Hepatitis C Virus
INCIDENCE
emerging epidemic
approx 4 million in US infected (1.8% of pop) (Jinnah)
new acutes have declined from 180,000 (early 80's) to 35,000/year in US
(needle exchanges, blood screening since 1992, HIV awareness, universal healthcare precautions)
40,000 new infx/year in US (when?)
70% of those with antibodies have evidence of chronic infx (viral DNA in serum)
cases emerging clinically now are peeps who've been infected for 10-30 years
leading cause of liver transplants in N America and Europe
~10,000 people/year die of hep C related dz
DX FLOW
episodic elevations in serum aminotransferases with normal/near-normal periods intervening
elevated LFTs-->ELISA test-->if pos RIBA or PCR to confirm
-->if pos start ND tx, consider BX, genotype, viral count
--consider Fibrosure eval instead of BX http://www.fairfoundation.org/news_letter/2010/02june/Fibrosure..pdf
-->depending on genotype, individual preferences, consider alpha interferon tx
HEPATITIS C VIRUS
formerly known as "non-A, non-B hepatitis"
major cause of liver dz worldwide
screening began in early 90's, before that this virus was known as "non-A non-B"
most common chronic blood bourne infx
accounts for half of all pts in US with chronic liver dz
SCREENING should be performed on anyone who ever: injected illegal drugs, received blood transfusions prior to 1992, been on long-term dialysis, received blood from donors who later tested positive for HCV, or have persistently abnormal ALT values.
TRANSMISSION RISK FACTORS
innoculation (infx drugs, tattoos/piercing, intranasal cocaine use), blood transfusions, and sex
before 1992 most infections dt blood transfusions (Jinnah)
10% dt transfusion before 1991 (older notes)
60% of cases dt IV drug use
5% hemodialysis patients and healthcare workers (accidental needle stick)
5-15% sexual transmission, depends on tissue disruption, more with rectal penetration, hemophilia
household contacts of infected individuals, CDC does not recommend condoms
homosexual males, hemodialysis pts, hemophiliacs and IV drug users
1-6% vertical transmission (births to infected mothers) (lower risk with hep C than B)
pts with unexplained cirr/hepatocell CA have anti-HCV antibody prevalence rates exceeding 50%
up to half of pts with HCV don't know how they got it
TESTING FOR HCV
ELISA
most commonly used initial blood test for hepatitis C
enzyme-linked immunosorbent assay, aka EIA
used for initial evaluation of all pts wth liver dz or increased ALT
positive Anti-HCV can mean current or resolved infx
long incubation: Anti-HCV may not appear until 3-6 months after exposure
false-negs: early acute, in immune compromised pts (hemodialysis, HIV)
false-positive very rare: in AI pts, polyarteritis nodosa, rheumatic fever, hypergammaglobulinemia, passive antibody transfer (ie breastmilk)
cost ~$40
confirm ELISA with an HCV RNA test
RIBA
detects the Anti-HCV = hep C antibody in serum
recombinant immunoblot assay
used to confirm a positive ELISA
blood banks use the RIBA to test donated blood, esp to confirm HCV-positive samples on ELISA
(does this put us at risk because of the window between exposure and appearance of antibodies????)
15% of acutes clear the virus and resolve without going into a chronic state
PCR
can dx before seroconversion (1-2 weeks post, conversion occurs at 2-3wks post exposure)
PCR amplification can detect very low levels of HCV RNA in serum (100-2000 copies/ml)
PCR not standardized among labs so use the same lab for monitoring viral load during treatment
cost ~$350
90% of chronics have persistent circulating HCV RNA in spite of presence of ABs
allows you to know the genotype
need to know for interferon tx choice
six known with 50 subtypes
type Ib has the highest risk of hepatocellular cancer
type I hardest to clear
qualitative HCV RNA PCR = evidence or viral replication (if neg then resolved)
use qualitative HCV RNA test for those who test + for Anti-HCV (ELISA)
to determine if infection is active or resolved
use quantitative HCV RNA to monitor viral load and antiviral therapy
viral load under 2 million copies/ml have better response to treatment
viral load does not correlate wtih severity or prognosis (why not???)
< 1 million = low viral load
1-5 million = moderate
> 5 million = high load
DrJ observes that pts with high viral counts have less liver damage and vice versa
lower counts correlate with more damage
theory: liver damage mbdt high immune activation and cross reactivity
FIBROSURE
a new serum test that may replace biopsy
http://www.fairfoundation.org/news_letter/2010/02june/Fibrosure..pdf
correlates best at high and low levels of pathology
one OHSU physician thinks it may be more accurate than biopsy
for revealing overall level of liver cirrhosis
recommended for pts with viral hepatitis, not for pts with only alcoholic liver dz (why?)
