Flashcards in 5 - Viral Hepatitis Deck (61)
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1
What is Hepatitis?
Inflammation of the liver
Almost always implies elevation in liver enzymes
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Key liver enzymes
AST and ALT
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Other liver enzymes of consequence in hepatitis
Bilirubin
Albumin
Alkaline Phosphatase
GGT
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Causes of Acute Hepatitis
Viruses A through E (hepatotrophic)
CMV & EBV (non-hepatotrophic)
Other infectious etiologies (TB, MAI, Fungus)
Alcoholic hepatitis
Drug hepatitis
Ischemic hepatitis
Biliary disease (Choledocholithiasis)
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Human Hepatitis Viruses
HAV
HBV
HCV
HDV
HEV
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RNA Hepatitis Viruses
HAV
HCV
HDV
HEV
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Double Stranded DNA Hepatitis Viruses
HBV
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Hepatitis A
ssRNA
7.5 kb Genome
No Envelope
Picornaviridae Hepatovirus
One Serotype
Multiple Genotypes
Acid/Heat Stable
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Hepatitis B
dsDNA
3.2 kb Genome
Envelope
Hepadnaviridae
Multiple serotypes and genotypes (A - F)
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Hepatitis C
ssRNA
9.6 kb Genome
Envelope
Flaviviridae Hepacivirus
Genotypes - 1 to 6
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Hepatitis D
ssRNA
1.7 kb Genome
Envelope
Unclassified (viroid) delta virus
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Hepatitis E
ssRNA
7.5 kb Genome
No Envelope
Unclassified togavirus and alpha virus-like
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Other infectious etiologies of Acute Hepatitis
CMV - Immunocompromised Host
EBV - Mononucleosis, lymphadenopathy, splenomegaly
TB & M. Avium Intracellurare
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Symptoms of Acute Viral Hepatitis
Complaint: Intense Fatigue, Nausea, Anorexia
Yellow Eyes/Skin, Dark Urine
Low Grade fever, Abdominal Pain
Arthralgia, myalgia, headache
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Signs of Acute Viral Hepatitis
Jaundice
Hepatomegaly w/ RUQ tenderness
Fever - Low Grade
Splenomegaly - infrequent
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Liver Blood Test Abnormalities - Acute Viral Hepatitis
AST & ALT: 500 - 5000 IU
Bilirubin: Generally elevated, both conjugated and unconjugated
Alkaline Phosphatase: Minimally elevated
Bilirubin and Urobilinogen in Urine: Increased (Coca cola color)
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Normal AST/ALT
40 +/- 5 or 10
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What is Alkaline Phosphatase elevation associated with?
Biliary Disease
Infiltrative Disease
Not so much viral
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Outcomes of Acute Viral Hepatitis
Chronic Hepatitis
OR
Cure
OR
Fulminant Hepatitis
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Fulminant Hepatitis
Overwhelming inflammatory response directed by the immune system against the body
Patient gets very sick
75% - 85% Mortality
Seen with HAV, HBV, HCV
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Hepatitis A Virus - In Vitro
Monkey & Human Cell Cultures
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Hepatitis A Virus - In Vivo Replication
In Cytoplasm of Hepatocyte
(Human and other primates)
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Hepatitis A - Transmission
Oral Fecal
Excreted in stool 2 weeks PRIOR to clinical illness
Therefore it spreads in the military
1 month incubation period
Children often asymptomatic
NEVER causes chronic hepatitis
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Serologic Course
1st Month - Fecal excretion
2nd Month - Symptoms & Increase in ALT
2nd - 6th month IgM Antibody spikes
3rd - 4th month, symptoms resolve
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Marker for acute HAV infection
IgM anti-HAV spike
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Hepatitis A - Prevention and Treatment
No treatment available
Passive immunity with Gamma Globulin can ameliorate disease in early stages of the infections
Gamma Globulin can prevent disease pre-exposure
Vaccine available to induce active immunity
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Hepatitis B - In Vitro
Primary hepatocyte culture and transfection of cloned HBV DNA
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Hepatitis B - In Vivo Replication
In cytoplasm, cccDNA in nucleus
Hepatocyte and other tissues
(Human and other primates)
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Diagnosing Hepatitis B - Useful
E Antigen
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Hepatitis C - Replicates in
Cytplasm
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Hepatitis B - Viral Replication
Viral Entry
Uncoating (in Cytoplasm)
DNA Repair (in Nucleus)
Transcription (in Nucleus)
Export to Cytoplasm
Priming, Translation via Reverse Transcriptase
You can treat with NRTIs
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Hepatitis B Virus - Immunopathogenesis
Typical B Cell and T Cell response
Results in hepatocyte apoptosis
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Hepatitis B - Transmission
Horizontal - Parenteral, secretions, sexual
Vertical - Mother to child
6 - 8 week incubation
20% of patients have "serum sickness" prodrome
4% of adult patients develop chronic hepatitis
Treatment and vaccine available
NO CURE!!!!!!!!!!!!!!!
