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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

2

Key liver enzymes

AST and ALT

3

Other liver enzymes of consequence in hepatitis

Bilirubin
Albumin
Alkaline Phosphatase
GGT

4

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)

5

Human Hepatitis Viruses

HAV
HBV
HCV
HDV
HEV

6

RNA Hepatitis Viruses

HAV
HCV
HDV
HEV

7

Double Stranded DNA Hepatitis Viruses

HBV

8

Hepatitis A

ssRNA
7.5 kb Genome
No Envelope
Picornaviridae Hepatovirus

One Serotype
Multiple Genotypes
Acid/Heat Stable

9

Hepatitis B

dsDNA
3.2 kb Genome
Envelope
Hepadnaviridae

Multiple serotypes and genotypes (A - F)

10

Hepatitis C

ssRNA
9.6 kb Genome
Envelope
Flaviviridae Hepacivirus

Genotypes - 1 to 6

11

Hepatitis D

ssRNA
1.7 kb Genome
Envelope
Unclassified (viroid) delta virus

12

Hepatitis E

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

13

Other infectious etiologies of Acute Hepatitis

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

14

Symptoms of Acute Viral Hepatitis

Complaint: Intense Fatigue, Nausea, Anorexia

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

15

Signs of Acute Viral Hepatitis

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

16

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)

17

Normal AST/ALT

40 +/- 5 or 10

18

What is Alkaline Phosphatase elevation associated with?

Biliary Disease
Infiltrative Disease

Not so much viral

19

Outcomes of Acute Viral Hepatitis

Chronic Hepatitis

OR

Cure

OR

Fulminant Hepatitis

20

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

21

Hepatitis A Virus - In Vitro

Monkey & Human Cell Cultures

22

Hepatitis A Virus - In Vivo Replication

In Cytoplasm of Hepatocyte
(Human and other primates)

23

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

24

Serologic Course

1st Month - Fecal excretion
2nd Month - Symptoms & Increase in ALT
2nd - 6th month IgM Antibody spikes
3rd - 4th month, symptoms resolve

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