Sent Liver Grafts Do Not Have a Detrimental Impact on Post-transplant Outcome.

INTRODUCTION: "Sent livers" (SL) (interregional allocated organs) are considered extended donor criteria grafts. These grafts influence post-transplant outcome. In our donor allocation program, the number of allocated SLs is increasing. The aim of our study is to provide data supporting the possibility to enlarge the use of SLs through adequate donor-to-recipient matching. METHODS: A retrospective analysis was carried out from our prospective-collected database during 2014. RESULTS: Fifty-seven liver transplantations (LTs) were included: 22 SLs and 35 grafts procured by us (nSLs). Only donor risk index among donor characteristics showed a trend toward significant values (SL 1.901 vs nSL 1.726, P = .07). Among LT variables, the number of patients who received interleukin-2 inhibitor induction (SL 7 vs nSL 20, P < .05) and the presence of hepatocellular carcinoma (SL 50% vs nSL 34%, P < .05) reached statistical significance. One case of primary nonfunction occurred in the nSL group. No major retrieval injuries were observed. Retransplantation was performed in 6 cases (2 SLs and 4 nSLs). One patient in the SL group died after retransplantation. Graft survival rates at 1, 3, 6, and 12 months were 100%, 100%, 90%, 86% and 91%, 86%, 86%, 86% (P = .79) in SL and nSL groups, respectively. DISCUSSION: SL performance did not differ from that of nSL. SLs were usually allocated to noncritical candidates, and nSLs were transplanted more frequently in decompensated recipients. Despite this peculiar donor-recipient match, grafts survival was similar in the 2 groups of patients.

Arterial anastomosis in liver transplantation for Rendu-Osler-Weber disease: two case reports.

Liver transplantation (LT) in patients with hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber, disease is a problematic procedure. In patients with hepatic involvement due to clinically significant arterovenous malformations, there is high risk of intraoperative bleeding and intra- or perioperative complications. Some surgical corrections have been proposed for venous problems, concerning the vena caval anastomosis. A common finding in HHT is arterial enlargement of the celiac trunk and of the common hepatic artery. We report 2 cases of LT in HHT where the arterial anastomosis was successfully performed using the splenic artery of the recipient, which shows less tendency for enlargement than the celiac trunk.

Balancing donor and recipient risk factors in liver transplantation: the value of D-MELD with particular reference to HCV recipients.

Donor-recipient match is a matter of debate in liver transplantation. D-MELD (donor age × recipient biochemical model for end-stage liver disease [MELD]) and other factors were analyzed on a national Italian database recording 5946 liver transplants. Primary endpoint was to determine factors predictive of 3-year patient survival. D-MELD cutoff predictive of 5-year patient survival <50% (5yrsPS<50%) was investigated. A prognosis calculator was implemented (http://www.D-MELD.com). Differences among D-MELD deciles allowed their regrouping into three D-MELD classes (A < 338, B 338-1628, C >1628). At 3 years, the odds ratio (OR) for death was 2.03 (95% confidence interval [CI], 1.44-2.85) in D-MELD class C versus B. The OR was 0.40 (95% CI, 0.24-0.66) in class A versus class B. Other predictors were hepatitis C virus (HCV; OR = 1.42; 95% CI, 1.11-1.81), hepatitis B virus (HBV; OR = 0.69; 95% CI, 0.51-0.93), retransplant (OR = 1.82; 95% CI, 1.16-2.87) and low-volume center (OR = 1.48; 95% CI, 1.11-1.99). Cox regressions up to 90 months confirmed results. The hazard ratio was 1.97 (95% CI, 1.59-2.43) for D-MELD class C versus class B and 0.42 (95% CI, 0.29-0.60) for D-MELD class A versus class B. Recipient age, HCV, HBV and retransplant were also significant. The 5yrsPS<50% cutoff was identified only in HCV patients (D-MELD ≥ 1750). The innovative approach offered by D-MELD and covariates is helpful in predicting outcome after liver transplantation, especially in HCV recipients.

Hypoperfusion of segment 4 in right in situ split-liver transplantation.

