Ramón Gómez

Steroid withdrawal is safe and beneficial in stable cyclosporine-treated liver transplant patients

BACKGROUND In the immunosuppression of orthotopic liver transplant recipients, steroids are used despite their unspecific action and long-term side effects. Few studies have been carried out on steroid withdrawal and many aspects remain to be elucidated. METHODS A prospective study was performed to analyse the effect of steroid withdrawal on 86 patients with stable graft function, more than 1 year after orthotopic liver transplant. Thirty patients had chronic hepatitis in the graft. Seventy-two continued with cyclosporine (CsA) and 14 with CsA-azathioprine (AZA) therapy. The follow-up was 23.2 +/- 8.1 months (range 12-52 months). A paired t-test was used for statistical analysis. RESULTS No acute or chronic rejection occurred, and steroids were not reinstituted. There were no changes in serum transaminase levels, but bilirubin levels decreased (p < 0.01). At the end of the follow-up, we found improvements in blood pressure in hypertensive patients (systolic 156.1 +/- 8.4 mmHg vs. 139.4 +/- 8.7 mmHg, p < 0.001); body weight (72 +/- 13.5 kg vs. 70.8 +/- 13 kg, p < 0.05); serum cholesterol (211.3 +/- 42 mg/dl vs. 191.6 +/- 43.5 mg/dl, p < 0.001) and bone mineral density in lumbar spine (0.823 +/- 0.13 g/cm2 vs. 0.893 +/- 0.135 g/cm2, p < 0.001). Four of ten diabetic patients were no longer insulin-dependent and insulin requirements decreased in the remaining six. No significant biochemical changes were found in patients with hepatitis in the graft, and we found an improvement in inflammatory activity in the nine biopsied patients. CONCLUSIONS Steroid withdrawal with CsA monotherapy is feasible, safe and beneficial in patients who have stable liver graft function 1 year after orthotopic liver transplant. We consider that AZA therapy is not necessary unless drastic reduction of CsA levels is required because of renal dysfunction.

Incidence and risk factors for the development of lung tumors after liver transplantation

Tobacco and immunosuppression are risk factors for developing upper aerodigestive and lung tumors after transplantation. This study comprises 701 adult recipients who survived more than 2 months after transplant: 276 patients underwent orthotopic liver transplantation (OLT) for alcoholic cirrhosis (AC) and 425 for nonalcoholic disease. The aim is to analyze the incidence, clinical characteristics, risk factors, and outcome of patients who develop lung malignancies after OLT. Incidence of lung cancer was 2.1% (15 patients): 4.3% (12 patients) in the alcoholic group and 0.7% (three patients) in the nonalcoholic group (P < 0.001). Mean time from OLT to tumor diagnosis was 86 months. Thirteen patients were smokers; 12 patients were heavy drinkers; and 11 were drinkers and smokers. Squamous cell carcinoma was diagnosed in nine patients, large cell carcinoma in three, adenocarcinoma in two, and broncoalveolar in one. Tumor staging: 10 patients at stage IV; three at stage IIIB; and two at stage IIB. Tumor resection was performed in one patient, and three also received chemotherapy. Mean survival after tumor diagnosis was 5.4 months. There is a higher risk of lung cancer in smoker patients who have undergone OLT for AC, and have a very poor prognosis because tumors are diagnosed at advanced stages.

Reuse of Liver Grafts after Early Death of the First Recipient

Abstract. Three cases are reported of reuse of a transplanted liver graft after early death of the first recipient due to cerebral hemorrhage. The good condition of the donors; the excellent biochemical evolution of the graft in the first recipients; total ABO compatibility and donor-recipient crossmatch; the absence of positivity to hepatitis B virus (HBV), hepatitis C virus (HCV), and bacteriologic cultures; and early death made reuse possible. The shortage of donors in relation to patients on the waiting list and the poor clinical condition of the second recipients made it necessary to adopt the decision to reuse the graft in an attempt to save their lives. The evolution of the patients and the reused grafts was satisfactory, and there were no complications that could be attributed to the fact that the graft had been transplanted before.

