Lec 31 Viral Hepatitis Flashcards
What is viral hepatitis?
inflammation of liver caused by a virus
What are symptoms of viral hepatitis?
- jaundice [yellow skin/eyes]
- fatigue
- ab pain
- loss of appetite
- nausea
- vomit
- diarrhea
- low fever
- headache
or may not have symptoms!
What virus/name for hep A?
virus: picornavirus
name: infectious hepatitis
What virus/name for hep B?
virus: hepadnavirus
name: serum hepatitis
What virus/name for hep C?
virus: flaviviridae
name: Non-A, non-B hepatitis
What virus/name for hep d?
virus: deltavirus
name: delta agent
What virus/name for hep E?
virus: hepevirus
name: enteric non-A, non-B hepatitis
What are similarities between the Hepatitis viruses?
- similar symptoms
- liver tropism and infect hepatocytes
- primary/exclusively associated with liver disease
Hep A: onset, severity, chronicity?
onset: abrupt
severity: mild
chronic: no
Hep B: onset, severity, chronicity?
onset: slow
severity: occasionally severe
chronic: yes
Hep C: onset, severity, chronicity?
onset: slow
severity: usually subclinical
chronic: yes
Hep d: onset, severity, chronicity?
onset: abrupt
severity: occasionally severe
chronic: yes
Hep E: onset, severity, chronicity?
onset: abrupt
severity: severe in pregnant
chronic: no
Hep A: Is there a vaccine? treatment?
vaccine: children > 1 yr, travelers, at risk
treat: none
Hep B: Is there a vaccine? treatment?
vaccine: for infants and adults at risk
treat: yes, rarely cures
Hep C: Is there a vaccine? treatment?
vaccine: none
treat: yes
Hep d: Is there a vaccine? treatment?
vaccine: none
treat: none
Hep E: Is there a vaccine? treatment?
vaccine: none
treat: none
Who gets Hep B?
- common in high risk groups –> IV drug users
What are viral characteristics of HBV [including family + genus]?
family: hepadnaviridae
genus: orthohepadnavirus
- spherical particle
- enveloped
- partially double stranded
- circular DNA
- small genome
How does replication of HBV occur?
via RNA intermediate by reverse transcription
What are possible outcomes of acute HBV infection?
if have effective T cell response: get subclinical disease or acute hepatitis and then recover [<1% get fulminant hepatitis and die]
if limited T cell response: get persistant infection leading to recovery or chronic hepatitis and then cirrhosis
– limited response more likely in perinatally infected infants and immunocompromised
What is immune response to acut hep B? How does this differ in chronic Heb B
- production anti-HBsAg, anti-HBeAg, anti-HBc-Ag
- in chronic hep B no anti-HBs
What are levels of anti-HBc Igm, Anti-HBc IgG, HBsAg, and Anti-HBs in resolved acute HBV?
anti HBc IgM: negative
anti HBc IgG: pos
HBsAg: neg
Anti-HBs: pos
What are levels of anti-HBc Igm, Anti-HBc IgG, HBsAg, and Anti-HBs in chronic HBV?
anti HBc IgM: neg
anti HBc IgG: pos
HBsAg: pos
Anti-HBs: neg
What is virus theory of mech for induction of hepatocellular carcinoma?
- viral products act as oncogenes
- get integration of viral genome and disruption of cellular gene expression
What is indirect/nodular cirrhosis theory of mech for induction of hepatocellular carcinoma?
- chronic hepatic injury and repair processes lead to genetic changes causing uncontrolled growth
What are the 2 treatments for chronic HBV?
- pegylated interferon alpha = antiviral cytokine
- reverse transcriptase inhibitors [almivudine, entecavir, tenofovir]
Who do you treat for chornic HBV?
