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Objectives: Children with physical disabilities (CWPD) have historically experienced inadequate and insensitive care across medical settings. A lack of comfort and knowledge about CWPD is prevalent among healthcare provider trainees. We developed a new, readily distributable educational resource about CWPD for healthcare students and conducted a study to determine its efficacy in improving their attitudes toward CWPD., Methods: We collaborated with a working group of stakeholders in the disability community to develop an educational resource for healthcare students. We developed nine short video clips (with a cumulative duration of 27 min) of a primary care visit using simulated participants and embedded them into a 50-min workshop. We conducted a study of the workshop's utility for volunteer healthcare students using synchronous videoconferencing. Participating students completed assessments at baseline and after the workshop. Our primary outcome measure was a change in the Attitudes to Disabled Persons-Original (ATDP-O) scale., Results: Forty-nine healthcare students participated in the training session: 29 (59%) from medicine, and 21 (41%) from physician assistant or nursing programs. The materials were easy to deliver virtually. The workshop resulted in measurable change in attitudes regarding physical disabilities, with improvement in ATDP-O scores between baseline ( M  = 31.2, SD  = 8.9) and endpoint ( M  = 34.8, SD  = 10.1) scores ( t (49) = 3.28, P  = .002, Cohen's d  = 0.38)., Conclusion: This video-based educational resource on CWPD is readily distributable and can be delivered virtually as a workshop. The video-enhanced workshop improved healthcare students' perceptions and attitudes toward CWPDs. All materials are available to view, download, or adapt by end-use instructors., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Objectives: In a population-based study, we examined time trends in chronic liver disease (CLD)-related hospitalizations in a large and diverse metroplex., Methods: We examined all CLD-related inpatient encounters (2000-2015) in Dallas-Fort Worth (DFW) using data from the DFW council collaborative that captures claims data from 97% of all hospitalizations in DFW (10.7 million regional patients)., Results: There were 83,539 CLD-related hospitalizations in 48,580 unique patients across 84 hospitals. The age and gender standardized annual rate of CLD-related hospitalization increased from 48.9 per 100,000 in 2000 to 125.7 per 100,000 in 2014. Mean age at hospitalization increased from 54.0 (14.1) to 58.5 (13.5) years; the proportion of CLD patients above 65 years increased from 24.2% to 33.1%. HCV-related hospitalizations plateaued, whereas an increase was seen in hospitalizations related to alcohol (9.1 to 22.7 per 100,000) or fatty liver (1.4 per 100,000 to 19.5 per 100,000). The prevalence of medical comorbidities increased for CLD patients: coronary artery disease (4.8% to 14.3%), obesity (2.8% to 14.6%), chronic kidney disease (2.8% to 18.2%), and diabetes (18.0% to 33.2%). Overall hospitalizations with traditional complications of portal hypertension (ascites, varices, and peritonitis) remained stable over time. However, hospitalization with complications related to infection increased from 54.7% to 66.4%, and renal failure increased by sevenfold (2.7% to 19.5%)., Conclusions: CLD-related hospitalizations have increased twofold over the last decade. Hospitalized CLD patients are older and sicker with multiple chronic conditions. Traditional complications of portal hypertension have been superseded by infection and renal failure, warranting a need to redefine what it means to have decompensated CLD.

