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.
This study’s aim was to assess the histological and metabolic effects of N-3 polyunsaturated fatty acids (PUFA) versus placebo while adjusting for the impact of age and weight change in NASH patients. (ClinicalTrials.gov: NCT00681408). Methods Forty-one subjects with non-cirrhotic NASH were enrolled, and 34 completed the study. 17 received N-3 fish oil 3000 mg/day and 17 received placebo daily for 1 year with typical counseling on caloric intake and physical activity for all subjects. Results N-3- and placebo-treated groups showed no significant difference for the primary endpoint of NAS reduction ≥ 2 points without fibrosis progression after adjustment for known covariates (N-3, 4/17 (23.5%); placebo, 3/17, (17.6%), p=0.99). Among subjects with increased or stable weight, N-3 subjects showed a larger decrease in liver fat content by MRI than placebo-treated subjects (p=0.014 for 2nd quartile, p=0.003 for 3rd quartile of weight change). N-3 treatment showed significant fat reduction on paired analysis of image-assisted fat morphometry regardless of weight loss or gain. Exercise capacity remained markedly reduced in all subjects. No independent effects on markers of hepatocyte injury or insulin sensitivity indices were observed. Conclusion N-3 PUFA at 3000 mg/day for one year did not lead to improvement in the primary outcome of histological activity in NASH patients (≥ 2 point NAS reduction). N-3 led to reduced liver fat by multiple measures. Other metabolic effects were not seen, although no detrimental effects were apparent. Whether longer duration, higher dose, or different composition of N-3 therapy would lead to additional benefit is uncertain.
The Model for End-Stage Liver Disease (MELD) allocation system for liver transplantation provides "exceptions" for diseases such as hepatocellular carcinoma (HCC). It was the aim of this study to assess equipoise between exception candidates and nonexception candidates on the waiting list and to assess if the exception system contributes to steadily increasing regional MELD at transplant. In all, 78,595 adult liver transplant candidates between January 2005 and December 2012 were analyzed. Yearly trends in waiting list characteristics and transplantation rates were analyzed for statistical association with MELD exceptions. Regional variations in these associations and the effect of exceptions on regional MELD scores at transplant were also analyzed. 27.29% of the waiting list was occupied by candidates with exceptions. Candidates with exceptions fared much better on the waiting list compared to those without exceptions in mean days waiting (HCC 237 versus non-HCC 426), transplantation rates (HCC 79.05% versus non-HCC 40.60%), and waiting list death rates (HCC 4.49% versus non-HCC 24.63%). Strong regional variation in exception use occurred but exceptions were highly correlated with waiting list death rates, transplantation rates, and MELD score at removal in all regions. In a multivariate model predicting MELD score at transplant within regions, the percentage of HCC MELD exceptions was the strongest independent predictor of regional MELD score at transplant. Conclusion: Liver transplant candidates with MELD exceptions have superior outcomes compared to nonexception candidates and the current MELD exception system is largely responsible for steadily increasing MELD scores at transplant independent of geography. (HEPATOLOGY 2015;61:285-291) See Editorial on Page 28 T he advent of the Model for End-Stage Liver Disease (MELD) allocation system 1 for deceased donor liver transplant recipients in February 2002 profoundly changed the organ allocation system in the U.S. It was understood at the time, however, that MELD would not reflect mortality risk in certain diseases. These diseases were generally not associated with progressively worsened liver function but had a high risk of death or eventual mortality without transplant. Of these "exceptional" diseases, the most prevalent was hepatocellular carcinoma (HCC).Built into the MELD allocation system was an "exception" to the MELD score for HCC and this exception was designed to give extra MELD points to those transplant candidates with early HCC in order to allow them to compete fairly for deceased donor liver grafts despite having relatively preserved liver function in many cases. Fundamentally, the exception system was designed to allow equal access to liver transplantation between candidates with progressive liver dysfunction and those with morbid conditions who's risk of death was not reflected by the calculated MELD score. After 3 years of adjustments in the number of MELD points assigned to candidates with Abbreviations: HCC, hepatocellular carcinoma; MELD, M...
Portal vein thrombosis (PVT) is a common complication of cirrhosis sometimes implicated in hepatic decompensation. There are no consistent epidemiologic data to suggest an increased risk of thrombotic complications in nonalcoholic steatohepatitis (NASH); however, research suggests an increased risk of thrombosis. Our aim was to examine the independent association between NASH cirrhosis and PVT in patients who underwent liver transplantation (LT) in a cross-sectional study. Data on all LTs occurring in the United States between January 1, 2003 and December 31, 2012 were obtained from the United Network for Organ Sharing. Multivariable models were constructed to assess the statistical associations and risk factors for the development of PVT. A total of 33,368 patients underwent transplantation. Of these, 2096 (6.3%) had PVT. Of the patients with PVT, 12.0% had NASH. When we compared these patients to a composite of all other causes of cirrhosis, an increased prevalence of PVT was again found, with 10.1% having PVT at the time of transplantation versus 6.0% without NASH (P < 0.001). The strongest risk factor independently associated with a diagnosis of PVT in a multivariable analysis was NASH cirrhosis (odds ratio, 1.55; 95% confidence interval, 1.33-1.81; P < 0.001). NASH cirrhosis appears to predispose a patient to PVT independently of other risk factors. These epidemiological findings provide support for the idea that NASH is a prothrombotic state, and they should lead to more research in treatment and prevention in this population. Liver
The use of thromboprophylaxis in hospitalized cirrhosis patients is not associated with high rates of gastrointestinal bleeding or death.
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