Right hemiliver transplants from cadavers or living donors: a comparative analysis.

INTRODUCTION: The aim of this article was to compare the results of right hemiliver transplants from living versus cadaver donors in a single institution. METHODS: Between March 1999 and May 2003, we performed 10 right hemiliver transplants from living donors (LD) and 8 right hemiliver transplants from cadavers (CD). The procedure consisted of grafting liver segments 5, 6, 7, and 8. The procedure was performed with a fully perfused liver also in the CD group (in situ split). RESULTS: With follow-up between 7 days and 26 months in the LD group, 2 patients died with functioning grafts: 1 patient died because of massive pulmonary bleeding due to Rendu-Osler Syndrome; the other one died as a consequence of systemic aspergillosis. One patient underwent retransplantation due to arterial thrombosis. In the CD group with a follow-up between 31 days and 48 months, 3 patients died due to sepsis, including 2 who were status 2A. There were 4 early complications among the LD group and 5 in the CD group. The patient and graft survival rates were 80% and 70%, respectively, in the LD group; and both about 62% in the CD group. CONCLUSION: Right hemiliver grafts are at high risk due to technical and septic complications. A higher morbidity is observed in the CD group, where the vascular and biliary tree anatomy cannot be investigated with accuracy. We must avoid transplanting status 2A recipients with this kind of graft.

Right hemiliver transplants from living donors: report of 10 cases.

INTRODUCTION: A right lobe living related liver transplantation (LRLT) was performed for the first time in Italy on March 16, 2001 at our institution. METHODS: All donors underwent celiac and mesenteric axis angiography. Computed tomography scan to determinate the liver size and anatomical vascular variation, cholangio-magnetic resonance imaging, intraoperative cholangiography, and ultrasonography. All recipients were status 2B on the waiting list for cadaveric liver transplants. The surgical procedures were carried out by grafting segments 5, 6, 7, and 8 of the donor liver. RESULTS: Of the donors, all are alive; 4 had uneventful postoperative courses, 3 had moderate right pleural effusions; 3 had bilious drainage that resolved spontaneously: and 1 had a biliary leak and a pulmonary embolism. Of the recipients, 8 are alive with well-functioning grafts. One recipient has undergone retransplantation due to an arterial thrombosis and another recipient developed a stricture of the biliary anastomosis. Two recipients died: one because of pulmonary hemorrhage in Rendu-Osler syndrome, the other as a consequence of overwhelming systemic aspergillosis. CONCLUSIONS: Our experience suggests that few anatomical vascular and biliary variations are considered contraindications for right lobe LRLT. This challenging surgical procedure seems effective for well-selected recipients of United Network for Organ Sharing II B status. Appropriate recipient selection is crucial as we face a living donor.

Combined therapy with interferon and low-dose ribavirin in posttransplantation recurrent hepatitis C: a pragmatic study.

Recurrent hepatitis C is a common problem after liver transplantation that can progress to liver cirrhosis of the graft. Preliminary reports of combination treatment with interferon (IFN) and ribavirin have been promising, but long-term follow-up data are not yet available. We report our experience with 1 year of combination therapy with IFN (3 million units thrice weekly) and low-dose ribavirin (600 mg/d), followed by long-term ribavirin monotherapy in 18 patients with moderate to severe recurrent hepatitis C and a median follow-up of 32 months after the completion of combined therapy. All patients were followed up clinically and histologically at regular intervals. Overall, in an intention-to-treat analysis, 15 patients had normal alanine aminotransferase levels (biochemical end-treatment response [ETR], 83%), and 8 patients were also hepatitis C virus RNA negative in serum (virological ETR, 44%) at the end of combined treatment. At last follow-up after the completion of combined therapy (median, 32 months; range, 18 to 73 months), 13 patients were biochemical responders (biochemical long term-sustained response [LT-SR], 72%), and 5 patients also maintained viral clearance (virological LT-SR, 27%). Comparison of liver biopsy specimens before and after 12 months of combined therapy showed improvement in grading scores of at least two points in the majority of the patients (73%). Notably, a trend toward fibrotic progression was only noted in nonresponders. Regarding side effects, despite the low dose of ribavirn, almost half the patients developed hemolytic anemia requiring dose reductions. In addition, long-term ribavirin monotherapy was not associated with iron accumulation. We conclude that combined therapy with low-dose ribavirin followed by long-term ribavirin monotherapy can be recommended because it favorably modifies the natural history of recurrent hepatitis C in most patients and possibly halts histological disease progression without causing iron accumulation.

Incidence and clinical characteristics of posttransplant lymphoproliferative disorders: report from a single center.

