Our experience in liver transplantation in patients over 65 yr of age.

OBJECTIVES: The aim of this study was to analyze short- and long-term results of liver transplantation (LT) in patients over 65 yr. MATERIAL AND METHODS: Between 1996 and 2004, 386 patients underwent 415 LT at our center. The main indication for LT was post-necrotic cirrhosis in 59%, followed by hepatocellular carcinoma (HCC) over cirrhosis in 33%. Half of the patients (53%) were hepatitis C virus (HCV) +. Overall, 72 patients were >65 yr of age. Actuarial survival, causes of mortality and postoperative complications were compared between groups: patients under and over 65 yr. Risk factors for poor outcome in patients over 65 yr were also analyzed. RESULTS: The older group had more patients at Child A stage, more HCC as an indication for LT and more HCV (+) patients, p < 0.05. No differences were observed in donor and surgery characteristics, except for lower multi-transfusion and higher incidence of grafts with steatosis in the older group (p < 0.05). Actuarial survival at one, three, five and 10 yr was 82%, 75%, 72%, and 70% for the <65 yr group vs. 77%, 66%, 55%, and 55% for the >65 yr group (p = 0.03). Main causes of mortality in patients >65 yr were recurrence of underlying disease and medical causes. In the older age group, fewer infections (p = ns) and rejections (p = 0.017) occurred in the postoperative period. Risk factor for poor outcome in the group of patients over 65 yr in multivariate analyses was pre-LT renal insufficiency (odds ratio 3.5, p = 0.002, 95% confidence interval 1.58-7.82). CONCLUSION: Results in patients >65 yr are comparable to those <65 yr if older LT candidates are carefully selected. Overimmunosuppression should be avoided in older candidates, as its effects could worsen the pre-existing diseases common in elderly patients.

[Krukenberg's tumor as the first clinical manifestation of fibrolamellar hepatocarcinoma]. / Tumor de Krukenberg como manifestación inicial de hepatocarcinoma fibrolamelar.

Krukenberg's tumor refers to unilateral or bilateral ovarian metastatic tumors whose origin may be known or unknown. The incidence of this type of tumor is difficult to evaluate but may represent between 3% and 8% of ovarian tumors. In most cases, the primary tumor is identified and is usually digestive (basically gastric or colorectal). There are some references to primary hepatic tumors (gall bladder tumor and hepatocarcinoma) but none to fibrolamellar hepatocarcinoma as the primary tumor. We present the case of a 45-year-old woman who presented with lower hemiabdominal pain and who was diagnosed with Krukenberg's tumor of hepatic origin. Although ovarian involvement in primary digestive tumors is possible, hepatic origin is rare.

Liver transplantation in HIV-HCV coinfected patients: a case-control study.

Liver transplantation (LT) for hepatitis C virus (HCV)-associated cirrhosis in human immunodeficiency virus (HIV)-infected patients was compared with non-HIV patients. Nine patients with HIV-HCV coinfection were compared with patients transplanted before and after each HIV patient (control group). Immunosuppression consisted in tacrolimus with steroids or mycophenolate mofetil. Acute cellular rejection and three-year actuarial patient survival were respectively 44% and 87.5% in HIV group and 22% and 93.7% in the control group (P=NS). Acute hepatitis C virus occurred earlier (2.3 vs. 4.3 months) and was more cholestatic (mean bilirubin: 10.8 vs. 1.6 mg/dL) in the HIV group. Eight (100%) HIV and nine (64.3%) control patients received antiviral treatment with pegylated interferon and ribavirin. One patient (11.1%) of the control group and one patient (20%) of the HIV group presented a sustained virologic response (P=NS). Short- to midterm results of LT in HIV-HCV co-infected patients were excellent and similar to non-HIV patients.

[Hepatic angiomyolipoma in two patients infected with hepatitis C virus]. / Angiomiolipoma hepático en dos pacientes con infección por el virus de la hepatitis C.

