Faculty Bibliography

BACKGROUND:Restrictive staging criteria for liver transplant (LT) patients with HCC in the U.S. have resulted in favorable long-term recurrence-free survival, but these criteria exclude a subgroup of patients who, despite tumor size beyond T2 stage, demonstrate an acceptable outcome. The aim of this study was to assess the waiting list and post-transplant mortality of patients with HCC tumors greater than Milan T2 stage. METHODS:The U.S. OPTN standard transplant dataset was analyzed for patients with a diagnosis of HCC who were listed for liver transplantation between February 2002 and 2008. Those patients with Milan T3 stage tumors were compared to patients with T1 and T2 lesions. Multivariate survival models were developed to investigate independent predictors of death or tumor recurrence post-transplant. RESULTS:7,391 patients with HCC were identified. 351 (4.75%) had T3 lesions. Compared to non-T3 patients, total tumor burden was greater and total alpha-fetoprotein (AFP) was higher in the T3 patients. T3 patients also were more likely to receive pretransplant locoregional therapy. There were no significant differences between T3 patients and non-T3 patients in demographic variables or physiologic MELD score at the time of transplant, waiting time, or donor risk index. Waiting list mortality was increased for T3 patients compared to non-T3 and tumor progression while waiting was higher. Independent predictors of waiting list mortality included physiologic MELD score at the time of listing, total tumor burden, and serum AFP. There was significant regional variation in the utilization of exceptions for T3 patients and UNOS regions 4, 9, and 10 performed a higher percentage of their transplants in T3 patients compared to other regions. There was no difference in post transplant survival between T3 and non-T3 patients. Independent predictors of post-transplant mortality included physiologic MELD score at the time of transplant, recipient age, and donor risk index. In patients with T3 tumors, total tumor burden was not an independent predictor of post transplant survival. CONCLUSIONS:Patients who are listed for liver transplantation with Milan stage T3 HCC have higher waiting list mortality but have similar post-transplant survival compared to patients with T1 and T2 HCC.

BACKGROUND:Percutaneous endoscopic gastrostomy (PEG) tube placement can improve the nutritional status and the ability of a patient with cirrhosis to recover from surgery such as orthotopic liver transplantation. However, cirrhosis has been considered a significant contraindication to PEG tube placement. OBJECTIVE:Our aim in this study was to describe the mortality and complications in a series of cirrhotic patients who underwent PEG at our institution. DESIGN/METHODS:Retrospective, single-institution case series. PATIENTS/METHODS:This study involved 26 consecutive patients with cirrhosis who underwent PEG between 1995 and 2005. INTERVENTION/METHODS:PEG tube placement. MAIN OUTCOME MEASUREMENTS AND RESULTS/RESULTS:The 30-day mortality of the series of patients was 10 of 26 (38.5%), whereas the 90-day mortality was 11 of 26 (42.3%). Nine of the 10 patients who died in the first 30 days had ascites at the time of PEG tube placement. Two patients died as a direct consequence of complications from the PEG procedure, whereas the other deaths were related to progression of liver disease or factors not directly related to the PEG. LIMITATIONS/CONCLUSIONS:The patients in this case series had varying levels of illness and reasons for PEG tube placement such that a generalization of outcomes may not be possible. CONCLUSIONS:The overall mortality of patients with cirrhosis who underwent PEG is high. Although there is an increased risk, PEG tube placement in cirrhotic patients without ascites may be less risky. The benefits of PEG tube placement in patients with cirrhosis should be weighed heavily against the risks.

Patients with chronic or acute liver failure frequently show profound abnormalities in their hemostatic system. Whereas routine laboratory tests of hemostasis suggest these hemostatic alterations result in a bleeding diathesis, accumulating evidence from both clinical and laboratory studies suggest that the situation is more complex. The average patient with liver failure may be in hemostatic balance despite prolonged routine coagulation tests, since both pro- and antihemostatic factors are affected, the latter of which are not well reflected in routine coagulation testing. However, this balance may easily tip towards a hypo- or hypercoagulable situation. Indeed, patients with liver disease may encounter both hemostasis-related bleeding episodes as well as thrombotic events. During the 3rd International Symposium on Coagulopathy and Liver disease, held in Groningen, The Netherlands (18-19 September 2009), a multidisciplinary panel of experts critically reviewed the current data concerning pathophysiology and clinical consequences of hemostatic disorders in patients with liver disease. Highlights of this symposium are summarized in this review.

