Hepatitis B Virus: Causes, Symptoms, and Treatment

Viral Characteristics 

HBV is mostly replicated in the liver and is a DNA virus that is a member of the hepaDNAvirus family. The pancreas, kidneys, lymphocytes, and spleen are among the additional locations. It contains eleven genotypes, represented by the letters A through J: A is pandemic, B and C are limited to Asia, and I is only found in India and Southeast Asia. The most prevalent way that HBV is spread is through blood or blood products. Additionally, tattoo needles, drug misuse, and tainted IV needles can all spread it, Intercourse. Breastfeeding (perhaps insignificant transfer; mother to child transmission during delivery).

Viral Genome And Proteins

• P-Gene: This gene codes for the replication-promoting viral DNA polymerase.
• S-Gene: It codes for HBsAg, the traditional HBV surface antigen.
• Pre-S1 and pre-S2 genes are the genes that come before the s-gene.
• Medium-chain proteins are produced by the expression of the preS2 and S2 genes.
• Large chain proteins are produced when the preS1, preS2, and S2 genes are expressed.
• C-Gene: It codes for HBcAg, an antigen found in the nucleocapsid core. The pre-C gene is a nearby area that it possesses.
• The expression of the C and pre-C genes together results in the production of the blood-sequestered protein known as HBeAg. It suggests a recent infection.
• X-Gene: It codes for the HBxAg antigens. According to recent research, the protein causes P53 to alter functionally, which results in HBV-associated carcinogenesis.

Unlike other strains, HBV does not cause cytopathies; instead, it can cause immune-related problems. The most widely used marker is HBsAg. Because HBcAg is not released into the bloodstream and is a nuclear capsid core antigen. High infectivity, or active viral replication, is indicated by the presence of HBeAg in the blood. HBeAg also correlates with HBV DNA levels, which can be ascertained by PCR methods. 

Neonatal transmission happens at the moment of birth. The following are risk factors for perinatal transmission:- Mother infection, as indicated by the presence of HBsAg and HBeAg. Significant maternal overload
A prior baby who, in spite of prevention, contracted HBV

Risk Of Chronicity In HBV

When a patient has HBsAg in their blood for longer than six months, their HBV infection is considered chronic. Age and the risk of chronicity are inversely correlated. For children under one year old, it is 90%; for children aged one to five, it is 30%; and for adults, it is 2%. 

Hepatocytic carcinoma and other chronic liver disorders can result from persistent HBV. The development of cirrhosis from chronic liver illnesses does not increase the likelihood of developing cancer.

Mechanism Of Chronicity

Usually during the perinatal stage, the body does not mount an immunological defense against HBV; instead, it tolerates its effects.
Non-recognition of MHC-1 or the core antigen and non-activation of cytotoxic cells are two ways that tolerance might develop. The viral load remains in these patients despite normal liver function tests.
While the risk of liver carcinogenesis rises, the risk of end-stage liver disease does not.

 Q. Acute Liver Failure has been seen in infants of chronic carrier mothers who have anti-Hbe or are infected with a precore-mutant strain. Why? 

Infants of chronic carriers exposed to HbeAg in utero are likely to develop a tolerance to the virus after postnatal infection.
This exposure won't occur in a mother who has anti-Hbe, indicating no tolerance. As a result, T cells will attack the liver severely, and the patient will develop ALF. 

Clinical Features Of Acute HBV Infection

While some people experience a more severe sickness resembling HAV, many remain asymptomatic. Elevated chance of extrahepatic feature development  a prodrome resembling serum sickness may occur before to illness in certain youngsters. Arthralgia and skin lesions such as purpuric, urticarial, macular, or maculopapular rashes are its hallmarks. 

Another possibility is papular acrodermatitis, commonly referred to as Gianotti-Crosti syndrome. The duration of acute HBV is 6–8 weeks. Ninety percent of patients make a full recovery, while some become chronic. 

The following are examples of extrahepatic symptoms that are caused by immune complexes.

• Polyarticular nodosity.
• MPGN and GN membranes.
• Rheumatic polymyalgia.
• Vascular leukocytoclastic disease.
• GBS. 

Chronic HBV

• It displays the following three stages.
• Phase of Immune Tolerance: This stage allows for the detection of viral HBV DNA. The signs and symptoms may go away or become better.
• ALT and AST on LFTs are normal.
  • This phase is known as the immune active or replicative phase. During this phase, the virus actively replicates, increasing the amount of HBV DNA. Signs and symptoms may also occur. LFTs reveal elevated AST and ALT.
• Inactive phase: A patient who has reached the inactive phase is said to have undergone seroconversion, which is characterized by the production of an antibody against HBe and the 4-5% annual reduction of HBeAg in the immune tolerant phase.

Causes Of Flare Or Reactivation In Chronic HBV

When an acute hepatitis-like characteristic appears, the patient transitions from the tolerant to the active phase, a process known as reactivation.

These are the reasons.

• Idiopathic or spontaneous reactions
• Immunosuppression brought on by a viral infection or steroids
• Antiviral treatment using nucleoside and interferon analogs. The second or third month after the start of the regimen is when the risk is largest.
• Stopping treatment; • Receiving HIV medication, such as HAART; • Contracting another hepatitis virus; • Having core promoter mutations or cures.