In the period 1973-1998, among 2139 allograft recipients treated with standard immunosuppression, posttransplant lymphoproliferative disorders (PTLD) developed in 19 patients (0.9%): one plasmacytic hyperplasia, two polymorphic PTLD, one myeloma, and 15 lymphomas. PTLD developed 1 year after transplantation (tx) in 14 patients. Five patients were diagnosed at autopsy, 2 were lost to follow up, 3 died before therapy could be instituted, and 1 patient has just started chemotherapy. Of the 8 evaluable patients, 2 received acyclovir and are alive in complete remission (CR) and 6 received chemotherapy +/- surgery. Of these 6, 4 died of lymphoma and/or infection, 1 died of unrelated causes in CR, and 1 is alive in CR. PTLD is a severe complication of tx, usually running an aggressive course which may preclude prompt diagnosis and treatment. Nevertheless, therapy is feasible and must be tailored on the histologic subtype. Seventy-four percent of patients were diagnosed with late-onset PTLD stressing the need for long-term follow up.

Influence of immunogenetic background on the outcome of recurrent hepatitis C after liver transplantation.

In immunocompetent patients, specific human leukocyte antigen (HLA) class II alleles have been associated with the severity of hepatitis C virus (HCV)-related disease, in particular, HLA-DRB1*11 has been found to exert a protective effect. The authors have analyzed the role of HLA class I and II alleles in determining the frequency, timing, and progression of histologically proven recurrent hepatitis C in 89 patients who underwent a liver transplant for HCV-related cirrhosis. In addition, the influence of HLA mismatch between donor and recipient, HCV genotype, and use of steroid pulses was also evaluated. Median patient follow up was 35 months (range 4-119). HLA-DRB1 typing was performed by genomic analysis in all cases. Liver biopsies were obtained routinely and at least at yearly intervals. Histologically proven recurrent hepatitis was observed in 46 patients (52%), 10 patients progressing to stage 5-6 fibrosis in most cases within 2 years after transplant. By univariate analysis, 3 variables, HLA-B14, HLA-DRB1*04, and HLA-DRB1 donor/recipient mismatch, showed a significant effect on time to recurrent hepatitis C disease. These parameters were included in a multivariate regression model along with HCV genotype, treatment with steroid pulses and DRB1*11. HLA-B14, HLA-DRB1*04, and HLA-DRB1 donor/recipient mismatch were confirmed to provide a significant and independent contribution to the risk of hepatitic disease recurrence. As for the severity of the disease, none of the 10 patients with stage 5-6 hepatitis carried the HLA-DRB1*11 allele, in line with what was observed in nontransplant subjects. Our results suggest that in posttransplant recurrent hepatitis C, immunogenetic factors are relevant in determining HCV infection outcome.

Orthotopic liver transplantation in a patient with severe haemophilia A and with advanced liver cirrhosis.

A patient with severe haemophilia A underwent orthotopic liver transplantation because of changes correlated to end-stage liver cirrhosis due to hepatitis B, C and D infection. Replacement therapy was carried out for 4 days and the clinical course was uneventful. At the time of reporting the patient has a normal working life. FVIII plasma concentration is normal. The indirect hyperbilirubinaemia may be related to the Gilbert's anomaly of the donor.

HGV/GBV-C infection in liver transplant recipients: antibodies to the viral E2 envelope glycoprotein protect from de novo infection.

BACKGROUND/AIMS: Liver transplantation for endstage liver cirrhosis provides a useful model to investigate the pathogenetic role of hepatotropic viral agents. Recently, a new member of the Flaviviridae family, provisionally named HGV/GBV-C virus, has been associated with acute and chronic non A-E hepatitis. We studied 136 patients with cirrhosis consecutively transplanted at our institution for evidence of hepatitis G virus infection and correlation with the patients' clinical course. METHODS: All patients survived for at least 6 months after transplantation (median follow-up 44 months) and underwent routine liver biopsies. Hepatitis G virus infection was studied using both direct viral RNA identification by RT-PCR and indirect detection of antibodies to the E2 glycoprotein. RESULTS: There was a high frequency of the hepatitis G virus among patients undergoing liver transplantation, with HGV RNA and anti-E2 prevalence rates of 18.4% and 26.5%, respectively. HGV RNA prevalences significantly increased after transplantation (47.8%), with 47.3% rate of new infections in susceptible subjects. Anti-E2 antibodies were significantly more prevalent among patients transplanted for HCV-related cirrhosis and represented a strong protective factor against hepatitis G virus reinfection or recurrent infection. No correlation was found between HGV RNA or anti-E2 prevalences and survival after transplantation or rates of recurrent liver damage. CONCLUSIONS: All available evidence suggests that, although liver transplant patients are heavily exposed to hepatitis G virus both before and after transplantation, hepatitis G virus does not induce liver disease in this setting. Most infections appear to be self-limited and induce a protective immunity which is marked by the presence of anti-E2 antibodies.

