Chapter 19. Hepatitis & Liver Disease

How is HAV transmitted?

Fecal-oral route due to improper handwashing after exposure to an infected person or ingestion of contaminated food/water

What can HBV and HCV lead to?

Cirrhosis of the liver
Liver cancer / failure

How is HBV and HCV transmitted?

Blood or bodily fluids (having sex with an infected person)
Sharing contaminated needles to inject drugs
Infected mother to new newborn (perinatal transmission)

What is the 1st line treatment for HCV?

What is the 1st line treatment for HCV?

DAA combination (direct-acting antiviral)
(2-3 DAAs with different mechanisms x 8-12 weeks)

What drugs can be used in patients who are treatment-naive without cirrhosis?

Mavyret (Glecaprevir/pibrentasvir)

Epclusa (Sofosbuvir/velpatasvir)

What drug classes are DAAs?

NS3/4A protease inhibitors
NS5A replication complex inhibitors
NS5B polymerase inhibitors

What drugs are NS3/4A protease inhibitors?

-PREVIR

What drugs are NS5A replication complex inhibitors?

-ASVIR

What drugs are NS5B polymerase inhibitors?

-BUVIR

What DAAs should not be used with amiodarone?

Sofosbuvir-containing regimens (Epclusa)

Can cause symptomatic bradycardia

What needs to be monitored with all DAAs?

HCV-RNA

What is an important counseling note with Mavyret?

Use with ethinyl estradiol (alternative contraception during treatment)

What is contraindicated with Mavyret use?

History of hepatic decompensation

Use with strong CYP3A4 inducers (decrease concentration of Mavyret)

What drugs are strong CYP3A4 inducers?

INducer = PS PORC
Phenobarbital
St. John's Wort
Phenytoin
Oxcarbazepine
Rifampin/Rifabutin
Carbamazepine

Can Sofosbuvir be used alone?

No; not effective and not recommended

Which DAAs must be dispensed in the original container?

Sovaldi, Epclusa, Havroni, Vosevi

Which DAA is approved for 8-week course of therapy?

Mavyret

Which DAAs are approved for salvage therapy (failed all previous therapies)?

Vosevi
Mavyret

Most DAAs increase concentration of what drug class?

Statins → increased myopathy risk

What drug is an oral antiviral that inhibits replication of RNA & DNA viruses?

RIBAVARIN

What are important counseling notes for ribavirin?

What are important counseling notes for ribavirin?

Avoid pregnancy in females & partners for 6 months during and after completion

2 reliable forms of effective contraception are required

What is the mechanism of action of NRTIs?

Inhibit HBV replication by inhibiting HBV polymerase --> DNA chain termination

How should HBV NRTIs be dosed if CrCl is < 50 mL/min?

Decrease dose or frequency

What drugs are NRTIs?

Tenofovir disproxil fumarate (TDF; Viread)
** Preferred

Tenofovir alafenamide (TAF;Vemlidy) - Does not need dosing adjustments
** Preferred

Entecavir (Baraclude)
** Preferred

Lamivudine (Epivir HBV)

Adefovir (Hepsera)

What are BBWs with TDF (Viread) and TAF (Vemlidy) use?

Renal toxicity (Faconi syndrome, osteomalacia, decrease BMD)

What is a BBW with lamivudine (Epivir HBV)?

Do not use for treatment of HIV. Can result in HIV resistance

What is a BBW with adefovir (Hepsera)?

Caution with renal impairment (renal toxicity)

TAF (Vemlidy) should be avoided in which drugs?

TAF is a P-gp substrate

Do not use with CYP Inducers
Phenytoin
St. John's Wort
Phenobarbital
Oxcarbamazepine
Carbamazepine

What drug can increase lamivudine levels (due to excretion)?

bactrim

How are INF administered? (Route of administration)

subcutaneous

What are warnings with INFs?

CNS effects (fatigue, depression, GI upset, increased LFTs, flu-like symptoms)

What should be taken before taking INFs?

Pre-treat with acetaminophen and an antihistamine

What is cirrhosis?

Advanced fibrosis (scarring) of the liver

What are the common causes of cirrhosis?

Hepatitis C
Alcohol consumption

What are the complications of cirrhosis / what can it lead to?

