Search

Determination of cardiac output (CO) is crucial for perioperative monitoring of orthotopic liver transplant (OLT) recipients. A pulmonary artery catheter (PAC) has always been considered the "gold standard" of hemodynamic monitoring. The aim of this study was to evaluate the suitability of a transesophageal echo-Doppler device (ED) as a minimally invasive device to measure CO in OLT. ED was compared with the standard PAC technique taking into account the disease severity of OLT recipients as defined by the model for end-stage liver disease (MELD) score. We enrolled 42 cirrhotic patients scheduled for OLT 3 thermodilution CO measurements were taken by a PAC and the most recent ED measurement (CO(ED)) was also recorded. Paired measurements of CO were performed at standard times, unless there were additional clinical needs. Recipients were stratified into 3 groups according to MELD score: MELD score < or = 15 (14 patients); MELD score between 16 and 28 (17 patients); and MELD score > or = 29 (11 patients). We performed 495 paired measurements of CO. Mean bias was 0.34 +/- 0.9 L/min and limits of agreement were -1.46 and 2.14 L/min. In patients with MELD score <15, the bias was 0.12 +/- 0.55. The ED results were not interchangeable with PAC, because of the large limits of agreement. However, in cirrhotic patients with MELD scores <15, the precision of the new method was similar to that of PAC; therefore, in this subset of patients, it may represent a reliable alternative to PAC.

Chronic hepatitis C virus (HCV) infection has been associated with a wide number of immunologic disorders, ranging from clinically silent laboratory abnormalities (eg, autoantibody positivity) to severe systemic diseases (eg, cryoglobulinemic vasculitis). Autoimmune hemolytic anemia (AIHA), due to the production of antibodies against erythrocyte membrane antigens, is an uncommon extrahepatic manifestation in the setting of chronic hepatitis C. Herein we have reported the case of a 57-year-old woman with decompensated HCV-related cirrhosis awaiting orthotopic liver transplantation (OLT) who experienced severe AIHA. After 1 month of treatment with prednisone (1 mg/kg body weight/d), there was no significant amelioration of anemia. Rituximab, an anti-CD20 monoclonal antibody that depletes B-lymphocytes reducing serum immunoglobulins, was initiated (375 mg/m(2) IV, weekly for 4 weeks) with a prompt, sustained increase in hemoglobin. The drug was well tolerated; it did not interfere with the course of the liver disease. Thirty-one months after rituximab therapy with resolution of AIHA, the patient successfully underwent OLT using immunosuppression with tacrolimus and low-dose steroids. The patient was discharged on postoperative day 36. No infectious event occurred in the postoperative period. At 18 months follow-up after OLT, there has been no infectious or hematological event. Our experience supported the safety of rituximab use in patients with advanced HCV-related liver disease before OLT.

The indications for liver transplantation among patients with post-hepatitis B virus (HBV)-related cirrhosis have changed over the past 35 years. We reviewed the long-term results of 47 patients treated with liver transplantation for HBV-related cirrhosis. Patients were classified into 3 groups according to the perioperative regimen. In the initial experience, no immunoprophylaxis was adopted (no-IP; n=5). From 1988-1996, an immunoprophylaxis scheme was adopted (HBIg; n=16). From 1997-2007, we adopted the combination of lamivudine and HBIg (LAM-HBIg; n=26). We calculated the prevalence of serological reinfection and patient survival at 1 to 20 years, using the 3 regimens. The recurrence rate was 75% in the group of untreated patients; 30% in the HBIg group; and 9% in the LAM-HBIg group. The overall survival was 67% at 5 years, and 64% at 10 and 20 years. The long-term survival for each of the 3 therapeutic approaches, namely, for the patients who did not receive any treatment, for the HBIg group, and for the LAM-HBIg group, were 20%, 50%, and 84%, respectively. We suggest to use the LAM-HBIg combination.

