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What is the clinical significance behind the high genetic variability of Hepatitis C virus?

High replication rate and a lack of proof-reading function of viral RNA polymerase limits the ability to develop vaccines and for the host immune system to control the virus. This virus has 6 serotypes, in which Genotype 1 is common in the US.


Define the major trend in the incidence of Hepatitis C

Hepatitis C incidence rates REFLECT the growing rates of IV drug use in the opioid epidemic. 60-80% of people with Hep C develop a CHRONIC infection.


What age group has the HIGHEST increase in Hep C incidence rates?

Ages 20 - 29


List at least 5 factors that propagate the transmission of HCV.

1. IV Drug users
2. Multiple partners
3. MSM (homosexuals)
4. Incarceration
5. Contaminated piercings


What proportion of HCV patients will develop a chronic infection? Name 3 end-stage manifestations of the disease.

80% develop chronic HCV infection;
Cirrhosis, jaundice or carcinoma can develop as end-stage factors.


Briefly describe the diagnostic tests used for HCV.

1. Antibody - 99% sensitive and specific
2. Real time PCR (aka NAAT)


What 2 non-invasive tests can be used to assess the extent of liver fibrosis in an HCV patient?

1. Fibrosure - combination tests that gauges the degree of fibrosis
2. Elastography - ultrasound measures liver stiffness.


Classify the type of virus that Hepatitis C is.

HCV = enveloped, (+) sense RNA virus that is a human infection. It can now be curable and eradicated if everyone in the world were treated for it.


What is the importance of SVR as it pertains to HCV treatment?

Sustained Virologic Response after 12 weeks of oral anti-viral regimen is the measure of cure for Hep C. People with SVR > 12 have lower mortality rates, cirrhosis and less need for liver transplant


What are some common treatments that can be used for Hepatitis C infection?

1. Ribavirin
2. Protease Inhibitors
3. IFN-alpha


What is the Direct Acting Antiviral Treatment (DAA) for HCV.

This is an oral regimen that targets specific non-structural proteins for HCV to impair viral replication


What is an example of a "pan-genotypic" protease inhibitor (DAA)?

Velpatasvir is a pan-genotypic DAA. It's highly effective against all 6 genotypes.


In what 3 ways does Hepatitis B differ from Hepatitis C?

Hepatitis B:
1. enveloped DNA virus
2. Only 5-10% develop chronic infection
3. majority of people have (+) serology for HBV as asymptomatic children (inactive carrier state)


What patient population is most likely to acquire chronic HBV?

Perinatal or young children are likely to develop chronic HBV infection. They present in an inactive carrier state.


What are the relative levels of AST and ALT liver enzymes in alcoholic vs viral hepatitis?

Alcoholic Hepatitis = AST "S for sauced" is greater;
Viral Hepatitis = ALT is usually greater


How infectious is HBV compared to the other hepatitis infections? How is it transmitted?

HBV is the most infectious hepatitis virus, even more infectious than HIV. It's transmitted via IV drug users, sex or mixing of blood during birth.


Any patient with chronically elevated _____ should be tested for HBV and HCV.

Chronically elevated ALT (indicates viral hepatitis)


What is a diagnostic marker for Hepatitis B infection? What of HBV immunity?

HbsAg (HBV antigen) is the infection diagnostic marker. This remains positive throughout life. Anti-HBs is a marker for immunity.


What is the HBV diagnostic marker for acute infection?

Anti-HBc IgM = marker for ACUTE infection;
very rare to get a positive


What is the HBV diagnostic marker for any previous infection (no matter the stage of life)?

Anti-HBc IgG = marker of PREVIOUS infection, no matter when you someone got infected


What is the diagnostic marker for very active viral replication of HBV? What reflects immune control for this?

HBeAg (marker for the transition of tolerant to ACTIVE PHASE in perinatal infection);
Seroconversion to Anti-Hbe


What is the expected hepatitis B serological panel for a young adult up to date with their vaccines/ (HBsAg, anti-HBc, anti-HBs)

HBsAg (negative), anti-HBc (negative), anti-HBs (POSITIVE)


What is the diagnostic serology for someone who is acutely infected with HBV? (HBsAg, anti-HBc, IgM anti-HBc)

IgM anti-Hbc (core = POSITIVE), HBsAg and anti-HBc (positive too)


What are the unique diagnostic serology markers for someone chronically infected with HBV? (IgM anti-HBc, anti-HBs, HBsAg, anti-HBc)

IgM anti-HBc and anti-HBs (both NEGATIVE); HBsAg and anti-HBc (both positive)


Define the immune tolerance phase of Hepatitis B.

Levels of viral DNA remain high from perinatal to young adult years. Liver enzymes are normal and there is no liver pathology.


Define the immune clearance phase of Hepatitis B.

In an infected person's 20s-30s a seroconversion of HBeAg to anti-HBe occurs. Liver enzymes go up and viral DNA begins to decrease.


Define the inactive carrier state of Hepatitis B patients.

At infected person's 40s, viral DNA is low and liver enzymes are normal or slightly elevated.


What 2 substances are used to treat chronic HBV disease?

1. Alpha-interferon
2. Reverse-transcriptase inhibitor 3TC


Define the HBV surface antigen.

HbsAg is present in both infectious virions and empty HBV particles. It is the main diagnostic marker for infectious HBV disease.


Define the HBV core antigen.

HbcAg is present only in infectious virions.