Hepatitis Flashcards
Hepatitis (disease in general)
Inflammation of the liver
Acute hepatitis is associated with fatigue, abdominal pain, loss of appetite, nausea and vomiting, darkening of the urine, followed by jaundice.
Yellow
Jaundice - yellowing in skin, eyes
caused by buildup of Bilirubin in the blood: a byproduct of hemoglobin metabolism due to liver not liver properly metabolizing and excreting it.
Types of Hepatitis
Hepatitis A virus - HAV (“infectious hepatitis”) Hepatitis B virus - HBV (“serum hepatitis”)
Hepatitis C virus - HCV (formerly “non-A, non-B hepatitis virus”) Hepatitis D virus - HDV (delta particle)
A,B,C: >90% of cases of viral hepatitis
Hepatitis E virus Hepatitis G virus
HSV, CMV, EBV, Yellow Fever Virus can also cause hepatitis
Alcohol abuse, some drugs (e.g. acetaminophen), toxic chemicals (e.g. some organic solvents) can also cause or worsen hepatitis.
Hepatitis A structure
- Picornavirus family
- ssRNA genome
- non-enveloped
- Typical enterovirus in most ways
- mostly released from cells by exocytosis.
There is some cell lysis, but
disease pathogenesis is the result of the T cell immune response in the liver
How does Hepatitis A cause disease?
the T cell immune response is causing inflammation in the liver. You’re getting an aggressive cell mediated immune response. CD8 cells are coming in and killing infected cells and that inflammation is what’s causing the liver disease.
The virus itself just leaves via exocytosis
Hepatitis A
estimated 2,500 acute hepatitis A infections in the United States.
Mostly fecal-oral transmission - often in localized outbreaks. Contaminated food: vegetables, shellfish.
“short incubation hepatitis” 15-45 day incubations period
Shedding of virus in stool occurs for 2 weeks prior to symptoms.
Causes acute infection only - no chronic carrier state as for HBV or HCV. No fulminant hepatitis. Lifelong ab protection after infection.
Symptoms typically last 8 weeks and include: Fatigue Abdominal pain Loss of appetite Nausea, vomiting Dark urine Jaundice - 70-80% of adults
90% of childhood infections are asymptomatic
<0.5% mortality
Testing for Hepatitis A
Tests: IgM and IgG against HAV elevated liver enzymes (Aminotransferases) (general hepatitis)
Prevention and Treatment of HAV
Hygiene, e.g. hand washing by food preparers
Vaccine with inactivated HAV is ~100% effective recommended to travelers to developing nationS
Immune serum containing antibodies can be given pre-exposure if traveling too soon for a vaccine to become effective.
Immune serum can also be given as prevention post exposure. Vaccine can be administered up to 2 weeks post exposure.
Type of vaccine for HAV
HAV vaccine is an inactivated or “killed” virus vaccine
Hepatitis B
Serum hepatitis” or “long incubation hepatitis” incubation period averages 90 days (4-25 weeks variation)
Endemic in many developing countries 1-2 million people infected in US
Spread via mother-fetus, or during childhood where endemic.
A predominantly sexually or blood transmitted disease in the developed world.
HBV is the virus that led to the development of universal precaution recommendations of the ADA and CDC for dentists in the 1970’s following a series of disease clusters in dental practices.
Largest Concentration of Hepatitis B in what region?
Western Africa
Hepatitis B Infection
Symptoms begin an average of 90 days (range: 60–150 days) after exposure to HBV.
30% of infected people are asymptomatic Infection can be:
- Acute with resolution - 90% in adults
- Chronic
> Chronic carrier - can continue to spread infection
despite lack of symptoms
> Chronic persistent hepatitis
Infection of infants and children increases the risk of chronic infection to 90% and 25-50% respectively
Acute symptoms are like HAV infection but with joint pain
Like HIV, HBV produces 1010 - 1011 virions per day and mutates rapidly
Chronic Hepatitis (HBV)
6 months of liver inflammation, detected by:
Alanine aminotransferase ALT in blood ALT is a liver-specific enzyme, so its presence in blood indicates injury to the liver
Cancer Caused by HBV
Chronic infection can lead to cirrhosis of the liver liver cancer - Hepatocellular carcinoma
Acute vs. Chronic Asymptomatic vs. Symptomatic HBV
Determined by IMMUNE RESPONSE
Outcome is determined by the cellular (T cell) immune response.
