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Stepan Sembera,
Craig Lammert,
Jayant A Talwalkar,
Schuyler O Sanderson,
John J Poterucha, J Eileen Hay,
Russell H Wiesner,
Gregory J Gores,
Charles B Rosen,
Julie K Heimbach,
Michael R Charlton
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ABSTRACT: Drug-induced liver injury (DILI) is increasingly being recognized as a common cause of acute hepatitis. The clinical impact of DILI after liver transplantation (LT) is not known. The aim of this study was to describe the frequency, clinical presentation, and outcomes of DILI in LT recipients. LT recipients with possible DILI were identified with electronic pathology records and clinical note database retrieval tools. Diagnostic criteria were applied to identify cases of DILI. Twenty-nine of 1689 LT recipients (1.7%) were identified with DILI. The mean age was 52 years, and 52% were women. The major indications for LT were primary sclerosing cholangitis (28%), cholangiocarcinoma (14%), and hepatocellular carcinoma (14%). The severity of DILI was mild or moderate in 92% of the cases. Nausea or diarrhea (31%), jaundice (24%), and pruritus (10%) were the most common symptoms at the time of diagnosis. The mean biochemistry values were as follows: alanine aminotransferase, 204 ± 263 U/L; aspartate aminotransferase, 108 ± 237 U/L; alkaline phosphatase, 469 ± 689 U/L; and total bilirubin, 1.9 ± 10.3 mg/dL. The median duration of medication use until the diagnosis of DILI was 57 days, and the major agent classes were antibiotics (48%), immunosuppressive agents (14%), and antihyperlipidemic drugs (7%). Trimethoprim-sulfamethoxazole was the most common implicated agent (n = 11). Serum liver enzymes improved within a median time of 34 days (range = 5-246 days) after drug withdrawal. Hepatic retransplantation or death did not occur. Among the 50 cases with possible DILI explained by other causes, 13 individuals (26%) had no alternative diagnosis despite histological findings compatible with DILI. In conclusion, DILI is a rare yet underrecognized event among LT recipients. The majority of cases are not clinically severe, and they resolve after drug cessation without hepatic retransplantation or death.
Liver Transplantation 03/2012; 18(7):803-10. · 3.39 Impact Factor
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ABSTRACT: Older age is considered a poor prognostic factor in acute liver failure (ALF) and may still be considered a relative contraindication for liver transplantation for ALF. We aimed to evaluate the impact of older age, defined as age > or = 60 years, on outcomes in patients with ALF. One thousand one hundred twenty-six consecutive prospective patients from the US Acute Liver Failure Study Group registry were studied. The median age was 38 years (range, 15-81 years). One thousand sixteen patients (90.2%) were younger than 60 years (group 1), and 499 (49.1%) of these had acetaminophen-induced ALF; this rate of acetaminophen-induced ALF was significantly higher than that in patients > or = 60 years (group 2; n = 110; 23.6% with acetaminophen-induced ALF, P < 0.001). The overall survival rate was 72.7% in group 1 and 60.0% in group 2 (not significant) for acetaminophen patients and 67.9% in group 1 and 48.2% in group 2 for non-acetaminophen patients (P < 0.001). The spontaneous survival rate (ie, survival without liver transplantation) was 64.9% in group 1 and 60.0% in group 2 (not significant) for acetaminophen patients and 30.8% in group 1 and 24.7% in group 2 for non-acetaminophen patients (P = 0.27). Age was not a significant predictor of spontaneous survival in multiple logistic regression analyses. Group 2 patients were listed for liver transplantation significantly less than group 1 patients. Age was listed as a contraindication for transplantation in 5 patients. In conclusion, in contrast to previous studies, we have demonstrated a relatively good spontaneous survival rate for older patients with ALF when it is corrected for etiology. However, overall survival was better for younger non-acetaminophen patients. Fewer older patients were listed for transplantation.
