Download HIV and viral hepatitis co

HIV and viral hepatitis co-infection
Wirach Maek-a-nantawat, MD.
11 July 2011
Contents
•
•
•
•
•
Epidemiology
Natural history
Lab for diagnosis and treatment
Prevention and vaccination
Postexposure prophylaxis for HCP
Epidemiology
• High prevalence of HBV infection in Thailand
Prevalence (HBV) 4.6-8%
 Prevalence (HIV-HBV)= 8 – 10%
 Genotype C (58-87%) predominating
genotypes B (11-24%) and A (1-5%)
 2 Subtypes: adr (80%) and adw (20%)
Genotype C significantly more common
in HCC patients <40 years old
Zone of High HBV prevelence (>8%)
Duanthanorm T, J Sci Soc Thailand 2004
Suwqnnqkarn K, et al. 2005
Tangkijvanich P, et al. World J Gastroenterol 2005
 Routes of transmission of HBV
coinfection
- IDU, MSM (high prevalence)
- Perinatal esp. young age
Prevalence of HCV/HIV co-infection
in Thailand
USA
16%*
89%†
Spain
69%*
88%†
Europe
34%*
75%†
Asia
26%
Australia
13%*
* General HIV-infected population
† IVDU population
•HIV/HCV infection = 7-9%
• Risk factor: IDU, MSM
• Among IDUs, HCV 49.5% in HIV
contrast with 2.2% in non-HIV
• Among Pregnant women, HCV
3.8% in HIV VS 0.3% in non-HIV
• Among military conscripts, HCV
8.4% in HIV VS 2.2% in non-HIV
• Genotype 3 most prevalent (70%)
- Genotype 6  30%
Chanbancherd P, et al SEA J Trop Med Public Health 2003
Beyrer C, et al. AIDS 2005
Jamieson DJ, et al. Infec Dis Obstet Gynecol 2008
Jatapai A, et al. Am J Trop Med Hyg 2010
Natural History of Chronic HBV
Non-replicative
Reactivation
Hepatic Flare
Natural Progression of CHB
15%–40% of CHB patients may experience disease progression
Liver
Cancer (HCC)
5%–10%
10%–15% in 5 yr
Chronic
Infection
30%
Cirrhosis
Liver
Transplantation
Death
23% in 5 yr
Acute flare
Liver Failure
Adapted from: Fattovich, et al. Gastroenterology. 2004;127:S35-S50. Torresi, et al. Gastroenterology. 2000;118:S83-S103.
Fattovich, et al. Hepatology. 1995;21:77-82. Perrillo, et al. Hepatology. 2001;33:424-432.
Factors Influencing Natural History of HBV
HBV viral load
Age at infection Host immune
status
Gender
HBV infection
-Perinatal
-IDU, MSM
-Heterosexual
Viral
mutations
Disease progression
HBeAg Alcohol
status
use
Fattovich. Semin Liver Dis. 2003;23:47-58.
Chen, et al. JAMA. 2006;295:65-73.
Liver cirrhosis
Hepatocarcinoma
Liver failure
Death
Co-infection with
HCV or HIV
Influence of HIV on HBV
• Longer period of acute infection with lower rates of
clearance of HBeAg
• Increased serum HBV DNA viral load
• Less hepatic necroinflammation in
immunocompromised
• Reactivation of hepatitis in asymptomatic carriers
• Increased liver injury associated CD4 cell counts
• Faster fibrosis cirrhosis and HCC
• Higher mortality and morbidity
Gilson RJ, et al. AIDS 1997
Manegold C, et al. CID 2001
Thio C, et al. Lancet 2002
Di Martino V, Gastroenterology 2002
Hepatitis B Virus – Replication
Export
Viral entry
Uncoating
ER
Assembly &
budding
Positive
strand
synthesis
HBsAg
Nuclear
import
Removal of
pregenome
cccDNA
Repair
Transcription
Viral accessory proteins:
HBeAg and HBX
5’
5’
3’
3.5 kb RNA
CL Thio, Clinical Update, August 2006.
