Gabriela A. Berlakovich

Efficacy of liver transplantation for alcoholic cirrhosis with respect to recidivism and compliance.

Many transplant centers are reluctant to accept alcoholic patients for OLT because of their supposed potential for alcoholic recidivism and poor compliance with the required immunosuppressive regimen, both of which result in graft failure. Only inconclusive data related to these arguments are available. From May 1982 to January 1993, 58 patients received OLT at our institution for end-stage cirrhosis, where alcohol was the only toxic component. The indication for OLT in these patients was considered with particular attention to recidivism and compliance. Overall survival in this group was 71% and 63% at 1 and 5 years, respectively, with an average survival time of 78 months. Actuarial survival of patients transplanted since January 1989 (n = 37) was 86% and 83% at 1 and 2 years (average survival 42 months). Nonfatal clinical endpoints were analyzed in those patients surviving at least 3 months (n = 44). Return to alcohol abuse has been documented in 14 persons at routine short-term outpatient checkups. The estimated risk for alcoholic recidivism amounts to 31%, with a median follow-up of 33 months. Compliance with immunosuppressive regimen was expressed as a dependent value of acute rejection episodes (0.3 per patient, median follow-up 33 months), chronic rejection (occurred in none of the patients), and measurements of CsA HPLC blood trough level (92.2% within the target range). The preversus postoperative improvement of employment, marital, and social status after OLT showed a statistically significant difference. Unwillingness to offer OLT to individuals with alcoholic liver disease because of failure to demonstrate 100% long-term abstinence appears difficult to defend in the face of good results in survival, compliance, and social rehabilitation.

Proceedings From an International Consensus Meeting on Posttransplantation Diabetes Mellitus: Recommendations and Future Directions

A consensus meeting was held in Vienna on September 8–9, 2013, to discuss diagnostic and therapeutic challenges surrounding development of diabetes mellitus after transplantation. The International Expert Panel comprised 24 transplant nephrologists, surgeons, diabetologists and clinical scientists, which met with the aim to review previous guidelines in light of emerging clinical data and research. Recommendations from the consensus discussions are provided in this article. Although the meeting was kidney‐centric, reflecting the expertise present, these recommendations are likely to be relevant to other solid organ transplant recipients. Our recommendations include: terminology revision from new‐onset diabetes after transplantation to posttransplantation diabetes mellitus (PTDM), exclusion of transient posttransplant hyperglycemia from PTDM diagnosis, expansion of screening strategies (incorporating postprandial glucose and HbA1c) and opinion‐based guidance regarding pharmacological therapy in light of recent clinical evidence. Future research in the field was discussed with the aim of establishing collaborative working groups to address unresolved questions. These recommendations are opinion‐based and intended to serve as a template for planned guidelines update, based on systematic and graded literature review, on the diagnosis and management of PTDM.

Comparison of invasive and noninvasive measurement of plasma disappearance rate of indocyanine green in patients undergoing liver transplantation: A prospective investigator-blinded study

Plasma disappearance rate of indocyanine green (PDRICG) has been proposed for assessment of liver function in liver transplants donors and recipients, in patients with chronic liver failure, and as a prognostic factor in critically ill patients. The assessment of PDRICG using a newly developed noninvasive digital pulse densitometry method was simultaneously compared to invasive aortic fiber‐optic method in patients undergoing orthotopic liver transplantation (OLT). Fourteen consecutive liver transplant candidates (11 male, 3 female) were prospectively enrolled into the study. A 4F aortic catheter with an integrated fiber‐optic device and a thermistor was inserted via a femoral artery sheath for invasive aortic (INV) PDRICG assessment in all patients. The fiber‐optic device was connected to a computer system (COLD‐Z021, PULSION Medical Systems, Munich, Germany). A finger‐piece sensor was used for non‐invasive (NINV) pulse‐densitometric PDRICG assessment. For the PDRICG assessment .5 mg/kg of ICG in cooled saline (10‐15 mL) was injected through a central venous catheter. The assessments of PDRICG were performed after induction of anesthesia, after clamping of the hepatic artery, after clamping of the inferior vena cava, after reperfusion of the graft, and on the first postoperative day. During the PDRICG measurements, the investigators were blinded for the results of the noninvasive monitoring. Seventy‐one pairs of measurements were performed successfully. PDRICG ranged from 0%/min to 43.8 %/min (11.6%/min ± 9.6 %/min, mean ± SD) for invasive and from 2.6%/min to 36.1 %/min (10%/min ± 7.6 %/min, mean ± SD) for noninvasive assessment method. The linear regression analysis yielded the equation: PDRICGNINV = 1.493 ± 0.735 × PDRICGINV, with a correlation coefficient of r = 0.93 (P < .0001). The analysis according to Bland and Altman showed a good agreement between the PDRICGNINV and PDRICGINV with a mean bias 1.5 ± 3.8 for all measurements. In conclusion, according to these results, the noninvasive transcutaneous pulse‐densitometric method correlates well with the invasive aortic fiber‐optic method and thus can be used in patients undergoing liver transplantation. (Liver Transpl 2004;10:1060–1064.)

