Conversion from twice-daily to once-daily Tacrolimus administration in liver transplant patient: results of long term follow-up.

OBJECTIVES: The aim of this study was to assess the long term effects of once-daily tacrolimus (OD-TAC) in a cohort of stable liver recipients converted from the twice daily tacrolimus (TD TAC), with a particular attention on the possible effects on renal function. PATIENTS AND METHODS: Between September 2008 and September 2010 conversion from TD-TAC to OD-TAC was proposed in adult stable liver transplant recipients who were followed as outpatients in our Transplant centre. Conversion from TC-TAC to OD-TAC was based on a 1 mg: 1 mg proportion. Tacrolimus through levels, laboratory parameters, metabolic disorders and any adverse events were evaluated at 1, 3, 6, 12 and 24 months after conversion. Renal function was evaluated using creatinine plasma levels and estimated glomerular filtration rate (GFR) derived from the Modification of Diet in Renal Disease (MDRD). Analysis of variance and t test for paired data were utilised for the comparison of the results obtained at the scheduled controls. RESULTS: Sixty-five patients were enrolled in the study (50 males, 15 females, mean age 59±8 years). Median time since liver transplant (LT) was 39 months (range: 6 to 83 months). All patients were followed for a minimum of 12 months. Ninety per cent of patients stabilized their blood levels within 45 days. Liver function, glucose and plasma lipids concentration and arterial blood pressure remained stable during the study. Renal function improved during the 24 months of follow-up. No adverse events or acute rejection episodes were recorded during the study. CONCLUSIONS: Considering the advantage on patient compliance, the equivalent efficacy and the adequate safety of OD-TAC formulation may represent a useful option in liver transplant patients, with a possible advantage on renal function.

Acquired cow's milk sensitization after liver transplant in an adult: "clinical implications" and future strategies.

BACKGROUND: Identifying the mechanisms responsible for the development of food allergy in liver transplant recipients is more complex as there are several different clinical scenarios related to the immunological function of the liver. CASE PRESENTATION: We describe the first case of Transplant Acquired Food Allergy (TAFA) to cow milk in an adult following LT from a donor dead because of anaphylactic shock. A 67-year-old woman with primary biliary cirrhosis was referred to the Transplant Center of our hospital because of an acute-on-chronic liver failure. The donor was a 15-year-old girl deceased for anoxic encephalopathy due to food induced anaphylaxis after eating a biscuit. In the donor's history food allergies to cow milk and eggs were present. CONCLUSION: This case emphasizes the need for a standardized assessment of both solid-organ donors and recipients including donor allergy history in order to detect recipients at risk for anaphylaxis due to passive IgE transfer. Despite several reports of TAFA after solid organ, especially liver, an appropriate protocol to avoid risk for the recipient doesn't exist at the moment. The SPT (skin prick test) or specific IgE level are not enough to ensure a correct management in these cases and a correct education of the patients and the medical staff involved is absolutely necessary. It is the first case of milk allergy sensitization after solid organ transplant by passive transfer of IgE.

Combined liver-kidney transplantation in polycystic disease: case reports.

Polycystic disease causes a progressive decrease in renal function and liver degeneration. The progression of the disease evolves separately between organs and transplantation options vary: simultaneous or sequential liver-kidney transplantation or single-organ transplantation. From September 2006 to June 2007 3 combined liver kidney transplantations (CLKT) were performed for polycystic disease with end-stage renal disease: 2 with polycystic liver disease, and 1 with hepatic failure due to congenital hepatic fibrosis. The widest dimensions of the polycystic liver of 50 and 60 cm diameter were due to extensive cystic degeneration. We performed 1 simultaneous CLKT and 2 sequential transplantations: 1 liver after kidney, and 1 kidney after liver. At present all patients are alive with 100% graft function. Median creatinine level at discharge was 0.9 mg/dL (ranges, +/-0.2). Good liver graft function was reported in all 3 cases. Transplant benefit in polycystic liver-kidney disease has been already demonstrated; conservative surgical options may result in a high incidence of complications in highly involved polycystic livers. Delaying transplantation results in a more difficult surgical technique, a higher rate of postoperative complications, and a disturbance of optimal graft retrieval because of the worse preoperative condition of the patients.

The anionic peptide fraction is present on the gallbladder apical epithelium and favours biliary cholesterol absorption.