Liver Transplantation 11/2009; 15(11):1481-7. · 3.39 Impact Factor
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J Eileen Hay
Nature Clinical Practice Gastroenterology & Hepatology 05/2008; 5(4):190-1. · 5.33 Impact Factor
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J Eileen Hay
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ABSTRACT: Abnormal liver tests occur in 3%-5% of pregnancies, with many potential causes, including coincidental liver disease (most commonly viral hepatitis or gallstones) and underlying chronic liver disease. However, most liver dysfunction in pregnancy is pregnancy-related and caused by 1 of the 5 liver diseases unique to the pregnant state: these fall into 2 main categories depending on their association with or without preeclampsia. The preeclampsia-associated liver diseases are preeclampsia itself, the hemolysis (H), elevated liver tests (EL), and low platelet count (LP) (HELLP) syndrome, and acute fatty liver of pregnancy. Hyperemesis gravidarum and intrahepatic cholestasis of pregnancy have no relationship to preeclampsia. Although still enigmatic, there have been recent interesting advances in understanding of these unique pregnancy-related liver diseases. Hyperemesis gravidarum is intractable, dehydrating vomiting in the first trimester of pregnancy; 50% of patients with this condition have liver dysfunction. Intrahepatic cholestasis of pregnancy is pruritus and elevated bile acids in the second half of pregnancy, accompanied by high levels of aminotransferases and mild jaundice. Maternal management is symptomatic with ursodeoxycholic acid; for the fetus, however, this is a high-risk pregnancy requiring close fetal monitoring and early delivery. Severe preeclampsia itself is the commonest cause of hepatic tenderness and liver dysfunction in pregnancy, and 2%-12% of cases are further complicated by hemolysis (H), elevated liver tests (EL), and low platelet count (LP)-the HELLP syndrome. Immediate delivery is the only definitive therapy, but many maternal complications can occur, including abruptio placentae, renal failure, subcapsular hematomas, and hepatic rupture. Acute fatty liver of pregnancy is a sudden catastrophic illness occurring almost exclusively in the third trimester; microvesicular fatty infiltration of hepatocytes causes acute liver failure with coagulopathy and encephalopathy. Early diagnosis and immediate delivery are essential for maternal and fetal survival.
Hepatology 04/2008; 47(3):1067-76. · 11.66 Impact Factor
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ABSTRACT: With early posttransplant bone loss, orthotopic liver transplantation (OLT) recipients experience a high rate of fracturing and some avascular necrosis (AVN), but little is known about the incidence of and predictive factors for these skeletal complications. We studied 360 consecutive patients who underwent transplantation for primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) and assessed both vertebral and nonvertebral (rib, pelvic, and femur) fractures in a protocolized fashion. Before OLT, 20% of the patients had experienced fracturing, and 1.4% of the patients had experienced AVN. Following OLT, there was a sharp increase in fracturing, with a 30% cumulative incidence of fractures at 1 year and 46% at 8 years after transplantation. In contrast to previous studies, there was a similar incidence of posttransplant vertebral and nonvertebral fractures. The greatest risk factors for posttransplant fracturing were pretransplant fracturing and the severity of osteopenia and posttransplant glucocorticoids. Nine percent of the liver recipients experienced AVN after OLT, and this correlated with pretransplant and posttransplant lipid metabolism, bone disease (bone mineral density and fracturing), and posttransplant glucocorticoids. A novel association between cholestasis and AVN was also identified, the mechanism for which is not known. CONCLUSION: Fortunately, recent years have seen an increase in the bone mass of liver recipients and, along with this, less fracturing and less AVN. Nonetheless, 25% of patients undergoing OLT for chronic cholestatic liver disease still develop de novo fractures after OLT; this situation demands an ongoing search for effective therapeutic agents for these patients.
Hepatology 11/2007; 46(4):1198-207. · 11.66 Impact Factor
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ABSTRACT: Serum concentrations of the actin scavenger Gc-globulin may provide prognostic information in acute liver failure (ALF). The fraction of Gc-globulin not bound to actin is postulated to represent a better marker than total Gc-globulin but has been difficult to measure. We tested a new rapid assay for actin-free Gc-globulin to determine its prognostic value when compared with the King's College Hospital (KCH) criteria in a large number of patients with ALF. A total of 252 patients with varying etiologies from the U.S. ALF Study Group registry were included; the first 178 patients constituted the learning set, and the last 74 patients served as the validation set. Actin-free Gc-globulin was determined with a commercial enzyme-linked immunosorbent assay kit. The median (range) actin-free Gc-globulin level at admission for the learning set was significantly reduced compared with controls (47 [0-183] mg/L vs. 204 [101-365] mg/L, respectively, P < 0.001). Gc-globulin levels were significantly higher in spontaneous survivors than in patients who died or were transplanted (53 [0-129] mg/L vs. 37 [0-183] mg/L, P = 0.002). A receiver operating characteristic curve analysis showed that a 40 mg/L cutoff level carried the best prognostic information, yielding positive and negative predictive values of 68% and 67%, respectively, in the validation set. The corresponding figures for the KCH criteria were 72% and 64%. A new enzyme-linked immunosorbent assay for actin-free Gc-globulin provides the same (but not optimal) prognostic information as KCH criteria in a single measurement at admission.
