Closing Plenary - 8th Annual Canadian Conference on HIV/AIDs Research
The Shifting EpidemicL HIV & hepatitis C Co-infection
Speakers: Jenny Heathcote, James Kreppner, Martin Schechter
Moderator: Mike O'Shaughnessy
Dr. Schechter conducted a review of the literature on the epidemiology of hepatitis C. Hepatitis C and hepatitis B are responsible for 75 percent of all liver Disease. HCV affects 3% of the world population. The highest prevalence includes Bolivia, Egypt, Mongolia and Tanzia. Countries with the prevalence rate of a greater than 5% are Egypt with 18.10%, Bolivia with the 16.3%, and Cameroon with 12.5%.
In North America the U.S. prevalence is estimated to be 1.8% or an approximate 3.9 million infected individuals. The bracket with the highest rate is a 32 to 49 year olds with 3 to 4%, blacks 30 to 49 years old are affected in the 9 to 10% range and Hispanics have to 2.1%.
In Canada the prevalence has been estimated in the 0.8% range. In BC the rate is1.4% and in Newfoundland it is 0.08%. There are approximately 240,000 Canadians infected with deep male: female ratio being 2:1. 36,000 or 15% were infected by a blood transfusion. 204,000 or 85% were infected by other means that include casual & regular IDU and others.
In British Columbia there was a prenatal study which found approximately 0.9% transmission in pregnant women. In Quebec they found a rate of 0.64% which was higher in Montreal.
The Phylogenic Tree of HCV Types
There are six broad general types in hepatitis C numbering from 1 - 6. 7,8,9,10 & 11 are subtype species. In Canada the most common are types 1a/b, 2a/b, and 3a.
Globally
Types 1, 2, & 3 are global.
Type 2 is global with the highest concentration in Japan and China
Type 4 is most common in Africa, Congo and Egypt.
In a study of blood donors (n=157) and patients (n=201)
Genotype 1= 62.8%
à the least responsive to therapy.2= 14.2%
3= 13.7%
4= 3.98%
257 people typed in Kelowna
1a= 48%
1b= 19%
Or 67% type 1 (total)
2a/b = 6/3%
3a= 22% IVDU associated mode of transmission or geographical evidence that it is growing? Possibly due to immigration??
Transmission
Vertical- earlier has higher rates - between 5-10%
A study in Tuscany (BMJ98)- 13 of 403 (3.2%) infants with HIV/HCV. All mothers were RNA positive.
0 from RNA negative mothers.
The transmission rate was higher in IDU.
Meta Analysis (Int J Epid 98)
28 studies with 978 woman- less than 10% transmission- 8.4%. When HIV infected, HCV transmission increased 3 fold.
NY Bellevue
54 co-infeted. 16 % HCV transmission and 7 fold increase when HIV infected.
Breast Milk
Conflicting evidence- some found low levels in colostrum (Saudi).
Sexual Transmission
Issues- types of tests and confirm tests. Lots of reporting biases. Confounded by IDU and sexual behaviour. Long term sex partners versus long term household/ occult/ parenteral exposure.
Early Studies
An increase in the lifetime number of partners lead to an increased risk of prevalence 1-10%. Increased risk in non IDU.
CDC (90-95)- 15% report sexual contact as the only risk factor.
NIH- 481 volunteers
Oxford 104 Hemophiliacs
2.9% in female partners. All had other risk factors.
California 170 heterosexuals
HCV associated with blood transfusion, IDU but NOT with sexual contact.
Italy 1379 same household.
Evidence conflicts.
Nosocomial Transmission
Dialysis- 10-20% (independent of blood transfusion). Dialysis associated acute outbreaks exist.
One surgeon in Spain infected 5 patients.
Occupational Transmission
HCW 1-3% which is double the population rate. As high as 10% when RNA positive needlestick.
Blood Transfusion- 90% effective. 15% of all infections in Canada.
Blood Products
Highly infective before 1985. Lead to a lot of co-infection with different subtypes of HCV.
VIDUS HCV data
Baseline prevalence- 1041 (83%) of 1256 HCV positive.
Incidence - 129 initially HCV negative with follow-up Kaplan Meier estimate at 24 months
à 48.4% +/-5.6% à Young drug user almost guaranteed to get HCV.CDC- acute cases from 91-95.
43% IDU, sexual 15%, occupational 4%, household 3%, unknown 1%.
High Risk 30%- previous IDU 11%, snorting 5%, prison 1%, low SES 9% and STD Hx 4%.
Dr. Jenny Heathcote-
HCV: The Effect of Co-infection with HIV
HCV is an RNA virus that is enveloped. It is 10,000 nucleotides. Several genotypes exist but there are many quasispecies. The virus mutates every 8 hours.
