Hepatology_UW Flashcards
What is non-alcoholic fatty liver disease? It is further classfied by histology into what?
Hepatic steatosis on imaging or biopsy (resembles alcohol-induced liver injury on histology). Exclusion of significant alcohol use. Exclusion of other causes of fatty liver. Further classified into 1) fatty liver disease and 2) nonalcoholic steatohepatitis (which progresses further into fibrosis/cirrhosis)
What is the pathophysiology of non-alcoholic fatty liver disease?
Likely due to peripheral insulin resistance => increased lipolysis, TAG synthesis and hepatic uptake of fatty acids => intra-hepatic FA oxidation => increases oxidative stress and proinflammatory cytokines (like TNF-alpha) => liver inflammation, increased fat accumulation and fibrosis/cirrhosis.
What are the major risk factors for non-alcoholic steatohepatitis (NASH)?
Top 3 risk factors - obesity, diabetes mellitus, hypertriglyceridemia. Other risk factors (certain medications, corticosteroids, HAART, tamoxifen, diltiazem, amiodarone), TPN, endocrinopathies.
What is the criteria for initiating tx for chronic hepatitis C?
1) Age > 18 2) detected HCV RNA in serum 3) liver biopsy with bridging fibrosis (or worse) and chronic hepatitis 4) compensated liver disease (i.e., albumin greater than 3.4mg/dL, no ascities, bilirubin
What are the contraindications for HCV tx?
Ongoing alcohol or drug abuse, major uncontrolled depression.
What is the initial treatment for treatment-naïve HCV patients? What additional tx do patients with HCV genotype 1 receive?
pegylated interforon + ribavirin. Additional protease inhibitor (telaprevir + boceprevir).
Chronic HBV tx is recommended for?
1) Patients with acute liver failure 2) Clinical complications of cirrhosis 3) Advanced cirrhosis wih high serum HBV DNA levels 4) patients without cirrhosis but with positive HBeAg, HBV DNA >20,000 IU/mL and serum ALT >2x upper limit level 5) patients during chemotherapy or immunosuppression so as to prevent HBV reactivation.
What are the available treatments for HBV?
Interferon (usually just short-term treatment and used for younger patients with compensated liver disease), Lamivudine (is showing high levels of resistance to this drug), Entecavir, Tenofovir. Last two most potent, there’s least drug resistance to these.
Medical control of bleeding may be accomplished by what kind of drugs?
vasoconstrictors like Terlipressin (synthetic analogue of vasopression), octeotride, or somatostatin.
All patients with newly diagnosed Hep C infection should be evaluated for?
Antiviral treatment with the goal of eradication HCV RNA and to prevent progression of hepatitis to cirrhosis.
Why should liver biopsy be offered to patients with newly diagnosed HCV infection?
Offers best clinical predictor of disease progression, and helps assess likely response to tx. Patients with moderate to severe inflammation and some fibrosis have higher chance of progression to cirrhosis and respond better. Liver biopsy also determines the stage of the disease, rule other other concomitant liver disease (like hemochromatosis), and guide tx decisions.
Having a detectable level of HCV RNA means?
You have chronic hepatitis C
What is hepatic encephalopathy? What is the pathophysiology?
Alteration in CNS function due to liver’s inability to convert ammonia to urea. Although other toxins may be responsible. These toxins stimulate the inhibitory (GABA) and impair the excitatory pathways in the brain.
What are the sx of hepatic encephalopathy?
Hepatic encephalopathy can be graded in stages. Stage 1 can be altered sleep patterns (diurnal sleep patterns) to Stage 4 (stupor and coma).
What is the treatment for hepatic encephalopathy?
