Assessment of ISGLS definition of posthepatectomy liver failure and its effect on outcome in patients with hepatocellular carcinoma.

BACKGROUND: Posthepatectomy liver failure (PHLF) is a major complication after hepatectomy. As there was no standardized definition, the International Study Group of Liver Surgery (ISGLS) defined PHLF as increased international normalized ratio and hyperbilirubinemia on or after postoperative day 5 in 2010. We evaluated the impact of the ISGLS definition of PHLF on hepatocellular carcinoma (HCC) patients. METHODS: We retrospectively analyzed 210 consecutive HCC patients who underwent curative hepatectomy at our facility from 2005 to 2010. The median follow-up period after hepatectomy was 35.2 months. RESULTS: Thirty-nine (18.6%) patients fulfilled the ISGLS definition of PHLF. Overall survival (OS) rates at 1, 3, and 5 years in patients with/without PHLF were 69.1/93.5, 45.1/72.5, and 45.1/57.8%, respectively (P = 0.002). Recurrence-free survival (RFS) rates at 1, 3, and 5 years in patients with/without PHLF were 40.9/65.9, 15.7/38.3, and 15.7/20.3%, respectively (P = 0.003). Multivariate analysis revealed that PHLF was significantly associated with both OS (P = 0.047) and RFS (P = 0.019). Extent of resection (P < 0.001), intraoperative blood loss (P = 0.002), and fibrosis stage (P = 0.040) were identified as independent risk factors for developing PHLF. CONCLUSION: The ISGLS definition of PHLF was associated with OS and RFS in HCC patients, and long-term survival will be improved by reducing the incidence of PHLF.

Risk factors for liver transplant waitlist dropout in patients with hepatocellular carcinoma.

Loco-regional therapy has been developed to reduce waitlist dropout in patients with hepatocellular carcinoma (HCC) awaiting liver transplantation. We evaluated the probability of transplantation and waitlist dropout, and analyzed risk factors for waitlist dropout, in 76 patients with HCC from September 2004 to August 2006. Seventy-three (96.1%) patients received one or more preoperative loco-regional treatments and 55 (72.3%) received an orthotopic liver transplantation with a median wait time of seven months (range, 2-26 months). There were 11 dropouts (14.5%) associated with tumor progression or hepatic decompensation (median waiting time; 5.4 months and range, 0.4-13 months). Cumulative probabilities of transplantation at three, six, nine, 12, 15, and 18 months were 5.4%, 35.4%, 67.5%, 78.8%, 80.7%, and 80.7%, respectively and those of waitlist dropout at three, six, nine, 12, 15, and 18 months were 3.9%, 8.7%, 12.8%, 22.9%, 29.3%, and 29.3%, respectively. A laboratory model for end-stage liver disease (MELD) score >15 or multiple tumors at the time of UNOS listing were significant risk factors for waitlist dropout (p = 0.006 and 0.026, respectively). Patients with HCC being managed with loco-regional therapy who have a laboratory MELD score >15 or multiple tumors should be considered for earlier access to liver transplantation to prevent waitlist dropout.

Should liver transplantation in patients with model for end-stage liver disease scores

Studies have shown that liver transplantation offers no survival benefits to patients with Model for End-Stage Liver Disease (MELD) scores or=18 years) listed for or undergoing primary liver transplantation in the United States for chronic liver disease from 1/1/2003 through 12/31/2007 with follow-up until 2/1/2008. The "Rule 14" policy gave a 3% improvement in overall patient survival over the present system at 1, 2, 3, and 4 years and predicted a 13% decrease in overall waitlist time for patients with MELD scores of 15 to 40. Patients with the greatest benefit from a "Rule 14" policy were those with MELD scores of 6 to 10, for whom a 17% survival advantage was predicted from waiting on the list versus undergoing transplantation. Our analysis supports changing the national liver allocation policy to not allow liver transplantation for patients with MELD

Model for End-Stage Liver Disease (MELD) score and organ allocation from cadaveric donors for 198 liver transplantation procedures performed in a single center.

