M Jimenez

Effectiveness and safety of mycophenolate mofetil as monotherapy in liver transplantation

Introduction Calcineurin inhibitors (CIs) cause substantial long-term morbidity and mortality among orthotopic liver transplantation (OLT) patients. Our aim was to evaluate the effectiveness and safety of mycophenolate mofetil (MMF) among OLT patients with CI-related side effects. Patients Thirty three adult patients, including 29 men and 4 women of mean age 57 years, underwent OLT between 1986 and 2000 under treatment with CIs (28 cyclosporine and five tacrolimus). Mean follow-up after OLT was 59 months. Adverse effects were renal dysfunction in 26, hypertension in 23, and neurotoxicity in two. MMF was added gradually while simultaneously reducing the dosage of CI. Results After a mean 15-months follow-up of MMF treatment, CIs had been withdrawn in 28 patients (85%). The mean time from the initiation of MMF and CI withdrawal was 5 months. During the first year of follow-up chronic renal dysfunction improved in 16 of 26 patients (61.6%) accompanied by a decreased serum creatinine and urea and an increase in creatinine clearance. Among 13/23 (56.5%) hypertensive patients, there was a significant decrease in blood pressure or the number of antihypertensive drugs (P < .05). One patient with neurotoxicity improved. Twenty-two patients (66%) displayed adverse events: five rejections (15%) including four acute episodes, controlled by CI re-introduction, and one chronic reaction. The most frequent adverse effects were herpes simplex infection in 10 patients (30%), asthenia in nine (27%), diarrhea in five (15%) and thrombocytopenia in four (12%). Nevertheless, only six patients (19%) required MMF dose reduction, namely, three patients with GI intolerance, two with repeated VHS infections, and one with anemia. Conclusions MMF monotherapy improves renal function and blood pressure levels in more than 50% of patients with chronic renal impairment and hypertension after OLT. Many of the side effects of MMF were mild; it was safe accompanied by a low incidence of rejection reactions.

De novo malignancies and liver transplantation

INTRODUCTION De novo tumors (DNTs) are the leading cause of late death among liver transplant recipients with an incidence of 5% to 15%, which is significantly greater than the general population. In this retrospective study, we compared this complication in liver transplant recipients to sex- and age-matched controls. PATIENTS Among 410 patients who received liver allografts between March 1986 and December 2000, 32 (7.8%) developed a DNT. Epidermoid tumors were the most frequent histologic lineage. A complete response was observed in 19 patients (59.4%), a partial response in eight (25%), and no response in five (15%). Survival was lower among liver transplant recipients than controls, a difference that was statistically significant. Treatment consisted of surgery in 76.7%, radiotherapy in 16.7%, chemotherapy in 13.3%, and reduction of immunosuppression in 10%. RESULTS The mean survival time in transplant patients of 122.97 months (95% CI; range 98-147 months) was significantly shorter than controls, 156.5 months (95% CI; range 141-171 months). About 50% of patients were smokers (active or ex-smokers), compared to 20.7% of controls (P=.049). Significant differences were also found when the three subgroups (smokers, previous smokers, and nonsmokers) were analyzed separately (P=.013). Patients were smokers (active or nonactive) among 45% of cases of skin tumors; 60% of hematological tumors; 71.4% of epidermoids; and 33% of sarcomas. CONCLUSIONS DNTs, a complication of long-term immunosuppression in patients after liver transplantation, most frequently presented as skin tumors and PTLD. Occurrence of a DNT was an adverse prognostic factor for survival. Smoking represents an independent risk factor for these tumors.

Incidence and results of arterial complications in liver transplantation: experience in a series of 400 transplants.

THE BASIC aim of vascular reconstruction in liver transplantation (LT) is to achieve an optimal arterial flow that ensures graft viability. Disturbances in arterial perfusion of the liver graft after transplantation are frequently due to technical problems leading to postoperative morbidity and mortality, which translate into graft failure, sepsis, and biliary complications. The incidence of arterial complications varies between 2% and 25% among liver transplant patients, of whom approximately 50% require retransplant. From the clinical point of view, thrombosis, stenoses, pseudoaneurysms, and steal syndromes can arise as complications in arterial reconstruction after liver transplantation. The purpose of this study was to examine the incidence and results of arterial complications in our liver transplant patients.

Breakthrough rhinocerebral mucormycosis in a liver transplant patient receiving caspofungin.

