Transcript The True Meaning of Trismus

Hepatitis C and HIV Co-Infection
Robert Bradsher, M.D.
Director, Division of Infectious Diseases
University of Arkansas for Medical Sciences
Hepatitis C
adapted from
Hepatitis Branch
Centers for Disease Control and Prevention
Features of Hepatitis C Virus Infection
Incubation period
Average 6-7 weeks
Range 2-26 weeks
Acute illness (jaundice)
Mild (<20%)
Case fatality rate
Low
Chronic infection
75%-85%
Chronic hepatitis
70% (most asx)
Cirrhosis
10%-20%
Mortality from CLD
1%-5%
Chronic Hepatitis C
Factors Promoting Progression or Severity
• Increased alcohol intake
• Age > 40 years at time of infection
• HIV co-infection
• ?Other
• Male gender
• Other co-infections (e.g., HBV)
Serologic Pattern of Acute HCV Infection
with Recovery
anti-HCV
Symptoms +/-
Titer
HCV RNA
ALT
Normal
0
1
2
3
4
Months
5
6
1
2
3
Years
Time after Exposure
4
Serologic Pattern of Acute HCV Infection
with Progression to Chronic Infection
anti-HCV
Symptoms +/-
Titer
HCV RNA
ALT
Normal
0
1
2
3
4
Months
5
6
1
2
3
Years
Time after Exposure
4
Hepatitis C Virus Infection
United States
New infections (cases)/year 1985-89
1998
242,000 (42,000)
40,000 (6,500)
Deaths from acute liver failure
Rare
Persons ever infected (1.8%)
3.9 million (3.1-4.8)*
Persons with chronic infection
2.7 million (2.4-3.0)*
Of chronic liver disease - HCV-related
40% - 60%
Deaths from chronic disease/year
8,000-10,000
.
*95% Confidence Interval
Transmission of HCV
• Percutaneous
•
•
•
•
Injecting drug use
Clotting factors before viral inactivation
Transfusion, transplant from infected donor
Therapeutic (contaminated equipment, unsafe
injection practices)
• Occupational (needlestick)
• Permucosal
• Perinatal
• Sexual
Reported Cases of Acute Hepatitis C by
Selected Risk Factors United States 1983-1998*
Percentage of Cases
80
70
Injecting drug use
60
50
40
30
20
Sexual
10
Health related work
Transfusion
0
83-84
85-86
87-88
89-90
91-92
93-94
Year
* 1983-1990 based on non-A, non-B hepatitis
Source: CDC Sentinel
Counties Study
Source: CDC Sentinel Counties
95-96
97-98
Sources of Infection for
Persons with Hepatitis C
Injecting drug use 60%
Sexual 15%
Transfusion 10%
(before screening)
Other* 5%
Unknown 10%
*Nosocomial; Health-care work; Perinatal
Source: Sentinel Counties, CDC
Source: Centers for Disease Control and Prevention
Posttransfusion Hepatitis C
All volunteer donors
HBsAg
% of Recipients Infected
30
25
20
Donor Screening for HIV Risk Factors
Anti-HIV
ALT/Anti-HBc
15
10
Anti-HCV
5
0
1965
1970
1975
1980
1985
1990
Improved
HCV Tests
1995
2000
Year
Adapted from HJ Alter and Tobler and Busch, Clin Chem 1997
Injecting Drug Use and
HCV Transmission
• Highly efficient among injection drug users
• Rapidly acquired after initiation
• Four times more common than HIV
• Prevalence 60-90% after 5 years
Nosocomial Transmission of HCV
• Recognized primarily in context of
outbreaks
• Contaminated equipment
• hemodialysis*
• endoscopy
• Unsafe injection practices
• plasmapheresis,* phlebotomy
• multiple dose medication vials
• therapeutic injections
* Reported in U.S.
Sexual Transmission of HCV
• Case-control, cross sectional studies
• infected partner, multiple partners, early sex,
non-use of condoms, other STDs, sex with
trauma
• MSM no higher risk than heterosexuals
• Partner studies
• low prevalence (1.5%) among long-term
partners
• infections might be due to common percutaneous exposures
(e.g., unsafe injections, drug use)
• male to female transmission more efficient
• more indicative of sexual transmission
Sexual Transmission of HCV
• Occurs, but efficiency is low
• Rare between long-term steady partners
• Factors that facilitate transmission between
partners unknown (e.g., viral titer)
• Accounts for 15-20% of acute and
chronic infections in the United States
• Sex is a common behavior
• Large chronic reservoir provides multiple
opportunities for exposure to potentially infectious
partners
HCV Counseling
Preventing HCV Transmission
Avoid Direct Exposure to Blood
• Do not donate blood, body organs,
other tissue or semen
• Do not share items that might have
blood on them
• personal care (e.g., razor, toothbrush)
• home therapy (e.g., needles)
• Cover cuts and sores on the skin
HCV Counseling
Sexual Transmission of HCV
Persons with One Long-Term Sex Partner
• Do not need to change their sexual
practices
• Should discuss with their partner
• Risk (low but not absent) of sexual
transmission
• Routine testing not recommended but
counseling and testing of partner should be
individualized
• May provide couple with reassurance
• Some couples might decide to use barrier precautions to
lower limited risk further
HCV Counseling
Sexual Transmission of HCV
Persons with High-Risk Sexual Behaviors
• At risk for sexually transmitted diseases,
e.g., HIV, HBV, gonorrhea, chlamydia, etc.