In liver transplantation the identification of risk factors and the risk quantification for each single case represent a field of great interest. There are donor-related and recipient-related risk factors. Donor risk index (DRI) was retrospectively calculated in 223 liver transplant cases. We did not include patients with preoperative diagnosis of hepatocarcinoma and retransplants. The cases were stratified into two classes according to the DRI (low risk, DRI<1.7, and high risk, DRI >or= 1.7). A new index, namely the organ patient index (OPI) was calculated adding the Model for End-stage Liver Disease (MELD) score to the DRI. Patients were stratified into two classes according to the OPI (low risk, OPI 2.85). The cases with low DRI (n=144) showed better survival than the cases with high DRI (n=82; P< .02). The cases with low OPI (n=173) showed better survival than cases with high OPI (n=50; P< .01). The OPI predicted outcomes better than DRI, increasing the gap in the long-term graft survival between the low- and the high-risk class. The inclusion of the MELD in the new index allowed better prediction of graft survival.

Successful treatment of chronic hepatitis C virus (HCV) infection can prevent reinfection after orthotopic liver transplantation (OLT). Pegylated interferon (PEG-IFN) may ameliorate virological response (VR), making the risk-to-benefit ratio of therapy favorable in waiting list patients. From January 2001 to April 2006, we treated 15 HCV cirrhotics with PEG-IFN alpha-2b (1.5 microg/kg/week) and ribavirin (RIBA; >or=10.6 mg/kg/d). Their mean age was 51.5 years. There were 9 men. In 6 cases the genotype was 1b. With Child-Pugh scores >or=9 (range 9-12) and Model for End-Stage Liver Disease (MELD) scores >or=14 (range, 14-22). Adverse events occurred in all subjects: thrombocytopenia (<40,000/microL) in 8; neutropenia (<700/microL) in 10; anemia (Hb <8.5 g/dL) in 1; grade III hepatic encephalopathy in 2; pelvic infection in 1; variceal hemorrhage in 1; and hepatocellular carcinoma (HCC) recurrence in 1. Adverse events caused treatment withdrawal in 6 (40.0%) and RIBA and/or PEG-IFN dose reduction in 10 (66.6%). Early VR (EVR) was obtained in 9 subjects (60.0%), end-of-treatment (EOT) VR in 7 (46.6%), and sustained VR (SVR) in 3 (20.0%). Three subjects--2 nonresponder and 1 breakthrough--were transplanted at 25, 23, and 16 months after the EOT, respectively. Three subjects died at 6, 8, and 15 months after the EOT due to HCC, spontaneous bacterial peritonitis, and liver failure. Nine patients are awaiting OLT. The risk-to-benefit ratio is against PEG-INF and RIBA treatment of severely decompensated cirrhotics infected with genotype 1 awaiting OLT, but therapy is probably beneficial in genotype 2 subjects, due to an expected SVR rate of more than 40%. However, one must carefully consider the high risk for severe adverse events.

Various artificial liver support systems are currently used in patients with decompensated chronic liver disease or acute liver failure as a bridge to recovery or to orthotopic liver transplantation (OLT). Between June 2004 and September 2006, 9 subjects were treated with plasma exchange (PE) for acute decompensation on chronic liver disease or chronic decompensation in end-stage liver disease. All of them were awaiting OLT or were listed at the moment of decompensation. Grade II to III hepatic encephalopathy (HE) was present in 4 patients, significant renal dysfunction in 3 patients, and ascites in 6 patients. Baseline serum total bilirubin was 35.1+/-11.2 mg/dL (mean value+/-SD). The patients underwent a mean of 12.1 2-hour exchanges over 1 to 8 weeks. The 3 who recovered were alive after a mean follow-up of 22.7+/-10.3 months. There were 3 patients who underwent transplantation and 3 who died due to liver failure during treatment. Only subjects with acute decompensation and without HE or significant renal dysfunction survived without OLT. PE did not significantly modify the grade of HE or the renal function. PE seemed to be a safe, long-term, effective therapeutic option for acute decompensation among subjects with chronic liver disease without brain or renal dysfunction.