Long-term efficacy of endoscopic stenting in patients with stricture of the biliary anastomosis after orthotopic liver transplantation.

BACKGROUND AND STUDY AIMS: The choledocho-choledochostomy (CCS) stricture is one of the most frequent complications occurring after liver transplantation. Endoscopic retrograde cholangiography (ERCP) is the most sensitive method used to define the presence and narrowness of the stricture. Endoscopic stenting of the strictured anastomosis could provide an effective alternative to the surgical intervention. PATIENTS AND METHOD: ERCP was performed in 36 of 210 patients with liver transplantation and acute cholestasis or jaundice: in 15 cases biliary anastomotic stricture was found. These patients were endoscopically treated by long-term stenting of the common bile duct (CBD) (1 year) and followed up for more than 12 months after stent removal. RESULTS: In all cases the stenting procedure resolved the biliary obstruction syndrome within 7 days. At the end of the stenting period the CCS was dilated enough to allow adequate bile flow and absence of cholestasis. Moreover, in most patients (10) the anastomosis was kept patient for more than 1 year after stent removal, whereas only two patients had stricture recurrence and needed endoscopic restenting. Four patients dropped out of the study, respectively because of liver rejection (two), acute liver failure (one) and myocardial infarction (one). One patient who developed a stone of the transplanted CBD underwent surgical intervention. CONCLUSIONS: According to our data, the endoscopic stenting of the CBD might be considered as the first choice procedure in the setting of the biliary anastomotic strictures occurring after liver transplantation. It has proved to be safe and effective, avoiding the need for more invasive surgery, which in any case should be considered for nonresponsive patients.

Hepatocellular carcinoma: comparison between liver transplantation, resective surgery, ethanol injection, and chemoembolization.

Between January 1989 and June 1997, 533 patients (423 male, 110 female, mean age 61 years, range 22-89 years) with hepatocellular carcinoma (HCC) were observed at our center. We report on 419 patients retrospectively compared for different treatments: liver transplantation (LT; 55 patients), resective surgery (RS; 41 patients), transarterial chemoembolization (TACE; 171 patients) and percutaneous ethanol injection (PEI; 152 patients). The 3- and 5-year actuarial survival rates were, respectively, 72% and 68% for LT, 64 and 44% for RS, 54 and 36% for PEI, and 32 and 22% for TACE. Survival curves were compared for sex, age, tumor characteristics, alphafetoprotein level, Child class, and etiology of cirrhosis. All patient-related characteristics examined (sex, age) are not significantly related to patient survival. Tumor-related variables and associated liver disease variables significantly conditioned survival in relation to different treatments. LT seems to be the treatment of choice for monofocal HCC less then 5 cm in diameter and in selected cases of plurifocal HCC.

Early cyclosporine monotherapy in liver transplantation: a 5-year follow-up of a prospective, randomized trial.

Maintenance of adequate immunosuppression and avoidance of side-effects are the goals of long-term management of all organ-transplanted patients. We here report the final results of a prospective, randomized trial comparing early cyclosporine monotherapy versus double-drug therapy (cyclosporine and steroids) in adult liver transplantation patients. One hundred four patients were randomized 3 months after transplantation either to continue (Group I = 50 patients) or to stop steroids (Group II = 54 patients). Patients on a double-drug regimen were maintained long term on methylprednisolone at a dose of 0.1 mg/kg/d. Target cyclosporine trough levels were between 150 and 250 ng/mL in both groups. Our main points of interest were the prevalence of acute and chronic rejections and steroid-related side-effects in the two groups of patients. Mean follow-up was 41 +/- 16 months (range, 4-68 months). Patient actuarial survival 2 and 5 years after randomization was similar in the two groups (82% vs. 83% and 82% vs. 77%). The prevalence of acute rejections after randomization was, respectively, 8% and 4%. A single episode of chronic rejection was observed only in a patient on long-term steroid therapy. Side-effects of steroid therapy were less frequent in patients weaned off steroids, and when considering hypertension and diabetes, the differences between the two groups were statistically significant. Early cyclosporine monotherapy is a safe undertaking in liver transplantation because it allows a significant reduction of steroid-related side-effects without increasing the risk of acute and chronic rejection. After 5 years, patient survival was similar in patients with or without steroids.