Viral Hepatitis Flashcards
What is hepatitis? What is viral hepatitis?
Hepatitis: Inflammation of the liver
Viral hepatitis: Hepatitis caused by one of at least five distinct viruses - hepatitis A, B, C, E, or delta virus
What are the characterisitics of viral hepatitis?
Hepatotrophic – systemic infections that primarily affect the liver
RNA viruses – except HBV (which is a DNA virus)
All can produce an acute illness
* Nausea, anorexia, fever, malaise, and abdominal pain
* Jaundice or elevated liver transaminases
What are the modes of transmission of hepatitis A?
main transmission: fecal-oral; Close personal contact or sexual contact with an infected
person; Ingestion of contaminated food or water
perinatal transmission: no
What is the pathogenesis of hepatitis A?
- Classified as a picornavirus
- Replicates in the liver, excreted in the bile, and is shed in the stool
What are the symptoms of hepatitis A?
Can be asymptomatic or symptomatic (varies based on age)
Abrupt onset, usually lasts less than 2 months
* Abdominal pain, nausea, and/or vomiting
* Dark urine or clay-colored stools
* Diarrhea
* Fatigue
* Fever
* Jaundice
* Joint pain
* Loss of appetite
What is the diagnosis and serologic testing of hepatitis A?
Diagnosis of acute HAV requires the detection of either:
* IgM anti-HAV in serum (usually becomes 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) is used to assess immunity
What is the management of hepatitis A?
- Supportive care
- No role of antiviral agents for treatment
What are the modes of transmission of hepatitis B?
main transmission: blood, sexual
percutaneous or mucosal contact: sexual contact, injecting drug use, mother-to-child transmission, contact with blood or open sores, needle sticks, sharing razors or toothbrushes
perinatal transmission: yes
What is the pathogenesis of hepatitis B?
- Classified as a hepadnavirus
- The virus enters the liver through the bloodstream, replicates in the liver
What are the symptoms of hepatitis B?
- Acute symptoms: same as HAV infection (except no diarrhea)
- Chronic infection is typically asymptomatic until onset of cirrhosis, end-stage liver disease or hepatocellular carcinoma (HCC)
- 15-25% of people with chronic HBV infection are at risk for premature death from cirrhosis and HCC
What are the screening recommendations for hepatitis B?
- Screen 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 and history of testing
- People who are at ongoing risk for exposure should be tested periodically
- Test anyone who requests HBV testing regardless of disclosure of risk
What are the modes of transmission of hepatitis C?
main transmission: blood; spread through large or repeated percutaneous exposures to infected blood
perinatal transmission: yes
What are the risk factors of hepatitis A?
Direct contact with someone with HAV; International travelers; Men who have sex with men; People who use or inject drugs; People with occupational risk for exposure; People who anticipate close personal contact with an international adoptee; People experiencing homelessness
What are the risk factors of hepatitis B?
Born to infected mother
* People born in certain countries where hepatitis B is common
* People born in the United States who were not vaccinated as infants
and whose parents were born in countries with high rates of hepatitis B
* People who have hepatitis C.
* People who have sexually transmitted infections, such as HIV
* People who are on dialysis
* People who have liver damage or inflammation
* People who have been in jail or prison
* People who inject drugs or share needles, syringes, and other types of
drug equipment
* Sex partners of people who have hepatitis B
* Men who have sex with men
* People who live with someone who has hepatitis B
* Health care and public safety workers who are exposed to blood on the
job
What are the risk factors of hepatitis C?
Injection drug use
What are the methods of prevention of heptatitis A?
HAV vaccine:
* Two dose series given at 0 and 6-12 months
* Inactivated vaccine – safe in pregnancy
* Pre- and post-vaccination serologic screening is typically not recommended
* Post-exposure prophylaxis should be given ASAP after exposure (within 2 weeks): Vaccine for people >12 months of age; IM immune globulin if <12 months; Give both if >40 years with increased risk of severe disease
What are the methods of prevention of heptatitis B?
HBV vaccine
What are the methods of prevention of heptatitis C?
