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5 - Viral Hepatitis Flashcards

1
Q

What is Hepatitis?

A

Inflammation of the liver

Almost always implies elevation in liver enzymes

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2
Q

Key liver enzymes

A

AST and ALT

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3
Q

Other liver enzymes of consequence in hepatitis

A

Bilirubin
Albumin
Alkaline Phosphatase
GGT

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4
Q

Causes of Acute Hepatitis

A 
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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5
Q

Human Hepatitis Viruses

A 
HAV
HBV
HCV
HDV
HEV
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6
Q

RNA Hepatitis Viruses

A

HAV
HCV
HDV
HEV

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7
Q

Double Stranded DNA Hepatitis Viruses

A

HBV

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8
Q

Hepatitis A

A

ssRNA
7.5 kb Genome
No Envelope
Picornaviridae Hepatovirus

One Serotype
Multiple Genotypes
Acid/Heat Stable

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9
Q

Hepatitis B

A

dsDNA
3.2 kb Genome
Envelope
Hepadnaviridae

Multiple serotypes and genotypes (A - F)

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10
Q

Hepatitis C

A

ssRNA
9.6 kb Genome
Envelope
Flaviviridae Hepacivirus

Genotypes - 1 to 6

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11
Q

Hepatitis D

A

ssRNA
1.7 kb Genome
Envelope
Unclassified (viroid) delta virus

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12
Q

Hepatitis E

A

ssRNA
7.5 kb Genome
No Envelope
Unclassified togavirus and alpha virus-like

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13
Q

Other infectious etiologies of Acute Hepatitis

A

CMV - Immunocompromised Host
EBV - Mononucleosis, lymphadenopathy, splenomegaly
TB & M. Avium Intracellurare

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14
Q

Symptoms of Acute Viral Hepatitis

A

Complaint: Intense Fatigue, Nausea, Anorexia

Yellow Eyes/Skin, Dark Urine
Low Grade fever, Abdominal Pain
Arthralgia, myalgia, headache

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15
Q

Signs of Acute Viral Hepatitis

A

Jaundice
Hepatomegaly w/ RUQ tenderness
Fever - Low Grade
Splenomegaly - infrequent

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16
Q

Liver Blood Test Abnormalities - Acute Viral Hepatitis

A

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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17
Q

Normal AST/ALT

A

40 +/- 5 or 10

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18
Q

What is Alkaline Phosphatase elevation associated with?

A

Biliary Disease
Infiltrative Disease

Not so much viral

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19
Q

Outcomes of Acute Viral Hepatitis

A

Chronic Hepatitis

OR

Cure

OR

Fulminant Hepatitis

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20
Q

Fulminant Hepatitis

A

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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21
Q

Hepatitis A Virus - In Vitro

A

Monkey & Human Cell Cultures

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22
Q

Hepatitis A Virus - In Vivo Replication

A

In Cytoplasm of Hepatocyte

Human and other primates

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23
Q

Hepatitis A - Transmission

A 
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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24
Q

Serologic Course

A

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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25
Marker for acute HAV infection
IgM anti-HAV spike
26
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
27
Hepatitis B - In Vitro
Primary hepatocyte culture and transfection of cloned HBV DNA
28
Hepatitis B - In Vivo Replication
In cytoplasm, cccDNA in nucleus Hepatocyte and other tissues (Human and other primates)
29
Diagnosing Hepatitis B - Useful
E Antigen
30
Hepatitis C - Replicates in
Cytplasm
31
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 ```
32
Hepatitis B Virus - Immunopathogenesis
Typical B Cell and T Cell response | Results in hepatocyte apoptosis
33
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!!!!!!!!!!!!!!!
34
If you get hepatitis B early
You're likely to get chronic hep B | You don't have symptoms
35
If you get hep b late
You're not likely to get chronic hep b | You do have symptoms
36
Hepatitis B Diagnosis
Antigens and Antibodies | Many specifics to know
37
Acute HBV Infection
IgM Anti-HBcore | Order Anti-Core IgM - Separates out ACUTE infection
38
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
39
Hepatitis C Virus - In Vitro
Primary hepatocyte and T Cell cultures (Replicon system)
40
Hepatitis C Virus - In Vivo Replication
In Cytoplasm Hepatocyte and lymphocyte (Human and other primates)
41
Hep C Replication
``` Binds to hepatocyte, enters Uncoats Translates IN CYTOPLASM RNA translated Protein products synthesized in ER Progeny genome created New virus assembled ```
42
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
43
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 ```
44
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
45
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 ```
46
Hepatitis D
Known as Delta Agent Uses the HBsAg protein coat Hep B must be present (coinfection or preexisting)
47
Hepatitis E
Waterborne resembling Hepatitis A Endemic in Asia, Northern Africa and MExico Rarely seen in the USA Antibody testing is not standardized
48
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
49
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 ```
50
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
51
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
52
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
53
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
54
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)
55
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)
56
The more HBV DNA in your body
The higher chance you have of getting cirrhosis
57
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!
58
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
59
Hepatitis C Treatments
90 - 100% CURE rates!! ``` Sofosbuvir Simeprevir Daclatasvir Ledipasvir Ombitasvir Paritaprevir Ritonavir Dasabuvir ```
60
Factors affecting response to HCV Rx
Virus - Genotype, Viral Load | Host - IL28B
61
IL28B
``` SNP Chromosome 19 Near IL28B Gene Encoding IFN - Lamda3 Associated with twofold changes in response to treatment ```

GI / Hepatology (28 decks)

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