Liver Transplantation 10/2007; 13(9):1324-9. · 3.39 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: Fracturing after liver transplantation (OLT) occurs due to the combination of preexisting low bone mineral density (BMD) and early posttransplant bone loss, the risk factors for which are poorly defined. The prevalence and predictive factors for hepatic osteopenia and osteoporosis, posttransplant bone loss, and subsequent bone gain were studied by the long-term posttransplant follow-up of 360 consecutive adult patients with end-stage primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Only 20% of patients with advanced PBC or PSC have normal bone mass. Risk factors for low spinal BMD are low body mass index, older age, postmenopausal status, muscle wasting, high alkaline phosphatase and low serum albumin. A high rate of spinal bone loss occurred in the first 4 posttransplant months (annual rate of 16%) especially in those with younger age, PSC, higher pretransplant bone density, no inflammatory bowel disease, shorter duration of liver disease, current smoking, and ongoing cholestasis at 4 months. Factors favoring spinal bone gain from 4 to 24 months after transplantation were lower baseline and/or 4-month bone density, premenopausal status, lower cumulative glucocorticoids, no ongoing cholestasis, and higher levels of vitamin D and parathyroid hormone. Bone mass therefore improves most in patients with lowest pretransplant BMD who undergo successful transplantation with normal hepatic function and improved gonadal and nutritional status. Patients transplanted most recently have improved bone mass before OLT, and although bone loss still occurs early after OLT, these patients also have a greater recovery in BMD over the years following OLT.
Liver Transplantation 10/2006; 12(9):1390-402. · 3.39 Impact Factor
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ABSTRACT: We have previously reported that low hepatic tissue cyclosporine levels correlate with early cellular rejectionafter liver transplantation. The aim of this study is to determine whether there is a similar relationship in patients treated with FK506. Twenty-five liver biopsies were performed in 10 patients immunosuppressed with FK506 without cellular rejection: day 7 = 10; day 14 = 3; day 21 = 9; day 28 = 1; day 35 = 1; and day 42 = 1. These 10 patients without cellular rejection were compared with 7 patients immunosuppressed with FK506 with cellular rejection who underwent a total of 23 liver biopsies, including 9 biopsies that showed rejection: day 7 = 4; day 14 = 2; day 21 = 1; day 28 = 1; and day 49 = 1. There was no significant difference between the nonrejection and current rejection groups in the median plasma concentration of FK506, 0.9 ng/mL versus 0.9 ng/mL (P = 0.50). In contrast, the median hepatic tissue concentration of FK506 was significantly higher in the nonrejection group than it was in the current rejection group, 144 ng/g versus 48 ng/g (P = 0.02). In the current rejection group, 7 of 9 hepatic tissue concentrations of FK506 were <100 ng/g, and in the nonrejection group, 18 of 25 hepatic tissue concentrations were >100 ng/g. Low hepatic tissue concentrations of FK506 correlate with the occurrence of early cellular rejection after liver transplantation, in contrast to plasma concentrations of FK506. A hepatic tissue concentration of FK506 <100 ng/g is 78% sensitive and 72% specific for cellular rejection. These findings support the hypothesis that low hepatic tissue concentrations of immunosuppressives may lead to cellular rejection after liver transplantation. (Hepatology 1995;21:70–76).
Hepatology 12/2005; 21(1):70 - 76. · 11.66 Impact Factor
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Hepatology 12/2005; 16(5):1290 - 1299. · 11.66 Impact Factor
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ABSTRACT: This article discusses the clinical importance of hepatic osteopenia, the identification of risk factors for the individual patient, and the selection of patients, timing, and methods for diagnostic screening. General supportive measures to maximize bone health should be used in all patients at risk. In addition, for the patient with established osteoporosis, specific therapeutic measures may be justified, despite the lack of adequate randomized trials of these agents in patients with hepatic osteopenia.
