Direct Oral Anticoagulants in Cirrhosis Patients Pose Similar Risks of Bleeding When Compared to Traditional Anticoagulation.

BACKGROUND AND AIMS: Direct oral anticoagulants (DOAC) are important new anticoagulant therapies that are not well studied in patients with chronic liver disease. The aim of this study was to compare rates of bleeding in cirrhosis patients treated with DOAC (factor Xa inhibitors: rivaroxaban and apixaban) to those in cirrhosis patients treated with traditional anticoagulation (warfarin and low molecular weight heparin). METHODS: We identified a total of 39 patients with cirrhosis who received anticoagulation therapy over a 3-year period (20 DOAC and 19 traditional anticoagulation) from a research database. Medical records were reviewed to obtain clinical data to compare between the groups. RESULTS: Clinical characteristics between the two groups were similar. There were three documented bleeding events in the traditional anticoagulation group and four bleeding events in the DOAC group (p = 0.9). There were two major bleeding events in the traditional anticoagulation group and one major bleeding event in the DOAC group. There were no documented reports of drug-induced liver injury during this study period. Among all patients, no significant predictors of bleeding were identified using univariate regression and Cox proportional hazard modeling. CONCLUSIONS: This is the first clinical study evaluating the use of DOAC in patients with cirrhosis. DOAC display similar safety characteristics when compared to traditional anticoagulation in patients with cirrhosis and are potentially attractive agents for anticoagulation therapy. Larger studies are now needed to better understand the safety and efficacy of these agents in cirrhosis.

Regional variability in symptom-based MELD exceptions: a response to organ shortage?

MELD (model for end-stage liver disease) exception awards affect the liver allocation process. Award rates of specific nonhepatocellular carcinoma exceptions, termed symptom-based exceptions (SBE), differ across UNOS regions. We aimed to characterize the regional variability in SBE awards and examine predictive factors for receiving a SBE in the MELD era. The OPTN liver transplant and waiting list dataset was analyzed for waiting list registrants during the MELD allocation on February 27, 2002, until November 22, 2006. Competing risks proportional hazards regression analysis was used to examine predictors for receiving a SBE in 39 169 registrants. The hazard ratios for receiving a SBE differed significantly across regions when adjusted for multiple variables including age, gender, ethnicity, physiologic MELD score, blood group, functional status, etiology of liver disease, insurer and education level. Utilization of SBE is highly significantly variable across UNOS regions, and does not correlate with organ availability as estimated by the regional mean physiologic MELD score at transplantation. Patients with Medicaid as their primary payer have a lower likelihood of receiving a SBE award, while patients with cryptogenic/NASH cirrhosis or cholestatic liver disease have a higher likelihood of receiving a SBE. Reasons for these regional and demographic disparities deserve further investigation.

Partially covered self-expandable metallic stents for benign biliary strictures due to chronic pancreatitis.

BACKGROUND AND STUDY AIMS: Benign biliary strictures (BBS) may occur in patients with chronic pancreatitis and may lead to secondary biliary cirrhosis or recurrent cholangitis. Although surgical diversion may provide definitive therapy, it can be associated with significant morbidity. Endoscopic therapy with plastic stents has been used as an alternative to surgery but has resulted in unsatisfactory long-term outcomes. We evaluated the temporary placement of partially covered self-expandable metallic stents (PCMS) in patients with BBS due to chronic pancreatitis. PATIENTS AND METHODS: A total of 20 patients with BBS due to chronic pancreatitis underwent temporary placement of PCMS over a 6-year period. The primary outcome of interest was the proportion of patients with stricture resolution persisting 6 months after stent removal. Secondary outcomes included the stent failure rate, number of endoscopic sessions required to achieve biliary drainage, total duration of stenting, and complication rate. RESULTS: Adequate biliary drainage was achieved in 19 patients with PCMS (95%). Eighteen of the 20 patients (90%) had persistent stricture resolution 6 months after PCMS removal. In two of the 20 patients (10%), PCMS stenting failed and these patients underwent alternative therapies. Complications occurred in four patients (20%). Median duration of PCMS placement was 5 months, requiring a median of two endoscopic procedures. CONCLUSION: In this series of patients with BBS due to chronic pancreatitis, temporary PCMS placement achieved persistent stricture resolution in the majority of patients with acceptable complication rates. Comparative trials evaluating temporary PCMS placement and plastic stenting in patients with BBS due to chronic pancreatitis are needed.

Hypercoagulation and thrombophilia in liver disease.

A complex balance exists between endogenous procoagulants and the anticoagulant system in liver disease patients. Hypercoagulable events occur in cirrhosis patients despite the well-known bleeding diathesis of liver disease. These events may be clinically evident, such as in portal vein thrombosis or pulmonary embolism, but these conditions may also be a silent contributor to certain disease states, such as portopulmonary hypertension or parenchymal extinction with liver atrophy as well as thrombosis of extracorporeal circuits in dialysis or liver assist devices. Moreover, liver disease-related hypercoagulability may contribute to vascular disease in the increasingly common condition of non-alcoholic fatty liver disease. Despite the incidence of these problems, there are few widely accessible and practical laboratory tests to evaluate the risk of a hypercoagulable event in cirrhosis patients. Furthermore, there is little research on the use of commonly accepted anticoagulants in patients with liver disease. This article is a result of an international symposium on coagulation disorders in liver disease and addresses several areas of specific interest in hypercoagulation in liver disease. Critical areas lacking clinical information are highlighted and future areas of research interest are defined with an aim to foster clinical research in this field.

