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ID exam 3 > viral hepatitis > Flashcards

viral hepatitis Flashcards

1
Q

hepatitis

A

inflammation of the liver

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2
Q

viral hepatits

A

hepatitis caused by one of at least five distinct viruses

  • Hepatitis A virus (HAV)
  • Hepatitis B virus (HBV)
  • Hepatitis C virus (HCV)
  • Hepatitis delta virus (HDV) - requires HBV coinfection
  • HEV
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3
Q

characteristics of viral hepatitus

A

hepatotrophic - systemic infections that primarily affect the liver
RNA viruses - except HBV (which is DNA)
all can produce an acute illness with nausea, anorexia, fever, malaise and abd pain; and jaundice or elevated liver transaminases (sxs range from asymptomatic to fatal)
HBV and HCV can produce a chronic infection (ranges from subclinical to cirrhosis)

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4
Q

difference in hepatitides A B and C

A 
A - 
-source of virus: feces
-route: fecal oral
-couse: actue, then resolves
B - 
-course: acute, then sometimes resovles
C - 
-course: acute, then usually chronic
-protective immunity: no
-vaccine available: no
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5
Q

virology and pathogensis of HAV

A

classified as a picornavirus
replicated in the liver, excreted in the bile and is shed in the stool
average incubation period of 28 days

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6
Q

transmission of HAV

A

person to person through fecal-oral
-ingestion of something contaminated with feces of an infected person
-most infections occur from close personal contact with a household member or sex partner
exposure to fecally contaminated food or water
-uncooked/undercooked HAV-contaminated food or water - virus killed by heating to 185 for 1 minute
-food contaminated by food handlers after cooking
-waterbourne outbreaks uncommon in developed countries
risk groups:
-travelers to areas with high or intermediate HAV infection
-MSM
-illegal drug use
-clotting factor disorder
-work with non-human primates susceptible to HAV infection

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7
Q

HAV sxs

A

can be asymptomatic
-usually in children under 6 and when sxs do occur, usually no jaundice
-in older children and adults, usually sxs and usually jaundice
abrput onset: fever, fatigue, loss of appetite, NV, abd pain, dark urine, clay colored stool, joint pain, jaundice
sxs usually last 2 months
rarely fatal

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8
Q

HAV diagnosis

A

serologic testing for IgM anit-HAV

IgG anti-HAV appears early in the infection, remains detectable providing lifelong immunity

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9
Q

HAV management

A

supportive care

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10
Q

HAV prevention

A

vaccination
who should be vaccinated? children at age 1, children and adolescents 2-18 who live in an area of high incidence of HAV, people traveling or working in areas with high-intermediate rates of HAV, MSM, users of illegal drugs, people w chronic liver disease, clotting factor disorders
vaccination is safe in pregnancy, 2 dose series
prevaccination serologic screening for immunity is typically not recommended except in certain patient
postvaccination serologic testing is generally not recommended due to high immunogenicity
routine vaccination is NOT needed for: food service, sewage, health care, children under 12, child care attendees

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11
Q

postexposure HAV prophylaxis

A

administer single-agent vaccine or immune globulin ASAP, within 2 weeks

  • vaccine preferred for healthy people aged 1-40
  • immune globulin preferred for over 40 and under 1
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12
Q

HBV virology and pathogenesis

A

hepaDNAVIRUS
the virus enters the liver through the bloodstream, replicates in the liver
average incubation period is 90 days to onset of jaundice and 60 days to onset of abnormal ALT levels

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13
Q

HBV transmission

A

spread through percutaneous (skin puncture) or mucosal conact with blood or body fluids (sexual contact, inj drug use, mother-to-child, contact with blood, needle sticks, sharing razors or toothbrushers) - CANNOT be transmitted including food, water, eating utensils, breastfeeding, kissing, coughing, sneezing
risk: infants born to infected mothers, sex with infected individuals, people w multiple partners, MSM, inj drug users, household contact, healthcare workers at risk of exposure, hemodialysis, residents and staff of developmentally disabled, travelers to countries with high or intermediate prevalence of HBV infection

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14
Q

HBV sxs

A

acute sxs are same as HAV infection
fatality rate higher than HAV (0.5-1.5%)
chronic infection is typically asympomatic until onset of cirrhosis, end-stage liver disease or hepatocellular carcinoma (HCC)
3000 deaths each year
15-25% of people with chronic HBV are at risk for premature death from cirrhosis and HCC

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15
Q

HBsAg

A

hepatitis B surface antigen
marker of presence of ongoing infection
is the patient infectious?