There is growing interest in the quality of health care delivery in liver transplantation. Multiple stakeholders, including patients, transplant providers and their hospitals, payers, and regulatory bodies have an interest in measuring and monitoring quality in the liver transplant process, and understanding differences in quality across centres. This article aims to provide an overview of quality measurement and regulatory issues in liver transplantation performed within the United States. We review how broader definitions of health care quality should be applied to liver transplant care models. We outline the status quo including the current regulatory agencies, public reporting mechanisms, and requirements around quality assurance and performance improvement (QAPI) activities. Additionally, we further discuss unintended consequences and opportunities for growth in quality measurement. Quality measurement and the integration of quality improvement strategies into liver transplant programmes hold significant promise, but multiple challenges to successful implementation must be addressed to optimise value., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Patients with primary sclerosing cholangitis (PSC) may be at higher risk of malignancy after liver transplantation (LT) compared to other LT recipients. We aimed to determine the cumulative incidence of/risk factors for long-term cancer-related mortality in patients with PSC after LT., Methods: All adult patients underwent LT for PSC without cholangiocarcinoma from 1984 to 2012, with follow-up through June 2015. We estimated cumulative incidence, risk factors, and mortality from de novo malignancies after LT., Results: Two hundred ninety-three patients were identified (mean [SD] age, 47 [12] years; 63.3% males; 2.4% smoking at LT). Over a median of 11.5 years (range, 6.4-18.6 years), 64 patients (21.8%) developed 73 nonskin cancers, including 46 solid-organ cancers (renal, 11; colorectal, 11; prostate, 7; breast, 5; pancreas, 5; ovarian/endometrial/vulvar cancers, 3; and de novo cholangiocarcinoma, 4). Twenty-two patients developed hematologic malignancies (posttransplant lymphoproliferative diseases, 18; Hodgkin disease, 2; and myelodysplastic syndrome, 2). Five patients developed melanoma. The 1-, 5-, 10-, and 20-year cumulative incidences of cancer were 2.1%, 8.6%, 18.7%, and 27%, respectively. Mortality of patients with PSC who developed cancer was higher than that of patients with PSC without cancer (hazard ratio, 2.2; P < 0.01). On multivariate analysis, recipient's age and elevated pre-LT international normalized ratio were associated with increased risk of de novo (nonskin) malignancy., Conclusion: The 10-year cumulative risk of cancer after LT for advanced-stage PSC was 18.7%, with posttransplant lymphoproliferative diseases, colorectal cancer, and renal cell cancer being the most common. Post-LT de novo nonskin cancer decreased overall posttransplant survival. Only recipient's age and elevated international normalized ratio at LT were associated with increased nonskin cancer risk.

Background & Aims: The Drug-Induced Liver Injury Network is conducting a prospective study of patients with DILI in the United States. We present characteristics and subgroup analyses from the first 1257 patients enrolled in the study., Methods: In an observational longitudinal study, we began collecting data on eligible individuals with suspected DILI in 2004, following them for 6 months or longer. Subjects were evaluated systematically for other etiologies, causes, and severity of DILI., Results: Among 1257 enrolled subjects with suspected DILI, the causality was assessed in 1091 patients, and 899 were considered to have definite, highly likely, or probable DILI. Ten percent of patients died or underwent liver transplantation, and 17% had chronic liver injury. In the 89 patients (10%) with pre-existing liver disease, DILI appeared to be more severe than in those without (difference not statistically significant; P = .09) and mortality was significantly higher (16% vs 5.2%; P < .001). Azithromycin was the implicated agent in a higher proportion of patients with pre-existing liver disease compared with those without liver disease (6.7% vs 1.5%; P = .006). Forty-one cases with latency ≤7 days were caused predominantly by antimicrobial agents (71%). Two most common causes for 60 DILI cases with latency >365 days were nitrofurantoin (25%) or minocycline (17%). There were no differences in outcomes of patients with short vs long latency of DILI. Compared with individuals younger than 65 years, individuals 65 years or older (n = 149) were more likely to have cholestatic injury, although mortality and rate of liver transplantation did not differ. Nine patients (1%) had concomitant severe skin reactions; implicated agents were lamotrigine, azithromycin, carbamazepine, moxifloxacin, cephalexin, diclofenac, and nitrofurantoin. Four of these patients died., Conclusions: Mortality from DILI is significantly higher in individuals with pre-existing liver disease or concomitant severe skin reactions compared with patients without. Additional studies are needed to confirm the association between azithromycin and increased DILI in patients with chronic liver disease. Older age and short or long latencies are not associated with DILI mortality., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Limited data are available regarding the role of magnetic resonance imaging (MRI), particularly the new generation 3 Tesla technology, and especially diffusion-weighted imaging (DWI) in predicting liver fibrosis. The aim of our pilot study was to assess the clinical performance of the apparent diffusion coefficient (ADC) of liver parenchyma for the assessment of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD)., Methods: 18 patients with biopsy-proven NAFLD underwent DWI with 3 Tesla MRI. DWI was performed with single-shot echo-planar technique at b values of 0-500 and 0-1000 s/mm 2 . ADC was measured in four locations in the liver and the mean ADC value was used for analysis. Staging of fibrosis was performed according to the METAVIR system., Results: The median age of patients was 52 years (range 23-73). The distribution of patients in different fibrosis stages was: 0 (n=1), 1 (n=7), 2 (n=1), 3 (n=5), 4 (n=4). Fibrosis stage was poorly associated with ADC at b value of 0-500 s/mm 2 (r= -0.30, P=0.27). However it was significantly associated with ADC at b value of 0-1000 s/mm 2 (r= -0.57, P=0.01). For this b value (0-1000 s/mm 2 ) the area under receiver-operating characteristic curve was 0.93 for fibrosis stage ≥3 and the optimal ADC cut-off value was 1.16 ×10 -3 mm 2 /s., Conclusion: 3 Tesla DWI can possibly predict the presence of advanced fibrosis in patients with NAFLD.