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If you get hepatitis B early
You're likely to get chronic hep B
You don't have symptoms
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If you get hep b late
You're not likely to get chronic hep b
You do have symptoms
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Hepatitis B Diagnosis
Antigens and Antibodies
Many specifics to know
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Acute HBV Infection
IgM Anti-HBcore
Order Anti-Core IgM - Separates out ACUTE infection
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HBV Prevention
HBV Infection can be prevented with both passive and active immunity
High titer immunoglobulins can be administered at birth or post exposure to prevent acute HBV
Recombinant vaccine available to induce active immunity
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Hepatitis C Virus - In Vitro
Primary hepatocyte and T Cell cultures (Replicon system)
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Hepatitis C Virus - In Vivo Replication
In Cytoplasm
Hepatocyte and lymphocyte
(Human and other primates)
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Hep C Replication
Binds to hepatocyte, enters
Uncoats
Translates IN CYTOPLASM
RNA translated
Protein products synthesized in ER
Progeny genome created
New virus assembled
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Hepatitis C Immunopathogenesis
Virus secreted in blood
B Cells aren't neutralizing Ab - Only marks, doesn't clear
ELISA screening Ab test for Ab produced by B cells
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Hepatitis C Clinical
Most common cause of chronic hepatitis in USA
1.5% of population in USA carries the virus
Parenteral transmission - blood, sexual
6 - 8 week incubation period
Acute infection generally mild
80% develop chronic disease
No vaccine available
Treatment - 80 - 99% cure rate
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Acute Hepatitis C Serologic Pattern
ALT goes up over the first 3 months
ALT goes down over the second 3 months
Anti HCV Ab goes up at about 6 months
Acute Hep C, 20% get better, 80% get chronic
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Outcome following Hep C Infection
Acute Hep C
80% of those go to chronic infection
70% of those go to chronic hepatitis
20% of those get cirrhosis
1 - 4% of those/yr get HCC OR 4 - 5% get Decompensation
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Hepatitis D
Known as Delta Agent
Uses the HBsAg protein coat
Hep B must be present (coinfection or preexisting)
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Hepatitis E
Waterborne resembling Hepatitis A
Endemic in Asia, Northern Africa and MExico
Rarely seen in the USA
Antibody testing is not standardized
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Chronic Hepatitis
Elevated AST and/or ALT for greater than 6 months
Characteristic path findings
Many different diseases cause chronic hepatitis
Liver biopsy frequently performed for definitive diagnosis
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Chronic Hepatitis - Path
Portal Tracts, Peri-portal regions and lobules involved
Liver biopsy:
Chronic inflammation
Increased inflammatory cells
Many plasma cells and lymphocytes
Inflammation > Fibrosis > Cirrhosis
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Chronic Liver Enzyme Elevation - Etiology
Viral Infection - B & C
Autoimmune
Drugs
Metabolic - Wilson's
Fatty Liver - Steatohepatitis
Alcohol
Others - CHF, hemochromatosis, ulcerative colitis, celiac disease, others
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Chronic Hepatitis B & C
Cirrhosis in 20% of patients
Liver failure and hepatoma develop in 1/2 of cirrhotics
Treatment available with varying success rates
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Diagnosis of Chronic Hepatitis B or C
Chronic AST or ALT elevations (though some patients have normal enzymes)
Positive serology - HBsAG or Anti HCV
Positive DNA or RNA in blood
Diagnostic Liver Biopsy
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Difference between acute and chronic hep B serologically
Surface antigen NEVER disappears (chronic)
DNA is continuously present in the blood
E antigen is
HE WAS NOT CLEAR 9:45am
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Chronic HBV - 4 Phases of Disease over Decades
Immune Tolerant
Immune Clearance (HBeAg positive, Chronic HBV)
Inactive Carrier (Chronic HBV, surface Ag positive, low DNA, low transaminase)
Reactivation (HBeAg negative, Chronic HBV, IT IS A MUTANT)
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Serologic Events in HBV Infection
Surface Antigen - Acute Hep B or some form of Chronic
No Surface Antigen - Vaccine responder or immune
Anti HBs - Vaccine Responder (but no anti-core) or Exposed and cured (with anti-core)
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The more HBV DNA in your body
The higher chance you have of getting cirrhosis
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Therapeutic Options of Hepatitis B Treatment
Most often:
Tenofovir (Viread)
Entecavir (Baraclude)
Peg-Interferon (Pegasys or PegIntron)
Telbivudine (Tyzeka)
Lamivudine (Epivir)
Adefovir (Hepsera)
Emtricitabine (FTC)
These drugs don't get rid of episomal DNA in the nucleus. When treatment stops, virus comes back!
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Chronic HCV Infection
ALT goes up, ALT goes down
Chronic mild ALT elevations
HCV RNA measurable in the blood chronically
Ab measurable but doesn't do anything to clear virus
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Hepatitis C Treatments
90 - 100% CURE rates!!
Sofosbuvir
Simeprevir
Daclatasvir
Ledipasvir
Ombitasvir
Paritaprevir
Ritonavir
Dasabuvir
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Factors affecting response to HCV Rx
Virus - Genotype, Viral Load
Host - IL28B
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