Hepatitis & Liver Disease Flashcards
Symptoms
Nausea, loss of appetite, vomiting, diarrhea, malaise, abdominal pain in the upper right quadrant, yellowed skin and eyes, darkened urine, clay stool
Hepatitis
Inflammation of the liver
Causes: viral hepatitis, drugs, alcohol
Diagnostic criteria
ALT: normal (7-55 u/L) AST: normal (8-48) Decreased albumin Increased Alk phos Increased bili Increased prothrombin time
The higher the value the worse the liver disease
Child-Pugh
Class A: mild disease (score <7)
Class B: moderate disease (score 7-9)
Class C: severe disease (score 10-15)
Natural products
Milk thistle does not significantly influence the course of a patient with alcoholic liver disease
Hepatotoxic drugs
Examples: acetaminophen, amiodarone, carbamazepine, estrogen, fenofibrate, gemfibrozil, isoniazid, ketoconazole, ketorolac, methimazole, methotrexate, NNRTIs, NRTIs, PIs, phenytoin, rifampin, tamoxifen
Stopped when the levels are greater than three times the upper limit of normal
Alcoholic liver disease
Fatty liver (steatosis): chronic consumption results in the secretion of pro-inflammatory cytokines, oxidative stress, lipid peroxidation, and acetaldehyde toxicity
Benzos used for alcohol withdrawal inpatient and anticonvulsants used outpatient
Naltrexone (ReVia), acamprosate, disulfiram (Antabuse) are used to prevent relapses
Treatment of alcoholic liver disease
Alcohol cessation
Proper nutrition: vitamins and trace minerals including many B vitamins (thiamine, folate, pyridoxine)
Complications of liver disease
- Portal HTN and visceral bleeding:
Non-selective beta blockers (an doll land propranolol) and/or variceal ligation used for prevention
Nadolol (Corgard) and propranolol (inderal LA)
BB warning: do not withdrawal abruptly, gradually taper 1 to 2 weeks to avoid acute tachycardia, hypertension, and/or ischemia
Contraindications: sinus bradycardia, second or third degree heart block, sick sinus syndrome, cardiogenic shock, severe hyperactive airway disease
Side effects: decrease heart rate, hypotension, dec. libido, impotence
Hepatic encephalopathy
Symptoms: musty area of the breath and/or urine, changes in thinking, confusion, forgetfulness, mood changes, drowsiness, worsening tremors, sluggish movements and risk of coma
Symptoms of hepatic encephalopathy result from an accumulation of got derived nitrogenous substances in the blood (ammonia)
Treatment of hepatic encephalopathy
Diet: reduce the amount of protein to prevent the accumulation of ammonia (plant protein preferred over animal)
Drug therapy (prevention): lactulose Acute job therapy: rifaxamin, neomycin, metronidazole) and lactulose
Lactulose
Converts ammonia to ammonium which cannot pass into the blood and enhances the diffusion of ammonia into the colon for excretion
Side effects: flatulence, diarrhea, dyspepsia, abdominal discomfort, hypokalemia
Neomycin
Blackbox warning: neurotoxicity including hearing loss, vertigo, ataxia; nephrotoxicity; neuromuscular blockade and respiratory paralysis especially when given soon after anesthesia or with muscle relaxants
Side effects: G.I. upset, ototoxicity, nephrotoxicity
Rifaxamin (xifaxan)
side effects: preferable edema, dizziness, fatigue, nausea, ascites, flatulence, headache
Monitoring: mental status, ammonia
Metronidazole (flagyl)
Blackbox warning: possibly carcinogenic
Contraindications: first trimester pregnancy; use of disulfiram within the past two weeks; use of alcohol during therapy or within three days of therapy discontinuation
Do not use long-term due to peripheral neuropathy
Take extended release tablets on and empties stomach
Ascites
Fluid accumulation within peritoneal space that can result in bacterial peritonitis and hepatorenal syndrome.
Treatment: dietary sodium restriction (<2g/day), avoid NSAIDs, use diuretics (combination of furosemide and spironolactone at 40mg:100mg)
Spontaneous bacterial peritonitis
Target streptococci and enteric gram negative pathogens with ceftriaxone for 5-7 days
Some pts receive bactrim prophylactically
Hepatorenal syndrome
Occurs in pts with advanced cirrhosis
Renal vasoconstriction via RAAS
Treat with renal vasodilators: fenoldopam and dopamine
Viral hepatitis
Causes: HepA, HepB, HepC, herpes, CMV, Epstein-Barr virus, and adenovirus
Hepatitis A
Fecal-oral route through improper hand washing or via contaminated food or water
HepA vaccine: Havrix, Vaqta)
HepA vaccine is given to children at one year of age as two shots and to adults if risk factors are present
Treatment of HepA is supportive treatment and no antiviral agents are needed
HepB
Can lead to chronic infection, cirrhosis (scaring) of liver, liver cancer, liver failure and death.