BACKGROUND/AIMS: We investigated (a) in vitro and in vivo the changes of biliary mass of the anionic peptide fraction, apolipoproteinA-I, immunoglobulin-A, albumin and cholesterol over time in the excluded gallbladder and (b) in vivo the localization in the gallbladder epithelium of the anionic peptide fraction and cholesterol absorbed from bile. METHODS: Native bile was substituted with pig bile containing radiolabeled cholesterol in the in vitro isolated intra-arterially perfused pig gallbladder (n=9) and in vivo in anestethized pigs with excluded gallbladders (n=6). The amount of cholesterol (scintillation counting) and proteins (enzyme-linked immunosorbent assay) in gallbladder bile were measured over time. The localization of the anionic peptide fraction and cholesterol absorbed from bile in the gallbladder epithelium was studied in vivo by immunohistochemistry and fluoro-phospho-imager analysis. RESULTS: The rate of biliary cholesterol disappeared from bile was a function of the initial concentration and of the biliary mass changes over time of the anionic peptide fraction, but not of that of the other biliary proteins. The anionic peptide fraction colocalized with biliary cholesterol absorbed by the gallbladder on the apical side of gallbladder epithelial cells. CONCLUSIONS: These data indirectly suggest that biliary anionic peptide fraction could favour biliary cholesterol absorption by the gallbladder epithelium.

Clinical effects of use polymyxin B fixed on fibers in liver transplant patients with severe sepsis or septic shock.

UNLABELLED: Polymyxin B (PMX-B) is a polycationic antibiotic, known to bind the lipid A portion of endotoxin, a cell wall component exclusively found in gram-negative bacteria (GNB). An extracorporeal hemoperfusion device (TORAYMYXIN) has been developed: PMX is covalently bound to the surface of an insoluble carrier material to inactivate endotoxin in blood without exerting toxicity on the brain or the kidney. The aim of this study was to evaluate the efficacy, safety, and clinical effects of direct hemoperfusion with an immobilized polymyxin B fiber column (DHP-PMX) among liver transplant patients with severe sepsis or septic shock. METHODS: From June 2004 to May 2005, 10 patients (6 men and 4 women) of overall mean age of 55 years (46-65 range) underwent orthotopic liver transplantation (OLT) and developed severe sepsis or septic shock according to The Consensus Conference of American College Physicians/Society of Critical Care Medicine (ACCP/SCCM) criteria. GNB were detected in all treated patients who received conventional antibiotic therapy, vasopressor or inotropic agents, and ventilatory support. The DHP-PMX treatment was performed three times in each patient. Hemodynamic and respiratory parameters and dosages of vasopressor or inotropic drugs were assessed at baseline and after each treatment. RESULTS: No adverse events occurred. From baseline to the third treatment the mean arterial pressure increased from 64 +/- 5 mm Hg to 89 +/- 4 mm Hg); while the dosages of dobutamine and norepinephrine were reduced: 6.4 to 1 mcg/kg/min and 1.3 to 0.001 mcg/kg per min, respectively. The PaO(2)/FiO(2) ratio increased: 214 to 291 mm Hg. CONCLUSION: The use of DHP-PMX may be an important aid in patients with sepsis in association with conventional therapy.

Outcome after liver transplantation in patients with cirrhosis and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is considered an optimal indication for liver transplantation (LT) because it may eliminate both the tumor and the underlying liver disease. The present study sought to compare cumulative survival, rate of HCC recurrence, and causes of death among patients with cirrhosis and HCC before and after the adoption of more restrictive criteria (Milan selection criteria) at the time of patient listing. Among 226 adult patients who received an elective liver transplantation between 1999 and 2005, 58 (27%) had a diagnosis of HCC at the time. The 38 patients who underwent transplantation for HCC in the period 1989 to 1998 were considered the "historical group." After LT (mean follow-up, 34 + 28 months), the cumulative survival rate was better among HCC versus non-HCC recipients (93% vs 71% at 1 year and 81% vs 67% at 3 years, respectively; P < .046), although the difference tended to attenuate after 5 years (66% vs 67%, respectively). Tumor recurrence (evaluated in patients surviving at least 3 months after LT) was observed in 10/31 in the historical group versus 4/53 among those who underwent transplantation after 1999. Among the causes of death, recurrence represented 50% in the old series and 23% in patients who underwent transplantation after 1999. Cumulative survival significantly improved among HCC patients who underwent transplantation after 1999 (93% vs 66% at 1 year and 81% vs 50% at 3 years; P < .00001). The 58 patients who underwent transplantation with a diagnosis of cirrhosis and concomitant HCC after 1999 showed even better survival than patients who underwent transplantation for end-stage liver disease without malignancy.

