Hepatitis Flashcards
1
Q
which hepatitis viruses are there vaccinations for?
A
A, B, E
2
Q
What else can cause the symptoms of heptatits?
A
- reactions to prescription meds
- med interactions
- acetaminophen OD
- ecstasy
- rule these out first
3
Q
Hep A Virology
A
- human restricted picornavirus (enterovirus 72)
- fecal oral transmission, similar replication cycle as other enteroviruses
- if sanitation level is low, contaminated stool reaches drinking water
- highly environmentally stable
- only one serotype exists
- neutralizing antibodies recognize virion proteins 1 and 3
- IgG is protective against reinfection (vaccine)
4
Q
Hep A disease
A
- US is a low endemic area
- CDC rec routine vax in 2006 for 1 year olds
- viral replication often asymptomatic, but alternatively can keep an adult out of work for a month (worst acute hep)
- predominantly portal and periportal lymphocytic infiltrate and a varying degree of necrosis
- symptoms are immunogenic
- over 99% of patients recover completely, no chronic infection
- rare patients develop fulminant hep, of those, 40% mortality
- transplant is an option, but most patients don’t need one
5
Q
what are the risk factors for a fulminant hep A infection?
A
- elderly
- pre-existing liver disease
6
Q
hep A on exam
A
- jaundice
- smokers don’t like taste of tobacco anymore
- anorexia
- nausea/ vomiting
- tenderness around liver, hepatomegaly
- dark urine, pale feces
- leg rash
- fatigue, some fever
- severity of symptoms directly correlate with age of patient
7
Q
questions to ask someone to help you see if its Hep A
A
-vaccinated?
-travel?
-daycare?
-shellfish?
-institutionalization?
-poverty?
MSM?
-IV drugs?
8
Q
hepatitis A lab
A
- Enzyme immunoassay (EIA) for IgM- acute infection
- IgG- past infection or vax
- elevated ALT- ongoing damage
- bili, AST, alkP high during acute phase
- US or biopsy if concerned about fulminant failure
- incubation period may be shorter if infecting dose is high
9
Q
hep A treatment
A
- PREVENTION!
- handwashing, sanitation, water treatment, vaccine
- prophylaxis: Ig
- trt- bed rest, hydration, careful with Tylenol
- usual prognosis is good. elderly patients can relapse, rare complications do occur, most recover with lasting immunity
- if transmitted human to human, trace contacts, alert local public health
10
Q
Hep E virology
A
- small, naked, +ssRNA virus
- hepevirus
- fecal oral transmission (waterborne)
- not necessarily human restricted; there may be an animal reservoir
- principal cause of acute hepatitis in Asia/ Africa, Mexico
- largest epidemic in NW China 1986-88, 120,000 cases and >700 deaths
- only one serotype
11
Q
Hep E Disease
A
- very similar to A- acute, self limited, complications somewhat more common
- mortality rate is 4% (>10x HepA)
- mortality in pregnant women is 20%, fatal fulminant hep, encephalopathy, DIC
- may also reactivate in liver transplant recipients
12
Q
Hep E exam
A
Biphasic!
Prodrome: anorexia, N/V/D, tender around liver, HSM, fatigue, fever
Icteric phase: Jaundice, dark urine, pale feces, leg rash
-Are they vaccinated? Did they travel?
