In this video, Lauren Yang, MD, discusses what learned at the recent American Association for the Study of Liver Diseases annual meeting about research into managing hepatitis B. 

Lauren Yang, MD, is a clinical fellow in transplant hepatology at Beth Israel Deaconess Medical Center in Boston.

My name is Lauren Yang, and I'm the clinical fellow in transplant hepatology at Beth Israel Deaconess Medical Center this year. I want to share some of the exciting things I heard about hepatitis B this year at the digital AASLD meeting.

There are four big things I took home. The first was about changing chronic hepatitis B populations and how certain comorbidities factor into how we think about our patients.

Dr. Mindie Nguyen at Stanford discussed her research showing that hepatitis B patients all over the world are increasingly older and more comorbid. They have higher rates of CKD, hypertension, diabetes, and bone disease than in the past.

You can probably see where I'm going with this. The increasing evidence of metabolic comorbidities raises the question about how fatty liver and NASH will interact with chronic hepatitis B.

She looked into this and reported that not too surprisingly when patients have chronic hepatitis B with advanced fibrosis with coexistent NASH, they're more likely to experience liver decompensations.

A related finding that was slightly more surprising was that fatty liver as seen on imaging was not necessarily related to worst outcomes. This is good because up to a third of patients who have hepatitis B also have fatty liver on imaging. It suggests that simple fatty liver may not be so bad for our patients, but it is important to know when they have inflammation related to steatohepatitis.

She also looked at populations in the US, Japan, and Korea and noted a trend over the last decade towards older age. Between this, and the chronic kidney disease, and bone disease trends, it suggested to me that we're going to have an even stronger preference for tenofovir alafenamide in the future than we already have because of its favorable side-effect profile.

This brings me to the second big thing I learned, which was also about tenofovir alafenamide. Calvin Pan reported on a retrospective analysis of the safety and efficacy of this new formulation in pregnancy.

The news is good, in that it appears very effective when tested in expecting mothers with high viral loads, and that there were no concerning signs or signals that the infants have worse outcomes. Kim Lee Zhang offered similar findings through a prospective study on the topic.

The third topic I learned a lot about was about withdrawing antiviral therapy. I felt like this topic was everywhere I looked this year. Dr. Anna Loch in the postgrad course covered some of the details. Dr. Norah Terrault and many more in parallel sessions also talked about it.

There wasn't much to say at the conference about starting therapy. It seems everyone agrees the AASLD practice guideline update from 2018 was still more or less the standard and consistent with EASL and the Asian Pacific Society as well, but there's a lot of withdrawal studies trying to figure out how we can move beyond these guidelines.

You can tell it's a hot topic because the 3 big societies have different recommendations. For e-antigen positive patients without cirrhosis, there's more or less agreement between the 3 societies that you should continue until seroconversion and at least 1 to 3 years of consolidation therapy before considering withdrawal.

However, in the e-antigen negative patients with cirrhosis, there's more discrepancy. They recommend treatment until the viral load is suppressed, and ideally, s-antigen is lost, but the majority of patients won't seroconvert on nucleotide/nucleoside analog therapy, meaning that treatment will be lifelong.

There is more evidence that patients seroconvert at a higher rate after you withdraw therapy, but this potential benefit of being able to stop a daily pill, daily medication has to be balanced with the fact that about 35% of them will experience a flare, at least by ALT value.

The majority can be controlled again by restarting therapy, but it's one of those things that we're still not sure exactly where the narrow path in between these risks and benefits is.

I feel like I should be clear in saying that most of the experts recommend against stopping therapy in patients with cirrhosis or when there's viral resistance concerns. You have to have a patient who's onboard, reliable, and willing to undergo frequent monitoring for signs of  a flare.

In patients who may be appropriate, some factors that Dr.Terrault identified that may suggest a better chance at sustained response include being younger at the time of seroconversion, having a longer duration of consolidation therapy, and having undetectable hepatitis B viral DNA at the end of treatment right before you withdraw.

I think as we gain more experience with this, we'll see protocolized guidance in future years about when, and who, and how to withdraw the antiviral therapy. For now, it seems like this is mostly in the wheelhouse of people who specialize in hepatitis B or liver disease in general.

The fourth take-home for me was about future directions. Nothing seems ready for prime time yet, but a lot of basic and translational research has been done to decode the life cycle of hepatitis B.

As you know, it's been hard to find a cure for hepatitis B because of the cccDNA, which stands for covalently closed circular DNA, as well as the integrated DNA. Many are optimistic that creating a treatment regimen through a combination of methods may lead to a functional cure in the future.

There are ongoing clinical trials using the nucleotide/nucleoside analogs in conjunction with RNA interference, capsid assembly modulators, nucleic acid polymers, interferon, and immunomodulation through medication or vaccinations. This still seemed like it was many years away from general practice, but something to keep your eye out for.

Those 4 things were my big take-homes from the meeting this year about hepatitis B. I have to say every time I learn more about it, I appreciate that this remains a very nuanced topic, and there are so many frontiers for future research. I hope that you find these points interesting. Thank you for watching.