Hepatitis Flashcards

1
Q

Hepatitis (disease in general)

A

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.

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2
Q

Types of Hepatitis

A

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.

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3
Q

Hepatitis A structure

A
  • 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

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4
Q

How does Hepatitis A cause disease?

A

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

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5
Q

Hepatitis A

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

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6
Q

Testing for Hepatitis A

A

Tests: IgM and IgG against HAV elevated liver enzymes (Aminotransferases) (general hepatitis)

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7
Q

Prevention and Treatment of HAV

A

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.

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8
Q

Type of vaccine for HAV

A

HAV vaccine is an inactivated or “killed” virus vaccine

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9
Q

Hepatitis B

A

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.

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10
Q

Largest Concentration of Hepatitis B in what region?

A

Western Africa

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11
Q

Hepatitis B Infection

A

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

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12
Q

Chronic Hepatitis (HBV)

A

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

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13
Q

Cancer Caused by HBV

A

Chronic infection can lead to cirrhosis of the liver liver cancer - Hepatocellular carcinoma

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14
Q

Acute vs. Chronic Asymptomatic vs. Symptomatic HBV

A

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.

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15
Q

Infectious Part of HBV virion

A

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.

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16
Q

Immune Decoys

A

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

17
Q

Test for HBV

A

surface antigen and DNA; HEP. B IS A DNA VIRUS

18
Q

Prevention/Treatment of HBV

A

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.

19
Q

Hepatocellular Carcinoma

aka PHC - Primary Hepatocellular Carcinoma

A

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

20
Q

Hepatitis C

A

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.

21
Q

Hepatitis C infection

A

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

22
Q

Hepatitis C Structure

A

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.

23
Q

Hepatitis C Prevention and Treatment

A

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

24
Q

Similarities between Hep. C and HIV

A
  • both enveloped
  • icosahedral
  • (+) ss RNA viruses with 9kb genomes
  • transmitted through bodily fluids
  • mutate rapidly
  • cause chronic infections
25
Q

Difference between Hep C. and HIV

A

HIV becomes a DNA virus when it enters your cells and then integrates into your cells. All the cells have to be eliminated that have the integrated virus. With Hepatitis C, it’s an RNA virus. It’s going to degrade in any of the cells. If you can just stop it from replicating, that RNA genome is going to be chewed up from the cell eventually so you can clear it from the body