Disorders of the Liver Part 2 COPY Flashcards
Which hepatitis is fecal-oral?
Hep A
Which Hep is blood-borne?
Hep B and C and D
D is associated with B only!
What kind of virus is Hep A?
RNA
What is unique about having Hep A?
There is no chronic carrier state.
How does Hep A typically present?
- Worse in adults
- Distaste for smoking
- Low grade fever
- Malaise, arthralgia, URI, fatigued
- Mild constant abdominal pain in RUQ aggravated by exertion/jarring
When does jaundice tend to occur in Hep A?
5-10 days after
What kind of stool is Hep A?
Acholic (mashed potatoes?)
Who should we suspect Hep A infection in?
- Abrupt onset of prodromal symptoms (N, anorexia, fever, malaise, or abd pain)
- Jaundice
- Elevated aminotransferase levels
How is a Hep A diagnosis established?
IgM anti-HAV antibodies
What is the best indicator of a previous exposure, non-infectivity, and immunity of hep A?
IgG
What is the ALT/AST ratio in Hep A?
ALT > AST
What does a blood smear look like for Hep A?
Atypical large lymphocytes
How do you treat and prevent hep A?
- Treatment: rest and fluids, avoid exertion
- Prevention: VACCINATION, washing hands, can get shot if you get exposed.
What are the essentials of diagnosis of Hep A?
- Infection acquired via fecal-oral route and is self-limited
- Relapsing infection and protracted cholestatic phase
- IgM antibody test
- IgG development leads to protection and lifelong immunity
What are the components of the Hep B virus?
- Inner core: HBcAg and HBeAg
- Outer surface: HBsAg
8 different genotypes as a result! 2^3
HBcAg = Hep B core antigen
HBeAg = Hep B e antigen
HBsAg = Hep B surface antigen
How is Hep B transmitted and prevented?
- Transmission: Blood-borne and sexual intercourse
- Prevention: VACCINATION
Who are the greatest risk factors for Hep B?
- MSM
- Hemodialysis center staff and pts
- Clinical pathology and blood banks
- STD or incarcerated
How long does it take Hep B to incubate?
6 weeks to 6 months
How does Hep B infection typically present?
- Losing your appetite
- Jaundice
- Fever
- Dark urine
- Pale poop
- N/V
- RUQ pain
- Joint pain
What are the serologic markers for Hep B?
- HBsAg
- Anti-HBs
- Anti-HBc
- HBeAg
What is the FIRST serologic marker to elevate in Hep B?
HBsAG
Past 6 months of elevation = chronic
What serologic marker changes suggest recovery from an acute Hep B infection?
- Anti-HBs appearance
- HBsAG Decrease
What serologic marker changes suggest Hep B immunity?
- Anti-HBs persistence
- No elevated HBsAG
When does IgM anti-HBc tend to appear in a Hep B infection?
1 month after HBsAG appears
When does IgG anti-HBc appearance suggest during a Hep B infection?
Persists indefinitely
* With recovery => IgG occurs with anti-HBs
* With chronic => IgG occurs with HBsAG
What does the appearance of HBeAG suggest?
Indicates viral replication and infectivity, aka most infectious time
Followed by anti-HBe as viral replication diminishes
Appearance of what Hep B antibody suggests that the patient is a low infectious risk?
HBeAG
What is slightly more sensitive than HBeAG in terms of viral replication and infectivity?
HBV DNA
Summary graph of serologic markers of Hep B
What serologic markers characterize a previous Hep B infection?
- Anti-HBs
- IgG anti-HBc
What serologic markers suggest Vaccination of Hep B?
Only anti-HBs
What serologic markers suggest recovery from Hep B and immunity?
- Anti-HBs
- IgG Anti-HBc
- Potentially anti-HBe
What is the AST/ALT ratio in Hep B?
ALT > AST (more than Hep A usually)
What is PT prolongation associated with in terms of Hep B?
Fulminant Hep B
How do you treat Hep B?
- Rest, fluids
- antiviral therapy is not indicated in acute infection
- 3-6 months
- Liver manifestations = hospitalization
- HBIG (immune globulin) must be given within 7 days to shorten duration and reduce severity
If an infant is born to a HBV+ mother, what do we do?
HBIG + vaccine series within 12 hours of birth
How many doses is the HBV series and who gest it?
- All children
- Healthcare workers
- 3 series (Initial, 1 month, 6 months)
What chronic conditions does HBV increase the risk of?
- Hepatocellular carcinoma
- Cirrhosis
- Liver failure
What patients get antiviral therapy for HBV?
- Active viral replication
- Acute on chronic (HBeAG + HBV DNA)
- S/Sx of liver failure or cirrhosis
What is the antiviral therapy for HBV?
