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Gastroenterology 11/2012; · 11.68 Impact Factor
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ABSTRACT: Patients with acute liver failure (ALF) have high mortality and frequently require liver transplantation (LT); few reliable prognostic markers are available. Levels of M30, a cleavage product of cytokeratin-18 caspase, are significantly increased in serum samples from patients with ALF who die or undergo LT. We developed a prognostic index for ALF based on level of M30 and commonly measured clinical variables (called the Acute Liver Failure Study Group [ALFSG] index) and compared its accuracy with that of the King's College criteria (KCC) and Model for End Stage Liver Disease (MELD). We also validated our model in an independent group of patients with ALF.
Serum levels of M30 and M65 antigen (the total cytokeratin-18 fragment, a marker of apoptosis and necrosis) were measured on 3 of the first 4 days following admission of 250 patients with ALF. Logistic regression was used to determine whether the following factors, measured on day 1, were associated with LT or death: age, etiology; coma grade; international normalized ratio (INR); serum pH; body mass index; levels of creatinine, bilirubin, phosphorus, arterial ammonia, and lactate; and log(10) M30 and log(10) M65. The area under the receiver operating characteristic (AUROC) was calculated for the ALFSG and other indices.
Coma grade, INR, levels of bilirubin and phosphorus, and log(10) M30 value at study entry most accurately identified patients who would require LT or die. The ALFSG index identified these patients with 85.6% sensitivity and 64.7% specificity. Based on comparison of AUROC values, the ALFSG Index (AUROC, 0.822) better identified patients most likely to require LT or die than the KCC (AUROC, 0.654) or MELD (AUROC, 0.704) (P = .0002 and P = .0010, respectively). We validated these findings in a separate group of 250 patients with ALF.
The ALFSG index, a combination of clinical markers and measurements of the apoptosis biomarker M30, better predicts outcomes of patients with ALF than the KCC or MELD; ClinicalTrials.gov, number NCT00518440.
Gastroenterology 08/2012; 143(5):1237-43. · 11.68 Impact Factor
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ABSTRACT: Depression is a common problem among patients awaiting organ transplantation, but little is known about the impact of depression and its treatment on the outcomes of liver transplantation. In this retrospective cohort analysis, we studied all patients over 18 years of age who underwent liver transplantation during a 5-year period (2004-2008) at a single center. Among 179 recipients, 65 patients had depression, as defined by a health care provider assessment, before transplantation. Depression was defined as past or active depression or an adjustment disorder. The associations between pretransplant depression and various outcomes (time to death, graft failure, first acute cellular rejection episode, first infection, and first rehospitalization) were assessed. In the entire sample, more patients with depression required posttransplant psychiatric care (37% versus 18%); the adjusted hazard ratio was 2.28 (1.27-4.11). The rates of other outcomes, including hospital readmission, acute cellular rejection, graft failure, mortality, and infection, were similar for patients with depression and patients without depression. Among those with depression, patients on antidepressants at the time of transplantation had acute cellular rejection less frequently than those not taking antidepressants (13% versus 40%); the adjusted hazard ratio was 0.14 (0.03-0.62). The rates of other outcomes were similar between these 2 groups. These data indicate that depression affects posttransplant psychiatric morbidity but not other medical outcomes of liver transplantation. Pharmacological treatment of depression may significantly reduce the incidence of acute cellular rejection in patients undergoing liver transplantation. However, future prospective studies of mental health and liver transplantation are required to definitively assess the effects of antidepressant medications on medical outcomes.
Liver Transplantation 03/2011; 17(3):251-60. · 3.39 Impact Factor
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ABSTRACT: Acute liver failure (ALF) occurs when the extent of hepatocyte death exceeds the liver's regenerative capacity. Despite vast differences in causes, the mode of cell death typically follows one of two patterns: necrosis or apoptosis. Necrosis and apoptosis have traditionally been considered separate entities within various etiologies of ALF; however, there is increasing evidence that they are alternative outcomes of the same initiating factors and signaling pathways, a process known as necroapoptosis. Here we review mechanisms of liver cell injury in ALF, including evolving knowledge of pathways leading to apoptosis, necrosis, and necroapoptosis, as well as how these pathways are potential therapeutic targets in ALF. We also discuss hepatic regeneration and the cytokines and growth factors involved in both the replication of differentiated hepatocytes as well as activation of intrahepatic progenitor cells, two pathways of hepatocyte regeneration that are dependent on the type and extent of hepatic insult in ALF.