Transmission: infectious blood, semen, or other body fluids
Vaccine: 3 IM injections (Engerix-B)
Treatment: antivirals (NRTIs) and interferons are used for chronic therapy for usually 1 year
HepC
Non-vaccine preventable disease
Transmission: blood and body fluid ( more common with IV drug abusers)
Treatment: peginterferon, ribavirin, PIs, and/or new agent sofosbuvir
Interferon Alfa:
Interferon-a-2b (intron)—HepB, HepC
Pegylated interferon-a-2b (pEG-Intron)—HepC
Pegylated interferon a-2a (pegasys)—HepB & C
Interferon alfacon-1 (infergen)—HepC
Combo of interferon a-2b and ribavirin (rebetron)
Indicated for HepB and HepC
Antiviral effects
Black box warning: May cause or exacerbate autoimmune disorders; may cause or aggravate infectious disease disorders; may cause or aggravate ischemic or hemorrhagic cerebrovascular events; combination treatment with ribavirin may cause birth defects and/or fetal mortality and/or hemolytic anemia
Contraindications: autoimmune hepatitis, decompensated liver disease and Cirrhotic patients, and infants/neonates
Warnings: neuropsychiatric, cardiovascular, endocrine disorders, retinopathy, dec. vision, pancreatitis
Adverse events:(associated with many adverse events) flulike syndrome 1 to 2 hours after administration (can pretreat with acetaminophen, antihistamine); CNS effects (fatigue, anxiety, depression), G.I. upset (nausea, vomiting, anorexia, and weight loss), increased LFTs
Note must dispense medguide and must reduce dose if thrombocytopenia or neutropenia is present
Interferon alfa counseling
Injection technique: prefilled refrigerated syringes; or vials with syringes
Interferons are injected into the abdomen if the patient is too thin, the top of the thigh or the outer surface of the upper arm, ALWAYS rotate sites
Nucleoside reverse transcriptase inhibitors (NRTIs)
FOR HEPATITIS B ONLY (inhibit HepB replication)
Dosing: decrease dose if creatinine clearance is less than 50ml/min
Blackbox warning: lactic acidosis (seek medical attention right away if you feel very weak or tired have unusual muscle pain, have trouble breathing, have stomach pain with nausea and vomiting, and feel dizzy or lightheaded) and severe hepatomegaly with steatosis which may be fatal; exacerbations of hepatitis B may occur upon discontinuation monitor closely
Drug interactions: ribavirin can increase hepatotoxic effects of all NRTIs; Bactrim can increase Lamivudine levels due to reduced excretion
Examples of NRTIs
Lamivudine (epivir HBV): do not use for treatment of HIV; contains too low dose of lamivudine
Adefovir (hepsera): may cause HIV resistance in patients with unrecognized or untreated HIV infection; use caution in patients with renal impairment or those at risk of renal toxicity
Tenofovir (viread): (1st line) May cause Fanconi syndrome, renal insufficiency, osteomalacia and decreased bone density
* avoid concomitant tx with didanosine due to increased risk of virologic failure
Enters or (baraclude): (first-line) take on an empty stomach (food reduces the AUC by 20%); may cause HIV resistance in patients with unrecognized or untreated HIV; may also cause peripheral edema
Telbivudine (Tyzeka): increased CPK, increased LFTs
Ribavirin (Copegus, Rebetol, Ribasphere, RibaPak, Virazole)
Used in combination with interferon for treating hepatitis C
Stop if there is not an early final response by week 12; not recommended for monotherapy against hepatitis C
Not recommended in patients with CrCl <50, autoimmune hepatitis, concomitant use with didanosine
Protease inhibitors
Indicated for the treatment of chronic hepatitis C when used in combination with Peginterferon alfa and ribavirin
Drugs: boceprevir (Victrelis), teleprevir (incivek), and simeprevir (olysio)
Notes: watch for drug interactions as is an inhibitor and substrate of cyp3A4
Boceprevir (Victrelis)
usually started on week 5 of peginterferon and ribavirin therapy. Contraindications include those for Peg interferon and ribavirin especially pregnancy and then his female partner is pregnant. Side effects include fatigue, anemia, neutropenia, taste distortion (dysgeusia). Never reduce the dose or interrupt therapy and never use as monotherapy
Teleprevir (Incivek)
Contraindications of the same as Peginterferon ribavirin and boceprevir
Side effects: serious skin rash discontinue all treatment of progression or severe, fatigue, itching, taste distortion, anemia, anorectal disorders, nausea, diarrhea
Note: never reduce the dose or interrupt therapy as treatment failure may result. Never use as monotherapy must always be combined with Peg interferon and ribavirin
Simeprevir (olysio)
Contraindications: same as the previous medications
Side effects: rash or photosensitivity, pruritis and nausea
Notes: NS3 Q80K polymorphism testing recommended as patients with this polymorphism will not respond and alternative therapy should be given; never uses monotherapy must always be combined with Peg interferon and ribavirin
Sofosbuvir (sovaldi)
Inhibitor of hepatitis C RNA dependent RNA polymerase which is essential for viral replication
Nucleotide prodrug and is indicated for hepatitis C only
Should be used with ribavirin but can be used with out Interferon alpha in certain genotypes or patients who are interferon ineligible
Drug interactions: avoid with PGP inducers such a St. John’s wort and rifampin. Also avoid with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin and tipranivir/ritonavir
