Mcaulliffe - Hepatitis Flashcards
What class of virus does Hepatitis C fall under?
Flaviviridae
What is the nucleic acid structure of Hep C?
Positive strand RNA genome
What proteins does Hep C encode?
Structural proteins:
- core = E1
- envelope = E2
Non-structural proteins:
- various enzymes involved in viral replication
Hepatitis C virology
- very high replication rate
- high genetic variability
- lack of proof-reading function of viral RNA polymerase
- 6 Major genotypes (1-6) that are all only 30% sequence similarity
- genotype 1 is most common in the US
How is Hep C usually transmitted?
IV DRUG USE, blood transfusion, sex, from infected mother to infant
Acute Hepatitis C infection
Often asymptomatic but if illness arises, it is usually in infants or young woman. This is because they are better able to clear the virus so it is only chronic.
Chronic Hep C infection
Often asymptomatic but could have fatigue.
Could have an elevated ALT/AST
Signs of liver disease is usually absent
Some progress into advanced liver disease, cirrhosis, and hepatocellular carcinoma (HCC)
Screening for Hep C
HCV antibody via ELISA Rapid test (OraQuick) - point of care
What risk factor makes makes people with Hep C likely to progress into cirrhosis?
Level of inflammation
What else are Hep C patients at risk for?
Hepatocellular carcinoma (HCC) due to cirrhosis from Hep C
Treatment goals for chronic Hep C
Eradicate HCV as reflected in a sustained virologic response (SVR) to therapy
- SVR = absence of HCV RNA by PCR for 6 months following completion of treatment course.
Sustained virologic response (SVR)
Absence of HCV RNA for 6 months following treatment via PCR
Current treatment of Hep C
Interferon + Ribavarin
Who should be screened for Hep B infection?
- individuals born in high areas of high or intermediate prevalence rates (Asia, Africa, Middle East, South America etc.)
- US born individuals not vaccinated whose parents were born in high endemicity regions
- household and sexual contacts of HBsAg carriers
- Drug users
- men who have sex with men
- prisoners
- chronic ALT elevation , or HCV or HIV infection
- patients who will receive immunosuppressive therapy
- all pregnant women
Serologic markers for Hep B infection
HBsAg - hepatitis B surface antigen - marker for active infection
Anti-HBs - antibody to surface antigen - best correlate for immunity. Either tells us that patient has properly been vaccinated or was infected and then recovered.
- Anti-HBcore IgM - appears during acute infection and during flares of chronic hepatitis
- Anti-HBcore IgG/total - lifelong marker of Hep B virus infection, no correlate of activity or immunity.
What are the stages of chronic Hep B virus?
1) immune tolerance
2) immune clearance
3) non-replicative phase
Immune tolerance phase (of chronic Hep B)
- normal ALT
- asymptomatic
- high HBV DNA levels
- HBeAg +
- minimal or no change on liver biopsy
- high rate of maternal-fetal transmission
Immune clearance phase
- AST/ALT may be elevated intermittently or constantly
- severe hepatitis may occur leading to more rapid progression to cirrhosis
- males are at a higher risk
- Non-Asians are more likely to convert HBeAg to anti-HBe and less likely to have hepatitis flares
Non-replicative phase (of Hep B virus)
HBeAg - HBsAg + HBV DNA low or undetectable ALT normal/mildly elevated Reduced inflammation score on biopsy
Chronic HBV
Basically, the story here is that people who are in the immune tolerant phase were usually infected. Very early in life when their immune systems ere still very immature so they don’t view the Hep B virus as foreign. This is why the viral DNA numbers are very high but the ASL/ALT numbers are normal. Then for some odd reason, at some point later in life the body starts to mount an immune response against the virus and that is when the AST/ALT numbers go up. Then t some point you get into the non-replicative phase in which DNA numbers come down, AST/ALT numbers ae pretty normal, and there is little inflammation in the liver.
Treatment goals of Hep B
Sustained virologic response (Low HBV DNA)
Remission of liver disease (ALT levels)
Prevent cirrhosis, hepatic failure, and hepatic cell carcinoma
Prevent transmission to others
Recommended Hep B drugs
Tenofovir
Entecavir
- ET
What family does Hep A virus belong to?
Picornaviridae
- If you remember, picornaviridae has a mnemonic - PERCH - in which the H stands for Hep A
Transmission of Hep A
Fecal-oral
Person to person
Food borne
Vertical (from mom to child)
Risk factors for Hep A
Person to person contact Men who have sex with men Contaminated food/water Daycare Military IV drug use Blood transfusion
HIV disease
Incubation is 15-50 days
Replication site appears to go only in the liver
Though, there is no major cytopathic effect (the liver cells don’t appear to be destroyed)
Immune-mediated injury
Clinically: there can be jaundice vs. non-jaundice that varies with age.
Illness is non-specific
What would you see first, second, and third, in a Hep A infection?
1) Viremia
2) Hep A virus in the feces
3) symptoms
How do you diagnose Hep A?
Elevated liver chemistries - ALT/AST and bilirubin
Diagnosis by serology - anti-HAV IgM
There is no chronic form of Hep A infection and a full recovery is infected
Contagious during incubation period and one week after and ice appears
Hep A vaccines
HAVRIX
VAQTA
Twinrix
When treating someone who has hepatitis B and will be immunocomprimised say due to chemo, what do you do?
Treat prophylactically with antivirals prior to starting treatment and for 6 months following chemo treatment.
