Newest Hep B studies - December 2021 edition

Dear all,

The hepatitis B foundation has started a new initiative where they have invited some emerging scholars in the field (full disclosure: I am one of these) to suggest newly published studies that they think are most impactful or significant. This will be updated monthly and can be accessed here:

I thought that the community here might be interested in what the newest happenings are in the research space. This month we have the following top picks (the full list can be found through the URL above)

Basic Science Pick(s) of the month

Álvarez EG, Demeulemeester J, Otero P, Jolly C, García-Souto D, Pequeño-Valtierra A, Zamora J, Tojo M, Temes J, Baez-Ortega A, Rodriguez-Martin B, Oitaben A, Bruzos AL, Martínez-Fernández M, Haase K, Zumalave S, Abal R, Rodríguez-Castro J, Rodriguez-Casanova A, Diaz-Lagares A, Li Y, Raine KM, Butler AP, Otero I, Ono A, Aikata H, Chayama K, Ueno M, Hayami S, Yamaue H, Maejima K, Blanco MG, Forns X, Rivas C, Ruiz-Bañobre J, Pérez-Del-Pulgar S, Torres-Ruiz R, Rodriguez-Perales S, Garaigorta U, Campbell PJ, Nakagawa H, Van Loo P, Tubio JMC.
Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture.
Nature Communications 2021 Nov 25;12(1):6910. doi: 10.1038/s41467-021-26805-8. PMID: 34824211; PMCID: PMC8617174 Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture | Nature Communications

This paper talks about HBV DNA integrations: this is when the virus DNA jumps into the cell’s DNA. This paper is showing that when the virus integrates, it can change the structure of the cell’s DNA structure in a way that could induce cancer. This is important to show exactly how the virus causes liver cancer, and so we can come up with ways to prevent it.

Wang Y, Li Y, Zai W, Hu K, Zhu Y, Deng Q, Wu M, Li Y, Chen J, Yuan Z.
Hepatitis B Virus cccDNA Minichromosomes in Distinct Epigenetic Transcriptional States Differ in Their Vulnerability to Damage.
Hepatology 2021 Nov 15. doi: 10.1002/hep.32245. Epub ahead of print. PMID: 34779008. DOI: 10.1002/hep.32245 HBV covalently closed circular DNA minichromosomes in distinct epigenetic transcriptional states differ in their vulnerability to damage - PubMed

This paper is about how cccDNA is actually pretty diverse: for example, there are active forms and non-active forms. This paper is suggesting that inactive forms are more resistant to new potential therapies (e.g. CRISPR). These results lets us understand how we can improve potential HBV cures.

Clinical Science Pick(s) of the month

Hirode, Grishma, et al.
Off-therapy response after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B: An international, multi-center, multi-ethnic cohort (RETRACT-B study).
Gastroenterology (2021).

This study is trying to address a big question in the field: are there some people who can stop their antiviral treatment and become HBs-negative (functional cure). Here they found that if 1) HBV DNA was undetectable; 2) they were HBeAg-negative; and 3) HBs levels are below 100 (or below 1000 in Caucasian people) their chances of HBsAg loss is higher. But the rates were still low (~3% per year) and people still needed to be under monitoring to make sure they were safe.

Liu S, Deng R, Zhou B, Liang X, Liu Z, Peng J, Chen J, Zhou Y, Guo Y, Chen Y, Li W, Shen S, Lu X, Zhao S, Liao X, Liang H, Lan Y, Hou J, Fan R, Sun J.
Association of serum hepatitis B virus RNA with hepatocellular carcinoma risk in chronic hepatitis B patients under nucleos(t)ide analogues therapy
Journal of Infectious Diseases 2021 Dec 21:jiab597. doi: 10.1093/infdis/jiab597. Online ahead of print. PMID: 34931674.
Association of serum hepatitis B virus RNA with hepatocellular carcinoma risk in chronic hepatitis B patients under nucleos(t)ide analogues therapy - PubMed

This paper is studying the role of a new blood test that might be able to predict liver cancer. They found that high levels of HBV RNA (different from DNA) was associated with greater risk of liver cancer, though this was not in and of itself predictive (i.e. just because you have high levels doesn’t mean you definitely have cancer). These results suggest that this new test could be used in conjugation with others to get a better idea about who might need more monitoring for cancer (though more work has to be done).

Public Health Pick(s) of the month

He WQ, Guo GN, Li C. The impact of hepatitis B vaccination in United States, 1999‐2018.
Hepatology 2021 Dec 2

This study looked in detail about something we’ve known for a while: Hep B vaccines work and save lives. Here, the authors look at death rates among those who have been vaccinated vs. those who haven’t. They show that all-cause mortality and cancer-related mortality are significantly reduced in people who have been vaccinated.

Périères L, Diallo A, Marcellin F, Nishimwe ML, Ba EH, Coste M, Lo G, Halfon P, Touré Kane C, Maradan G, Carrieri P, Diouf A, Shimakawa Y, Sokhna C, Boyer S; ANRS 12356 AmBASS Survey Study Group.
Hepatitis B in Senegal: A Successful Infant Vaccination Program but Urgent Need to Scale Up Screening and Treatment (ANRS 12356 AmBASS survey).
Hepatology Communications 2021 Dec 17. doi: 10.1002/hep4.1879. Online ahead of print.

This study looked at how well the vaccine works at preventing Hep B infection and the success in infant vaccination. Long story short, the vaccines work and we need to expand the infant vaccination program so that everyone can benefit and fewer people get chronic infections.

Hope this might be useful for some of you!