W3P3 Flashcards
What is Viral Hepatitis
Viruses that cause infection and destruction of hepatocytes
Some can cause chronic hepatitis
- Host immune system unable to clear acute infection
- Continuous hepatocyte injury
- End-point: cirrhosis (inflammation/fibrosis within liver)
What are the types of Hepatitis Viruses
- Nucleic Acid
Hep A: ssRNA Hep B: ds DNA Hep C: ss RNA hep delta: ssRNA Hep E: ss RNA
only Hep B is DNA
Transmission of the 5 Hep viruses
Hep A and Hep E: Fecal oral, [sexual, small]
Hep B, C, Delta: Sexual, Vertical, Parenteral
parenteral: administered or occurring elsewhere in the body than the mouth and alimentary canal.
Relation between the Hepatitis Viruses
Bottom line: none of the hepatitis viruses are related (different genetic material, different structures, different classification…)
Only grouped together because they all affect the liver
Hepatitis A
- transmission route
Fecal-oral transmission
Consumption of contaminated water, shellfish, other food
Not associated with chronic hepatitis and no link to hepatic cancers
Hep A clinical manifestations
- Prevention
Kids: mild disease (jaundice, fatigue)
Adults: jaundice, other symptoms of liver inflammation, in rare cases: fulminant hepatic failure
Prevention:
Vaccination
(alone or in combination with HBV)
Post exposure prophylaxis:
Anti-Hep A immunoglobulin if young age or immunocompromised
Otherwise: HAV vaccine within 14 days of exposure
Which antibodies should you measure for Hep A
IgM: will peak first: good if you’re measuring early after exposure, however they will drop
IgG: will rise as IgM falls and STAY high, so this should be measured 8 weeks after infection
Hepatitis E
- transmission
Similar to Hepatitis A in terms of transmission (fecal-oral) and symptoms
Usually no chronic hepatitis
Infection may lead to fulminant hepatic failure in pregnant women
common in farms/travellers
Hepatitis B
- Modes of Transmission
HBV transmitted via blood (highest levels), semen. Virus also found in saliva, cervical secretions.
Can survive for long periods of time on environmental surfaces: potential for horizontal transmission in daycares, institutions for disabled, etc.
IVDU, sexual occupation; high in americas
Perinatal: Africa
Childhood/horizontal: Asia
Which hep infections lead to chronic hepatitis
Hep B and Hep C
Natural history of Hep B
- Areas with high prevalence of disease
Perinatal infx leads to 90% chance of chronic infection - Areas with low prevalence of disease
Adult infection leads to acute hepatitis and there is less than 5% chance it leads to chronic infection
- immune tolerance [inflammation and fibrosis] can last for decades in perinatal infection vs within months for adult
so congential/vertical transmission is WORSE
Hep B viral structure
Hep B core antigen (HBcAg)
Hep B surface antigen (HBsAg)
Acute vs Chronic Hep B serology
Acute Hep B serology:
HBsAg peaks and falss first, IgM anti-HBc same
anti HBs only rises and falls AFTER anti HBsAg falls
total anti HBc rises and STAYS high
Chronic Hep B serology:
HBsAg rises first and STAYs high along with total Anti-HBc
Since HBsAg never falls, there is no anti-HBs
IgM anti HBc rises and falls similar to acute
SO your anti CORE bodies are useless to distinguish because they are the same for chronic vs acute
your HBsAg levels after 24 weeks can determine if the infection is chronic
if there is presence of anti-HBs = this is an ACUTE infection
IMPORTANT:
What Hep B serology test would you order if
a. Is my patient currently infected with hepatitis B?
b. Has my patient ever been infected with hepatitis B?
c. Is my patient immune to hepatitis B?
d. Does my patient have acute hepatitis B infection?
Is my patient currently infected with hepatitis B?
HepBsAg (surface antigen)
Has my patient ever been infected with hepatitis B?
HepBcIgG (core IgG)
Is my patient immune to hepatitis B?
HepBsAb (surface antibody)
Does my patient have acute hepatitis B infection?