To expand the donor pool, split-liver transplantation has been implemented in recent years. In the classic technique, the arterial axis with the artery for segment 4 (S4) coming from the left hepatic artery (HA) is included with the right graft. To give a surgical advantage to pediatric recipients in our center, the left HA, the common HA, and the celiac trunk are generally retained with the left liver. Thus the artery for S4 is sacrificed. We compared the outcomes of S4 in 290 whole grafts (WG; group A) with 28 right in situ split-liver grafts (SSLG; group B), which were transplanted over the past 10 years (January 1999-December 2009). The rates of major biliary and of hemorrhagic complications were similar. In most of cases (16/24, 66%) S4, on computerized tomographic scan appeared to show signs of hypoperfusion, sometimes with a peripheral aspect of hyperperfusion in the arterial phase. S1 showed signs of hypoperfusion in only 2 cases. A biliary collection near the resection line present in 8 cases was treated in 6 of them with percutaneous drainage and in 2 with laparotomy. These complications did not influence graft or patient survival. Graft survivals at 1, 5, and 10 years for WG and SSLG were not different among the groups: 85%, 74%, and 66% vs 89%, 79%, and 63%, respectively (P = .8). Although our technique cannot be considered to be anatomically correct, the ischemia of S4 did not influence the outcome. The rate of retransplantations for hepatic artery thrombosis was 17.9% in RSSG and 3.4% in WG (P = .001), which was probably due at least in part to the insertion of interposition grafts.

Liver transplantation for hepatitis B virus patients: long-term results of three therapeutic approaches.

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.

A risk score and a flowchart for liver retransplantation.

Rates of overall graft survival after liver retransplantation (RETX) are still 20% lower than those after primary liver transplantation (TX). On the basis of previous mathematical approaches from other authors who tried to identify prognostic variables for survival and prognostic risk scores for liver RETX, we studied 12 categorical and 17 continuous variables from the donor, the recipient, and the surgical procedure, among patients who underwent liver retransplantation. Data were retrieved in a retrospective study over the last 12 years, in order to overcome the possible gap of other series that often included RETX performed many years ago. We considered 394 consecutive cadaveric liver TXs in adult patients, namely, 351 primary TXs and 43 RETXs. Using multivariate logistic regression, we calculated the following equation for 1-year risk of death for patients undergoing liver RETX: log(Odds)= -4.81+2.23 x Recipient Sex + 1.86 x Donor Age + 1.60 x MELD Score (where: Recipient Sex: F=0, M=1; Donor Age (years): <40=0, 40-59=1; 60+ =2; MELD Score: <26=0, 26+ =1). With this formula, we built a decision tree to predict the individual risk of death based on the subject's profile. Keeping in mind that mathematical models can only help our decisional process and are not conclusive, our data needs to be validated on a larger scale.

Back-table arterial reconstructions in liver transplantation: single-center experience.

Anatomic variations of the arterial supply to donor liver grafts often require complex hepatic artery reconstructions on the back table. Therefore, because of the additional anastomoses, there is a greater risk of arterial thrombosis and graft loss. Among the 620 orthotopic liver transplantations (OLT) in 549 adult and pediatric patients performed from June 1983 through August 2004, the rates and types of donor hepatic artery variations (HAV) and the type of reconstructions were reviewed as well as the 1- and 5-year grafts and patient survival rates after OLT. At least 1 HAV was present in 133 liver grafts (21.4%). The most frequent variations were as follows: right hepatic artery (RHA) from superior mesenteric artery (SMA) (44 cases); RHA from aorta (4 cases); and RHA from SMA, combined with a left hepatic artery (LHA) from left gastric artery (3 cases). No graft was discarded. Fifty-six of 133 (42%) HAV required arterial reconstructions, generally a termino-terminal (TT) anastomosis between RHA and splenic artery (26 cases, 46.4%). Less frequently performed anastomoses were the "fold-over" technique (15 cases, 26.8%) and the anastomosis between the RHA and the gastro-duodenal artery (6 cases, 10.6%); rare reconstructions were performed in 9 cases (16.0%). The rate of hepatic artery thrombosis was 5.4% (3 of 56 OLT) in complex hepatic artery reconstructions and 2.2% in other grafts. One- and 5-years graft and patient actuarial survival rates have been respectively 73.2%- 71.4% in hepatic artery reconstructions and 78.6%-76.8% in the absence of an artery reconstruction, respectively.

A "steroid-free" tacrolimus and low-dose mycophenolate mofetil primary immunosuppression does not prevent early acute rejection after liver transplantation.

To assess the efficacy and safety of a primary immunosuppressive regimen with tacrolimus (Tac) and low-dose mycophenolate mofetil (MMF) without steroids and to determine the exposure to mycophenolic acid (MPA) in the early postoperative period, we performed a single-center, randomized 1:1, open-label, controlled study planned to be 60 liver transplantation patients randomized into 2 groups: group A, tacrolimus + MMF (750 mg orally twice a day); and group B, tacrolimus + MMF (750 mg orally twice a day) + steroids. After an interim analysis by the ethical committee patient enrollment was stopped. Data from 30 patients (12 in group A and 18 in group B with a mean follow-up period of 31 +/- 7 months) showed a patient survival rate of 91.7% in group A and 100% in group B and a graft survival rate of 91.7% and 88.9%, respectively. Nine patients (75%) in group A suffered an acute rejection episode, whereas in group B only 3 patients (16.7%) showed acute rejection (P = .002). All rejection episodes occurred in both groups at 1 week after transplantation. The difference in histological grading was statistically significant (P = .021). The toxicity profiles were similar in both groups. A primary immunosuppressive regimen based on Tac and low-dose MMF without steroids is safe but unable to prevent acute rejection at 1 week after transplantation even if early acute rejection does not affect the outcome in terms of morbidity and graft or patient survival.