AIM: The aim of this study is to present our experience with two cases of hepatic angiomyolioma in hepatitis C virus (HCV) positive patients, and to up-date the clinical manage, diagnostic and treatment of this entity. CLINICAL OBSERVATIONS: Both cases were presented in women in their 4-5th decade of life. Clinical presentation was with symptoms in one but incidental in the other. Both were HCV positive. Values of alpha-fetoprotein were normal. Radiological imaging was not diagnostic. Histopathological examination and immunohistochemical findings gave the diagnosis of angiomyolipoma. At time of diagnosis the size of tumours was 4.8 and 8 cm of diameter. Both cases were treated with surgery in order to definetly rule out malignancy. After 6 and 3 years of follow-up, there is no evidence of recurrence. DISCUSSION AND CONCLUSION: The hepatic angiomyolipoma is a rare benign tumour, mimicking other liver tumours. Although no patognomonic features, there are some radiological findings that point out to the diagnosis of angiomy olipoma. Nevertheless, definitive diagnosis is done by his tological and immunohistochemical findings (HMB-45). The hepatic angiomyolipoma consists of varing proportion of three elements, mature fat cells, smooth muscle cells and blood vessels. Although it is a benign tumour, the difficulty in ruling out malignancy, prompted surgical management. It is not described its relation with HCV virus, thus we consider our cases as an coincident finding.

Early antiviral treatment of hepatitis C virus recurrence after liver transplantation in HIV-infected patients.

OBJECTIVE: To investigate the efficacy of early antiviral treatment for hepatitis C virus (HCV) recurrence in HIV/HCV-coinfected patients undergoing liver transplantation for end-stage liver disease. METHODS: Open prospective trial of early treatment of HCV recurrence in consecutive HIV/HCV-coinfected patients transplanted at a tertiary hospital in Barcelona between 2002 and 2004. All patients had indication for liver transplantation, no previous CDC class C HIV-associated opportunistic events, a CD4+ T-cell count >100cells/microl, and undetectable plasma HIV RNA on highly active antiretroviral therapy. Treatment with pegylated interferon-alpha2b (1.5 microg/kg/week) and ribavirin (800-1000 mg/day) was given for 24 to 48 weeks, as soon as HCV recurrence was histologically documented. RESULTS: Of six patients who underwent transplant, five patients surviving the early post-transplantation period developed HCV recurrence, presenting as severe cholestatic hepatitis in three, and were started on antiviral treatment a median of 12 weeks (range: 5-31) after transplantation. After a median follow-up of 24 months all treated patients were alive. Biochemical response was achieved in all patients, although only one achieved a sustained virological response. Mild rejection before HCV recurrence occurred in two cases. Treatment was well tolerated with no episodes of rejection or mitochondrial toxicity. No patient required modification of the antiretroviral regimen. Liver biopsies performed in patients without virological response, 12-34 months after transplantation, showed cirrhosis in two and moderate chronic active hepatitis in the remainder. CONCLUSIONS: Despite early antiviral treatment, severe HCV recurrence after liver transplantation may compromise long-term survival in HIV-infected patients. Improved treatment strategies for these patients are urgently required.

Immunosuppression based on mycophenolate mofetil in stable liver transplanted patients.

AIM: To analyze our results with mycophenolate mofetil (MMF) in stable liver transplantation (LT) patients presenting with adverse events (AE) related to prolonged use of calcineurin inhibitors (CNI). METHODS: Conversion to MMF was performed in 56 out of 323 LT patients from 91-02: 24 (43%) were converted to MMF in monotherapy and 32 (57%) to MMF+low doses of CNI. The indication for conversion was chronic renal insufficiency (CRI) in all patients. The mean time between AE and conversion was 38.7+/-30 months (r: 2-101 m). Post-conversion follow-up was 39+/-20 months (r: 3-72 m). RESULTS: The calculated creatinine clearance (Crauckoft), improved significantly in all patients. In those converted to MMF, improvement was seen during the first 18 months for urea and during the first 6 months for creatinine. In patients converted to MMF+CNI, improvement was maintained throughout the conversion period for both urea and creatinine. Eleven (19.6%) patients underwent acute rejection (2 severe episodes in the MMF group and 1 death). Hypertension was present in 31 patients but only improved in 4 (7%). Dyslipemia was found in 12 and improved in 4 (7%). DM was present in 14 and improved in 1 (2%). CONCLUSIONS: Conversion to MMF in monotherapy is useful in stable LT patients with CRI due to CNI, although this result is offset by more severe rejections. Therefore, for AE secondary to CNI, we propose an early conversion to MMF+low doses of CNI as a first step. If liver function remains stable and AEs persist or progress, conversion to MMF in monotherapy is recommended, as a second step, with close monitoring of the patient.