3’
2.4/2.1 kb RNA
Translation
Negative
strand
synthesis
Encapsidation
HBV Treatment Landscape in 2010
Peginterferon
alfa-2a
Entecavir
Lamivudine
1990
Interferon
alfa-2b
1998
2002
Adefovir
2005 2006
Tenofovir
2008
Telbivudine
Undetectable* HBV DNA After 1 Yr of
Treatment
Undetectable* HBV DNA (%)
Not head-to-head trials; different patient populations and trial designs
HBeAg Positive
100
76
80
60
60
HBeAg Negative
100
80
67
88
90
93
60-73
63
51-63
60
40-44
40
40
20
0
25
13-21
LAM
ADV
20
LdT
ETV
TDF
PegIFN
0
LAM
ADV
LdT
*By PCR-based assay (LLD ~ 50 IU/mL) except for some LAM studies.
Lok AS, et al. Hepatology. 2007;45:507-539. Lok AS, et al. Hepatology. 2009;50:661-662.
ETV
TDF
PegIFN
Cumulative Rates of Resistance With
Oral Agents in Nucleos(t)ide-Naive
Patients
Not head-to-head trials; different patient populations and trial designs
Yr 5 Yr 6
Yr 1
Yr 2
Yr 3
Yr 4
1st LAM
24%
38%
49%
67%
70%
ADV
2nd
LdT
ETV
3rd TDF
0%
3%
11%
18%
29%
1.2%
0%
1.2%
1.2%
Drug
Generation
4%
0.2%
0%
17%
0.5%
0%
EASL. J Hepatol. 2009;50:227-242. Tenny DJ, et al. EASL 2009. Abstract 20.
Marcellin P, et al. AASLD 2009. Abstract 481. Heathcote E, et al. AASLD 2009. Abstract 483.
1.2%
Why treat HBV in HIV-infected persons
• Co-infection is common-10% of HIV-infected
• More rapid progression of liver disease
• Increased risk of liver-related mortality
• Increased risk of HAART-related
hepatotoxicity
• ?Immune reconstitution syndrome
Strategies to treat HBV and HIV
• All of the following should be used with HAART
• LMV naive
– First line: TDF plus LMV/FTC (emtricitabine)
– Other considerations
• Entecavir +/- TDF
• PEG-IFN
• LMV experienced
– First line: Add TDF to LMV
– Other considerations
• Entecavir 1.0 mg- resistance with LMV-R HBV
• Add ADV
Natural history of HCV infection
HCV infection
4%
20 yr
Chronic infection
70-85%
Hepatoma
17%
3.6%
Death
15-25 yr
15-25%
Cirrhosis
Resolved
Extrahepatic manifectations
Arthritis
Glomerulonephritis
Mixed cryoglobulinemia
13%
Complications
and Liver failure
Risk Factors Associated with
Transmission of HCV
 Transfusion or transplant from infected donor
 Injecting drug use
 Hemodialysis (yrs on treatment)
 Accidental injuries with needles/sharps
 Sexual/household exposure to anti-HCV-positive
contact
 Multiple sex partners
 Birth to HCV-infected mother
Impact of HIV on HCV
• HIV infection worsens HCV-related liver
disease (in pre-HAART era)
– ALT levels higher
– Fibrosis more severe
– Cirrhosis, liver failure, and HCC more common
– Death rates higher
– Vertical HCV transmission enhanced
Predictors of liver death in 812 HIV+ :
age adjusted HR for liver death of risk factors for liver injury according
to Cox’s proportional hazards model
Infectious Diseases Dept. – Brescia, Italy
Variable
HR
95% CI
p
HCVRNA+
10.35
2.46- 43.57
0.0014
Alcohol abuse°
2.71
1.47- 4.99
0.0014
HBsAg
2.91
1.42-5.98
0.0036
LTH*
2.25
1.02-4.98
0.0453
*LTH life threatening hepatotoxicity; time dependent covariate
°Daily alcohol consumption > 80 g (men) or 60 g (women) for > 5 years
Impact of HCV on HIV
• Impaired Th1 function in HIV infection affects
appropriate immune response to HCV
• Conflicting clinical results
• More rapid progression to AIDS or death for
HCV genotype 1
• Increasing HIV RNA and decreasing CD4 more
likely in co-infected pts
HCV Treatment Rationale
• HCV is curable disease.