Counsel infected patients how to avoid transmission
Post-exposure prophylaxis for health-care personnel
What’s the potential for chronic infection of hepatitis A?
none
Acute, then resolved
What’s the potential for chronic infection of hepatitis B?
can produce a chronic infection; 90% of infants, 25-50% of children ages 1-5, 5% of adults; Symptoms ranges from subclinical to cirrhosis or hepatocellular carcinoma (HCC)
treatment is curative
What’s the potential for chronic infection of hepatitis C?
can produce a chronic infection; >50% develop
chronic infection; Symptoms ranges from subclinical to cirrhosis or hepatocellular carcinoma (HCC)
treatment is curative
How do you interpret hepatitis B serologic test results? - Hepatitis B surface antigen
Hepatitis B surface antigen (HBsAg) - Marker of presence of ongoing infection; answers the question “Is the patient infectious?”
How do you interpret hepatitis B serologic test results? - Antibody to hepatitis B surface antigen
Antibody to hepatitis B surface antigen (anti-HBs) - Marker of immunity (indistinguishable whether acquired from disease or vaccination); answers the question “is the patient immune?”
How do you interpret hepatitis B serologic test results? - Antibody to hepatitis B core antigen
Antibody to hepatitis B core antigen (total anti-HBc) - Marker of exposure to the infection (persists for life, does not account for time since infection); answers the question “Has the patient been exposed to the virus?”
How do you interpret hepatitis B serologic test results? - Immunoglobulin M class of antibody to hepatitis B core antigen
Immunoglobulin M class of antibody to hepatitis B core antigen (IgM anti-HBc) - Marker of acute or recently acquired HBV infection (can give false positives); answers the question “Has the patient been recently exposed to the virus?”
HBsAg, anti-HBs, and anti-HBc all negative
clinical state: Susceptible, never infected
action: Offer HepB vaccine per ACIP recommendations
HBsAg - negative; anti-HBs - positive; anti-HBc - positive
clinical state: Resolved infection
action: Counsel about HBV infection reactivation risk
HBsAg - negative; anti-HBs - positive; anti-HBc - negative
clinical state: Immune from receipt of prior vaccination (if documented complete series)
action: If not vaccinated, then complete vaccine series
HBsAg - positive; anti-HBs - negative; anti-HBc - positive; IgM anti-HBc - positive
clinical state: Acute infection
action: Link to hepatitis B care
HBsAg - positive; anti-HBs - negative; anti-HBc - positive; IgM anti-HBc - negative
clinical state: Chronic infection
action: Link to hepatitis B care
What is the management of hepatitis B?
- Acute infection: No treatment; Supportive care
- Chronic infection: Goals of therapy
1. Achieve sustained suppression of HBV replication
2. Remission of liver disease
3. Prevent cirrhosis, hepatic failure, and HCC
4. functional cure – HBsAg loss with or without anti-HBe gain – is attainable
5. virological cure – eradication of cccDNA from hepatocyte nuclei – is not yet attainable
What is the management of chronic infection hepatitis B?
Initial evaluation:
* History (risk factors) and physical exam
* CBC, liver panel, INR, HBeAg, anti-HBe, HBV DNA PCR
* Test for coinfection with HCV, HDV, HIV, anti-HAV
* Baseline alfa fetoprotein assay (AFP), abdominal US, and fibrosis staging (via elastography or fibrosis panel) to assess for evidence of HCC
* Liver biopsy (diagnostic gold standard) is becoming rare
What are the phases of chronic HBV?
based on HBeAg, ALT, HBV DNA, and presence of cirrhosis
e+ immune-tolerant, e+ immune-active, e+ cirrhosis
e- inactive (carrier), e- immune reactivation, e- cirrhosis
e+ immune-tolerant
normal ALT
elevated HBV DNA
monitor
e+ immune-active
elevated ALT
elevated HBV DNA
treat if ALT > 2xULN, HBV DNA >20,000 IU/mL, otherwise monitor
e+ cirrhosis
elevated ALT
elevated HBV DNA
low albumin, low platelets
treat indefinitely if HBV DNA > 2,000 IU/mL, otherwise monitor
e- inactive
normal ALT
low/undetectable HBV DNA
monitor
e- immune reactivation
elevated ALT
elevated HBV DNA
treat indefinitely if ALT >2xULN, HBV DNA >2,000 IU/mL, otherwise monitor
e- cirrhosis
elevated ALT
elevated HBV DNA
low albumin, low platelets
treat indefinitely if HBV DNA >2,000 IU/mL, otherwise monitor
What is the upper limit of normal for alanine aminotransferase (ALT) for females?
25 U/L
What is the upper limit of normal for alanine aminotransferase (ALT) for males?
