Hepatitis B: what it is and how to prevent it

The hepatitis B virus causes a potentially fatal liver infection known as hepatitis B. (HBV). The infection can range from a moderate, transient illness lasting a few weeks to a severe, chronic condition that can persist for many years, leading to complications including cirrhosis, liver failure, and hepatocellular carcinoma. This article examines all aspects of hepatitis B, including its virology, epidemiology, clinical characteristics, diagnosis, treatment, and prevention.

1. Hepatitis B Virus: Structure and Classification

The hepatitis B virus (HBV) is a compact DNA virus with an envelope that belongs to the Hepadnaviridae family. The DNA genome of the virus is approximately 3,200 kilobases in length and is partially double-stranded. Due to its replication strategy, which entails reverse transcription of an RNA intermediate, HBV is unique among human DNA viruses.

Large (L), middle (M), and small (S) surface antigens (HBsAg) are present on the viral envelope. (S). The nucleocapsid, which is composed of the core antigen (HBcAg) and the viral DNA, is located at the center of the virus. The HBV genome encodes additional proteins, such as polymerase, X protein, and e antigen. (HBeAg).

2. Epidemiology and Pathogenesis OF Hepaitis B

An estimated 257 million individuals live with chronic HBV infection, making hepatitis B a worldwide public health concern. The prevalence of HBV infection varies significantly across regions, with high endemicity in sub-Saharan Africa, East Asia, and the Pacific Islands and minimal endemicity in North America, Western Europe, and Australia.

HBV is transmitted through contact with blood or other physiological fluids containing the virus. Common transmission routes include:

Mother-to-child transmission (perinatal): In areas of high endemicity, mother-to-child transmission (perinatal) is the most common route of infection.
Sexual transmission: intercourse with an infected partner without protection
Percutaneous exposure: Sharing needles, syringes, or other drug injection equipment can result in percutaneous exposure.
Healthcare-associated transmission:Needlestick injuries, insufficient sterilization of medical apparatus, and transfusion of contaminated blood products are examples of healthcare-associated transmission.
Household transmission:Sharing intimate items such as razors or toothbrushes with an infected individual constitutes household transmission.

3. Factors of risk and populations at risk

Certain populations and factors increase the likelihood of contracting hepatitis B, including:

• Infants born to mothers contaminated with HBV
• Sexual companions of those afflicted with HBV
• Men who engage in sexual relations with other men (MSM)
• Injection substance consumers
• Workers in the healthcare industry who are exposed to blood or physiological secretions in the course of their duties are at risk for contracting hepati
• People who have had multiple sexual partners or who have a history of sexually transmitted infections
• Travelers to regions with a high prevalence of HBV
• Blood transfusion, organ transplant, and hemodialysis recipients
  individuals living with HIV

4. Pathobiology and Immunity

HBV travels to the liver after entering the bloodstream, where it infects hepatocytes, the primary liver cells. The virus replicates within hepatocytes, resulting in the discharge of new viral particles that can infect other hepatocytes.

The immune response of the host is essential for controlling HBV infection and determining the clinical outcome. Initial control of viral replication is facilitated in part by the innate immune response, which includes the production of interferons and activation of natural killer cells. The adaptive immune response, comprised of HBV-specific T cells and B cells, is essential for viral clearance and protection from reinfection. However, a prolonged or excessive immune response can also contribute to liver injury and disease progression.

5. Characteristics and Complications

The average incubation period for hepatitis B is 90 days, ranging from 45 to 160 days. The disease’s clinical trajectory can be divided into two categories:

• Acute hepatitis B : self-limiting infection with symptoms including fatigue, nausea, vomiting, abdominal pain, jaundice, dark urine, and pallid feces that lasts a few weeks to a few months. The vast majority of adults with HBV infection will eliminate the virus and develop immunity.
• Chronic hepatitis B : an infection that lasts longer than six months and is typically caused by exposure to the virus in infancy or early childhood. Chronic hepatitis B can be asymptomatic or manifest with vague symptoms, but over time it can lead to complications. The risk of developing chronic hepatitis B varies with the age of infection, with a higher risk among those contaminated at birth or in early infancy.