Portal HTN
Gastroesophageal varices
Ascites
Hepatic encephalopathy

What lab test indicate cirrhosis?

What lab test indicate cirrhosis?

Increased AST/ALT, Alk phos, Tbili, LDH, PT/INR

Decreased albumin

What lab test indicate alcoholic liver disease?

Increase AST/ALT, gamma-glutamyl transpeptidase (GGT)

What lab test indicates hepatic encephalopathy?

Increased ammonia

What lab test indicates jaundice?

Increase Tbili

What are symptoms of cirrhosis?

Loss of appetite, vomiting, diarrhea
Pain in the upper right quadrant of abdomen
Jaundice / darkened urine
Light / white colored urine (from decreased bile)

What liver enzymes need to be monitored with cirrhosis?

AST (aspartate aminotransferase)
ALT (alanine aminotransferase)

What is used to measure the severity of liver disease?

Child-Pugh classification system

What natural medicines are hepatotoxins?

Kava *

Comfrey
Flavocoxid

When should drugs be stopped due to hepatotoxicity?

LFTs are 3x normal limit (>150 units/L of ALT or AST)

What drugs have a boxed warning for liver damage?

Acetaminophen
Amiodarone
Isoniazid
Ketoconazole (oral)
MTX
Nefazodone
Nevirapine
NRTIs
PTU
Valproic acid

What supplement is used to help prevent and treat Wenicke-Korsakoff syndrome?

Thiamine

vit b1

What are treatment options for variceal bleeding?

Band ligation
Sclerotherapy

Octreotide (selective)
Vasopressin

What drug class can be used for primary and secondary prevention of variceal bleeding?

Non-selective B-blockers

What is the generic name for Sanfdostatin?

Octreotide

What are side effects of vasoconstricting medications for variceal bleeding?

Bradycardia (remember, they're B-blockers; slows down heart rate)
Cholelithiasis
Biliary sludge

What non-selective B-blockers can be used for variceal bleeding?

Nadolol
Propranolol

How do non-selective B-blockers help with preventing variceal bleeding?

Reduces portal pressure

Remember, they act on the afferent arteriole

What is the target HR when taking a non-selective B-blocker?

55-60

What are the BBW with non-selective B-blockers?

Do not withdrawal abruptly (in CAD/IHD). Gradually taper over 1-2 weeks to avoid tachycardia, HTN, and/or ischemia

What are warnings with non-selective B-blockers?

Caution with diabetes, can mask hypoglycemia or hyperglycemia
Caution with asthma/COPD
Caution with Raynaud's / PVD and pheochromocytoma
Can mask hyperthyroidism

Propranolol = can cross BBB and can cause more CNS side effects

What are symptoms of hepatic encephalopathy?

Musty odor of breath and/or urine
Changes in thinking
Confusion / forgetfulness
Hand tremors (asterixis)

What causes hepatic encephalopathy (HE)?

Accumulation of gut-derived nitrogenous substances in the blood (ammonia)

How can hepatic encephalopathy be treated?

Reducing blood ammonia levels through diet (limiting the animal proteins)

What drugs can be used to treat hepatic encephalopathy?

Using non-absorbable disaccharides (lactulose) and antibiotics (rifaximin, neomycin)

What is the first line of therapy for hepatic encephalopathy?

Lactulose

What is the mechanism of action of lactulose?

Converts ammonia produced by intestinal bacteria to ammonium (which is polar and cannot readily diffuse into the blood)

What is ascites?

Fluid accumulation within the peritoneal space

What type of patient should consider liver transplant?

Cirrhosis
Ascites

What diet should be considered in patients with ascites due to portal HTN?

Sodium restriction to < 2 grams/day

What diuretics can be used for ascites?

Spironolactone monotherapy

Spironolactone + furosemide
(if possible, ratio of 40 mg furosemide to 100 mg spironolactone)

Furosemide mono is ineffective

What is spontaneous bacterial peritonitis (SBP)?

An acute infection of ascitic fluid

What drug can be used to treat SBP?

What drug can be used to treat SBP?

Ceftriaxone
(Targets streptococci and enteric gram negative pathogens) x 5-7 days

What can be used as secondary prophylaxis for SBP?

Ciprofloxacin
Bactrim