Liver disease & viral hepatitis Flashcards
What are the main functions of the liver?
glycogenolysis
cholesterol met, bilirubin met. urea cycle, steroid metabolism
gluconeogenesis
clotting factors, albumin, bile production
drug metabolism
what are the Phase I and phase II drug metabolism reactions
Phase I: oxidations by the cytochrome p450 systemic
Phase II: glucoronidation
WQhich labs can you look for liver function?
AST ALT ALk phos GGT T. Bilirubin albumin PT
When elevated, what do AST and ALT indicated?
hepatic necrosis
when elevated, what to Alk Phos and GGT indicate?
biliary obstruction if both are elevated
inc GGT can also indicat chorlnic liver disease
what is the normal value of AST
16-41 U/L
what is the normal level for ALT?
12-59 U/L
Normal value for Alk phos?
29-111 u/L
what is direct bilirubin and what does it mean when it is elevated?
Direct bilirubin= conjugated bilirubin which is elevated with bile duct obstruction or impaired intrahepatic excreition (hepatitis drugs, etc )(AFTER the liver)
what is indirect bilirubin and what does it mean when it is elevated?
Indirect bilirubin= unconjugated bilirubin is elevated in hemolysis (BEFORE the liver)
what is a normal albumin level? what does it mean when its is low or high?
3.4-4.7g/dL
i. If its low means that there is decreased hepatic synthetic capacity. Reasons it could be low: malnutrition, fluid overload, protein losing syndromes
ii. If it is high it can mean the person is dehydrated
what is the normal prothrombin time?
12 seconds
which clotting factors are made by the liver?
i. Major clotting factors 1,2,5, 7, 9, 10 are made in liver except 8
What does an elevated PT indicate?
problems with hepatic synthetic capacity
iii. Thrombocytopenia can occur due to portal hypertension and pooling in the spleen, decrease hepatic synthesis, and immune mediated destruction
what is the pathophysiology of cirrhosis?
i. when there is injury to hepatocytes, stellate cells, which reside in the sinusoid spaces start secreting collagen that lead to fibrosis in the sinusoid tissue. This fibrosis leads to increase in blood pressure of the portal vein. Additional changessucha ans changes in vasodilatory (NO) and vasocontricting (endothelin) mediators add to the pathophysiology
what are the main consequences of cirrhosis?
ascites, portal hypertension, esophageal vaircies, hepatic encephalopathy and coagulation disorders
what are the signs and symptoms of liver cirrhosis?
Weakness/fatigue, loss of appetite, diarrhea, abdominal pain the RUQ, yellow skin, dark urine or light clay colored stool
NVD
hypoalbuninemia, cogulaopathy, jaundice, glucose intolerance, hypolycmeia, hepatic encephalopathy, thrombocytopenia, inc AST, ALT, GGT
portal hypertension: esophageal/gastric varicies, splenomegaly, leukopenia/thrombocytopenia, ascites
what is the child-Pugh score and what is it used for ? What is the MELD score?
i. Quantifies the effects of cirrhosis in terms of labs and clinical manifestations. Usually when there are drug dosing adjustments for liver failure , you use this score.
ii. Both of the systems are used to define severity of cirrhosis, patient survival prediction, surgical outcome, risk of variceal bleeding
what are common causes for acute liver failure?
: viral hepatitis (HAV, HBV, EBV, CMV), drug induced APAP, INH, amanita phalloides mushroom, Wilson’s disease, Reye’s syndrome, toxins (CCL4, hydrazines), cryptogenic
what are examples of acute liver failure?
fulminant hepatic failure, subfulminant hepatic failure
what are common causes for chronic liver failure?
viral (HCV, HBV ), alcoholic cirrhosis, primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, malignancy, cryptogenic
what is the general treatment approach in fulminant hepatic failure?
treat it depending on the symptoms that they are having
what is the definition of fulminant hepatic failure?
i. Hepatic encephalopathy within 8 weeks of onset of symptoms or within 2 weeks of the onset of jaundice. No prior history of liver disease
ii. Cerebral edema is common, portal hypertension complications are rare, can be reversible
what is the definition of subfulminant hepatic failure?
iii. Subfulminant is hepatic encephalopathy within 2 weeks and 3 months of onset of jaundice
what is tx for pts with fulminant hep failure and cerebral edema?