Long-term outcome of right split in situ grafts in adults.

In situ split liver transplants represent a technical progression from ex situ split procedures conceived to retrieve grafts for pediatric recipients. The transection line runs along the falciform ligament, so the main artery to the right graft is the right proper artery, whereas the left graft retains the main arterial axis with the celiac trunk. Although the major advantages are for pediatric recipients, due to the expanded pool of grafts available, for adult recipients the results of right split in situ grafts must be compared with whole grafts. We considered two groups of consecutive grafts transplanted since 1993 as first grafts: 20 of the former and 261 of the latter. Groups were comparable for donor gender, recipient age and gender, perfusion solution, ischemia time, and follow-up time, but not for donor age and for the number of arterial anastomoses. Although there were more major surgical complications in the former compared with the latter group (40% vs 25%), the only statistically significant difference was found in retransplantation rate for arterial complications (15% vs 2.2%). No statistical difference was observed in graft or patient actuarial survival rates at 1, 3, or 6 years after transplantation; for right split grafts these were 85%, 69%, and 69% and 95%, 79%, and 79%, respectively.

Endothelial targeting with C1-inhibitor reduces complement activation in vitro and during ex vivo reperfusion of pig liver.

Tissue damage during cold storage and reperfusion remains a major obstacle to wider use of transplantation. Vascular endothelial cells and complement activation are thought to be involved in the inflammatory reactions following reperfusion, so endothelial targeting of complement inhibitors is of great interest. Using an in vitro model of human umbilical vein endothelial cells (HUVEC) cold storage and an animal model of ex vivo liver reperfusion after cold ischaemia, we assessed the effect of C1-INH on cell functions and liver damage. We found that in vitro C1-INH bound to HUVEC in a manner depending on the duration of cold storage. Cell-bound C1-INH was functionally active since retained the ability to inhibit exogenous C1s. To assess the ability of cell-bound C1-INH to prevent complement activation during organ reperfusion, we added C1-INH to the preservation solution in an animal model of extracorporeal liver reperfusion. Ex vivo liver reperfusion after 8 h of cold ischaemia resulted in plasma C3 activation and reduction of total serum haemolytic activity, and at tissue level deposition of C3 associated with variable level of inflammatory cell infiltration and tissue damage. These findings were reduced when livers were stored in preservation solution containing C1-INH. Immunohistochemical analysis of C1-INH-treated livers showed immunoreactivity localized on the sinusoidal pole of the liver trabeculae, linked to sinusoidal endothelium, so it is likely that the protective effect was due to C1-INH retained by the livers. These results suggest that adding C1-INH to the preservation solution may be useful to reduce complement activation and tissue injury during the reperfusion of an ischaemic liver.

[Severe mitral insufficiency caused by the rupture of the chordae tendinae in acromegaly. Report of a case]. / Insufficienza mitralica severa da rottura di corda tendinea in acromegalia. Descrizione di un caso.

Cardiovascular disease is a common finding in patients with acromegaly. In such patients, heart failure frequently leads to death. Cardiovascular manifestations of acromegaly include cardiomegaly and very often hypertension, coronary atherosclerosis, and diabetes. Primary valvular disease is less commonly observed. Because it is not clear whether acromegaly-related cardiomyopathy is a specific entity and since there are not many necropsy reports regarding mitral valve prolapse in acromegalic patients, we report the case of severe mitral regurgitation due to rupture of the chordae tendinae in a patient with mitral valve prolapse and acromegaly.

Randomized trial of lamivudine versus hepatitis B immunoglobulin for long-term prophylaxis of hepatitis B recurrence after liver transplantation.