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16
Q

anti-HBs

A

antibody to hep B surface antigen
marker of immunity (disease or vaccination)
is the patient immune?

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17
Q

HBcAg

A

Hep B core antigen

ass not available commercially because no free HBcAg circulates in the blood

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18
Q

total anti-HBc

A

antibody to hepatitis B core antigen
marker of exposure to the infection
has the patient been exposed to the antigen, ever?

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19
Q

IgM anti-HBc

A 
immunoglobulin M class of antibody to hepatitis B core antigen
marker of acute or recently acquired HBV infection (can give false positives)
Has the patient been recently (within the past 6 months) exposed to the virus?
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20
Q

HBeAg

A

Hepatits B e antigen
marker of high infectivity in acute or chronic HBV infection (corresponds to viral replication and high viral levels)
is the virus actively replicating?

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21
Q

anti-HBe

A

antibody to hepatitis B e antigen
marker of loss of viral replication and lower levels of virus
has the virus recently stopped replicating?

22
Q

management of acute HBV infection

A

no treatment - supportive care

23
Q

goals of management of chronic HBV infection

A

achieve sustained suppression of HBV replication
remission of liver disease
prevent cirrhosis, hepatic failure and HCC
immunological cure is attainable, virological cure is not yet attainable

24
Q

initial evalution of HBV

A

hx and PE (elicit risk factors)
CBC, liver panel, INR, HBeAg, anti-HBe, HBV DNA PCR assay
test for coinfection for HCV, HDV, HIV and anti-HAV
alfa-fetoprotein (AFP), abd ultrasound and fibrosis staging from elastography or fibrosis panel to assess severity of fibrosis/cirrhosis

25
Q

clincal phases of chronic HBV

A

not a linear progression
e+ immune-tolerant: normal ALT, elevated HBV DNA (++++)
e- inactive (carrier): normal ALT, low/undetectable HBV DNA(+/-)
e+ immune-active: elevated ALT, elevated HBV DNA (+++)
e- immune reactivation: elevated ALT, elevated HBV DNA (+++)
e+ cirrhosis: elevated ALT, elevated HBV DNA (++), low albumin, low platelets
e- cirrhosis: elevated ALT, elevated HBV DNA (++), low albumin, low platelets

26
Q

fundamental principles of treatment of HBV

A

HBV DNA over 2000 IU/mL** is assocaited with increased risk of cirrhosis and HCC, and forms the clinical threshold for most treatment
the ALT upper limit of normal (ULN) is 30 U/L for males** and 19 IU/L for females**, regardless of reference laboratory ranges
treatment foes not eradicate HBV
combination therapy has not shown higher response rates than monotherapy
optimal duration of therapy is not known and has limited long-term efficacy
-patients with e- immune reactivation and all patients with cirrhosis should receive indefinite therapy
-for e+ patients, treatment should be continued for at least 12 months after loss of BHeAg and gain of anti-HBe OR until HBsAg loss

27
Q

who to treat for HBV

A

e+ immune tolerant: MONITOR
e- inactive (carrier): MONITOR
e+ immune-active: TREAT if ALT > 2x ULN, HBV DNA > 20,000* IU/mL, otherwise MONITOR
e- immune reactivation: TREAT INDEFINITELY if ALT > 2xULN, HBV DNA > 2,000 IU/mL, otherwise MONITOR
e+ cirrhosis: TREAT INDEFINITELY if HBV DNA > 2000 IU/mL, otherwise MONITOR
e- cirrhosis: TREAT INDEFINITELY if HBV DNA > 2,000 IU/mL, otherwise MONITOR
“2/3 ain’t bad” - HBV > 2,000, ALT > 2xULN, cirrhosis