Clinical effects of direct hemoperfusion using a polymyxin-B immobilized column in solid organ transplanted patients with signs of severe sepsis and septic shock. A pilot study.

BACKGROUND: Polymyxin B (PMX-B) is a polycationic antibiotic, known to bind the lipid A portion of endotoxin, a cell wall component found exclusively in gram negative bacteria (GNB). An extracorporeal hemoperfusion device (TORAYMYXIN) has been developed: PMX is covalently bound on the surface of an insoluble carrier material so that the endotoxin can be inactivated in the blood without exerting its toxicity on the brain and kidney. The aim of this study was to clarify the efficacy, safety and clinical effects of direct hemoperfusion with an immobilized polymyxin-B fiber column (DHP-PMX) in solid organ transplanted patients with severe sepsis or septic shock. METHODS: From June 2004 to May 2005, 15 patients (10 men and 5 women), mean age 55 years old (46-65 range), underwent kidney or liver transplantation and developed severe sepsis or septic shock, as defined by the Consensus Conference of American College Physicians/Society of Critical Care Medicine (ACCP/SCCM) criteria. GNB were detected in all the patients receiving conventional treatments including antibiotic therapy, vasopressive or inotropic agents, and ventilation support. The DHP-PMX treatment was performed three times in each patient. Hemodynamic and respiratory parameters, dosage of vasopressor/inotropic drugs were assessed at baseline and after each treatment. RESULTS: No adverse events occurred. From baseline to 3rd treatment, mean arterial pressure (MAP) was increased (from 63+/-5 to 83+/-4 mmHg), while the dosage of dobutamine (from 7.5+/-3 to 3+/-2 mcg/kg/min) and noradrenaline (from 1.3+/-0.45 to 0.05+/-0.02 mcg/kg/min) were reduced. The PaO2/FiO2 ratio increased (from 234+/-38.47 to 290+/-107.48 mmHg). CONCLUSION: The use of DHP-PMX in association with conventional therapy may be an important aid in patients with sepsis.

Differential patterns of lipid-protein association in fast and slow cholesterol nucleating human gallbladder biles: implications for cholesterol nucleation from biliary lipid carriers.

We compared the protein/lipid structure and Ch-nucleating capacity of individual lipid carriers in two groups of human gallbladder biles: 11 with Fast cholesterol nucleation (2.2 +/- 1.3 days) and 10 with Slow cholesterol nucleation (19.2 +/- 4.4 days). The groups had comparable cholesterol-saturation (1.31 vs. 1.28), total lipids (9.9 vs. 8.5 g/dl) and proteins (8.5 vs. 7.6 mg/ml). Bile was ultracentrifuged (2 h at 150,000 x g) and the resulting isotropic phase was incubated with [3H]Ch and [14C]lecithin and gel-chromatographed on a Superose 6 column with a buffer containing 7.0 mM sodium-taurocholate. Seven protein peaks were identified (280 nm and biochemistry), with the following molecular mass ranges (kDa): 1 (Void volume), 2 (155-205), 3 (50-79), 4 (20-29), 5 (6-15), 6 (3.5-6), 7 (2-3.5). Peaks 2 and 3 were identified as vesicles and micelles, respectively. Fast vs. Slow Ch nucleating biles had: (a) more (P less than 0.02) cholesterol coeluting with vesicles, (b) more (P less than 0.01) lecithin coeluting with low m.w. peaks (Nos. 5-6), (c) less (P less than 0.01) cholesterol and lecithin coeluting with micelles. An inverse correlation (P less than 0.001) was observed between the amount of proteins coeluting with the micellar peak and the cholesterol nucleation of both whole bile and isolated micellar fractions. A marked shift of cholesterol and lecithin from micelles to vesicles was apparent, in the whole bile, after cholesterol nucleation had occurred. Incubation and sequential analysis of isolated and radiolabeled micelles showed a progressive transfer of lecithin and cholesterol molecules to low molecular weight fractions and to vesicles before cholesterol nucleation. We conclude that pro-nucleating biliary vesicles develop from micelles, due to the phasing out and redistribution of micellar cholesterol and lecithin, which are probably induced by biliary proteins.

Transport, utilization and biliary secretion of lysophosphatidylcholine in the rat liver.

