TABLE 2
Immunosuppressive medications and interactions after liver transplantation
| MEDICATION | SIDE EFFECTS | MONITORING | COMMON DRUG INTERACTIONS |
|---|---|---|---|
| Corticosteroids | Weight gain, diabetes, hypertension, high lipids, neurotoxic, cataracts, osteoporosis | Glucose | |
| Blood pressure | |||
| Lipids | |||
| Tacrolimus | Diabetes, hypertension, high lipids, nephrotoxic, neurotoxic, gastrointestinal, high potassium, low magnesium | As above | Increased levels with azole antifungals, macrolide antibiotics, diltiazem, verapamil, danazol, metoclopromide |
| Drug levels | Decreased levels with rifampicin, phenobarbital, phenytoin, carbamazepine, St. John ’ s wort | ||
| Renal function | |||
| Electrolytes | |||
| Cyclosporine | Same as tacrolimus+gingival hyperplasia, hirsutism, rare hepatotoxicity | As tacrolimus | As tacrolimus; increased levels with grapefruit juice and sirolimus |
| Mycophenylate mofetil | Anemia, leukopenia, thrombocytopenia, gastrointestinal | CBC | May increase acyclovir levels Antacids, cholestyramine: lower absorption |
| Azathioprine | Same as mycophenylate+pancreatitis, hepatotoxicity | CBC Liver function tests | Allopurinol, ACE inhibitors, sirolimus: may potentiate marrow toxicity |
| Liver function tests | May lower anticoagulation effect of warfarin | ||
| Sirolimus | Same as mycophenylate+hyperlipidemia, hypertension, hypokalemia, diarrhea | CBC | |
| Lipids | |||
| Abbreviations: ACE, angiotensin-converting enzyme; CBC, complete blood count. | |||
Long-term complications
Cardiovascular disease
Up to 20% of late deaths after OLT are caused by cardiovascular disease. 4 Uncontrollable factors, such as preexisting cardiac disease, male sex, family history of cardiac disease, and advanced age contribute to the incidence of cardiovascular disease. However, a number of potentially controllable factors, such as hypertension, hyperlipidemia, obesity, and diabetes are common after OLT and should be addressed.
Hypertension. Hypertension occurs in 40% to 75% of OLT patients. 5 Causes include calcineurin-inhibitor (cyclosporine, tacrolimus) therapy, high-dose corticosteroids, and renal insufficiency. Calcineurin inhibitors cause renal vasoconstriction, leading to sodium retention and hypertension. Reducing the doses of these medications by the transplant center typically improves blood pressure control.
Treatment of choice for hypertension depends on how recently the transplant was performed. In the first 6 months following the procedure, dihydropyridine calcium-channel blockers (eg, amlodipine) and alpha-blockers are the mainstay of therapy, although peripheral edema and orthostatic hypotension may affect their tolerability. Diuretics can also be used in volume-overloaded patients.
After 6 months, other pharmacologic agents, such as angiotensin-converting enzyme (ACE) inhibitors and beta-blockers, can be administered to patients with stable renal function and without other contraindications (strength of recommendation [SOR]: C ). Long-term management of hypertension does not differ significantly from that in non-transplant patients.
Hyperlipidemia/obesity. Obesity and hyperlipidemia may affect up to half of OLT patients. Factors that contribute to both disorders include immunosuppressive drugs, increased appetite, diabetes, pretransplant hyperlipidemia, and history of cholestatic liver disease.
For hyperlipidemia, lifestyle modifications, such as diet and exercise, are recommended. If these measures are ineffective, statins are first-line agents. Avoid bile acid binding resins, which may interfere with the absorption of all medications. For refractory cases, switching from cyclosporine to tacrolimus under the direction of the transplant center might be indicated.
Treatment of obesity following OLT should also focus on lifestyle changes, as the safety of pharmacotherapy and surgery for obesity is uncertain in these patients.
Glucose intolerance and diabetes. Many patients will have glucose intolerance that resolves after steroid withdrawal. Main risk factors are pre-OLT diabetes, episodes of steroid-resistant rejection, and obesity. Post-OLT onset of diabetes will persist for only a small percentage of patients. 6
Overview of liver transplantation
More than 56,000 liver transplants have been performed since the United Network for Organ Sharing created a national database for liver transplantation in 1988. In 2002, more than 5000 liver transplants were performed and more than 17,000 patients were on the waiting list for transplantation. Approximately 70% to 80% of these patients will survive to 5 years after transplantation and sustain a high quality of life long-term.
The most common indications for OLT in the US are shown in the FIGURE .7 Cirrhosis due to hepatitis C, chronic alcohol use, and idiopathic/autoimmune causes comprise almost 60% of the indications. Patients who meet minimal listing criteria may be placed on the waiting list for liver transplantation.
On February 27, 2002, a new nationwide system called MELD (Model for End-Stage Liver Disease) was adopted to rank patients on the waiting list based on the severity of liver disease and remove the subjectivity associated with the previous ranking system.8 The MELD score, which ranges from 6 to 40, is a mathematical computation based on the patient ’ s bilirubin, creatinine, and international normalized ratio (INR). Although early in use, the MELD system appears to be a good predictor of the need for transplantation and posttransplantation outcome.
Treatment of post-transplant diabetes is similar to that for any patient. Insulin is often required initially, but with reduction in immunosuppression and corticosteroids, patients can usually be switched to oral agents. Though there is no absolute contraindication to using any antidiabetes medications, most physicians try to avoid those with potential hepatotoxicity, such as the thiazolidinediones (SOR: C).