Liver 2 Flashcards by Tony Ward

what are the various presentations of hepatitis?

Asymptomatic (infection without disease)
AST & ALT elevated (GGT elevated as well; but elevated when sick, Tylenol usage, etc.)

Acute Hepatitis:
flu-like symptoms, abdominal pain, jaundice, scleral icterus, pale stools, dark urine
Usually will have sx

Acute Fulminant (overwhelm the liver) Hepatitis:
Rare, but may be fatal

Chronic Persistent Hepatitis:
delayed recovery with minimal liver damage but failure to develop antibody (carrier state)

Chronic Active Hepatitis:
progressive liver damage, failure to develop antibody, may be asymptomatic

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Hepatitis A Virus is what?

RNA Virus

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Transmission of Hep A

fecal-oral
more likely to occur in travel to countries with high rates, poor conditions & hygiene, overcrowding; contaminated food or water

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Vaccines HEp A

Havrix®, Avaxim®, Vaqta®, Twinrix (Hep A and B)

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Hep A Sx

> 70% of patients are symptomatic with fever, jaundice, and scleral icterus. Hepatomegaly is evident on physical exam.

Less common signs include splenomegaly, skin rash, arthralgia

The time from exposure to clinical manifestations is approximately 30 days (range 15–50)

Symptoms usually last ~3 months

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Hep A complications

fulminant hepatitis is rare; you recover and are cured when you recover

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Is Hep A chronic?

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Tx Hep A

supportive:
healthy diet, rest, maintaining fluid balance, avoiding hepatotoxic drugs and ETOH
no clear role for pharmacologic therapy

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Prvention of Hep A Pharmacist ROle

vaccine for high-risk individuals (2 doses, 6 months apart)

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Post-exposure prophylaxis Hep A

Hepatitis A vaccine given within 14 days of exposure
Immunglobulin (Ig) given ASAP if vaccine unavailable, contraindicated or patient is <1 – passive immunity; not long term

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Hep A serological Markers

Total anti-HAV (total antibody to HAV) represents total immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to HAV

+ total anti-HAV may indicate acute, resolved infection or immunity

+ anti-HAV IgG represents immunity from either vaccination or previous exposure. It is detectable for life and confers lifelong protection

+ anti-HAV IgM indicates acute HAV infection

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Hep B Virus is what type?

DNA Virus

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Heb B Transmission

Perinatal, sexual, blood (IVDU)

Sexual contact highest, highes risk of needle transmission out of HEB C or HIV

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Vaccine Hep B

Engerix-B®, Recombivax HB®, {Twinrix® (A&B)}

SK currently immunizes gr 6 students, high risk individuals, healthcare workers free of charge for Hep B (3 doses)

Antibody response in general decreases with age

Revaccinating with a single booster dose, a complete series or using a vaccine formulation with higher concentration may be needed in hyporesponders

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Sx Hep B

Approximately 70% of patients are anicteric (jaundice not available) or subclinical.

Younger patients most likely to be asymptomatic

If symptoms occur, jaundice, dark urine, white stool, abdominal pain, fatigue, fever, chills, loss of appetite, and pruritus possible

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Chronic Hep B Stats

90% in neonatal infection
25-50% children aged 1-5
10% in adults

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Complications Hep B

fulminant hepatitis (0.1-1%), cirrhosis (20-25%), hepatic carcinoma (5%)

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Hep B serological Markers

HBsAg (HBV surface antigen): + indicates HBV infection, acute or chronic – marker of byremia (first test done)

Anti-HBs (antibody to HBV surface antigen): marker of HBV immunity; in cases where both HBsAg and anti-HBs are present, HBV infection persists

HBV-DNA: a marker of viral replication/infectivity detectable at the start of acute infection and used to assess and monitor the treatment of chronic HBV infection (look at if someone is on tx an indicates if virus is replicating)

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Screening Hep B

Universal screening at least once for >18

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Hep B Tx Recommeded when

Treatment is recommended if

In general, treat during immune active HBV (increased HBV-DNA & ALT; liver inflammation

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Tx for Hep B

interferon
Peginterferon alfa-2a

OR
nucleoside analogues

lamivudine
Tenofovir (TDF, TAF),
entecavir
Adefovir

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Tx of Hep B Goals

permanent suppression/elimination of the virus
prevent cirrhosis, liver failure and hepatocellular carcinoma

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Goalof Hep B tx? Definition?