ACUTE HEP C
acute infx usually undetected clinically, flulike sx
~85% of individuals prgress to chronic
in symptomatic acutes anti-HCV antibodies are detected in only 50-70% of pts
in the rest the antibodies emerge after 3-6 weeks
clinical course is mider than HBV
severe acutes mb indistinguishable from HAV or HBV except by serum testing
DZ PROGRESSION
after acute (asx or flulike) have long asymptomatic period
INCUBATION: 2-26 weeks, mean incubation of 6-12 weeks, 2-12 weeks from another class
20-30% develop liver cirrhosis over a period of 20 ish years
30 ish years to develop liver cancer
factors that accelerate dz progression:
genotype I, alcohol/chemicals, HIV, Hep A, other viral infx (EBV, HSV), high Fe, smoking, IR
genotype I is most common in US, about 75% of US Hep C cases
co-infx with HIV or Hep A mb lethal: recommend Hep A & B vaccine for all pts with Hep C
SX OF CHRONIC INFX
gradually increasing fatigue
headaches
poor sleep
digestive disturbances
mild dull liver area pain
depression
ADVANCED DZ SX
jaundice, cholestasis, hepatomegaly, portal HTN
ascites, hepatic encephalopathy
skin changes, hormonal and electrolye imbalances, clotting factor disorders
CONDITIONS ASSOCIATED WITH HEP C
essential mixed cryoglobulinemia and membranoproliferative glomerulonephiritis (strong assoc)
EMC = immune complexes block small BVs-->Raynaud's, neuropathies, purpura, glomerulonephritis
porphyria cutanea tarda
B-cell non-Hodgkin's lymphoma
Mooren corneal ulcers http://www.nejm.org/doi/full/10.1056/NEJM199307013290118
AI: thyroiditis, thrombocytopenia, Sjogren's, SLE, RA
hep c assoc w incr AI markers for come AI dz
!!! add hep C testing to AI protocol checklist
diabetes
fibromyalgia
pulmonary fibrosis
CONVENTIONAL TREATMENT
INTERFERON
pegylated interferon approved in 01
time release form = pegylation
one IM injx/wk
effective in sustained viral clearance (SVR) in 30% of pts !!! ONLY 30% CLEAR THE VIRUS
SVR = still clear 6 mo post tx
BAD SEs: myalgia, fever, anxiety, depression, severe fatigue, insomnia, hair loss, anorexia
genotype I: tx for 48 weeks
genotype II: tx for 24 weeks
IF THIS TX FAILS IT IS UNLIKELY TO BE EFFECTIVE A SECOND TIME
RIBAVIRIN
oral taken bid
if doing IFN then do ribavirin too
increases effectiveness of peginterferon to roughly 50%
(genotype I 40%, genotype 2-6 80%)
risk of birth defects: FERTILE FEMALES must use birth control
SEs: hemolytic anemia
TELAPREVIR
new tx, protease inhibitor
add this to IFN and ribavirin for max punch
not approved yet, but in use
2009 studies show genotype I clearance-->60-69%
SEs: pruritis, rash and anemia
ND TX = COMMON SENSE
quit drinking, smoking, avoid chems that challenge liver
liver support foods and supps
antioxidants bigtime
haven't mined the Jinnah hep C notes yet, he has doses, etc
NOTES FROM MILLER SHIFT 2/21/11
other liver challenges: acetomenophen, amanita/mycotoxins, benzenes/carbon tetrachloride, ketoconazole, fat soluble vits, Wilson's, hemochromatosis
hep A & E are only acute
B, C, and D can be chronic, B&D are BAD
B&D, acetomenophen and amanitas can cause fulminant liver failure
amoeba histolytica likes the liver, schistosomiasis also
mallory bodies = fibrin deposition found in alc, hemochromatosis, hep
LFTs
transaminases = enzymes released when hepatic cells injured or destroyed
bili--direct and indirect (unconj), bili over 2-3 will show jaundice
GGT
PT
hemorrhoids in portal HTN
asterixis = the liver flap, have pt put hands palm up and flick fingers down-->wrist fluctuance
sign of hepatic encephalopathy, and renal failure and wilson's
fetor hepatus? bad breath