Overall Bottom Line
- With recipients living longer after undergoing LT, it has been noted that significant causes of morbidity and mortality post-transplantation are not related to recurrent liver disease.
- The lifelong use of immunosuppressive agents places these recipients at risk for a variety of general medical conditions.
- These medical conditions include renal disease, hypertension, diabetes mellitus, dyslipidemia, obesity and osteoporosis.
Section 1: Background
Definition of disease
- With continued improvement of both graft and patient survival, long-term transplant recipients are at risk for developing general medical problems, particularly cardiovascular and metabolic diseases.
- Most of these complications are related to immunosuppressive therapy; management strategies are similar to the non-transplanted population.
Incidence/prevalence
- In long-term survivors after LT, up to a third will develop significant renal dysfunction or cardiovascular mortality.
- More than half of all LT recipients will develop some aspect of the metabolic syndrome.
Pathology/pathogenesis
- The table “Complications and associated risk factors” illustrates the common medical conditions seen after LT and their associated risk factors. In general, long-term immunosuppression medication is the primary risk factor.
Complications and associated risk factors
| Complication | Associated/risk factor |
|---|---|
| Renal disease | CNIs, sirolimus, diabetes mellitus, hypertension |
| Hypertension | CNIs, obesity |
| Diabetes mellitus | Corticosteroids, CNIs, sirolimus, obesity |
| Dyslipidemia | Sirolimus |
| Malignancy | Immunosuppression |
| Osteoporosis | Vitamin D deficiency |
Section 2: Prevention
Bottom Line/Clinical Pearls
- Prevention of general medical conditions after LT relies on screening appropriately (cancer screening per national guidelines, and regular dermatology assessment for skin cancer) and controlling risk factors for cardiovascular disease.
Screening
- It is appropriate to adhere to national cancer screening guidelines in LT recipients.
- It is imperative that all LT recipients have a PCP who should see them regularly and monitor for diabetes, hypertension and dyslipidemia, and other cardiovascular risk factors.
- We typically ask all patients to obtain routine laboratory tests (CBC, chemistry panel and immunosuppression level) every 3 months.
- Regular screening for bone density is recommended.
Primary prevention
- Although there are no proven primary prevention strategies for the main medical complications seen after LT, we recommend yearly cancer screening and vaccination for influenza.
Secondary prevention
- It is important to control the metabolic syndrome after LT to try and reduce the risk of cardiovascular and renal disease.
- In patients with renal disease immunosuppression should be kept to a minimum and consideration should be given to switching to a renal sparing immunosuppression regimen.
- Osteoporosis should be treated appropriately to reduce fracture risk.
Section 3: Diagnosis
Bottom Line/Clinical Pearls
- LT recipients who do well after surgery are at risk for general medical conditions. They should be followed regularly by a PCP. We follow all long-term survivors annually. At office visits patients should have a complete review of symptoms, and a full medication and psychosocial history should be obtained including smoking and alcohol use.
- The examination should focus on vital signs, particularly blood pressure and weight.
- Investigations should include CBC, chemistry panel, immunosuppression level, urinalysis and other tests depending on any concerns in the history or physical examination.
- Routine imaging is not required.
Section 4: Treatment
Clinical Pearls
- Long-term survivors after LT should regularly visit their PCP and be subject to laboratory tests every 3 months.
- Regular health maintenance should include adhering to cancer screening and vaccination guidelines, dermatology assessment and bone densitometry.
Renal dysfunction
Incidence
- After LT the risk of developing CKD Stage 4 (GFR <30 mL/min) is 8% at 1 year, 18% at 5 years, 28% at 10 years.
- Mortality risk increases as GFR decreases: 5-year survival rates for patients with CKD 3, CKD 4, and ESRD were 84%, 68%, and 49%, respectively.
Risk factors
- CNI nephrotoxicity (cyclosporine).
- Mechanisms of CNI nephrotoxicity include:
- Acute causes: afferent arteriolar vasospasm, renal hypoperfusion.
- Chronic causes: renal hypoperfusion, obliterative arteriopathy, focal ischemia from tubular atrophy/interstitial fibrosis/glomerulosclerosis.
- Acute causes: afferent arteriolar vasospasm, renal hypoperfusion.
- All of these mechanisms can result in a decrease in the GFR.
- Diabetes mellitus.
- Hypertension.
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