We reviewed the incidence and the impact of posttransplant lymphoproliferative disorders (PTLDs) on patient survival among a consecutive series of 255 patients. Five cases of PTLD were observed in adults: two cases were early (less than 1 year) and three cases, late lymphomas. The EBV positivity and the degree of immunosuppression were the main risk factors. We labeled cases as early or late according to whether the time elapsed from the transplant to the first clinical evidence of PTLD was less than 12 months. The median time from transplant to diagnosis of PTLD was 8 (early) and 108 (late) months. All cases were treated by reduction in immunosuppressive therapy with conventional chemotherapy and rituximab. The early cases with lymphoma located at the hepatic hilum died due to local complications (biliary sepsis and hemobilia), after an initial partial response to chemotherapy. The three patients with late cases are in remission after a mean follow-up of 23 months.

We described the characteristics of livers already labeled as marginal, nonstandard, or selected with extended criteria: donors of elderly age, steatosis, hemodynamic instability, long cold ischemia time, high serum Na, HbcAb-positive status, HCVAb-positive status. Recipients characteristics (gender, UNOS status, MELD score, indication for transplan- tation) and their best possible match to nonstandard donors were evaluated with a report of the recent guidelines and the specific algorithms to optimize recipient identification.

The model for End-stage Liver Disease (MELD) has been adopted by the Organ Procurement and Transplantation Network (OPTN) in 2002 as the standard priority rule for the liver transplantation waiting list. We retrospectively calculated the pretransplant MELD scores of 226 consecutive adult grafts. We did not correct for hepatocellular carcinoma comorbidity or for the etiology of liver disease. Cases were categorized according to the MELD score: class I, MELD scores between 6 and 14 (low MELD, n = 116); class II, MELD score between 15 and 24 (intermediate MELD, n = 78); class III, MELD score between 25 and 42 (high MELD, n = 32). All patients were transplanted using deceased donors. Grafts were categorized also according to donor quality (standard donor vs nonstandard donor). Sorting into categories was performed before transplant by officers of the Central-South Italian Transplant Organization overregional organ procurement agencies, namely OCST. Differences in Kaplan-Meier graft survivals (GS) between low MELD class and high MELD class were statistically significant (P < .01). Among standard donors, the 6-month GS were 83%, 94%, and 63% for the low, intermediate, and high MELD subset, respectively, differences that did not reach statistical significance. Among nonstandard donors, the 6-month GS were 77%, 71%, and 38% for the low, intermediate, and high MELD classes, respectively. Differences between low MELD class and intermediate MELD class and between low MELD class and high MELD class were statistically significant (P < .01). We strongly suggest that the utilization of nonstandard organs should be avoided for patients with high MELD scoresfor patients with high MELD scores.

The University of Wisconsin solution (UW) and the Bretschneider solution (HTK) were used in 39 adult cadaveric donors: 22 perfused with UW (group 1) and 17 with HTK (group II). Donors were flushed through the aorta (UW, 5 to 6 L; HTK, 8 to 10 L) and through the portal vein (UW or HTK, 1 L). Grafts perfused with HTK showed lower levels of SGOT at postoperative day 7 than those transplanted with UW (38 +/- 19 vs 58 +/- 31, P < .05). No difference was observed in other functional and outcome parameters. No cases of primary dysfunction were observed. Six-month graft survival was 85.7% in HTK group and 80.9% in UW group (P = NS). Six unrelated deaths were observed. Five biliary complications were observed in five patients: three in the UW group and two in the HTK group. In conclusion, data fail to show major differences between the two solutions used.

