Chapter 49 MEDICAL PROBLEMS AFTER LIVER TRANSPLANTATION
REJECTION OF THE LIVER GRAFT
Chronic rejection
Chronic rejection, despite the inference that it is a late event, can occur within 6 weeks of liver transplantation. It is characterised by an elevated serum bilirubin, alkaline phosphatase and gamma-glutamyltransferase. It is more insidious in progression than acute rejection and is characterised by histological features of paucity of bile ducts associated with arteriole obstruction by foamy macrophages. Chronic rejection does not respond to pulse methylprednisolone. Some patients who are on cyclosporine will benefit from conversion to tacrolimus, and patients already using tacrolimus may benefit from an increased dosage to achieve higher serum levels.
INFECTIONS IN THE LIVER TRANSPLANT RECIPIENT
It is useful to consider the type of infections in relationship to the time since liver transplantation. Bacterial infections are extremely common in the first month after liver transplantation and common sites of infection include the abdomen (peritonitis, cholangitis, hepatic abscess, wound infection), chest (pneumonia, empyema), urinary tract (a consequence of prolonged catheterisation) and intravenous access sites. A definitive focus of bacterial sepsis may not be found or may be unusually located (e.g. teeth or prostate gland). The viral infections that occur early after liver transplantation include herpes simplex virus (HSV) reactivation, which may be manifest by oral or genital lesions, and HHV-6, which may cause pancytopenia and interstitial pneumonia. Cytomegalovirus (CMV) is extremely common after liver transplant but tends to occur after the first month. The clinical manifestations may be protean and include cytopenia, hepatitis, upper and lower gastrointestinal tract ulceration, pulmonary involvement and an infectious mononucleosis syndrome. Diagnosis may be confirmed by the characteristic histological appearance of inclusion bodies in addition to the detection of a circulating structural protein (pp65) and direct identification of virus by polymerase chain reaction (PCR). However, it is recognised that diagnosis may be very difficult on occasions. Ganciclovir is the antiviral of choice and dose adjustments are required for patients with renal failure (see below for antimetabolite interactions). Similarly, reactivation of varicella tends to occur slightly later after liver transplant and can manifest as shingles, disseminated cutaneous disease or visceral involvement. Epstein-Barr virus infection tends to present as a post-transplant lymphoproliferative disorder that may respond to a reduction in the intensity of immunosuppression. The prevalence of opportunistic infections also relates to the intensity of the immunosuppressive regime. While the frequency of opportunistic infection is proportional to the intensity of the immunosuppression regime, patients are always at risk. Vigilance is required for infections with fungi (Aspergillus, Cryptococcus, Candida), protozoans (Pneumocystis carinii, Toxoplasma gondii) and bacteria (Nocardia, Legionella).