Since February 2002, the United Network for Organ Sharing (UNOS) proposed to adopt a modified version of the Model for End-Stage Liver Disease (MELD) to assign priority on the waiting list for orthotopic liver transplantation (OLT). In this study, we evaluated the impact of MELD score on liver allocation in a single center series of 198 liver recipients (mean age of patients, 52.21+/-8.92 years), considering the relationship between clinical urgency derived from MELD score (overall MELD, 18.7+/-6.83; MELD <15 in 69 patients, MELD >or=15 in 129 patients) and geographical distribution of cadaveric donors (inside/outside Liguria Region, 125/73). The waiting time for OLT was 230+/-248 days, whereas the 3-month and 1-year patient survivals were 87.37% and 79.79%, respectively. No difference was observed for MELD score retrospectively calculated for patients who underwent OLT before February 2002 (n=71) compared with MELD score calculated for patients who received a liver thereafter (18.26+/-6.68 vs 18.94+/-6.92; P= .504). No significant difference was found in waiting time before and after adoption of MELD score (213+/-183 vs 238+/-278 days; P= .500), or by stratifying patients for MELD <15/>or=15 (225+/-234 vs 232+/-256 days; P= .851). Using the geographical distribution of donors as a grouping variable (outside vs inside Liguria Region), no significance occurred for MELD score (19.68+/-7.42 vs 18.17+/-6.42; P= .135) or waiting time (211+/-226 vs 242+/-261 days; P= .394). In our series, more OLTs were performed among sicker patients and no differences were found in the management of livers procured from cadaveric donors outside or inside Liguria Region. However, further efforts are needed to reduce the waiting time among patients with higher MELD scores.

Overview of the MELD score and the UNOS adult liver allocation system.

On February 27, 2002, the United Network for Organ Sharing (UNOS) introduced a new allocation policy for cadaveric liver transplants, based on the Model for End-Stage Liver Disease (MELD) score. This new policy stratifies the patients based on their risk of death while on the waiting list. We analyzed the background and main features of this new allocation policy to evaluate the effects on waiting list dynamics as well as the accuracy of MELD as a predictor of pretransplantation mortality and posttransplantation outcome. MELD has proved to be accurate as a predictor of waiting list mortality, but seems to be less accurate to predict posttransplantation outcome. Immediate effects of the new policy were a reduction in the waiting list, while organs were primarily directed to sicker patients with reduced waiting times. There was a statistically but not significantly reduced number of patients removed from the list due to death or severity of sickness. The balance between medical urgency and transplant benefit is still to be defined as is the relationship between pretransplantation criteria and posttransplantation outcomes, and the way this relationship should be included in the allocation policy.

A new priority policy for patients with hepatocellular carcinoma awaiting liver transplantation within the model for end-stage liver disease system.

The best prioritization of patients with hepatocellular carcinoma (HCC) waiting for liver transplantation under the model for end-stage liver disease (MELD) allocation system is still being debated. We analyzed the impact of a MELD adjustment for HCC, which consisted of the addition of an extra score (based on the HCC stage and waiting time) to the native MELD score. The outcome was analyzed for 301 patients with chronic liver disease listed for liver transplantation between March 1, 2001 and February 28, 2003 [United Network for Organ Sharing (UNOS)-Child-Turcotte-Pugh (CTP) era, 163 patients, 28.8% with HCC] and between March 1, 2003 and February 28, 2004 (HCC-MELD era, 138 patients, 29.7% with HCC). In the HCC-MELD era, the cumulative dropout risk at 6 months was 17.6% for patients with HCC versus 22.3% for those patients without HCC (P = NS), similar to that in the UNOS-CTP era. The cumulative probability of transplantation at 6 months was 70.3% versus 39.0% (P = 0.005), being higher than that in the UNOS-CTP era for patients with HCC (P = 0.02). At the end of the HCC-MELD era, 12 patients with HCC (29.3%) versus 57 without HCC (58.8%) were still on the list (P = 0.001). Both native and adjusted MELD scores were higher (P < 0.05) and progressed more in patients with HCC who dropped out than in those who underwent transplantation or remained on the list (the initial-final native MELD scores were 17.3-23.1, 15.5-15.6, and 12.8-14.1, respectively). The patients without HCC remaining on the list showed stable MELD scores (initial-final: 15.1-15.4). In conclusion, the present data support the strategy of including the native MELD scores in the allocation system for HCC. This model allows the timely transplantation of patients with HCC without severely affecting the outcome of patients without HCC.

Use of a pediatric end-stage liver disease score for deceased donor allocation: the United States experience.

The Pediatric end-stage liver disease (PELD) score was developed as a measure of the severity of chronic liver disease that would predict mortality or children awaiting liver transplant. From multivariate analyses a model was derived that included five objective factors which together comprise the PELD score. The factors are growth failure, age less than 1 year, international normalized ratio (INR), serum albumin and total bilirubin.