Combination of extended donor criteria and changes in the Model for End-Stage Liver Disease score predict patient survival and primary dysfunction in liver transplantation: a retrospective analysis.

Background. The purpose of this study was to analyze the impact of extended donor criteria (EDC) and of changes in the Model for End-Stage Liver Disease (MELD) score while waiting for liver-transplantation (&Dgr;-MELD) on patient survival and initial graft function. Methods. We included 386 consecutive patients with end-stage liver disease who underwent orthotopic liver transplantation at the Medical University Vienna between 1997 and 2003. Primary outcome was patient survival and secondary outcome was initial graft function. EDC included: age >60 years, >4 days intensive medical care, cold ischemia time >10 hr, need for noradrenalin >0.2 &mgr;g/kg/min or doputamin >6 &mgr;g/kg/min, a donor peak serum sodium >155 mEq/L, a donor serum creatinine >1.2 mg/100 mL, and a body mass index >30. Results. &Dgr;-MELD was significantly higher in the nonsurvivor population (P=0.01) and EDC showed a significant influence on initial graft function (P=0.01). Worsening in either &Dgr;-MELD or the presence of at least two EDC was not associated with an increased risk of primary graft dysfunction and death. Worsening in &Dgr;-MELD and the presence of at least two EDC was significantly associated with primary graft dysfunction (P=0.01) and death (P=0.008). Conclusion. The combination of a liver recipient with worsening &Dgr;-MELD and a potential donor with at least two EDC should be avoided.

Short-term induction therapy with anti-thymocyte globulin and delayed use of calcineurin inhibitors in orthotopic liver transplantation.

The appropriate time point for starting immunosuppressive treatment with calcineurin inhibitors after orthotopic liver transplantation (OLT) has been a subject of debate. The aim of the study was to analyze the effects of anti‐thymocyte globulin (ATG) induction therapy on rejection, renal function, infection, tumor rate, and survival. We retrospectively analyzed 391 patients after OLT who had either received calcineurin inhibitors immediately after OLT (n = 129) or after an initial short‐term Thymoglobulin induction therapy (n = 262). The 1‐year acute rejection rate was 14.5% vs. 31.8% in favor of ATG (P = 0.0008). Rejection grades and the need for treatment also differed significantly (7.3% vs. 23.3%; P = 0.001). Serum creatinine at transplantation was similar in both groups (1.14 mg/dL vs.1.18 mg/dL; P = NS). Postoperative hemofiltration was less frequently seen after induction therapy (P < 0.05). Reduced renal function at 1 year was commonly observed, but serum creatinine (1.26 mg/dL vs. 1.37mg/dL; P = 0.015) and glomerular filtration rate (81 mL/min vs. 75 mL/min; P = 0.02) were far better in the ATG group. Undesired side effects occurred at a similar rate in both groups. Five‐year patient survival was also similar in the 2 groups (70.1% and 74.3%; P > 0.05). Short‐term ATG induction therapy with delayed administration of calcineurin inhibitors led to a more favorable rejection rate and an improved clinical course in case of a rejection episode. It has beneficial effects on renal function immediately after OLT as well as later, and no additional harmful effects. Liver Transpl 13:1039–1044, 2007.

Is MELD score sufficient to predict not only death on waiting list, but also post-transplant survival?

Model for end‐stage liver disease (MELD) score has emerged as a useful tool in predicting mortality in patients awaiting liver transplantation. There is still, however, discussion as to whether further parameters could improve the sensitivity and specificity of the MELD score. From 1997 to 2003, 621 adult patients with end‐stage liver disease were listed for orthotopic liver transplantation (OLT). Patients suffering from hepatoma were excluded from analysis (113 patients). The MELD score was investigated at the time of listing (MELD ON) and of coming off the list (MELD OFF). Patients who died while on the waiting list showed a significant increase in their MELD score during the waiting time (MELD ON: 21 ± 7 vs. MELD OFF: 28 ± 9) as well as a significantly higher MELD ON compared with patients who were transplanted (MELD ON: 16 ± 5 vs. MELD OFF: 17 ± 7) or removed from the waiting list (MELD ON: 16 ± 6 vs. MELD OFF: 12 ± 3). Multivariate analysis identified MELD ON, ascites and recurrent infection as independent risk factors for death on the waiting list (P < 0.01). MELD score was not identified as a predictor for the post‐transplant survival rate. MELD score is a strong predictor for death on the waiting list, but refractory ascites and recurrent infection are independent risk factors, too.