HepBcIgM (core IgM)
Interpreting Hep B serology, what values for HBsAg, HBsAb, HBcAb would you expect in the following cases:
No prior exposure
Vaccination
Resolved Acute infection
No prior exposure: all three negative
Vaccination: only HBsAb is positive
Resolved Acute infection: only HBsAb and HBcAb are positive
Interpreting Hep B serology, what values for HBsAg, HBsAb, HBcAb would you expect in the following cases:
Acute or chronic infection *
Chronic infection
Acute or chronic infection: HBsAg, positive. HBsAb NEGATIVE. HBcAB positive
- unable to develop surface antibodies during an active infection. we do develop core antibodies^
Chronic infection, late: HBsAg positive. HBsAb negative. HBcAb positive
yes they are the SAME, you can’t tell the difference with these two measures you need to look at HBeAg which is negative for chronic infection
Prevention of Hepatitis B
Vaccinate, vaccinate, vaccinate
Safer sex practices
Screen pregnant women and protect babies of HBV positive women (give babies hepatitis B Ig and vaccine immediately after birth)
Prevention of Hepatitis B
Vaccinate, vaccinate, vaccinate
Safer sex practices
Screen pregnant women and protect babies of HBV positive women (give babies hepatitis B Ig and vaccine immediately after birth)
Prevention of Hepatitis B
Vaccinate, vaccinate, vaccinate
Safer sex practices
Screen pregnant women and protect babies of HBV positive women (give babies hepatitis B Ig and vaccine immediately after birth)
Treatment of Hep B Goals
Goals
suppress HBV replication (treat patients with high HBV DNA)
Prevent liver-related complications
cirrhosis, hepatocellular carcinoma (20-40% lifetime risk in chronic infection!)
Recall HBV is a DNA virus, so it’ll be there for life* can’t get rid of it only manage it.
Treatment for Hep B
Tenofovir
Entecavir
Laminvudine
HDV
Dependent on HBV for production of envelope proteins; ie. You can only get HDV infection in the presence of HBV
HBV/HDV coinfection occurs commonly in Mediterranean area and parts of South America
Get more severe hepatitis when both viruses are present, and increased risk of complications
Hep C epidemiology in Canada
- greatest route of transmission
Risk factors (Canada):
60%: IDU * [ greatest route of transmission]
20%: immigrants
10% contaminated blood products
Steps for HCV diagnosis
Initial test: test for HCV Ab
If positive: test for HCV RNA
much simpler than HBV diagnosis!!
- much simpler than HBV diagnosis (recall we had to check for core vs surface antibodies/antigens)
Hepatitis C disease
- progression
- Symptoms
Progresses to chronic disease in approx. 80% of people infected
Symptoms:
Most are asymptomatic
If symptoms: anorexia, vague abdominal discomfort, nausea, fatigue, and fever
Long-term: cirrhosis, liver failure (#1 indication for liver transplantation in most centres)
Hep C prevention vs treatment
OPPOSITE compared to HBV
Prevention:
No vaccine!
Blood bank screening, precautions to avoid exposure to blood, safer sex practices (MSM), needle-exchange programs
Treatment:
goal is to CURE, this is RNA virus so we can get rid of it
Direct-acting anti-viral Rx (DAAs)
- shorter treatment - less side effects - much more effective (especially for genotype 1)
Hepatitis and Needlestick injuries
- most to least infectious
Concern re. transmission of HBV, HCV and HIV
HBV most infectious > HCV > HIV
approx 30%/ 3% / 0.3%
What to do if non-immune to HBV:
ASAP: HBV vaccine and ‘HBIg’ (anti- HepBsAg)
Define
Diarrhea
Acute vs Chronic
Diarrhea: ≥ 3 loose or watery stools per day
Acute: ≤ 14 days duration
Chronic: > 30 days duration
Major cause of infant mortality** (malnutrition)
How do people die from Diarrhea
Dehydration (water loss)
Salt imbalances (especially sodium and/or potassium)
Acidosis (bicarbonate losses)
Hemorrhage (if dysentery)
Chronic anemia (hematochezia)
Malnutrition
Sepsis (due to bowel perforation or bacterial translocation into the blood)
Causes of Bacterial Infectious Diarrhea in the Developed World
Escherichia coli* Enterohemorrhagic (EHEC) -> HAMBURGERS DIARRHEA O157:H7 Enterotoxigenic* (ETEC) -> HEMORRAGIC DIARRHEA Salmonella spp* - Non-typhi and typhi Shigella spp* Yersinia enterocolitica Campylobacter jejuni Clostridium difficile Listeria Monocytogenes