- pts positive for HBsAg for > 6 mos
- high HBV DNA levels
- high ALT
- evidence of liver disease
What is mech of lamivudine? administration? resistance? cost?
mech: nucleoside analog reverse transcriptase inhibitor, similar to deoxyC, terminates chain
admin: oral
resistance: high levels
cost: low
What is mech of entecavir? administration? resistance? cost?
mech: nucleoside analog reverse transcriptase inhibitor, similar to deoxyG, terminates chain
admin: oral
resistance: low levels, cross-resistant with lamivudine
cost: high
What is mech of tenofovir? administration? resistance? cost?
mech: nucleoside analog reverse transcriptase inhibitor, similar to deoxyA, terminates chain
admin: oral
resistance: none, use in pts with lamivudine or entecavir resistance
cost: intermediate
What are vaccines for HBV?
- early ones used HBsAg
- current uses non-glycosylated HBsAg in yeast and adjuvant alum
- requires multiple immunization, failure common in HIV
- can give along with hep B Ig in neonates born to infected mothers just after birth to prevent infection
What is hep delta virus? who gets it? symptoms?
- subviral satellite virus –> needs HBV to provide envelope proteins for assembly
- only infects HBV+
- increases incidence of active hepatitis, cirrhosis, hepatocellular carcinoma in chronic HBV and likelihood of death from fulminant hep
What are top sources of HCV infection?
- IV drug use
- sexual
- transfusion
What are viral properties of HCV including family/genus?
family: flaviviridae
genus: hepacivirus
- single strand
- pos sense RNA
- high mutation rate [error-prone RNA pol]
- exists to quasispecies
What is significance of HCV as a quasispecies?
- allows to escape from immune response
- often resistant to treatment
What are outcomes of HCV infection?
acute –> 80% get chronic
- -> 35% get stable chronic
- -> 65% slowly progressive with some symptoms –> leads to cirrhosis in 30% –> can get slowly progressive cirrhosis or liver failure/cancer/death
What is mech of ineffective cellular immune response to HCV?
- co infection with HIV
- viral evasion of innate immune response
- impaired NK cell, dendritic cell function
- glycosylated envelope proteins protect against Ab mediated neutralization
- sequence variations allows immune escape for T & B cell
How do you diagnose/assess HCV infection?
- serology: look for antibodies to core, NS3 and NS5 detected within 6-8 wks of exposure
- RT-PCR: measure viral load in serum, genotype via sequence
- liver biopsy: assess stage of liver injury
how do you treat HCV?
indirect antivral:
- PEG-interferon-alpha + ribavirin
direct acting
- telaprevir/bocoprevir [protease inhibitors] + PEG-IFN-a + ribavirin
- sofusbuvir [polymerase inhibit]
- simepravir [protease inhibit]
What are downsides of telpravir/bocoprevir as treatment for HCV?
- only targets genotype 1
- get anemia, rash, interforon still need, 8 hr dosing
What are downsides of sofubuvir as treatment for HCV?
- no side effects
- interacts with P-glycoprotein substrate, avoid P-gp inducers [rifampin, st johns wort]
What are downsides of simepravir as treatment for HCV?
side effect: photosensitivity/rash
drug interactions: CYP3A4 inducers/inhibitors
How is Hep A transmitted?
person to person via fecal-oral route
What are clinical features of hep A [time frame, complications]
- self limited [3 wks]
- can profress to fulminant hep failure in pts with underlying liver diesase [HBV or HCV]
How do you diagnose HAV?
- symptoms of acute viral hepatitis
- detection of HAV-specific IgM anitbody in acute-phase serum
What is treatment for HAV?
supportive
How do you prevent HAV?
vaccination [recommend at under 1 yr old]
What is typical course of acute hep A?
- jaundice symptoms coincide with peak ALT, then ALT lower, IgM Anti-HAV lowers, Anti-HAV stays high
What is clinical presentation of Hep E? Who gets it?
- similar clinical to HAV
- found in developing countries with fecal contamination of drinking water
- self limited followed by recovery
- chronic infection does not occur
- occassionaly get fulminant hep in pregnant women
How is hep E transmitted?
fecal oral = fecal contamination of drinking water in developing countries
What does it mean if you have negative Anit-HBc IgM, anti-HBc IgG, and HBsAg by positive Anti-HBs for HBV?
means you were not infected but had a prior acute vaccination for HBV
