Renal Transplantation for HIV/HCV
Co-infected Patients
Solid Organ Transplantation and People
With HIV: Ethics and Policy Conference
David Oldach & Robert Redfield
Institute of Human Virology, U of MD
Our Questions:

Are the inclusion/exclusion criteria adequate to
protect our subjects from progressive liver
disease?


(Currently, cirrhosis is our study-wide exclusion
criterion)
Given the poor efficacy and side effect profile of
current therapies, should RX decisions continue to
be left to the patient and their primary care
provider?
Relevant Background Information

Impact of HIV on HCV-attributed disease

HIV & HCV coinfection in Baltimore (Evelyn Jordan
center, institute of human virology)
HIV Influence on HCV Infection

Increased HCV viral load as immune
deficiency progressesn

Acceleration of natural history of HCV
(cirrhosis in 33% vs 11%)

Increased risk of liver failure (40% vs
6.8%)

Increased perinatal transmission of HCV
Eyster ME, et al, Blood 1994;84:1022-23
Bonacini M, Puoti M, Arch Intern Med 2000;160(22): 3365-73.
HCV-HIV Co-Infection in Baltimore

Among IVDA population, HCV transmission to 90%+ within
first year if needle sharing…

Prevalence of HCV co-infection at EJC (Institute of Human
Virology HIV clinic) approximately 60%….

Preliminary results of liver biopsies done to screen for
presence of significant liver disease….
---Biopsies NOT PERFORMED if--
frank cirrhosis present

HCV RNA negative

treatment not desired, or not reasonable
Liver Histology in HIV/HCV
Coinfected Patients

Over 36 months, approximately 75 liver biopsies
performed at IHV/U of MD for treatment evaluation
and clinical staging in HIV/HCV co-infected patients.

Biopsies scored using both the Knodell and
modified Ishak systems

ALT, CD4, HIV and HCV viral load data, and alcohol
consumption histories reviewed for each patient.
Knodell Scoring system for liver bx:

Four components:
Peri-portal piecemeal necrosis (0-10)
Intralobular degeneration and necrosis (0-4)
Portal inflammation (0-4)
Liver Bx Score for fibrosis ( 0-4)

Composite Scores (0-22)
Liver Biopsy Fibrosis Score
HIV/HCV Co-Infection Patients, EJC (n=42)
25
Number of Patients
20
15
10
5
0
0
N=22
1
2
3
4
N=14
N=3
N=3
N=0
Score for Fibrosis
Liver Fibrosis Scores: Ishak
N=50

Grade-0 (no fibrosis)
22 (44%)

Grade-1 (portal fibrosis, some)
16 (32%)

Grade-2 (portal fibrosis, most)
4
(8%)

Grade-3 (occasional P-P bridging ) 1
(2%)

Grade-4 (marked P-P bridging)
2
(4%)

Grade-5 (incomplete cirrhosis)
3
(6%)

Grade-6 (micronodular cirrhosis)
2
(4%)
Liver Biopsy - Knodell Score
EJC HIV/HCV Co-Infection Patients
25
Number of Patients
20
15
10
5
0
0-3
N=2
0
4-7
N=12
Total Score
8-12
N=10
ALT History For Liver Biopsy Patients
EJC HIV/HCV Co-Infection Patients
25
Number of Patients
20
15
10
5
0
never elevated
N=14
elevated, >ULN but <2X ULN
N=1
elevated, >2xULN
N=1
Fibrosis Score Grouped by ALT History
EJC HIV/HCV Co-Infection Patients
12
Number of Patients
10
8
6
4
2
0
0
1
2
3
Fibrosis Score
Never Elevated
Elevated, >ULN
but <2x ULN
Elevated, >2xULN
Total Score Grouped by ALT History
EJC HIV/HCV Co-Infection Patients
12
Number of Patients
10
8
6
4
2
0
0-3
Never Elevated
4-7
Total Score
Elevated, >ULN
but <2x ULN
8-12
Elevated, >2xULN
Summary

Data are preliminary, and are not from
HIV/HCV/ESRD population: however

At least 44% of patients studied to date have no
evidence of HCV related hepatic fibrosis, the single
best predictor of later development of significant
HCV related liver disease.

The prognostic significance of Grade-1 fibrosis in
these co-infected patients (an additional 32%)
remains uncertain.
Significance of Excluding HCV+
Patients From Consideration:
If HCV prevalence among HIV/ESRD patients in our population
mirrors that in the general HIV population in this urban setting,
up to 60% of candidates would be denied therapy….
Among that group, more than 1/3 may have liver histology and
ALT profiles that do not warrant a summary exclusion from
consideration….
If this patient population (HIV/HCV/ESRD patients) are excluded
from consideration, we will most certainly have to return to the
question at a later date….
Case Presentation for Discussion

58 y.o. male

HIV (dx, 1986, RF=MSM)


Rx- AZT, 3TC, Indinavir

CD4- 560 (nadir never <200)

HIV VL-<400 x >18 months)
ESRD (uncertain etiology))


Hemodialysis x 4 years
HCV (RF= above, +(transfusions 1973, 1981, 1986)

HCV VL- >1,000,000 RNA copies/ml
Case Presentation for Discussion

Liver biopsy

“chronic HCV with minimal inflammatory
activity and no significant fibrosis ”

ISHAK

Periportal Necrosis: 1 (0-4)

Confluent necrosis:
0 (0-4)

Apoptosis:
0 (0-4)

Portal inflammation: 1 (0-4)

Fibrosis:
0 (0-6)
First, Do No Harm
(Is withholding tx harmful?)

HCV + ESRD patients (without HIV infection) have
higher survival post renal transplant than HCV+
ESRD patients remaining on dialysis therapy….

(the same is true for patients with ESRD without HIV
or HCV infection)

It is unknown whether the same survival benefit can
be obtained in HIV/HCV/ESRD patients…..
First, Do No Harm
(Is offering tx harmful?)

Significant HCV related disease is more common
(occurs earlier, in a higher percentage of patients) in
HIV/HCV co-infected patients…

This individual, an HCV ‘carrier’, has no evidence of
HCV related disease, despite HIV infection and a
demonstrated high HCV viral load…

Would TX-related immunosuppression alter this
dynamic? Will accelerated HCV related disease
ensue?
Back to Question 1:

Are the inclusion/exclusion criteria adequate to
protect our subjects from progressive liver
disease?
Consider:

In general: limit renal transplantation only to those
individuals with ‘relatively benign’ histology: i.e.,
Fibrosis scores of 0, and perhaps stage 1.

Consider pre-transplant HCV treatment for all
patients, and require successful treatment for any
patient with fibrosis on biopsy (stage 1 or higher).

Consider on case-by-case basis offering renal
transplantation to individuals with prior HCV,
successfully treated, if with higher fibrosis scores.
Back to Question 2:

Given the poor efficacy and side effect profile of current
therapies, should RX decisions continue to be left to the
patient and their primary care provider?
Until better data are available regarding outcomes of HCV-rx
in HIV/HCV/ESRD, we do not believe that we can mandate
therapy for inclusion in the transplantation study.
However, we believe that most HIV/HCV/ESRD patients
should be offered IFN or PEG-IFN rx prior to
transplantation. We should approach this problem in the
same multi-center study context that we are now
proposing for transplantation itself.