1) Supportive care (such as volume repletion) 2) treatment of the underlying problem/precipitating cause (meds, hypovolemia, infection xs nitrogen, or electrolyte abnormalities such as HYPOKALEMIA), and 3) lowering serum ammonia. TX: 1) non-absorbable disaccharides such as LACTULOSE. Colonic bacteria metabolize lactulose to short-chain FA which acidifies the colon and stimulates the conversion of absorbable ammonia to non-absorbable ammonia and also causes a catharsis. 2) Antibiotics such as Rifaximin can decrease the number of ammonia producing bacteria in the colon. Usually added to lactulose if no improvement with lactulose is seen within 48 hours. 3) Laxatives that cause catharsis.
What is the clinical presentation of Hep C?
Asymptomatic or develop fatigue (most common), can show other non-specific signs like arthralgias, myalgias, weakness, weight loss, nausea, serum transaminases can be elevated or normal, can progress to cirrhosis in up to 20% of patients, increased risk of hepatocellular carcinoma
What are the common extrahepatic manifestations of chronic HCV?
1) heme: essential mixed cryoglobulinemia which is due to circulating immune complexes that deposit in small and medium vessels. May be a/w with low serum complement levels. Patients can develop palpable purpura, arthralgias and 2) renal complications (usually MPGN) 3) Skin: porphyria cutanea tardea (PCT) - fragile sensitive skin, photosensitivity, vesicles and erosions on dorsum of hands, lichen planus 4) endocrine: inreased risk of diabetes.
What is porcelain gallbladder? How does it present? What does it look like on x-ray and CT? and what is usually recommended in this patient population?
WHAT: Calcium-laden gall bladder with bluish discoloration that can develop in patients with chronic cholecystitis. Thought that calcium salts deposit intramurally secondary to chronic inflammation from gallstones or the natural progression of chronic inflammation. PPT: Can be asymptomatic or present with RUQ pain or a firm, non-tender mass in the RUQ. IMAGING: x-ray - calcification, CT - calcification with central bile filled dark area. RECOMMENDATION: Cholecystectomy because up to 33% of patients with develop gallbladder carcinoma (mostly adenocarcinoma).
Gallstones (choleithiasis) are common in what? (phrase)
Fat, forty, female fertile women.
What are the major types of gallstones and which are the most common?
1) Cholesterol 2) pigment 3) mixed. Cholesterol and mixed gallstones are the most common type of gallstones in the US and cholelithiasis is more common in the west compared to the east.
Which gallstones are radiolucent?
Cholestserol and mixed gallstones.
What is primary biliary cirrhosis?
Chronic liver disease that is characterized by auto-immune destruction of intrahepatic bile ducts and cholestasis.
What is the ppt of primary biliary cirrhosis (age, onset, first sx, physical findings)
Usually in middle aged WOMEN with insidious onset. First sx is usually pruritus and it may be very severe, especially at night. PE findings: hepatosplenomegaly, xanthomatous lesions in the eyelids or in the skin/tendons. With disease progression, patient may get jaundice, portal HTN, steatorrhea, osteopenia.
How is primary biliary cirrhosis dx confirmed?
Anti-mitochondrial antibodies in the serum.
What other conditions is primary biliary cirrhosis a/w
Sjogren’s syndrome, Raynaud’s syndrome, scleroderma, autoimmune thyroid disease, hypothyroidism, and celiac disease. Hepatobiliary malginancy risk is elevated in PBC patients.
What is the drug of choice in treating primary biliary cirrhosis?
Ursodeoxycholic acid is the drug of choice. Relieves symptoms and also lengthens transplant free survival time. Methotrexate and colchicine have also shown to be of moderate benefit.
Whats more common - liver mets or HCC?
Liver mets (20x more common than HCC). Also, AFP is elevated with HCC.
How should acute pancreatitis be managed?
Conservative treatment - analgesis (meperidine over morphine), IV fluids, and nothing by mouth to avoid further inflammation of the pancreas.
Anti-1 antitrypsin deficiency is a/w?
Panacinar emphysema and liver cirrhosis.
How is the diagnosis of A1AT deficiency established?
Measurement of A1AT serum level, followed by confirmatory genetic testing.
In the liver, hepatocytic inclusions of A1AT stains with what agent
Stain with Periodic-Acid Schiff reaction and also resists digestion by elastase.
