Long-term management of the liver transplant patient: recommendations for the primary care doctor.

No official document has been published for primary care physicians regarding the management of liver transplant patients. With no official source of reference, primary care physicians often question their care of these patients. The following guidelines have been approved by the American Society of Transplantation and represent the position of the association. The data presented are based on formal review and analysis of published literature in the field and the clinical experience of the authors. These guidelines address drug interactions and side effects of immunosuppressive agents, allograft dysfunction, renal dysfunction, metabolic disorders, preventive medicine, malignancies, disability and productivity in the workforce, issues specific to pregnancy and sexual function, and pediatric patient concerns. These guidelines are intended to provide a bridge between transplant centers and primary care physicians in the long-term management of the liver transplant patient.

The use of screening and preventive therapies for gastroesophageal varices in patients referred for evaluation of orthotopic liver transplantation.

OBJECTIVE: Screening for varices has been recommended in patients with cirrhosis to prevent variceal hemorrhage (primary prophylaxis). In addition, therapy is recommended after the initial episode of variceal bleeding to prevent recurrence (secondary prophylaxis). However, the degree of adherence to these recommendations remains unclear. The purpose of our study was to determine whether these recommendations are being followed in patients presenting for evaluation of orthotopic liver transplantation. METHODS: One hundred twenty-five patients referred for liver transplantation were evaluated. Data regarding demographics, clinical information, relevant time intervals (diagnosis of cirrhosis to screening, screening to initial variceal bleeding, variceal bleeding to referral, diagnosis of cirrhosis to referral), screening strategies used, and implementation of primary or secondary prophylaxis was obtained. The differences among quantitative variables were analyzed with Student's t test. Qualitative variables were evaluated with the Mantel-Haenzel chi2 test or Fisher's exact test. Statistical significance was designated at p < 0.05. RESULTS: Our study found that 46% of patients presenting for evaluation of liver transplantation had screening endoscopy or radiological studies to detect the presence of varices. On the contrary, secondary prophylaxis was performed in all patients with a prior history of variceal hemorrhage. Screening for varices displayed no regional differences. CONCLUSIONS: In our cohort, screening for varices is not being consistently performed, thus delaying the timely implementation of primary prophylaxis. Therefore, the adherence to currently available practice guidelines and the education of physicians to implement screening in this patient population is an important goal.

Safety of endoscopy in patients with end-stage liver disease.

Patients with end-stage liver disease routinely undergo an upper endoscopy for the diagnosis and management of complications of portal hypertension. These cirrhotic patients inherently have additional risks and higher rates of complications secondary to their liver disease and the presence of portal hypertension. Additional considerations and precautions must be taken into account to ensure that the endoscopic procedure is performed with the minimal risks possible. This article discusses the management of cirrhotic patients undergoing endoscopy. It addresses clinical clues for identifying the cirrhotic patient, the use of medications and monitoring equipment for vital signs during endoscopy, blood product administration in acute upper gastrointestinal bleeding, and elective and urgent procedures to diagnose and treat cirrhotic patients.

Combined cardiac surgery and liver transplantation.

During evaluation for liver transplantation, a 63-year-old man with cirrhosis secondary to hepatitis C was diagnosed with severe aortic stenosis (aortic valve area, 0.87 cm(2)) and coronary artery disease. A combined procedure involving aortic valve replacement (pericardial xenograft), coronary artery bypass surgery, and orthotopic liver transplantation was performed. Convalescence was uneventful, and at 2 years after the procedure, the patient has normal cardiac function, good prosthetic valve function, and biochemically normal liver function.

Liver transplantation in the era of cost constraints.

BACKGROUND: The issue of containing cost has had a significant impact on organ transplantation. After our institution's 500th liver transplant, we critically examined the impact of the changing health care environment on liver transplantation. METHODS: We retrospectively analyzed 500 consecutive liver transplants done in the period of 1989 to 1998. RESULTS: Comparing the first 100 liver transplants to the last 100, patient demographics did not change significantly; however, mean waiting times increased significantly, from 30.4 days to 146.7 days, and median hospital stay decreased from 20.2 days to 10.9 days. One-year patient and graft survivals were not significantly different, 93.6% versus 96.5% and 88.0% versus 95.7%, respectively. CONCLUSIONS: Despite transplants in patients at higher risk and discharging patients sooner after transplantation, surgical results and patient survivals remained excellent. This was accomplished through improvements and modification of immunosuppression, outpatient treatment of uncomplicated acute rejection, and emphasis on close outpatient follow-up.

