Flashcards in Hepatic & Biliary Pathology Deck (67)
Causes of Chronic Liver Disease
- nonalcoholic fatty liver disease, viral hepatitis, alcohol, toxins, hereditary disorders, immune mediated disorders, drug reactions
Nonalcoholic Fatty Liver Disease (NAFLD) is associated with __________ and __________.
- obesity and type II diabetes
- the metabolic syndrome (insulin resistance)
- HTN and dyslipidemia are also linked
T or F: in viral hepatitis, the viruses do NOT directly injure the liver cells.
- instead, the immune system targets the infected cells and is responsible for the damage
What are three inherited disorders that can lead to Chronic Liver Disease?
- Wilson's disease
- alpha-1 anti-trypsin deficiency
Compare the duration, symptoms, and hepatic liver enzymes in acute viral hepatitis vs. chronic viral hepatitis.
- acute: less than 6 months duration, jaundice is slightly more common, ALT and AST are in the 1000's, ALT greater than AST
- chronic: greater than 6 months duration, jaundice uncommon, ALT and AST are in the 100's, ALT greater than AST
- symptoms common to both: malaise, lethargy, RUQ discomfort (**symptoms in viral hepatitis are RARE**)
Which hepatitis viruses are DNA viruses?
- only HBV
- (all others are RNA viruses)
Which hepatitis viruses can cause chronic hepatitis? How is each transmitted?
- (obviously, all can cause acute hepatitis)
- A: ssRNA, not chronic, fecal-oral
- B: dsDNA, chronic, parenteral
- C: ssRNA, chronic, parenteral
- D: ssRNA, chronic, requires HBV to be present
- E: ssRNA, not chronic, fecal-oral
Other than the hepatitis viruses, list three other viruses that are known to cause hepatitis.
- cytomegalovirus, Epstein-Barr virus, herpes virus
- (these viruses are associated with more systemic infections)
What are the top three most common types of hepatitis?
- hep A, then hep C, then hep B
Hepatitis ___ most commonly affects children. Why? What prophylaxis or treatment is there?
- hep A most commonly affects kids because of their hygiene (HAV is spread fecal-orally)
- there is a hep A vaccine (although the virus is rarely fatal)
How is hepatitis C spread parenterally? What percentage of patients will spontaneously clear the virus? Develop a chronic infection? Develop cirrhosis? What prophylaxis or treatment is there?
- hep C is spread parenterally via blood-to-blood transmission
- 30% with spontaneously clear the virus, 70% will develop chronic infection, 10% of whom will develop cirrhosis
- no vaccine, treat with PEGylated interferon and Ribavirin (for genotypes 3, 4, 5, 6; for genotype 1 and 2, replace PEGylated interferon with oral antivirals)
How is hepatitis B spread parenterally? What prophylaxis or treatment is there?
- hep A is spread parenterally via blood, birthing, and baby-making
- there is a hep B vaccine, treat with PEGylated interferon and nucleoside analogs
T or F: treating hepatitis B and hepatitis C has a 60% cure rate.
- true and false!
- cure rate for hep C IS 60%
- cure rate for hep B is very low, the goal of treatment being viral suppression rather than curative
Neonates infected with HBV will most likely develop ACUTE/CHRONIC hepatitis, while infected adults will most likely develop ACUTE/CHRONIC hepatitis.
- neonates w/ HBV: most (90%) will develop chronic hepatitis
- adults w/ HBV: most will develop acute hepatitis and then get better (10% will develop chronic disease)
Which serology marker indicates an ongoing HBV infection? Which indicates an immunity to HBV?
- HBsAg (the HBV surface antigen) indicates an ongoing infection
- aHBs (anti-HBV surface antigen antibody) indicates immunity
What is Hemochromatosis? What mutation is involved? What causes the damage? When does it typically present?
- an autosomal recessive inherited defect (C282Y mutation of the HFE gene on chromosome 6p) that can lead to chronic liver disease
- mutations result in excess iron deposition and storage, especially in the liver, pancreas, heart, skin, and gonads
- iron generates free radicals, which damage these organs
- typically presents in late adulthood as the accumulation takes a while
What is used to screen for Hemochromatosis? What is the classic triad of symptoms/clinical findings?
- transferrin saturation (if greater than 0.45 --> indicative of hemochromatosis)
- classic triad: cirrhosis (liver), diabetes (pancreas), and bronze skin
- (also: cardiac arrhythmia and gonadal dysfunction)
What is Wilsons' Disease? What mutation is involved? When does it typically present?
- an autosomal recessive inherited defect that can lead to chronic liver disease
- mutations in ATP7B gene (chromosome 13) coding for ATP-mediated hepatocyte copper transport result in excess copper accumulation (in liver, brain, cornea, kidneys, and joints), resulting in acute liver failure, cirrhosis, and neurological disease
- copper fails to enter the circulation as ceruloplasmin
- presents in childhood, unlike hemochromatosis
- much more rare than hemochromatosis
Which phenotype is responsible for alpha-1 anti-trypsin deficiency?
- a recessive PiZ/PiZ phenotype
- (normal allele is PiM)
- (note that only 10% of patients will develop liver disease; emphysema is much more common)
Give three examples of immune disorders that can cause chronic liver disease.
- autoimmune hepatitis (AIH)
- primary biliary cirrhosis (PBC)
- primary sclerosing cholangitis (PSC)
Autoimmune Hepatitis (AIH) usually involves elevated ____ levels. What do we use to treat it?
- AIH usually has elevated IgG levels
- treat with prednisone
Primary Biliary Cirrhosis (PBC) usually involves elevated ____ levels. What do we use to treat it? What is targeted in this autoimmune disorder?
- PBC usually has elevated IgM levels
- treat with ursodeoxycholic acid
- targets the mitochondria of intrahepatic/intralobular bile ducts (granulomatous destruction)
What is meant by "impaired synthetic function" and "decompensated liver disease"?
- impaired synthetic function: abnormalities in prothrombin time and serum albumin
- decompensated liver disease: issues w/ fluid accumulation, ascites, edema, and encephalopathy
Why does liver disease cause encephalopathy? What are the 4 grades of encephalopathy?
- in severe liver disease, blood is shunted past the liver, so many toxins in the blood are unable to be cleared; when this toxic blood enters the brain/nervous system = impaired consciousness
- grade 1: sleep inversion --> grade 2: asterixis --> grade 3: progression into a coma --> grade 4: coma
3 Major Life-Threatening Complications of Cirrhosis
- variceal hemorrhages, spontaneous bacterial peritonitis, and hepatocellular carcinoma
How can we differentiate between ascites due to portal hypertension or due to another cause?
- ascites in portal hypertension: albumin gradient increases, but total protein is decreased
- ascites in another setting: albumin gradient increases, and total protein increases
What is Spontaneous Bacterial Peritonitis (SBP)?
- infection of the ascitic fluid
- it is very dangerous and often asymptomatic
Why are patients with varices commonly given antibiotics?
- it's used as a prophylaxis against sepsis if the varices rupture (variceal rupture is often associated with sepsis)
What are the main causes of cirrhosis in the Western world? What about worldwide?
- western world: alcoholic and metabolic liver disease
- worldwide: viral hepatitis B and C