Exam #5: Viral Hepatitis Flashcards
What is hepatitis?
Disease marked by inflammation of the liver.
What are the non-viral causes of hepatits i.e. what is your differential diagnosis when a patient has abnormal LFTs?
- Alcoholism
- Drug abuse
- Drug overdose/ toxin (Tylenol especially)
- Metabolic disorder
Viral Hepatitis
What is acute viral hepatitis? What are the symptoms?
Viral hepatitis <6 months of symptoms:
- Jaundice–increased bilirubin leading to yellowing of the skin & sclera
- Liver inflammation– RUQ abdominal pain
- Dark urine
- Acholic stool–clay-colored stool caused by a reduction in bile production
What is the prodrome prior to the onset of hepatits?
Headache myalgia arthralgia fatigue nausea vomiting pharyngitis mild fever
What is bilirubin? Why is hyperbilirubinemia seen in viral hepatitis?
Bilirubin is the end-product in the recycling of heme from dying RBCs. It is normally excreted as bile, which requires conjugation in the liver. Viral hepatitis interferes with liver function & prevents normal conjugation of bilirubin; thus, higher than normal levels are seen in the blood & urine.
What are the bilirubin levels that are seen in hepatitis? How do they correlate with the symptoms?
Bilirubin levels of 5-20 mg/dL are common in viral hepatitis.
- 3 mg/dL= jaundice
- Higher= bilirubin in urine (diagnostic of liver disease)
What liver enzymes are elevated in hepatitis?
AST (aspartate aminotransferase)
ALT (alanine aminotransferase)
What is the definition of chronic viral hepatitis? What are the potential complications of chronic hepatitis?
Hepatitis that does not resolve in 6 months
Predisposition to primary hepatocellular carcinoma & cirrhosis*
*Usually it takes 15-40 years to see these symptoms
What causes tissue damage in chronic hepatitis? Why are primary heptacellular carcinoma & cirrhosis associated with chronic hepatitis?
Continued replication of hepatitis virus & subsequent immune response leads to an inflammatory response & tissue destruction
Note that the the liver regenerates; long-term/ continued regeneration is what predisposes to the development of primary hepatocellular carcinoma
What is fulminant viral hepatitis? What are the symptoms of fulminant hepatitis? What are some of the complications of fulminant hepatits?
This is the most severe form of viral hepatitis that affects BRAIN function. There is a massive hepatic necrosis in fulminant hepatitis, which leads to hyperammonemia.
- Encephalopathy–>confusion, disorientation, coma.
- Ascites & edema are indicative of liver failure
- Life threatening complications
*Liver transplant can be lifesaving
What virus family is Hepatitis A a part of? How is it transmitted? Does it lead to chronic infection?
Picornovirus
Fecal-Oral
No
What virus family is Hepatitis B a part of? How is it transmitted? Does it lead to chronic infection?
Hepadnavirus
Body fluids
Yes
What virus family is Hepatitis C a part of? How is it transmitted? Does it lead to chronic infection?
Flavivirus
Body fluids
Yes
What virus family is Hepatitis D a part of? How is it transmitted? Does it lead to chronic infection?
Deltavirus
Body fluids
Yes
- Helper-dependent
- Direct damage
- Remember that HDV is helper-Dependent & causes Direct Damage
What virus family is Hepatitis E a part of? How is it transmitted? Does it lead to chronic infection?
Hepevirus
Fecal-Oral
No
List the characteristics of Hepatitis A.
Picornovirus family
+ssRNA
What are the clinical manifestations of Hepatitis A infection?
Incubation period is 28 days
Presents as acute hepatitis
Does NOT cause chronic
Rarely causes fulminant hepatitis
How is Hepatitis A diagnosed?
- anti-HAV IgM antibodies are indicative of ACUTE infection
- anti-HAV IgG antibodies provide protection against re-infection and are indicative of vaccine or prior infection
How is Hepatitis A prevented?
Vaccination:
- inactivated whole HAV vaccine
- IM (2x doses)
- Given to children (12-23 months)
- High risk groups
Post-exposure prophylaxis
- Vaccine can be used as post-exposure prophylaxis
- anti-HAV IgG can also be given as post-exposure prophylaxis
List the characteristics of Hepatitis B. Describe the proteins associated with HBV.
