Following the clear successes in treating Hepatitis C, which were achieved in about 95% of cases using a unique class of antiviral drugs operating with the "Functional Cure" approach, the field of hepatology continues its efforts, with a great deal of hope, to achieve similar successes in treating Hepatitis B using the same therapeutic approach.

In fact, numerous research initiatives are underway to find a "Functional Cure" (as will be explained) for Hepatitis B. Among the most significant are reports on the commencement of "Phase 3 Clinical Trials" to establish the efficacy and safety of an antiviral medication known as "Bepirovirsen," aimed at achieving a "functional" overcoming of the Hepatitis B virus. This is for the treatment of individuals with "Chronic Viral Hepatitis B" in order to "neutralize the virus's activity" in their bodies. The two trials are named "B Well-1" and "B Well-2."

It is well-known that "stages" of clinical trials play a crucial role in the development of any type of treatment for human diseases, to confirm its efficacy and safety before obtaining global health authorities' approval for therapeutic use.

Chronic Viral Infection

Chronic Hepatitis B Infection remains a significant burden on public health worldwide. The World Health Organization states that "Hepatitis B is a major global health issue. In 2019, an estimated 296 million people were living with chronic Hepatitis B infection. There are approximately 1.5 million new cases every year worldwide. Hepatitis B caused about 820,000 deaths in 2019, the majority of which were due to liver cirrhosis and hepatocellular carcinoma."

A scientific review by researchers from the United States, Taiwan, and Singapore, titled "The Global Burden of Hepatitis B: Current Status, Lost Opportunities, and a Call to Action," published in the April 2021 issue of "Nature Reviews Gastroenterology & Hepatology," reported that Hepatitis B virus is the primary cause of liver cirrhosis and cancer globally. Furthermore, Hepatitis B-related liver cancer deaths increased between 2010 and 2019, with Hepatitis B still suffering from a significant lack of diagnosis and effective measures to prevent infection and disease progression. The researchers also noted, "Global annual deaths caused by Hepatitis B are expected to increase by 39% from 2015 to 2030 if the current situation continues."

Preventive Vaccine

The Hepatitis B Virus (HBV) Vaccine has been a significant step forward in humanity's quest to prevent this viral infection and its complications in infected individuals and to mitigate its material, social, and psychological ramifications at the public health level. The World Health Organization says, "Hepatitis B can be prevented with safe and effective vaccines. The vaccine is typically administered shortly after birth, followed by booster doses after a few weeks. The vaccine prevents infection with the virus in almost 100% of cases."

Examples of the vaccine's success include medical statistics from various regions of the world that show a decrease in infection rates. For instance, medical statistics from the United States indicate that Acute Hepatitis B Infections declined by 82% between 1991, when vaccination for infants was first recommended, and 2009.

However, despite the availability of a safe and effective vaccine, no therapeutic regimen has been established to induce a "Functional Cure." What is promising is that many of these novel therapeutic approaches are currently under development, referred to by researchers as "Functional Cure."

Functional Cure

Experts in hepatology define the "Functional Cure for the Hepatitis B Virus" as achieving three things:

1. Permanent clearance of the "Hepatitis B Surface Antigen (HBsAg)" from the blood, meaning the absence of "Hepatitis B Virus DNA" (the complete virus) or the viral capsid protein upon blood examination.

2. Maintaining long-term virus suppression and reducing the risk of liver cancer, even after stopping treatment once the required duration is complete.

3. Completing all of this success through a limited time frame of treatment.

That is, "Functional Cure" means taking medication for a limited time, not for many years, and achieving complete neutralization of the virus's disease activity.

What has paved the way for this step, which the field of hepatology greatly relies on to be a decisive therapeutic advance, is the development of a precise approach by researchers to study "Chronic Viral Hepatitis B" in the laboratory, allowing for a better understanding of many of the virus's behaviors and characteristics during an important part of its life cycle.

Researchers have noted that the Hepatitis B virus is classified among DNA viruses, yet its genome goes through an RNA intermediary during the viral replication process. Researchers are "exploiting" this feature in the virus's life cycle by initiating the replication of the Hepatitis B virus genome using RNA. This approach has excellent characteristics concerning the "Signal-To-Noise Ratio."