- Elevate head
- Mannitol
- Hyperventilate
what is tx for pts with fulminant hep failure and hypoglycemia?
d10w infusion
what is tx for pts with fulminant hep failure and coagulopathy ?
- Vitamin K (if deficient) : phytonadione (vit K) 10mg SQ daily x 3 days
- FFP (fresh frozen plasma for invasive procedures),
- factor VIIa
what is tx for pts with fulminant hep failure and GI bleed ?
stress ulcer prophylaxis: H2 blockers or omeprazole
what is tx for pts with fulminant hep failure and hepatic encephalopathy ?
avoid drugs that alter mental status and lactulose is not effective
what is hepatic encephalopathy and what is the proposed pathophys?
a. Syndrome characterized by AMS (confusion→ coma)
b. Accumulation of ammonia, production of false neurotransmitters, activation of GABA receptors, altered cerebral metabolism
what are the 4 stages of hepatic encephalopathy?
I. restlessness, forgetfulness, mild confusion
II. Drowsiness, lethargic, can’t perform mental tasks, disoriented, amnesia, ataxia, asterixis
III. Somnolent but arousable, unable to perform mental tasks, disoriented to time/place, incomprehensible speech
IV. comatose
what are the main treatment options for chronic hepatic encephalopathy? DOC?
lactulose =DOC
rifamixin- second line
neomycin
what is the non pharm Tx for HE
limit protain intake 0.81g/kg/day
avoid red meat, fish, vegtable protein the best
Lactulose
I= chronic HE
MOA: bacteria in the intestinal tract covert it to lactic and formic acid. The acidic environment causes NH3 from the blood to flow into the intestine and bind the acid. NH4+ cannot be absorbed back to blood because it is charged. There is an osmotic effect that draws water into the intestines (causing catharsis: diarrhea)
Dose:
a. ORAL 30ml po TID (concentration is 10g/15ml syrup. Titrate to mental status and 3-4 bowel mvment/day
b. IF it is stage III or IV, can give po or NG every 1-2 hours titatrated to mental status or 5-6 bowel movents /day
c. Other doses for enema available
SE: flatulence, bloating, diarrhea, hypernatremia, too sweet (can try kristalose)
Rifamixin
- MOA: antibiotic that is not well absorbed in the GI tract. Kills off Urease producing bacteria
- Dose: 550mg po bid or 400mg pot id
- SE: headache, flatulence, nausea, rash
neomycin
- MOA: aminoglycoside not well absorbed in the GI tract. Kills off urease producing bacteria
- Dose: 500mg po QID (2-4 g/day)
- SE: nephrotoxicity, ototoxicity
what is the pathophysiology of portal hypertension?
b. due to increased resistance to blood flow through the liver because of altered lobular and vascular architecture (fibrosisis in the sinusoids). Leads to back up in the portal vein. This leads to back up in the left gastric vein→ esophageal varices etc.
what defines portal hypertension?
> 10mmHG wedge hepatic vein pressure
what is the treatment approach for portal htn?
prevent the first bleeding episode (primary ppx), 2. Treat acute variceal bleeding 3. Secondary prophyalxis
what are the signs and symptoms of portal hypertension?
Splenomegaly esophageal varices Gastric varices portal hypertensive gastropathy hemorrhoids
what is the treatment for preventing bleeding from varices? doses?
Propranolol 20mg po tid max 320mg/day
nadolol 20mg-40 po daily max 40mg /day
normally you used nitrates with BB
what is the MOA in preventing bleeding from hemorrhage?
decreased cardiac output & vasoconstriction of splanchnic bed results in decreased portal blood flow
what are the nitrate doses for variceal bleeding prevention?
- Isosorbidide dinitrate 5-10mg pot id
2. Isosorbid monotintrated 15-30mg po daily
MOA and side effects of nitrates to prevent bleeding from varices?
- MOA: vasodilation causes venous blood pooling which induces splanchnic vasoconstriction and resulting in decreased portal pressure
- SE: hypotension, bradycardia, wheezing, confusion
what is the tx for variceal bleeding?
- fist start with fluid resucitation and ruling out other forms of bleeding.
start pharmacological treatment to stop variceal bleeding.
then do an endoscopic examination.
most effective combination is EBL + pharmacotherapy
what is involved in EIS? what does it stand for?