The hepatic uptake, transport and utilization of plasma lysophosphatidylcholine (lysoPC) and its contribution to biliary lipid secretion have been investigated in bile-fistula rats. The animals were given a single intravenous dose of sn-1-[1-14C]palmitoyl-lysoPC, under constant intravenous sodium taurocholate infusion (1 mumol/min), and the fate of the label was followed in blood, bile and liver for up to 3 h. The livers were excised at given time points, extracted and/or homogenized to determine the lipid distribution and subcellular location of radioactivity. LysoPC was rapidly cleared from plasma, though a consistent fraction of the label persisted in plasma over the experimental time-period in the form of either lysoPC or PC. Recovery of radioactivity in the liver varied from 15.6% after 5 min to 19.5% after 3 h. Hepatic lysoPC underwent rapid microsomal acylation to form specific PC molecular species (mainly 16:0-20:4 and, to a lesser extent, 16:0-18:2 and 16:0-16:1). Ultrafiltration, dialysis and gel-chromatographic analyses of cytosolic fractions (post 105,000 X g supernatants) indicated that lysoPC is transported to the site of acylation mostly as a macromolecular aggregate with an approx. Mr of 14,400. Small amounts of radioactivity were secreted into bile over 3 h (20% in the form of lysoPC and the remainder as 16:0-18:2 and 16:0-20:4 PC species). Plasma lysoPC, taken up by the liver, is mostly transported by a cytosolic carrier with a molecular weight close to fatty-acid-binding proteins; it then enters a distinct acylation pathway, selective for some polyunsaturated-PC species and does not contribute significantly to biliary secretion, either directly, or through its products.

Development and validation of a quantitative assay for cholesterol crystal growth in human gallbladder bile.

Crystal observation time is a rough estimate of the first microscopic appearance of cholesterol monohydrate crystals in an isotropic bile, and does not provide information on crystal growth kinetics. We have developed a method for quantitating cholesterol crystal growth in gallbladder bile. Crystals were separated from other biliary particles by ultracentrifugation on a discontinuous NaBr gradient, after bile density adjustment to d = 1.060 g/ml. More than 95% of crystals, both of native or synthetic source, floated in the density range 1.045-1.055. This density fraction was collected and crystal mass was measured by photometric turbidity, after calibration with suspensions of different-sized cholesterol crystals. The recovery of crystals added to original bile samples averaged 96.0 +/- 2.8%. Contamination with vesicles, which may potentially interfere with the turbidimetric assay, was excluded by gel-chromatography. The method was sequentially applied, until the 20th day of incubation, to biles obtained at surgery from patients with (A, n = 6) or without cholesterol gallstone (B, n = 4), and from gallstone patients pretreated for 1 week with oral ursodeoxycholic acid (C, n = 5). Crystal growth curves greatly differed, being much steeper in group A and almost flat in patients receiving ursodeoxycholic acid. The mean percent mass of biliary cholesterol in crystalline form at the 20th day was 19.2 +/- 13.5%, 1.2 +/- 0.8% and 2.7 +/- 1.1% in A, B and C, respectively (A vs. B: P = 0.014; A vs. C: P = 0.008). We conclude that the method allows a precise estimate of cholesterol crystal growth and can be usefully applied to human gallbladder biles.

Influence of tauroursodeoxycholic and taurodeoxycholic acids on hepatic metabolism and biliary secretion of phosphatidylcholine in the isolated rat liver.

Studies were carried out using an isolated rat liver system to define: the contribution of exogenous phosphatidylcholine (PC) to biliary phospholipid secretion; and its hepatic metabolism during perfusion of the livers with conjugated bile salts with different hydrophilic/hydrophobic properties. A tracer dose of sn-1-palmitoyl-sn-2-[14C]linoleoylPC was injected as a bolus into the recirculating liver perfusate, under constant infusion of 0.75 mumol/min of tauroursodeoxycholate or taurodeoxycholate. The effects on bile flow, biliary lipid secretion, 14C disappearance from the perfusate and its appearance in bile, as well as hepatic and biliary biotransformation were determined. With both the bile salts, about 40% of the [14C]PC was taken up by the liver from the perfusate over 100 min. During the same period less than 2% of the given radioactivity was secreted into bile. More than 95% of the 14C recovered in bile was located within the identical injected PC molecular species. The biliary secretion of labeled as well as unlabeled PC, however, was significantly higher in livers perfused with taurodeoxycholate than tauroursodeoxycholate, while the reverse was observed with respect to bile flow and total bile salt secretion. The exogenous PC underwent extensive hepatic metabolization which appeared to be influenced by the type of bile salt perfusing the liver. After 2 h perfusion, the liver radioactivity was found, in decreasing order, in PC, triacylglycerol, phosphatidylethanolamine and diacylglycerol. In addition, the specific activity of triacylglycerol was significantly higher in tauroursodeoxycholate than in taurodeoxycholate-perfused livers (P less than 0.025), while the reverse was true for the specific activity of hepatic PC (P less than 0.01). Because taurodeoxycholate and tauroursodeoxycholate showed opposite effects on both biliary lipid secretion and hepatic PC biotransformations, we conclude that the hepatic metabolism of glycerolipids is influenced by the physiochemical properties of bile salts.

