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Hepatitis B

Disease Details

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Description: Hepatitis B is a viral infection that primarily affects the liver, leading to both acute and chronic disease.
Type: Hepatitis B is a viral infection that primarily affects the liver. It is caused by the Hepatitis B Virus (HBV), which is a DNA virus. Hepatitis B is not transmitted genetically; instead, it is spread through exposure to infectious body fluids, such as blood, semen, and vaginal secretions. Common modes of transmission include perinatal transmission (from mother to baby at birth), unprotected sex, sharing of needles, and contact with infected blood.
Signs And Symptoms: Acute infection with hepatitis B virus is associated with acute viral hepatitis, an illness that begins with general ill-health, loss of appetite, nausea, vomiting, body aches, mild fever, and dark urine, and then progresses to development of jaundice. The illness lasts for a few weeks and then gradually improves in most affected people. A few people may have a more severe form of liver disease known as fulminant hepatic failure and may die as a result. The infection may be entirely asymptomatic and may go unrecognized.Chronic infection with hepatitis B virus may be asymptomatic or may be associated with chronic inflammation of the liver (chronic hepatitis), leading to cirrhosis over a period of several years. This type of infection dramatically increases the incidence of hepatocellular carcinoma (HCC; liver cancer). Across Europe, hepatitis B and C cause approximately 50% of hepatocellular carcinomas. Chronic carriers are encouraged to avoid consuming alcohol as it increases their risk for cirrhosis and liver cancer. Hepatitis B virus has been linked to the development of membranous glomerulonephritis (MGN).Symptoms outside of the liver are present in 1–10% of HBV-infected people and include serum-sickness–like syndrome, acute necrotizing vasculitis (polyarteritis nodosa), membranous glomerulonephritis, and papular acrodermatitis of childhood (Gianotti–Crosti syndrome). The serum-sickness–like syndrome occurs in the setting of acute hepatitis B, often preceding the onset of jaundice. The clinical features are fever, skin rash, and polyarteritis. The symptoms often subside shortly after the onset of jaundice but can persist throughout the duration of acute hepatitis B. About 30–50% of people with acute necrotizing vasculitis (polyarteritis nodosa) are HBV carriers. HBV-associated nephropathy has been described in adults but is more common in children. Membranous glomerulonephritis is the most common form. Other immune-mediated hematological disorders, such as essential mixed cryoglobulinemia and aplastic anemia have been described as part of the extrahepatic manifestations of HBV infection, but their association is not as well-defined; therefore, they probably should not be considered etiologically linked to HBV.
Prognosis: Hepatitis B virus infection may be either acute (self-limiting) or chronic (long-standing). Persons with self-limiting infection clear the infection spontaneously within weeks to months.
Children are less likely than adults to clear the infection. More than 95% of people who become infected as adults or older children will stage a full recovery and develop protective immunity to the virus. However, this drops to 30% for younger children, and only 5% of newborns that acquire the infection from their mother at birth will clear the infection. This population has a 40% lifetime risk of death from cirrhosis or hepatocellular carcinoma. Of those infected between the age of one to six, 70% will clear the infection.Hepatitis D (HDV) can occur only with a concomitant hepatitis B infection, because HDV uses the HBV surface antigen to form a capsid. Co-infection with hepatitis D increases the risk of liver cirrhosis and liver cancer. Polyarteritis nodosa is more common in people with hepatitis B infection.
Onset: Hepatitis B typically has an onset period of 1 to 4 months after exposure to the virus. Symptoms, if they appear, can include fatigue, jaundice, abdominal pain, and nausea.
Prevalence: The global prevalence of Hepatitis B varies significantly by region. Approximately 296 million people were living with chronic Hepatitis B infection in 2019. The prevalence is highest in the Western Pacific and African regions, where 6.2% and 6.1% of the adult population, respectively, are infected. North America and Western Europe have lower prevalence rates, generally below 1%.
Epidemiology: At least 296 million people, or 3.8% of the world's population, had chronic HBV infection as of 2019. Another 1.5 million cases of acute HBV infection also occurred that year. Regional prevalences across the globe range from around 7.5% in Africa to 0.5% in the Americas.The primary method of HBV transmission and the prevalence of chronic HBV infection in specific regions often correspond with one another. In populations where HBV infection rates are 8% or higher, which are classified as high prevalence, vertical transmission (usually occurring during birth) is most common, though rates of early childhood transmission can also be significant among these populations. In 2021, 19 African countries had infection rates ranging between 8-19%, placing them in the high prevalence category.In moderate prevalence areas where 2–7% of the population is chronically infected, the disease is predominantly spread horizontally, often among children, or vertically. China's HBV infection rate is at the higher end of the moderate prevalence classification with an infection rate of 6.89% as of 2019. HBV prevalence in India is also moderate, with studies placing India's infection rate between 2-4%.Countries with low HBV prevalence include Australia (0.9%), those in the WHO European Region (which average 1.5%), and most countries in North and South America (which average 0.28%).
In the United States, an estimated 0.26% of the population was living with HBV infection as of 2018.
Intractability: Hepatitis B is not generally considered intractable. It can be managed with antiviral medications, and in many cases, especially with acute infections, the body's immune system can clear the virus on its own. Chronic Hepatitis B can be managed and controlled to prevent liver damage, although it is not often curable. Regular monitoring and appropriate medical treatment can lead to a good quality of life for many patients.
Disease Severity: Severity of hepatitis B can vary. Some individuals may experience mild or no symptoms, while others can develop severe acute or chronic conditions. Chronic hepatitis B can lead to serious complications such as liver cirrhosis and liver cancer. Monitoring and medical management are crucial for those with chronic infections.
Healthcare Professionals: Disease Ontology ID - DOID:2043
Pathophysiology: Pathophysiology of Hepatitis B:
Hepatitis B is caused by the Hepatitis B virus (HBV), a DNA virus that primarily infects the liver. Upon entry into the liver cells (hepatocytes), HBV replicates by converting its DNA into covalently closed circular DNA (cccDNA), which serves as a template for transcription of viral mRNAs and pregenomic RNA. This viral replication leads to an immune response that can result in inflammation and damage to liver tissue. The severity of liver injury is related to the immune response, with chronic infection often leading to persistent inflammation, fibrosis, cirrhosis, and an increased risk of hepatocellular carcinoma.
Carrier Status: Hepatitis B carrier status refers to the presence of the virus in the blood for more than six months without symptoms of acute illness. These individuals can still transmit the virus to others and may develop liver complications later. Carrier status is typically identified through blood tests detecting the surface antigen (HBsAg) and other markers of the virus.