• Treatment can improve HCV outcomes
– Decrease fibrosis
– Increase T-cell responsiveness to HCV antigens
– Decrease rate of fatal hepatocellular carcinomas
• Treatment may improve HIV outcomes
– Reduce hepatic toxicity of ARVs
HCV Treatment Options
• Pegylated Interferon-ribavirin combination
therapy
– Trials ongoing
– Preliminary findings encouraging
– Short duration for genotype 2/3
• New protease inhibitors: Boceprevir,
Telaprevir (combined with pegIFN+RBV for
genotype 1)
– No data
Host IL28B genotype and other important
characteristics to help predict response to therapy
Reginal distribution of IL-28B polymorphism
Thomas DL, et al. Nature 2009
Access to Therapy
Only a minority of HCV-HIV and HBV-HIV
coinfected are treated for their hepatitis.
To increase the applicability and availability
of treatment especially in vulnerable
groups such as in immigrants, IDUs,
prisoners, people with psychiatric illnesses
and people with excessive use of alcohol
Lower rate of screening for hepatitis
virus infection
• 58% were screened for HBV and 43% screened for HCV
infection in tertiary care institutes
• 9.7% had HBV infection and 8.8% had HCV infection
• LEE prior to the initiation of ART and undetectable HIV RNA at
screening significantly associated with the finding of HBV coinfection.
• The limited resources for HIV, HBV and HCV treatment & care
in a resource-limited setting and unawareness of long term
complications may affect rate of screening for HBV and HCV
infections.
Sungkanuparph S, et al. Southeast Asian J Trop Med Public Health 2008
Chotiprasitsakul D, et al. J Infect Dis Antimicrob Agents 2010
HBV Virological Assessment
A. Immunological Assays
1. HBsAg/Anti-HBs
2. HBeAg/Anti-HBe
3. Anti-HBc and Anti-HBc IgM
B. Molecular or nucleic acid assays
1. Quantitative HBV-DNA
2. HBV Genotyping
3. HBV Resistance evaluation
(sequencing Pol)
Diagnosis
• HBsAg - Used as a general marker of infection.
• HBsAb - Used to document recovery and/or immunity to HBV
infection.
• anti-HBc IgM - Marker of acute infection.
• anti-HBc IgG - Past or chronic infection.
• HBeAg - Active replication of virus and therefore infectiveness.
• Anti-HBe - No longer viral replication. However, the patient can
still be positive for HBsAg which is made by integrated HBV.
• HBV-DNA - Indicating active replication of virus, more accurate
than HBeAg especially in cases of escape mutants. Used
mainly for monitoring response to therapy.
Acute Hepatitis B with Recovery
Incubation
Acute infection
Early recovery
Recovery
4-12 weeks
(2-12 weeks)
(12-24 weeks)
(24-48 weeks)
Symptoms
HBeAg
HBV-DNA
anti-HBe
Total anti-HBc
Titer
0
4
anti-HBs
IgM anti-HBc
HBsAg
8
12
16
20
24
28
32
Weeks after Exposure
36
52
100
Typical Serologic Course in Chronic HBV Infection
Incubation
4-12 weeks
Acute
(6 months)
Chronic
(Years)
HBeAg
anti-HBe
HBV-DNA
HBsAg
Total anti-HBc
Titer
IgM anti-HBc
0
4
8 12 16 20 24 28 32 36
52
Weeks after Exposure
Years
Isolated antibody to HB core antigen
• Frequently detected in HIV/HBV co-infection
(20%-30%)
• IVDU (OR 30.8, p < 0.001) and anti-HCV
seropositive (OR 6.7, p = 0.002) were
independent risk factors
• Low anamnestic response to hepatitis B
vaccination (7%)
Jongjirawisan Y, et al. J Med Assoc Thai 2006
Challenges in HBsAg Serological Diagnosis
• Analytic sensitivity: WHO standard 0.028–0.156IU/ml
Abbott ad standard 0.18–0.73 ng/ml
Abbot ay standard 0.13–0.26 ng/ml
• Clinical sensitivity:
89.3–99.8%
• Specificity:
97.6–100%
• Surface mutants
• Detection of HBV serotypes
Initial serologic assessment in HBV/HIV
HBV history and markers in Thailand
• Significant higher ALT in genotype C than B
• HBeAg significantly more frequent in genotype C than B patients
(50.8 VS 30.8%,p=0.03)
• Levels of HBV DNA were comparable in both genotypes
• Genotype C showed higher ALT levels and more necroinflammation
activity and fibrosis of liver
• Progression to cirrhosis and HCC trended to be younger in
genotype C
• Lower response rate to IFNα therapy in genotype C
• The risk of development of HCC may not be different between
genotypes B and C-related chronic liver disease.