- MOA: vasodilation causes venous blood pooling which induces splanchnic vasoconstriction and resulting in decreased portal pressure
- SE: hypotension, bradycardia, wheezing, confusion
what is involved in EBL? what does it stand for?
- EBL: endoscopic band ligation: they place rubber bands around the varix with an endoscope.
why use EBL over EIS?
- EBL is»_space; effective than EIS and EIS = drug therapy. Safer and requires fewer sessions to obliterate varices. Improves survival
what do you do if endoscopic methods fail?
tamponade, transjuular intrahepatic protsystemic shunting (TIPS), or surgical shunting.
5. TIPS can be used if endoscopic and pharmacology fails. TIPS involves the placement of one or more stents between the hepatic vain and portal vein. Its as effective and portable shunts but 30% get HE and 50% shunts malfunction
what is the DOC for variceal bleeding?
ocreotide
ocreotide
a. MOA; polypeptide analog of somatostatin that vasoconstric the splanchnic bed and results in decreased portal vein flow and pressure.
b. Use: + is that athe vasoconstriction is selective for the mesenteric circulation vs vasopressin is not. Meta analysis ccomparing ocreotide with vasopressil, terlipressin or placebo found it controlled bleeding than any other agents.
c. Dose: LD: 50-200mcg IV push then 50-100mcg/hr infusion
d. Monitor: hypo or hyperglycemia
e. Side effects: bradycardia (w/ large IV bolus), ileus, choestatis, hypoglycemia (generally few side effcts)
what is second line for variceal bleeding?
vassopressin + nitroglycerin
vasopressin + nitroglycerine moa and use
a. MOA: peptide hormone form posterior pituitary (ADH) that causes vasoconstriction of small arterioles and capillaries resulting in dec blood flow to the splanchinic bed, coronary arteries, GI tract, pancreas, skin and muscle
b. Use: V not a selective vasoconstrictor so u get systemic effects vs. ocreotide. Using it with nitroglycerine has been shown to improve control of bleeding with less side effects
d. SE: myocardia ischemia, arrhythmias, hypertension, water intoxication/hyponatremia
e. Dose: start infusion at 0.2-04 Units/min and titrate to a maximum of 1U/min + nitroglycerin 10-40mcg/min as conintinusous infusion, titrate to SBP of 90-100mmhg or nitroglycerin patch 10mg/24h (0.4mg/hr)
what is the secondary prophylaxis for bleeding again from varices? should it be given?
everyone who has had a previous bleeding varice should get it
first line is beta blockers + EBL
what is ascites?
a. Accumulation of fluid in peritoneal cavity for increased production or decreases absorption of peritoneal fluid.
sx of ascites
i. Edema
1. Bulging flanks, increased abdominal girth
2. Fluid wave/shifting dullness on exam
3. Abdominal fullness bloating
4. Low urinary sodium and urinary output
5. Ascities on ultrasound
6. Hepatorenal syndrome
ii. Increase weight
1. Impaired ambulation
2. GERD
3. Low back pain
4. Impaired pulmonary function
non pharm tx of ascites?
- Bed rest because standing increases renin activity
- Sodium restriction < 2g/day if patient has portal hypertension. fluid restriction 1-1.5L perday if severe hyponatremia
- Stop alcohol
tx options of ascities
loop diurteics and potassium sparing diuretics. Use loops alone or in combo with K sparing diuretics. watch fro electrolyte abnormalities
what is the goal for therapy for ascites?
a. Lose 0.5kg/day loss of weight if pt does not have edema, 1kg/day in patients with edema
surgical tx of ascites
- Large volume paracentesis
a. Ascetic fluid is directly drained form the peritoneal cavity (1-12L)
b. Must give albumin to prevent hemodynamic complications. Albumin 25$ 50ml (12.5g) per liter of ascites removed
c. Expensive, infections, hypotension, precipitation of renal failure - Shunt
- TIPS
- Liver transplant
most common agents that cause SBP?
e.coli*, klebsiealla sp, streptoccus pneumonia
sx of sbp?
i. abdominal pain, worsened renal function, fever, malaise, leukocytosis, increased ascites worsened hepatic encephalopathy
ii. diagnose: >250 neutrophils/mm3 in ascetic fluid and potsitive ascetic fluid culture
tx of sbp?