Alpha-SMA expression in hepatic stellate cells and quantitative analysis of hepatic fibrosis in cirrhosis and in recurrent chronic hepatitis after liver transplantation.

BACKGROUND: The alpha isotype of actin expressed by hepatic stellate cells reflects their activation to myofibroblast-like cell and has been directly related to experimental liver fibrogenesis, and indirectly to human fibrosis in chronic liver disease. AIMS: To evaluate the changes in distribution and percentage of alpha-smooth muscle actin-positive hepatic stellate cells and the correlation with the degree of the fibrosis in cirrhotic livers, as well as in patients with recurrent HCV chronic hepatitis after liver transplantation. METHODS: Human liver biopsies were divided in four groups: (1) normal livers obtained from cadaveric liver donors (n=35), (2) cirrhosis post-HBV hepatitis (n=11), (3) cirrhosis post-HCV hepatitis (n=10), and (4) post-transplant recurrent HCV chronic hepatitis (n=13). Samples were stained with anti-alpha-smooth muscle actin antibody by immunoperoxidase method and semi-quantitatively evaluated. Liver fibrosis was assessed from specimens stained with Masson's trichrome and quantified by computer image analysis. RESULTS: The percentage of alpha-smooth muscle actin-positive hepatic stellate cells was significantly higher in the HBV cirrhosis, HCV cirrhosis and post-transplant HCV recurrent hepatitis groups (36.1+/-15.2, 23.8+/-19.7 and 27.8+/-16.4%, respectively) compared to the liver donor group (2.9+/-4.0%). The alpha-smooth muscle actin-positive hepatic stellate cells to fibrous tissue ratio were significantly higher in the post-transplant recurrent HCV hepatitis group (2.36+/-1.12) compared to both the donor livers and the HCV cirrhosis groups (0.74+/-1.09 and 1.03+/-0.91, respectively). The alpha-smooth muscle actin-positive hepatic stellate cell percentage and fibrosis correlated positively in the post-transplant recurrent HCV hepatitis group and negatively in the HCV cirrhosis group. No difference in the immunohistochemical and morphometrical variables was found between the HCV cirrhosis and HBV cirrhosis groups. CONCLUSIONS: These results indirectly confirm that, in vivo, alpha-smooth muscle actin expression is a reliable marker of hepatic stellate cells activation which precedes fibrous tissue deposition even in the setting of recurrent HCV chronic hepatitis after liver transplantation, and it could be useful to identify the earliest stages of hepatic fibrosis and monitoring the efficacy of the therapy. In the presence of advanced cirrhosis other factors, rather than alpha-smooth muscle actin-positive hepatic stellate cells, may sustain fibrosis deposition.

Predictive factors of outcome after liver transplantation in patients with cirrhosis and hepatocellular carcinoma.

Studies to define the optimal upper limits of tumor size and number as predictors of outcome after orthotopic liver transplantation (OLT) have yielded conflicting results. We analyzed 72 patients with cirrhosis and hepatocellular carcinoma (HCC) who underwent OLT over a 12-year period in a single center. Predictive factors for survival and tumor recurrence, according to the Milan criteria, were also examined. Our cohort included 60 men and 12 women of mean age 54 +/- 8 years and mean follow-up of 40 +/- 39 months. Origin of cirrhosis was postviral in 70% and Child class B or C in two thirds of patients. HCC was multifocal in 61%; about one fifth of patients had micro- or macrovascular involvement or positive nodes upon histologic examination. The cumulative size of the lesions was <3 cm in 17 patients; >3 to < or =5 cm in 28 patients; >5 to < or =8 cm in 14 patients; and >8 cm in 13 patients. According to the number and size of tumor nodules, 49 patients met the Milan criteria. During follow-up 25 patients died, 13 due to tumor recurrence. The 1- and 2-year survivals were 90% and 85% for patients who met the Milan criteria versus 57% and 51% for patients exceeding those limits (P = .006). A cumulative tumor size >8 cm was predictive of survival and tumor recurrence upon multivariate analysis. The adoption of Milan criteria for selection of cirrhotic patients has improved survival and reduced the rate of tumor recurrence. The evaluation of cumulative tumor size might further improve patient selection.