Over the past decade, several advances have been made in the non-invasive assessment of liver fibrosis. Both serum markers and imaging-based tissue elastography predict the presence of advanced fibrosis compared with liver biopsy. Serum markers may be indirect or direct markers of liver structure and function. Imaging-based techniques measure liver stiffness as a surrogate for fibrosis and include ultrasound and MRI-based methods. Most non-invasive techniques work well at identifying subjects at the extremes of fibrosis but may not accurately discern intermediate stages. In addition to being a diagnostic tool, elastography may have an evolving role in prognosis. Increasing stiffness is associated with higher rates of liver decompensation, need for transplantation, hepatocellular carcinoma, and death. There are special populations of patients where elastography may serve as a non-invasive method to impart useful clinical information, such as patients after liver transplantation, those with congenital heart disease and those being treated for chronic viral hepatitis. The role of non-invasive markers in accurately predicting the presence of fibrosis in obese patients needs to be further refined.

Unlabelled: The Drug-Induced Liver Injury Network (DILIN) studies hepatotoxicity caused by conventional medications as well as herbals and dietary supplements (HDS). To characterize hepatotoxicity and its outcomes from HDS versus medications, patients with hepatotoxicity attributed to medications or HDS were enrolled prospectively between 2004 and 2013. The study took place among eight U.S. referral centers that are part of the DILIN. Consecutive patients with liver injury referred to a DILIN center were eligible. The final sample comprised 130 (15.5%) of all subjects enrolled (839) who were judged to have experienced liver injury caused by HDS. Hepatotoxicity caused by HDS was evaluated by expert opinion. Demographic and clinical characteristics and outcome assessments, including death and liver transplantation (LT), were ascertained. Cases were stratified and compared according to the type of agent implicated in liver injury; 45 had injury caused by bodybuilding HDS, 85 by nonbodybuilding HDS, and 709 by medications. Liver injury caused by HDS increased from 7% to 20% (P < 0.001) during the study period. Bodybuilding HDS caused prolonged jaundice (median, 91 days) in young men, but did not result in any fatalities or LT. The remaining HDS cases presented as hepatocellular injury, predominantly in middle-aged women, and, more frequently, led to death or transplantation, compared to injury from medications (13% vs. 3%; P < 0.05)., Conclusions: The proportion of liver injury cases attributed to HDS in DILIN has increased significantly. Liver injury from nonbodybuilding HDS is more severe than from bodybuilding HDS or medications, as evidenced by differences in unfavorable outcomes (death and transplantation). (Hepatology 2014;60:1399-1408)., (© 2014 by the American Association for the Study of Liver Diseases.)