Characteristics of waitlisted patients for liver transplantation at a liver transplantation unit in the city of Ribeirão Preto, São Paulo, Brazil, especially considering Child and Model for End Stage Liver Disease (MELD) scores.

Liver transplantation represents the most effective therapy for patients suffering from chronic end-stage liver disease. Until recently, in Brazil liver allocation was based on the Child-Turcotte-Pugh score and the waiting list followed a chronological criterion. The aim of this study was to show the clinical and laboratory patterns of our patients awaiting a liver transplantation. Seventy-nine medical records were reviewed in January 2005 to classify patients according to their age, sex, cause of cirrhosis, and Child and Model for End Stage Liver Disease (MELD) scores. The mean age of patients was 47 years; 70% were men. The main diagnosis was liver cirrhosis (97%): 27% alcoholic, 26% viral hepatitis, 20% alcoholic plus viral hepatitis, 13% cryptogenic, and 11% other causes. Sixty-three patients (80%) were Child B or C. The average MELD, scores for Child A, B, and C were 10 +/- 5, 13 +/- 3.4, and 21 +/- 4.3, respectively. Nine deaths (11%) on the waiting list occurred in 2005. Among these, 1 patient was Child B with MELD 10, while the others were Child C, with mean MELD scores of 21 +/- 3.8. Twelve patients (15%) received cadaveric orthotopic liver transplantation. Thus, in this small series, the higher MELD scores corresponded to Child C class and mortality on the waiting list.

Waiting list removal rates among patients with chronic and malignant liver diseases.

Equitable liver allocation should ensure that nonelective removal rates are fairly distributed among waiting candidates. We compared removal rates for adults entered with nonmalignant (NM) (N = 9379) and hepatocellular cancer (HCC) (N = 2052) diagnoses on the Organ Procurement and Transplantation Network (OPTN) list between April 30, 2003, and December 31, 2004. Unadjusted removal rates for NM vs. HCC diagnoses were 9.4% vs. 8.7%, 13.5% vs. 16.9% and 19.1% vs. 31.8% at 90, 180 and 365 days, respectively after listing. For NM candidates, model for end-stage liver disease (MELD) score (RR = 1.16), age (RR = 1.03) and metabolic disease diagnoses (RR = 1.66) had higher risks of removal; and PSC (RR = 0.62) and alcoholic cirrhosis (RR = 0.82) had lower risks of removal. For HCC candidates, MELD score at listing (RR = 1.09), AFP (RR = 1.02), maximum tumor size (RR = 1.16) and age at listing (RR = 1.02) had increased risks of removal. The equation 1 - 0.920 exp[0.09369 (MELD at listing - 12.48) + 0.00193 (AFP - 97.4) + 0.1505 (maximum tumor size - 2.59) defined the probability of dropout for HCC candidates within 90 days of listing. We conclude that factors associated with the risk of removal for HCC are different from NM candidates, although MELD score at listing remains the most predictive for both groups. Liver transplant candidates with HCC may be prioritized using a risk score analogous to the MELD score.

Liver transplantation in the era of model for end-stage liver disease.

Liver transplantation is challenged by organ shortage and prolonged waiting list time. The goal of the ideal organ allocation system is to transplant individuals least likely to survive without a liver transplantation, and maintain appropriate rates of postoperative survival. Currently, liver allocation in the United States is based on the model for end-stage liver disease (MELD). Studies have shown MELD to be objective and accurate in predicting short-term survival in patients with cirrhosis.

Anthropometric assessment of the nutritional status of patients with liver cirrhosis in an Italian population.

A poor nutritional status has repeatedly been described in advanced liver cirrhosis, but the exact prevalence of the defect and its relation to the aetiology and severity of liver disease in the Italian population are only partly known. Anthropometric measurements were carried out in 200 patients with cirrhosis (135 M, 65 F). Liver disease was related to alcohol abuse in 77 cases, but most patients had stopped alcohol for at least 6 months before study. In comparison to a normal elderly Italian and to an age-matched North-American population, 5 to 45% of male patients with cirrhosis and 10 to 30% of females had signs of malnutrition, the proportion being variable according to the test used. Male patients showed a remarkable reduction in muscle mass (30-45% of patients, mainly in the presence of moderate-to-severe or severe liver failure), whereas female patients showed a more remarkable reduction of fat stores (15-30% of cases), with advancing liver failure, and a less severe reduction in muscle mass. No direct effect of alcohol was demonstrated in this selected population.