Hepatopulmonary syndrome and venous emboli causing intracerebral hemorrhages after liver transplantation: a case report.

Increasing experience has fostered the acceptance of liver transplantation as a treatment for patients with hepatopulmonary syndrome. Morbidity and mortality is most commonly attributed to progressive arterial hypoxemia postoperatively. A cerebral hemorrhage has been reported in one patient with hepatopulmonary syndrome after transplantation. However, a postmortem examination of the brain was not performed and the pathogenesis or type of cerebral hemorrhage was undefined. We report on a patient with severe hepatopulmonary syndrome who developed multiple intracranial hemorrhages after transplantation. The intracerebral hemorrhages were most consistent with an embolic etiology on postmortem examination. We postulate that venous embolization, caused by the manipulation of a Swan Ganz catheter in a thrombosed central vein, resulted in pulmonary emboli that passed through dilated intrapulmonary vessels into the cerebral microcirculation. Special attention to central venous catheters and avoidance of manipulation may be warranted in subjects with severe hepatopulmonary syndrome after liver transplantation.

Race: a critical factor in organ donation, patient referral and selection, and orthotopic liver transplantation?

The influence of ethnic origin on organ donation and renal allograft survival after renal transplantation has been controversial. Several large studies have reported inferior renal allograft survival in black recipients, whereas others have reported equal survival. However, the issue of race as it relates to organ donation, patient referral, and patient selection in orthotopic liver transplantation has not been investigated. We retrospectively reviewed our results of organ donation, patient referral and selection, and orthotopic liver transplantation since 1989. Because of a concerted educational effort by this organ procurement organization, the percentage of black donors has increased from 6.1% in 1988 to 21.9% in 1996. Since the inception of the Liver Transplant Program in 1989, 844 patients have been referred to our transplant center for organ transplant evaluation. Disproportionately fewer black patients (119; 14.1%) were referred for liver transplantation than white patients (725; 85.9%) based on the prevalence of end-stage liver disease in these populations. The acceptance rate for listing for transplantation was similar between the two groups. The percentage of patient referrals who actually underwent transplantation was similar across racial lines (43% black v 42% white patients). However, it appeared that black patients were referred for liver transplantation at a later stage and were more critically ill at the time of referral. Nevertheless, the patient and graft survival were similar between black and white patients. The 1- and 3-year survival rates in white recipients was 88% and 81%, respectively, versus 96% and 84% in black recipients. Within this organ procurement organization, black donation has increased over the past 10 years. Unfortunately, there may be a selection bias at the level of referral for liver transplantation. However, once patients are referred to this center for liver transplantation, the rate of transplantation and survival is similar between white and black patients.

Complications of cirrhosis. Why they occur and what to do about them.

Cirrhosis is a chronic disease of the liver in which dense bands of fibrosis enclose regenerative hepatocellular nodules. Clinical and radiologic features of advanced liver disease provide presumptive evidence for the presence of cirrhosis. Major complications are related to the increased hepatic resistance, increased sodium and water retention, and hyperdynamic changes of the circulatory system. Patient management should consist of appropriate prophylaxis for the life-threatening complications of variceal bleeding and spontaneous bacterial peritonitis and treatment of other complications as signs and symptoms develop.

