Hepatitis is inflammation of the liver. The most common cause of hepatitis is Viral Hepatitis, but there are many other disease processes such as fatty liver disease, alcohol, medications, hereditary diseases, and autoimmune diseases that can cause hepatitis. We will cover those topics in other videos. This video will focus on Viral Hepatitis, but it should also be noted that other viruses (such as EBV, CMV and herpes) can cause liver inflammation. In Viral Hepatitis damage to liver results from Cytotoxic CD8 T-Cells killing hepatocytes (liver cells) infected with the virus.
Types of Viral Hepatitis:
- HAV – Hepatitis A Virus
- HBV – Hepatitis B Virus
- HCV – Hepatitis C Virus
- HDV – Hepatitis D (Delta) Virus
- HEV – Hepatitis E Virus
Although the 5 viruses listed above have similar sounding names and can have similar clinical presentations it is actually a diverse group of unrelated viruses. Each virus is within a different classification. The family and order of these viruses is low yield so I’m not going to cover it, but I will cover the genome and envelope. Hep B is a double stranded DNA virus, while Hep A C D & E are all single stranded RNA viruses. Hep B C & D are enveloped while Hep A & E are naked.
Hep B, Hep C, and Hep D are transmitted through IV drug use, blood transfusions (before 1985 when screening was implemented), and needle sticks. Hep B can also be transmitted sexually or from mother to fetus (vertical transmission) more commonly than the others. Hep A and Hep E are transmitted by the fecal-oral route in food or water. Undercooked seafood is another source for Hepatitis A and Hepatitis E. Prevention for these viruses includes improved sanitation, clean water, better hand hygiene, and heating food properly. Since these viruses are more common in developing countries, the question stem often mentions recent travel. Hepatitis Delta cannot infect a host on its own, because it does not have all of the necessary “machinery” for replication. Therefore, Hep D only infects patients who also have Hep B. The presence of Hep D increases the severity of Hep B.
Viral Hepatitis can have a wide variety of clinic presentations and given the large amount of overlap between the different viruses you cannot make a diagnosis based solely on clinical presentation. Viral Hepatitis is often subclinical (asymptomatic), but these individuals can still spread the disease to others. When symptomatic it is primarily characterized by anorexia, nausea/vomiting, jaundice (yellow skin), dark urine, malaise and fever. There may also be hepatomegaly (enlarged liver) and associated RUQ pain. These symptoms often don’t arise until multiple weeks after infection. Hepatitis B is associated with PAN (Polyarteritis Nodosa) which we will discuss in further detail in the vasculitis section.
In most cases of viral hepatitis acute inflammation is self-limited and quickly resolves without causing permanent damage. However, certain types of Hepatitis can progress from acute hepatitis to chronic hepatitis (inflammation >6 months). Chronic Hepatitis can be symptomatic or subclinical (referred to as a “Chronic Carrier”). Long term complications from chronic infection include fibrosis/scarring/cirrhosis and increased risk of hepatocellular carcinoma. Hep B, Hep C, and Hep D can progress to chronic hepatitis. About 10% of Hep B cases progresses to chronic hepatitis, while about 90% of Hep C progresses to chronic hepatitis. Hep A & Hep E can’t progress to chronic hepatitis (Think A for “Acute only”).Fulminant Hepatitis is a type of acute liver failure that is rare (<1%) among Hep A, Hep B, and Hep C. However, when present it can lead to death within weeks if transplant is not received expediently.
Hepatitis has elevated Liver Enzymes (AKA Liver Function Tests or Transaminases) as these enzymes are leaked into the blood as hepatocytes are damaged. Both Alanine Aminotransferase (ALT or SGPT) and Aspartate Aminotransferase (AST or SGOT) are elevated, but ALT is elevated more. This is the opposite of alcoholic liver damage which usually has AST>ALT. ALT is usually >1000 in acute hepatitis, while levels can vary during chronic hepatitis. LFTs do not necessarily correlate with the severity of the disease. Hepatitis will also have elevated bilirubin (conjugated and unconjugated) as bile duct cells are injured. In severe cases of chronic hepatitis a liver biopsy may be performed to rule out diagnoses or determine the severity of liver damage. If active infection is present you may be lymphocytic infiltrates, hepatic swelling, necrosis/fibrosis, or acidophilic bodies called Councilman Bodies which signify apoptosis.
Hepatitis Serum Serology:
- Hepatitis B Surface Antigen (HBsAg) – Proteins in the outer lipid envelope of Hepatitis B. Can test serum for presence. Hep B Vaccine is mostly made up of HBsAg.
- Hepatitis B Surface Antibody (Anti-HBs or HBsAb) – Antibody directed against Hep B surface antigen. IgM early on and then later IgG. Can test serum for presence. Confers immunity to Hep B
- Hepatitis B Core Antigen (HBcAg) – Core antigen in capsid. Not detectable in serum, because it covered by the envelope.
- Hepatitis B Core Antibody – Antibody directed against core antigen. IgM early on and then later IgG. Can test serum for presence. Does not necessarily signify immunity to Hep B
- Window Period – Short period during acute infection (or vaccination) when there is no HBsAg or Anti-HBs found on serum testing. Both are present, but they are bound together and therefore are not detectable by the test. During this period one could accidentally misdiagnose a patient as not having Hep B. During acute infection HBeAg and Anti-HBc may be present during the window period.
Hepatitis B e Antigen (HBeAg) is another protein that can be tested in a patient’s serum. I did not include it in the above pictures because it would have further complicated an already difficult concept. HBeAg is a protein involved with viral replication. All you need to know is that if HBeAg is present or positive it signifies that there is an infection (either acute or chronic), that the virus is actively replicating, and it is highly infectious. This means the virus is more likely to be spread, for example from mother to fetus. It doesn’t show up as often on the exam, but you can also test for HBV Viral DNA (AKA HBV Viral Load) using PCR. A positive result (or high quantitative reading) can be interpreted similar to a positive HBeAg result. It means the virus is actively replicating and is more contagious. A positive HBeAg or viral load signifies that treatment is necessary for chronic Hep B.
For antigen and antibody testing I have just discussed HBV so far since it is by far the highest yield and the most complicated. However, similar tests can be used for other viruses and the same principles apply. For example, the presence of Anti-HAV IgG signifies previous vaccination or recovery from a previous acute infection. Anti-HAV IgM signifies active but resolving acute infection. Also HCV Viral RNA (AKA HCV Viral Load) and Hepatitis C Antibody can be used to diagnose HCV.
Hep A & E only require supportive treatment as they are self-limited. Acute hepatitis due to Hep B & C usually do not require specific treatment. Chronic cases of Hep B & C do sometimes require treatment. Treatment is usually indicated in chronic hepatitis if there is a high viral load or positive HBeAg. Interferon is the first line treatment option for Hep B, while the selection of medications for Hep C treatment is based on a number of factors including the specific genetype present. Hep C pharmacotherapy is beyond the scope of Step 1. We will discuss antivirals more in a later video. Transplant may be indicated in severe cases of chronic infection or fulminant hepatitis.
There is a vaccine for Hepatitis A and Hepatitis B, but none for the other types of hepatitis. The Hep A vaccine is available in inactive or live attenuated versions. It is often given to travelers before going to an endemic area. The Hep B vaccine is a recombinant vaccine that is made using yeast cells to create the Hepatitis B surface antigen. It is routinely given in the US to 1 day old newborns. Additional doses follow.