Costs and benefits of the passive prophylaxis of hepatitis B in an Italian hospital.

The authors report the clinical results and the cost/benefit analysis of a protocol of passive prophylaxis of hepatitis B based on the administration of two doses of three ml each of HBIG and on the control of anti-HBs levels by RIA for six months after accidental exposure in health-care personnel. Only two out of 351 susceptible subjects developed viral hepatitis instead of the expected 70 if passive prophylaxis had not been performed. The cost/benefit analysis showed a saving of 356 509 US$ in the past 36 months. Furthermore, the cost of each case of hepatitis prevented was 2194 US$, whereas the cost of one case of acute, benign hepatitis was 6180 US$. Since a saving of 3.39 US$ for each dollar spent is achieved, this protocol of passive prophylaxis appears more than adequate both clinically and economically. It is believed that the adoption of some general prophylactic measures will further stress the advantages of this procedure.

Low-dose intramuscular hepatitis B immune globulin and lamivudine for long-term prophylaxis of hepatitis B recurrence after liver transplantation.

The combination of lamivudine and hepatitis B immunoglobulins (HBIg) to prevent recurrence of HBV hepatitis has significantly improved the survival of patients transplanted for HBV-related end-stage liver disease. Generally, HBIg are administered intravenously. We evaluated the efficacy, tolerability, and cost savings of long-term intramuscular HBIg and lamivudine in 28 patients (23 men and 5 women), who received liver transplants for acute or chronic HBV-related liver disease. Twelve patients started lamivudine before and 16 at the time of liver transplantation. HBIg were administered intravenously during the first week (50 to 70,000 IU) and intramuscularly thereafter (1200 IU every 3 to 6 weeks) to maintain an HbsAb titer >100 IU/L. Mean follow-up was 20 +/- 13 months. Only one patient experienced HBV recurrence (9 months after transplantation). This patient had failed to follow the scheduled prophylaxis. Cumulative survival at 3 years was 83%. Intramuscular HBIg were well tolerated in all cases. Cost analysis comparing intramuscular vs intravenous HBIg administration showed that 39,490 Euros were saved per patient per year. These preliminary results show that low-dose intramuscular HBIg and lamivudine are efficacious and cost-effective for long-term prophylaxis of hepatitis B recurrence after liver transplantation.

From listing to transplant: nephrologic monitoring in cirrhotic patients awaiting liver transplantation.

Nephrologic monitoring of end-stage liver disease (ESLD) patients is part of evaluation for orthotopic liver transplantation (OLT). The numerous causes of renal dysfunction in ESLD patients sometimes relate to the extent of liver damage or sometimes more closely to organic nephropathy. The aim of this study was to evaluate renal function through a specific nephrologic form applied in our outpatient clinic to optimize nephrologic monitoring in ESLD patients awaiting OLT. We enrolled 69 cirrhotic patients (56 men, 13 women) awaiting OLT from April 2008 to January 2012. All patients were evaluated at listing and every 3 months until OLT. The most interesting result was the stable values of serum creatinine from listing to transplantation. We think that dedicated liver transplant nephrologic evaluation is important in the follow-up of ESLD patients awaiting OLT, because the presence of renal dysfunction may represent an important criterion for specific therapeutic interventions to minimize pre-OLT renal injuries that limit the effect of impaired renal function on patient outcomes.

Stages of early acute renal dysfunction in liver transplantation: the influence of graft function.

