Robert Calandra

Vaccination with the COVID-19 mRNA vaccine may do more than protect against the virus for patients with hepatitis B, according to a recently published article in the Japanese Society of Internal Medicine.

In the three cases documented by researchers, hepatitis B surface antigen (HBsAG) levels were reduced by more than 50% after Japan began its COVID-19 vaccination program. That is a significant, rapid, and uncommon decrease in HBsAG that is not easy to achieve, writes Yosuke Osawa, lead author of the paper. Indeed, the annual reduction rate with current therapies is less than one percent at 24 to 48 weeks of treatment.

“Although the involvement of vaccination in HBsAG reduction was not statistically proven, the results suggest that the administration of COVID-19 vaccines may have been involved in HBsAG reduction in patients with chronic hepatitis B,” Osawa writes.

In the first case cited by the paper, a 74-year-old Japanese woman had an HBsAG level of 64,521 when she was examined in 2019. She was treated with oral therapies and a year later her HBsAG dropped to 29,734. After receiving three mRNA COVID-19 vaccines, her HBsAG fell to 140.2.

The second patient, a 33-year-old Japanese man, saw his HBsAG levels scaled down from 13,234 in 2020, to 136.1, and finally to 3.7 after receiving a total of three mRNA vaccine injections.

The third case was a 67-year-old Japanese woman who presented with an HBsAG level of 17,722.3 in 2020. She received two injections of the BNT162h2 vaccine. The third was an mRNA vaccine. After 707 days, her HBsAG levels dropped to 152.2.

Rapidly declining HBsAG values are uncommon, Osawa writes. The COVID-19 vaccines appeared to be the reason behind the swiftly dropping HBsAG numbers experienced by the three patients. The team then began comparing the number of patients in their hospital who experienced rapid reduction in HBsAG before and after the initiation of Japan’s vaccine program.

It found that an HBsAG reduction of greater than 50% before the vaccination program happened in just three patients compared to 11 patients in the post-vaccination program period. The difference, Osawa writes, was “statistically significant.”

The group issued questionnaries to the 11 patients who had a greater than 50% reduction in their numbers and to 45 patients who experienced a 10% decrease or an increase in their HBsAG levels. The results found that 10 patients (100%) in the reduction group had been injected with the COVID-19 vaccine before their last HBsAG measurement during the post-vaccination program period.

In contrast, the paper reports, 29 patients (78.4%) had received the vaccine while 8 (21.6%) had not received the vaccine before their last measurement.

While noting that the results are not statistically significant, the findings do suggest that COVID-19 vaccines “may be involved in HBsAG reduction” and that it is reasonable to conclude that COVID vaccines have antiviral activity against hepatitis B.

“In conclusion, the number of patients whose HBsAG level was reduced by 50% or greater per year during the post-vaccination program period was larger than that during the pre-vaccination-program period,” Osawa writes. “Thus, COVID-19 vaccines may be involved in HBsAG reduction. However, large-scale studies will be required to address this issue.”

This article originally appeared on Managed Healthcare Executive.

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In the 3 cases documented by researchers, hepatitis B surface antigen (HBsAG) levels were reduced by more than 50% after Japan began its COVID-19 vaccination program.

Does the COVID-19 Vaccine Help Hepatitis B Patients?

With the surge in the development of drugs for hepatitis B over the last few years, researchers from the Institute of Hepatology Foundation for Liver Research at King’s College London recently published a comprehensive overview of the therapeutics being evaluated.

Chronic hepatitis B viral infection remains one the biggest threats to global public health, with 296 million chronically infected people worldwide, according to a 2019 report from the World Health Organization. The WHO estimates that 1.5 million people are newly infected each year. Around the world, an estimated 820,000 people die each year from hepatitis B and related complications.

The goal of current hepatitis B therapies is to suppress viral replication to reduce liver damage and improve the patient survival rate, noted 

 late last year. But advances in hepatitis research, the success of curative antiviral treatments for chronic hepatitis C and promising compounds undergoing clinical evaluation, offer hope for new and better treatments for patients with chronic hepatitis B.

The hepatitis B drugs in development have introduced many novel therapies aimed at multiple targets that have shown “profound” antiviral properties, moving researchers closer to a functional cure, which Phillips, Jagatia and Chokshi say is characterized by a sustained undetectable viraemia with a durable loss of hepatitis surface antigen (HBsAg) with or without seroconversion to HBsAg antibody. Functional cure is associated with an end to liver injury, they said, and with a decrease in the risk of developing hepatocellular carcinoma.

Here is a rundown on some of the promising research highlighted by Phillips, Jagatia and Chokshi

Clinical trials are underway of direct-acting antivirals that could target and disrupt different steps of the HBV life cycle. Those therapeutics could lead to a functional cure, that is, liver injury is resolved, and the risk of cancer decreased to the point of viral clearance.

Researchers are making headway with new and different classes of core protein allosteric modulators, which change a receptor’s response to a stimulator. These core proteins would be used individually or in combination with other drugs.

Therapies that target HBV mRNA are in early stages of development. One approach would inhibit all five HBV mRNA transcripts with a single molecule by degrading mRNA or suppressing their translation thus limiting HBV protein production.

Host targeting therapies would act on the host factors implicated in the HBV replicative cycle rather than acting directly on HBV. The method, however, requires rigorous testing for toxic events.

A recently identified liver-specific bile acid transporter that acts as a host entry factor for HBV, has opened another possible avenue for blocking and reducing viral spread. But because it does not directly attack or deplete viruses in the cell nucleus, it would most likely be used in tandem with other therapies.

Host proteins called cyclophilins are implicated in the HBV life cycle. The effect of antiviral blocking of cyclophilins has been confirmed in experiments in-vitro and in mice. A second generation of cyclophilin inhibitors is currently being studied.

The review paper concludes that, given the complexity of HBV’s replication life cycle and other factors, the, the pathway to a cure will likely involve combinational therapies and agents with specific modes of action. The good news is that pharmaceutical companies across the globe are working together to find a cure for HBV.

“It is clear that significant challenges remain,” concluded Phillips, Jagatia and Chokshi, “but for the first time in 20 years, there is renewed hope that a cure for CHB (chronic hepatitis B) is in sight.”

This article originally appeared in Managed Healthcare Executive.

A trio of leading hepatitis researchers survey the treatments in development for chronic hepatitis B. They end on a high note: That for the first time in 20 years, a cure is in sight.