We assessed the safety and clinical efficacy of the Molecular Adsorbent Recirculating System (MARS) in liver failure patients admitted to our intensive care unit (ICU) from May 2000 to February 2006. Of 28 adult patients with bilirubin >15 mg/dL and hepatic encephalopathy (HE) grade > or =2 or hepato-renal syndrome, 22 patients were included in the study, because 6 patients were older than 65 years of age or showed recent alcohol abuse or extrahepatic malignancy. Patients were assigned to 2 groups according to whether MARS therapy was associated with a transplantation procedure: 11 patients received MARS therapy and liver transplantation (OLT group) and 11 patients received MARS therapy alone (non-OLT group). Five of 11 patients in the OLT group were listed for transplantation and 6 patients with graft failure for retransplantation. The patients in the OLT and non-OLT groups were similar in MELD, SOFA, and SAPS scores. All patients were stable and free from complications. MARS significantly reduced bilirubin, bile acids, and blood urea nitrogen (BUN) levels in both groups (P < .05), whereas a significant decrease in ammonia level was observed in the OLT group. Patient survival rates at 3 and 6 months in the OLT group were 91% and 73%, respectively, and in the non-OLT group, 9% and 9%, respectively (P < .001). MARS was safe and well tolerated, improving biochemical parameters, neurological function, and pruritus. In terms of survival, the use of MARS alone was not effective due to the high rate of multiple organ failure. Nevertheless, the association of MARS with a transplant/retransplantation procedure was highly effective

MELD and PELD scores of 255 consecutive grafts were calculated (236 adult cases and 19 pediatric cases). No correction for the etiology of liver disease was performed. Retransplants were excluded. Three categories of patients were identified: low MELD (scores <12, n = 61); intermediate MELD (scores between 12-24, n = 159); high MELD (scores > or =25, n = 35). Grafts were categorized according to donor quality: standard livers (n = 199), vs nonstandard livers (n = 56). Nonstandard livers were identified by age > or =60, or at least by two of the following conditions: severe hemodynamic instability, ultrasound evidence of steatosis, natriemia > or =155 mEq/L, ICU stay >7 days, liver trauma, protracted anoxia as cause of brain death, transaminases levels x 4. In standard livers, the 12-month graft survival (GS) for low, intermediate, and high MELD classes were 88%, 74%, and 77%, respectively. In nonstandard livers, the 12-month GS for the low, intermediate, and high MELD classes were 84%, 55%, and 44%, respectively; differences between low MELD class and both intermediate and high MELD classes were significant (P < .05). Cox regression analysis of all cases identified the following parameters as independent predictors of GS: donor status; donor age; and recipient creatinine. The highest correlation with GS was found using donor age and recipient creatinine as covariates. In standard livers no variable was able to predict GS. In nonstandard livers the MELD-PELD score was the unique variable able to predict GS. We suggest avoiding the use of nonstandard livers for patients with high MELD scores.

Two hundred seventy-six liver transplants were retrospectively reviewed to analyze 6-month graft survival in relation to the combination of donor quality (standard donor vs nonstandard donor) and risk related to the severity of recipient liver disease low-risk, ie, United Network for Organ Sharing [UNOS] status 3/2b; high-risk, ie, UNOS status 1/2a). The overall 6-month survival rate of 82% was stratified into 4 classes: (1) standard donor to low-risk recipient = 88%; (2) standard donor to high-risk recipient = 86%; (3) nonstandard donor to low-risk recipient = 84%; and (4) nonstandard donor to high-risk recipient = 67%. According to the observed graft survival in the 4 different classes, 2 simulations were performed: the "match simulation" (transplantation of all low-risk recipients using standard donors, and transplantation of all high-risk recipients using nonstandard donors), and the "mismatch simulation" (transplantation of all the high-risk patients using low-risk donors and transplantation of low-risk patients using high-risk donors). The 6-month survival rates, calculated using the match simulation, were 74% and using the mismatch simulation, 84%. The authors suggest that, in the era of marginal donors, the recipient should be selected in relation to the characteristics of the donor according to the mismatch model.

