EXAM #2: LIVER PATHOLOGY II Flashcards
Which Hepatitis viruses are transmitted via the fecal-oral route?
1) HAV
2) HEV
How is HAV commonly acquired?
Traveling
How is HEV commonly acquired?
1) Contaminated water
2) Undercooked seafood
What is the clinical manifestation of HAV or HEV infection?
Acute hepatitis; no chronic state
What marks active infection with HAV or HEV?
anti-HAV or HEV IgM
What marks prior exposure (or immunization) to HAV/ HEV?
anti-HAV or HEV IgM
In a patient with anti-HAV IgG antibodies, what are the possible interpretations?
1) Prior infection
2) Immunization
In what patient population can HEV infection lead to fulminant hepatitis?
Pregnant women
How is HBV transmitted?
Parenterally
- Childbirth
- Unprotected intercourse
- ID drug abuse (IVDA)
What is the clinical manifestation of HBV infection?
Acute hepatitis (only 20% chronic)
How is HCV transmitted?
Parenterally
- IVDA
- Unprotected sex
What is the clinical manifestation of HCV infection?
BOTH acute and chronic hepatitis
How is HCV infection diagnosed?
HCV-RNA
In evaluating a patient with HCV, what do declining HCV-RNA level indicate? What is levels remain the same?
Recovery vs. persistence/ chronic infection
How does then HBV virus differ from the other hepatitis viruses?
- dsDNA virus vs. ssRNA
- Hepadnavirus vs. picorna virus
What is HDV infection dependent on? Why?
HDV infection requires infection with HBV
- Requires HBsAg to infect (Hepatitis B Surface Antigen)
What is HDV coinfection?
HBV + HDV infect at the same time
What is HDV superinfection?
Pre-existing HBV infection THEN HDV infection
Which is worse, coinfection of superinfection with HDV?
Superinfection–chronic hepatitis and cirrhosis are common complications
What are the extrahepatic manifestations of Hepatitis B? How do these differ in adults and children?
Children= glomerulonephritis
Adults= polyarteritis nodosa
*Antigen/antibody complexes are deposits in the nephrons or medium sized vessels.
What are the extrahepatic manifestations of Hepatitis C?
1) Cryoglobulinemia (cold temperature induced agglutination of RBCs)
2) Thyroiditis
3) Glomerulonephritis
4) Thrombocytopenia
Which genotype of HCV is associated with more severe inflammation?
HCV-2
Note that HCV-1 in the US is associated with resistance to treatment
What happens with HCV and Alcoholism?
Accelerated progression to cirrhosis
What factors predispose HCV infection to HCC?
- Cirrhosis
- Age
- Male sex
- Alcohol
How does Acute Viral Hepatitis appear microscopically?
- Swelling of hepatocytes
- Cholestasis (jaundice)
- Lobular disarray (with impaired blood flow and bile flow)
What is a Councilman Body?
Apoptotic hepatocyte
How does Chronic Viral Hepatitis appear microscopically?
- Piecemeal necrosis
- Bridging fibrosis
- Nodules/ cirrhosis
What is the classic appearance of HBV histologically?
“Ground-glass”
What histologic feature is associated with HCV?
Lymphoid aggregates in portal tracts
What are the serologic markers for HBV infection?
1) HBsAG
2) HBcAB (core antibody) –IgM
What serologic marker will be present in the window period of HBV infection?
HBcAB–IgM
What serologic marker indicates resolution of HBV infection?
HBsAB–IgG
What are the serologic markers for chronic HBV infection?
1) HBsAG
2) HBeAG (envelope) or HBV DNA
3) HBcAB–IgG
What serologic markers indicate infectivity in HBV infection?
HBeAG or HBV DNA
What serologic marker is indicative of HBV immunization? How can you tell the difference between immunization and resolved infection?
Immunization= HBsAB–IgG
Resolved infection= HBcAB AND HBsAB–IgG
How does acute Hepatitis present?
1) Mixed UCB and CB jaundice
2) Dark urine
3) Fever
4) Malaise
5) Nausea
6) Elevated liver enzyme
What is the classic elevation of AST and ALT in Hepatitis?
ALT is more elevated than AST
What time period is characteristic of acute Hepatitis? Chronic?
Less than 6 months vs. more than 6 months
Outline the etiology of Hepatitis.
1) Viral infection
2) Presentation of viral antigen on MHC class I
3) CD8+ T-cell activation
Cytotoxic effects of CD8+ T-cells mediate the inflammation seen in Hepatitis.
Why is there an elevation of both CB and UCB in Hepatitis?
Inflammation of BOTH:
1) Hepatocytes–> UCB
2) Small bile ducts–> CB
What is Primary Biliary Cirrhosis?
Autoimmune disorder that causes inflammation of the small bile ducts
- Referred to as “granulomatous cholangitis”
- Granulomas affecting the small bile ducts
Describe the etiology of Primary Biliary Cirrhosis.
Etiology is unclear, but there is T-cell mediated cytotoxicity
What are the clinical associations with Primary Biliary Cirrhosis?
- More frequent in middle-aged females
- Seen in patients with other autoimmune disorders
- Anti-mitochondiral antibodies present (AMA)
What type of cancer are patients with Primary Biliary Cirrhosis more susceptible to?
Hepatocellular Carcinoma
What are the clinical features of Primary Biliary Cirrhosis?
Patient presents with FATIGUE and PRURITUS that progresses over 10-15 years, and then presents with JAUNDICE. Other symptoms include:
1) Steatorrhea
2) Xanthomas
3) Portal HTN
4) Hepatic failure
5) Osteoporosis/osteomalacia
What lab findings are associated with Primary Biliary Cirrhosis?
- AMA, anti-M2, anti PDH-E2
- IgM
- ALP/5-NT/GGT
- Cholesterol
What are the buzzwords for the four stages of Primary Biliary Cirrhosis?
1) “Florid ductal inflammation” i.e. bile duct inflammation
2) Ductular proliferation
3) Cholestasis
4) Cirrhosis
What is Primary Sclerosing Cholangitis?
Fibrosis of the large bile ducts
What are the clinical associations with Primary Sclerosing Cholangitis?
1) More common in males
2) Ulcerative colitis
What is pathognmeomic for Primary Sclerosing Cholangitis on ERCP?
“Beads on a string” bile duct
Endoscopic Retrograde Cholangiography
What lab findings are associated with Primary Sclerosing Cholangitis?
Elevations in:
- ALP
- GGT
- 5’-NT
- ALT/AST
What antibody is most specific to Primary Sclerosing Cholangitis?
p-ANCA
What cell type initially mediates the Fibrosis seen in Primary Sclerosing Cholangitis?
Neutrophils
What carcinoma is associated with Primary Sclerosing Cholangitis?
Cholangiocarcinoma i.e. carcinoma of the bile duct epithelium
What is autoimmune hepatitis?
Autoimmune “attack” of hepatocytes
What antibodies are specific to autoimmune hepatitis?
ANA
SMA
LKM1
What is Type I autoimmune hepatitis?
- Most common
- Autoimmune hepatitis seen from 10-elderly
- SMA and ANA antibody association
What is Type II autoimmune hepatitis?
- Less common
- Seen in young patients, 2-14
- Anti-LKM1 antibody
- Poor prognosis
What is Type III autoimmune hepatitis?
- Less common
- 30-50
- Anti-SLA/LP
What is the typically progression seen in autoimmune hepatitis?
Very quick progression to cirrhosis
- Initially managed with corticosteroids
- If unable to manage with corticosteroids, patient will require liver transplant