Transplant-Related Accelerated Progression of Hepatitis C
| Status: | Completed |
|---|---|
| Conditions: | Gastrointestinal, Hepatitis, Hepatitis |
| Therapuetic Areas: | Gastroenterology, Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | June 2006 |
| End Date: | January 2009 |
Transplant-Related Accelerated Progression of Hepatitis C (TRAP-C)
This study will explore why severe scarring of the liver (cirrhosis) develops so rapidly in
hepatitis C-infected patients who have had a liver transplant and possibly in kidney
transplant patients as well. The hepatitis C virus (HCV) can cause cirrhosis in about 20
percent of infected persons. Generally, it takes 20 years or more for cirrhosis to develop.
After liver transplantation, however, patients may develop cirrhosis in as little as 5
years. Cirrhosis does not develop as rapidly in kidney transplant patients, but it may
develop faster than in people who do not undergo transplantation. The study will look at the
possible role of immune-suppressing medications given to liver and kidney transplant
patients in increasing the severity of hepatitis C infection and in speeding the cirrhotic
process.
Patients 18 years of age and older with chronic HCV infection who require a liver transplant
for end-stage liver disease or a kidney transplant for kidney failure may be eligible for
this study. Liver transplant patients are recruited from the Inova Fairfax Liver Transplant
Center in Fairfax, Virginia, and from the Georgetown University Medical Center Liver
Transplant Institute in Washington, D.C. Kidney transplant patients are recruited from the
Transplantation Branch of the National Institute of Diabetes and Digestive and Kidney
Diseases.
Participants undergo the following procedures:
- Regular care: As part of their regular transplant-related treatment, patients have a
medical history, physical examinations and blood draws before their transplant and on
regularly scheduled visits after the transplant.
- Blood draws for research: Special blood tests are done to measure the immune response
to HCV. They measure the amount of HCV in the blood, the number of HCV strains present
and how they change over time and the HCV antibodies in the blood.
- Liver biopsies: This procedure is done at 3 months, 1 year, 3 years and 5 years after
the transplant to determine the extent of scarring of the liver and to study the immune
responses within the liver, the proportion of liver cells infected with HCV and the
presence of scar-producing cells. The biopsy is done during a 1- to 2-day inpatient
hospital stay. The patients are given a sedative medication through a vein before the
procedure. The skin over the biopsy site is numbed and the biopsy needle is passed
rapidly into and out of the liver to collect a small sample of liver tissue for study.
- Apheresis: This procedure is done to collect a large number of white blood cells needed
to test the immune response to the HCV. On the day before each liver biopsy, blood is
drawn through a needle from a vein in one arm and run through a machine that separates
and collects the white cells. The red cells and plasma are returned to the patient's
body through the same needle or a second needle in the other arm.
hepatitis C-infected patients who have had a liver transplant and possibly in kidney
transplant patients as well. The hepatitis C virus (HCV) can cause cirrhosis in about 20
percent of infected persons. Generally, it takes 20 years or more for cirrhosis to develop.
After liver transplantation, however, patients may develop cirrhosis in as little as 5
years. Cirrhosis does not develop as rapidly in kidney transplant patients, but it may
develop faster than in people who do not undergo transplantation. The study will look at the
possible role of immune-suppressing medications given to liver and kidney transplant
patients in increasing the severity of hepatitis C infection and in speeding the cirrhotic
process.
Patients 18 years of age and older with chronic HCV infection who require a liver transplant
for end-stage liver disease or a kidney transplant for kidney failure may be eligible for
this study. Liver transplant patients are recruited from the Inova Fairfax Liver Transplant
Center in Fairfax, Virginia, and from the Georgetown University Medical Center Liver
Transplant Institute in Washington, D.C. Kidney transplant patients are recruited from the
Transplantation Branch of the National Institute of Diabetes and Digestive and Kidney
Diseases.
Participants undergo the following procedures:
- Regular care: As part of their regular transplant-related treatment, patients have a
medical history, physical examinations and blood draws before their transplant and on
regularly scheduled visits after the transplant.
- Blood draws for research: Special blood tests are done to measure the immune response
to HCV. They measure the amount of HCV in the blood, the number of HCV strains present
and how they change over time and the HCV antibodies in the blood.
- Liver biopsies: This procedure is done at 3 months, 1 year, 3 years and 5 years after
the transplant to determine the extent of scarring of the liver and to study the immune
responses within the liver, the proportion of liver cells infected with HCV and the
presence of scar-producing cells. The biopsy is done during a 1- to 2-day inpatient
hospital stay. The patients are given a sedative medication through a vein before the
procedure. The skin over the biopsy site is numbed and the biopsy needle is passed
rapidly into and out of the liver to collect a small sample of liver tissue for study.
- Apheresis: This procedure is done to collect a large number of white blood cells needed
to test the immune response to the HCV. On the day before each liver biopsy, blood is
drawn through a needle from a vein in one arm and run through a machine that separates
and collects the white cells. The red cells and plasma are returned to the patient's
body through the same needle or a second needle in the other arm.