PHYSICAL PERFORMANCE AND HEALTH-RELATED QUALITY OF LIFE IN MEN ON A LIVER TRANSPLANTATION WAITING LIST

Twenty-six men on a liver transplant waiting list (12 had alcoholic cirrhosis, 8 suffered from posthepatitic cirrhosis, and 6 from cirrhosis of other etiologies) were eligible for this observation. Nineteen subjects underwent exercise testing to determine oxygen uptake at anaerobic threshold. In all patients dynamometry was performed to determine isokinetic muscle strength of knee extensor muscles, and handgrip. Quality of life was evaluated in all patients with the MOS SF-36 questionnaire. Child-Pugh A patients showed 54 +/- 8%, Child-Pugh B patients 36 +/- 2%, and Child-Pugh C patients 31 +/- 4% of VO2 max predicted at the anaerobic threshold (Kruskal-Wallis ANOVA, p < 0.05). Isokinetic muscle strength of the quadriceps femoris (left/right) was 149 +/- 20/134 +/- 14 Nm in Child-Pugh A, 108 +/- 16/114 +/- 19 Nm in Child-Pugh B, and 89 +/- 10/81 +/- 11 Nm in Child-Pugh C patients (Kruskal-Wallis ANOVA, p < 0.05). MOS-SF36 revealed a Child-Pugh class dependent reduced functional status (Kruskal-Wallis ANOVA, p < 0.05). No significant differences in target parameters were found when analysed according to the etiology of cirrhosis. Patients on the liver transplant waiting list do have a stage dependent reduction in physical health. These data are the basis for longitudinal studies measuring the effects of preoperative rehabilitation programs in these patients.

CARBOHYDRATE DEFICIENT TRANSFERRIN FOR DETECTION OF ALCOHOL RELAPSE AFTER ORTHOTOPIC LIVER TRANSPLANTATION FOR ALCOHOLIC CIRRHOSIS

Early diagnosis and monitoring of an alcohol relapse in patients after orthotopic liver transplantation for alcoholic cirrhosis is of importance for the long-term outcome. A prospective study of 97 patients who underwent orthotopic liver transplant for alcoholic cirrhosis has been performed. All of the recipients considered for analysis survived for at least 3 months and were under the care of one specialist psychologist. Mean follow-up amounted to 48.5+/-1.4 months. The rates of alcohol relapse at 1 and 3 years after orthotopic liver transplant were 6 and 9%, respectively. Carbohydrate-deficient transferrin is a biological marker for alcohol abuse independently of liver disease and has been used for the first time ever in liver graft recipients. A total of 830 values were included prospectively in the study population. Detection of alcohol relapse had a sensitivity of 92% and a specificity of 98%. Changes in carbohydrate-deficient transferrin levels indicated clandestine and sporadic drinking after transplantation. Furthermore, clinical events were not found to influence carbohydrate-deficient transferrin, either in patients with or without alcoholic relapse. In our opinion, carbohydrate-deficient transferrin is a useful screening marker for alcohol relapse in patients after orthotopic liver transplant for alcoholic cirrhosis, to select those patients who need special attention from the psychologist.

Accuracy of Multiphasic Helical Computed Tomography and Intraoperative Sonography in Patients Undergoing Orthotopic Liver Transplantation for Hepatoma: What is the Truth?

ObjectiveTo determine the real value of liver imaging in cirrhosis by macro- and histomorphologic examination of the entire organ after orthotopic liver transplantation for hepatocellular carcinoma (HCC). Summary Background DataIn comparative studies, a virtual sensitivity of up to 94% is described for helical computed tomography in HCC staging. The tumor detection rate of intraoperative ultrasonography (IOUS) is reported to be almost 100%. MethodsThis prospective observational study comprised 23 patients with HCC in cirrhosis admitted for orthotopic liver transplantation. Results of preoperative triphasic helical computed tomography (HCT) and IOUS were correlated with histopathologic results after 3-mm-slicing of the explanted liver. ResultsOverall, 179 liver segments were examined by HCT, IOUS, and MHM. Fifty-two malignant lesions and 10 dysplastic nodules were revealed by MHM. Using HCT, 13 HCCs could not be identified in 8 patients and 15 results were falsely positive in 10 patients. The detection rate of dysplastic nodes was 40% for HCT and 60% for IOUS. IOUS missed four HCCs in four patients and had six false-positive results in six patients. In a segment-based analysis, the overall accuracy of IOUS was significantly higher for IOUS (95.5%) versus HCT (89.9%). In the lesion-by-lesion analysis, the sensitivity was 92.3% for IOUS and 75.0% for HCT, with a significant difference. ConclusionsCorrelation of explanted liver pathologic results offers precise evaluation of imaging modalities. The data of this histopathologically based study confirm that IOUS is significantly superior in staging HCC in cirrhosis versus CT, even after technical refinements through enhanced multiphasic high-velocity helical scanning.

Alterations in Gene Expression in Cadaveric vs. Live Donor Kidneys Suggest Impaired Tubular Counterbalance of Oxidative Stress at Implantation

Recipients of live donor transplant kidneys (LIV) exhibit a significantly longer allograft half‐life compared with cadaveric donor organs (CADs). The reasons are incompletely understood. Therefore this study sought to elucidate the genome‐wide gene expression profiles in microdissected transplant kidney biopsies obtained from five cadaveric and five matched live donors before transplantation. cDNA microarrays were used to determine the transcripts in isolated glomeruli (G) and the tubulointerstitial (TI) compartment. Data were subjected to hierarchical clustering, maxT adjustment and a jackknife procedure to ensure robustness of reported findings; validation was performed by independent analysis of split biopsies and TaqMan‐PCR.