Organ donors are screened for the hepatitis C antibody (anti-HCV) and those with positive tests can be used under extended criteria donation. However, there is still a question of long-term organ viability. The aim of this study was to assess the long-term outcomes of anti-HCV positive (HCV+) liver grafts. The US Organ Procurement and Transplantation Network Scientific Registry was reviewed for the period from April 1994 to February 6, 2008 and 56,275 liver transplantations were analyzed. In total, there were 19,496 HCV+ recipients and 934 HCV+ donors. Patient and graft survival were assessed accounting for both donor and recipient anti-HCV status. Multivariable proportional hazards survival models were developed to adjust for factors known to affect post-transplant survival. With anti-HCV negative (HCV-) recipient/HCV- donor as the reference, the adjusted hazard ratio for death was similar for HCV+ recipient/HCV- donor compared with HCV+ recipient/HCV+ donor (1.176 vs. 1.165, P = 0.91). Our results suggest that HCV+ liver donors do not subject the HCV+ recipient to an increased risk for death over the HCV- donor, keeping in mind that careful donor and recipient selection is critical for the proper use of these extended criteria donors.

BACKGROUND AND AIMS/OBJECTIVE:Partially covered metal stents have been extensively used for palliation of obstructive jaundice in malignant distal biliary strictures and can be removed in cases of malfunction or need for tissue diagnosis. We investigated independent predictors of mortality in patients undergoing partially covered metal stents revision (i.e., removal and replacement). METHODS:Patients with a distal malignant biliary obstruction palliated with a partially covered metal stent were followed-up prospectively over 5 years until malfunction or death. All patients who required removal of their partially covered metal stents were captured in a specific database. Multivariate analysis was performed on non-surgical patients to assess for independent predictors of death using known risk factors including type of malignancy (adenocarcinoma versus all others), age greater than 55, gender, and exposure to adjuvant chemotherapy and/or radiotherapy. RESULTS:Forty-two patients (28 men, mean age of 62±12 years) underwent partially covered metal stents removal. Of these, biliary drainage was achieved in 38 patients by placement of a new partially covered metal stent (n=32) or plastic stent (n=6). The remaining 4 patients did not undergo stent replacement because of refusal (2), resolution of obstruction (1) and unrelated death (1). Long-term follow-up post removal in patients who were not surgical candidates (n=31) was 35 weeks (95% CI 28-40), with a survival rate of 29% at 10 months. Logistic regression analysis in the 31 patients with unresectable disease showed that a histologic diagnosis of adenocarcinoma was associated with increased mortality post partially covered metal stents revision. CONCLUSIONS:Partially covered metal stents revision should be undertaken especially when dealing with a non-adenocarcinoma type cancer.

The Model for End-Stage Liver Disease system has given priority on the liver transplant waiting list to candidates with renal failure. This study determined the predictors of spontaneous recovery of renal function after transplantation in 1041 liver transplant recipients on renal replacement therapy (RRT) at the time of transplant (from February 2002 to January 2007). Data from these patients were obtained from the US Organ Procurement and Transplantation Network and US Renal Data System databases. Univariate and multivariate survival models were constructed along with multivariate logistic regression models to find independent predictors of spontaneous renal recovery. Seven hundred seven recipients (67.9%) had spontaneous recovery of renal function after liver transplantation. Those recovering spontaneously had a significantly shorter course of RRT in the pretransplant time period (15.6 versus 36.6 days, P < 0.001). Recovery of renal function was observed in 70.8% and 11.5% of recipients on RRT for less than 30 days and more than 90 days, respectively. Other statistically significant pretransplant variables independently associated with recovery of renal function included recipient age, recipient pretransplant diabetes, and donor age. In conclusion, the duration of pretransplant RRT is highly predictive of spontaneous renal recovery post-transplant. Liver transplant candidates requiring less than 30 days of pretransplant RRT are likely to spontaneously recover renal function after liver transplantation, whereas those on RRT for more than 90 days are not.