- Hepadnavirus family
- Partially dsDNA genome (some ss)
- Reverse transcription is part of its lifecycle
(most commonly passed via sexual contact)
Note that there are three relevant viral proteins (clinically)
1) HBsAg= surface antigen
2) HBcAg= core antigen (between viral genome and HBsAg) –NOT soluble i.e. NOT in serum
3) HBeAg= core protein that IS SOLUBLE
What are the morphological characteristics of Hepatitis B? Which are infectious? What are the antigens associated with each?
- Tubules & Spheres= noninfectious products of HBsAg (surface antigen)
- Dane particles= infectious, virion coated in tubules & spheres
Note that the presence of tubules & spheres in the bloodstream is indicative of ACTIVE HBV infection.
Serologically, how do you tell the difference between acute & chronic hepatitis?
HBsAg= marker of active infection (either acute or chronic)
HBsAb (antibody)= is present in vaccinated or previous infected patients, but NOT active infection
HBcAb- IgM= acute infection
HBcAb- IgG= chronic infection (or prior infection)
HBeAg+HBcAb- IgG= chronic replicative
The presence of ONLY antibodies in serum is indicative or RESOLVED infection.
What is HBsAg a serologic marker of?
Both acute & chronic Infection
How many HBV infections progress to chronic infection in the following populations: a) neonates, b) 5 year-olds, c) general population?
a) 90% in neonates
b) 15% in 5 year-old
c) 5-10% in general population
*Note that chronic infection increases the risk for liver cirrhosis & primary heptocellular carcinoma
What are the symptoms of Hepatitis B infection?
Less severe infection than acute HAV
How is HBV infection treated?
Acute= none
Chronic=
- Lamivudine= reverse transcriptase inhibitor
- Famcylovir/Adefovir= nucleoside inhibitor, which can be done with or without Interferon-alpha
What is the HBV vaccine?
Recombinant HBV surface protein (HBsAg)
- IM injection
- Recommended for all infants with the first dose given soon after delivery
Describe the post-exposure phrophylaxis protocol for HBV.
HBV vaccine & Hepatitis B Immune globin (HBIG) are used for post-exposure prophylaxis.
- Premature infants with unknown maternal HBV status & HBV positive receive BOTH
- Unvaccinated exposed receive (e.g. healthcare worker) receive just vaccine
List the characteristics of HCV.
Flavivirus family
Enveloped
+ssRNA
- Highly associated with IV drug use
- Note that there are six genotypes (most common in the US is Type 1)
How is HCV diagnosed?
Screening Test with ELISA
Confirmatory Test with Western Blot
Note that this protocol is similar to what is done with HIV
What are the serologic features of HCV?
- ALT & Anti-HCV elevations seen ~2months post-expsoure
- HCV RNA seen early (acute infection)
What are the disease outcomes of HCV?
HCV has a higher propensity to develop into chronic hepatitis than HAV (none) & HBV
- 15% of patients develop acute hepatitis that is more mild than HAV or HBV (self-resolving)
- 15% progress to rapid cirrhosis
- 70% develop chronic/ persistent HCV infection
How is HCV treated?
- Treatment is for CHRONIC infection ONLY
- Treatment regimen differs depending on the exact genotype, but currently, antiviral protocols contain sofosbuvir for every genoptye
- Sofosbuvir is an RNA dependent RNA polymease inhibitor
*Note that while this new drug has an improved efficacy, it comes at a heavy cost (~1,000 dollars a pill)
How is HCV prevented?
No vaccine
Reduce risk behavior
Screen blood supply
List the characteristics of HDV.
Deltavirus
Circular ssRNA
Encodes delta proteins
“Helper-dependent” (needs “co” or prior infection by HBV)
What is unique about the lifecycle of HDV?
Replication requires HBV proteins; thus, it only infects cells that have been previously or concurrently infected with Hepatitis B virus.
What is most likely to cause fulminant hepatits?
Concurrent infection with HBV & HDV
What is the only hepatitis virus that damage hepatocytes directly?
HDV
How is HDV diagnsed?
ELISA to detect:
- anti-HDV antibodies
- delta proteins
How is HDV treated?
No specific antiviral treatments; thus, supportive therapy ONLY
How is HDV prevented?
Because HDV absolutely requires HBV infection, prevention includes HBV prevention (HBV vaccination)
List the characteristics of HEV.
Hepeviridae family
+ssRNA
non-enveloped
How is HEV treated?
Supportive therapy
How is HEV prevented?
HEV is spread through the fecal-oral route; thus, prevention entails preventative sanitation measures
There is NO vaccine for HEV