Diagnosis Of HBV

1^st to appear: HBsAG. "Circulating HBsAg remains detectable throughout the entire icteric or symptomatic phase of acute hepatitis B and beyond," According to Harrison, 20th Ed., and it does so two to six weeks before elevations of serum aminotransferase activity and clinical symptoms. After a month or two, HBsAg levels drop sharply and eventually vanish after six months.

• HBeAg: Manifests in blood either just after or concurrently with HBsAg.
• HbeAg and HBV-DNA, which can be tested individually, correlate well.
• IgM Anti-HBc is elevated shortly after, and after six months, IgG Anti-HBc gradually takes its place.
• The appearance of Anti-HBs and the elimination of HBsAg are correlated.

Summary Of Serological Patterns And Interpretation For HBV Infection

HBV DNA: Positive in Acute and Chronic Infections.

Also Read: Hepatitis A Virus : Characteristics, Clinical Features

Complications In HBV

Severe liver failure. Patients with impaired immune systems and those who co-infect HBV and HIV are at a higher risk. It is more common in HBV than in other types. Patients require liver transplants, and the death rate is 30%. End-stage liver disease, cirrhosis, and hepatocytic carcinoma are caused by chronic HBV infection. The condition known as membrane glomerulonephritis is brought on by complement and HBeAg deposits in glomerular capillaries.

Natural History Of Acute Hepatitis

Fulminant hepatitis, which can be fatal, occurs in about 1.5% of people with acute hepatitis. On the other hand, orthotopic liver transplantation can save patients.  As patients gain immunity, the recovery rate is 5% for those under a year, 70% for those between one and five years, and 95% for those beyond five years.  Individuals with chronic infections acquire chronic hepatitis or become carriers, which can result in liver cirrhosis and HCC.

Treatment

Treatment for the symptoms of acute hepatitis must be supportive.
Specific treatment is required for chronic hepatitis, which has increased ALT/AST. The therapy's objectives are to: Reduce viral replication to lower serum viral load; and • Seroconversion into inactive form. HBeAg disappears as anti-HBeAg develops. Anti-HBeAg development declines
Progression of fibrosis;  Infectivity;  Active hepatic inflammation and damage; and  HCC risk.

Also Read: Hepatitis C And Hepatitis D Virus

Management Of Chronic Active HBV

It includes the following therapy

INF-Alpha 2b

It is an immunomodulator that does not cause resistance and has a 25% long-term response rate.  The drawbacks consist of
• Administration using subcutaneous means
• Continuous use for a full month
• Contraindicated in decompensated cirrhosis; side effects include flu-like symptoms, BM suppression, autoimmunity, and depression.

Pegylated IFN-alpha2

It is administered once a week as its effects last longer.

Lamivudine

It is a 52-week treatment with an outstanding safety profile that inhibits viral reverse transcriptase; on the other hand, it must be continued for more than six months following viral clearance.  Sturdy strains such as the YMDD strain have surfaced.  Combining IFN and lamivudine has no further benefits.

Entecavir

This nucleoside analogue demonstrates 21% seroconversion with reduced resistance, and it is approved for use in patients over the age of two years.

Adefovir

It is a nucleotide analogue approved for the age above 12 years and can achieve a 23% seroconversion rate.

Tenofovir

It can achieve a 21% seroconversion rate with low resistance; it is a nucleotide analogue approved for patients over the age of twelve. Moreover, it can lower nephropathy risk and BMD.

Also Read: Pediatric TB - Guidelines, Diagnosis And Management

Prevention Of HBV

Vaccination is the main method of prevention. After three doses, the vaccine can reach a 95% seroconversion rate since it contains recombinant HBsAg.  More than 10 mIU/mL of antibody titre is protective. Anti-HBs is examined. 

Four doses are included in the national vaccination schedule and IAP. The subsequent doses are administered in the sixth, tenth, and fourteen weeks after the first dose, which is given within 24 hours of delivery.
Research indicates that doses administered in the 0th, 1st, and 6th months had higher rates of seroconversion. (India doesn't adhere to this.) 

Giving an unimmunized person the HBV vaccination plus immunoglobulin is known as post-exposure prophylaxis. Three doses comprise the active vaccination: one at the onset of HBIG, one one month later, and the third one after 6 months

Prevention in a baby born to an HBV-positive mother.  Among moms who test negative for HBeAg, 1% of cases of chronicity are associated with HBsAg and HBeAg. Preventative use of antiviral medicine during the third trimester is advised for moms whose HBV DNA viral load exceeds 20,000 IU/mL.  The newborn receives the HBV and HBIG vaccinations within 24 hours of birth. Delays longer than seven days are pointless.

Special Populations

1. Patients with cirrhosis: Repeating anti-HBs titres is recommended since they do not respond to the HBV vaccination.  The dosage should be increased, or the time between doses should be shortened.
2. Individuals with Inflammatory Bowel Disease (IBD): • When starting infliximab, they may have lower anti-HB levels and are more likely to experience fulminant HBV. They might so require boosters.

Hope you found this blog helpful for your NEET SS Pediatrics Infections preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.