Viral Hepatitis & Liver Fibrosis Diagnostics

What is hepatitis?

inflammation of the liver

What are causes of hepatitis?

• viruses

• alcohol

• medications

• toxins

• sepsis

• autoimmune

• other hepatitis/GI diseases

What are the different types of hepatitis, and what type of virus is each?

• A (RNA)

• B (DNA)

• C (RNA)

• D (RNA)

• E (RNA)

What must you have in order to get a Hep D infection?

must have Hep B; it can happen at the same time or separate, but there needs to be a hx

Why do symptoms usually take weeks to appear in hepatitis?

because the virus needs time for the hepatocytes to replicate

What is viral hepatitis responsible for making?

the ECM, the fibrous stuff between cells, which is the cause of fibrosis

What does the hepatitis B serologic testing usually include?

usually a “triple panel:”

• HBsAg

• HBsAb

• total HBcAb (with reflex IgM)

What hepatitis viruses are transmitted fecal-orally?

Hepatitis A and Hepatitis E.

What hepatitis viruses are transmitted percutaneous/sexual/perinatal?

Hepatitis B, Hepatitis D, Hepatitis C.

What additional transmission routes exist for Hepatitis A?

blood transfusions/IV drugs.

What additional transmission routes exist for Hepatitis E?

• blood transfusions

• perinatal transmission

• possibly breast milk.

What are the animal reservoirs for Hepatitis E?

• Swine

• shellfish

• rodents.

What defines acute viral hepatitis?

Hepatocellular injury lasting < 6 months.

How does the viral agent cause hepatocellular injury in acute hepatitis?

viral agent infects hepatocyte and causes cell death via direct injury or immune-mediated destruction.

What follows hepatocellular injury in acute hepatitis?

changes in liver function studies.

What is the range of signs and symptoms in acute hepatitis?

Range from very mild to acute liver failure.

What defines chronic viral hepatitis?

> 6 months of hepatocellular injury → fibrosis → cirrhosis.

What causes chronic hepatitis injury?

Immune-mediated attack on liver secondary to persistence of hepatitis virus.

Which hepatitis viruses can become chronic?

Hepatitis B, C, D, & E.

What are the hepatic function tests?

• Aspartate aminotransferase (AST)

• Alanine aminotransferase (ALT)

• Alkaline phosphatase

• Bilirubin

• Albumin

• PT/INR.

What do albumin and PT/INR indicate?

liver’s synthetic function.

What is the AST:ALT ratio pattern in viral hepatitis?

AST:ALT ratio

What is the variability of presentation in viral hepatitis?

WIDE variability in presentation (asymptomatic to hepatic failure).

What are acute viral hepatitis symptoms?

Malaise, fatigue, fever

What happens to constitutional symptoms with onset of jaundice in acute hepatitis?

Constitutional sx’s usually improve with onset of jaundice.

What are chronic viral hepatitis symptoms?

Malaise, fatigue, fever

What is the end result of chronic viral hepatitis?

Cirrhosis.

What are signs of cirrhosis in chronic hepatitis?

• Ascites

• Jaundice

• Encephalopathy

• Coagulopathy

• Variceal bleeding.

What is the incubation period of Hepatitis A?

15-50 days (avg 28).

When is peak stool shedding in Hepatitis A?

2 weeks prior to sxs.

How does stool shedding change with jaundice in Hepatitis A?

Declines rapidly with onset of jaundice (can be prolonged several months in kids).

What are the diagnostic tests for Hepatitis A?

• IgM

• IgG

• Total anti-HAV antibody (IgM + IgG).

What antibody do we look for in Hep A?

look for IgM because Hep A can't be chronic, and IgG is the one that persists for life.

How long does Hep A IgM last?

shows up right away and can last for about 6 months.

What does HAV-IgM antibody indicate?

First to appear. Indicates ACUTE INFX.

When is HAV-IgM detectable?

Detectable 5-10 days before clinical symptoms.

When does HAV-IgM become negative?

within 6 months.

When does HAV-IgG antibody appear?

Appears approximately 2 weeks after IgM begins to increase.

How long can HAV-IgG remain detectable?

Can remain detectable for years after infection (detectable indefinitely).

What does HAV-IgG signify?

Lifelong immunity (after infx) OR Vaccination.

What does Total anti-HAV (IgM plus IgG) indicate?

Does not differentiate IgM from IgG → Not useful to dx acute infx.

What is needed if Total anti-HAV is positive?

reflex testing for IgM to determine acute or chronic.

What is true of Total Anti-HAV in acute or past Hepatitis A infection?

Total Anti-HAV is POSITIVE.

What indicates acute Hepatitis A?

IgM positive.

What indicates previous infection with Hepatitis A or prior vaccination?

IgM negative.

When do Hepatitis B symptoms appear?

9–21 weeks after exposure (avg 12 weeks).