28
Q

first line agents for HBV

A

peginterferon alfa 2a 180 mcg SQ qweek for 48 weeks - “sustained response”
-cytokine with antiviral, antiproliferative and immunomodulatory effects
-overall response is poor: 8-14% of e+ and 19% of e- patients maintain suppressed HBV DNA 6 mo after completion of 48 weeks of therapy
-11% of e+ and 6% of e- maintained HBsAg loss at 3 years post-therapy
-if a response is obtained, it is usually long lasting (over 4-8 weeks)
-an expected increae in ALT can occur 4-8 weeks into treatment
-contraindicated in patients with a hx of current psychosis, severe depression, neutropenia, thrombocytopenia, symptomatic heart disease, decompensated liver disease and uncontrolled seizures; use caution in autoimmune disorders
tenofovir disoproxil fumarate (TDF) 300 mg PO daily - maintained response (use indefinitely)
-76% of e+ and 93% of e- maintain suppressed HBV DNA levels after 2-3 years of therapy
-maintenance of HBsAg loss: e+ 8% after 3 years; e- 0% after 1 year
-potential aLT flares on withdrawal
-new prodrug tenofovir alafenamide (TAF) 25 mg PO daily has improved safety (less renal impairment, less bone mineral density changes); not yet in guidelines
entecavir 0.5 mg PO daily in nucleoside-naive patients; 1 mg PO daily in nucleoside-experienced patients
-61% of e+ and 90% of e- maintain suppressed HBV DNA levels after 2-3 years of therapy
-maintenance of HBsAg loss: e+ 4-5% after 2 years; e- 0-1% after 1 year
-potential ALT flares on withdrawal

29
Q

other agents for HBV treatment

A

nucleoside analogs - not first-line d/t high rates of resistance - Iamivudine, adefovir, telbivudine 600 mg PO daily
interferon alfa-2b - not first line d/t more frequent dosing - interferon alfa 5 million units/day or 10 million units 3/week; studied duraion is 16-24 weeks for HBeAg+; 12 months for HBeAg-

30
Q

Peg-IFN-2a for HBV

A

dose: 180 mcg SQ weekly for 48 weeks, renally adjust, preg category C, SE: flu-like symptoms, fatigue, mood disturbances, psychosis, anxiety, cytopenias, autoimmune disorders, anorexia, thyroid dysfunction, neuropathy, insomnia, alopecia; monitoring: CBC, TSH, clinical monitoring for autoimmune, ishemic, neuropsychiatric and infectious complications

31
Q

entecavir for HBV

A

0.5 mg daily (naive), 1 mg PO daily (experienced or decompensated cirrhosis), renally adjust, preg categroy C, SE: lactic acidosis, monitoring: lactic acid levels if clinical concern

32
Q

tenofovir disoproxil fumarate for HBV

A

300 mg PO daily, renally adjust, preg B, SE: neuropathy, faconi syndrome, osteomalacia, lactic acidosis; monitor: CrCL at baseline; if risk for renal impairment, CrCl, serum posphate, urine glucose and protein at least annually; consider bone density study at baseline and during treatment in persons w hx of fracture or risks for osteopenia; lactic acidosis if clinical concern

33
Q

monitoring for HBV

A

for immune tolerant patients, monitor ALT q3-6 months, eAg q6-12 months
for e- inactive patients, monitor ALT q6-12 months
for patients on therapy, HBV DNA levels should be monitored q3mo on NA therapy until undetectable (suppression should be attained within 96 weeks); then q3-6 mo thereafter
resistance can develop to the nucleotide analogs (resistance rates after 5 years: Iamivudine 65%, adefovir 20%, entecavir 1.2%, tenofovir 0%)
once therapy is stopped, monitor patients every 3 mo for at least one year for recurrent viremia, ALT flares, seroreversion and decompensation
all HBsAg+ patients should receive HCC surveillance every 6 mo (AFP + abd ultrasound), even if on treatment

34
Q

treating HBV in special populations

A

renal insufficiency - adjust dose of nucleotide analog
pregnancy - to minimize risk of perinatal transmission, beginning at week 28-32 of gestation, treat pregnant women with HBV DNA > 200,000 with tenofovir DF; infants should receive HBV vaccination +/- immunoglobulin
HIV coinfection - some nucleoside analogs used for HBV also have antiretroviral activity against HIV, fully suppressive 3-drug therapy should be initiated against HIV when treatment for HBV is warranted to decrease risk of resistance, emtricitabine/tenofovir combo frequently used

35
Q

HBV prevention

A

vaccine (1982) has drasticallty reduced incidence of infection, essentially everyone should be vaccinated
all HBV vaccines are inactive - safe in pregnancy
vaccination - most often 3 inj, administed at 0, 1 and 6 mo; if series interrupted, no need to restart; postvaccination testing for immunity is recommended for: infants bron for HBsAg+ mothers, health care workers at risk for occupational exposure, immunocompromised patients, sex partners of people with chronic HBV infection