Tangkijvanich P, 2004
Tangkijvanich P, 2005
Available HBV DNA Assays
Artus Biotech
Real Art HBV LC PCR
HBV Digene Hybrid-Capture I
Digene Corp.
HBV Digene Hybrid-Capture II
Ultra-Sensitive Digene
Hybrid-Capture II
Roche
Molecular
Systems
Amplicor HBV Monitor
Cobas Amplicor HBV Monitor
Cobas Taqman 48 HBV
Bayer Corp.
Versant HBV DNA 1.0 NA
Versant HBV DNA 3.0
10 102 103 104 105 106 107 108 109 1010
HBV DNA IU/mL
Other HBV DNA Assays not CE marked are NAXCOR and TMA-HPA
Locarnini et al., Antiv.Therapy 2004
1
HBV DNA Log copies/mL
HBV DNA levels in HBV chronic carriers
10
9
8
7
6
5
4
3
2
Chronic
Chronic
Hepatitis B Hepatitis B
HBeAgHBeAg+
Liquid Hybridization
bDNA - Hybrid Capture 1
Hybrid Capture 2
Amplicor PCR
Inactive
carriers
COBAS PCR
Villeneuve JP et al. Gastroenterology 1994; Martinot –Peignoux M et al. J.Hepatol 2002;
Hsu et al Hepatology 2002; Mommeja-Marin H et al. Hepatology 2003; Manno, Gastroenterology 2004
Serum HBV DNA (copies/ml)
HBV mono-infection:
HBV DNA and CHB
1010
109
108
107
106
105
104
103
102
In HIV co-infected ?
CHB
HBeAg +
CHB
HBeAg –
~30%
Virological
objective
Inactive
Patients
Villeneuve JP et al. Gastroenterology 1994. Martinot –Peignoux M et al. J.Hepatol 2002. Hsu YS et al.
Hepatology 2002. Mommeja-Marin H et al. Hepatology 2003
Management plan
Antiviral Treatment Effect
Antiviral treatment effect is defined as a sustained ≥1
log10 IU/ml reduction of HBV DNA from baseline
levels during therapy and within 3 months of starting
therapy. A decrease of ≥1 log10 IU/ml can be used to
assess the early virological response. Development of
resistance while on treatment is characterized by a
rise of ≥1 log10 IU/ml.
Primary Antiviral Treatment Failure
Log HBV DNA
+1.0
0.0
Antiviral Drug
1 log
-1.0
-2.0
-3.0
-4.0
Secondary Antiviral Treatment Failure
Log HBV DNA
+1.0
0.0
Antiviral Drug
1 log
-1.0
-2.0
-3.0
-4.0
1 log
Demonstration of HBV Resistance in Clinical Practice with
Approved Anti-HBV Drugs
1. Diagnose primary or secondary treatment failure
- HBV DNA assay
2. Eliminate non-HBV-related causes of failure
- drug dosage
3. Demonstrate emergence of HBV mutant during
therapy
- direct sequencing
Two options:
•
The selected mutant is known to be associated with viral resistance to
the drug: HBV resistance is diagnosed
•
The selected mutant is not known to be associated with
viral resistance: further characterization is needed
Antiviral Resistance Testing
• Genotypic Assays
• Phenotypic Assays
• Virtual Phenotyping
Genotypic Assays
Genotyping
– Analysis of the nucleic acid sequence of the region of the HBV
genome that is targeted by the antiviral of interest
– Identify signature sequences and/or amino acid substitutions at
specific positions
Assays
– Direct sequencing of PCR products (population)
• Full sequence of the analysed fragment
• Detect any mutation
– Line Probe Assay (LiPA)
• Detect selected known mutations associated with drug resistance
– Sequencing molecular clones (quasispecies)
Genotypic Assays
TRUGENE HBV 1.0
Sequences a region of 507 nucleotides
– RT codons 110 – 278
– S protein codons 100 – 227
Generates a genotype report (genotypes A–H)
– Based on closest match to a panel of consensus reference
sequences (% homology)
Generates a mutation report
– A list of observed changes when compared against the closest
match reference sequence, sorted by published, unpublished
and silent changes
INNO-LiPA HBV DR v2
• Can detect:
– Wild-type
– Mutant motifs for LAM
resistance and compensatory
mutations:
• M204V/I/S, L80V/I, V/G173L, L180M
– ADV resistance mutations:
• A181T/V and N236T
INNO-LiPA HBV DR v2
prototype strip
Doutreloigne J et al., AASLD 2004

600 500 -
ALT (U/L)
Example of a
patient
treated with
LAM

-7
200 -
-6
150 -
-5

100 50 -
01
INNO-LiPA assay:
Results
-8
148
325

407

450

519
-4
-3
542
Codon 180 L
L
L/M
M
M
M
M
Codon 204 M
M
M
M
M
M/V
V
Codon 207 V
V
V
V
V
V
V
HBV DNA log copies:mLU/ml
Lamivudine 100mg/day
Days
YMDD (V204)
mutation is
detected on
day 450
INNO-LiPA HBV Genotyping
Identification of HBV genotypes A to G
Halfon et al., EASL 2003.