Seminars in Liver Disease 06/2008; 28(2):167-74. · 7.05 Impact Factor
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ABSTRACT: Diabetes and obesity affect development of nonalcoholic fatty liver disease. Nonalcoholic fatty liver disease increases susceptibility to hepatic injury and limits regenerative capacity, which might increase adverse outcomes in acute liver failure. There is no difference in the prevalence of diabetes in acute liver failure patients when compared with the general population, but no large studies have examined the relationship of obesity to incidence or outcome of acute liver failure.
Seven hundred eighty-two adult patients with acute liver failure were prospectively enrolled from 1998-2004. Body mass index, history of diabetes, and outcome were recorded. Multivariable logistic regression was used for the analysis.
Compared with 30.4% of adults in the National Health and Nutrition Examination Survey III, 29.1% of adult patients with acute liver failure were obese (P=.542). Obese patients had 1.63 times the odds of transplantation or death as nonobese patients (1.04-2.55, P=.033). Severely obese patients had 1.93 times the odds of transplantation or death (1.02-3.62, P=.042). There were no differences in the proportion of patients listed for transplantation, with body mass index greater or less than 30, 35, or 40 (P=.264, P=.112, P=.244, respectively). Obese patients had 3.4 times the odds of dying after transplantation (1.29-8.87, P=.01).
Obesity does not appear to be more prevalent in acute liver failure. However, obese and severely obese patients had significantly poorer outcomes when they developed acute liver failure. This difference is not explained by weight discrimination in listing patients for transplantation, despite evidence for poorer post-transplant outcomes.
Clinical Gastroenterology and Hepatology 01/2007; 4(12):1544-9. · 5.63 Impact Factor
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ABSTRACT: In an attempt to improve quality of care for patients admitted to our medical service we have implemented the use of pathways. These are printed standards of care and a mechanism for daily multidisciplinary documentation. The goals of our pathways are to: improve quality using printed standards of care; improve documentation of the care delivered; improve communication about daily goals between all team members, patients and families; standardize our in-patient chart format throughout the hospital; and increase efficiency of care. Pathways were designed to provide physicians and nurses with the standards for care and provide a mechanism for multidisciplinary documentation on our in-patient charts. We now have 2 pathways in use on our medical service. One is a clinical care plan (CCP) and the other is a Pancreatitis Pathway (PP) for patients admitted with acute pancreatitis and the other a guideline for care for all patients. The pathways were developed by teams including attending physicians (General Internists and Gastroenterologists), medicine house officers, nurses, and care coordinators. The pathways are used for all patients admitted to our medical service if they are admitted to one of 2 floors. This paper includes a comparison of outcomes for our first 9 patients who were managed using the pancreatitis pathway versus 7 patients cared for without the pathway. Significant differences in the pancreatitis pathway treated patients included: 1) less intense pain on day 2, (P = 0.04); 2) less pain on day of refeeding (P = 0.004); and 3) less IV fluids administered (P = 0.05). We also describe several lessons we have learned about using pathways for in-patients on a medical service in an academic medical center. We have learned the following lessons. Nursing documentation is improved. Physicians need ongoing encouragement and education about the value of pathways. There is considerable work involved for unit coordinators, care coordinators, and nursing in using pathways on a medical-surgical floor. There must be physician and nurse champions. There must be ongoing feedback to users. There must be input from users and edits. We believe the use of pathways as a process to remind clinicians of quality standards will improve the care of our patients by decreasing variation, improving team communication, and enhancing patient and family education.
Critical pathways in cardiology 04/2004; 3(1):35-41.
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