Hepatitis & Liver Disease

Question 0

Symptoms

Answer 0

Nausea, loss of appetite, vomiting, diarrhea, malaise, abdominal pain in the upper right quadrant, yellowed skin and eyes, darkened urine, clay stool

Question 1

Hepatitis

Answer 1

Inflammation of the liver

Causes: viral hepatitis, drugs, alcohol

Question 2

Diagnostic criteria

Answer 2

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

Question 3

Child-Pugh

Answer 3

Class A: mild disease (score <7)
Class B: moderate disease (score 7-9)
Class C: severe disease (score 10-15)

Question 4

Natural products

Answer 4

Milk thistle does not significantly influence the course of a patient with alcoholic liver disease

Question 5

Hepatotoxic drugs

Answer 5

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

Question 6

Alcoholic liver disease

Answer 6

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

Question 7

Treatment of alcoholic liver disease

Answer 7

Alcohol cessation

Proper nutrition: vitamins and trace minerals including many B vitamins (thiamine, folate, pyridoxine)

Question 8

Complications of liver disease

Answer 8

1. Portal HTN and visceral bleeding:

Non-selective beta blockers (an doll land propranolol) and/or variceal ligation used for prevention

Question 9

Nadolol (Corgard) and propranolol (inderal LA)

Answer 9

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

Question 10

Hepatic encephalopathy

Answer 10

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)

Question 11

Treatment of hepatic encephalopathy

Answer 11

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

Question 12

Lactulose

Answer 12

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

Question 13

Neomycin

Answer 13

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

Question 14

Rifaxamin (xifaxan)

Answer 14

side effects: preferable edema, dizziness, fatigue, nausea, ascites, flatulence, headache

Monitoring: mental status, ammonia

Question 15

Metronidazole (flagyl)

Answer 15

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

Question 16

Ascites

Answer 16

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)

Question 17

Spontaneous bacterial peritonitis

Answer 17

Target streptococci and enteric gram negative pathogens with ceftriaxone for 5-7 days

Some pts receive bactrim prophylactically

Question 18

Hepatorenal syndrome

Answer 18

Occurs in pts with advanced cirrhosis

Renal vasoconstriction via RAAS

Treat with renal vasodilators: fenoldopam and dopamine

Question 19

Viral hepatitis

Answer 19

Causes: HepA, HepB, HepC, herpes, CMV, Epstein-Barr virus, and adenovirus

Question 20

Hepatitis A

Answer 20

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

Question 21

HepB

Answer 21

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

Question 22

HepC

Answer 22

Non-vaccine preventable disease

Transmission: blood and body fluid ( more common with IV drug abusers)

Treatment: peginterferon, ribavirin, PIs, and/or new agent sofosbuvir

Question 23

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)

Answer 23

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

Question 24

Interferon alfa counseling

Answer 24

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

Question 25

Nucleoside reverse transcriptase inhibitors (NRTIs)

Answer 25

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

Question 26

Examples of NRTIs

Answer 26

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

Question 27

Ribavirin (Copegus, Rebetol, Ribasphere, RibaPak, Virazole) Used in combination with interferon for treating hepatitis C

Answer 27

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

Question 28

Protease inhibitors

Answer 28

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

Question 29

Boceprevir (Victrelis)

Answer 29

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

Question 30

Teleprevir (Incivek)

Answer 30

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

Question 31

Simeprevir (olysio)

Answer 31

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

Question 32

Sofosbuvir (sovaldi)

Answer 32

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