13
Q
Hep E lab
A
- serology not widely available, send to CDC
- high ALT, AST, bili with negative antibodies for other hep
- US care clarify HSM, rule out biliary obstruction
- livery Bx not indicated for diagnosis, but if one is performed would see cholestasis, swollen hepatocytes, foam cells, acidophil bodies, IF infiltrate, expanded portal areas
14
Q
hep E treatment/prevention
A
- when traveling, boil water, cook fish, clean/cook produce
- IgG prophylaxis not available
- HEV239 vax is new, safe and effective so far
- no specific treatment
- light activity is better than bed rest
- fluid and electrolyte replacement
- LFT monitoring
- discontinue alcohol and contraindicated drugs
15
Q
Hep B virology
A
- human restricted hepadnavirus
- small, enveloped, DNA virus, partly double stranded
- messy virus- 1000x more HBsAg decoys than virions
- unusually stable for enveloped virus
- only one serotype, HBsAb protective against reinfections, effective vax available
- even though its DNA, carries reverse transcriptase and replicates through RNA intermediate
- replicates in hepatocytes and leaves behind integrated copies of viral DNA
16
Q
Hep B pathogenesis
A
- transmitted efficiently by injection of contaminated blood, less efficiently by sexual or birth contact
- 1/3 human population seropositive worldwide
- in US, 200k new cases annually, 5000 deaths, 5-10% of end stage liver failure, 10-15% of HCC
17
Q
HBsAg
A
- appears early
- ceases being detectable as surface antibody is produced
- resumes being detectable in chronic infection
18
Q
HBsAb
A
- becomes detectable as surface antigen levels fall
- signifies immunity in vax person
19
Q
HBcAb
A
- arises later, stays
- IgM for acute, IgG for resolved or chronic
20
Q
HBeAg
A
-detectable when virus is mores transmissible
21
Q
four stages of Hep B
A
- immune tolerance
- immunogenic symptoms
- clearing virus
- virus cleared
22
Q
- immune tolerance in Hep B
A
- virus replicates without symptoms
- 2-4 weeks, decades in newborns
- DNA and antigens in serum, little antibody
23
Q
- immunogenic symptoms of hep B
A
- ALT rises, Hep B DNA decreases
- 3-4 week symptomatic period- acute or lasts for years, leading to cirrhosis
24
Q
- clearing the virus in hep B
A
- viral replication shuts down
- HBeAb detected
- no DNA
- ALT decreases
- HBsAg remains
25
Q
- virus cleared in hep B
A
- no antigens
- permanent HBsAb IgG
26
Q
HBV outcomes
A
- 90% resolution, 1% fulminant hep
- 9% have HBsAg for >6 mo
- of those 9%, 50 % resolve or go into asymptomatic carrier
- some have chronic persistent hep, those can develop extrahepatic PAN or glomerulonephritis
- some have chronic active hepatitis- they can have extrahepatic disease, or cirrhosis or HCC
27
Q
pathogenesis of chronic Hep B infection
A
- ongoing cytotoxic T cell response against infected hepatocytes causes permanent cirrhosis
- accumulation of hep antigen/antibody complex leads to kidney damage and arthritis (membranous glomerulonephritis)
- virus genome integration, expression of viral transcriptional transactivators, and chronic inflammation lead to cancer (HCC)
28
Q
Hep B presentations
A
- most common US presentation: Asian born adult infected vertically as a newborn
- second most common: socioeconomically disadvantaged sexually transmitted
29
Q
Hep B acute non icteric exam
A
-flu like or no symptoms
30
Q
Hep B acute icteric phase
A
- fatigue, fever, jaundice
- aversion to food and cigarettes
- anorexia, nausea, vomiting
- RUQ pain
- myalgia
- hepatomegaly
- hepatic encephalopathy, sleep disturbances, mental confusion, coma
- splenomegaly
- are the vaccinated or an immigrant?
31
Q
hep B chronic phase exam
A
- spider angioma
- palmar erythema
- hepatomegaly
- jaundice
- variceal bleeding
- caput medusae
- peripheral edema
- gynecomastia
- ascites
- testicular atrophy
32
Q
Hep B lab
A
- serology panel
- remember the earth thing–i think its easier than what she has.
- antigens and antibodies
- ALT, AST, bili
- US/CT MRI to rule out bili obstruction
- PCR can be performed
- if infection is active chronic- bx
33
Q
active chronic hep B biopsy
A
- inflammation around portal tracts
- ground glass cytopathology
- positive for Hep B antigens
34
Q
hep B treatment
A
- best option was vaccination, rec for all kids and at risk adults
- recombinant HBsAg produced in yeast- raises antibody
- antibody prophylaxis- HBIG admin shortly prior to exposure
- combo of both given for needle sticks and babies
- supportive care for acute hep
- drug if chronic, cure rate is low. 1 year of pol inhibitors (lamivudine, adefovir, entecavir, telbivudine)
- PLUS 4 mo of PEG-INF
- transplant may be indicated for late stage if treatment fauls
- watch LFTs/ mental status
- patient education- sexually transmitted. CONDOMS
35
Q
interferon
A
- normally good for us in small amounts as a paracrine signal
- when all over body, you feel like shit.