Xanthine oxidoreductase and preservation injury in human liver transplantation.

BACKGROUND: Preservation injury is a major cause of primary graft dysfunction in liver transplantation (LT). Oxidative damage is considered to be the first event leading to graft damage. Xanthine oxidoreductase (XOR) and neutrophil activation, two sources of reactive oxygen species, could play a role in the development of graft dysfunction. METHODS: We determined activities of XOR forms, polymorphonuclear elastase (PMN-E), aminotransferases, and hyaluronic acid in plasma of 20 patients undergoing LT. Samples were taken from the radial artery (RA) before the anhepatic phase; from the portal vein (PV) before reperfusion; from graft caval effluent (CE) at reperfusion; and from RA, PV, and the hepatic vein (HV) 10 and 90 min postreperfusion. RESULTS: The graft, but not recipient bowel, released XOR into blood (XOR in CE, median, 61.2 mU/g protein [range, 1.9-160.4 vs. undetectable in PV before reperfusion). Circulating XOR was transformed from dehydrogenase to reversible oxidase (XOrev) (XOrev-to-XOR ratio, 48.1% in CE and 65.1% in HV 90 min postreperfusion). Neutrophil activation was detected in the recipients before reperfusion, and in liver at early post-reperfusion (median PMN-E was 0.85 microg/g protein [range, 0.01-1.58] in RA before the anhepatic phase; 2.22 microg/g protein [range, 0.20-5.88] in PV prereperfu-sion; and 3.60 microg/g protein [range, 0.48-6.78] in HV 10 min postreperfusion). XOR, but none of the other markers, was higher in the CE of patients with moderate primary graft dysfunction than in those with slight primary graft dysfunction. CONCLUSIONS: XOR release and neutrophil activation are produced during LT, and they are potentially injurious mechanisms associated with this therapy.

Analysis of growth during prepubertal years in long-term survivors after pediatric orthotopic liver transplantation.

BACKGROUND: Growth after pediatric liver transplantation (LT) has been the subject of reviews. The conclusions have not been consistent. OBJECTIVE: To describe post-LT growth patterns in prepubertal liver transplant recipients and identify variables affecting their growth. METHODS: Sixty-seven prepubertal transplant recipients met the inclusion criteria. Variables assessed were age, sex, pretransplant lack of growth, type of transplantation, primary diagnosis, liver and kidney function at one year post-LT, complications and retransplantation, prednisone therapy duration, allograft rejection episodes during the first year, cholesterol, triglycerides and immunosuppressive regimen. Mean follow-up was 3.5 years (range: 2-6 years). RESULTS: Growth according to baseline z-score, indications for transplantation and steroid withdrawal showed significant differences at 2 years post-LT. CONCLUSIONS: The causes of poorest z-scores in height post-LT were: height z-scores under -2.0 at transplantation, metabolic diagnosis, and use of steroids beyond 1 year post-LT.

A prospective randomized trial comparing tacrolimus and steroids with tacrolimus monotherapy in liver transplantation: the impact on recurrence of hepatitis C.

The aim of this prospective randomized trial was to study the efficacy and safety of tacrolimus monotherapy (TACRO) and compare it with our standard treatment of tacrolimus plus steroids (TACRO + ST) after liver transplant (LT). Furthermore, the impact of steroid-free immunosuppression on outcome of hepatitis C virus (HCV) was analysed. Between 1998 and 2000, 60 patients (mean age: 57 years) were included in the study and randomized to receive TACRO (n = 28) or TACRO + ST (n = 32). Indication for LT was postnecrotic cirrhosis in all cases (58.3% were HCV-positive). Mean follow-up was 44 months. Survival, incidence of rejection, infection and side-effects were compared between the two groups. In patients with HCV infection, incidence and severity of acute hepatitis C, long-term outcome of recurrent hepatitis C and survival were studied in an intention-to-treat analysis or in the real group analysis (real-TACRO versus real-TACRO + ST). Patient survival at 1, 3 and 5 years, tacrolimus pharmacokinetics, incidence of rejection infections and side-effects were similar. In patients with HCV, the incidence and severity of graft hepatitis C tended to be lower in TACRO (47%) compared with TACRO + ST (67%) (P = NS), and also in real-TACRO (42%) compared with real-TACRO + ST (61%) (P = NS). A poor outcome considered as evolution to cirrhosis at 3 years was observed in one (9%) living patient in real-TACRO and nine (45%) in real-TACRO + ST (P = 0.04). Patient survival at 1, 3 and 5 years was 92%, 92% and 73% for real-TACRO and 78%, 61% and 51% for real TACRO + ST (P = 0.07). Steroid-free immunosuppression appears to be safe and efficacious. The main advantage of this regimen could be in HCV patients, as recurrence of hepatitis in the graft was less severe in the group of patients in whom steroids could be avoided completely.