• Reduce risk
•
•
•
•
Limit number of partners
Use latex condoms
Get vaccinated against hepatitis B
MSMs also get vaccinated against hepatitis A
HIV & HCV Co-Infection
HIV & HCV Co-Infection
• As death rates from HIV have declined
with HAART, a new focus on morbidity
and mortality from Hep C and ESLD
• Interactions between HIV and Hep C
influence diagnosis, evaluation,
treatment, and overall management
HIV & HCV Co-Infection
• Viral Replication
• HIV (retrovirus) and HCV (flavivirus) are
prolific RNA viruses.
• HIV produces 1010 virions per day.
• HCV produces 1012 virions per day.
• In seting of HIV, HCV RNA levels are even
greater.
• The level of HCV viremia is inversely
correlated with CD4 counts.
HIV & HCV Co-Infection
• Genetic Heterogeneity
• HIV & HCV are single stranded RNA viruse with
lack of DNA proof reading mechanisms
• Leads to genetically distinct viral variants called
quasi-species
• HIV: each and every possible single-point mutation
occurs from 104 to 105 times per day
• HCV: Random nucleotide errors from 10-2 to 10-3 per
site per year.
HIV & HCV Co-Infection
• Epidemiology
• Coinfection is common since both share similar
routes of transmission
• In USA, approximately 30% of 1M HIV infected
also have HCV
• Ranges from 72% in IVDA to 3% in patients at
lower risk.
• HCV much more efficient at IV transmission
• HIV much more efficient at sexual transmission
HIV & HCV Co-Infection
• Epidemiology
• Garten RJ, Zhang J, Lai S, Liu W, Chen J, Yu
XF. Coinfection among IDU in Southern China
Clinical Infectious Diseases 2005; 41 (Suppl 1) S18-24
• Longitudinal cohort of 547 IDU pt from Guangxi
• Coinfection in 17.6% of IDUs.
• HCV in 95% of HIV + pt and 70% of HIV - pt.
• HIV in 23% of HCV + pt and 3.6% of HCV - pt.
• HCV genotypes of 6a, 3b, 1a > rest
HIV & HCV Co-Infection
• Diagnosis
• HCV EIAs have decreased sensitivity with HIV
• HIV patients have lost antibody to HCV even
though still viremic with HCV
• HIV patients more likely to be viremic with
HCV than those without HIV
HIV & HCV Co-Infection
• Effect of HIV on Natural History of HCV
• HCV progresses to cirrhosis faster with HIV
• More severe necroinflammatory changes
• Suppression of HIV with HAART may
decrease the rate of liver disease
• HIV causes HCV progression to
decompensated ESLD, hepatocellular
carcinoma and death
HIV & HCV Co-Infection
• Effect of HCV on natural history of HIV
• Conflicting results on HIV progression
• Cohort of 1955 pts, no difference
• 3111 pts on HAART, HCV was independent risk
factor on progression to OI or death
• Large VA observation study, no difference
HIV & HCV Co-Infection
• Effect of HCV on natural history of HIV
• Miller JF, Haley C, Koziel MJ, Rowley CF. Meta-analysis of impact
of HCV on immune restoration in HIV pts who start HAART.
Clinical Infectious Diseases 2005; 41:713-20, (1 September)
• 8 trials of 6216 pt analyzed. Mean increase in
CD4 count 33 cells/mm3 less than HIV pt
without HCV
• Suggests that less immune reconstitution with
HAART than HIV alone
HIV & HCV Co-Infection
• HCV and hepatotoxicity with HAART
• HCV increases risk of hepatotoxicity with
HAART although some only found this with
ritonavir and nevirapine
• Estimates of 10% develop severe toxicity
• Benefit of HAART suggests that therapy
should not be withheld from HIV pt
• Hepatotoxicity could be immune reconstitution
HIV & HCV Co-Infection
• Therapeutic Regimens for HCV
• Eradication of HCV is possible, not HIV
• Benefit may also exist even in pt without
eradication of HCV
• May protect against cirrhosis in coinfected
• Trials demonstrate superiority of pegylated
interferon and ribaviran
HIV & HCV Co-Infection
• Therapeutic Regimens for HCV
• Standard interferon monotherapy
• Response depends on immune status – 33%
• Standard interferon plus ribaviran
• Sustained response depended on HCV type
• Pegylated interferon plus ribaviran
• Response rates towards ~ 45%
HIV & HCV Co-Infection
• Therapeutic Regimens for HCV
•
•
•
•
Myriad of potential side effects
Significant weight loss
Decline in CD4 counts but not percentage
Thrombocytopenia, depression, flu-like Sx
with interferon may be worse with HIV
• Ribavirin may increase the mitochondrial
damage from NRTIs: lactic acidosis,
pancreatitis, myopathy, neuropathy
HIV & HCV Co-Infection
• Summary
• Coinfection is common since both share
similar routes of transmission
• Multiple studies indicate HCV & HIV
progresses faster to cirrhosis and ESLD
• Counsel patients against alcohol use
• HAART benefit outweighs risk of toxicity
• HCV treatment experience is accumulating
and appears that peg-IFN & ribavirin is more
effective than standard IFN