Clinics in Liver Disease 12/2005; 9(4):747-66, viii. · 3.18 Impact Factor
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ABSTRACT: Bone loss occurs early after orthotopic liver transplantation (OLT) in all liver transplant recipients and leads to postoperative fractures, especially in cholestatic patients with the lowest bone mass. Little is known about the underlying changes in bone metabolism after OLT or about the etiology of these changes. Histomorphometric analysis of bone biopsies, a method that allows assessment of bone volume, resorption, and formation, has shown improved bone metabolism at 4 months after OLT. It has further suggested that accelerated posttransplant bone loss occurs in the first 1-2 months after OLT, probably by an additional insult to bone formation. This study attempts to correlate the histomorphometric bone changes in paired bone biopsies (OLT and 4 months after OLT) of 33 patients undergoing OLT for chronic cholestatic liver disease with the many clinical and biochemical changes in these patients over the same period. Cumulative steroid dosage early after OLT is shown to be important, presumably by decreasing bone formation rates. The actual effect of calcineurin inhibitors on this early phase of bone loss is less clear, although posttransplant histomorphometric findings suggest that tacrolimus-treated patients have an earlier recovery of bone metabolism and trabecular structure compared with cyclosporine patients. Other factors important in the recovery of bone metabolism after the early phase of bone loss are recovery of liver and gonadal function and better calcium balance.
Liver Transplantation 06/2004; 10(5):638-47. · 3.39 Impact Factor
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J Eileen Hay
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ABSTRACT: Acute liver failure (ALF) is an uncommon medical emergency whose rapid progression and high mortality demand early diagnosis and expert management, including immediate transfer of any potential case to facilities for intensive care and orthotopic liver transplantation (OLT). All patients with ALF must be screened aggressively for acetaminophen toxicity (history, serum levels, "hyperacute" presentation with renal failure), for other drugs, and viral hepatitis; rare causes of ALF should also be considered. After an acetaminophen overdose, N-acetylcysteine must be given as early as possible, preferably in the emergency room, but any patient with ALF should promptly receive N-acetylcysteine if there is suspicion of acetaminophen toxicity irrespective of the time of ingestion. Supportive care for all patients with ALF includes adequate enteral nutrition, aggressive screening and treatment of infection, prophylactic broad-spectrum antibiotics, and antifungal agents. Sedation with propofol is given for severe agitation or mechanical ventilation. With advanced coma grades, intensive care is needed with hemodynamic monitoring, ventilatory support, continuous renal replacement for renal failure, and intracranial pressure monitoring. Intracranial hypertension is treated with mannitol and/or acute short-term hyperventilation, but if the patient is refractory to treatment, mild-moderate hypothermia is achieved by a cooling blanket that is continued throughout OLT. Barbiturate coma is only used in refractory cases as the last treatment modality. Seizures are aggressively treated with phenytoin, with additional diazepam as needed. Candidacy and activation for OLT should be completed as early as possible in the course of ALF, especially in "hyperacute" cases such as acetaminophen toxicity. The final decision to proceed with OLT is made when a donor organ becomes available. King's College Hospital criteria for OLT are still the best prognostic assessment for fatal outcome in ALF, but the criteria fail to identify some patients who will die.
Current Treatment Options in Gastroenterology 02/2004; 7(6):459-468.
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ABSTRACT: Thirty-three patients with cholestatic liver disease underwent histomorphometric assessment of paired bone biopsy specimens at time of orthotopic liver transplantation (OLT) and 4 months thereafter. At 4 months after OLT, bone metabolism improved, with bone formation increasing to normal and no change in bone resorption. Early post-transplant bone loss may be attributed to an additional insult to bone formation early after transplantation.
Patients with advanced liver disease, especially chronic cholestasis, often have osteopenia, which worsens early after orthotopic liver transplantation (OLT) before starting to recover. The changes in bone metabolism leading to this rapid loss of bone after OLT, and to its recovery, are poorly defined.
In thirty-three patients with advanced chronic cholestatic liver disease, tetracycline-labeled bone biopsy specimens were analyzed prospectively at time of OLT and at 4 months after OLT, as part of a randomized trial to study the efficacy of calcitonin on post-transplant bone loss. Hierarchical cluster analysis of histomorphometric parameters was performed in an attempt to establish the functional grouping of individual histomorphometric parameters before and after OLT.