Unlabelled: Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the United-States. The aim of the study was to describe serum immune profiles associated with acute DILI, to investigate whether there are profiles associated with clinical features or types of DILI and/or with prognosis, and to assess temporal changes in levels. Twenty-seven immune analytes were measured in the sera of 78 DILI subjects in the Drug-Induced Liver Injury Network (DILIN) and compared with 40 healthy controls. Immune analytes (14 cytokines, 7 chemokines and 6 growth factors) were measured by BioPlex multiplex ELISA at DILI onset and after 6 months. A modeling process utilizing immune principles was used to select a final set of variables among 27 immune analytes and several additional clinical lab values for prediction of early death (within 6 months of DILI onset). Nineteen of the 27 immune analytes were differentially expressed among healthy control, DILI onset and 6-month cohorts. Disparate patterns of immune responses, especially innate and adaptive cellular (mostly TH17) immunity were evident. Low values of four immune analytes (IL-9, IL-17, PDGF-bb and RANTES) and serum albumin are predictive of early death [PPV = 88% (95% CI, 65%-100%), NPV = 97% (95% CI, 93%-100%), accuracy = 96% (95% CI, 92%-100%)]., Conclusions: Acute DILI is associated with robust and varying immune responses. High levels of expression of cytokines associated with innate immunity are associated with a poor prognosis, whereas high levels of expression of adaptive cytokines are associated with good long-term prognosis and eventual recovery. Serum immune analyte profiles at DILI onset appear to be of prognostic, and perhaps, diagnostic significance.

Objective: To describe a collaborative approach for developing an electronic health record (EHR) phenotyping algorithm for drug-induced liver injury (DILI)., Methods: We analyzed types and causes of differences in DILI case definitions provided by two institutions-Columbia University and Mayo Clinic; harmonized two EHR phenotyping algorithms; and assessed the performance, measured by sensitivity, specificity, positive predictive value, and negative predictive value, of the resulting algorithm at three institutions except that sensitivity was measured only at Columbia University., Results: Although these sites had the same case definition, their phenotyping methods differed by selection of liver injury diagnoses, inclusion of drugs cited in DILI cases, laboratory tests assessed, laboratory thresholds for liver injury, exclusion criteria, and approaches to validating phenotypes. We reached consensus on a DILI phenotyping algorithm and implemented it at three institutions. The algorithm was adapted locally to account for differences in populations and data access. Implementations collectively yielded 117 algorithm-selected cases and 23 confirmed true positive cases., Discussion: Phenotyping for rare conditions benefits significantly from pooling data across institutions. Despite the heterogeneity of EHRs and varied algorithm implementations, we demonstrated the portability of this algorithm across three institutions. The performance of this algorithm for identifying DILI was comparable with other computerized approaches to identify adverse drug events., Conclusions: Phenotyping algorithms developed for rare and complex conditions are likely to require adaptive implementation at multiple institutions. Better approaches are also needed to share algorithms. Early agreement on goals, data sources, and validation methods may improve the portability of the algorithms.

Purpose: To provide a fully automated algorithm for obtaining stiffness measurements from hepatic magnetic resonance elastography (MRE) images that are consistent with measurements performed by expert readers., Materials and Methods: An initial liver contour was found using an adaptive threshold and expanded using an active contour to select a homogeneous area of the liver. The confidence map generated during the stiffness calculation was used to select a region of reliable wave propagation. The average stiffness within the automatically generated region of interest (ROI) was compared to measurements by two trained readers in a set of 88 clinical test cases ranging from healthy to severely fibrotic., Results: The stiffness measurements reported by the readers differed by -6.76% ± 22.8% (95% confidence) and had an intraclass correlation coefficient (ICC) of 0.972 (P < 0.05). The algorithm and the more experienced reader differed by 4.32% ± 14.9 with an ICC of 0.987., Conclusion: The automated algorithm performed reliably, even though MRE acquisitions often have motion artifacts present. The correlation between the automated measurements and those from the trained readers was superior to the correlation between the readers., (Copyright © 2013 Wiley Periodicals, Inc.)