Based on the presence or absence of HBeAg, viral load, and the degree of liver inflammation, chronic hepatitis B can be further subdivided into the following phases:

• Immunotolerant phase: marked by high viral replication, HBeAg positivity, and low hepatic inflammation. This phase is more prevalent in individuals infected at birth or during early childhood, and it can last for several years or even decades without causing significant liver harm or symptomatology.
• Immune-active phase: characterized by a decline in viral replication, HBeAg seroconversion (loss of HBeAg and development of anti-HBe antibodies), increased liver inflammation, and the possibility of liver injury. In a subset of individuals, this phase can progress to the development of cirrhosis or hepatocellular carcinoma.
• Inactive carrier state: Low or undetectable viral replication, HBeAg negativity, and minimal liver inflammation characterize the inactive carrier state. Individuals in this phase have a lower risk of developing liver complications, but they may still develop cirrhosis or hepatocellular carcinoma over time, especially if they already have liver injury.
• Reactivation phase: occurs in some patients with a resurgence of viral replication, HBeAg reversion, and increased liver inflammation. This phase is linked to an increased risk of liver complications and can be precipitated by immunosuppression or coinfection with other hepatotropic viruses.

Among the complications of chronic hepatitis B are:

• Cirrhosis: Cirrhosis is the scarring of liver tissue, which can impair liver function and result in portal hypertension, ascites, and esophageal varices.
• Hepatocellular carcinoma: a primary liver malignancy resulting from chronic liver injury and inflammation.
• Liver failure: a life-threatening condition characterized by the liver’s inability to execute its essential functions.
• Extrahepatic manifestations:  Less frequent complications that can affect other organs and systems, including glomerulonephritis, polyarteritis nodosa, and peripheral neuropathy.

6.Diagnosis and Differential Diagnosis

Hepatitis B is diagnosed through the detection of specific antigens and antibodies in the blood. Key diagnostic indicators consist of:

• HBsAg: The presence of HBsAg indicates an active HBV infection.
• Anti-HBs: the presence of these antibodies indicates HBV immunity, either from a previous infection or vaccination.
• HBeAg and anti-HBe: the presence of HBeAg indicates a high level of viral replication, whereas anti-HBe suggests a lower level of viral replication.
• HBV DNA: the presence of viral DNA in the blood indicates ongoing viral replication and can be used to monitor disease activity and treatment response.
  

For assessing liver inflammation and injury, liver function tests, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are also essential.

Other causes of hepatitis, such as hepatitis A, C, D, and E, as well as non-viral causes such as alcoholic hepatitis, drug-induced liver injury, autoimmune hepatitis, and metabolic liver diseases, should be considered during differential diagnosis.

7. Management and Treatment

The objectives of hepatitis B treatment are to inhibit viral replication, reduce liver inflammation and fibrosis, and prevent complications including cirrhosis and hepatocellular carcinoma. Options for treatment include:

• Antiviral medications:  Nucleos(t)ide analogs, including entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide, which inhibit HBV replication by targeting the viral polymerase. These drugs are generally well tolerated and can result in long-term viral suppression and improvement in liver histology.
• Interferon therapy: pegylated interferon-alpha is an immunomodulatory agent administered subcutaneously that can be used to treat hepatitis B, especially in patients with HBeAg-positive disease. Interferon therapy is utilized less frequently due to its adverse effects and frequent injection requirements.
  Individualized treatment decisions should be based on disease stage, viral burden, liver inflammation, and the presence of cirrhosis or hepatocellular cancer. Individuals with end-stage liver disease or hepatocellular carcinoma may contemplate liver transplantation in certain circumstances.