Permanent suppression’ is the goal because elimination is not always possible. Defined as an undetectable HBV DNA level and a normalization of liver enzymes

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What is a functional cure of hep b? Common?

defined as HBsAg loss with or without appearance of antibodies to HBsAg (anti-HBs), is the most desirable goal; but rare and not the specific goal of most treatments

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Interferons MOA, Course, and USE

Cytokines with direct antiviral and immunomodulatory properties

16-48wk course, 30% successful in developing immunity

Mainly used in patients with lower HBV DNA levels and elevated serum aminotransferase values

Advanatges of inteferons

Shorter course of therapy
- Absence of resistance
- A chance at full seroconversion

Disadvatages of interferons

Contraindicated in decompensated cirrhosis

Increased risk of life-threatening infections and possible worsening of hepatic decompensation

Subcutaneous injection

Many side effects!
Influenza-like illness, emotional lability, myleosuppressive effects, hyper/hypothyroidism

Nucleoside Analogue Efficacy

> 90% response, 10-15% success in developing immunity (40-50% seroconversion in 5 years, varies with agent)

Advatage nucleoside analogue

Safer
fewer side-effects
Po

Diasdvantage nucleoside analogues

chronic therapy –
endpoint is seroconversion + 12 months(durability 75%)
This can take years and some may require treatment indefinitely
drug resistance

adjust in renal dysfunction

Nucleoside analogues HEP B

Lamivudune
Adefovir
Tenofovir (TDF and TAf)
Enetcavir

Lamivudune MOA, Tolerability, Main Use Now

Pyrimidine nucleoside analogue inhibitor of HBV

Well tolerated and effective, but high resistance rates

Resistance may promote cross resistance with others therefore no longer DOC

Main use now:
Prophylaxis for those on immunosuppression

Adefovir MOA, USe, S/e

Nucleotide analogue

Less potent & does not achieve viral suppression in most in the first year (likely from low approved daily dose)

Useful add on in lamivudine resistance

Side effects: nephrotoxicity, hypophosphatemia

Tenofovir Examples, What are they? zDifefrrences?

Tenofovir disoproxil fumarate (VIREAD™)(TDF)
Tenofovir alafenamide (VEMLIDY™) (TAF)

Both prodrugs of tenofovir diphosphate

TAF produces higher levels of tenofovir diphosphate in cells than TDF and can be administered in lower dose

Tenofovir MOA.Use and benefit?

Purine nucleotide reverse transcriptase inhibitor

Licensed for HIV and potent HBV activity

DOC in lamivudine resistant and HIV/HBV coinfection with HAART

Most potent with low chance of resistance

Entecavir MOA

Selective guanosine analogue and potent inhibitor of HBV DNA replication

More effective than lamivudine but should not be used to rescue in lamivudine resistance (as may confer resistance)

Combo Tx Hep B

People with cirrhosis who have resistance may have a flare, which could be fatal
Generally an add on approach
Examples: Lamivudine + tenofovir; tenofovir + entecavir

Hep C virus is what?

Single-stranded RNA virus

Trasnmisison Hep C

perinatal, sexual, blood
Parenteral most effective
Efficiency of transmission by sexual transmission is very low
No data to suggest household transmission occurs

Hep C Vaccine

None

Sx Hep C

Approximately 70% of patients are asymptomatic. If symptoms occur, jaundice, dark urine, white stool, abdominal pain, fatigue, fever, chills, loss of appetite, and pruritus are possible.

Complications Hep C.Clinical presentation?

chronic disease (75%; 25% spontaneously resolve), cirrhosis, hepatocellular cancer 5%,

first clinical presentation may be as late as 20-30y post exposure (accelerated in HIV/HCV coinfection 10-15y)

Serological MArkers Hep-C

Anti-HCV (antibody to HCV): indicates infection, either acute or chronic.
It may be negative during the first 6 weeks after exposure.
Needs additional HCVRNA to confirm an acute infection.
This test will remain positive for life despite clearance of infection.

