Gastroenterology Hepatology

Primary care in liver transplant recipients

How can I be sure that the patient has clinical features associated with liver transplant recipients?

Diseases associated with liver transplant recipients

Metabolic syndrome. A constellation of obesity, hyperlipidemia, hypertension, and hyperglycemia that has a prevalence in up to 58% of post-liver-transplant recipients. Immunosuppression medications, obesity, and etiology of liver disease (nonalcoholic steatohepatitis) all lead to insulin resistance and development of this syndrome. This syndrome results in increased morbidity and mortality.

Bone disease. Common, post liver transplant (5-35%), with risk factors including cholestatic liver disease, lower body weight, older age, female gender, and immunosuppression.

Inflammatory bowel disease. Inflammatory bowel disease can be either the exacerbation of preexisting disease or de novo disease. Those patients with preexisting disease had a flare of disease of up to 30 % within 1 year of liver transplant, whereas de novo disease develops in about 11% of patients. Risk factors for exacerbation include use of tacrolimus, active disease at transplantation, long duration of disease, and discontinuation of steroids. Risks for de novo inflammatory bowel disease includes cytomegalovirus (CMV) infection, CMV mismatch, and autoimmune hepatitis etiology for liver transplantation.

Gout. Hyperuricemia is common, post liver transplant, due to impaired excretion of uric acid.

Primary care problems associated with liver transplant recipient

Preventive Care. Perform yearly review of vaccinations, dental care, smoking history, patient weight, medications, bone disease, and surveillance for malignancy. The overall risk of malignancy is 2 to 4 times higher in liver-transplant patients and accounts for up to 30% of post-liver-transplant deaths.

Pregnancy post liver transplant. Pregnancy after liver transplantation have noted favorable maternal and fetal outcomes. Birth weights were lower (50%) and mean gestational age also was lower (average 36 weeks). The risk of acute rejection during pregnancy is reported to be 1% to 5% and graft loss less than 2% (more common in those transplanted for autoimmune hepatitis).

A tabular or chart listing of features and signs and symptoms

See Table I and Table II.

Table I.

Findings and abnormal laboratory testing after liver transplantation
Obesity Body Mass index >30
Hypertriglycerides >150 mg/dL
High-density lipoprotein <40 mg/dL
Blood pressure >130/85
Hyperglycemia >100 mg/dL

Table II.

Medications following liver transplantation
Drug Category B Category C
Prednisone X
Cyclosporine X
Tacrolimus X
Mycophenolate mofetil X
Rapamycin X
Azathioprine Category D

How can I confirm the diagnosis?

Bone disease. DEXA bone scan with T-score higher than –1.5.

Inflammatory bowel disease. Colonoscopy with biopsies for histological evaluation.

Gout. Physical examination with inflammation of joints with hyperuricemia.

Malignancy. The most frequently diagnosed cancers are non-melanoma skin cancer, post-transplant lymphoproliferative disease, colorectal cancer, lung cancer, and oropharyngeal and urological tumors. Breast, cervical, and prostate cancers are similar to those in the general population.

What other diseases, conditions, or complications should I look for in patients with liver transplants?

N/A

What is the right therapy for the liver transplant recipient?

Metabolic syndrome

Obesity

  • – Nutrition consultation with target weight loss of 1 to 2 labs/week with calorie restriction to less than 1500 Kcals/day.

  • – Annual evaluation for weight gain in a yearly physical.

Hyperlipidemia

  • – Review of immunosuppresant agents (elimination of steroids, mTOR inhibitor)

  • – Use of statins (simvastatin 40 mg/d, atorvastatin 40 mg/d, pravastian 20 mg/d, tricor 145 mg/d).

  • – Target guideline goals of total cholesterol <200 mg/dL, low-density lipoprotein <100 mg/dL, high-density lipoproteins > 60 mg/dL, and triglycerides of <150 mg/dL with biannual blood draw of lipid panel.

Hypertension

  • – Prior studies have noted treatment with single agents were successful in 58%, 2 agents in 29%, and 3 agents in 10% of patients.

  • – First-line drug therapy is usually with diuretics or calcium channel blockers; however, diabetics may benefit with angiotension-converting enzyme inhibitors.

  • – Second-line therapy with beta-blockers or clonidine is helpful.

Diabetes. New-onset diabetes, post liver transplant, is noted in up to 10 % of patients. Prior studies have noted use of insulin in 39% of patients and oral antiglycemia medications in 39% and both in 21%.

Initial management of diabetes includes weight control, exercise, and diabetic diet. Second-line use of oral antidiabetic drugs in patients with normal renal function. Lastly, use of insulin with a goal of euglycemia with a hemoglobin A1C of less than 6.5% with consultation of endocrinology.

Bone disease. Osteoporosis calcium 1500 mg/d, vitamin D 1000 IU/d, oral bisphosphonates (fosamax 70 mg orally weekly).

Inflammatory bowel disease.Use of aminosalicylates and steroids.

Gout

  • – In patients with histories of gout and hyperuricemia, treatment with allopurinol 100 mg/d.

  • – For acute gout, treatment with colchicine, 0.6 mg every 2 hours, of up to 5 doses.

  • – In patients that do not respond to cholchicine, treatment with prednisone 20 mg/d for 2 weeks.

  • – Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is to be discouraged.