Nan, or Nucleic Acid Amplification Testing (NAAT), is a technique used to detect the genetic material of the hepatitis B virus. It is highly sensitive and can identify active infection even when viral levels are low, aiding in diagnosing and managing hepatitis B effectively.
Mechanism: Hepatitis B is a liver infection caused by the hepatitis B virus (HBV).

**Mechanism:**
The virus infects liver cells (hepatocytes) and causes the immune system to attack these infected cells, leading to liver inflammation and potential liver damage. HBV is transmitted through contact with infectious body fluids, such as blood, semen, and vaginal fluids.

**Molecular Mechanisms:**
1. **Attachment and Entry:** HBV uses its surface antigen (HBsAg) to bind to the sodium taurocholate cotransporting polypeptide (NTCP) receptor on the surface of hepatocytes, facilitating entry into the cell.
2. **Replication:** Once inside the hepatocyte, the virus's relaxed circular DNA (rcDNA) is transported to the nucleus, where it is converted to covalently closed circular DNA (cccDNA). This cccDNA acts as a template for the transcription of viral mRNA.
3. **Translation:** The viral mRNA is then translated into viral proteins, including the core protein (HBcAg), polymerase, and envelope proteins (HBsAg).
4. **Assembly:** New viral particles are assembled in the cytoplasm, incorporating the replicated viral DNA and proteins.
5. **Release:** The mature virions are then packaged into vesicles and secreted out of the liver cells, entering the bloodstream to infect new cells.

The persistence of cccDNA in the nucleus is a major reason for the chronic nature of hepatitis B infection, as it serves as a reservoir for ongoing viral replication. The immune response to HBV can result in varying degrees of liver inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma over time.
Treatment: Acute hepatitis B infection does not usually require treatment and most adults clear the infection spontaneously. Early antiviral treatment may be required in fewer than 1% of people, whose infection takes a very aggressive course (fulminant hepatitis) or who are immunocompromised. On the other hand, treatment of chronic infection may be necessary to reduce the risk of cirrhosis and liver cancer. Chronically infected individuals with persistently elevated serum alanine aminotransferase, a marker of liver damage, and HBV DNA levels are candidates for therapy. Treatment lasts from six months to a year, depending on medication and genotype. Treatment duration when medication is taken by mouth, however, is more variable and usually longer than one year.Although none of the available medications can clear the infection, they can stop the virus from replicating, thus minimizing liver damage. As of 2018, there are eight medications licensed for the treatment of hepatitis B infection in the United States. These include antiviral medications lamivudine, adefovir, tenofovir disoproxil, tenofovir alafenamide, telbivudine, and entecavir, and the two immune system modulators interferon alpha-2a and PEGylated interferon alpha-2a. In 2015, the World Health Organization recommended tenofovir or entecavir as first-line agents. Those with current cirrhosis are in most need of treatment.The use of interferon, which requires injections daily or thrice weekly, has been supplanted by long-acting PEGylated interferon, which is injected only once weekly. However, some individuals are much more likely to respond than others, and this might be because of the genotype of the infecting virus or the person's heredity. The treatment reduces viral replication in the liver, thereby reducing the viral load (the amount of virus particles as measured in the blood). Response to treatment differs between the genotypes. Interferon treatment may produce an e antigen seroconversion rate of 37% in genotype A but only a 6% seroconversion in type D. Genotype B has similar seroconversion rates to type A while type C seroconverts only in 15% of cases. Sustained e antigen loss after treatment is ~45% in types A and B but only 25–30% in types C and D.It seems unlikely that the disease will be eliminated by 2030, the goal set in 2016 by WHO. However, progress is being made in developing therapeutic treatments. In 2010, the Hepatitis B Foundation reported that 3 preclinical and 11 clinical-stage drugs were under development, based on largely similar mechanisms. In 2020, they reported that there were 17 preclinical- and 32 clinical-stage drugs under development, using diverse mechanisms.
Compassionate Use Treatment: Compassionate use treatment for hepatitis B refers to the use of investigational drugs outside of clinical trials for patients with serious or life-threatening conditions who have exhausted other treatment options. These treatments are not yet approved by regulatory agencies but may be granted on a case-by-case basis.

