Because of the donor shortage, there are concerns for liver transplantation in patients with alcoholic cirrhosis. We therefore analyzed patients transplanted for alcoholic cirrhosis at our center with respect to patient and graft survival, recurrence of disease, and postoperative complications. Out of 1000 liver transplantations performed in 911 patients, 167 patients were transplanted for alcoholic cirrhosis; 91 patients received CsA- and 76 patients FK506-based immunosuppression. Recurrence was diagnosed by patient's or relative's declaration, blood alcohol determination, and delirium. Diagnosis and treatment of acute and chronic rejection was performed as previously described. One- (96.8% versus 91.3%) and 9-year patient survival (83.3% versus 80%) compared well with other indications. Five of 15 patients died due to disease recurrence. Recurrence of disease was significantly related to the duration of alcohol abstinence prior to transplantation. In patients who were abstinent for less than 6 months (17.1%), recurrence rate was 65%, including four of the five patients who died of recurrence. Recurrence rate decreased to 11.8%, when abstinence time was 6-12 months and to 5.5%, when the abstinence times was > 2 years. Next to duration of abstinence, alcohol relapse was significantly related to sex, social environment, and psychological stability. The incidence of acute rejection compared well with other indications (38.1%); CsA: 40.1% versus 33.3% in FK506 patients. In all, 18.2% of CsA patients experienced steroid-resistant rejection compared with 2.6% of FK506 patients. Seven patients (7.6%) in the CsA group and one patient (1.3%) in the FK506 group developed chronic rejection. A total of 57.1% developed infections; 5.7% were life-threatening. CMV infections were observed in 14.3% (versus 25% for other indications). New onset of insulin-dependent diabetes was observed in 8.6% and hypertension in 32.4%. In conclusion, alcoholic cirrhosis is a good indication for liver transplantation with respect to graft and patient survival and development of postoperative complications. FK506 therapy was favourable to CsA treatment. Patient selection is a major issue and established criteria should be strictly adhered to. Patients with alcohol abstinence times shorter than 6 months should be excluded, since recurrence and death due to recurrence was markedly increased in this group of patients.

Adult↗

PubMed2000

Perioperative factors influencing patient outcome after liver transplantation.

We have previously shown that the development of multiple organ dysfunction syndrome (MODS) after liver transplantation significantly reduced patient survival. Therefore, the question arises of which are the most prominent perioperative donor and recipient factors leading to MODS after transplantation. In total, 634 patients with 700 liver transplants were analyzed. Donor factors included age, increase in transaminases, sex mismatch, requirement for catecholamines, intensive care time, histology, and macroscopic graft appearance. Recipient factors included Child classification, preoperative gastrointestinal (GI) bleeding, mechanical ventilation, hemodialysis, and requirement for catecholamines. MODS was defined by more than two severe organ dysfunctions. The cumulative 2 to 9-year patient survival was 90.9% in patients developing less than 3 severe organ dysfunctions following transplantation. Survival decreased to 60.3% in patients with MODS. Neither any of the donor factors nor the duration of cold ischemia (CIT) was associated with an increase in MODS or decrease in survival. On the other hand, duration of warm ischemia, amount of blood loss, requirement for red packed blood cells, and reoperation had an influence on the development of MODS (40%-56%) and decreased patient survival to 58%-69%. Preoperative therapy with catecholamines, GI bleeding, mechanical ventilation, and hemodialysis were associated with the development of MODS in 54%-88%. Patient survival following MODS decreased to 50%-74%. Initial graft function had a slight influence on the development of MODS, but no influence on the long-term patient survival. In conclusion, patient survival was significantly influenced by the development of postoperative MODS. The most prominent factors in this were recipient and intraoperative ones. No major influence was observed for donor factors, CIT, and initial graft function. Prevention of MODS will further improve the outcome after liver transplantation.

Age Factors↗

PubMed2000

Basement membrane changes associated with cold temperature.

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Animals↗

PubMed2000

L-arginine application improves graft morphology and mucosal barrier function after small bowel transplantation.

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Animals↗

PubMed1998

The extracellular matrix: an early target of preservation/reperfusion injury and acute rejection after small bowel transplantation.

BACKGROUND: Endothelial cells are known to be an early target of preservation/reperfusion injury and acute rejection, whereas the extracellular matrix (ECM) may also play an equally important role in the sequelae of both events. METHODS: Syngeneic and allogeneic rat small bowel transplantations (SBTX) were performed after 6 hr of preservation. Animals were subsequently killed at defined time points for determination of ECM parameters within the graft and in plasma. RESULTS: Laminin levels were significantly increased 20 min after reperfusion (syngeneic SBTX: 357+/-65.9 ng/ml; allogeneic SBTX: 361+/-79.6 ng/ml; P< or =0.01). After syngeneic transplantation, laminin levels normalized by postoperative day (POD) 7, whereas there was a rejection-induced increase after allogeneic SBTX (POD 7: 179+/-60.1 ng/ml; POD 9: 333+/-13.6 ng/ml; P< or =0.01 vs. syngeneic SBTX). This increase was accompanied by an increase in tumor necrosis factor-alpha levels at POD 9. Hyaluronic acid levels were significantly elevated after 24 hr (syngeneic SBTX: 1086+/-176 microg/L; allogeneic SBTX: 918+/-108 microg/L; P< or =0.01). After syngeneic SBTX, hyaluronic acid levels normalized by POD 7, whereas persistently higher levels were observed after allogeneic SBTX. Immunohistochemistry confirmed early changes (20 min after reperfusion) at the ECM. Anti-laminin and anti-CD44 staining normalized at POD 5 after syngeneic SBTX. After allogeneic SBTX, rejection-specific changes were evident with anti-laminin staining commencing on POD 5 and progressing until POD 9. At similar time points, increased expression of fibronectin- and interferon-gamma-positive material was evident. CONCLUSIONS: The ECM can be considered to be an early target of preservation/reperfusion injury and acute rejection. Plasma parameters reliably reflected the changes observed within the graft. Laminin and hyaluronic acid levels may be used as indicators of initial graft function. Furthermore, the increase in laminin levels was an early indicator of acute rejection. Determination of these parameters may significantly improve monitoring after SBTX.