8. Protection and Immunization

Prevention of hepatitis B infection is an essential component of global disease burden reduction strategies. Key preventive measures consist of:

• Vaccination:  Vaccination is recommended for all neonates, children, and adults at risk, as the hepatitis B vaccine is highly effective at preventing HBV infection. The vaccine is typically administered in a series of three or four injections, with the majority of individuals developing long-lasting immunity.
• Screening and prevention of mother-to-child transmission: Pregnant women should be screened for HBsAg, and infants born to HBsAg-positive mothers should receive hepatitis B immunoglobulin (HBIG) and the first dose of the hepatitis B vaccine within 12 hours of birth, followed by the remaining doses according to the recommended schedule. This strategy can substantially reduce the risk of HBV transmission during pregnancy.
• Safe sex practices: Using barrier protection, such as condoms, and limiting the number of sexual partners can reduce the risk of HBV transmission through sexual contact.
• Harm reduction strategies for injection drug users: providing access to sterile needles and syringes and secure injection facilities can help reduce the risk of transmission among injection drug users.
• Infection control in healthcare settings: standard precautions and appropriate sterilization techniques can reduce the risk of HBV transmission associated with healthcare.
• Blood and organ donor screening: Blood and organ donor screening: screening donors for HBsAg and other HBV infection markers can aid in preventing transmission via blood transfusions and organ transplants.

9. Outbreaks of Hepatitis B: Case Studies and Lessons Learned

Throughout history, there have been a number of notable hepatitis B epidemics that shed light on the challenges and opportunities associated with disease control and prevention. Some examples include:

This pandemic among Alaska Natives led to a high prevalence of chronic hepatitis B and associated complications during the 1960s and 1970s in Alaska. Eventually, the introduction of the hepatitis B vaccine and a comprehensive vaccination program targeting neonates and children led to a significant decline in HBV infection rates and a decrease in the incidence of liver cancer among this population.
The outbreak that occurred in Romania in the late 1980s and early 1990s was primarily caused by healthcare-associated transmission, specifically the reuse of contaminated needles and syringes in pediatric healthcare settings. The outbreak highlighted the need for universal hepatitis B vaccination and the significance of infection control measures.
This outbreak highlighted the risk of HBV transmission among those who share syringes and other injection equipment. Harm reduction strategies, such as syringe exchange programs and opioid replacement therapy, played a crucial role in reducing transmission among this high-risk population.

10.Strategies for Public Health and Global Initiatives

To combat the burden of hepatitis B, a number of public health strategies and global initiatives have been developed, including:

Through prevention, diagnosis, and treatment, the World Health Organization (WHO) Global Hepatitis Programme seeks to reduce the global burden of viral hepatitis, including hepatitis B. The World Health Organization (WHO) has set ambitious goals for the elimination of hepatitis B as a public health hazard by 2030, including a 90% reduction in new cases, a 65% reduction in hepatitis B-related fatalities, and an 80% treatment coverage for eligible individuals.
This partnership supports the introduction and scale-up of hepatitis B vaccination in low-income countries, with an emphasis on strengthening routine immunization programs and targeting high-risk populations.
National hepatitis B control programs: Numerous nations have enacted national strategies to combat hepatitis B, including vaccination programs, screening and prevention of mother-to-child transmission, and access to diagnosis and treatment.

11. Future Research and Directions

Several research areas hold promise for advancing hepatitis B prevention, diagnosis, and treatment, including:

• New antiviral agents: The development of novel antiviral medications with enhanced potency, resistance profiles, and safety could benefit the management of chronic hepatitis B.
• Immunotherapeutic approaches:  Novel immunotherapies, such as therapeutic vaccines and immune checkpoint inhibitors, are being studied for their potential to boost the immune response against HBV and achieve functional cure or viral eradication.
• Point-of-care diagnostics: The development of rapid, low-cost, and accurate diagnostic assays for hepatitis B could enhance case detection and care linkage, especially in settings with limited resources.
• Implementation research: Identifying effective strategies to increase hepatitis B vaccination coverage, enhance access to diagnosis and treatment, and decrease health disparities can inform hepatitis B control policy and practice.