Liver 2 Flashcards
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
Hepatitis A Virus is what?
RNA Virus
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
Vaccines HEp A
Havrix®, Avaxim®, Vaqta®, Twinrix (Hep A and B)
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
Hep A complications
fulminant hepatitis is rare; you recover and are cured when you recover
Is Hep A chronic?
NO
Tx Hep A
supportive:
healthy diet, rest, maintaining fluid balance, avoiding hepatotoxic drugs and ETOH
no clear role for pharmacologic therapy
Prvention of Hep A Pharmacist ROle
vaccine for high-risk individuals (2 doses, 6 months apart)
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
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
Hep B Virus is what type?
DNA Virus
Heb B Transmission
Perinatal, sexual, blood (IVDU)
- Sexual contact highest, highes risk of needle transmission out of HEB C or HIV
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
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
Chronic Hep B Stats
90% in neonatal infection
25-50% children aged 1-5
10% in adults
Complications Hep B
fulminant hepatitis (0.1-1%), cirrhosis (20-25%), hepatic carcinoma (5%)
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)
Screening Hep B
Universal screening at least once for >18
Hep B Tx Recommeded when
Treatment is recommended if
In general, treat during immune active HBV (increased HBV-DNA & ALT; liver inflammation
Tx for Hep B
interferon
Peginterferon alfa-2a
OR
nucleoside analogues
lamivudine
Tenofovir (TDF, TAF),
entecavir
Adefovir
Tx of Hep B Goals
permanent suppression/elimination of the virus
prevent cirrhosis, liver failure and hepatocellular carcinoma
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
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
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