35 U/L
What is the treatment eligibility for HBV?
HBV DNA > 2,000 IU/mL (most important predictor)
PLUS
ALT > 2xULN or cirrhosis
What is the MOA of first line nucleoside analogs?
- Inhibit HBV replication through incorporation into viral DNA
by the HBV reverse transcriptase - Results in DNA chain-termination
What are examples of nucleoside analogs?
1st line: tenofovir, tenofovir alafenamide, entecavir
non 1st line: lamivudine, adefovir, telbivudine
What is the MOA of cytokines? What is an example?
Cytokine with antiviral, antiproliferative, and immunomodulatory effects
Ex. peginterferon alfa 2a
Cytokines are contraindicated in what patients?
current psychosis, severe depression, neutropenia, thrombocytopenia, symptomatic heart disease, decompensated liver disease!!, and uncontrolled seizures
What do you monitor in HBV?
ALT, HBV DNA levels, HCC surveillance
HBV in pregnancy
To minimize risk of perinatal transmission, beginning at week 28-32 of gestation, treat pregnant women with HBV DNA > 200,000 IU/mL with tenofovir DF
Infants should receive HBV vaccination + immunoglobulin
HBV vaccine - use in pregnancy?
All are inactivated – safe in pregnancy
administered at 0, 1, and 6 mo
What is the diagnosis and serologic testing for HCV?
anti-HCV only indicates past exposue to HCV
HCV RNA is diagnostic of current HCV infection
All direct acting antivirals carry a warning for what?
risk of Hepatitis B Virus reactivation
What are the therapeutic agents of HCV?
Direct Acting Antivirals (DAAs)
* NS3/4A protease inhibitors
* NS5B polymerase inhibitors: Nucleoside/Nucleotide and Nonnucleoside
* NS5A replication complex inhibitors
ribavirin
interferons
What are NS3/4A protease inhibitors?
NS3/4A serine protease cleaves the HCV RNA- encoded polyprotein into its functional units - NS3/4A protease inhibitors block this process
ex. boceprevir, telaprevir, simeprevir, peritaprevir, grazoprevir; glecaprevir; voxilaprevir
What are the NS5B polymerase inhibitors?
Inhibit the RNA NS5B polymerase responsible for replication of HCV
two different MOAs: Nucleotide analog competes for the enzyme active site and Nonnucleoside agent binds to an allosteric site inhibiting polymerase activity
Ex. sofosbuvir (nucleotide analog) - avoid amiodarone coadmin due to bradycardia; dasabuvir (nonnucleoside analog)
What are NS5A replication complex inhibitors?
Inhibit the protein NS5A, needed for HCV RNA replication and assembly
ex. ledipasvir - need to space apart acid reducing agents; ombitasvir; daclatasvir - metabolized by CYP3A4; elbasvir; velpatasvir; pibrentasvir
What special pre-treatment testing is considered prior to initiation of elbasvir?
Prior to use in patients with genotype 1a, an NS5a genotype must be performed to screen for presence of resistance-associated substitutions (RASs) at baseline
Presence of any subsitutions at codons 28, 30, 31, or 93 (12% prevalence) requires an extended 16-week course + ribavirin
What special pre-treatment testing is considered prior to initiation of velpatasvir?
Prior to use in compensated cirrhotic patients with genotype 3, an NS5A genotype must be performed to screen for presence of the Y93H substitution (9% prevalence); presence requires added ribavirin or voxilaprevir
What is the special on-treatment monitoring parameter for grazoprevir?
monitor ALT, d/c if >5xULN
Notes on ribavirin
Adverse effects: hemolytic anemia (10%), pancreatitis, pulmonary dysfunction (dyspnea, pulmonary infiltrate, pneumonitis), insomnia, pruritis
Teratogenic – category X
Contraindicated in patients with creatinine clearance <50 mL/min
Monitor CBC: decrease dose if Hgb <10 g/dL; d/c if Hgb <8.5 g/dL
How long to treat for all regimens?
12 weeks
Treatment duration for elbasvir/gasoprevir?
if 1b: 8 week course considered for pts with mild fibrosis
Treatment duration for pibrentasvir/glecprevir?
8 weeks
Treatment duration for vepatasvir/sofosbuvir/voxilaprevir?
Treatment duration for ledipasvir/sofosbuvir?
Treatment duration for velpatasvir/sofosbuvir?