BACKGROUND: Hepatitis C virus (HCV) recurrence in HCV+ liver transplant recipients is almost inevitable and may be promoted by immunosuppression. We compared the amount of liver damage with regard to usage of steroids and basiliximab. METHODS: A total of 140 HCV+ adult liver transplant recipients were randomly allocated to basiliximab + steroids or basiliximab + placebo (plus cyclosporine and azathioprine). Primary endpoint: hepatitis C histological recurrence (liver damage as for Ishak grading score >or=8 by biopsy at 12 months); secondary endpoints: treatment failure (death, graft loss, patient withdrawal), biopsy proven acute rejection (BPAR), treated acute rejection (tAR), allograft and patient survival rates at 12 months. RESULTS: Any significant difference has been observed in the 12-month hepatitis C histological recurrence rate (41.2% basiliximab + steroids, 37.5% basiliximab + placebo, P = 0.354). The treatment failure rate was significantly higher in basiliximab + steroids (28.8%) than in basiliximab + placebo (15.6%), P = 0.03; the combination test for the evaluation of the joint hypothesis resulted in a borderline nonsignificant overall result (P = 0.059). BPAR rate was significantly lower in the group treated with steroids (24.3% basiliximab + steroids, 39.4% basiliximab + placebo, P = 0.04), while the tAR rate was similar (29.7% basiliximab + steroids and 37.9% basiliximab + placebo). Any significant differences in 1-year graft and patient survival rates have been observed (72.9% and 84.8% basiliximab+steroids; 81.5% and 89.0% basiliximab + placebo). CONCLUSIONS: Results suggest that steroid-free therapy is associated with a significantly lower treatment failure rate, although histological recurrence rate of hepatitis C is similar in the two groups. This benefit is not offset by an evident increase in graft rejection rate requiring treatment.

The outcome of liver transplantation (LTx) has been correlated with several donor and recipient factors.

BACKGROUND: The outcome of liver transplantation (LTx) has been correlated with several donor and recipient factors. METHODS: A database of 191 consecutive LTx cases was analyzed using Kaplan-Meier and Cox regression statistics based on 80 variables. To avoid additional effects of late events on patient survival, the chosen endpoint was 6 months. Data were evaluated using SPSS statistical software. RESULTS: Kaplan-Meier analysis revealed a difference in 1- to 6-month graft survival between patients transplanted with organs from donors older versus younger than 60 years (Breslow, P <.01). Differences in 1- to 6-month graft survivals were observed between patients listed as UNOS status 3, 2B, 2A, and 1: the outcomes for UNOS status 2B versus UNOS status 2A and UNOS status 2B versus status 1 were significant (P <.05). Differences in 1- to 6-month graft survival rates were found between patients with versus without sepsis (P <.05), and with versus without rejection episodes (P <.01). Cox regression analysis revealed only three of the variables to be independent prognostic predictors of graft failure: donor age; postoperative septic status; and rejection. The best mathematical multivariate Cox regression model linked donor age + donor Na + rejection + sepsis to 1- to 6-month graft survival (chi-square = 29.06, P <.001). CONCLUSION: Factors predictive of 1- to 6-month graft survival after liver transplantation include donor age; UNOS status; sepsis; and rejection.

Lamivudine-induced muscle mitochondrial toxicity

Renal vasoconstriction commonly occurs in decompensated liver cirrhosis and is entirely reversible after hepatic transplantation. In this study we evaluated by Doppler ultrasonography the changes of renal vascular resistance occurring during the first month after transplantation. In 16 cirrhotic patients the intrarenal resistive index at the level of interlobar arteries and the blood urea nitrogen and serum creatinine levels were measured before (range, 1 to 34 days) and after transplantation (days 1, 3, 7, 14, 30). Before transplantation the median resistive index value was 0.69 (95% CI, 0.65 to 0.71) and eight of 16 patients showed abnormal values (0.70 or more). After transplantation, the median resistive index was significantly decreased on all the evaluation days, and no patient had abnormal values on posttransplantation day 7. No significant correlation was found between resistive index and serum creatinine or blood urea nitrogen levels. Doppler ultrasonography is a simple tool to evaluate the recovery of normal intrarenal arterial resistance levels after liver transplantation. One week appears to be the optimal timing to evaluate the renal resistive index in the posttransplantation period.

Primary dysfunction after liver transplan- tation, today remains an important determinant of patient survival even with recent improvements in postoperative support therapy. PD is a multifactorial event and donor factors probably play a minor role in determining PD; recipient factors, particularly preoperative bilirubin level, intraoperative blood infusion, and bypass time are the strongest predictors of PD. The combination of donor and recipient factors, their multiplicity, and the low grade of correlation between each factor and PD explain the difficulty in the reduction of primary dysfunction after liver transplantation.

