Management of HCV-Positive Liver Transplant Recipient
Management of HCV-Positive Liver Transplant Recipient
What are the latest recommendations regarding treatment of a liver transplant recipient who is hepatitis virus C (HCV)-positive at the time of transplantation?
First, the criteria for diagnosing acute and/or chronic rejection and recurrent HCV are still somewhat controversial. However, strict adherence to the criterion for rejection (portal inflammation with inflammatory bile duct damage, with or without mononuclear perivenular inflammation) helps to distinguish rejection from recurrent HCV, which is more likely to show steatosis, spotty hepatocyte necrosis, lobular disarray, and Kupffer cell hypertrophy.
Chronic rejection may have less clear delineation. Chronic HCV is characterized by mononuclear portal inflammation that may show mild bile duct damage, but is usually less extensive than with chronic rejection. In addition, the timing from transplantation to histopathologic findings may also help to point to the pathophysiology of liver dysfunction. Early dysfunction (less than 90 days) is more likely to represent acute rejection, whereas dysfunction after that is more likely to represent recurrent HCV. Again, the timing overlap of recurrent HCV and chronic rejection is problematic.
Having said this, acute rejection is often treated with adjustment of baseline calcineurin levels upwards, with or without corticosteroids, depending on the clinical urgency and degree of acute rejection. Based on several studies, use of antilymphocyte antibodies in the setting of acute rejection should be avoided. Since corticosteroids may also exacerbate HCV following treatment of acute rejection, the minimal amount needed to reverse rejection seems advisable.
With chronic rejection, a trial of increasing baseline calcineurin levels alone may be warranted. However, since recurrent HCV is often associated with higher levels of HCV-RNA in the face of high HCV-RNA, a trial of interferon alpha with or without ribavirin also seems justified.
What are the latest recommendations regarding treatment of a liver transplant recipient who is hepatitis virus C (HCV)-positive at the time of transplantation?
First, the criteria for diagnosing acute and/or chronic rejection and recurrent HCV are still somewhat controversial. However, strict adherence to the criterion for rejection (portal inflammation with inflammatory bile duct damage, with or without mononuclear perivenular inflammation) helps to distinguish rejection from recurrent HCV, which is more likely to show steatosis, spotty hepatocyte necrosis, lobular disarray, and Kupffer cell hypertrophy.
Chronic rejection may have less clear delineation. Chronic HCV is characterized by mononuclear portal inflammation that may show mild bile duct damage, but is usually less extensive than with chronic rejection. In addition, the timing from transplantation to histopathologic findings may also help to point to the pathophysiology of liver dysfunction. Early dysfunction (less than 90 days) is more likely to represent acute rejection, whereas dysfunction after that is more likely to represent recurrent HCV. Again, the timing overlap of recurrent HCV and chronic rejection is problematic.
Having said this, acute rejection is often treated with adjustment of baseline calcineurin levels upwards, with or without corticosteroids, depending on the clinical urgency and degree of acute rejection. Based on several studies, use of antilymphocyte antibodies in the setting of acute rejection should be avoided. Since corticosteroids may also exacerbate HCV following treatment of acute rejection, the minimal amount needed to reverse rejection seems advisable.
With chronic rejection, a trial of increasing baseline calcineurin levels alone may be warranted. However, since recurrent HCV is often associated with higher levels of HCV-RNA in the face of high HCV-RNA, a trial of interferon alpha with or without ribavirin also seems justified.
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