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown etiology despite advances in medical research that have focused on uncovering its pathogenesis. Recent developments in the diagnosis of PSC including technological advances in magnetic resonanace cholangiography and the recognition of distinct clinical subtypes have led to more frequent early detection and appropriate therapy when indicated. Continued work in the areas of identifying genetic predisposing factors and novel molecular therapeutic targets are expected to create new opportunities for treating patients suffering from this chronic illness. In this review we highlight recent advances in PSC pathogenesis, diagnosis and management.

Magnetic Resonance Elastography (MRE) is an MRI-based technique that is used for the clinical diagnosis and staging of liver fibrosis by quantitatively measuring the stiffness of the liver. Due to the complexity of the signal characteristics and the presence of artifacts both in the acquired images and in the resulting stiffness images, the selection of the ROI for the stiffness measurement is currently performed manually, which may lead to significant inter- and intrareader variability. An algorithm has been developed to fully automate this analysis for liver MRE images. Automated segmentation of liver MRE images is challenging due to signal inhomogeneity, low contrast, and variability in patient anatomy. An initial liver contour is found by fitting Gaussian peaks to the image histogram and selecting the peak that comprises intensities in the expected range and produces a mask near the expected location of the liver. After correction to reduce intensity inhomogeneity, an active contour based on intensity, with morphology used to implicitly enforce smoothness, is used to segment liver tissue while avoiding blood vessels. The resulting mask is used to initialize another segmentation which splits the region of the elastogram belonging to the liver into homogeneous liver tissue and areas with inclusions, partial volume effects, and artifacts. In a set of 88 cases the algorithm had a -6.0 ± 14.2% stiffness difference from an experienced reader, which was superior to the 6.8 ± 22.8% difference between two readers. The segmentation was run on an additional 200 cases and the final ROIs were subjectively rated by a radiologist. The ROIs in 98% of cases received an average rating of "good" or "acceptable."

Background/objectives: Circulating endothelial cells (CECs) are indicative of vascular injury and correlate with severity of vascular diseases. A pilot study showed that the ratio of CEC to platelet count (CEC/PC) was effective in predicting cirrhosis. Therefore, we evaluated CEC/PC in a larger cohort of patients, correlated it with cirrhosis, and compared its operating characteristics with previously described biomarker for cirrhosis, the AST/platelet ratio index (APRI)., Methods: Fifty-three patients with cirrhosis, 20 matched healthy controls, and 9 patients with noncirrhotic liver disease were recruited. Peripheral blood sample was collected and analyzed to enumerate nucleated CEC CD146+, CD105+, CD45- using a commercial assay., Results: Median CEC counts were significantly higher in patients with cirrhosis (62 cells/4 mL, interquartile range [IQR]: 43.5-121) as compared with controls (31 cells/4 mL, IQR: 22.2-40). The CEC/PC was also significantly elevated in cirrhotics (0.69, IQR: 0.39-1.48) compared with controls (0.12, IQR: 0.09-0.20) and noncirrhotics (0.21, IQR: 0.08-0.43). Receiver operator characteristic (ROC) analysis revealed that CEC cutoff value of ≥37 cells/4 mL showed sensitivity of 81% and specificity of 75% for differentiating cirrhosis from controls (area under the curve [AUC]: 0.80; 95% confidence interval [CI] 0.67-0.91). The CEC/PC ratio cutoff value of ≥0.23 showed sensitivity of 91% and specificity of 82% (AUC: 0.92; 95% CI 0.83-0.99). The APRI cutoff value of ≥0.4 showed sensitivity of 94% and specificity of 85% for differentiating cirrhosis from control patients (AUC: 0.96; 95% CI 0.90-1.0). A product of CEC and APRI, termed CAPRI (CEC-APRI), effectively distinguished patients with cirrhosis from controls; with cutoff value of ≥12.7, showing higher sensitivity of 98% and specificity of 85% (AUC: 0.98; 95% CI 0.96-1.0)., Conclusion: The CEC/PC ratio is significantly elevated in patients with cirrhosis and demonstrates comparable operating characteristics to previously described APRI. Furthermore, CAPRI, compiled as product of CEC to APRI showed outstanding ability to distinguish patients with cirrhosis from controls, although larger studies are necessary for validation.