i. ceftriaxone 1g IV daily x 5-10 days or cefotaxime 1-2 g IV q 8h x 5-10 days
ii. penicillin allergy : ciprofloxacin 400mg IV q 12 h 5-10 days, vancomycin 10-15mg/kg IV q 12h if concerned about gram + cocci
prophylaxis of sbp?
i. regimens are continued ofr life or until day of transplantation
ii. primary and secondary
1. cipro 750mg po q week ** most common
2. cipro 500mg po daily
3. TMP/SMX 1 ds tab po Monday – Friday
4. Norfloxacin 400mg po daily to bid
5. Ofloxacin 400mg po daily
what is a natural product people use for the liver?
milk thistle: most studies show benefit but have not been designed well enough to say that there is a benefit. it is well tolerated
when do you stops most medications that cause liver damage?
usually when > 3x ULN >150 AST/ALT
three natural products that can damage the liver?
comfrey
kava
chaparral
common meds that cause liver damage?
APAP, Amiodarone, Azoles CBZ Fibrates HIV meds INH Niacins rifampin Statins
which vitamin should alcoholics take? what does it prevent?
vitamin B1 (thiamine) prevetns Wernicke’s Korsakoff syndrome : a type of encephalopathy that leads to brain damage
What should you include with each fill of an intron medication?
A med guide
Hepatitis C interferons
Intron A Peg intron Pegasys Infergen Rebetron
Hepatitis b interferons
Intron A
Pegasys
How often do you dose the pegylated forms of the introns?
Once weekly (pegintron & pegasys)
What is the BBW for interferons?
Can aggravate autoimmune & neuropsychiatric disorders, ischemic or infectious disorders. You must stope the drug if this happens
What are the main adverse effects of interferons?
Flu like symptoms 1-2 hours after the administration and car last up to 24 hours
How can you prevent the flu like symptoms of introns?
Can pretreat patient with APAP AND an antihistamine
What lab value is expected to increase after using interferon?
Liver enzymes
At what ANC & platelet count should you stop interferons?
ANC <25,000 platelets
Where do you inject interferon injections in the body?
In the abdomen but not if pt is too thin, top of the thigh, or outer surface of the upper arm
What is Ribavirin indicated to be used with? What other agent
Should be used with interferon alpha 2a/2b
What should you always dispense Ribavirin with ?
A med guide
BBW FOR Ribavirin
Significant teratogenic effects
Possible hemolytic anemia 1-2 weeks after starting the medication
Contraindications of Ribavirin
Clcr <50 ml/ min
Pregnancy or a women who might get pregnant
The male partner of a pregnant woman
What type of protection should a woman have if she is taking Ribavirin?
Two reliable forms of oral contraceptives during treatment and 6 months after the end of her treatment. They must also have birth control tests to show that they are not pregnant.
Counseling for Ribavirin
Use contraception during and 6 months after the therapy
Female partners of males with therapy also need contraception
The oral solution; wash the spoon
Can cause anemia so you should have baseline and other blood cell count checks with therapy
Victrelis
Boceprevir
Boceprevir brand
Victrelis
How do you take your boceprevir?
800mg po tid with food starting on week 5 of your therapy with Ribavirin and interferon
Main side effects of boceprevir
Fatigue
Anemia
Neutropenia
Taste distortion
Incivek
Telepravir
Telepravir brand
Incivek
How do you take your Telepravir?
With at least 20 grams of fat for 12 weeks
Main side effects of Telepravir
Severe skin rash Fatigue Itching Taste distortion Anemia Anorrectal disorders
Drug drug interactions of boceprevir and Telepravir
Cyp 3a4 inhibitors and substrates
NRTIS used for hepatitis b
Lamivudine Adefovir Tenofovir Entecavir Telbivudine
Epivir HBV
Lamivudine
Hepsera
Adefovir
Lamivudine dose for HBV
100 mg po bid
Lamivudine dose for HBV and HIV coinfection
150 po bid
Tenofovir dose for HBV
300 mg po daily
Can you use epivir HBV for HIV?
No the dose is too low and can cause resistance. This is a black box warning
Which patients are at risk of toxicity from adefovir and tenofovir?
People with renal impairment
What are the main side effects of tenofovir?
Fanconis syndrome
Renal insufficiency
Osteomalacia and decrease in bone density
Viread
Tenofovir
Baraclude
Entecavir
How should you take your baraclude?
On an empty stomach
Tyzeka
Telbivudine
Side effects of telbivudine
Myopathy and myalgia