Donor factors predicting recipient survival after liver retransplantation: the retransplant donor risk index.

The use of extended criteria liver donors (ECD) is controversial, especially in the setting of retransplantation. The aims of this study are to investigate the effects of ECD grafts on retransplantation and to develop a predictive mortality index in liver retransplantation based on the previously established donor risk index. The United Network for Organ Sharing (UNOS) liver transplant dataset was analyzed for all adult, non-status 1, liver retransplantations occurring in the United States since February 2002. All donors were categorized for multiple characteristics of ECD, and using multivariate survival models a retransplant donor risk index (ReTxDRI) was developed. A total of 1327 retransplants were analyzed. There were 611 (46%) recipients who received livers with at least one ECD criterion. The use of ECD grafts in recipients with HCV did not incur worse survival than the non-ECD grafts. The addition of the cause of recipient graft failure to the donor risk index formed the ReTxDRI. After adjusting for multiple recipient factors, the ReTxDRI was predictive of overall recipient survival and was a strongly independent predictor of death after retransplantation (HR 2.49, 95% CI 1.89-3.27, p < 0.0001). The use of the ReTxDRI can improve recipient and donor matching and help to optimize posttransplant survival in liver retransplantation.

Enbucrilate for gastric varices: extended experience in 92 patients.

AIM: We assessed N-2-butyl-cyanoacrylate (enbucrilate) in 92 patients with gastric variceal bleeding under an FDA-approved investigation. These results extend our prior report of the first 44 patients. METHOD: Injection was performed with enbucrilate and ethiodol (1:1). Eighty patients had portal hypertension and 12 had splenic vein thrombosis. RESULTS: In the portal hypertensive group, re-bleeding from gastric varices was seen in 4 of 80 (5%) from 0 to 72 h, 5 of 76 (6.5%) from > 72 h to 3 months and 9 of 51 (17%) from > 3 months to 1 year. Re-bleeding and survival were significantly related to the Child-Pugh class. In the splenic vein thrombosis group (n = 12), there was early rebleeding in 2 (17%) patients from 0 to 72 h, 1 (8%) from > 72 h to 3 months and none in the chronic phase (> 3 months to 1 year) although 1-year survival in this group was only 6 (50%) due to the underlying malignancy in most. Serious embolization was suspected in 2 patients (2%). CONCLUSION: Enbucrilate offers an important intervention in gastric variceal bleeding which should be further studied in the US. A randomized trial is warranted to compare this intervention to radiological therapy.

Covered self-expandable metal stents in pancreatic malignancy regardless of resectability: a new concept validated by a decision analysis.

BACKGROUND AND STUDY AIMS: The current treatment model for the management of malignant biliary obstruction is to place a plastic stent for unstaged pancreatic cancer. In patients with unresectable disease but a life expectancy of more than 6 months, self-expandable metal stents (SEMS) are favored because of their more prolonged patency. We analyzed the efficacy and cost-effectiveness of covered SEMS (CSEMS) in patients with pancreatic cancer and distal biliary obstruction without regard to surgical resectability. PATIENTS AND METHODS: Between March 2001 and March 2005, 101 consecutive patients with obstructive jaundice secondary to pancreatic cancer underwent placement of a CSEMS. Patients with resectable tumor were offered pancreaticoduodenectomy. A model was developed to compare the costs of CSEMS and polyethylene and DoubleLayer stents. RESULTS: A total of 21 patients underwent staging laparoscopy, of whom 16 had a resection (76%). The 85 patients who did not have a resection had a mean survival of 5.9 months (range 1-25 months) and a mean CSEMS patency duration of 5.5 months (range 1-16 months). Life-table analysis demonstrated CSEMS patency rates of 97% at 3 months, 85% at 6 months, and 68% at 12 months. In a cost model that accounted for polyethylene and DoubleLayer stent malfunction and surgical resections, initial CSEMS placement (3177 euros per patient) was a less costly intervention than either DoubleLayer stent placement (3224 euros per patient) or polyethylene stent placement with revision (3570 euros per patient). CONCLUSIONS: Covered SEMS are an effective treatment for distal biliary obstructions caused by pancreatic carcinoma. Their prolonged patency and removability makes them an attractive option for biliary decompression, regardless of resectability. The strategy of initial covered SEMS placement might be the most cost-effective strategy in these patients.

Survival after adult liver transplantation does not correlate with transplant center case volume in the MELD era.

It has been demonstrated that low-volume orthotopic liver transplant centers have poorer outcomes compared to high-volume centers. In light of the recent significant changes in liver transplantation, we performed an analysis of transplant center procedure volume and mortality with data from the Model for End-stage Liver Disease (MELD) era. We analyzed 9909 adult liver transplants performed in the United States since the beginning of the MELD allocation system. Transplant centers were categorized by volume of transplants performed per year. Multivariate survival models were constructed with raw survival as the primary endpoint for both high- and low-volume centers. Thirty percent of centers were categorized as low volume (< or =20 liver transplants per year) and 8.2% of all transplants were performed at low-volume centers. The unadjusted raw mortality rate at 1-year post-transplant at high-volume centers (9.5%, 95% CI 9.4-9.5) was significantly lower than the rate at low-volume centers (10.9%, 95% CI 10.4-11.4), p < 0.001. However, after adjusting for disease severity and multiple donor and recipient factors, transplant center volume was no longer a significant predictor of post-transplant survival (HR 0.99, 95% CI 0.99-1.00, p = 0.22). We conclude that transplant center case volume is no longer a significant predictor of post-transplant survival in the MELD era and factors which are currently unaccounted for in present survival models should be investigated.