Results showed that from the time of OLT to 4 months after OLT, bone mineral density of the lumbar spine and histomorphometric parameters of bone volume decreased, consistent with early post-transplant bone loss. Histomorphometric resorption parameters were increased before OLT, with no change after OLT. Histomorphometric formation parameters increased from low values before OLT to normal values at 4 months after OLT, with the exception of mean wall thickness values, which further decreased after OLT, suggesting an additional insult to bone formation during the study period. Histomorphometric changes after OLT were similar in female and male patients, pre- and postmenopausal women, and in patients treated and not treated with calcitonin. Hierarchical cluster analysis suggested that before OLT, bone resorption was functioning independently of bone formation, but that by 4 months after OLT, their coupled relationship had improved. Therefore, despite post-transplant bone loss, by 4 months after OLT, bone metabolism had improved, with increased bone formation and more coupled bone balance, as suggested by hierarchical cluster analysis.
Journal of Bone and Mineral Research 01/2004; 18(12):2190-9. · 6.37 Impact Factor
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Frank V. Schiødt,
Evren Atillasoy,
A. Obaid Shakil,
Eugene R. Schiff,
Cary Caldwell,
Kris V. Kowdley,
Risë Stribling,
Jeffrey S. Crippin,
Steven Flamm,
Kenneth A. Somberg,
Hugo Rosen,
Tim M. McCashland, J. Eileen Hay,
William M. Lee
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ABSTRACT: Little information is available on acute liver failure (ALF) in the United States. We gathered demographic data retrospectively for a 2-year period from July 1994 to June 1996 on all cases of ALF from 13 hospitals (12 liver transplant centers). Data on the patients included age, hepatic coma grade on admission, presumed cause, transplantation, and outcome. Among 295 patients, 74 (25%) survived spontaneously, 121 (41%) underwent transplantation, and 99 (34%) died without undergoing transplantation. Ninety-two of 121 patients (76%) survived 1 year after transplantation. Acetaminophen overdose was the most frequent cause (60 patients; 20%), followed by cryptogenic/non A non B non C (NANBNC; 15%), idiosyncratic drug reactions (12%), hepatitis B (10%), and hepatitis A (7%). Spontaneous survival rates were highest for patients with acetaminophen overdose (57%) and hepatitis A (40%) and lowest for those with Wilson's disease (no survivors of 18 patients). The transplantation rate was highest for Wilson's disease (17 of 18 patients; 94%) and lowest for autoimmune hepatitis (29%) and acetaminophen overdose (12%). Age did not differ between survivors and nonsurvivors, perhaps reflecting a selection bias for patients transferred to liver transplant centers. Coma grade on admission was not a significant determinant of outcome, but showed a trend toward affecting both survival and transplantation rate. These findings on retrospectively studied patients from the United States differ from those previously gathered in the United Kingdom and France, highlighting the need for further study of trends in each country.
Liver Transplantation 12/2003; 5(1):29 - 34. · 3.39 Impact Factor
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Ivo W. Graziadei,
Russell H. Wiesner M.D,
Paul J. Marotta,
Michael K. Porayko, J. Eileen Hay,
Michael R. Charlton,
John J. Poterucha,
Charles B. Rosen,
Gregory J. Gores,
Nicholas F. LaRusso,
Ruud A. F. Krom
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ABSTRACT: Liver transplantation is the only effective therapeutic option for patients with end-stage liver disease due to primary sclerosing cholangitis (PSC). In this study, we analyzed a single center's experience with 150 consecutive PSC patients who received 174 liver allografts. Mean follow-up was 55 months. Actuarial patient survival at 1, 2, 5, and 10 years was 93.7%, 92.2%, 86.4%, and 69.8%, respectively, whereas graft survival was 83.4%, 83.4%, 79.0%, and 60.5%, respectively. The main indication for retransplantation was hepatic artery thrombosis, and the major cause of death was severe infection. Patients with PSC had a higher incidence of acute cellular and chronic ductopenic rejection compared to a non-PSC control group. Chronic ductopenic rejection adversely affected patient and graft survival. Biliary strictures, both anastomotic and nonanastomotic, were frequent and occurred in 16.2% and 27.2% of patients, respectively. The incidence of recurrent PSC was 20%. A negative impact on patient survival was not seen in patients with either postoperative biliary strictures or recurrence of PSC. Six patients (4%) had cholangiocarcinoma and 1 patient died related to recurrence of malignant disease. Seventy-eight percent of PSC patients had associated inflammatory bowel disease, most commonly chronic ulcerative colitis, which did not adversely impact patient outcome posttransplantation. Nine patients required proctocolectomy after liver transplantation; 5 because of intractable symptoms related to inflammatory bowel disease and 4 due to the development of colorectal carcinoma/high-grade dysplasia. Our data show that liver transplantation provides excellent long-term patient and graft survival for patients with end-stage PSC.