Antiviral Resistance Testing
Phenotypic Assays
Phenotyping
– Measure the ability of viruses to grow in various
concentrations of antiviral drugs
– Could predict the clinical response to these drugs
Assays
–
–
–
–
Cell-culture-based
Enzymatic
Animal models
Patient-derived clones
Antiviral Resistance Testing
Phenotypic Assays
IC50
– Concentration of drug that inhibits 50% of viral replication
Fold increase in IC50 or fold resistance
– Ratio of the IC50s of the tested virus and the reference virus
(wt)
% viral replication
100
75
50
25
0
0.001
0.01
0.1
1
IC50
Drug Concentration
10
HBV Phenotyping Using
Patient-Derived HBV Clones
Patient
Serum
PCR
Cloning
Whole genome
HBV clones
Transient
Transfection
(Fitness assay)
Southern
analysis
HepG2
• Clones reliably obtained when viral load >105
• On average, 70% of clones replicate in vitro
Yang H et al., EASL 2003
Virtual Phenotyping
• Matching polymerase sequences from a HBV strain to (near)
identical sequences with known antiviral drug phenotype
held in a large database
• A “virtual” phenotype is assigned by extrapolation
– providing a mean IC50 of all matched sequences
– and a fold change to wild-type
• If insufficient matches are found in the database
– a “rules-based” interpretation is provided
• Virco, SeqHepB (VIDRL)
The complex natural history of HBV
serological markers
Acute hepatitis B
Immunological
Immune response tolerance
Chronic hepatitis B
HBeAg (+)
Resolution
HBV DNA (+)
ALT normal/raised
Spontaneous
Anti-HBe (+)
HBV DNA (+)
ALT raised
Anti-HBe (+)
HBV DNA (+)
ALT raised
Hepatitis
Immune response
Viral mutations
Antiviral therapy
HBsAg +
Anti-HBe (+)
HBV DNA (low)
Immune response
Cirrhosis
Hepatic
decompensation
HCC
Transplant
Occult HBV Infection
Persistence of HBV genomes in liver tissue
(± serum) by PCR-based methods in the absence of
HBsAg in serum
Chronic hepatitis
HCC
Haemodialysis pts
32.8%
63.5%
3.5 - 36 %
IDU
45 %
Haemophiliac pts
51.2 %
Cacciola et al, NEJM 1999
Pollicino et al, Gastroenterology 2004
Minuk et al, Hepatology 2004
Besissik et al, J Hepatol 2003
Torbenson et al, Hepatology 2004
Toyoda et al, J Med Virol 2004
Chronic hepatitis B: Criteria for HCC
Surveillance
• Evidence supports surveillance in:
Cirrhosis
Family history of HCC
Asian men over 40 and women over 50 years age
Africans over 20 years age
>40 years age with high HBV DNA and high ALT
• Frequency: Every 6 months
• Method: Liver ultrasound +/- alpha-fetoprotein
(Bruix & Sherman 2005)
Thai Guidelines for HIV/HBV coinfection
• All HIV/HBV infected individuals should be evaluated: LFT, αFP, HBe Ag, (±HBV DNA)
advised:
- alcohol abstinence, safe sex practices,
Hep A vaccination (if HAV Ab neg)
• If ART or HBV treatment (+hepatitis) is indicated, the
prefered regimen should include TDF/3TC or FTC as a
background regimen.
