Newest Hep B studies - January 2022 edition

A new batch for this month put up here: https://www.hepb.org/news-and-events/reports/journal-articles-recommended-by-emerging-scholars/

Translational Science

Hsu YC, Suri V, Nguyen MH, Huang YT, Chen CY, Chang IW, Tseng CH, Wu CY, Lin JT, Pan DZ, Gaggar A, Podlaha O.

Inhibition of Viral Replication Reduces Transcriptionally Active Distinct Hepatitis B Virus Integrations with Implications on Host Gene Dysregulation.

Gastroenterology 2022;S0016-5085(22)00006-3. doi:10.1053/j.gastro.2021.12.286.

Inhibition of Viral Replication Reduces Transcriptionally Active Distinct Hepatitis B Virus Integrations With Implications on Host Gene Dysregulation - ScienceDirect

This study shows that integrated HBV DNA (which is associated with liver cancer) can be reduced if people are given antivirals. Very interesting study because it means that we can reduce cancer risk not only by lowering inflammation, but also by this mechanism.

Alex S. Genshaft, Sonu Subudhi, Arlin Keo, Juan D. Sanchez Vasquez, Nádia Conceição-Neto, Deeqa Mahamed, Lauke L. Boeijen, Nadia Alatrakchi, Chris Oetheimer, Mike Vilme, Riley Drake, Ira Fleming, Nancy Tran, Constantine Tzouanas, Jasmin Joseph-Chazan, Martin Arreola Villanueva, Harmen J. G. van de Werken, Gertine W. van Oord, Zwier M.A. Groothuismink, Boris J. Beudeker, Zgjim Osmani, Shirin Nkongolo, Aman Mehrotra, Jordan Feld, Raymond T. Chung, Robert J. de Knegt, Harry L. A. Janssen, Jeroen Aerssens, Jacques Bollekens, Nir Hacohen, Georg M. Lauer, Andre Boonstra, Alex K. Shalek, Adam Gehring.

Clinical implementation of single-cell RNA sequencing using liver fine needle aspirate tissue sampling and centralized processing captures compartment specific immuno-diversity.

Biorxiv Jan 2022. doi: https://doi.org/10.1101/2021.11.30.470634

Really high-tech analysis of liver tissue from people with hepatitis B infection. Basically most studies look at a large batch of tissue, blend it up like a smoothie, and see if that’s different from a smoothie from someone else who had different clinical outcomes. This group is showing how separate the ingredients of that smoothie and analyse each of them separately (on a single cell level) to see what is contributing to the disease.

Clinical Science

Hu HH, Jeng WJ, Pan MH, Luo WS, Chang CL, Huang YT, Su CY, Chiang CT, Jen CL, Chien YC, Lu SN, Wang LY, Huang LR, Lee MH, Liu J, Nguyen MH, Chen CJ, Yang HI.

Serum soluble programmed cell death 1 levels predict spontaneous functional cure in inactive carriers with chronic hepatitis B.

Alimentary Pharmacology & Therapeutics 2022 Jan 14.

Serum soluble programmed cell death 1 levels predict spontaneous functional cure in inactive carriers with chronic hepatitis B - PubMed Epub ahead of print. PMID: 35032052.

There are some people with chronic HBV infection who can clear their infection. This group has shown that if a particular protein is lower in their blood, they are more likely to clear the infection. This is a protein that the immune system uses to quieten down inflammation, so this possibly lets us know something about how the virus is maintained in the body.

Public Health

Lempp FA, Roggenbach I, Nkongolo S, Sakin V, Schlund F, Schnitzler P, Wedemeyer H, Le Gal F, Gordien E, Yurdaydin C, Urban S.

A Rapid Point-of-Care Test for the Serodiagnosis of Hepatitis Delta Virus Infection.

Viruses . 2021 Nov 26;13(12):2371. doi: 10.3390/v13122371. PMID: 34960640; PMCID: PMC8703323

A Rapid Point-of-Care Test for the Serodiagnosis of Hepatitis Delta Virus Infection - PubMed

This is from the group that I used to work with in Germany. They have developed a new rapid test for Hepatitis Delta (similar to Rapid antigen tests for SARSCov2), basically making it very easy to diagnose people on a large scale. It has a big potential to diagnose people everywhere with Delta and try to get them into appropriate clinical care.

Su S, Wong WC, Zou Z, Cheng DD, Ong JJ, Chan P, Ji F, Yuen MF, Zhuang G, Seto WK, Zhang L.

Cost-effectiveness of universal screening for chronic hepatitis B virus infection in China: an economic evaluation.

Lancet Global Health . 2022 Feb;10(2):e278-e287. doi: 10.1016/S2214-109X(21)00517-9. PMID: 35063115

Cost-effectiveness of universal screening for chronic hepatitis B virus infection in China: an economic evaluation - ScienceDirect

This paper does a whole lot of modelling to show that we should be screening everyone in China because it will actually save them money. By diagnosing people early and preventing liver disease, people take up fewer medical resources and that more than offsets the costs for screening.

Basic Science

Svicher V, Salpini R, Piermatteo L, Carioti L, Battisti A, Colagrossi L, Scutari R, Surdo M, Cacciafesta V, Nuccitelli A, Hansi N, Ceccherini Silberstein F, Perno CF, Gill US, Kennedy

Whole exome HBV DNA integration is independent of the intrahepatic HBV reservoir in HBeAg-negative chronic hepatitis B

Gut 2021 Dec;70(12):2337-2348.

https://gut.bmj.com/content/70/12/2337

As I mentioned above, there is an integrated form of the virus that is associated with cancer. So it would be great if there was a specific marker for it. What this group show is that we can’t use the other forms of the virus (e.g. cccDNA) to infer how much integrated DNA there is.

Michelet M, Alfaiate D, Chardès B, Salvetti A, Durantel D, Lucifora J. Inducers of NF-κB pathways impair hepatitis delta virus replication and strongly decrease progeny infectivity in vitro.

JHEP Reports 2021 (in press).

https://doi.org/10.1016/j.jhepr.2021.100415 - https://www.jhep-reports.eu/article/S2589-5559(21)00191-9/fulltext

Because there aren’t many effective therapies for HDV, we want to know about what we can do to suppress the virus. This group has shown that a group of drugs that target the same cellular signal can really suppress HDV replication. More like HCV than HBV, the HDV genome isn’t super stable, so dampening the replication could have a big clinical impact.

Pal S, Dey D, Chakraborty BC, Nandi M, Khatun M, Banerjee S, Santra A, Ghosh R, Ahammed SM, Chowdhury A, Datta S.

Diverse facets of MDSC in different phases of chronic HBV infection: impact on HBV specific T cell response and homing.

Hepatology . 2022 Jan 9. doi: 10.1002/hep.32331. Online ahead of print. PMID: 35000202

https://aasldpubs.onlinelibrary.wiley.com/doi/abs/10.1002/hep.32331

I won’t comment much on this paper because I’m not an immunologist and this stuff is pretty confusing for me. Perhaps there are some other @ScienceExperts that give a better summary of this study.

TT

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