The development of early acute renal dysfunction (eARD) occurring in the first week after orthotopic liver transplantation (OLT) is mainly influenced by more severe degrees of pre-OLT hepatic insufficiency and liver graft dysfunction. The aim of our study was to evaluate the incidence of eARD post-OLT as well as its association with pre- and post-OLT hepatic dysfunction. We selected 54 end-stage liver disease patients who underwent OLT from 2008 to 2011. The prevalence of eARD was 53.7% (29/54) classified according to AKIN criteria in ARD-Risk (55.2%), ARD-Injury (27.6%) and ARD-Failure (17.2%). The worst stage of post-OLT eARD (eARD-Failure) seems to be influenced by the poor pre-OLT hepatic function as well as by early suboptimal recovery of graft function.

Polyomavirus BK infection before liver transplantation in patients with chronic kidney disease.

End-stage liver disease (ESLD) and chronic kidney disease (CKD) patients are both immunocompromised populations but polyomavirus BK (BKV) replication before liver transplantation is rare. We evaluated BKV prevalence among liver transplant recipients with renal dysfunction and the possible role of CKD as a risk factor for BKV replication in ESLD. From 2010 to 2011 we selected 31 ESLD patients awaiting liver transplantation to identify, the presence of CKD: No CKD (n = 22; 18 males) and CKD group (n = 9; 5 males). BKV infection was defined on the basis of viremia evaluated using quantitative real-time polymerase chain reactions. The prevalence of viremia among the No CKD group was 14% versus 56% in the CKD group (Fisher test; P = .027). We hypothesized that the presence of CKD may represent an additional condition of immunologic dysfunction regarding antiviral surveillances other than the antibacterial one that characterizes ESLD immunodysfunction, which could have promoted BKV replication. The specific immunologic mechanisms involved in pretransplantation diseases may have a role in BKV reactivation that could become responsible for nephropathy after transplantation.

Occurrence of chronic renal failure in liver transplantation: monitoring of pre- and posttransplantation renal function.

The aim of our study was to evaluate the occurrence of middle and long-term chronic renal failure (CRF) after orthotopic liver transplantation (OLT) in relation to acute renal failure (ARF). We prospectively monitored 75 patients, studying renal function on the basis of serum creatinine and glomerular filtration rate as estimated using the Modification of Diet in Renal Disease formula before as well as 1,6, and 12 months after OLT. The prevalence of ARF was 56% classified by the Acute Kidney injury Network criteria (52% stage 1, 29% stage 2, and 19% stage 3). The occurrences of CRF were 18.6% (11/59), 11.5% (6/52), and 14% (6/43) at 1, 6, and 12 months after OLT, respectively. The occurrence of CRF before OLT was 14.7%. We did not find any association between ARF and post-OLT CRF. The most relevant result of our study was the association between CRF at 6 and 12 months after transplantation with pre-OLT CRF on univariate and multivariate analysis. We suggest that evaluation of pre-OLT renal function should always be considered in the follow-up of liver transplant patients. Pre-OLT renal dysfunction must be recognized to be a risk factor for post-OLT CRF, representing important criterion to define specific therapeutic interventions to reduce patient morbidity and mortality.

Does caval reconstruction technique affect early graft function after liver transplantation? A preliminary analysis.

BACKGROUND: In the past decades, the inferior vena cava (IVC) reconstruction technique has undergone several evolutions, such as biopump, piggyback technique (PB), and laterolateral approach (LLPB). Several advantages are reported comparing the PB technique to biopump use. However, comparison between PB and LLPB has not been as well investigated. The aim of this study was to compare the results in terms of immediate graft function and intermediate graft survival among 3 subgroups characterized by distinct caval reconstruction techniques. METHODS: We retrospectively analyzed a cohort of 200 consecutive adult patients who underwent liver transplantation from January 2001 to December 2009. The patients were stratified according to 3 caval reconstructive techniques: biopump (n=135), PB (n=32) and LLPB (n=33). RESULTS: The LLPB group showed the shortest cold and warm ischemia times and the best immediate postoperative graft function. Survival analysis revealed LLPB patients to present the best 1-year graft survival rates: namely, 90.9% versus 75.0% and 74.1% among the PB and biopump groups, respectively (log-rank tests: LLPB vs biopump: P=.03; LLPB vs PB: P=.05). In our experience, LLPB showed the best graft survivals with an evident reduction in both cold and warm ischemia times. However, it is hard to obtain an irrefutable conclusion owing to the retrospective nature of this study, the small sample, and the different periods in which the groups were transplanted. CONCLUSIONS: LLPB technique was a safe procedure that minimized the sequelal of ischemia-reperfusion damage. This technique yielded results superior to venovenous bypass. No definitive conclusions can to be obtained in this study comparing classic PB or LLPB.