• If TDF, 3TC or FTC is discontinued, need close monitoring
for hepatic flare or consider using adefovir dipivoxil or
telbivudine for preventing hepatic flares
National guidelines on HIV/AIDS diagnosis and treatment: Thailand 2010
Hepatitis B vaccination
• Thailand adopted the policy for HB immunization in
1988
• Universal HB vaccination
of newborns has been
integrated into the
national expanded
programme on immunization (EPI) since 1992.
• Coverage of HBV immunization in group age<18 yrold estimated 71.7%-91.3%
Chongsrisawan V, et al. 2006
Hepatitis B vaccination in HIV on ART
• Serologic response 54.8-71.4%
• CD4 counts or NNRTI may associate with
response of surface seroconversion
• Coverage of vaccine among HIV infection?
- lower rates of antibody response in HIV
- lower levels of antibody response in HIV
• Flare of HBV in cases of occult infection with
isolated core antibody
HIV-NAT unpublished data
Paitoonpong L, et al. 2008
Hepatitis C Virus Infection
Typical Serologic Course
Symptoms
antiHCV
Titre
ALT
Normal
2 3 4
0 1 2 3 4 5 6 1 Years
Months
Time after Exposure
Hepatitis C Virus Infection: Diagnosis
•
•
•
•
•
HCV antibody
HCV viral load
HCV genotype
Liver function tests
Liver biopsy is gold standard for assessing disease
status
– ALT and AST do not predict liver histology
– HCV RNA does not predict liver histology or outcomes
Laboratory Diagnosis
• HCV antibody - generally used for diagnosis
Not useful in the acute phase as it takes at least 4
weeks after infection before antibody appears.
• HCV-RNA - various techniques are available e.g.
PCR and branched DNA. May be used to diagnose
HCV infection in the acute phase. However, its main
use is in monitoring the response to antiviral therapy.
• HCV-antigen - an EIA for HCV antigen is available. It
is used in the same capacity as HCV-RNA tests but is
much easier to carry out.
Diagnostic tests
http://consensus.nih.gov/2002/2002HepatitisC2002116html. Accessed April 10, 2011.
Antibodies do not identify the presence of the virus or distinguish between
acute, chronic or resolved infection
HCV Diagnosis
• Enzyme immunoassays ( 2nd or 3rd gen EIA)
– Initial screening test for patients with liver disease
– False positives in low risk patients
– Occasional false negatives, esp. With HIV+
• Recombinant immunoblot assays (RIBA)
– Confirmatory test if EIA positive in low risk pt
• HCV RNA by PCR
– Confirmatory if RIBA is “indeterminant”
OraQuick HCV Rapid Test
» The first Rapid HCV Test
Approved for Sale in the U.S.
» uses whole blood drawn from a vein, does not require
laboratory processing, and returns results in about 20
minutes
Detection of antibodies to HCV (anti-HCV)
in HIV/HCV co-infected individuals
Anti-HCV screening with 3rd generation EIA
944 HIV-negative IDU
119
anti-HCV -
1
HCV-RNA +
825
anti-HCV +
118
HCV-RNA -
559 HIV-positive IDU
547
anti-HCV +
1
HCV-RNA +
12
anti-HCV -
11
HCV-RNA -
* Both anti-HCV negative HCV-RNA positive individuals became anti-HCV positive on their next visit
Thio et al, J Clin Microbiol 2000;38:575-7
Qualitative Detection of HCV-RNA
HCV monoinfected vs. HIV/HCV coinfected
HCV mono-infection
Anti-HCV positive
HCV/HIV co-infection
Anti-HCV positive
Confirm HCV clearance in acute hepatitis
Confirm HCV clearance in acute hepatitis
Confirm HCV replication if other
causes of liver disease
Confirm HCV replication if other
causes of liver disease
Confirm HCV clearance at the end of
treatment and follow-up
Confirm HCV clearance at the end of
treatment and follow-up
Anti-HCV negative
Anti-HCV negative
Acute hepatitis (window phase)
Acute hepatitis (window phase)
Severe immunosuppressed patients
Liver test abnormalities
HCV RNA Quantification Assays
10
102
103
104
105
106
107
Cobas Amplicor HCV
Monitor v2.0 (Roche)
LCx HCV RNA
Assay (Abbott)
Versant HCV RNA
3.0 (Bayer)
SuperQuant (NGI)
Cobas Taqman 48
(Roche)
HCV Quant ASR
(Abbott)
95% of untreated hepatitis C
108
Tests for treatment monitoring
Quantitative HCV-RNA
HCV mono-infection
HCV/HIV co-infection
HCV-RNA concentration
HCV-RNA concentration
Before therapy (predictor of response)
Before therapy (predictor of response)
Week 12 after treatment initiation
Week 12 after treatment initiation
Co-infected pregnant mother (risk of
transmission)
Which role for HCV genotypes ?