HCV RNA by PCR (HCV RNA by polymerase chain reaction): indicates virus replication activity; it appears at the start of an acute infection and level may fluctuate.
Its presence indicates ongoing viremia whereas a negative result indicates no active infection.

High-risk individuals should be screened annually with an anti-HCV; if previously successfully treated or spontaneously cleared the infection, HCV RNA should be performed

TX Hep C Goal

Traditionally Primary objective was complete elimination of virus defined as undetectable HCV RNA (termed sustained virological response or SVR) at least 24-48 weeks post treatment
Now, with newer drugs this may be possible after 12 weeks (SVR 12 & SVR 24 – SVR 12 is the standard)

Traditionally treatment has been guided by genotype and virological response

Tx of Chronic Hep C

Interferon AND Ribavirin in combo

Ribavarin MOA, DOse

Nucleoside analogue

Oral = Dosed bid

Ribvarin S/e.mRisk?

Side effects: hemolytic anemia, rash, depression, fatigue, insomnia

Potential teratogen
Male & female
Contraception x 6 months post completion

Ribavrin Activity:

Activity against a # of DNA, RNA, influenza, flavaviruses & viral hemmorhagic fevers

IFN Based Tx S/E

Harvoni Hpe C Tx Drugs, S/e

Harvoni® = LEDIPASVIR & SOFOSBUVIR (for g1,4,5,6)

S/e : mild to moderate in severity, fatigue, headache, insomnia, nausea;
Decreased absorption if administered with acid-suppressing drugs; watch co-administration with proton pump inhibitors

Zepatier Drugs, Use,Avoid in, Monitor

Zepatier® = GRAZOPREVIR + ELBASAVIR (g1,4)

Studies targeting patients that are difficult to treat, or have lack of data in literature(PWID, Renal) have been done

Need to add sofosbuvir for g3 patients

Transient increase in ALT around week 8, needs monitoring

Avoid in decompensated cirrhosis

Epclusa Drugs, USe

Epclusa® = SOFOSBUVIR + VELPATASVIR (pan-genotypic, some exceptions with g3)
99-100% cure rates (SVR)
May be a possibility to no longer need to genotype, except g3
If cirrhotic, g3 may require ribavirin (resistance testing Y93H)
Watch acid suppressing drugs*

Mavriet Genotypesand used in who?

Maviret ® = GLECAPREVIR + PIBRENTASVIR (all genotypes 1,2,3,4,5,6)
May be used in severe kidney failure (even dialysis); also in patients who receive a Hep C kidney transplant
Take with food

Vosevi Drugs

Vosevi ® = SOFOSBUVIR + VELPATASVIR + VOXILAPREVIR (all genotypes 1,2,3,4,5,6)
Role: Treatment failures
Take with food
Avoid in decompensated cirrhosis

Most COmmonly Used Now

Epclusa and Maviret most commonly used now (genotype not needed)

Tx Regimen Length Hep C tx

Treatment is usually 8-12 weeks (8 weeks for uncomplicated)

Population Testing

Population-based screening
Those born between 1945 – 75 (5x baseline risk)
(But new CDC recommendations suggest everyone over 18 at least once & during each pregnancy)

Risk-Based SCreening

Persons who inject drugs (PWID) or history of ever using injection drugs
Prior incarceration
Remote blood transfusion
Immigrants from endemic countries

Screening Test for HEP-C

Screening requires the following tests:
Hepatitis C antibody
If above positive, Hepatitis C antigen
If above is positive, Hepatitis C RNA PCR (HCV RNA)

Hep D Virus

RNA virus, occurs simultaneously with HBV
Transmission
perinatal, sexual, blood

Vaccine
Hepatitis B vaccine protects against

Sequelae
chronic disease, hepatic carcinoma, cirrhosis

Treatment
PEG INF at standard dosing x minimum of 12 months

Hep E Virus

RNA virus

Transmission:
fecal-oral

Vaccine:
no

Sequelae:
high mortality for pregnant women, otherwise patients fare very well

Lifestyle Hep C

Alcohol: abstain.
Use acetaminophen (< 2000mg/day) for pain. Avoid NSAIDs when possible.
Two forms of contraception are required while on RBV & for 6 mos after tx

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Liver 2 Flashcards

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