Pharmther - Liver Dz and Viral Hepatitis - Exam 5

nonselective BB

what is the mainstay of therapy for esophageal varice prophylaxis?

Nonselective BB

-shown to decrease risk of initial variceal bleeding by approx 40%

-reduce portal pressure by reducing portal venous inflow

-titrate to Rest Heart Rate of 55-60 bpm

propranolol 20mg-40mg BID PO and Nadolol 20mg-40mg PO daily

what are the nonselective BB used for esophageal varices primary prophylaxis?

Ascites - Tx Goals

-control fluid associated with ascites

-prevent/relieve ascites-related sx

-prevent life-threatening complications

Ascites - NonPharm Tx

-abstinence from alcohol

-sodium restriction of 2 g/day

-fluid restriction is unnecessary in treating most patients with cirrhosis and ascites; may restrict in those with serum sodium <120-125 mEq/L

Ascites - Diuretic Therapy

-required in ~90% of patients with ascites, especially those with moderate to tense ascites, positive sodium balance while on a sodium restricted diet

Ascites - Diuretic Therapy Goal

increased urinary excretion of sodium and water

Ascites - Initiation Diuretic Therapy

-combo therapy: spironolactone + furosemide (preferred)

-monotherapy: spironolactone

Spironolactone

-potassium sparing

-half-life: prolonged

-duration: 2-3 days

-dosing: starting dose 100 mg daily, max dose 400 mg daily

Furosemide

-potassium depleting

-onset: 30-60 min

-duration: 6-8 hr

-start at 40 mg daily, max dose 160 mg daily

SBP Empiric tx

1. IV 3rd gen cephalosporin x5 days --> preferred is cefotaxime 2g IV q8h

2. alternative: oral ofloxacin 400 mg BID x8 days

SBP - Oral Ofloxacin

-alternative option to 3rd gen cephalosporins in pts w/o vomiting, shock, significant hepatic encephalopathy, SCr >3 mg/dL, prior exposure to FQ

SBP - Albumin

-should be given in combo with abx for pts with any of the following: Scr >1 mg/dL, BUN >30 mg/dL, Total bilirubin >4 mg/dL (>1, >30, >4)

-Dose: 1.5 g albumin/kg body weight within 6 hr of detection and 1g/kg on day 3

Secondary prevention of SBP

-Hx of SBP AND low-protein ascites PLUS (one): SCr 1.2 mg/dL or greater, BUN 25 mg/dL or greater, Serum sodium 130 mg/dL or less, child-pugh score of at least 9

-ciprofloxacin 500 mg daily OR bactrim DS 800 mg/160 mg daily

lactulose, rifaximin

what drugs are used to treat hepatic encephalopathy?

lactulose

-first line pharm treatment for initial management and secondary prevention

-decreases ammonia levels

-initial episode: 16.7 g every 1-2 hr

-Prevention: 20-30 g 3-4x daily

Rifaximin

-effective add-on therapy to lactulose for secondary prevention and even after a secondary episode of HE has occurred

-mech: reduces the ammonia forming bacteria in the intestinal tract

-Prevention: 550 mg BID

-Tx: 400 mg TID x5-10 days

Hepatorenal Syndrome - Management

-discontinuing diuretics or additional meds that can decrease blood volume

-expand intravascular volume with IV albumin (1g/kg up to a max dose of 100g)

midodrine + octreotide + IV albumin

what is the treatment used to bridge patients with hepatorenal syndrome until liver transplant?

HAV - Tx

-no specific treatment options exist for HAV infections

-general supportive care

-prevention of transmission by practicing good hand hygiene

-active immunity through vaxx

-passive immunity through pre- and post-exposure prophylaxis

-avoid hepatotoxic drugs

hepatotoxic drugs

-acetaminophen

-isoniazid

-ketoconazole

-methotrexate

-nefazodone

-nevirapine

-NRTIs

-Propylthiouracil

-Tipranavir

-Valproic Acid

HAV - Vaccination

-all children at 1 year of age

-persons traveling to or working in an area of intermediate or high endemicity

-homosexual males

-users of injection and non-injection drugs

-persons with an occupational risk

-persons with chronic liver disease

-persons with clotting-factor disorders

-persons with direct-contact with others who have Hep A

HAV Pre-exposure prophylaxis (PrEP)

-immune globulin, GamaSTAN S/D

-mostly replaced by Hep A vaccination

-IG for pre-exposure may be used in children <6 months that need protection and international travelers unable to receive the vaccination

HAV Post-exposure Prophylaxis (PEP)

-IG

-persons exposed to hep A and who have not been vaccinated should receive one dose single-antigen of hep A vaccine or IG as soon as possible, within 2 weeks after exposure

yes

can IG be given concomitantly with the HAV vaccine?