Nearly all patients with hepatitis C virus (HCV) related end-stage liver disease who receive
an orthotopic liver transplant (OLT) develop hepatitis C reinfection of the graft after
transplantation. Most of these patients will progress to chronic hepatitis and 20-30% will
experience a rapid progression to cirrhosis. It is unclear why it generally takes 20 or more
years for progression to cirrhosis after the initial HCV infection, but as little as five
years after OLT. Additionally, it is paradoxical that hepatitis C, which is thought to be
immune-mediated, should advance more rapidly in patients who are immune suppressed. Rapid
fibrosis progression post-transplantation is likely related to complex interactions between
viral factors, host immune responses and induction and maintenance of immunosuppression for
the prevention of graft rejection.
This study has been designed as an observational, hypothesis-generating pilot study of
patients with chronic hepatitis C requiring organ transplantation and concomitant
immunosuppression. Patients who require a liver-transplant for chronic hepatitis C-related
end-stage liver disease and patients with hepatitis C who require a kidney transplant for
renal failure will be enrolled and followed for up to five years. Virologic, immunologic and
intrahepatic parameters will be correlated with the level of immunosuppression, degree of
fibrosis, progression to cirrhosis and liver-related deaths in study subjects. The
objectives of this study are to: 1) determine the proportion of patients with hepatitis C
that progress to bridging fibrosis or cirrhosis at three and five years after liver or
kidney transplantation (rapid-progressors); 2) compare virologic, host-immune and
intrahepatic factors in rapid-progressors to non-progressors and slow progressors; 3)
characterize the relationship between general and HCV-specific immune responses and the
extent of liver fibrosis; and 4) develop a predictive model that discriminates between
rapid-progressors and non- or slow-progressors.
an orthotopic liver transplant (OLT) develop hepatitis C reinfection of the graft after
transplantation. Most of these patients will progress to chronic hepatitis and 20-30% will
experience a rapid progression to cirrhosis. It is unclear why it generally takes 20 or more
years for progression to cirrhosis after the initial HCV infection, but as little as five
years after OLT. Additionally, it is paradoxical that hepatitis C, which is thought to be
immune-mediated, should advance more rapidly in patients who are immune suppressed. Rapid
fibrosis progression post-transplantation is likely related to complex interactions between
viral factors, host immune responses and induction and maintenance of immunosuppression for
the prevention of graft rejection.
This study has been designed as an observational, hypothesis-generating pilot study of
patients with chronic hepatitis C requiring organ transplantation and concomitant
immunosuppression. Patients who require a liver-transplant for chronic hepatitis C-related
end-stage liver disease and patients with hepatitis C who require a kidney transplant for
renal failure will be enrolled and followed for up to five years. Virologic, immunologic and
intrahepatic parameters will be correlated with the level of immunosuppression, degree of
fibrosis, progression to cirrhosis and liver-related deaths in study subjects. The
objectives of this study are to: 1) determine the proportion of patients with hepatitis C
that progress to bridging fibrosis or cirrhosis at three and five years after liver or
kidney transplantation (rapid-progressors); 2) compare virologic, host-immune and
intrahepatic factors in rapid-progressors to non-progressors and slow progressors; 3)
characterize the relationship between general and HCV-specific immune responses and the
extent of liver fibrosis; and 4) develop a predictive model that discriminates between
rapid-progressors and non- or slow-progressors.
- INCLUSION CRITERIA
To fulfill criteria for study entry, the patient must:
- be 18 years of age or older.
- have detectable HCV RNA
- require orthotopic liver transplantation for chronic hepatitis C induced cirrhosis or
require renal transplantation for end-stage kidney disease
- have a MELD score greater than 18 (for liver transplant patients) or have an
otherwise high probability of receiving a liver or kidney transplant within six
months of enrollment based on assessment by the clinical transplant team at each
hospital.
- be able/willing to travel to the collaborating center for blood sampling prior to
liver or kidney transplantation, and at 2, 3, 4, 5, 6, 8, 12, 16, 24 weeks after
transplantation and then bi-annually until the end of the study at 5 years
- be willing to have study-related liver biopsies at 3 months, and then 1, 3 and 5
years after transplantation
- provide informed consent.
EXCLUSION CRITERIA:
To fulfill criteria for study entry, the patient must NOT:
- be HIV or Hepatitis B virus (HBsAg) positive
- receive a liver graft from an anti-HCV antibody positive or HBV core positive donor
- have other forms of liver disease including primary biliary cirrhosis, autoimmune
hepatitis, hemochromatosis and Wilson's Disease
- have hepatocellular carcinoma if any single lesion is 5 cm. or more or if there are 3
or more lesions exceeding 3 cm.
- be on immunomodulatory medications such as corticosteroids within four weeks of
collection of blood for pre-transplant baseline laboratory testing
- have been diagnosed with any hereditary or acquired immunodeficiency state prior to
liver or kidney transplantation
We found this trial at
3
sites
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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Inova Fairfax Hospital Inova Fairfax Hospital, Inova's flagship hospital, is an 833-bed, nationally recognized regional...
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Georgetown University Georgetown University is one of the world's leading academic and research institutions, offering...
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