Immunosuppressive Treatment of Hbsag–Positive Chronic Liver Disease: Significance of Hbeag

Tage-Jensen, U; Aldershvile, Jan; Schlichting, P

doi:10.1002/hep.1840050111

Cited by 6 publications

(4 citation statements)

References 13 publications

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“…From the differential expression analyses, the two most informative results were (1) a region of the Hepatitis B genome that produced the HBeAg protein was overexpressed in the 'dead' patients and (2) allow the virus to persist in infected cells, and increase the risk of disease [56,57]. So our results,…”

Section: Comparing 'Dead' and 'Alive' Samples In The Hepb Subgroup Usmentioning

confidence: 72%

viGEN: An open source pipeline for the detection and quantification of viral RNA in human tumors

Bhuvaneshwar

Song

Madhavan

et al. 2017

Preprint

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An estimated 17% of cancers worldwide are associated with infectious causes. The extent and biological significance of viral presence/infection in actual tumor samples is generally unknown but could be measured using human transcriptome (RNA-seq) data from tumor samples.We present an open source bioinformatics pipeline viGEN, which combines existing well-known and novel RNA-seq tools for not only the detection and quantification of viral RNA, but also variants in the viral transcripts.The pipeline includes 4 major modules: The first module allows to align and filter out human RNA sequences; the second module maps and count (remaining un-aligned) reads against reference genomes of all known and sequenced human viruses; the third module quantifies read counts at the individual viral genes level thus allowing for downstream differential expression analysis of viral genes between experimental and controls groups. The fourth module calls variants in these viruses. To the best of our knowledge, there are no publicly available pipelines or packages that would provide this type of complete analysis in one open source package.In this paper, we applied the viGEN pipeline to two case studies. We first demonstrate the working of our pipeline on a large public dataset, the TCGA cervical cancer cohort. We also performed additional in-depth analyses on a small focused study of TCGA liver cancer patients. In this cohort, we perform viral-gene quantification, viral-variant extraction and survival analysis. This allowed us to find differentially expressed viraltranscripts and viral-variants between the groups of patients, and connect them to clinical outcome.From our analyses, we show that we were able to successfully detect the human papilloma virus among the TCGA cervical cancer patients. We compared the viGEN pipeline with two metagenomics tools and demonstrate similar sensitivity/specificity. We . CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/099788 doi: bioRxiv preprint first posted online Jan. 11, 2017; 2 were also able to quantify viral-transcripts and extract viral-variants using the liver cancer dataset. The results presented corresponded with published literature in terms of rate of detection, viral gene expression patterns and impact of several known variants of HBV genome. Results also show novel information about distinct patterns of expression and co-expression in Hepatitis B and the Human Endogenous Retrovirus (HERV) K113 viruses.This pipeline is generalizable, and can be used to provide novel biological insights into the significance of viral and other microbial infections in complex diseases, tumorigeneses and cancer immunology. The source code, with example data and tutorial is available at: https://github.com/ICBI/viGEN/.

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Section: Comparing 'Dead' and 'Alive' Samples In The Hepb Subgroup Usmentioning

confidence: 72%

viGEN: An open source pipeline for the detection and quantification of viral RNA in human tumors

Bhuvaneshwar

Song

Madhavan

et al. 2017

Preprint

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“…Typically, loss of HBeAg is an indicator of recovery from acute Hepatitis B infection. Active viral replication could allow the virus to persist in infected cells, and increase the risk of disease (Tage-Jensen et al, 1985 ; Liang, 2009 ). So our results, showing that antigens HBeAg and HBcAg were overexpressed in dead patients compared to alive patients makes sense, indicating that these patients never recovered from acute infection.…”

Section: Discussionmentioning

confidence: 99%

viGEN: An Open Source Pipeline for the Detection and Quantification of Viral RNA in Human Tumors