Off-label or experimental treatments for hepatitis B may include the use of medications approved for other conditions but not specifically for hepatitis B. Examples include:

1. **Tenofovir alafenamide (TAF)**: Though primarily approved for HIV, it's also used off-label in certain cases for hepatitis B.

2. **Peginterferon alfa-2a**: This antiviral drug is FDA-approved for hepatitis B but is also used for other viral infections.

3. **Combination therapies**: In some experimental settings, combining antiviral drugs like lamivudine, adefovir, or other agents may be tried to enhance efficacy.

4. **Newly emerging antiviral agents**: These could be in early stages of development or clinical trials.

Patients receiving off-label or experimental treatments should be under close medical supervision to monitor for efficacy and potential side effects.
Lifestyle Recommendations: ### Lifestyle Recommendations for Hepatitis B

1. **Avoid Alcohol**: Alcohol can accelerate liver damage and increase the risk of liver disease complications. Abstain from alcohol to protect your liver.

2. **Healthy Diet**: Consume a balanced diet rich in fruits, vegetables, lean proteins, and whole grains. Avoid fatty, processed, and sugary foods to maintain liver health.

3. **Regular Exercise**: Engage in regular physical activity to maintain a healthy weight and reduce liver fat.

4. **Safe Practices**: Avoid sharing needles, razors, toothbrushes, and ensure any tattoos or piercings are done with sterilized equipment to prevent spreading the virus.

5. **Medication Compliance**: If prescribed antiviral medication, adhere strictly to the regimen to control the virus and prevent liver damage.

6. **Regular Medical Checkups**: Visit your healthcare provider regularly to monitor liver function and manage any complications comprehensively.

7. **Vaccination for Others**: Encourage close contacts to get vaccinated against hepatitis B, especially those who live with or have regular contact with you.

8. **Avoid Liver Toxic Medications**: Consult your doctor before taking any new medications, including over-the-counter drugs and supplements, as some may be harmful to your liver.

Implementing these lifestyle changes can help manage hepatitis B effectively and promote liver health.
Medication: For hepatitis B, medications include antiviral drugs such as tenofovir, entecavir, and lamivudine. These medications help to reduce the viral load in the body and decrease liver damage. In some cases, pegylated interferon-alpha may be used to boost the immune system's response against the virus. Treatment plans should always be discussed and managed by a healthcare professional.
Repurposable Drugs: Repurposable drugs for hepatitis B include:

1. **Tenofovir** - Originally used for HIV, it has potent antiviral activity against HBV.
2. **Lamivudine** - Another antiretroviral drug effective in the treatment of HBV.
3. **Emtricitabine** - Used for HIV, this drug also exhibits activity against HBV.
4. **Entecavir** - First developed for hepatitis B, it is also being explored for other viral infections.

Note that while these drugs can be repurposed, their use should be supervised by a healthcare provider.
Metabolites: Hepatitis B is a viral infection that primarily affects the liver, caused by the hepatitis B virus (HBV). Metabolites associated with hepatitis B include alterations in liver enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Bile acids and bilirubin levels may also be impacted. The virus itself does not directly produce metabolites; rather, the infection leads to metabolic changes in the liver and the body’s response to the virus. It's important to note that metabolic changes can vary depending on the stage of infection and individual patient factors.
Nutraceuticals: Research on nutraceuticals for hepatitis B has been ongoing, focusing on supporting liver health and boosting the immune system. Some common nutraceuticals that have been studied include:

- **Milk Thistle (Silybum marianum)**: Contains silymarin, which may have liver-protective effects.
- **Phyllanthus amarus**: Some studies suggest it may have antiviral properties against hepatitis B.
- **Licorice Root (Glycyrrhiza glabra)**: Glycyrrhizin, an active compound, has shown some potential in inhibiting the hepatitis B virus.
- **Curcumin**: Found in turmeric, it has anti-inflammatory properties and may offer liver protection.

As with all supplements, their efficacy and safety can vary, and it is important to consult with healthcare professionals before use.
Peptides: Hepatitis B virus (HBV) infection involves various peptides that are components of the viral proteins, which can be targets for diagnostic and therapeutic interventions. Important peptides include the Hepatitis B surface antigen (HBsAg) and Hepatitis B core antigen (HBcAg). These peptides are recognized by the immune system and are used in vaccines to elicit an immune response. Nanotechnology can potentially be applied in the development of more effective HBV vaccines and drug delivery systems, enhancing the targeting and efficacy of treatments.