For clarity, "Signal-To-Noise Ratio" is an "indicator" that refers to the ability of a particular signal to be apparent and clear despite the presence of "noise" in the background. If the "signal" strength is greater than the "noise," then the noise disruption does not affect the success of that signal in appearing. One practical application in the field of drug production is that it allows researchers to identify and measure "Drug Resistant Variants" among people. "Monitoring drug resistance and addressing this obstacle" is a crucial element in the development of antiviral therapies, and hence, this approach may be beneficial for treatment efforts. Researchers also believe that this method may be helpful for early stages of drug discovery.

Achieving functional cure success mirrors what naturally occurs in an infected individual whose immune system has overcome the viral infection, thus eliminating the possibility of developing liver cancer.

"Bepirovirsen" represents a very promising treatment being developed to treat Hepatitis B, an experimental antiviral designed to prevent the production of viral proteins associated with the infection and propagation of this virus. By reducing Hepatitis B virus replication and suppressing viral antigens simultaneously, the treatment is hoped to stimulate the innate immune response and become a functional cure for patients.

Hepatitis B Varied Symptoms and Clinical Pathways

Mayo Clinic hepatologists point out that "symptoms of Hepatitis B range from mild to severe. They typically appear within about one to four months after infection, but patients may also feel them as early as the second week following the infection." They add that initial signs and symptoms of Hepatitis B may include:

- Abdominal pain.
- Dark urine.
- Fever.
- Joint pain.
- Loss of appetite.
- Nausea and vomiting.
- Weakness and fatigue.
- Yellowing of the skin and whites of the eyes, also known as jaundice.

Regarding the clinical course, Mayo Clinic doctors explain that Hepatitis B generally follows one of two paths: The first is the "Acute Hepatitis B Infection," where the Hepatitis B infection is short-lived. The other is "Chronic Hepatitis B Infection," where the Hepatitis B infection persists for a long chronic period, with most cases never fully clearing the infection.

They explain, "Acute Hepatitis B infection lasts for less than six months. Your immune system is likely to clear acute Hepatitis B from your body, and you should recover completely within a few months. Most adults who get Hepatitis B experience an acute infection, but it can lead to chronic infection." On the other hand, they say, "Chronic Hepatitis B infection lasts six months or longer. It persists because your immune system can't fight the infection. Chronic Hepatitis B infection could last for life, potentially leading to serious illnesses like cirrhosis and liver cancer. Some individuals with chronic Hepatitis B never develop symptoms. Chronic inflammation may go undetected for decades until a person becomes seriously ill due to liver disease. Some may experience persistent fatigue and mild symptoms of acute hepatitis."

About 300 million people worldwide are infected with chronic viral Hepatitis B

Treating Hepatitis B Viral Infection Current Aspirations Unfulfilled

The World Health Organization summarizes the reality of treating Hepatitis B cases by saying, "There is no specific treatment for acute Hepatitis B. Chronic Hepatitis B infection can be treated with medications. The care of those with acute Hepatitis B should focus on maintaining patient comfort. Patients should follow a healthy diet and drink plenty of fluids to prevent dehydration from vomiting and diarrhea."

The organization adds, "Chronic Hepatitis B infection can be treated with oral drugs, including Tenofovir or Entecavir." However, it clarifies that "the treatment is capable of the following:

- Slowing down the progression of cirrhosis of the liver.
- Reducing the incidence of liver cancer.
- Enhancing the long-term survival of patients."

That is, it does not remove the virus and its disease effects from the body, unlike current treatments available for the Hepatitis C virus.

They also add, "Most people who start taking medication for Hepatitis B will need to continue for life."

The organization also notes, "It is estimated that treatment will be necessary for between 12% and 25% of those with chronic Hepatitis B depending on the context and eligibility criteria. The 2023 update of WHO's guidelines on the treatment of Hepatitis B will expand eligibility for treatment and increase the number of people receiving it."