Preventive Care

Perform yearly review of dental care, vaccinations, smoking history, weight, and malignancy.

What is the most effective initial therapy?

Osteoporosis. Oral calcium 1500 mg/d with vitamin D 1000 IU/d.

Inflammatory bowel disease. Aminosalicylates at full dose, prednisone 40 mg every day with tapering dose over 2 to 3 months, down to lowest possible dose.

Diabetes. Weight loss, diabetic diet, and oral antidiabetic medications.

Preventive care

Administer yearly Influenza vaccinations and hepatitis A and B vaccinations, if not given pretransplantation. Pneumococcal vaccination should be given pretransplant; if not, use standard 23-valent vaccine, with revaccination 5 years post transplantation.

Patients transplanted for hepatitis B typically use hepatitis B immunoglobulin (HBIG) under center-specific guidelines for months to years. Continued use of nucleos(t)ide analog post transplantation is mandatory.

Malignancy surveillance

  • – Annual examination for skin cancer and use of sun screen lotion of SP 50 or higher.

  • – Mammograms and gynecological evaluation biannually for women.

  • – Yearly prostate-specific antigen in males of more than 50 years of age.

  • – Annual examination of mouth and throat.

  • – Patients with inflammatory bowel disease: annual colonoscopy with surveillance biopsies for dysplasia.

  • – Colonoscopy every 5 years for those without inflammatory bowel disease.

If a patient develops a solid organ malignancy, there is no data that alteration of immunosuppression may improve survival; however, those treated with chemotherapy may develop leukopenia and, therefore, lower doses of immunosuppression may be used.

Listing of usual initial therapeutic options, including guidelines for use, along with expected result of therapy.

N/A

A listing of a subset of second-line therapies, including guidelines for choosing and using these salvage therapies

Osteoporosis. Bisphosphonates (fosamax 70 mg/week).

Inflammatory bowel disease. Azathioprine 1.5 mg/kg.

Diabetes. Insulin.

Listing of these, including any guidelines for monitoring side effects.

N/A

How should I monitor the liver transplant recipient?

Metabolic syndrome. Obesity: yearly physical examination measurement of weight/body mass index.

Hyperlipidemia. Biannual lipid measurements.

Blood pressure. Biannual measurement of blood pressure.

Diabetes. Biannual hemoglobin A1C, daily blood glucose measurements in those with insulin use.

Osteoporosis. Every 2 years, DEXA scan in those with normal results; yearly DEXA scan in those with T scores higher than –1.5.

Inflammatory bowel disease. Yearly colonoscopy with surveillance biopsies (4 biopsies every 10 cm) in patients with known inflammatory bowel disease. If dysplasia is found on histology, colectomy is warranted.

Gout. In patients with histories of gout, measurement of uric acid yearly.

Preventive care

Monitoring vaccination response is typically not performed. However, in patients transplanted for hepatitis B, monitor for recurrent disease by monitoring for hepatitis B surface antigen, hepatitis B DNA level every 3 to 6 months.

Prophylaxis with antibiotics for dental care is not necessary, unless patient has high-risk conditions of prior endocarditis, prosthetic valves, or congenital heart disease.

Malignancy

  • – Biannual mammogram and gynecological evaluation.

  • – Prostate specific antigen yearly.

  • – Colonoscopy every year in those with inflammatory bowel disease and every 5 years in those without.

In patients transplanted for hepatocellular carcinoma, monitoring alfa-fetoprotein and imaging studies have not shown to improve post-transplant survival. However, most centers perform surveillance programs such as alfa feto protein every 6 months and imaging studies of ultrasound every 3 to 6 months.

What's the evidence?

Charlton, M. "Obesity, hyperlipidemia and metabolic syndrome". Liver Transplant. vol. 15. 2009. pp. S83-9.

Pagadala, M, Dasarathy, S, Eghtesas, B. "Post-transplant metabolic syndrome: an epidemic waiting to happen". Liver Transplant. vol. 15. 2009. pp. 1662-72.

Crippin, JS. "Bone disease after liver transplantation". Liver Transplant. vol. 7(Suppl1). 2001. pp. S27-35.

Compston, JE. "Osteoporosis after liver transplantation". Liver Transplant . vol. 9. 2003. pp. 321-30.

Verdonk, RC, Dijkstra, G, Haagsma, EB. "Inflammatory bowel disease in liver transplantation: risk factors for recurrence and de novo disease". Am J Transplant. vol. 6. 2006. pp. 1422-9.

Dvorchik, I, Subotin, M, Demetris, A. "Effect of liver transplantation on inflammatory bowel disease in patients with primary sclerosing cholangitis". Hepatology. vol. 35. 2002. pp. 380-4.

Neal, DAJ, Tom, BDM, Gimson, AES. "Hyperuricemia, gout, and renal function after liver transplantation". Transplantation. vol. 72. 2001. pp. 1689-91.

Watt, K, Pedersen, RA, Kremers, W. "Long-term probability of and mortality from de novo malignancy after liver transplantation". Gastroenterology. vol. 137. 2009. pp. 2010-17.

Watt, K, Pedersen, R, Kremers, W. "Evolution of causes and risk factors for mortality post-liver transplant: results of the NIDDK long-term follow-up study". Am J Transplant. vol. 10. 2010. pp. 1420-7.

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