BACKGROUND/AIMS: The long-term prophylaxis of hepatitis B after liver transplantation requires further optimization. In a randomized trial we investigated a regimen where the initially given hepatitis B immunoglobulin (HBIg) is replaced by long-term lamivudine treatment. METHODS: Twenty-four liver transplant recipients (all HBsAg-positive/HBV DNA-negative before transplantation), who had received HBIg for at least 6 months without HBV recurrence, were randomized to receive lamivudine (n = 12) or HBIg (n = 12) for 52 weeks. The efficacy criteria involved seronegativity for HBsAg and undetectable HBsAg/ HBcAg in the liver. RESULTS: Twenty-one of 24 patients completed the study without hepatitis B virus (HBV) recurrence (11 on HBIg, ten on lamivudine), while three patients became HBsAg-positive. Amongst those without HBV recurrence HBV DNA was detectable only by polymerase chain reaction, intermittently in serum and lymphocytes, and in liver specimens from six of eight patients receiving HBIg and five of seven receiving lamivudine. YMDD variant was found in four cases with no viral antigen expression. Eight patients continued lamivudine after the study and during an additional 6-22 months remained HBsAg-negative with normal graft function. CONCLUSIONS: Substitution of HBIg with lamivudine is effective for prevention of HBV recurrence in low-risk liver transplant recipients and offers a convenient and cost-effective alternative for long-term HBV prophylaxis.

European collaborative study on factors influencing outcome after liver transplantation for hepatitis C. European Concerted Action on Viral Hepatitis (EUROHEP) Group.

BACKGROUND & AIMS: Liver transplantation for hepatitis C virus (HCV)-related liver disease is characterized by frequent graft infection by HCV. The prognosis and risk factors for morbidity and mortality in this condition were determined. METHODS: A retrospective study of 652 consecutive anti-HCV-positive patients undergoing liver transplantation between 1984 and 1995 in 15 European centers was conducted; 102 patients coinfected with hepatitis B virus (HBV) received immunoglobulin prophylaxis for antibody to hepatitis B surface antigen. RESULTS: Overall, 5-year survival was 72%. Five-year actuarial rates of hepatitis and cirrhosis were 80% and 10%. Genotypes 1b, 1a, and 2 were detected in 214 (80%), 24 (9%), and 24 (9%) of 268 patients analyzed. The only discriminant factor for patient or graft survival was hepatocellular carcinoma as primary indication. Independent risk factors for recurrent hepatitis included the absence of HBV coinfection before transplantation (relative risk [RR], 1.7; 95% confidence interval [CI], 1.2-2.6; P = 0.005), genotype 1b (RR, 2; 95% CI, 1.3-2.9; P = 0.01), and age > 49 years (RR, 1.4; 95% CI, 1.1-1.8; P = 0.01). CONCLUSIONS: The results of transplantation for HCV-related disease are compromised by a significant risk of cirrhosis, although 5-year survival is satisfactory. Genotype 1b, age, and absence of pretransplantation coinfection by HBV are risk factors for recurrent HCV.

Analysis of three decision-making methods: a breast cancer patient as a model.

PURPOSE: To compare three decision making techniques using a common clinical problem. METHODS: Two recently developed methods, the analytic hierarchy process (AHP) and the analytic network process (ANP), were compared with a Markov process in the evaluation of the optimal post-lumpectomy treatment strategy for an elderly woman with a mammographically detected, nonpalpable early-stage breast cancer. The following treatment alternatives were considered: observation, radiation, tamoxifen, combination radiation and tamoxifen, and simple mastectomy. All three decision methods incorporated patient preferences. RESULTS: The models agreed on the ranking of the preferred treatment, radiation and tamoxifen, but there were variations in the rankings of the other treatment choices. Individual differences between the three models were uncovered. The Markov process provided estimates of quality-adjusted life expectancy and distribution of health events. Both AHP and ANP required less development time than the Markov process. CONCLUSION: All three methods may be useful tools to the clinician in analyzing complex medical problems. The Markov is the most labor-intensive method but provides detailed results, whereas the AHP and the ANP give only rank orders of the alternatives. The most important considerations in choosing between these methods are time to project completion and the detail of information sought.

Biotechnologies and acute hepatic failure.

Orthotopic liver transplantation survival for patients with acute liver failure is poor (50%). Mortality on the waiting list is high due to the lack of donors. For these reasons, the possibility of sustaining hepatic function by extra-corporeal liver perfusion must be considered. In this experimental research, two groups of pigs have been submitted to total de-vascularisation of the liver causing acute hepatic failure. In the first group (4 pigs) no extra-corporeal assistance has been used after total de-vascularisation. All pigs died between 16 and 33 hours after the acute hepatic failure was induced. In the second group (8 pigs) after complete hepatic de-vascularisation an extra-corporeal hepatic support by continuous allo-perfusion of isolated liver was performed using the Abouna-Costa extra-corporeal circuit. All pigs were observed during the acute hepatic failure which lasted from 6.30 to 7.30 hours. The data that were more positively influenced by the extra-corporeal assistance were ammonia and lactates that improved after the application of hepatic assistance.