- First-line: Nucleotide and Nucleoside analogs
- Second-line: Interferon (BBW for infections)
Hep B serology interpretation
What are the essentials of diagnosis of Hep B? (Image)
How is HCV typically transmitted?
IVDU
How many major genotypes does HCV have?
7
Who are the at-risk populations for HCV?
- IVDU
- Prison inmates
- Healthcare workers
What is the MC bloodborne infection in the entire US?
HCV
What other condition is often implicated with people with HCV?
HIV
What genotype spontaneously resolves in HCV?
CC
What do most people with HCV go on to develop?
Chronic hepatitis
What signifies an HCV infection?
Presence of HCV RNA
What signifies a past HCV infection?
Presence of anti-HCV without HCV RNA
Presence of what serologic marker indicates that hepatitis is due to Hep C?
HCV Antibodies
What conditions does HCV increase the risk of?
- Non-Hodgkin’s Lymphoma
- GN
- IPF
- Thyroiditis
Who does the CDC recommend gets screened for HCV?
- Anyone over 18
- All pregnant women
How do you treat HCV?
Direct acting antiviral (DAA): Iedipasvir/sofosbuvir
Prevents chronic Hep development for acute genotype 1
Who is highest risk for cirrhosis development secondary to HCV?
- Increased risk in men
- > 50g of alcohol daily
- HCV after 40yo
Drinking what slows progression of liver fibrosis?
Coffee
What does an HCV protease inhibitor do and what genotypes is it for?
- Inhibits replication
- Glecaprevir/pibrentasvir
- Genotypes 1-6
- 8 wk tx
What does an HCV polymerase inhibitor do and what genotypes is it for?
- Inhibits viral replication
- Sofobusvir + velpatasvir
- Genotypes 1-6 except 3 (12 week tx)
What are the essentials of HCV?
- Percutaneous exposure that commonly leads to chronic infection
- EIA for anti-HCV indicates infection or prior exposure. Can be falsely positive.
- Presence of HCV RNA indicates active infection and takes 1-2 weeks to be detectable.
- Liver biopsy is rarely necessary
When does Hep D occur?
Hep B coinfection with presence of HBsAG
How do you diagnose Hep D?
anti-HDV
What are the essentials of diagnosis of HDV?
- Infection with HDV occurs with HBV only and is detected by anti-HDV. IgM vs IgG is not useful.
- HDV RNA is found via PCR or molecular hybridization
- IgG positive suggests superinfection.
What is Hep E often seen in?
- Waterborne outbreaks.
- Suspect it in anyone with acute hepatitis post trip to an endemic area.
Where is Hep B endemic?
- Asia
- North Africa
- Middle East
What is the most common population for HEV?
Young adults, most severe among pregnant women.
How is HEV diagnosed?
IgM anti-HEV
How does HEV typically present?
- Prodrome of FLS
- Icteric phase of jaundice
- Extrahepatic manifestations (such as GBS or peripheral neuropathy)
How do you treat HEV?
3 months of PO ribavirin
Who is HEV most severe in?
Pregnant women
What are the essentials of diagnosis for HEV?
- Fecal-oral route with self-limited infection
- HEV is diagnosed via IgM anti-HEV or HEV RNA by PCR
- HEV is most severe in pregnant women
- No vaccine in da US :(
What is hemochromatosis?
- Autosomal recessive disorder
- Increased iron absorption from duodenum and stored in the liver
- Stores as hemosiderin and increased deposits everywhere
Who is hemochromatosis MC in?
Northern europeans and NA caucasians
Who is cirrhosis MC in for patients with hemochromatosis?
- Alcoholics
- Obesity
- Advanced age
- Diabetes
How does hemochromatosis typically present?
- Early: Fatigue, arthralgia
- Late: symmetric athropathy, hepatomegaly, hepatic dysfunction, bronze skin pigmentation, cardiac enlargement, DM, ED in males
How do you diagnose hemochromatosis?
- Iron studies and genetic testing
- Low TIBC
- HFE Mutations
How do you treat hemochromatosis?
- Low iron diet
- Weekly phlebotomy of 1-2 units of blood for 2-3 yrs
- Deferoxamine IV or Deferasirox PO for chelation
What is the demographic of Wilson’s disease?
- Rare autosomal recessive
- Prior to age 40
- Chromosome 13 defect causing increased absorption of copper and decreased excretion BY THE LIVER via low ceruloplasmin
Where does excess copper deposit in the body?
- Liver
- Brain
What is the pathognomic sign of Wilson’s?
Kayser-Fleischer Rings
How does Wilson’s typically present?
- Hepatitis
- Hepatosplenomegaly
- Personality changes
- Parkinson’s like symptoms
What labs suggest Wilson’s?
- Increased urinary copper excretion
- Low serum ceruloplasmin
- Liver biopsy
What is the DOC to treat Wilson’s?