Hepatology 12/2003; 30(5):1121 - 1127. · 11.66 Impact Factor
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ABSTRACT: Although best characterized in chronic cholestatic liver disease, osteopenic bone disease and fracturing are well-recognized complications of cirrhosis, particularly after liver transplantation. We sought to compare the prevalence of osteopenia and osteoporosis, to assess the effect of orthotopic liver transplantation (OLT) on bone density, and to determine fracture rates before and after OLT in three groups of patients with advanced cirrhosis: patients with cirrhosis from hepatitis C virus (HCV) alone, from alcohol abuse (ALD), and from HCV in conjunction with alcohol abuse (HCV+ALD). Between 1991 and 2001, 207 consecutive patients who underwent OLT for HCV (68 patients), ALD (66), and HCV+ALD (73) were assessed clinically, biochemically, radiologically, and by bone densitometry. The baseline mean T score was lower in the HCV group than in the ALD group (-1.43 versus -0.87, P =.048) despite ALD patients having more advanced liver disease; patients with HCV+ALD had intermediate T scores. The pattern of significant bone loss at 4 months and 12 months was similar for all three groups. The baseline fracture rate was lowest in the HCV group and highest in the ALD group, despite the latter having the highest bone density. Fractures occurred in 17% of patients in the first year after transplantation, the majority being vertebral compression fractures. Patients with cirrhosis caused by HCV, ALD, or a combination of both should be screened for osteopenia, especially before OLT.
Liver Transplantation 12/2003; 9(11):1166-73. · 3.39 Impact Factor
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J Eileen Hay
Journal of Hepatology 07/2003; 38(6):856-65. · 9.26 Impact Factor
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George Ostapowicz,
Robert J Fontana,
Frank V Schiødt,
Anne Larson,
Timothy J Davern,
Steven H B Han,
Timothy M McCashland,
A Obaid Shakil, J Eileen Hay,
Linda Hynan,
Jeffrey S Crippin,
Andres T Blei,
Grace Samuel,
Joan Reisch,
William M Lee
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ABSTRACT: Because acute liver failure is rare, related data have been sparse. Studies have suggested that viral hepatitis is the most common underlying cause of this condition.
To describe the clinical features, presumed causes, and short-term outcomes of acute liver failure.
Prospective cohort study.
17 tertiary care centers participating in the U.S. Acute Liver Failure Study Group.
308 consecutive patients with acute liver failure, admitted over a 41-month period.
Detailed clinical and laboratory data collected during hospitalization, including outcome 3 weeks after study admission.
73% of patients were women; median age was 38 years. Acetaminophen overdose was the most common apparent cause of acute liver failure, accounting for 39% of cases. Idiosyncratic drug reactions were the presumptive cause in 13% of cases, viral hepatitis A and B combined were implicated in 12% of cases, and 17% of cases were of indeterminate cause. Overall patient survival at 3 weeks was 67%. Twenty-nine percent of patients had liver transplantation, and 43% survived without transplantation. Short-term transplant-free survival varied greatly, from 68% for patients with acetaminophen-related liver failure to 25% and 17% for those with other drug reactions and liver failure of indeterminate cause, respectively. Coma grade at admission appeared to be associated with outcome, but age and symptom duration did not.
Acetaminophen overdose and idiosyncratic drug reactions have replaced viral hepatitis as the most frequent apparent causes of acute liver failure. Apparent cause and coma grade at admission were associated with outcome. Although transplantation may improve patient survival, it was unavailable or unnecessary for most patients.
Annals of internal medicine 01/2003; 137(12):947-54. · 16.73 Impact Factor
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Liver Transplantation 12/2002; 8(11):1080-1. · 3.39 Impact Factor
