Hepatitis B and Hepatitis D virus
Hepatitis B virus, or Hep B virus for short, is a member of the hepadnavirus family; hepatitis D virus, or Hep D virus, is a deltavirus.
They both cause hepatitis, or inflammation of the liver. Even though they both cause hepatitis, hepatitis D virus cannot cause the disease by itself, and needs hepatitis B virus to replicate.
Both hep B and D viruses are enveloped, so they’re surrounded by a membrane. To make things interesting, the membrane of both viruses contains hepatitis B viral proteins - specifically, they both have a surface antigen called HBs.
Beneath the membrane there is a protein shell called a capsid, which has more antigens. HB core, or HBc, is in the capsid of hepatitis B.
There is also an HB envelope or HBe antigen for short, which is a variant of HBc but it’s not really part of the virus. It’s secreted, and can be found in infected individuals' serum.
Delta antigen or HDAg for short is in the capsid of hepatitis D virus. Inside the capsid, there’s the viral genetic material.
Now, hep B is a DNA virus, which means that its capsid contains partial double-stranded circular DNA, which is made of a long and short strand, so there is a part where the long strand is single stranded.
And it also has DNA polymerase, which is an enzyme with DNA- and RNA-dependent activity, meaning it can convert DNA to RNA and vice versa.
On the other hand, hep D is an RNA virus, so its capsid contains single-stranded circular RNA in a rod-like folded structure, which is why host cell enzymes can use it as double-stranded DNA.The main source of hepatitis B virus is blood, but it can also be found in other bodily fluids like milk, amniotic fluid, vaginal secretions and semen.
So, routes of transmission include: sexual contact; contaminated blood, either following transfusions or injections with contaminated needles, the latter being more common in people who use intravenous drugs.
The virus can also be passed from an infected mother to the baby during childbirth. Rarely, during the pregnancy the virus can pass through the placental barrier, which is a kind of a very thin wall that brings the mother’s and fetus' blood very close, and allows them to exchange some substances like oxygen, IgG antibodies, waste products and unfortunately certain microbes.
More commonly the virus can pass from an infected individual to the child during birth because of the close contact between the individual's blood and secretions with the child.
It is still not certain if C section can protect against this kind of transmission. Hepatitis D virus spreads the same way, but it only causes disease in individuals with an active hepatitis B infection.
Alright, now, both these viruses target the liver, which is made of functional units called hepatic lobules. The main cells are called hepatocytes.
They pick up and detoxify harmful substances like drugs or alcohol; help maintain a normal blood glucose level; synthesize a variety of important proteins, like albumin and coagulation factors; store certain vitamins and some minerals; and convert cholesterol into bile salts, which, along with water and bilirubin, make up the bile.Hepatitis B virus enters the hepatocytes by fusing its membrane with the cell membrane and releasing the capsid into the cell.
The cell's polymerase elongates the shorter strand of the viral DNA, so that it now forms a complete double-stranded DNA with the long strand.
It then travels to the nucleus. There, it is transcribed by the cell's transcription elements into multiple mRNAs, which leave the nucleus and use the cell’s ribosomes to create viral proteins, like DNA polymerase and viral antigens: HBs, HB core and HBe antigen.
The largest mRNA is used by the viral DNA polymerase to replicate viral DNA. Viral antigens Hbs and Hb core are assembled into new viral particles.
Hbe, however, isn’t included in the viral particle, but leaves the cell and can be found in the serum. The viral DNA is replicated and packaged into capsid at the same time, which is why its replication is interrupted and the virus gets partial double-stranded DNA.
The capsid is then enveloped and released without damaging the cell, which is why the infection can persist for a long time without causing liver damage.
The damage actually comes from the body's immune system. T-cells find and eliminate infected hepatocytes, which causes liver damage.
B-cells react to the virus in the bloodstream and secrete antibodies against hep B antigens. Bilirubin with bile salts is released from the destroyed cells into the bloodstream and impregnates the tissue, causing jaundice, which is a yellowish pigmentation of the skin, mucosa and whites of the eyes.
The bile salts get into the skin, and cause itching. The bilirubin from the blood is filtered by the kidneys and ends up in the urine instead of the stool, making it dark, while the stool becomes pale.
An insufficient T-cell response, or, if large amounts of HBs antigen bind to neutralizing antibodies, it can lead to chronic hepatitis.
Acute hepatitis B becomes chronic in about 5 to 10% of cases. In some cases, liver damage can progress to scarring, cirrhosis and liver failure.
Chronic hepatitis also increases the risk of liver cancer called hepatocellular carcinoma.Hepatitis D virus enters the cell and the nucleus in the same way.
It then leaves the cell. Now, delta antigens are harmful to the cell and cause cell death and liver damage, so unlike hep B, hep D damages the cells directly.Hep D virus causes acute hepatitis in one of two ways.
