George Papatheodoridis / John Barbetseas

Diagnostics, Vol 11, Iss 75, p

Many Unanswered Questions in Clinical Practice

2021 Volume 75

Abstract: Cardiovascular (CV) complications represent the first non-graft-related cause of death and the third overall cause of death among patients undergoing liver transplantation (LT). History of coronary artery disease is related to increased CV mortality ... ...

Abstract	Cardiovascular (CV) complications represent the first non-graft-related cause of death and the third overall cause of death among patients undergoing liver transplantation (LT). History of coronary artery disease is related to increased CV mortality following LT. Although it is of paramount importance to stratify CV risk in pre-LT patients, there is no consensus regarding the choice of the optimal non-invasive cardiac imaging test. Algorithms proposed by scientific associations include non-traditional risk factors, which are associated with increased cardiac risk profiles. Thus, an individualized pre-LT evaluation protocol should be followed. As the average age of patients undergoing LT and the number of candidates continue to rise, the “3 W” questions still remain unanswered, Who, Which and When? Who should be screened for coronary artery disease (CAD), which screening modality should be used and when should the asymptomatic waitlisted patients repeat cardiac evaluation? Prospective studies with large sample sizes are warranted to define an algorithm that can provide better risk stratification and more reliable survival prediction.
Keywords	liver transplantation ; cardiovascular risk ; risk stratification ; prognosis ; screening ; coronary artery disease ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Hepatitis B, C and human immunodeficiency virus knowledge among the general greek population

Sylvia Kaskafetou / Argiro Karakosta / Vana Sypsa / Natasa Kalpourtzi / Magda Gavana / Apostolos Vantarakis / George Rachiotis / Grigoris Chlouverakis / Grigoris Trypsianis / Paraskevi V. Voulgari / Yannis Alamanos / George Papatheodoridis / Giota Touloumi / on behalf of the Hprolipsis study group

BMC Public Health, Vol 22, Iss 1, Pp 1-

results from the Hprolipsis nationwide survey

2022 Volume 10

Abstract: Abstract Background Although several studies on hepatitis B (HBV), C (HCV) and human immunodeficiency virus (HIV) infection have been conducted in Greece, little is known on the knowledge level of the Greek population towards these three infections. Our ... ...

Abstract	Abstract Background Although several studies on hepatitis B (HBV), C (HCV) and human immunodeficiency virus (HIV) infection have been conducted in Greece, little is known on the knowledge level of the Greek population towards these three infections. Our aim was to assess the knowledge level of the adult Greek general population about the HBV, HCV and HIV. Methods Data were derived from the first general population health survey, Hprolipsis. The sample was selected by multistage stratified random sampling. A standardized questionnaire was administered by trained interviewers during home visits. A knowledge score was constructed based on responses to 17 per infection selected items and categorized in three levels; high (12–17 correct replies) medium (6–11) and low (0–5). Among 8,341 eligible individuals, 6,006 were recruited (response rate: 72%) and 5,878 adults (≥ 18 years) were included in the analysis. The statistical analysis accounted for the study design. Results Only 30.4%, 21.6%, and 29.6% of the participants had a high overall knowledge level of HBV, HCV and HIV, respectively. These low percentages were mainly attributed to the high levels of misconception about transmission modes (65.9%, 67.2%, and 67.9%, respectively). Results showed that increasing age and living out of the big metropolitan cities were associated with decreased odds of having higher knowledge. Female gender, higher education level, higher monthly family income, higher medical risk score, history of testing and being born in Greece or Cyprus, were associated with increased odds of having higher knowledge. Conclusions There are significant knowledge gaps in the Greek general population regarding modes of transmission, preventive measures and treatment availability for HBV, HCV and HIV. There is an urgent need for large scale but also localized awareness activities targeted to less privileged populations, to fill the gaps in knowledge and increase population engagement in preventive measures.
Keywords	HCV ; HBV ; HIV ; Knowledge ; Risk factors ; Health survey ; Public aspects of medicine ; RA1-1270
Subject code	310
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SARS-CoV-2 Molecular Transmission Clusters and Containment Measures in Ten European Regions During the First Pandemic Wave

Maria Bousali / Aristea Dimadi / Evangelia-Georgia Kostaki / Sotirios Tsiodras / Georgios K. Nikolopoulos / Dionyssios N. Sgouras / Gkikas Magiorkinis / George Papatheodoridis / Vasiliki Pogka / Giota Lourida / Aikaterini Argyraki / Emmanouil Angelakis / George Sourvinos / Apostolos Beloukas / Dimitrios Paraskevis / Timokratis Karamitros

Life, Vol 11, Iss 219, p

2021 Volume 219

Abstract: Background: The spatiotemporal profiling of molecular transmission clusters (MTCs) using viral genomic data can effectively identify transmission networks in order to inform public health actions targeting SARS-CoV-2 spread. Methods: We used whole genome ...