The series shows that in liver transplant recipients, infections, and steroid-resistant rejection are major determinants of patient outcome. Steroid sensitive rejection identifies a subgroup of patients with a more favorable prognosis.

The role of donor, preop- erative, intraoperative, and postop- erative factors in predicting patient survival after liver transplantation was evaluated by the Bio Medicus data package on a database contain- ing 162 variables filled with records from 100 consecutive first-liver transplant cases. Donor data did not predict outcome. Recipient preop- erative data (Child status, HCV sta- tus) were predictive using life table and Cox regression methods. Recip- ient intraoperative data (by-pass time, warm ischemia time, delay in arterial revascularization, and packed red blood cell requirements) were predictive of outcome using life table analysis. Recipient post- operative data (rejection, sepsis, primary dysfunction, and hepatic ar- tery thrombosis) were predictive of outcome.

The use of marginal donors is well accepted by most centers for emergency situations, but there is debate on their use for patients on regular waiting lists. We report our experience of the 1-year survival for patients on waiting lists (n = 147, 1-year survival = 32%), patients transplanted from good donors (n = 60, 1-year survival = 84%), and patients transplanted from marginal donors (n = 15, 1-year survival = 56%). We concluded that liver transplantation from marginal donors (a) is a safe procedure (b) has a 1-year survival that is significantly better than that on a waiting list (c) is ethically justified especially in countries with donor shortages, and (d) may allow transplantation of "special" high risk and poor long-term outcome patients.

The aim of this study was to evaluate the efficiency of pulmonary gas exchange during the course of liver transplantation. We studied 25 adult cirrhotic patients undergoing transplantation, performed with venovenous bypass. A significant increase in PaO2, and a significant decrease in physiological shunt and alveolar-arterial partial pressure difference were observed just before the start of venovenous bypass. These changes were probably caused by modifications in respiratory mechanics, such as an increase in functional residual capacity. There were no other respiratory changes during the anhepatic and post-anhepatic phases.

The catalytic activities of some mitochondrial and cytoplasmic enzymes were measured in plasma from 19 patients after orthotopic liver transplantation, in order to detect and monitor the evolution of hepatocellular damage and to predict liver rejection. The enzymatic activities determined were: mitochondrial isoenzyme of aspartate aminotransferase, glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltranspeptidase and alkaline phosphatase. The results of all enzymatic activities were normalized by expressing them as multiples of the upper limit of the relevant reference range and then the necrosis index (NI) has been calculated. The proposed NI consists of percent ratio of the normalized mitochondrial enzymatic activities over the sum of cytoplasmic and mitochondrial normalized activities. We observed that NI values higher than 30% correctly identified all but two acute rejection events which were documented by liver biopsies showing a diagnostic sensitivity of 90%, specificity of 78% and a predictive value of 90%.

Primary non-function (PNF) of a transplanted liver is a postoperative condition characterized by absence of hepatic recovery due to various insults during harvesting, preservation or revascularization. Until recently early retransplantation (RTx) has been considered the policy of choice. Results of RTx for PNF are unsatisfactory (1-year survival rates ranging from 0 to 34%). The management of PNF by medical care without RTx with a recovery rate of 80% and a 1-year actuarial survival rate of 50% is reported for a series of 33 consecutive liver transplants. The guidelines for the medical care management are given and the results are discussed.

Primary dysfunction after liver transplantation, today remains an important determinant of patient survival even with recent improvements in postoperative support therapy. PD is a multifactorial event and donor factors probably play a minor role in determining PD; recipient factors, particularly preoperative bilirubin level, intraoperative blood infusion, and bypass time are the strongest predictors of PD. The combination of donor and recipient factors, their multiplicity, and the low grade of correlation between each factor and PD explain the difficulty in the reduction of primary dysfunction after liver transplantation.

x