Resection for hepatocellular carcinoma is a good option in Child-Turcotte-Pugh class A patients with cirrhosis who are eligible for liver transplantation.

The best treatment option for patients with single, early hepatocellular carcinoma (HCC) and cirrhosis, good liver function, and absence of portal hypertension remains to be established. The aim of this work was to compare the outcome of liver resection (LR) with that of liver transplantation (LT) for single, early HCC in Child-Turcotte-Pugh class A patients with cirrhosis younger than 70 years of age. Thirty-seven of 134 patients who underwent LR and 36 of 125 who underwent LT for HCC in our unit fulfilled the inclusion criteria. No differences were observed in mean tumor size (3 cm); HCV cirrhosis predominated in the LT group and older age in the LR group. Postoperative mortality was higher and hospital stay longer in the LT group. Patient survival was similar in both groups. Tumor recurrence was higher in the LR group (59% vs. 11%), extrahepatic recurrences predominated after LT and hepatic recurrences after LR. Disease-free survival was significantly better after LT. Eighteen patients presented hepatic recurrence after LR: 5 advanced and 13 early. Seventeen patients--13 with early HCC recurrence and 4 with liver failure--were potential candidates for salvage LT. However, 10 of 17 patients were older than 70 years at this time. Salvage LT could only be performed in 6 patients: 5 for HCC recurrence and 1 for liver failure. Results of salvage LT were similar to those of primary LT. In conclusion, only 27.6% of resected patients were eligible for LT. LR is a good option since it offers similar survival to LT. Salvage liver transplantation was performed in 16.2% of resected patients, with older age being the main contraindication. Outcome of salvage LT was similar to that of primary LT.

Combined treatment with pegylated interferon (alpha-2b) and ribavirin in the acute phase of hepatitis C virus recurrence after liver transplantation.

BACKGROUND/AIMS: The efficacy and safety of treatment with pegylated interferon alpha-2b (Peg-Intron, 1.5 microg/kg) and ribavirin (400-800 mg) in the acute phase of recurrent HCV after LT is presented. METHODS: Twenty-four patients (17 men) transplanted for HCV-associated cirrhosis (genotype 1b) were treated for at least 6 months and compared with 24 consecutive transplant patients (16 men) without antiviral therapy (controls). RESULTS: At completion of treatment, 14/24 treated patients (58%) achieved HCV-RNA negativity, compared to none of controls (P<0.0001). Sustained virological response (SVR) occurred in 8/23 treated patients (34.7%) who reached week 24 after treatment and none of controls (P<0.005). At 12 weeks after treatment, 15/24 patients (62.5%) had an early virological response (EVR) (seven tested HCV-RNA negative). SVR was associated with absence of corticosteroid bolus administration (P=0.01), presence of EVR (P=0.002) and absence of cytomegalovirus infection (P=0.001). Haematological adverse effects included anaemia, 17/24 cases (71%) and leukopenia, 23/24 cases (96%). One patient presented mild acute rejection that resolved by adjusting immunosuppressive dose. CONCLUSIONS: Treatment with pegylated interferon alpha-2b plus ribavirin in the acute phase of HCV reinfection yielded an EVR of 62.5% and a SVR of 34.7%. The combination was safe, with a low rate of therapy withdrawal.

Cardiac alterations in cirrhosis: reversibility after liver transplantation.