et al. 2018

View full text Add to dashboard Cite

An estimated 17% of cancers worldwide are associated with infectious causes. The extent and biological significance of viral presence/infection in actual tumor samples is generally unknown but could be measured using human transcriptome (RNA-seq) data from tumor samples. We present an open source bioinformatics pipeline viGEN, which allows for not only the detection and quantification of viral RNA, but also variants in the viral transcripts. The pipeline includes 4 major modules: The first module aligns and filter out human RNA sequences; the second module maps and count (remaining un-aligned) reads against reference genomes of all known and sequenced human viruses; the third module quantifies read counts at the individual viral-gene level thus allowing for downstream differential expression analysis of viral genes between case and controls groups. The fourth module calls variants in these viruses. To the best of our knowledge, there are no publicly available pipelines or packages that would provide this type of complete analysis in one open source package. In this paper, we applied the viGEN pipeline to two case studies. We first demonstrate the working of our pipeline on a large public dataset, the TCGA cervical cancer cohort. In the second case study, we performed an in-depth analysis on a small focused study of TCGA liver cancer patients. In the latter cohort, we performed viral-gene quantification, viral-variant extraction and survival analysis. This allowed us to find differentially expressed viral-transcripts and viral-variants between the groups of patients, and connect them to clinical outcome. From our analyses, we show that we were able to successfully detect the human papilloma virus among the TCGA cervical cancer patients. We compared the viGEN pipeline with two metagenomics tools and demonstrate similar sensitivity/specificity. We were also able to quantify viral-transcripts and extract viral-variants using the liver cancer dataset. The results presented corresponded with published literature in terms of rate of detection, and impact of several known variants of HBV genome. This pipeline is generalizable, and can be used to provide novel biological insights into microbial infections in complex diseases and tumorigeneses. Our viral pipeline could be used in conjunction with additional type of immuno-oncology analysis based on RNA-seq data of host RNA for cancer immunology applications. The source code, with example data and tutorial is available at: https://github.com/ICBI/viGEN/.

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“…Reactivation of hepatitis B virus (HBV) replication and exacerbation of liver disease have been reported in patients with chronic hepatitis B administered immunosuppressive or cytotoxic therapy. [1][2][3] Reactivation of HBV replication may occur not only in patients with replicative HBV infection (hepatitis B e antigen positive and detectable serum HBV DNA by non-polymerase chain reaction [PCR] assay), but also in patients with low or nonreplicative infection (hepatitis B e antigen negative and undetectable serum HBV DNA by non-PCR assay) and those with resolved infection (hepatitis B surface antigen [HBsAg] negative, antibody to HBsAg positive, and antibody to hepatitis B core antigen positive). This is related to the persistence of HBV, albeit at low levels, in the liver and circulating blood and the presence of HBV DNA in extrahepatic reser-voirs, especially peripheral-blood mononuclear cells (PBMCs).…”

Section: Commentsmentioning

confidence: 99%

“…Alcohol-related liver disease accounts for up to 50% of the patients who die of end-stage liver disease. 1 Patients with alcoholic cirrhosis have posttransplantation survival rates similar to those for patients who undergo transplantation for non-alcohol-related liver disease. [2][3][4] However, relapse has been a significant concern in this population.…”

Section: Introductionmentioning

confidence: 99%

Does OKT3 increase the risk of recurrent hepatitis B in patients transplanted for hepatitis B?

Chu

Lok

2003

Liver Transpl

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The aim of this work was to analyze whether the treatment of acute rejection of orthotopic liver transplants (OLT), either with corticoids or OKT3, has any effect on levels of hepatitis B virus (HBV)-DNA and HbsAg in individuals which were originally affected by cirrhosis or fulminant hepatic failure as a result of B virus. We have found that HBV-DNA is present in macrophages, B cells and both CD4؉ and CD8؉ T cells after OLT in all cases studied. Interestingly, the levels of HBV-DNA and HbsAg in the serum analyzed were increased extremely rapidly in the patients treated with OKT3 in an acute rejection episode. However, the serum levels of HBV-DNA and HbsAg found were lower when the patients were treated with steroids, and were not found in non-treated patients. As the serum levels of HBV-DNA increase, the process of liver reinfection could be accelerated; therefore, these results may help to understand how OKT3 and corticoids immunosuppressive therapy may accelerate the reinfection of OLT by HBV. In conclusion, our results suggest that special care must be taken in the use of OKT3 in the treatment of acute liver rejection episodes in chronic or fulminant HBV transplanted patients.

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Immunosuppressive Treatment of Hbsag–Positive Chronic Liver Disease: Significance of Hbeag

Cited by 6 publications

References 13 publications

viGEN: An open source pipeline for the detection and quantification of viral RNA in human tumors

viGEN: An open source pipeline for the detection and quantification of viral RNA in human tumors

viGEN: An Open Source Pipeline for the Detection and Quantification of Viral RNA in Human Tumors

Does OKT3 increase the risk of recurrent hepatitis B in patients transplanted for hepatitis B?

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