I will be continuing our previous blog.
In the last blog, I described about the significance of liver and why its damage will damage our routine and life. To recap about it, let me ask a simple question.
Q#1. Liver damage or cirrhosis by hepatitis leads to weakening of our immune system. Is it a true statement or not and why?
A#1. The statement is definitely a true statement.
Our liver cells or hepatocytes carry cytochrome p450 system which is an endogenous system where metabolism of drugs, toxins occurs and it helps fighting against pathogens. They carry monooxygenases which metabolise many xenobiotics (A#1) that may potentiate a complication.
A#1. Xenobiotics: These are any chemical that can be found without or within an organism (not necessarily produced by that organism) which may be grouped as a pollutant, drug, carcinogen or pesticide. This is what gets neutralized by hepatocytes.
Hope you have gotten it right. Now let us move into the understanding of viral hepatitis.
Virus: Hepatitis A virus or HAV is an ssRNA virus belonging to a family picornaviridae.
Transmission: To understand this, imagine a couple who is going to travel around the world after leaving their child in a day care. Such a shameless couple! But we are not here to judge. They shall be judged by the universe! Sorry for being overly dramatic. So, after eating sea foods such as oysters they found out that they have hepatitis. Well, here is the judgment. But what more, even their child got hepatitis. So, what does it say? It says about its transmission which is…
- Transmission is fecal-oral route.
- Can be referred to as traveler’s diarrhea as easily acquired during travelling.
- Can occur after eating shellfish which has been contaminated from virus containing water body.
- Children are easy targets when they get in contact with dirt like blood or stool, or eating or drinking contaminated food or water.
Though hepatitis A is self-limiting in few weeks to months in adults. In children, it remains asymptomatic for around a month due to their incubation period.
Symptoms: Symptoms of almost all viral hepatitis are similar.
- Jaundice (icterus)
- Abdominal pain
- Nausea or vomiting
- Appetite loss
- Lab findings are also similar for all hepatitis.
- Increase of AST and ALT in blood.
- Aspartate aminotransferase is an enzyme for amino acid metabolism that is produced by liver. Its normal range fluctuates between 8 to 45 units/liter. Therefore, above 45 U/L in serum indicates that there might be some liver damage. Though, it is just an indicative test and not confirmative as AST (some test may name it SGOT instead of AST as SGOT means serum glutamic-oxaloacetic transaminase which is the same) is also produced by cardiomyocytes, brain, pancreatic, lung, kidney cells etc.
- Therefore, often ALT (alanine aminotransferase or SGPT i.e. serum glutamic-pyruvic transaminase) is also measured as it is primarily produced by liver cells.
- Liver biopsy
- Hepatocyte inflammation. Well why not?
- Presence of monocytes in blood
- H and E staining test i.e. hematoxylin (base) and eosin (acid) staining where hepatocyte appear pink (characteristic of acidophilic cells otherwise purple in basophilic cells) due to presence of apoptotic councilman bodies (A#2).
- Antibody test
- Presence of IgM (earliest immunoglobulin to form during infection. If you want to know why, follow this link.) indicates the active stage of infection.
- IgG either indicates the immunisation or prior infection.
Prevention/treatment: Prevented by HepA vaccine which is administered in child of 12 months old or older and followed by another dose with 6 months apart.
A#2. Councilman body: Also called councilman hyaline body which is formed due to infected hepatocyte which are dying (by necrosis or apoptosis) and are, hence, surrounded by parenchyamtous material.
- Formed in hepatitis (viral often), yellow fever (caused by same vector that cause dengue fever i.e. female aedes aegypti).
Virus: HBV is an incomplete dsDNA i.e. the 2nd strand of the DNA is partial, containing virus. It has a unique enzyme i.e. DNA polymerase that can use either DNA or RNA templates for its activity.
- The partial strand completed by the DNA polymerase enzyme as the virus enters into the host cell.
- Then the enzyme transcribes mRNA from the viral closed circular DNA which makes the necessary viral protein molecules.
- Then with reverse transcriptase activity of the same enzyme, it forms DNA from viral RNA for the progeny viruses.
Transmission: By parenteral route i.e. by blood transmission through transfusion or IV drug abuse or by perinatal route i.e. from mother to child or by sexual intercourse.
- Initially appears- fever, body ache, allergic reactions such as rash. Though one should not confuse initial symptoms as the quickly developing symptoms as these symptoms also takes months to show up due to long incubation period.
- Mostly remains acute but 1/5th of the cases can turn chronic.
- Later it most probably can lead to hepatocellular carcinoma (A#3).
- Children are affected the worst.
- The characteristic identification of chronic hepB infection is presence of ground glassy appearance of hepatocytes.
- Hepatocytes are eosinophilic, granular and glassy due to accumulation of viral surface antigens in endoplasmic reticulum in the cytoplasm that makes the light microscopic study looks like a glassy showcase.
- Other techniques such as AST/ALT and Ig testing like already described in HepA can also be performed.
Prevention/treatment: HepA vaccine can prevent HepB infection also. Most of the adults get fully recovered. Though, they may become a carrier too. The risk group, like earlier mentioned, are children.