Purpose: To investigate the correlation between MR elastography (MRE) assessed spleen stiffness and direct portal vein pressure gradient (D-HVPG) measurements in a large animal model of portal hypertension., Materials and Methods: Cholestatic liver disease was established in adult canines by common bile duct ligation. A spin echo based echo planar imaging (EPI) MRE sequence was used to acquire three-dimensional/three axis (3D/3-axis) abdominal MRE data at baseline, 4 weeks, and 8 weeks. Liver biopsies, blood samples, and D-HVPG measurements were obtained simultaneously., Results: Animals developed portal hypertension (D-HVPG: 11.0 ± 5.1 mmHg) with only F1 fibrosis after 4 weeks. F3 fibrosis was confirmed after 8 weeks despite no further rise in portal hypertension (D-HVPG: 11.3 ± 3.2 mmHg). Mean stiffnesses of the spleen increased over two-fold from baseline (1.72 ± 0.33 kPa) to 4 weeks (3.54 ± 0.31 kPa), and stabilized at 8 weeks (3.38 ± 0.06 kPa) in a pattern consistent with changes in portal pressure. A positive correlation was observed between spleen stiffness and D-HVPG (r(2) = 0.86; P < 0.01)., Conclusion: These findings indicate a temporal relationship between portal hypertension and the development of liver fibrosis in a large animal model of cholestatic liver disease. The observed direct correlation between spleen stiffness and D-HVPG suggest a noninvasive MRE approach to diagnose and screen for portal hypertension., (Copyright © 2011 Wiley-Liss, Inc.)

Background & Aims: The importance of histologic analysis of biopsy samples in the diagnosis and management of patients with autoimmune hepatitis (AIH) is unclear., Methods: Patients with AIH were identified from a 10-year database. Individuals with overlap syndromes and decompensated liver disease were excluded. The proportion of patients who fulfilled the new simplified criteria for AIH was calculated., Results: A total of 257 patients (203 female) with a median age of 52 years (interquartile range, 39-63 y) were diagnosed with AIH. Overall, 183 of 257 (71%) were positive for antinuclear antibodies, 116 (45%) had positive smooth muscle antibodies, and 29 of 257 (11%) were seronegative. A total of 250 (97%) patients had increased levels of autoantibodies and/or γ-globulins. In 95% (243 of 257 cases), the histology was compatible with AIH whereas 5% (14 cases) had atypical histology. Overall, 77% had a score of at least 6, indicating probable or definite AIH according to most recent criteria; 22% were diagnosed with AIH with less than 6 points and 1 patient had nonalcoholic steatohepatitis based on biopsy analysis. Immunosuppression occurred in 93% of patients. Patients with atypical versus compatible histology were similar in terms of seronegativity or γ-globulins; 86% (12 of 14) received immunosuppressive therapy despite atypical histology., Conclusions: Most patients with features of AIH, based on laboratory analyses, are likely to have a compatible liver histology. Few patients have atypical histology and these findings have little impact on patient management. These findings indicate biopsy samples might not need to be collected from patients who meet other clinical criteria for AIH., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Drug-induced autoimmune hepatitis (DIAIH) has been reported to be caused by several drugs. There is a lack of data comparing these patients with other patients with autoimmune hepatitis (AIH). A search was performed using the Mayo Clinic diagnostic medical index for AIH patients and DIAIH patients identified over 10 years. Individuals with overlap syndromes and decompensated liver disease were excluded. Overall, 261 patients (204 females, median age 52) were identified, and 24 (9.2%) were DIAIH cases with a median age of 53 (interquartile range, 24-61). Two drugs, nitrofurantoin (n = 11) and minocycline (n = 11), were the main causes. A similar proportion of DIAIH patients had positive antinuclear antibodies (83% versus 70%) and smooth muscle antibodies (50% versus 45%) as compared with AIH patients. Histological grade and stage were similar in patients with DIAIH versus AIH; however, none of the DIAIH patients had cirrhosis at baseline; this was present in 20% of matched AIH cases. Liver imaging was normal in all minocycline cases. Eight of 11 (73%) nitrofurantoin patients had abnormalities on hepatic imaging (mainly liver atrophy), a finding seen in only 8 of 33 (24%) of a random sample of the rest of the AIH group (P = 0.0089). Corticosteroid responsiveness was similar in DIAIH and the AIH patients. Discontinuation of immunosuppression was tried and successful in 14 DIAIH cases, with no relapses (0%), whereas 65% of the AIH patients had a relapse after discontinuation of immunosuppression (P < 0.0001)., Conclusion: A significant proportion of patients with AIH have drug-induced AIH, mainly because of nitrofurantoin and minocycline. These two groups have similar clinical and histological patterns. However, DIAIH patients do not seem to require long-term immunosuppressive therapy.

