Hepatitis Flashcards
Hepatitis A overview
Fecal-oral
Perinatal transmission? No
Most common risk factor: direct contact with someone with HAV
Hepatitis B overview
Transmission: Blood, sexual
Perinatal transmission? Yes
Most common risk factor: born to infected mother
Hepatitis C overview
Transmission: blood
Perinatal transmission? Yes
Most common risk factor: injection drug use
HAV risk of chronic infection?
No
Acute, then resolved
HBV risk of chronic infection?
Yes
Course of infection: acute then sometimes chronic
- 90% of infants
- 20-25% of children ages 1-5
- 5% of adults
Treatment of chronic infection: Yes but no curable
HCV risk of chronic infection
Yes
Acute then sometimes chronic
- > 50% develop chronic infection
Treatment: Yes, curative
Hepatitis A Symptoms
Can be asymptomatic or symptomatic
Abrupt onset, usually last less than 2 months:
Abdominal pain, nausea, or vomiting
Dark urine or clay colored stools
Fatigue
Fever
Jaundice
Joint pain
Loss of appetite
Hepatitis A diagnosis
IgM anti-HAV serum (usually detectable within 5-10 days of symptom onset) OR HAV RNA in serum or stool
IgG anti-HAV appears early in the infection, remains detectable providing lifelong immunity
Total anti-HAV (measuring both IgG and IgM) used to assess immunity
Hepatitis A management
Supportive Care
Hepatitis A prevention (who should be vaccinated)
All children age 12-23 months
MSM
People who anticipate close contact
Pregnant women at risk for HAV
Homeless
People who use drugs
Unvaccinated ages 2-18
Anyone who requests vaccination
International traveler
People at risk for exposure
People with chronic liver disease or HIV
HAV vaccine
Inactivated–safe in pregnancy
Two doses at 0 and 6-12 months
Pre and post vaccination serologic screening is typically not recommended
Post exposure prophylaxis to be given ASAP after exposure
- > 12 months of age
- IM immune globulin if < 12 months
- give both if > 40 years with increased risk of severe disease
Hepatitis B transmission
Sexual contact
Injecting drugs
Mother to child
Contact with blood or open sores
Needle stick
Sharing razors or toothbrushes
CANNOT BE SPREAD by:
Food
water
sharing utensils
kissing
coughing
sneezing
holding hands
Hepatitis B symptoms
Similar to HAV expect don’t see much diarrhea
Chronic infection is typically asymptomatic until onset of cirrhosis, end-stage liver disease or hepatocellular carcinoma
Hepatitis B screening
All adults aged 18 years and older at least once in their lifetime using a triple panel test
Screen for HBsAg during each pregnancy regardless of vaccination status
People who are at ongoing risk for exposure should be tested periodically
Or anyone who requests it
Hepatitis B serologic markers
Hepatitis B surface antigen
- marker of presence of ongoing infection
- Is the patient infectious?
Antibody to hepatitis B surface antigen
- marker of immunity
- Is the patient immune?
Antibody to hepatitis B core antigen
- marker of exposure to infection
- How has the patient been exposed?
Interpreting HBV test results
HBsAg, anti-Hbs, anti-HBc: all negative, never infected, if not vaccination then offer vaccine
HbsAg: negative, anti-HBs: positive, anti-HBc: positive, resolved infection, counsel about HBV infection reactivation risk
HBsAg: negative, anti-HBs: positive, anti-HBc: negative, immune from receipt of prior vaccination, complete vaccine series
HBsAg: positive, anti-HBs: negative, anti-HBc: positive, IgM anti-HBc: positive, acute infection, link to hepatitis B care
HBsAg: positive, anti-HBs: negative, anti-HBc: positive, IgM anti-HBc: negative, chronic infection, link to hepatitis B care
Hepatitis B acute management
Acute infection: no treatment, supportive care
Hepatitis B chronic infection goals of therapy
Achieve sustained suppression of HBV replication
Remission of liver disease
Prevent cirrhosis, hepatic failure, and HCC
Functional cure: HBsAg loss with or without anti-HBe gain is attainable
Virological cure: eradication of cccDNA from hepatocyte nuclei– not yet attainable
Hepatitis B chronic infection management
History (risk factors) and physical exam
CBC, liver panel, INR, HBeAg, anti-HBe, HBV DNA PCR
Test for coinfection, HCV, HDV, HIV, anti-HAV
Baseline alfa fetoprotein assay, abdominal US, and fibrosis staging to assess for evidence of HCC
Phases of chronic HBV
e+ Immune-tolerant
- normal ALT
- elevated HBV DNA (++++)
- monitor ALT q2-6 months, eAg q6-12 months
e+ Immune-active
- elevated ALT
- elevated HBV DNA (+++)
- TREAT if ALT > 2x ULN, HBV DNA > 20,000 IU/mL, otherwise monitor
e+ cirrhosis
- elevated ALT
- elevated HBV DNA (++)
- low albumin, low platelets
- TREAT INDEFINITELY if HBV > 2,000 IU/mL, otherwise monitor
e- Inactive (carrier)
- normal ALT
- low/undetectable HBV DNA (+/-)
- monitor ALT q6-12 months