Animals↗

PubMed1998

Searching for the optimal management of hepatitis C patients after liver transplantation.

The optimal immunosuppressive regimen in patients transplanted for hepatitis C (HCV) is still under discussion. High immunosuppression may promote viral replication and recurrent graft hepatitis. But acute and chronic rejection frequently seen in conjunction with HCV recurrence may require some rescue therapy. One hundred and thirty-seven patients transplanted for HCV cirrhosis, who were HCV-RNA positive prior to transplantation, were analyzed. Seventy-nine patients received CSA-based immunosuppression and 58 patients FK506-based immunosuppression. One-month patient survival was 100% in both groups. Three month and 1-year survival rates and the cumulative 1-5-year patient survival was similar in CsA-treated [67/79 (84.8%)] and FK506-treated patients [50/58 (86.2%)]. Retransplantations for HCV recurrence were performed in 5.1% of CsA-treated patients and 6.9% of FK506-treated patients; it was successful in 50% and 75% of patients, respectively. Conversion from CsA to FK506 and vice versa was high with 25 out of 79 patients (31.6%) converting in the CsA group and 8 out of 58 patients (13.8%) converting in the FK506 group. Conversion to FK506 was performed due to acute and chronic rejection and to CsA because of toxicity and HCV recurrence. In both groups, 25% of converted patients died. Five patients of the CsA group and 9 of the FK506 group received OKT3; more than one-third of each group died. Five patients in the CsA group and 6 in the FK506 group received mycophenolate mofetil (MMF) for HCV recurrence or acute and chronic rejection in conjunction with HCV recurrence. All patients of this critical group are alive with good graft function. In conclusion, survival rates of HCV patients were similar to those seen for other indications. Conversion from CsA to FK506 and vice versa was high and reflects a critical group concerning patient survival. OKT3 treatment should be avoided. A promising therapeutic option for critical patients experiencing acute or chronic rejection in conjunction with HCV recurrence may be treatment with MMF.

Hepatitis C↗

PubMed1998

Changes at the extracellular matrix during acute and chronic rejection in human liver transplantation.

We have previously observed changes at the extracellular matrix (ECM) which significantly correlated with the extent of preservation and reperfusion injury. In the present study, we attempted to investigate whether the ECM may be also involved in the pathophysiological sequelae of acute and chronic rejection. Of 81 patients monitored for the ECM parameters laminin, hyaluronic acid, fibronectin receptor, and transforming growth factor (TGF)-beta, 28 patients developed acute rejection (< 1 month), in 14 patients (17.4%) acute rejection was steroid resistant, 4 patients (4.5%) developed early chronic rejection following acute steroid-resistant rejection. Acute and chronic rejection were confirmed by established clinical and histological criteria. Laminin levels were significantly increased in patients experiencing acute steroid-resistant rejection (4204 +/- 133 ng/ml; P < or = 0.01) compared with patients with steroid-sensitive rejection (1059 +/- 27.3 ng/ ml) and with an uneventful postoperative course (1214 +/- 17.4 ng/ml). No increase in laminin was observed in those four patients who developed early chronic rejection (1099 +/- 58.7 ng/ml). Hyaluronic acid, fibronectin receptor, and TGF-beta levels also increased in patients with acute steroid-resistant rejection; hyaluronic acid: 290 +/- 10.8 micrograms/l vs 154 +/- 13.6 micrograms/l and 131 +/- 11.7 micrograms/l in patients with steroid-sensitive and no rejection, respectively; fibronectin receptor: 1003 +/- 23.5 ng/ml vs 573 +/- 24.8 ng/ml and 428 +/- 13.6 ng/ ml in patients with steroid-sensitive and no rejection, respectively; and TGF-beta: 393 +/- 14.9 pg/ml versus 315 +/- 10.7 pg/ml and 233 +/- 8.9 pg/ml in patients with steroid-sensitive and no rejection, respectively. A further increase in hyaluronic acid levels was observed in patients who developed early chronic rejection, while fibronectin receptor and TGF-beta levels remained low, similarly to laminin levels. The increase in laminin, hyaluronic acid, fibronectin receptor, and TGF-beta during acute steroid-resistant rejection may be stimulated by the rejection-related release of cytokines and adhesion molecules which paralleled the increase in ECM parameters. The lack of increase in laminin and fibronectin receptor levels in those patients who developed early chronic rejection may reflect an inability to recover from acute rejection.

Acute Disease↗

PubMed1998