36
Q

HCV virology and pathogensis

A

flavivirus
differentiated into 6 major genotypes and furhter into subtypes - 1a and 1b are most common in US
average time from exposure to symptom onset is 4-12 weeks
spontaneously cleared by 15-25% of patients

37
Q

HCV transmission

A

spread through large or repeated percutaneous exposures to infected blood
risk: inj drug users, recipients of clotting factor prior to 1987, recipients of blood or SOT prior to 1992, hemodialysis, healthcare workers at risk, HIV infected, children born to HCV+ mothers
can also be spread infrequently through : sex with HCV+ partner (particulary MSM), sharing razors or toothbrushes

38
Q

HCV sxs

A

acute infection - most asymptomatic, but 1/3 of patients report symptoms similar to HAV and HBV acute infection
chronic infection - defined as persistently detectable HCV RNA for 6+ months
-most patients have few, if any, sxs: persistent fatigue is most common, RUQ pain, nausea, poor appetite, hepatomegaly on PE, other extrahepatic sxs can occur
likelihood of complications/100people infected with HCV
-75-85 will develop chronic infection
-60-70 will develop chronic liver disease
-5-20 will develop cirrhosis over 20-30 years
-1-5 will die from cirrhosis or HCC

39
Q

diagnosis of HCV

A

anti-HCV is detectable 4-10 weeks after infection - not used diagnostically for acute HCV because a third of infected patients test negative at onset of sxs
HCV RNA is detectable 2-3 weeks after infection
diagnosis of HCV is many times incidental after having persistently elevated LFTs
CDC recommends one-time screening of all persons born 1945-1965 (regardless of risk) and one-time screening of anyone in a risk group

40
Q

management of HCV

A

this is an area of rapidly changing pharmacotherapy
goals of therapy: obtain virological cure by achieving a sustained virological response (SVR) - HCV RNA undetectable 12 weeks after cessation of treatment; prevent complications and death

41
Q

fundamental principles of HCV management

A

therapy with SQ INF plus oral ribavirin has now been replaced by all-oral regimens which have a 95% likelihood of acheiving an SVR, combination therapy of direct acting antivirals (DAAs) prevents emergence of drug resistance, treatment is recommended for all persons with chronic HCV, except those with short life expectancies, initiation of DAAs is almost exclusively done in the outpatient setting, access to treatment due to high cost of these agents remains a significant hurdle, all DAAs carry a warning of risk if HBV reactivation
DAAs ALL VERY EXPENSIVE

42
Q

NS3/4A protease inhibitors for HCV

A

“-previr”
inhibit the viral NS3/4A serine protease which cleaves the HCV-RNA-encoded polyprotein into its functional units, thus preventing RNA replication
all NS3/4A protease inhibitors are potent CYP3A4 and thus are associated with mutliple clinically-significant drug interactions
agents in this class have low barrier to resistance
there are 5 FDA-approved agents in this class:
-boceprevir: discontinued
-telaprevir: d/c’ed
-simeprevir: 150 mg QD WF; AE: rash, pruritus, nausea; presence of NS3 Q89K polymorphism* at baseline is assocated with poorer outcomes in some regimens; hepatically cleared - avoid in child-pugh B or C
-peritaprevir: 150 mg PO QD WF, available only in coformulated tablets; requires ritonavir-boosting for once daily administration; AEs: fatigue, nausea, pruritis, skin reactions, insomnia; contraindicated in child-pugh B or C based on case reports of liver decompensation/failure or death
-grazoprevir: 100 mg PO QD w/wo food; available only coformulated; AEs: fatigue, HA, nausea, anemia, ALT elevations, patients should have ALT checked at 8 weeks, d/c if >5xULN, contraindicated in child-pugh B or C

43
Q

NS5B polmerase inhibitors for HCV

A

“-buvir”
inhibit the RNA NS5B polymerase responsible for replication of HCV
work by 2 different MOA: the nucleotide analog competes for the enzyme active site, whereas the nucleoside agent binds to an allosteric site inhibiting polymerase activity
high conversion of the NS5B polymerase active site across genotypes allows for pangenotypic coverage of the nucleotide analog with a high barrier to resistance - this is in contrast to the nonnucleoside agent which is more subtype specific and has a low barrier to resistance
there are 2 FDA-approved agents:
-sofosbuvir: 400 mg PO QD; AE: fatigue, headache; avoid amoidarone coadministration d/t risk of symptomatic bradycardia; no dose adjustment needed in hepatic impairment
-dasabuvir 250 mg PO BID; available only in coformulated tablets; requires ritonavir-boosting for once daily administration; AEs: fatigue, nausea, pruritis, skin reactions, insomnia; contraindicated in child-pugh B or C based on case reports of liver decompensation/failure or death