BACKGROUND/AIMS: Liver cirrhosis induces cardiac alterations. We aimed to define these alterations and assess their reversibility after transplantation. METHODS: Cirrhotic patients (n = 40) and controls (n = 15) underwent echocardiography and stress ventriculography. Fifteen cirrhotics were reevaluated 6-12 months after transplantation. RESULTS: Cirrhotics had higher left ventricular wall thickness (9.6+/-1.2 vs. 8.8+/-1.2 mm; P < 0.05) and ejection fraction (73+/-6 vs. 65+/-4%, P < 0.001) than controls. Basal diastolic function was similar. During stress, cirrhotics presented lower increases of heart rate, left ventricular ejection fraction, stroke volume and cardiac index (P < 0.05 for all), and diastolic dysfunction with lower ventricular peak filling rate (P = 0.001). Exercise capacity was reduced (48+/-21 vs. 76+/-24 W; P < 0.001). Ascitic patients exhibited more diastolic dysfunction at rest and during stress compared to non-ascitic patients. Liver transplantation caused regression of ventricular wall thickness (10.2+/-1.3 vs. 9.5+/-1.2 mm; P < 0.05), improvement of diastolic function, and normalization of systolic response and exercise capacity during stress (significant increases in heart rate, ventricular ejection fraction, stroke volume and cardiac index; P < 0.05 for all). CONCLUSIONS: Cardiac alterations in cirrhosis present with mild increases in ventricular wall thickness, diastolic dysfunction that worsens with ascites and physical stress, and abnormal systolic response to stress limiting exercise capacity. Liver transplantation reverses these alterations.

Corticosteroid-free immunosuppression with tacrolimus following induction with daclizumab: a large randomized clinical study.

This open, randomized (1 : 1), multicenter, 3-month study compared a dual tacrolimus plus steroids (Tac / steroids) regimen with a steroid-free immunosuppressive regimen of tacrolimus following daclizumab induction therapy (Tac / Dac) in adult liver transplant recipients. The full analysis set comprised 347 patients in the Tac / steroids group and 351 in the Tac / Dac group. Mean tacrolimus dose during month 3 was 0.11 mg/kg/day in both groups; mean whole-blood trough levels during month 3 were 10.9 ng/mL (Tac / steroids) and 10.6 ng/mL (Tac / Dac). The incidence of biopsy-confirmed acute rejection that required treatment was similar in both groups: 26.5% in the Tac / steroids group and 25.4% in the Tac / Dac group (P = .727). However, the incidence of biopsy-confirmed corticosteroid-resistant acute rejection was higher in the Tac / steroids group than in the Tac / Dac group (6.3 vs. 2.8%; P = .027). Kaplan-Meier estimates of graft survival (92.2 vs. 90.5%) and patient survival (94.5 vs. 93.7%) were similar in both groups. While also the overall adverse event profiles were similar, the incidences of diabetes mellitus (15.3 vs. 5.7%, respectively; P < .001) and cytomegalovirus infection (11.5 vs. 5.1%, respectively; P = .002) were higher in the Tac / steroids group compared with the Tac / Dac group. Mean cholesterol levels increased by 16% in the Tac / steroids group, but were unchanged in the Tac / Dac group during the study. In conclusion, tacrolimus monotherapy following daclizumab induction is an effective and safe regimen, with an advantage over concomitant steroid-maintenance therapy in terms of a lower incidence of diabetes and viral infection, and a lower incidence of steroid-resistant acute rejection.

Liver transplantation in infants weighing under 7 kilograms: management and outcome of PICU.

Liver transplantation (LT) is an established treatment for children with acute and chronic liver failure. Some reports suggest that infants under the age of 1 yr and children weighing under 13 kg are high-risk groups associated with less satisfactory results. This report describes our experience during the pediatric intensive care unit stay of 16 infants weighing <7 kg who received LT. We reviewed the records of 16 infants with median age 7.4 months and median weight 5.8 kg, who received 18 liver allografts, nine whole and nine reduced. We also reviewed the use of adrenergic agonist agents, anti-infectious agents, antihypertensive agents, diuretics, immunosuppression protocol, sedation-analgesia agents, others agents (prostaglandin E(1), heparin and dipyridamole), diagnosis and management of rejection episodes, follow-up examination, nutrition and outcome. Mean peri-operative blood transfusions were 204 mL/kg, 188 mL/kg of plasma and 36 mL/kg of platelets; mean operative time was 5 h. Primary abdominal wound closure was possible in nine patients. Median initial intensive care unit stay was 18 days. Reasons for an initial stay of more than 18 days were retransplantation (1), gastrointestinal bleeding (2), paralytic ileus and atelectasis (2), septic shock (2), diaphragmatic paralysis, renal impairment and acute respiratory distress syndrome (2). Mean requirement for artificial ventilation was 168 h. Mean use of dobutamine, prostaglandin E(1) and dopamine was 3.3, 7.5 and 8.8 days, respectively. Parenteral nutrition was started at a mean of 48 h and oral food intake was started at a mean of 72 h. The most frequent complications were infection, atelectasis, gastrointestinal bleeding, acute renal failure and hepatic artery thrombosis. Four children required six re-explorations and two received retransplantation. Mean overall survival rate was 82% and graft survival was 72%. Weight alone (under 7 kg) should not be considered as a contraindication for LT. The survival rate of children post-LT is excellent regardless of graft type.