Background: Fatigue was recently suggested to predict an increased risk of mortality in a primary biliary cirrhosis (PBC) cohort during follow-up., Aims: To analyse the impact of fatigue on prognosis in PBC., Methods: Patients with PBC who had earlier completed the fatigue impact scale (FIS) were identified. Prognosis in terms of death and liver transplantation (Tx) was determined., Results: FIS values at baseline were analysed from 208 patients (192 females; median age 59 years (interquartile range 51-67), median follow-up of 5 years. Overall, 181 patients were alive at follow-up, 22 (12%) died and five (2.4%) underwent transplantation. FIS at baseline was 28 (12-47) and FIS at follow-up was 25 (8-64) (P<0.001; r=0.69). Among survivors, FIS at baseline was 27 (12-43), 36 (12-72) in those who died (P=0.059) and 99 (41-102) in those who underwent transplantation (P=0.0008). FIS at baseline was 44 (12-88) in patients with death and/or Tx vs. 27 (12-43) in survivors (P=0.003). Age [hazard ratio (HR) 1.1 (confidence interval (CI) 1.0-1.2)] and aspartate aminotransferase [HR 2.0 (CI 1.3-3.0)] were independently associated with decreased survival on multivariate analysis. FIS scores over 40 [HR 9.6 (CI 2.3-39.7)] and bilirubin [HR 4.8 (CI 2.8-8.2)] were independently associated with a poor outcome in patients who underwent Tx or had a liver-related death., Conclusions: Fatigue seems to change little over time in PBC. Fatigue levels were higher at baseline in those who died or underwent Tx. High fatigue levels seem to be a predictor of risk of liver-related mortality and need for transplantation over time but not a predictor of non-liver-related mortality.

Background/aims: Peripheral circulating endothelial cells (CEC) have been proposed as a prognostic marker in cardiovascular diseases. Cirrhosis and portal hypertension are associated with vascular injury yet little is known about CEC count in these conditions. Therefore, we evaluated CEC count in patients with cirrhosis, and correlated it with markers of portal hypertension/disease severity., Patients/methods: Fifteen patients with cirrhosis/portal hypertension and 15 matched controls were prospectively recruited for study participation. An automated rare cell analysis system was used to enumerate CEC from peripheral blood and correlated with clinical features., Results: Median CEC levels were significantly higher in patients with cirrhosis as compared with controls (median [interquartile range (IQR)]; cirrhosis: 73.7 cells/4 ml [53.7-140.3]; controls: 28.7 cells/4 ml [21-58.7]; P=0.021). Ratio of CEC to platelet count (CEC/PC) also distinguished patients with cirrhosis from controls (IQR; cirrhosis: 0.723 [0.396-1.672]; controls: 0.126 [0.103-0.333]; P<0.001). Receiver operator characteristic analysis revealed that CEC cut-off of 42 cells/4 ml showed sensitivity of 87% and specificity of 74% for differentiating cirrhosis from controls (AUC: 0.74), while CEC/PC ratio at 0.21 showed sensitivity of 100% and specificity of 73% (AUC: 0.89). Furthermore, CEC/PC index was significantly elevated in patients with hepatic decompensation as defined by Child B/C (P<0.05). The intra- and interobserver variability correlation coefficients for CEC measurement were 0.9989 and 0.9986 respectively., Conclusion: Median CEC count and CEC/PC ratio are significantly elevated in patients with cirrhosis, with CEC/PC also increased in patients with decompensated cirrhosis. These data provide rationale for larger validation studies to assess if CEC may have prognostic utility in patients with cirrhosis and portal hypertension.