Penicillamine PO (Indefinitely) + B6 (pyridoxine)
What trace mineral promotes fecal excretion of copper?
Zinc
Hemochromatosis vs Wilson’s image
What characterizes Gilbert’s syndrome?
- Mild, unconjugated bilirubinemia
- Familial, MC in adolescents
- Recurrent episodes of jaundice
What enzyme has reduced activity in Gilbert’s syndrome?
Glucuronyl transferase
What triggers Gilbert’s syndrome?
- Dehydration
- Fasting
- Infection
- Menstruation
- Over-exertion
- Alcohol
How is Gilbert’s syndrome diagnosed?
- Unconjugated hyperbilirubinemia
- Normal everything else
How is Gilbert’s syndrome treated?
Benign, no treatment. Self-resolving.
What characterizes Crigler Najjar syndrome?
- Glucuronyl transferase deficiency
- Congenital, nonhemolytic jaundice
- Rare autosomal recessive
- Occurs in infancy
- Rapidly severe, high levels of hyperbilirubinemia
What are the two types of Unconjugated hyperbilirubinemia?
- Type 1: 20-50 mg/dL
- Type 2: < 20 mg/dL
- High levels = definitive for Crigler Najjar
How do you treat Crigler Najjar Syndrome?
- Phototherapy to oxidate bilirubin
- Plasmapheresis
- Liver transplant
- Type 2 is treatable with phenobarbital
What is Dubin Johnson Syndrome?
- Genetic mutation affecting transport proteins of bilirubin
- Elevations in conjugated serum bilirubin
How does Dubin Johnson syndrome present?
Intermittent jaundice and fatigue
How is Dubin Johnson Syndrome diagnosed?
- Conjugated hyperbilirubinemia in the absence of any other abnormality
- Darkly pigmented liver on inspection
How do you treat Dubin Johnson Syndrome?
Benign, no tx.
What is Rotor syndrome?
- Rare Genetic disorder
- Hepatic defect in storing conjugated bilirubin
- Presents the same as Dubin Johnson Syndrome
- Benign treatment
How do you differentiate between Dubin Johnson and Rotor Syndrome?
Injection of dye to observe the transport system of conjugated bilirubin or liver biopsy
What is Budd-Chiari Syndrome?
Hepatic venous outflow obstruction, often resulting in polycythemia vera or myeloproliferatie disorders
How does Budd-Chiari syndrome present?
- RUQ pain (tender and painful)
- Jaundice
- Splenomegaly
- Ascites
- Chronic: bleeding varices and hepatic encephalopathy
How is Budd-Chiari syndrome diagnosed?
Doppler US of IVC/hepatic veins or prominent caudate lobe
What is a good study to view the actual obstructed veins in Budd-Chiari syndrome?
MRI w/ con
How do you treat Budd-Chiari syndrome?
- LWMH for underlying hematologic disorder
- TIPS placement
- Balloon angioplasty
- Liver transplant
- Lifelong anticoagulatio and treatment of complications (such as ascites)
What is the prognosis of Budd-Chiari syndrome?
5year survival: 50-90% with treatment. (< 10% if no intervention)
What cell type does Hepatocellular carcinoma originate from?
Liver parenchymal cells
What is the majority of hepatocellular carcinoma due to?
Cirrhosis
What are the risk factors for hepatocellular carcinoma?
- Obesity
- Male
- Age > 55
- FMHx
- DM
- HCV or HBV
- Alcohol
What is the clinical presentation of hepatocellular carcinoma?
- Deterioration
- Cachexia, severe wt loss, anorexia, weakness, muscle wasting
- Bloody ascites
- Tender hepatomegaly
What biomarker is elevated in hepatocellular carcinoma?
Alpha fetoprotein (70%)
What liver enzyme gets elevated in Hepatocellular carcinoma?
ALP
What is the first-line imaging to identify a mass in hepatocellular carcinoma?
CT and MRI with contrast
What confirms hepatocellular carcinoma?
Liver biopsy
DO NOT need if CT w/ con has a mass + Alpha fetoprotein is elevated
At what T stage does vascular invasion occur?
T2 or higher
At what T stage does a tumor involve a major branch of the portal or hepatic vein?
T3
Invasion of what organ does not count as T4 in hepatocellular carcinoma?
Gallbladder
Who gets screened for Hepatocellular carcinoma and what does screening consist of?
- Cirrhosis or Chronic HBV/HCV
- Liver US and alpha fetoprotein q 6months
CT is better but more expensive
How do you treat hepatocellular carcinoma?
Resection if no vascular invasion (AKA T1 or lower)
What MELD score suggests poor post-transplant survival rates?
MELD = Model for end-liver disease staging
> = 20