Liver transplantation for malignant diseases: selection and pattern of recurrence.

Liver transplantation (LT) for malignant tumors should be accepted if, with adequate case selection, long-term results are similar to those in patients transplanted for benign diseases. The aim of the present study was to reexamine selection criteria for LT in malignant diseases with particular emphasis on hepatocellular carcinoma (HCC) in cirrhosis. One hundred-three of 369 patients transplanted in our unit had HCC in cirrhosis (28%), 15 of which were incidental tumors, and 234 patients underwent LT for non-cholestatic cirrhosis. Pretransplant arterial chemoembolization(TACE) was performed in 36 cases (41%) of known HCC. Only early,well-delimited tumors in advanced cirrhosis with no extrahepatic disease were accepted for LT. Hepatocellular carcinoma characteristics included mean tumor size (3.1 cm), multiple (59%), bilobular involvement (31%), and vascular invasion (9.2%). Postoperative mortality was 4%. Median follow-up was 67.5 months. Tumor recurrence rate was 14.5%, 33% (5/15) in incidental tumors and 11.4% (10/88) in known HCC and by tumor stage (pTNM): 7.7% (1/13) in stage I, 16.7%(5/30) in stage II, 15% (3/20) in stage III, and 17% (6/35) in stage IV. Mean time for recurrence was 20.6 months. Tumoral vascular invasion, tumor differentiation, and satellite tumors were significant factors for tumor recurrence in univariate analysis, whereas tumor vascular invasion was the only significant factor for tumor recurrence in multivariate analysis. Actuarial survival rates at 1, 3, and 5 years were 81%, 66%, 58%, respectively, in patients with HCC and were similar to those of cirrhotic patients 76%, 67%, 63%, respectively. In conclusion, patients with early HCC in cirrhosis are good candidates for LT; results are similar when compared with those of cirrhotic patients without tumor. Liver transplantation for other malignancies is admitted only in fibrolamellar hepatoma, hepatoblastoma, epithelioid hemangioendothelioma without extrahepatic disease, and in metastases from carcinoid tumors.

FK506 in the maturation of dendritic cells.

BACKGROUND AND OBJECTIVES: FK506 (tacrolimus) is a potent immunosuppressive agent that inhibits interleukin-2 (IL-2) and interferon-g production by CD4+ cells. The effect of this agent on dendritic cells (DCs), the highly professional antigen-presenting cells for T-cells, has not been completely defined. We investigated the effect of FK506 on DC differentiation from monocytes, and on the shift from immature to mature immunophenotypes. DESIGN AND METHODS: DCs were generated in vitro from monocytes of healthy donors. Cells were exposed to lipopolysaccharide (LPS) and two doses of FK506, with variations in time of exposure and sequence of FK506 and LPS addition. Immunophenotype analysis in immature and mature DCs under FK506 treatment was performed by flow cytometry at the end of cell culture. The Student's t-test was used for statistical analyses. RESULTS: FK506 did not affect dendritic cell generation or viability. There were no changes in cell surface markers with addition of FK506 at physiologic concentrations (10 ng/mL). We found a decrease in CD1a median fluorescence intensity (MFI) and an increase in percentage of CD86-positive cells with lengthy exposure (6 days) to FK506 at 5000 ng/mL. In the sequential study, 5000 ng/mL FK506 before LPS addition resulted in a significant decrease in CD1a MFI and in the percentage of cells co-expressing CD83 and CD86. INTERPRETATION AND CONCLUSIONS: Our results indicate that lengthy exposure to 5000 ng/mL FK506 modified the expression of some DC-cell surface markers, maintaining DCs in a low maturity stage.