36
Q
hep D
A
- not a complete virus
- needs B to replicate (B is helper virus)
- 1700 nucleotide circular -RNA genome only encodes delta antigen
- exterior looks like B
- spread by blood and sex
37
Q
is the delta antigen cytotoxic?
A
- YES!
- increases incidence in fulminant hep with B
- affects ~5% of hep B carriers
38
Q
coinfection
A
- acquired at the same time
- same clearance rate as B alone (90%)
39
Q
superinfection
A
- B already there and then get D
- pre existing B hepatocytes are weak and permissive to D- much worse outcome
40
Q
Hep D diagnosis
A
- same as Hep B, some exacerbation of sx if already B+
- primary screening with EIA for anti deltal antibodies
- Hep B serum panel with acute results if coinfection or chronic results if superinfection
- if co infected- wait and watch for spontaneous clearance
- follow up with RT-PCR for viral RNA
- if indications of liver failure or chonic active infection, liver bx will resemble hep B with positive delta staining
41
Q
hep D treatment
A
- prevent B with vax or prophylaxis
- halt IV drug use, alcohol, treat B
- after D infection, prog is grim
- can try 1 year PEG-INF, usually relapses after therapy stopped
- transplant is an option but graft tends to become infected
42
Q
Hep C virology
A
- human restricted flavivirus
- enveloped +RNA genome
- transmitted efficiently by blood, ineffeciently by sex
- just discovered in 1989, anyone who received blood before 1994 is at risk
- 3 million carriers in US, many unaware
- much higher potential for chronic infection than B, stronger association with HCC
- no vaccine
43
Q
Hep C pathogenesis
A
- infects hepatocytes and possible B lymphocytes (both have CD81)
- highly mutagenic, rdRNAP has no proofreading- generates quasispecies
- can produce 10 trillion new particles a day
- less than half of infectees clear it, requires strong cytotoxic T tresponse
44
Q
HCV outcomes
A
- 15% recovery and clearance
- 85% persistent infection, leading to chronic hepatitis
- of those, 6% liver failure, 20% cirrhosis, 4% HCC
45
Q
Hep C exam
A
- acute symptoms similar to HBV, somewhat milder
- red flag- travel to Egypt (22% HCV+)
- new infections in US now usually from IV drugs, but many old ones being uncovered
46
Q
extrahepatic sx of HCV
A
- sicca syndrome
- arthralgia
- myalgia
- pruritus
- paresthesias, sensory neuropathy
47
Q
liver failure from HCV on exam
A
- jaundice
- vasculitis, autoimmunity
- palmar erythema
- ascites
- HSM
- kidney faul
- icteric sclera, enlarged parotid, cyanosis
- lichen planus
- variceal bleeding
- peripheral edema
- testicular atrophy
48
Q
Hep C lab
A
- LFTs, autoantibodies, cryglob
- EIA followed by RIBA
- if pos, HCV genotyping
- RT-PCR for viral RNA levels to asses success of therapy
- liver biopsy not required, can be helpful in judging severity of disease
- screen for HIV, HBV, drug abuse
49
Q
RIBA for HCV
A
- confirm exposure
- HCV antigens on paper- then patients serum on top. then second tagged antibody. if patient has antibodies to HCV, they will light up
50
Q
Hep C treatment
A
- antibody not protective
- acute infection- short course of PEG-INF reduces rates of chronic
- may clear spontaneously without treatment
51
Q
second generation HCV treatment
A
-chronic infection with damage- treat
-ribavarin (antiviral and immunomodulatory)
PLUS
-PEG-INF
PLUS if serotype 1
-protease inhibitors- boceprevire and telaprevire
*virus makes a polyprotein molecule that is cleaved, which is why protease inhibitors work
52
Q
goal of HCV treatment
A
- sustained viral response (SVR)
- failed treatment may still reduce risk of HCC
53
Q
HCV serotypes and trt
A
-make it hard.
2 and 3 have >50% SVR with 6 mo peg-inf and ribavirin
-1 and 4 require 1-2 years therapy and still have lower recovery rates
-new protease inhibitors for 1 are less effective against 2 and 3
-ask about other meds they’re taking on their own!
54
Q
third generation HCV treatment
A
- simeprevir- PI “cure” serotype 1
- sofosbuvir (pol inhib)- SVR if combined with ledipasvir (NS5A inhib)
- sofosbuvir + ribavirin for genotypes 2 and 3