Tacrolimus (FK506) and mycophenolate mofetil combination therapy versus tacrolimus in adult liver transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) prolongs allograft survival in experimental animals, prevents acute rejection in humans, and has recently been approved for use in renal transplantation in combination with cyclosporine. Tacrolimus (Prograf) has been shown to be effective for the prevention and treatment of allograft rejection in liver transplantation. However, there has been limited experience with the combination of tacrolimus and MMF in liver transplantation. METHODS: This retrospective pilot study examined the results in 130 primary, consecutive, adult liver transplants under two separate immunosuppressive protocols. Patients in the study group received MMF (1 g p.o. b.i.d.), tacrolimus (0.1 mg/kg p.o. b.i.d.), and a standard steroid taper. MMF was also tapered and then discontinued within 3 months of transplantation. A historical control received tacrolimus (0.15 mg/kg p.o. b.i.d.) and the same steroid taper. RESULTS: Pretransplant demographics, including creatinine, were not significantly different between the groups. The 6-month patient and graft survivals of 96.3% (control) versus 92.0% (study) were not significantly different. The incidence of acute rejection was 45.0% in the control group versus 26.0% in the study group (P = 0.03). The study group had a lower incidence of rejection (mean episodes/patient +/- SEM): 0.28+/-0.07 vs. 0.61+/-0.10 (P = 0.007). All of the study group members responded to high-dose steroids. In the control group, three patients required monoclonal antibody therapy and two patients required the addition of MMF. The incidence of cytomegalovirus was similar in the study group and the control group (13.8% vs. 10.0%, P = NS). Early renal function was better preserved in the tacrolimus/MMF group (mean creatinine +/- SEM): 1.09 mg/dl +/- 0.05 vs. 1.51 mg/dl +/- 0.08 at 30 days, P = 0.0001. The study design required dosing with less tacrolimus (mean mg/day +/- SEM), which was achieved at 1 week (23.2+/-0.7 vs. 13.5+/-0.5); 1 month (18.7+/-0.8 vs. 11.4+/-0.5); 3 months (14.5+/-0.6 vs. 9+/-0.5); and 6 months (11.6+/-0.6 vs. 8.2+/-0.6); P = 0.0001, for all time points. CONCLUSION: Combination therapy with tacrolimus and MMF may significantly reduce the incidence of acute liver allograft rejection, allow a significant reduction in tacrolimus dosage, and decrease the incidence of nephrotoxicity. Long-term analysis will be necessary to assess any increased risk of opportunistic infections.

Small-cell carcinoma of the lung manifesting as acute hepatic failure.

In this report, we describe four cases of small-cell carcinoma of the lung manifesting as acute hepatic failure. These cases were noteworthy for the presence of hepatomegaly and substantially increased serum lactate dehydrogenase and uric acid levels. The ratio of normalized serum lactate dehydrogenase to normalized serum alanine aminotransferase from the 4 cases reported herein (mean +/- SE, 3.63 +/- 1.10) was significantly greater than the ratio obtained from the 12 cases of nonmalignant fulminant hepatic failure (mean +/- SE, 0.46 +/- 0.18; P < 0.001). Chest radiographs and abdominal imaging studies showed no neoplastic process in three of the four cases. Postmortem examinations disclosed extensive infiltration of the liver by metastatic small-cell carcinoma of the lung. A review of the literature revealed 13 additional similar cases. We conclude that metastatic small-cell carcinoma of the lung should be considered in cases of acute hepatic failure associated with hepatomegaly, substantially increased lactate dehydrogenase levels in comparison with alanine aminotransferase values, and increased uric acid levels even if imaging studies show no lesion. A liver biopsy done early during the hospital course is appropriate for diagnosis and for prevention of inappropriate transfer of the patient to a liver transplant center.

Review of support systems used in the management of fulminant hepatic failure.

Fulminant hepatic failure has an exceedingly high mortality. Liver transplantation is the treatment option of choice. Unfortunately, one-third of patients with fulminant hepatic failure die awaiting a donor liver. For over 35 years attempts to remove or dilute putative toxins in the blood have been unsuccessful in improving survival rates. The use of biocompatible interfaces with blood or plasma and current hepatocyte culture techniques have led to the development of new support systems. This generation of bioartificial livers will hopefully provide the necessary hepatic functions and prevent many of the complications associated with fulminant hepatic failure. This paper will review the support systems tried and currently under investigation, with an emphasis on bioartificial livers.

Celiac sprue in an asymptomatic elderly man.

The authors discuss the case of an asymptomatic patient with celiac sprue presenting with hematologic abnormalities on screening laboratory examination. The patient was initially treated for vitamin B-12 and folate deficiency, and subsequently for iron deficiency with limited success until the diagnosis was established. The absence of such classic features of celiac disease as steatorrhea and diarrhea is not an uncommon presentation. Unexplained iron deficiency should alert the clinician to the possibility of celiac sprue.

Methemoglobinemia resulting from absorption of nitrates.

Three cases of toxic methemoglobinemia resulted from absorption of nitrate salts through burned skin areas. In addition to the unusual route of intoxication, this report emphasizes the occupational hazard of methemoglobinemia in workers exposed to nitrogen salts and the importance of rapid diagnosis and treatment. The diagnosis of methemoglobinemia should be suspected in any case of cyanosis refractory to oxygen therapy. Appropriate treatment should include oxygen, methylene blue, and exchange transfusion in clinically severe cases.