• Independent predictors of response to therapy
• Some correlation with liver disease outcome
in HIV-negative patients
G3
steatosis
G2
hepatitis flares
Lonardo, Gastroenterology 2004; Rumi, Gut 2005
Predictors of Response
 Patients infected with genotype 2 and 3.
 low viral load (< 800,000 IU/ml).
 Absence of cirrhosis.
 Age <40 years.
 High ALT levels (>3x ULN).
 RVR at week 4 after RX
Thai Guidelines for HIV/HCV
co-infection
• All HIV/HCV infected individuals should be encouraged to get
early ART and HCV treatment
• If ART is indicated, should avoid using NVP, d4T, ddI (NRTIs).
• Avoid using AZT, d4T, ddI in a case treated with RBV
• Should monitor AST, ALT after ART at 1 mo and every 3 mo.
• Elevation of ALT ≥ 5 times ULN, investigate for HAV, HBV,
alcohol, liver disease, and may discontinue ART if suspecting
drug related causes.
National guidelines on HIV/AIDS diagnosis and treatment: Thailand 2010
PEP for HCP
Concentration of Hepatitis B Virus
in Various Body Fluids
High
Moderate
blood
serum
wound exudates
semen
vaginal fluid
saliva
Low/Not
Detectable
urine
feces
sweat
tears
breastmilk
Occupational Blood-borne Exposures
Relative Risk of Seroconversion with Percutanous Injury
Seroconversion %
50
50%
40
30
30%
20
10
2%
0.3%
0
HIV
HCV
.
From:
CDC. MMWR 2001;50 (RR11):1-42.
HBsAg+
HBeAg-
HBsAg+
HBeAg+
Risk for HBV in HCP
• Needle injuries with blood containing HBs Ag+
and HBe Ag+
– Developing clinical hepatitis 22-31%
– Seroconversion 37-62%
• Needle injuries with blood containing HBs Ag+
and HBe Ag – Developing clinical hepatitis 1-6%
– Seroconversion 23-37%
Werner BG, Grady GF. Ann Intern Med 1982
Hepatitis B can be prevented!
If you have never had hepatitis B,
you can get 3 shots . . .
1
2
3
. . . and get long lasting
protection.
How Is HCV Transmitted?
• Infected blood
– Needlestick
– Needle sharing
– Transfusion
• ?Infected body fluids
– Amniotic fluid
– Breast milk
– semen
Risk for HCV in HCP
• Percutaneous exposure from an HCV person is
1.8%
• Limited data on survival of HCV in the
environment
• Risk for transmission from exposure to fluids
other than blood expected to be low
MMWR 2001
Who Should Be Tested?
• Drug users
• Recipients of blood products or organ
transplant before 1992
• Long-term partners of infected individuals
• Persons with occupational exposures
• Children born to HCV-infected mothers
• HIV-infected individuals
Consider Testing For
• Persons with tattoos or body piercing
• Persons with multiple sexual partners
• Tissue transplant recipients
Take Home
• HBV/HCV + HIV is common
Screen For HBV in HIV infection
• HBV vaccination for all HIV+ patients who are HBsAg• Treat HBV where indicated and carefully select your
nucleotides
Screen for HCV in selected patients with risks
• Treat HCV where indicated/possible
• Beware of hepatotoxicity and dangerous
combinations