What is the hallmark of ischemic hepatopathy?
Huge increases in AST and ALT with milder associated increases in total bilirubin and and alkaline phosphatase.
What is the serology of patients that have had the Hep B vaccine?
Anti-HBsAg (positive) but negative for HBsAg and all other markers.
What are the serologic markers for Hepatitis B virus?
HBsAg: First virological marker after inoculation, precedes elevation of serum aminotransferases and onset of clinical sx. Remains detectable during the entire symptomatic phase of acute Hep B and suggests infectivity.
An elevated biliary sphincter pressure is highly specific for?
Sphincter of Oddi dysfunction
What is the tx of choice for sphincter of oddi dysfunction?
ERCP with sphincterectomy
Development of a palpable mass in the epigastrium with pain radiating to the back, 4 weeks after an episode of acute pancreatitis is highly suggestive of?
Pancreatic pseudocyst
What is a pancreatic pseudocyst?
It is not a true cyst as it doesn’t have a epithelial lining, rather it is encapsulated by a thick fibrous wall. It contains enzyme rich fluid, tissue, and debris that accumulates within the pancreas and creates an inflammatory response.
How is pancreatic pseudocyst best diagnosed?
Ultrasound and tends to resolve spontaneously.
Pancreatic carcinoma with tumors in the pancreatic body/tail present what way vs. tumors in the head?
Body/tail = pain and weight loss. Head = steatorrhea, jaundice.
What is Courvoisier’s sign? (possible sign of pancreatic cancer)
Nontender but palpable gallbladder at the right costal margin in a jaundiced patient.
What is Virchow’s node (possible sign of pancreatic cancer)
Left supraclavicular adenopathy in a patient with metastatic disease.
What is the initial imaging test for patients with jaundice? What next if the first test is non-diagnostic?
U/S. Abdominal CT next.
What is the presentation of Gilbert’s syndrome? Which part of the Bilirubin uptake process has the defect?
Icterus secondary to a mild, predominantly unconjugated hyperbilirubinemia (normal levels in these patients are
Which part of the Bilirubin uptake process has the defect?
Familial disroder of bilirubin glucoronidation - production of UDP glucuronyl transferase is reduced. (therefore problem of conjugating the bilirubin)
Dx of Gilbert’s is suggested by? Presumptive diagnosis is made by?
No apparent liver disease with mild uncongugated hyperbilirubinemia thought to be provoked by class trigger (hemolysis, fat free diet, physical exertion, febrile illness, stress, fatigue, fasting.) Presumptive dx made when uncongjuated hyperbilirubinemia persists with repeat testing, but LFTs, blood count, blood smear and retic count look normal.
What is the Tx for Gilberts?
Generally considered unnecessary but mode of inheritance should be discussed with patietns to prevent needless testing in family.
What is Criggler Najjar syndrome type 1? Where is the defect in bilirubin uptake/metabolism?
Autosomal recessive disorder of bilirubin metabolism with absent UDP glucuronyl transferase and therefore high levels of indirect biliruin levels (20-25mg/dl to as high as 50mgldl)
What are the findings of Criggler Najjar syndrome type 1?
In infants, severe jaundice and neurologic impairment due to kernicterus (bilirubin encephelopathy). Liver enzymes and histology are normal.
What is the tx for Criggler Najjar syndrome type 1?
Plasmapheresis or phototherapy helpful in short term. Only curative option is liver transplant
What is Criggler Najjar syndrome type 2? Liver enzymes and histology are?
Milder autosomal recessive disorder of bilirubin metabolism with lower serum bilirubin levels
If IV phenobarbital is administered in Criggler Najjar types 1 and 2, what happens?
Type 1 = Serum bilirubin level does not go down. Type 2 = Serum bilirubin levels go down.
Acute bleeding in patients (coagulopathy) with liver failure is best treated with?
Fresh frozen plasma which has all the clotting factors.
