Hepatitis Virus Notes 23.5

Viral Hepatitis

Hepatitis, denoted by the suffix "-itis", refers to inflammation of the liver. While hepatitis can be non-infectious, this discussion focuses on infectious viral hepatitis.

There are also non-viral causes of hepatitis, such as bacterial or fungal infections. However, these typically manifest as discrete abscesses rather than widespread liver inflammation. In the UK, viral hepatitis is the primary concern, whereas, globally, parasites like malaria can also significantly affect the liver.

Hepatitis serves as a practical example for understanding core microbiology concepts such as pathogenesis, epidemiology, and diagnostics. Familiarity with hepatitis viruses, particularly hepatitis C, is crucial for both clinical practice and research due to transmission risks, including needle stick injuries.

The taxonomy of viruses, especially hepatitis viruses, is unique compared to bacteria. Hepatitis viruses highlight the challenges in developing effective therapies compared to the numerous antibacterial options available.

Hepatitis A, B, C, D, E & Beyond

Hepatitis viruses are named A, B, C, D, E., often linked to the site of pathology. However, the liver, responsible for handling toxins, can be affected by viruses from other parts of the body. Viral tissue tropism determines which cells a virus can infect and replicate in. Viruses like yellow fever, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) can also affect the liver, and more such viruses are likely to be discovered.

The focus will be on hepatitis A, B, and C, which are categorized by their transmission routes. Hepatitis A and E are transmitted enterically through fecal contamination of water and food. Hepatitis B and C are transmitted parenterally, posing risks to healthcare workers through infected body fluids.

Viral Taxonomy

Despite being named hepatitis A, B, C, etc., these viruses are not closely related. Their classification is based on pathology rather than nucleic acid homology. For example, hepatitis C and hepatitis B viruses are distinct at the genus level and belong to different families. Viral taxonomy differs significantly from bacterial taxonomy.

Viral taxonomy uses Baltimore classification, categorizing viruses based on their nucleic acid type: double-stranded DNA, single-stranded DNA, double-stranded RNA, single-stranded RNA, and whether reverse transcription is required.

Post-Baltimore classification, viral taxonomy relies on factors like shape, presence of an envelope, host, and virulence. This system contrasts sharply with the standardized taxonomy used for bacteria, plants, and animals.

Viral structure

A relatively simple virus structure includes a DNA nucleus, a core for protection, and an outer section with antigens. These antigens are crucial for diagnostics, indicating the presence of the virus or antibodies against it, which reveals the stage of infection.

Viruses cannot replicate independently; they require the host cell machinery to replicate. They hijack the host machinery for their replication cycles.

Symptoms & Progression

Hepatitis typically begins with flu-like symptoms: elevated temperature, shakes, chills, fatigue, muscle, and joint pains. As the liver is affected, appetite decreases. Gastric symptoms such as nausea, vomiting, diarrhea, or constipation may develop, and the body's ability to process food and retain nutrients is impaired, which leads to malnutrition and weight loss.

Jaundice, a sign of significant liver damage, can vary in intensity. Changes in liver enzyme profiles in the blood, such as altered levels of alanine transaminase (ALT), indicate liver distress. Differential diagnosis is crucial to distinguish hepatitis from other conditions like liver or pancreatic cancer.

Pathogenesis of Hepatitis

Using the pathogenesis framework, the process begins with acquiring the virus. Hepatitis A and E spread through contaminated food and water via the fecal-oral route. Hepatitis B and C spread through contact with infected body fluids. Transmission can occur via shared needles, sexual contact, or, in some parts of the world, from mother to child during birth (neonatal infection).

Once inside the body, the virus concentrates in the liver, though it remains unclear exactly how it traverses the body to reach the liver. The virus enters the circulation but has stealthy characteristics because it does not trigger a strong innate immune response. The adaptive immune response is predominantly lymphocytic, involving CD4 and CD8 positive T cells.

The virus targets hepatocytes in the liver, gaining protection from the immune response. Like plasmodium that causes malaria, this protection allows the virus to replicate and reach a critical mass necessary to cause damage. The virus also re-enters the bloodstream, making it vulnerable to the body's defense mechanisms. At the end of its replication cycle, the virus lyses hepatocytes, releasing more viral particles and perpetuating the infection.

Damage & Immune Response

Viral lysis damages the liver, and the virus disrupts normal hepatocyte function, which leads to changes in blood markers. An upsurge in reactive oxygen species within the liver tissue further amplifies the immune response, potentially causing additional damage through inflammation.