Testing
ALT and HCV RNA
High CD4 count is associated with low HCV RNA.
Correlation with HCV RNA and degree of liver disease. (?) Cirrhosis linked to high HCV RNA.
-No correlation thought with respect to immunocompetent patients.
-Immunocompromised is a different case (HIV)- high HCV RNA leads to direct viral cytotoxicity.
Chronic HCV infection- Determinants of Disease Severity
-male gender
-acquisition >50yr old
-alcohol > 50g/day (5oz liquor, 3 beer)
-immunocompromised (HIV)
-route of infection (blood transfusion asssociated with >risk of cirrhosis and therefore of liver cancer)
-extra hepatic manifestations.
Effect of Alcohol
If fibrosis is >1 and alcohol >50g/day
à increased risk.NIH Transfusion Data
568 acquired HCV mortality rate equal to 984 non HCV. Did NOT die of liver disease. Most died of disease that required the transfusion. 6% due to liver disease versus 3% in control.
Albumin is a good indicator of liver function. This decreases as liver function decreases.
Survival of Patients co-infected with HCV & HIV
Mortality due to liver failure.
Co-infection
-leads to more rapid progression of fibrosis
à increased risk of HCC and a decrease in the function of the liver.Therapy
Standard is IFN 3 million unites three times a week and 1200mg of ribavirin orally. 6-12 months dependent on genotype. Sustained response (SR) is 40% with genotype 1a but only 25-29% with genotype 1b and 7% with genotypes 2 & 3. [IFN alone 3 million unites three times a week SR is 20-30%.] A major complication of IFN is cytopenia and hemolysis
à anemia from the ribavirin. If the WBC gets too low it can lead to cytocemia. If the neutrophils get lower than 500à bacteremia. Also hemoglobin that is too low can lead to a heart attack.What is a SR?
Normal ALT and RNA negative one month apart and then again in 6 months.
IFN in HCV & HIV
A longer duration of treatment with IFN alone leads to better results.
Combo Treatment in HIV treated patients- ribavirin causes a decrease in AZT levels.
Trials are ongoing on the effectiveness and safety of the combination therapy in co-infection.
Current HIV antiretrovirals
à increase in CD4 count which has no effect on HCV. Increase in CD4 levels à increase in ALT levels. We don't know if this could be due to HAART and be independent of CD4 levels.Liver Transplant
At present they are not recommended for patients with end stage liver disease and HIV. Largely due to the immunosuppressive drugs that must be taken in organ transplants.
Effects of HCV on HIV
- causes an increase in viral load. Especially with CD4 <200 It
-enhances the rate of vertical transmission.
-promotes more rapid progression
à cirrhosis-increased mortality in patients with CD4 <200.
*concerns brought up that hepatologists have been basing treatment decisions on old data.
James Kruppner- Co-infected with HIV and HCV. Also has hemophilia.
-the Canadian policy is that HIV should not automatically rule out liver transplants but to date there have been none. In the past, the majority view was that HIV was a death sentence. James was told he had 6 months to live 10 years ago. In the Transplant Journal a survey was done in Renal Centers. No transplants were given to asymptomatic HIV patients.
-when we look at the poor survival rate of co-infected transplants- were they on HAART and what was the viral load?
Concerns-
-"wasting" livers
-immune suppression for transplants might increase HIV. How big a problem? Cyclosporin has been explored in HIV. Prednisone may also have antiretroviral effects. 53 transplant patients that got HIV were better off with cyclosporin than controls.
-HIV infection is no longer a death sentecne. Earlier studies showed a high mortality but did not include today's therapy for HIV. Therefore the data is no longer applicable.
-An organ transplant committee already exists. This issue must be dealt with in depth.
Discussion & Questions
11,900 IDU - over 2000 are HIV positive and almost ALL were HCV positive. How do we treat? What will the drug interactions be? Almost no data available on this but the government is not funding.
High rate of incidence in IDU- what is the possible explanation?
-after burner effect?
-very transmissable
à prevalence is 90%. In IDU HCV infection is merely a matter of time.Peter Philips
à do we know enough to say that patients with normal ALTs should not be treated?????Dr. Heathcote: The consensus statement says that there must be fibrosis on biopsy. Treatment is not recommended if the ALT is persistently normal REGARDLESS of biopsy. Tends to be more mild damage. We don't know if it is possible to stir up the HCV?
On induction therapy
à 12 weeks of induction therapy shows a greater percentage loss of HCV RNA but also an increase in the relapse rate.Long acting PEG IFN almost equally successful SR rate as the combination therapy with far fewer side effects.
PEG IFN plus ribavirin - current trials are underway.