Abstract	Background: The spatiotemporal profiling of molecular transmission clusters (MTCs) using viral genomic data can effectively identify transmission networks in order to inform public health actions targeting SARS-CoV-2 spread. Methods: We used whole genome SARS-CoV-2 sequences derived from ten European regions belonging to eight countries to perform phylogenetic and phylodynamic analysis. We developed dedicated bioinformatics pipelines to identify regional MTCs and to assess demographic factors potentially associated with their formation. Results: The total number and the scale of MTCs varied from small household clusters identified in all regions, to a super-spreading event found in Uusimaa-FI. Specific age groups were more likely to belong to MTCs in different regions. The clustered sequences referring to the age groups 50–100 years old (y.o.) were increased in all regions two weeks after the establishment of the lockdown, while those referring to the age group 0–19 y.o. decreased only in those regions where schools’ closure was combined with a lockdown. Conclusions: The spatiotemporal profiling of the SARS-CoV-2 MTCs can be a useful tool to monitor the effectiveness of the interventions and to reveal cryptic transmissions that have not been identified through contact tracing.
Keywords	SARS-CoV-2 ; COVID-19 ; pandemic ; transmission ; clusters ; phylodynamics ; Science ; Q
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis

Huai Zhang / Rafael S. Rios / Jerome Boursier / Rodolphe Anty / Wah-Kheong Chan / Jacob George / Yusuf Yilmaz / Vincent Wai-Sun Wong / Jiangao Fan / Jean-François Dufour / George Papatheodoridis / Li Chen / Jörn M. Schattenberg / Junping Shi / Liang Xu / Grace Lai-Hung Wong / Naomi F. Lange / Margarita Papatheodoridi / Yuqiang Mi /

Yujie Zhou / Christopher D. Byrne / Giovanni Targher / Gong Feng / Minghua Zheng / Yuanyuan Ji

Chinese Medical Journal, Vol 136, Iss 3, Pp 341-

an international registry study

2023 Volume 350

Abstract: Abstract. Background:. Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in ... ...

Abstract	Abstract. Background:. Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH. Methods:. Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL). Results:. A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69–1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension (P < 0.001, P = 0.026 and P = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714–0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% [52%–59%]) and positive predictive value (59%) were not ideal. Conclusion:. This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	Wolters Kluwer
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Intestinal Bacteria Composition and Translocation of Bacteria in Inflammatory Bowel Disease.

Spyros Vrakas / Konstantinos C Mountzouris / George Michalopoulos / George Karamanolis / George Papatheodoridis / Charalampos Tzathas / Maria Gazouli

PLoS ONE, Vol 12, Iss 1, p e

2017 Volume 0170034

Abstract: Live commensal intestinal bacteria are present in the peripheral blood where they can induce inflammation.To evaluate the intestinal bacteria composition and translocation of bacteria in IBD.Both blood and tissue biopsy samples were collected from adult ... ...

Abstract	Live commensal intestinal bacteria are present in the peripheral blood where they can induce inflammation.To evaluate the intestinal bacteria composition and translocation of bacteria in IBD.Both blood and tissue biopsy samples were collected from adult patients with active/inactive Crohn's disease (CD), active/inactive ulcerative colitis (UC) and healthy individuals. Most of the patients were newly diagnosed and none of them received antibiotics. Using a reverse transcription-quantitative real-time PCR (RT-qPCR) method, we determined the composition of microbiota. NOD2/CARD15 genotyping was also studied.Total bacterial DNA concentration was increased in tissue and blood samples of IBD patients compared to healthy controls. Furthermore, the active IBD cases had higher total bacterial DNA concentration levels compared to the inactive cases. Three species characterized dysbiosis in IBD, namely an increase of Bacteroides spp in active and inactive IBD samples, and a decrease in Clostridium leptum group (IV), and Faecalibacterium prausnitzi in both active and inactive IBD patients. No significant association between bacterial translocation and NOD2/CARD15 mutations was found.The composition of the microbiota in IBD patients differs from that of healthy controls. The high rate of bacterial DNA in the blood samples indicates translocation in inflammatory bowel disease.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The impact of host metabolic factors on treatment outcome in chronic hepatitis C.

Savvoula, Savvidou / Dimitrios, Chrysagis / George, Papatheodoridis / Spilios, Manolakopoulos / Christos, Triantos / John, Goulis

Gastroenterology research and practice

2012 Volume 2012, Page(s) 420156

Abstract: Background. Recent data suggest that chronic hepatitis C has to be considered a metabolic disease further to a viral infection. The aim of this study was to elaborate on the complex interactions between hepatitis C virus, host metabolic factors, and ... ...

Abstract	Background. Recent data suggest that chronic hepatitis C has to be considered a metabolic disease further to a viral infection. The aim of this study was to elaborate on the complex interactions between hepatitis C virus, host metabolic factors, and treatment response. Methods. Demographic, virological, and histological data from 356 consecutive patients were analyzed retrospectively. Hepatic steatosis, obesity, and insulin resistance were examined in relation to their impact on treatment outcome. Comparison between genotype 1 and 3 patients was performed to identify differences in the determinants of hepatic steatosis. Results. Histological evidence of hepatic steatosis was found in 113 patients, distributed in 20.3%, 9.0%, and 2.5% for grades I, II, and III, respectively. Hepatic steatosis was associated with past alcohol abuse (P = 0.003) and histological evidence of advanced fibrosis (P < 0.001). Older age (OR 2.51, P = 0.002), genotype (OR 3.28, P < 0.001), cirrhosis (OR 4.23, P = 0.005), and hepatic steatosis (OR 2.48, P = 0.001) were independent predictors for nonresponse. Correlations of hepatic steatosis with alcohol, insulin resistance, and fibrosis stage were found similar for both genotypes 1 and 3. Conclusions. Host metabolic factors may predict treatment outcome, and this impact remains significant even in genotype 3, where steatosis has been believed to be exclusively virus related.
Language	English
Publishing date	2012-04-22
Publishing country	Egypt
Document type	Journal Article
ZDB-ID	2435460-0
ISSN	1687-630X ; 1687-6121
ISSN (online)	1687-630X
ISSN	1687-6121
DOI	10.1155/2012/420156
Database	MEDical Literature Analysis and Retrieval System OnLINE

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