Strong response causes liver disease in the short term but resolution of infection in the mid-term.
Weak cellular response leads to chronic infection and long term risk of advanced disease: liver scarring,
cirrhosis, liver cancer - primary hepatocellular carcinoma.
And person becomes a carrier who do not necessarily display overt symptoms but can spread virus.
Infection of infants frequently leads to them becoming chronically infected carriers.
Infectious Part of HBV virion
the DANE PARTICLE
It’s got surface antigen and it’s got the genome inside of it and it’s got a core antigen. It’s got all the pieces of a fully functional virus. It’s the circular form with a double coat. When you see these with the double rings that’s the infectious form of the virus.
Immune Decoys
Not infectious particles
These are simply made up of the surface antigen protein with a lipid envelope that attract antibodies in the body and prevent them from inhibiting the infectious virus
Formed by self assembly
the vaccine is artificially making these immune decoys which are not infectious because they don’t have the viral nucleic acid or anything else in them
Test for HBV
surface antigen and DNA; HEP. B IS A DNA VIRUS
Prevention/Treatment of HBV
Safe behavior - safe sex, no IV drug use (needle sharing)
There are no antivirals for acute infection, but chronic infection can be treated with RT inhibitors used for HIV also - e.g. Lamivudine.
Immune serum can be given after exposure and to newborns of HBV+ mothers
.
Recombivax vaccine is a subunit vaccine using recombinant DNA technology to make HBsAg particles. 3 injections and a titer test for antibodies to surface antigen.
Vaccination elicits an antibody response. This prevents virus from reaching liver.
Vaccine can be given to pregnant women and as a post-exposure prophylaxis.
Hepatocellular Carcinoma
aka PHC - Primary Hepatocellular Carcinoma
associated with HBV infection
Chronic HBV (and HCV) infection causes ongoing inflammatory responses and oxidative damage to chromosomal DNA of hepatocytes
HBV DNA sequences are found integrated into HCC tumor DNA
Integration of HBV DNA occurs in breaks in the cellular DNA of hepatocytes
Alcoholism is a risk factor for HCC
Hepatitis C
Most spread is through blood contact rather than through sex or food. IV drugs, tattooing, unsterilized surgical equipment
Mother to child during childbirth
2.7 - 4 million infected in US, 170 million in world.
Hepatitis C infection
Acute infection with resolution - 15%
Chronic persistent infection with chronic liver disease later in life - 70%
Rapid disease progression - cirrhosis - 15% Liver cancer in 5% of patients.
25% of hepatocellular carcinomas are associated with HCV
Hepatitis C Structure
Flavivirus: +ssRNA virus, enveloped
Mutates very rapidly (RNA virus)
there is a great diversity in the glycoproteins which are the major antigens.
6 major serotypes/genotypes. No cross-protection.
Like HIV and HBV, HCV produces 1010 - 1011 virions per day (helps rapid mutation).
Tissue damage is caused by the cell-mediated immune response to infected cells.
The virus itself is apparently non-cytopathic.
Hepatitis C Prevention and Treatment
Alcohol worsens liver damage
No vaccine - variability is one problem
Ribavirin +Pegylated Interferon-α was the standard of care until Sofosbuvir
Side effects are severe, cure rate 50%
Sofosbuvir recently approved to treat hep C
It inhibits the viral RNA polymerase - a chain terminator. Can cure Hep C in many cases
Similarities between Hep. C and HIV
- both enveloped
- icosahedral
- (+) ss RNA viruses with 9kb genomes
- transmitted through bodily fluids
- mutate rapidly
- cause chronic infections