- those shared in developing countries, INCLUDING:
Vibrio
Causes of Viral Infectious Diarrhea in the Developed world
Calicivirus/Norovirus
- Norwalk-like
Rotavirus
in developing countries
* HIV, influenze, SARS
Causes of Protozoal Infectious Diarrhea in the Developed World
Giardia lamblia Cyclospora cayetansis Cryptosporidium spp Microsporidium spp Isospora belli Entamoeba histolytica
Purely Toxin-mediated = BACTERIAL
Causes of Infectious Diarrhea : Developed World
Enterotoxigenic E. coli
Traveller’s diarrhea
In North America, which pathogen is most likely to cause diarrhea
VIRAL
Most infectious diarrhea is viral in origin
Over 90% of stool samples have no bacterial pathogen
Visibly bloody stool is a good predictor of isolation of a bacterial pathogen
Especially for EHEC
Blood Diarrhea
- Whare the common pathogens
sign hat is is most likely BACTERIAL Known as dysentery if GROSSLY visible blood Bacterial: SSCYE Shigella spp Salmonella spp Campylobacter jejuni Yersinia enterocolitica Escherichia coli O157
Viral:
None really
Parasitic:
Entamoeba histolytica
Which is the only parasite that causes bloody diarrhea
Entamoeba Histolytics
A closer look at bloody diarrhea
Escherichia coli O157 H7 (EHEC)
Gram negative enteric rods
- Contain a toxin created by a viral plasmid inside the cell
Reservoirs are mammalian GI tracts
A common cause of enteritis due to food poisoning
Most common cause of acute kidney failure in children
DISEASE = enteritis, starts about 1-2 days after infection and lasts for about 5-10 days
Severe cramps, diarrhea is usually very bloody, usually NO fever
Usually self limiting
2-7% develop Hemolytic Uremic Syndrome (HUS)
- Shigatoxin (also known as verotoxin)
- Renal failure
- Consumptive thrombocytopenia
- Vascular hemolysis (shearing of red blood cells called schistocytes or schizocytes)
- Stupor, confusion, and seizures
- Worsens with antibiotic therapy (release of the toxin)
DON’T TREAT WITH ANTIBIOTIC^
A closer look at bloody diarrhea
Salmonella spp
Gram negative enteric rods (only 2 types but many serogroups)
Reservoirs include poultry and reptile GI tracts
Need about 105 bacteria to cause disease
- Disease = diarrhea (usually bloody), abdominal cramps, and fever 2 days after infection
- Lasts about a week
Typhoid fever is the most serious form
Salmonella enterica serogroup typhi
Usually disseminates to various organs (blood, liver etc)
High fever, stupor, cramps, bloody diarrhea, blood sepsis
Fleeting rose spots on skin, leukopenia with left shift
Interestingly: bradycardia
RECURRENCE IS LINKED TO PRESENCE OF BILIARY STONES
Thyphoid we need to treat but the rest of the salmonellas that are non-thyphoid we don’t need to treat cause theyre self limiting
A closer look at bloody diarrhea
Shigella spp
Gram negative enteric rods
Reservoirs are only primates
Need ONNLYYY about 10 (yes..10!) bacteria to cause disease
Disease = DYSENTERY, abdominal cramps, and fever 1-2 days after infection
Lasts about a week
HIGHLY contagious:
High fever, stupor, cramps, bloody diarrhea
BLACK CURRANT JELLY-like stools
Seizures due to shigatoxin; SOMETIMES HUS
NEED TO TREAT, highly contagious
A closer look at bloody diarrhea
Campylobacter jejuni
Curved Gram negative enteric rods
Reservoirs are bird GI tract
Most common cause of bloody diarrhea in daycare settings
One of the most common causes of enteritis due to food poisoning
DISEASE = enteritis, starts about 2 days after infection and lasts for about a week
- Cramps, diarrhea may be bloody, SOMETIMES HUS
- Usually self limiting
- Guillain-Barré syndrome after about 2-3 weeks [*** this can cause peripheral nerve disease]
HIGHLY contagious
A closer look at bloody diarrhea
Yersinia enterocolitica
Gram negative enteric rod
Loves iron (uses it as a growth factor)
- High iron states are a risk factor
Various mammals are the reservoir
- Zoonosis
- Consumption of undercooked meat, or unpasteurized milk, or fecal oral contact
DISEASE = enteritis, starts within a week after infection and lasts 1-3 weeks, sepsis and bacteremia in immune suppressed people
In young children:
- Bloody diarrhea and terminal ileitis
- Mesenteric adenitis
In older children and adults:
- Severe abdominal cramps that may mimic appendicitis (pseudoappendicitis)
Post infectious arthritis