Predictive factors for early mortality following liver transplantation.

AIMS: To retrospectively review our liver transplant performance to identify factors that influenced early outcomes and to prospectively test their validity in predicting outcomes. METHODS: Clinical records from 190 patients with liver transplants (LT; n = 200) performed between 1991 and 1997 were reviewed and the data evaluated by univariate and multivariate analyses regarding clinical outcome. The prognostic model thus obtained was prospectively evaluated in 55 patients undergoing transplant between 1999 and 2000. RESULTS: Main indication for transplant was post-necrotic cirrhosis (61%), mostly HCV(+). The majority of patients were Child-Pugh C status (46%). Post-operative mortality at 3 months was 15.3%. Risk factors predicting death were: Child-Pugh C status (OR 1.3), pre-LT renal insufficiency (OR 5.8), malnutrition (OR 2.9) and technically complex surgery requiring cross-clamping with or without bypass (OR 4.9). None of the donor factors was significant. Prospectively applied to predict outcome in the 55 patients, the model had a sensitivity of 80% and a specificity of 88.8% with a higher-than-anticipated accuracy with a positive predictive value of 61.5% and a negative predictive value of 95.3%. CONCLUSIONS: Pre-LT renal insufficiency is the most significant risk factor for early mortality and suggests that LT should be performed before evidence of irreversible renal insufficiency becomes manifest.

Psychosocial adjustment to orthotopic liver transplantation in 266 recipients.

Although the survival rate of patients undergoing orthotopic liver transplantation (OLT) is highly satisfactory, one of the most important objectives for liver transplantation teams at the present time is to achieve the best possible quality of life and psychosocial functioning for these patients after transplantation. We present the preliminary results of a study designed to determine which domains of psychosocial functioning are most affected in liver transplant recipients, and to examine the factors associated with poorer adjustment after OLT, using a utility-based standardized measure. Patients who had undergone liver transplant more than 12 months previously were eligible. They were administered the Psychosocial Adjustment to Illness Scale (PAIS), and they provided the answers themselves. Multivariate regression models showed that attitudes toward health care were poorer in women (beta = 0.916, P <.001), in patients who were employed at the moment of transplantation (beta = 0.530, P =.032), and in patients of lower social class (beta = 0.722, P =.026) than in men, unemployed patients, and patients of higher social class. Sexual functioning was worse in women (beta = 0.907, P =.001) and older patients (beta = 0.999, P <.001) than in men or younger patients. Psychological distress was higher in women (beta = 0.981, P =.001) than in men, and lower in currently employed patients (beta = -0.937, P =.001) than in the unemployed. Only gender remained significantly associated with the total PAIS score (beta = 0.969, P <.001), with women showing a poorer overall psychosocial adjustment to OLT. In conclusion, there seems to be no doubt that liver transplantation improves quality of life, but special attention should be paid to female recipients, who seem to have more difficulty than their male counterparts in adjusting to the psychosocial consequences of the procedure.

Applicability of liver transplantation in Catalonia at the end of the millennium. A prospective study of adult patient selection for liver transplantation.

We prospectively studied the global applicability of liver transplantation in Catalonia, a region with a high rate of organ donation. We followed 232 adult patients assessed as possible candidates for liver transplantation over 12 months in the three hospitals that perform the procedure in this region. The liver disease leading to patient assessment was cirrhosis in most cases, alone (159 patients) or associated with hepatocellular carcinoma (57 patients). After being assessed, 150 patients (65%) were accepted for transplantation and included on the waiting list, and 82 (32%) were excluded. Death during the period of assessment, advanced tumoral disease, early stage of liver disease, and extrahepatic co-morbidities were the most important reasons for exclusion. The median time of assessment of patients accepted for transplantation was 40 days. Of the 150 patients included on the waiting list, 131 (87%) received transplants, 17 (11%) were removed from the list, and two were still waiting for transplantation at the end of the follow-up period. Death and tumor progression were the most important reasons for patients' removal from the waiting list. The median time on the waiting list was 59 days. In conclusion, among liver-transplant candidates the overall applicability of this therapy in Catalonia was relatively low (131 out of 232 transplant candidates finally underwent transplantation, 56%), and inadequate liver-transplant indications and death or tumor progression during the period of assessment or while the patient was on the waiting list were the most frequent reasons why liver transplantations did not proceed.