- HepB vaccine and immunoglobulins can also be used to prevent the progress if given within 24 hours of exposure.
- In infants, the 1st dose of vaccine given at the period of birth followed by 3 or more doses after months interval.
- Now-a-days, a recombinant DNA vaccine is popular named Engerix B.
- It contains non-infectious subunit of HBsAg i.e. hepB surface antigen.
- It is produced by genetic engineering by using Saccharomyces cerevisase or yeast.
- For treatment, oral antiviral drugs such as adefovir (Hepsera) or lamivudine (Epivir) are used that slows down the progression.
A#3. Hepatocellular carcinoma (HCC): Cancer of liver.
- Causes: Most common cause is HBV or HCV.
- Cirrhosis where liver cells are damaged by HBV or HCV, too much alcohol.
- Excess iron accumulation in the body that is stored in the liver.
- Obesity which leads to non-alcoholic fatty liver disease.
- Diabetic patients are at high risk.
- Symptoms: Pain in upper abdominal region.
- Weight loss
- Nausea or vomiting
- Bloating or feeling of fullness in belly
- Treatment: Like any cancer, it is also treated with chemotherapy, radiotherapy, immunotherapy or combination.
Virus: It is caused by an ssRNA containing virus.
Transmission: Most commonly through parenteral route i.e. IV drug abuse.
- Can be transmitted during sexual intercourse.
- Many people are scared of its transmission through kissing, exchange of saliva, using towel or utensil of infected person. But it is just fake information.
Symptoms: Can take months before appearing i.e. long incubation period.
- Very likely leads to chronic infection.
- Again can lead to formation of carcinoma or cirrhosis. Although, has less tendency than the hepB infection.
Diagnosis: Microscopic studies are done.
- Under microscope, hepatic macrovesicular steatosis is seen.
- In this, a large fat filled vacuole is seen in the hepatocyte displacing the nucleus to the periphery.
- Also can be confirmed by the presence of HCV RNA.
- If the repeated tests indicate the reduction of the RNA particles then it means the infection is improving otherwise persistent levels indicate chronic state.
Prevention/treatment: No vaccine available (Q#2).
- Though oral antiviral drugs are available and treatment is highly effective and treats almost all of the patients.
Q#2. Can you think of a reason of why no vaccines are there for HCV?
A#2. Here’s a hint. They show antigenic variation.
Now the question comes, why they show antigenic variation.
Actually, as you may know that hepatitis viruses are enveloped of lipid bilayer. This envelope also has surface proteins or antigens.
Therefore, in case of HCV, these antigenic variation is shown in case of surface proteins which occurs due to lack of 3′-5′ exonuclease activity i.e. polymerase enzyme lacks the ability to recognise and correct any incorrect base pair. This leads inability to proofread and creation of antigenic variation.
Virus: HDV is an ssRNA virus of genus deltavirus.
- The virus is unique on its own as it is highly associated with HBV. How? (Q#3)
- Well, HDV can either occur along with HBV or after chronic HBV infection leading to coinfection or superinfection respectively.
- Can you answer which one is more severe between both of these infections?
Transmission: Same as HBV.
Symptoms: Same as that of other hepatitis infections but have high chances of severe complications like liver failure, cirrhosis and cancer.
Diagnosis: Ground glass appearance with granular eosinophilic present cells just like in HBV infection.
Prevention/treatment: Currently there are no drugs or treatments available for HDV. Though, most of the cases whether it is a coinfection is limited to acute hepatitis.
- Although, as it is associated with HBV, vaccine against HBV also protects against HDV to some extent.
Q#3. Well we covered the association of HBV and HDV of how, but not why? I mean, what does HDV get from HBV and why it can only occur in presence of HBV?
A#3. Actually hepD can’t proliferate on its own and need hepB surface antigen for its multiplication. That’s why they almost have same mechanism and symptoms. This is the reason hepD is also called a defective RNA virus. Sometimes I wonder, if D means defective or delta.
Virus: HEV also contains ssRNA just like HAV. You will find out many such similarities between both.
- The virus is famous to cause epidemic in developing areas such Middle East Africa and Asia or in central America. Here is the direct link to WHO to know more about it.
Transmission: Just like HAV, it is also a waterborne infection i.e. via fecal-oral route.
Symptoms: Its incubation period is very short and leads to fulminant hepatitis in pregnant women.
- Leads to liver failure and necrosis within days.
- Though, it is not associated with cancer. But I believe, it doesn’t make much difference.
Diagnosis: During histological study, one can observe characteristic spotty necrosis i.e. hepatocytes death in clusters.
Prevention/treatment: Well I have mentioned that it will most likely lead to death of a pregnant lady. In other cases, it is not so serious. It only causes acute hepatitis and can be prevented by drinking sanitised and filtered water.
Well like I promised, I explained everything what I could do on the topic of hepatitis. I hope you have gained something from it.
Now you can answer and differentiate easily between all viral hepatitis types.
Leave the comment if you have any question and to show your love.