3 months

if Ig is admin first, wait at least _____________ to admin live vaccines

2 weeks

if a live vaccine (MMR or varicella) admin first, wait at least __________ to admin IG

HBV - vaccination

-all infants

-unvaccinated children <19 years of age

-people at risk for infection by sexual exposure

-people at risk for infection by exposure to blood

-traveler to countries with intermediate or high levels of endemic HBV

-people with HCV infection

-people with chronic liver dz

-people with HIV

-people who are incarcerated

-others seeking protection against HBV

Single-antigen HBV Vaccine

-ENGERIX-B

-RECOMBIVAX - HB

-HEPLISAV-B

Combo HBV Vaxx

-PEDIARIX

-TWINRIX

-VAXELIS

HBV PEP

-give in combo with Hep B vaccine for patients exposed to HbsAg positive source

-admin within 24 hr of exposure if possible

-within 12 hr of birth for perinatal transmission in combo with Hep B vaccine

-Hep B IG is NOT indicated for the tx of active hep B infection and is ineffective for chronic dz

general supportive care

what is the treatment for acute HBV?

Chronic HBV - Tx

-nucleoside/tide reverse transcriptase inhibitors --> entecavir, tenofovir

-peginterferon

HBV - Tx Goals

-decrease morbidity and mortality related to chronic HBV

-achieve immunological cure (sustained HBV DNA suppression)

NRTIs - HBV

-MOA: inhibit HBV replication by inhibiting HBV polymerase resulting in DNA chain termination

-approved as monotherapy for HBV

-prior to initiating HBV therapy, all patients should be tested for HIV

NRTIs - Boxed Warnings

-lactic acidosis and severe hepatomegaly with steatosis

-exacerbations of HBV can occur upon d/c; monitor closely

-HIV resistance in HBV patients with unrecognized/untreated HIV infection

HBV DNA, kidney, and liver functon

what should you monitor during oral antiviral therapy for HBV?

Preferred oral antiviral agents - HBV

-entecavir

-tenofovir disoproxil fumarate

-tenofovir alafenamide

ETV or TAF over TDF - indications

-Age >60 years

-Bone disease

-Renal alteration: CrCl <60 mL/min

TAF

what antiviral agent is preferred if the patient has prior exposure to NRTI therapy?

Peginterferon

-subcutaneous admin

-pegylated form has polyethylene glycol added; prolong the half-life and allows for once weekly dosing

-antiviral, antiproliferative, and immunomodulator

Peginterferon - Boxed Warnings

-can cause or exacerbate neuropsychiatric, autoimmune, ischemic, or infectious disorders

Peginterferon - SE

-CNS effects (fatigue, depression, anxiety, weakness), GI upset, increased LFTs, myelosuppression, flu-like syndrome (fever, chills, HA, malaise)

HCV - Treatment Initiation

-treatment is recommended for all patients with chronic HCV

-expectations: patients with short-life expectancy that cannot be remediated by HCV therapy, liver transplant, or another directed therapy

HCV - Tx Goal

-reduce all-cause mortality and liver-related health adverse consequences, including end-stage liver dz and hepatocellular carcinoma, by the achievement of virologic cure as evidence by a sustained virologic response

HCV - Prior to Initiating Tx

-eval for advanced fibrosis using liver bx, iomaging, and/or noninvasive markers

-assessment of potential drug-drug interactions

-lab tests within 12 wks prior to therapy

-HCV genotype and subtype

-HCV viral load

-HBV co-testing

-HIV assessment

Ribavirin

-inhibits replication of DNA and RNA viruses

-Indicated for HCV in combo with other agents

-monitor CBC w/ diff, PLTs, electrolytes, uric acid, LFTs, HCV-RNA, RSH, monthly pregnancy test

Ribavirin - BBOX

-significant teratogenic effects

-hemolytic anemia

-not effective for monotherapy of HCV

Ribavirin - CI

-pregnancy

-male partners of pregnant women

-CrCl <50 mL/min

Ribavirin - SE

-hemolytic anemia

-fatigue

-HA

-insomnia

-N/V/D

-anorexia

-myalgias

-hyperuricemia

during; 6 months

with ribavirin use, avoid pregnancy in females and female partners of male patients _________ therapy and _________ after completion

HCV - Preferred Regimen

2-3 direct acting antivirals with different mechanisms of action

Glecaprevir

-NS3/4 Protease Inhibitor

-HCV treatment

Pibrentasvir, Velpatasvir

-NS5A replication complex inhibitor

-HCV treatment

Sofosbuvir

-NS5B polymerase inhibitor

-HCV treatment

-serious symptomatic bradycardia when combined with amiodarone so don't combine

Direct-Acting Antivirals - HCV tx

-risk of reactivating HBV

-SE: well-tolerated, HA, fatigue, diarrhea, nausea

-Monitor LFTs, HCV-RNA

-DI: strong CYP3A4 inducers, increase concentration of statins

HCV - Tx Monitoring

-Clinic/telephone visits: adherence, adverse effects, DI

-Labs after 4 weeks and as indicated: HCV RNA, CBC, SCr and CrCl, Hepatic function panel

-Labs after 12 weeks: HCV RNA

no

is there a vaccine for HCV?

HCV - Simplified Tx Regimens

-Glecaprevir 100 mg/Pibrentasvir 40 mg 3 tabs orally daily with food x 8 weeks

-sofosbuvir 400 mg/velpatasvir 100 mg 1 tab orally daily with or w/o food x 12 weeks

-repeat HCV RNA and LFTs 12 weeks after completing therapy to assess cure and resolution of hepatic inflammation

Simplified Tx Regimens - Candidates

-HCV treatment naive

-AND no cirrhosis, no active HBV infxn, not pregnant, no history or suspicion of HCC, no hx of liver transplant