Viral Hepatitis

Question 1

What Hepatitis is DNA and what are all the others

Answer 1

HBV is DNA

The rest are SSRNA

Question 2

Acute Hepatitis Stages

Answer 2

1) Several week incubation
2) Prodrome (malaise, fatigue, hepatomegaly/tenderness, dark urin gray stools, LFT are high
3) Clinical Illness (jaundance, massive immune response, hepatic encephalopathy if build up of ammonia)
4) Resolution

Question 3

Complications of Acute Hepatitis

Answer 3

Sepsis
Lactic Acidosis
DIC
Fulminant hepatitis

Question 4

Chronic Hepatitis

Answer 4

Only with HBV/HDV and HCV
Continual viral replications BEYOND 6 MONTHS
Symptoms: hepatocyte death, fibrosis and nodule

Question 5

Complications of Chronic Hepatitis

Answer 5

Portal hypertension (block in the vein into the liver)
Ascites
Cirrhosis and hepatocellular

Question 6

Diagnosis of Hepatitis

Answer 6

LFT (increased ALT and AST)
Virus serology
PCR for viral genome (false positives)
IgM/IgG

Question 7

Hepatitis A Transmission

Answer 7

Fecal-Oral Transmission

Question 8

Hep A Incubation

Answer 8

Incubation period of 25 days which malaise and jaundice lasting 2-3 weeks

Question 9

Hep A progression

Answer 9

Life-long immunity

1% develop fulminant hepatitis

Question 10

Hep A Prevention

Answer 10

Vaccine (Havrix and Vaqta-inactivated virus) and gamma globulin immunoglobulin
NO TREATMENT

Question 11

Hep E

Answer 11

Fecal-oral transmission
NO vaccine
Pregnant + 3rd trimester + HEV = risk of fulminant hepatitis

Question 12

Common Characteristics of Hep B, C, and D

Answer 12

Infection by blood content
Chronic hepatitis development
Carriers are possible!!!
Predisposes to liver cancer

Question 13

Hep B General

Answer 13

DNA
Worldwide problem
Leading cause of chronic, cirrhosis and cancer

Question 14

Hep B Incubation

Answer 14

1-6 months

Question 15

Hep B Diagnosis

Answer 15

Surface antigen (ABsAg)
Core antigens (HBcAg)
Infectious antigen (HBeAg)

Question 16

HBV Replication

Answer 16

Viron attach to hepatocyte cell surface receptor
DNA converted into circular DNA
Viral DNA is transcribed to host RNA and codes for viral proteins via host ribosomes
Viral DNA is synthesized by reverse transcription
Goes to cytoplasm and either bud out or keep replicating

Question 17

HBV Caveat

Answer 17

The virus is not pathogenic to cells but the immune response is cytotoxic to hepatocytes

Question 18

Drug target in HBV replication

Answer 18

Viral reverse transcription and DNA polymerase

Question 19

HBV Acute Infection

Answer 19

Last 4-6 weeks
90% are self-healing
1-3% develop into fulminant
Symptoms: malaise, waekness, myalgias and arthralgis
NOT CYTOPATHIC, injury is immune related

Question 20

HBV Chronic Infection

Answer 20

10-15% are carriers
HBsAg present for greater than 6 months
20% have cirrhosis
MOST ONCOGENIC VIRUS KNOWN

Question 21

Acute HBV Time Course

Answer 21

Antigens go up and then come back down within 4-8 weeks

Question 22

Chronic HBV Time Course

Answer 22

Expression goes up and takes forever to come down

Question 23

HBV Treatment/Prevention

Answer 23

Vaccine (95% successful)
Avoid glucocorticoids (prednisone = immunosuppression)
T: interferone + ribavirn or lamivudine or liver transplant

Question 24

HDV General

Answer 24

Incomplete RNA virus

Needs HBV coat protein which = more severe than HBV alone

Question 25

HCV type, most common subtype, duration, risk

Answer 25

RNA virus - cytotoxic which cause immune induced hepatic damage Single protein that is cleaved into multiples via protease NS3 (1a is most common) Last 12 months (acute) High risk of becoming chronic and causing cancer COMMONLY CO-INFECTED WITH HIV!!!!

Question 26

HCV Diagnosis, symptoms, complications

Answer 26

Asymptomatic found through high transaminases Liver biopsy shows ongoing liver damage Extrahepatic complications excists

Question 27

HCV Prevention and Treatment

Answer 27

No vaccine | T: Interferon + Ribavirin

Question 28

Chornic HCV Time Course

Answer 28

Levels go up and come back down and then go up and level out

Question 29

Interferon Alpha Use and MOA

Answer 29

HBV and HCV Induce protection against viral attach in neighboring cells (inhibits protein synthesis) HCV Specific: via induced JACK/STAT pathway and causes lots of (antiviral) proteins to prevent replication of HCV and stimulates other cytokines/immune response

Question 30

Interferon + HCV

Answer 30

Induces sustained HCV clearance (lower response in subtype 1 and 4) Use pegylated IFN (increased response rate) COMBINATION with ribavirin improves therapeutic response

Question 31

IFN alpha 2A and 2b drugs

Answer 31

Roferon (2a) | IntronA (2b)

Question 32

Other IFN drugs

Answer 32

IFN alfacon-1 | Pegays and Peg-Intron are IFN + PEG

Question 33

***Specific to PegIFN

Answer 33

Once weekly Increased response rate SQ

Question 34

Cons of IFN

Answer 34

expensive!!! | Half-life is short but effects are long

Question 35

AE of IFN

Answer 35

Flu-like symptoms CI: Cardiac Disease and pregnancy, depression Myelosuppresion

Question 36

Ribavirin brand and MOA

Answer 36

Copegus for HCV - PO GUANOSINE analog Inhibits purine metabolism and viral RNA polymerase and induces mutations in viral genome

Question 37

Ribavirn CI

Answer 37

***Teratogenic!!!! Accumulates with erythrocytes, anemia and osmotic hemolysis Thalassemia Sickle-cell disease or renal failure

Question 38

Lamivudine MOA and Use

Answer 38

Epivir for HBV CYTOSINE analog Inhibits DNA polymerase FIRST LINE DRUG for HBV

Question 39

Lamivudine SE/problems

Answer 39

Bacterial infections | Virus can become resistant via mutations

Question 40

Alternatives to Lamivudine

Answer 40

Adefovir or entecavir (baraclude)

Question 41

Prevention of Hep Infections

Answer 41

``` Avoid contact with blood Avoid sexual contact with infected person (safe sex) Avoid IV drugs Wash hands Vaccines (HAV/HBV) ```