44
Q

NS5A replication comlex inhibitors for HCV

A

“-asvir”
inhibit the protein NS5A, needed for HCV RNA replication and assembly
these DAAs have a low barrier to resistance, but are very potent
there are 5 FDA approved agents in this class
-Iedipasvir 90 mg PO QD; available only in coformulation; AEs: fatigue, HA; Iedipasvir solubility decreases as pH increases, so spacing apart acid reducing agents is necessary; an abbreviated 8-week treatment course can be considered in naive patients with genotpye 1 without cirrhosis who have a pretreatment HCV RNA <6 million IU/mL; no dosage adjustment needed in hepatic impairment
-ombitasvir: 25 mg PO QD WF; available only in coformulated tablets; requires ritonavir-boosting for once daily administration; AEs: fatigue, nausea, pruritis, skin reactions, insomnia; contraindicated in child-pugh B or C based on case reports of liver decompensation/failure or death
-daclatasvir: 60 mg PO QD, AEs: fatigue, HA, nausea; metabolized by CYP 3A4, so dose must by reduced to 30 mg QD when coadministered with strong 3A4 inhibitor, and increased to 90 mg QD when coadministered with strong 3A4 inducer; no dose adjustment for hepatic impairment
-elbasvir: 100 mg PO QD; co-formlated with grazoprevir, prior to use in patients with genotype 1a, an NS5a genotype must be performed to screen for presence of resistance-associated variants at baseline; presence of any mutations at codons requires an extended 16-week course + ribavirin
-velpatasvir: 100 mg PO QD; available only in coformulations; AEs: fatigue, HA; approved for all gentypes; no dose adjustment needed in hepatic impairment

45
Q

ribavirin for HCV treatment

A

guanosine analog, exact mechanism unknown, orally available
weight based dosing
AEs: hemolytic anemia, pancreatitis, pulmonary dysfunction (dyspnea, pulmonary infiltrate, pneumonitis), insomnia, pruritis
teratogenic - category X (must have monthly preg tests and use 2 forms of contraception through 6 months after treatment stopped)
contraindicated in patients with CrCl under 50
monitor CBC - decrease dose if Hgb under 10, d/c if Hbg under 8.5, may use epoetin or darbepoetin to stimulate RBC production

46
Q

INFs for HCV

A

peginterferon alfa-2a, peginterferon alfa-2b and interferon alfa-2a are approved for HCV treatment, but seldom used d/t availability of better tolerated oral DAAs

47
Q

AASLD/IDSA treatment recommendations for HCV

A

all regimens 12 weeks unless otherwise noted
pretreatment labs: HCV genotype, resistance test (if considering elbasvir/grazoprevir), HCV RNA, fibrosis staging, CBC, CMP, pregnancy test
on treatment: HCV RNA at 4 weeks
post-treatment: HCV RNA 12 weeks after treatment, consider RNA after 52 weeks

48
Q

recommended treatments in 1a HCV GT without cirrhosis

A

recommended: ELB/GRZ (in whom no baseline NS5A RAVs for elbasvir are detected at amino acid positions 28, 30, 31, 93), OMB/PTV/RTV + DSV (RBV?), DCV + SOF, LDV/SOF (an 8-week course can be considered if pretreatment HCV RNA less than 6 million IU/mL), VEL/SOF, SIM + SOF
alternative: ELB/GRZ (RAV 16+RBV)

49
Q

recommended treatments in 1a HCV GT with cirrhosis

A

preferred: recommended: ELB/GRZ (in whom no baseline NS5A RAVs for elbasvir are detected at amino acid positions 28, 30, 31, 93), LDV/SOF, VEL/SOF
alternative: ELB/GRZ (RAV 16+RBV), OMP/PTV/RTV + DSV (24+RBV), DCV + SOF (24 +/- RBV, SIM + SOF (No Q80K 24+RBV)

50
Q

prevention of HSV

A

counsel infected patients how to avoid transmission/reinfection: avoid sharing toothbrushes, shaving equipment and cover any bleeding wound, stop using illicit drugs; if unable to, avoid reusing or sharing needles; do not donate blood, organs, tissue or semen
future therapies: many additional DAAs are in clinical trials, vaccines under development

ID exam 3 (8 decks)

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