Etiopathogenesis and prognosis of centrilobular necrosis in hepatic grafts

The incidence, contributing etiopathogenetic factors, and prognostic significance of centrilobular necrosis were investigated in 270 hepatic transplants to 215 immunosuppressed patients in whom 837 biopsies were performed. Twenty-six (9.6%) grafts demonstrated centrilobular necrosis in one or more biopsy specimens. The immunological, clinical, histopathological, and evolutionary features of this patient group (group A) were compared with a control group of patients who had undergone 92 consecutive transplants with no necrosis (group B). Group A was younger (p < 0.01), had a higher average of warm and cold-ischemia time (p < 0.05), a higher incidence (p < 0.001) and earlier appearance of acute rejection episodes (p < 0.01), and a closer association with evolution to chronic rejection (A: 53.8% vs B: 13.1%, p < 0.001). Survival rates for grafts and patients with necrosis at 12 and 30 months were significantly lower (p < 0.001). The 26 grafts were distributed into three chronological subgroups according to when necrosis appeared: (1) First week--All these grafts were lost (four through primary graft nonfunction and one due to protal recurrent thrombosis); (2) Second week--seven grafts with associated acute rejection, with three evolving to chronic rejection; (3) After the second week (116 +/- 82 days)--five with isolated necrosis, two with associated acute rejection, four with associated ductopenia, and three with associated acute rejection and ductopenia. In 11 grafts the necrosis persisted and evolved to chronic rejection. In conclusion, these findings indicate that centrilobular necrosis is a histopathological sign associated with poor prognosis in most hepatic grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Advanced donor age increases the risk of severe recurrent hepatitis C after liver transplantation

The association between donor age and the severity of recurrent hepatitis C and, whether there is any donor age above which severity of recurrence increases significantly, were analyzed. A total of 131 liver grafts of hepatitis C virus (HCV)‐infected recipients were selected for the study. Distribution of donor age was compared between grafts with and without severe recurrence. The risk of developing severe recurrence as well as the hepatitis‐free, severe hepatitis‐free and HCV‐related graft survival was compared between different donor age groups. Mean donor age was higher for grafts with severe recurrence (P = 0.007). The risk of developing severe recurrence within 2 years post‐transplant increased with donors aged ≥50 years (RR = 1.34) and donors aged ≥70 years (RR = 1.61). Five‐year severe hepatitis‐free survival rates decreased progressively when donor age was over 50 years (P < 0.001). The study shows 50 and 70 years as the donor age cut‐off points above which the evolution of HCV‐infected recipients worsens.

Choledochocholedochostomy conversion to hepaticojejunostomy due to biliary obstruction in liver transplantation.

Abstract. Choledochocholedochostomy with tutor (CC-T) or without (CC) is the technique of choice for biliary reconstruction in orthotopic liver transplantation (OLT), however, its rate of complications is high and does not decrease significantly over the years. Biliary obstruction is the most frequent complication and surgical treatment frequently involves conversion to hepaticojejunostomy (H-J). Out of 412 patients (448 OLTs) analyzed retrospectively, 74 (18%) presented biliary complications and 25 (6%) required conversion to H-J because of biliary obstruction, generally due to anastomotic stenosis (17 patients, 68%). Sixteen out of the 25 presented after the first 3 months, and in two patients, stenosis was secondary to arterial thrombosis. Anastomotic stenosis was more frequent in the CC group than in the CC-T group (9.9% versus 2.6%, p < 0.05). Sixteen patients (64%) underwent percutaneous dilatations, but the response was only transitory. There were no postoperative deaths. At the follow-up, three (12%) of the 17 surviving patients presented episodes of cholangitis which required percutaneous dilatations (1), revision of the H-J (1), or conversion to hepaticojejunoduodenostomy (1). Mean survival of patients with H-J was 70.9%, and the actuarial survival rate was 68% at 5 years. This does not differ from the actuarial survival in our series of transplanted patients (65%). CC or CC-T (in selected cases) is an adequate biliary reconstruction for OLT, in spite of the fact that a small number of patients will require conversion to H-J. H-J is an excellent technique of rescue in cases of biliary obstruction that are not possible to resolve by percutaneous dilatations.

Liver transplantation in patients with Budd-Chiari syndrome

Patients with Budd-Chiari syndrome (obstruction of the hepatic veins) and associated hepatic insufficiency may be candidates for orthotopic liver transplantation (OLT). In our series of 405 OLT patients, 3 were transplanted due to Budd-Chiari syndrome (0.7%). The indication for liver transplantation in these patients was severe hepatic insufficiency (chronic in two and acute in the third one). Morphologic study of the obstructions revealed apparently different causes, including thrombi, membranous webs in hepatic veins, and hydatid cyst compression. The surgical technique employed in these transplantations was similar to that for other etiologies. Due to its implications for the future course of OLT, it is important to determine the exact etiology of Budd-Chiari syndrome in the pretransplant period and to treat the patients with early and long-term anticoagulant therapy to avoid syndrome recurrence.