Zygomycetes are among the most frequent causes of non-Aspergillus mycelial fungal infections in transplant recipients. We have described a single case of breakthrough zygomycosis. A young Japanese woman presented because of idiopathic fulminant hepatitis and renal failure. On the third day of admission, she underwent orthotopic liver transplantation. A considerable amount of red blood cells and fresh frozen plasma were transfused during surgery. On posttransplant day 2, Candida albicans was isolated from respiratory secretions; prophylactic caspofungin was prescribed. During the next 6 days, C albicans was isolated from tracheal secretions, surgical wound, and exudates and stools. Ventilator-associated pneumonia was diagnosed day 4. Her renal function did not improve during the postoperative period; the patient continued on hemodialysis. On day 28, a dark blue eschar due to zygomycosis was detected on the skin of the nose. Tracheal and nasal exudates yielded Rhizopus sp. The patient died 12 hours later due to multiorgan failure with hypothermia. The fatal evolution in this case may be related to a presumed brain infarction after progressive vessel fungal invasion. The presented case had 2 risk factors related to zygomycosis. A high index of suspicion is required in transplant recipients with risk factors for zygomycosis. Early diagnosis and surgery with appropriate systemic fungal drugs (amphotericin B) are mandatory to improve the prognosis.

Usefulness of chemotherapy as prophylaxis of tumor recurrence after liver transplantation in advanced hepatocellular carcinomas

INTRODUCTION The effectiveness of chemotherapy as prophylaxis of tumor recurrence after liver transplantation in patients with advanced hepatocellular carcinoma is controversial. AIM Our goal was to assess the outcomes of patients with advanced hepatocellular carcinoma treated with chemotherapy after liver transplant. METHODS Ten patients with liver transplants performed between 1993-2002 were men of mean age 55 years. The etiology of cirrhosis was hepatitis C in four patients, alcoholic cirrhosis in four, and cryptogenic cirrhosis in two. Immunosuppressive therapy was cyclosporine in five patients and tacrolimus in five. The chemotherapy regimen used adriamycin (20 mg/m2 weekly for 20 weeks). Six patients were stage IVA and four stage III. Hepatocellular carcinoma was known in five patients and incidental in the other five. Pathology revealed well-differentiated hepatocellular carcinoma in six patients and moderately differentiated hepatocellular carcinoma in four. Five patients had vascular invasion. RESULTS After a mean posttransplant follow-up of 28 months, six patients (60%) were alive without tumor recurrence, three (30%) had died from tumor recurrence and one due to P. carinii pneumonia. Disease-free survival among patients with stage III was 50% and 80% for stage IVA. Three patients with vascular invasion died of tumor recurrence, and the other two are alive and free of disease. Disease-free survival rates were 83% in patients with well-differentiated hepatocellular carcinoma and 25% in those with moderately differentiated hepatocellular carcinoma. Tolerance of chemotherapy was good with two withdrawals due to nephrotoxicity and myelotoxicity and one death from pneumonia. CONCLUSION The use of adriamycin in patients undergoing liver transplant due to advanced hepatocellular carcinoma may be useful to prevent tumor recurrence; it is well tolerated. The presence of vascular tumor invasion and a lower grade of histologic differentiation were associated with a poor prognosis.

Right adrenal metastases of hepatocarcinoma after liver transplantation: case report and literature review.

BACKGROUND Hepatocellular carcinoma (HCC) represents one of the most common malignancies globally, accounting for nearly one million new cases per year. Although the treatment of extrahepatic metastases from primary liver tumors is essentially palliative, a solitary metastasis from such tumors offers a possibility of cure by surgical resection. The adrenal gland is an uncommon site for metastasis from primary liver tumors. METHODS We report a liver transplantation case of HCC and hepatitis B virus in a 23-year-old man with an excellent postoperative result. However, because an increased alpha-fetoprotein was evident and complete radiologic and blood tests were performed, all of which were normal. Three years posttransplantation, a right adrenal mass was identified by CT. PAAF was performed as well as adrenalectomy for a solitary adrenal metastasis from hepatocellular carcinoma. RESULTS The patient underwent adrenalectomy for the right adrenal metastasis at 3 years following liver transplantation for HCC. He is presently alive and disease-free 24 months after adrenalectomy. CONCLUSION Carefully selected patients with solitary metastasis from HCC may be considered for resection.

Influence of Infection by Aspergillus in Arterial Complications After Liver Transplantation: Evolution and Results in 670 Transplants

The incidence of fungal complications is frequent among liver transplanted subjects. Between March 1986 and June 2009, we performed 670 liver transplants in 593 patients, including 61% males and an overall average age of 46. The incidence of arterial complications in our center was 5.3% (32/593 patients), including 24 (75%) thromboses, 5 (16%) pseudoaneurysms, 2 anastomotic stenoses, and 1 an iliac graft rupture owing to a mycotic aneurysm. Four patients presented arterial complications associated with Aspergillus sp. Three of them were males of mean age 50 years and 3 had an acute rejection episode. Immunosuppression was cyclosporine (CsA), steroids, and azathioprine. Four arterial complications were diagnosed: 2 thromboses and 2 pseudoaneurysm ruptures. Two patients presented biliary complications associated with the arterial complication and Aspergillus infection. Treatment was expectant in 1 patient, interventional radiology in an other, and retransplantation in the other 2. All patients infected with Aspergillus sp. diad of sepsis and multiorgan failure. Arterial complications posttransplant associated with infection by Aspergillus sp., can be an important cause of retransplantation, sepsis and death.