e- Immune reactivation
- elevated ALT
- elevated HBV DNA (+++)
- TREAT INDEFINITELY if ALT > 2x ULN, HBV DNA > 2,000 IU/mL, otherwise monitor
e- Cirrhosis
- elevated ALT
- elevated HBV DNA (++)
- low albumin, low platelets
- TREAT INDEFINITELY if HBV > 2,000 IU/mL, otherwise monitor
HBV principles of treamtment
HBV DNA > 2,000 IU/mL (> 10,000 copies/mL) associated with increased risk of cirrhosis and HCC
ALT upper limit of normal (ULN) is 35 U/L for males and 25 U/L for females
Treatment does not eradicated HBV
Combination therapy has not shown higher response rates than monotherapy
For most, duration of NA therapy is indefinite
HBV treatment eligibility
HBV DNA > 2,000 IU/mL; plus
- ALT > 2x ULN; or if they have cirrhosis: if they meet the major one and 1 of the other two then offer treatment
Tenofovir 1st line treatment
MOA: inhibit HBV replication through incorporation into viral DNA by the HBV reverse transcriptase
300 mg PO daily
76% of e+ and 93% of e- maintain suppressed HBV DNA levels after 3 years of therapy
Maintenance of HBsAg loss after 3 years: e+ 8%, e- 0%
SE: nephropathy, faconi syndrome, osteomalacia, lactic acidosis
Tenofovir alafenamide 1st line
25 mg PO daily
Improved safety (less renal impairment)
73% of e+ and 90% of e- maintain suppressed HBV DNA levels after 2 years of therapy
maintenance of HBsAg loss after 2 years: e+1%, e- < 1%
SE: lactic acidosis
Entevacir 1st line
0.5 mg PO daily in nucleoside naive patients
1 mg PO daily in nucleoside-experienced patients
take on empty stomach
61% of e+ and 90% of e- maintain suppressed HBV DNA levels after 3 years of therapy
Maintenance of HBsAg loss after 3 years: e+ 4-5%, e- 0-1%
SE: lactic acidosis
Treatment monitoring
For patients on therapy, HBV DNA levels should be monitored q3 months on NA therapy until undetectable; then q3-6 months thereafter
If therapy is stopped, monitor q3 months for at least one year for recurrent viremia, ALT flares, seroreversion, and decompensation
All HBsAg+ patients with cirrhosis and high risk non-cirrhotics, should receive HCC surveillance (ultrasound of abdomen) q6 months
HBV reactivation/flares
Special populations
Renal insufficiency: adjust dose of NA
Pregnancy: to minimize risk of perinatal transmission, beginning at weeks 28-32 of gestation, treat pregnant women with HBV DNA > 200,000 IU/mL with tenofovir DF
HIV coinfection: some NA used for HBV also have antiretroviral activity against HIV, fully suppressive three-drug therapy should be initiated against HIV when treatment of HBV is warranted, combination of emtricitabine/tenofovir is frequently used
Who should be vaccinated?
All infants, beginning at birth
Unvaccinated children aged < 19 years
Adults 19-59
Adults aged 60 years or older with at least one of the risk factors (chronic liver dx, HIV, sexual exposure, drug use, percutaneous or mucosal risk for exposure to blood, people in jail, travelling)
HBV vaccine
All inactivated
3 injections at 0, 1, and 6 months
Post vaccination testing for immunity is recommended for: infants born with HBV, people at risk for exposure, immunocompromised, sex partners who have HBV chronic infection
HCV symptoms
> 50% with acute HCV will develop chronic infection
Persistently detectable HCV RNA for > 6 months
fatigue and depression
right upper quadrant pain
nausea
poor appetite
hepatomegaly on PE
HCV serologic testing
anti-HCV is detectable 8-11 weeks after infection
HCV RNA is diagnostic of current HCV infection: detectable 1-2 weeks after infection
A diagnosis of HCV is many times incidental after having persistent elevated LFTs
HCV goals of therapy
Obtain virological cure by achieving a sustained virological response (SVR): check 12 weeks after completion of treatment
Prevent complications
HCV agents
NS3/4A protease inhibitors
NS5B polymerase inhibitors: nucleoside/nucleotide, non-nucleoside
NS5A replication complex inhibitors
NS3/4A protease inhibitors
Blocks this: Serine protease cleaves the HCV RNA-encoded polyprotein into its functional units (NS4A, NS5B, NS5A, and NS5B)
CYP3A4 inhibitors
Grazoprevir
AE: fatigue, headache, nausea, anemia, ALT elevations
Patients should have ALT checked at 8 weeks; discontinue if > 5xULN
Contraindicated in Child-pugh class B and C
Sofosbuvir
NS5B Polymerase inhibitors
Avoid amiodarone coadministration due to risk of symptomatic bradycardia
No dose adjustment needed in hepatic impairment
Elbasvir
Prior to use in patients with genotype 1a, and NS5a genotype must be performed to screen for presence of resistance-associated substitutions (RASs) at baseline
Velpatasvir
Check for genotype 3 must be performed to screen for presence of the Y93H substitution; presence requires ribavirin or voxilaprevir
No dose adjustment in hepatic impairment
Ribavirin