What percentage of adults with Hepatitis B have significant acute symptoms?

70%.

How do children present with Hepatitis B?

mild or no symptoms.

What percentage of Hepatitis B cases progress to chronic disease?

up to ~10%.

How does chronic Hepatitis B usually present?

usually asymptomatic.

What are the inner core components of Hepatitis B virus?

core antigen (HBcAg) and “e”/early antigen (HBeAg).

What is the outer envelope component of Hepatitis B virus?

surface antigen (HBsAg).

What are the Hepatitis B antigens?

• Hepatitis B Surface antigen (HBsAg)

• Hepatitis B Core antigen (HBcAg)

• Hepatitis B e-antigen (HBeAg).

What are the Hepatitis B antibodies?

• Hepatitis B surface antibody (HBsAb or anti-HBs)

• Hepatitis B core antibody (HBcAb or anti-HBc)

• Hepatitis B e-antibody (HBeAb or anti-HBe).

What is notable about Hepatitis B core antigen (HBcAg)?

No clinical test for this!

What does Hepatitis B surface antigen (HBsAg) indicate?

active hepatitis B infection (both acute and chronic).

What generates sickness in Hepatitis B?

Surface antigen = Sickness is generated.

What is the first Hepatitis B serologic marker to increase?

HBsAg.

When does HBsAg rise?

Rises within 9 weeks after exposure to the virus.

When do Hepatitis B symptoms usually occur?

9–21 weeks.

When do HBsAg and HBV DNA become undetectable in self-limited cases?

by 15 weeks after signs and symptoms, should happen within 6 months.

What does persistence of HBsAg >6 months indicate?

chronic infection.

What does Hepatitis B surface antibody (HBsAb) indicate?

Surface antibody = Sickness is out of the body.

When does Hepatitis B surface antibody appear?

Appears several weeks after HBsAg disappears.

What does the appearance of Hepatitis B surface antibody signify?

Appears after the virus has been successfully cleared from the body.

How long does it take for Hepatitis B surface antibody to appear after the virus leaves the body?

Takes about a month or two to appear after the virus leaves the body.

What does Hepatitis B surface antibody signify regarding infection?

Signifies resolved infection.

What immunity does Hepatitis B surface antibody indicate?

Immunity to subsequent infection.

What else can cause a positive Hepatitis B surface antibody?

immunity after administration of Hepatitis B vaccine.

How long can Hepatitis B surface antibody persist?

Can persist for life.

What does Hepatitis B core antibody represent?

Core Antibody = Contact between virus and body.

What does Total HBcAb consist of?

IgM and IgG.

When does Hepatitis B core IgG appear?

IgG appears within 4–8 weeks after exposure.

How long does Hepatitis B core IgG persist?

persists indefinitely.

What does Total HBcAb indicate?

previous infection / convalescent stage.

When is Total HBcAb generated?

Will only be generated when the disease has come in contact with the body.

What does IgM HBcAb indicate?

acute infection.

When is IgM HBcAb detectable?

Detectable at onset of symptoms.

When does IgM HBcAb become undetectable?

Undetectable in 6–9 months.

What test does not exist for Hepatitis B core antigen?

No test for HBcAg (Antigen).

What does Hepatitis B E antigen (HBeAg) generate?

E antigen = generates exposure.

What does HBeAg correlate with?

high levels of viremia, infectivity, ongoing liver injury.

What does the presence of HBeAb mean?

less viral replication, less infectivity, less liver inflammation.

What does Hepatitis B DNA measure?

Direct measurement of HBV viral load.

How does Hepatitis B DNA compare to HBeAg?

more precise and sensitive than HBeAg.

Why might HBeAg be absent in some Hepatitis B variants?

HBV variants that do not lead to HBeAg due to gene variation.

What is Hepatitis B DNA helpful in?

Early detection of disease

What is the incubation period of Hepatitis C?

2–26 weeks (usually 6–7 weeks after exposure).

How does acute Hepatitis C commonly present?

most commonly asymptomatic/unrecognized by patient.

What symptoms can occur in acute Hepatitis C?

• Fatigue

• fever

• N/V

• jaundice

• RUQ pain.

What percentage of Hepatitis C cases progress to chronic disease?

~85%.

What is the initial screening test for Hepatitis C?

Anti-HCV antibody.

Does Anti-HCV antibody confer immunity?

Does NOT confer immunity.

When is Anti-HCV detectable?

80% by 15 weeks s/p exposure

What is the confirmatory test for Hepatitis C?

HCV RNA.

Is HCV RNA required for diagnosis?

yes

When is HCV RNA detectable?

Usually detectable within 1–2 weeks after exposure.

What is HCV RNA useful for?

monitor response to therapy/determine viral clearance.

What is sustained virologic response (SVR)?

undetectable HCV in serum 12 weeks after completing tx.

What does a nonreactive anti-HCV test indicate?

No disease.