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GI / Hepatology > 5 - Viral Hepatitis > Flashcards

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
Q

Marker for acute HAV infection

A

IgM anti-HAV spike

26
Q

Hepatitis A - Prevention and Treatment

A

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
Q

Hepatitis B - In Vitro

A

Primary hepatocyte culture and transfection of cloned HBV DNA

28
Q

Hepatitis B - In Vivo Replication

A

In cytoplasm, cccDNA in nucleus
Hepatocyte and other tissues
(Human and other primates)

29
Q

Diagnosing Hepatitis B - Useful

A

E Antigen

30
Q

Hepatitis C - Replicates in

A

Cytplasm

31
Q

Hepatitis B - Viral Replication

A 
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
Q

Hepatitis B Virus - Immunopathogenesis

A

Typical B Cell and T Cell response

Results in hepatocyte apoptosis

33
Q

Hepatitis B - Transmission

A

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
Q

If you get hepatitis B early

A

You’re likely to get chronic hep B

You don’t have symptoms

35
Q

If you get hep b late

A

You’re not likely to get chronic hep b

You do have symptoms

36
Q

Hepatitis B Diagnosis

A

Antigens and Antibodies

Many specifics to know

37
Q

Acute HBV Infection

A

IgM Anti-HBcore

Order Anti-Core IgM - Separates out ACUTE infection

38
Q

HBV Prevention

A

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
Q

Hepatitis C Virus - In Vitro

A

Primary hepatocyte and T Cell cultures (Replicon system)

40
Q

Hepatitis C Virus - In Vivo Replication

A

In Cytoplasm
Hepatocyte and lymphocyte
(Human and other primates)

41
Q

Hep C Replication

A 
Binds to hepatocyte, enters
Uncoats
Translates IN CYTOPLASM
RNA translated
Protein products synthesized in ER
Progeny genome created
New virus assembled
42
Q

Hepatitis C Immunopathogenesis

A

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
Q

Hepatitis C Clinical

A 
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
Q

Acute Hepatitis C Serologic Pattern

A

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
Q

Outcome following Hep C Infection

A 
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
Q

Hepatitis D

A

Known as Delta Agent
Uses the HBsAg protein coat
Hep B must be present (coinfection or preexisting)

47
Q

Hepatitis E

A

Waterborne resembling Hepatitis A
Endemic in Asia, Northern Africa and MExico
Rarely seen in the USA
Antibody testing is not standardized

48
Q

Chronic Hepatitis

A

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
Q

Chronic Hepatitis - Path

A 
Portal Tracts, Peri-portal regions and lobules involved
Liver biopsy:
Chronic inflammation
Increased inflammatory cells
Many plasma cells and lymphocytes
Inflammation > Fibrosis > Cirrhosis
50
Q

Chronic Liver Enzyme Elevation - Etiology

A

Viral Infection - B & C
Autoimmune
Drugs
Metabolic - Wilson’s

Fatty Liver - Steatohepatitis
Alcohol
Others - CHF, hemochromatosis, ulcerative colitis, celiac disease, others

51
Q

Chronic Hepatitis B & C

A

Cirrhosis in 20% of patients
Liver failure and hepatoma develop in 1/2 of cirrhotics
Treatment available with varying success rates

52
Q

Diagnosis of Chronic Hepatitis B or C

A

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
Q

Difference between acute and chronic hep B serologically

A

Surface antigen NEVER disappears (chronic)
DNA is continuously present in the blood
E antigen is

HE WAS NOT CLEAR 9:45am

54
Q

Chronic HBV - 4 Phases of Disease over Decades

A

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
Q

Serologic Events in HBV Infection

A

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
Q

The more HBV DNA in your body

A

The higher chance you have of getting cirrhosis

57
Q

Therapeutic Options of Hepatitis B Treatment

A

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
Q

Chronic HCV Infection

A

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
Q

Hepatitis C Treatments

A

90 - 100% CURE rates!!

Sofosbuvir
Simeprevir
Daclatasvir
Ledipasvir
Ombitasvir
Paritaprevir
Ritonavir
Dasabuvir
60
Q

Factors affecting response to HCV Rx

A

Virus - Genotype, Viral Load

Host - IL28B

61
Q

IL28B

A 
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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