First, there’s co-infection with hep B, when the two viruses infect the liver at the same time; second, there’s superinfection, which is when hep D infects individuals with chronic hepatitis B, which is more severe.
Hep D increases the severity of the hep B infection. These individuals are more likely to develop fulminant hepatitis, massive liver necrosis, and hepatic encephalopathy, when the brain function is affected.
Hep B has a long incubation period of 1-6 months, usually 2-3 months. About two-thirds of affected individuals develop mild, asymptomatic acute hepatitis that is usually undetected.
Symptomatic hepatitis usually starts as a preicteric phase with fever, fatigue, body aches and nausea. It lasts a few days to a week and is followed by the icteric phase, with jaundice and dark urine.
It usually lasts 1 to 2 weeks, after which the recovery phase happens. Very rarely, an individual can develop fulminant hepatitis with liver failure, usually marked by sudden fever, abdominal pain, vomiting, jaundice, confusion and even coma.
Symptoms of chronic hep B are typically similar to the acute hepatitis but milder. The diagnosis of hep B or B and D coinfection is based on the antigen and antibody findings in the blood.
HBs antigen is the first to appear and can be detected in the first 1-2 weeks after exposure. HBe antigen appears shortly after but clears quickly.
Shortly after its clearing, HBe antibodies appear. Anti HB core IgM antibodies usually appear shortly before the symptoms, followed by anti HB core IgG antibodies 1-2 weeks after.
Anti HBs antibodies appear during recovery. Hepatitis B DNA can be detected at any time during the disease.
In the recovery phase, also called the window phase, only anti HB core IgM and anti HBe antibodies can be detected.In chronic hepatitis B, anti HB core IgM is negative, while anti HB core IgG antibodies and HBs antigen are present for longer than 6 months, and viral DNA can also be detected.
HBe antigen and antibody can be present as well. Anti HB core IgG antibody is the marker of resolved hepatitis.
Anti HBs and HBe antibodies can also be present, but no antigens, anti HB core IgM or viral DNA are present. Serum alanine and aspartate aminotransferase (or ALT and AST) are elevated during the active acute and chronic infection, but ALT is more elevated than AST.
Finally, vaccinated individuals have only anti HBs antibodies present.A liver biopsy can be done to confirm the diagnosis of chronic hepatitis B, and evaluate the damage.
It usually shows hepatocytes with granular cytoplasm called ground glass hepatocytes.In severe cases, hepatitis B and D coinfection/superinfection can be suspected.
The presence of hepatitis D RNA, delta antigen or anti hepatitis D antibodies confirm the suspicion. Acute hepatitis B infection usually requires no treatment.
Severe cases like fulminant hepatitis and chronic hepatitis are treated with antiviral medication and immune system modulators like interferon alpha and pegylated interferon.
For hepatitis B, prevention is much more important. Screening of donated blood for hepatitis B is done to prevent the spread of the virus.
Individuals can avoid a lifestyle that puts them at risk of infection, like unprotected sex and the use of intravenous drugs.
Finally, high risk individuals like babies of mothers with chronic hepatitis B, intravenous drug users, people who have multiple sex partners, individuals on dialysis, health care providers, and so on, can be vaccinated against the disease.
However if the individual is exposed to the virus, hepatitis B immune globulin can be given within a week after exposure to prevent the disease.
There is no specific treatment for hepatitis D. Because it is dependent on hepatitis B, treatment and prevention of hepatitis B also protects from hepatitis D virus.
All right, as a quick recap…Hepatitis B virus is a DNA virus, transmitted by blood, sexually or during birth that causes acute or chronic hepatitis by infecting liver cells, while the damage is caused by the immune system.
Initial symptoms of acute hepatitis include fever, fatigue, body aches and nausea, after which the jaundice develops. Rarely, severe fulminant hepatitis can develop.
Chronic hepatitis has similar symptoms but is milder, and it increases the risk of hepatocellular carcinoma. Diagnosis is based on clinical course and antigen and antibody findings.
It can be prevented by avoiding risky behavior and vaccination. Acute hepatitis usually requires no treatment, but severe cases and chronic hepatitis can be treated by antiviral drugs and interferons.
Hepatitis D is an RNA virus transmitted similarly to hepatitis B virus. It can only infect individuals with active hepatitis B infection and increases the severity and a chance of fulminant hepatitis.
It is diagnosed by antigen and antibody findings. No special treatment is required, as treating and preventing hepatitis B treats hepatitis D as well.
and it interference. Hepatitis B is an RNA virus transmitted, similarly to Hepatitis B.
Virus can only infect individuals with active hepatitis B, infection and increases the severity and a chance of fulminant.
Hepatitis. Is diagnosed by antigen-antibody findings?
No special treatment is required as treating and preventing Hepatitis B treats hepatitis D as
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