A T-cell mediated response can lead to self-clearance of the infection in most adults. However, in cases where the adaptive response is insufficient, chronic high-level carriers can develop, increasing the risk of liver cancer because the viruses can mutate the DNA within the liver cells.

The understanding of hepatitis pathogenesis remains limited compared to bacterial infections due to the difficulty of conducting studies on human hosts. Factors such as high-risk behaviors (e.g., needle sharing, unprotected sex) and the presence of a satellite virus like hepatitis D can impact the disease's progression.(it's a bit of a parasite, really. It's piggybacking on the behaviours of another virus in order to replicate itself.)

Hepatitis D requires the presence of another hepatitis virus to replicate, as it lacks the full capacity to use the host machinery alone. It piggybacks on the enzymes of other viruses.

Global Impact

Globally, an estimated 2 billion people (1 in 3) are infected with hepatitis B. The UK has a relatively low incidence compared to other parts of the world.

Historically, hepatitis diagnosis involved tissue culture, which was time-consuming. Current methods primarily rely on serology and molecular techniques. Serological methods detect antibodies and antigens in the blood, while molecular methods provide more detailed information.

The presence of surface antigens indicates current infection, with levels rising to a peak around 20 weeks. The hepatitis envelope antigen is present in high levels during early infection. Antibody levels rise later in the infection cycle. The core antigen presence decreases over time. Knowing the stage of infection cycle is crucial for accurate diagnosis.

Clinical labs use algorithms and national standard methods to guide testing. Clinical details are essential for determining the appropriate tests, particularly in cases with ambiguous results. Additional testing may be necessary based on clinical findings and discussion within the clinical lab.

Prevention and Treatment

Vaccines are available for hepatitis A and B which are effective for prevention. Hepatitis A vaccine is recommended for travelers to endemic areas and those at high risk of exposure. The vaccine is also offered to people in the sewage industry because of the risk of contamination.

Hepatitis B vaccine has been introduced into the childhood immunization schedule in the UK as part of the 6-1 jab (4-6 months old), but booster shots may be needed later in life. The WHO is driving the Hepatitis B eradication because it is a disease that is present in so many places around the world. Improved sanitation, education, safe blood products, and proper disposal of clinical waste are key prevention strategies.

Treatment options for hepatitis are limited because there are only a few target areas to block viral replication (block viral entry, block viral assembly and exit of the cell, prevent replication although its being done by the hosts own cellular machinery which makes it hard or boost the immune response). Acute infections are typically not treated, while chronic infections require treatment to reduce the risk of cirrhosis and cancer. Peginterferon alpha 2a is the primary treatment in the UK for hep b. Antibody therapy is used for needle stick injuries and in children born to infected mothers. Newer drugs have shown promise against hepatitis C, but there is no vaccine available yet.

Epidemiology

Epidemiological data is essential for understanding the intervention strategies. Various factors influence epidemiological data, including increased awareness, improved testing methods, and changes in diagnostic practices. The Disability Adjusted Life Years (DALY) attempts to quantify the burden of a disease on an individual, community, or country.

In England and Wales, hepatitis B incidence was low (around 1.2 cases per 100,000 in 2008) and declining due to strategies implemented. Factors contributing to this decline include improved food hygiene, screening of blood donors, safe sex education, drug education, and needle exchange schemes.

Globally, hepatitis B incidence varies, with higher rates in middle-income countries and lower rates in Western countries. Disparities also exist within countries, with higher incidence among indigenous populations and immigrant populations. 2015 data from the WHO estimated that 257 million people were living with chronic hep b infection, WHO estimated that 887,000 people died of long term effects of hep b including cirrhosis and hepatocellular cancer, WHO regions of africa and western pacific have rates around 6% of adult population infected, A WHO analysis in 2024 suggests that the worls has not been making the required progress to enable elimination by 2030- the UK is one of about 12 countries that are on track.

Hepatitis C cases increased due to starting to test for them so it looked like an increase because they started looking for it. Around 65% of cases in males each year, estimated in 2020 that 89,000 people in england are chronic hep c carriers.

Hepatitis A cases are very low in England and Wales. MenhaveSexwithMen (MSM) populations have risk factors. Hepatitis A prevalence is higher in the southern hemisphere and is associated with natural disasters due to watercourse contamination. Hepatitis B eradication is underway, but setbacks have occurred due to the COVID-19 pandemic.