Objectives: Primary biliary cirrhosis (PBC) with features consistent with autoimmune hepatitis (AIH) has been described as an overlap syndrome. Recently, a simplified AIH scoring system has been proposed by the International Autoimmune Hepatitis Group (IAIHG), which is based on only four clinical components. We aimed to evaluate the performance of the new simplified AIH scoring system as a diagnostic instrument for PBC-AIH overlap syndrome compared with the revised 1999 IAIHG criteria. Furthermore, we sought to compare the outcome in PBC patients with and without the features of AIH overlap., Methods: Retrospective analysis of PBC patients was carried out. Parameters relevant to the revised criteria were recorded, and outcomes were compared between those with and without features of overlap., Results: Of 368 patients (318 females) with a definite diagnosis of PBC, 43 (12%) were diagnosed as probable PBC-AIH overlap with the revised criteria and 23 (6%) with the simplified criteria. In both scoring systems the frequency of cirrhosis, portal hypertension, gastrointestinal (GI) bleeding, ascites, and esophageal varices was significantly higher in the overlap group at the time of follow-up. Patients with features of overlap according to the new criteria had more frequent liver-related death and liver transplantation (P=0.0025, log rank test)., Conclusions: The simplified AIH scoring system appears to be more specific in patients with PBC and could assist in clinical assessment. Worse outcome was observed in patients with overlap features, demonstrated as increased liver-related mortality with the new criteria. The new criteria should be able to replace the revised criteria for the diagnosis of PBC-AIH overlap syndrome.

The design of clinical trials in hepatocellular carcinoma (HCC) is complex because many patients have concurrent liver disease, which can confound the assessment of clinical benefit. There is an urgent need for high-quality trials in this disease. An expert panel was convened by the American Association for the Study of Liver Diseases to develop guidelines that provide a common framework for designing trials to facilitate comparability of results. According to these guidelines, randomized phase 2 trials with a time-to-event primary endpoint, such as time to progression, are pivotal in clinical research on HCC. Survival remains the main endpoint to measure effectiveness in phase 3 studies, whereas time to recurrence is proposed as an appropriate endpoint in the adjuvant setting. Because progression-free survival and disease-free survival are composite endpoints, they are more vulnerable than others in HCC clinical studies and may not be able to capture clinical benefits. Selection of the target population should be based on the Barcelona Clinic Liver Cancer staging system. New drugs should be tested in patients with well-preserved liver function (Child-Pugh A class). Patients assigned to the control arm should receive standard-of-care therapy, that is, chemoembolization for patients with intermediate-stage disease and sorafenib for patients with advanced-stage disease. Further research is needed to incorporate biomarkers and molecular imaging into clinical research in HCC. These surrogate markers may help to enrich study populations and maximize the cost-benefit ratio of trial execution. Design and conduct of phase 3 trials should be coordinated by centers with appropriate expertise in HCC.

Graft-vs.-host disease (GVHD) is a rare, serious complication of orthotopic liver transplantation (OLT). We have treated 5 patients to date with GVHD after OLT. A total of 78 patients worldwide have been reported to have experienced this complication. The means by which GVHD after OLT has been managed is guided by experience with the more common GVHD that occurs after stem cell transplantation. However, despite the use of various treatment modalities, the mortality of GVHD after OLT remains high. This case series and review of the literature demonstrates that successful resolution of GVHD after OLT cannot be expected with the use of those modalities that have been tried to date. It is imperative that new treatments be applied to GVHD after OLT in order to improve the prognosis of patients with this diagnosis., (Copyright (c) 2007 AASLD.)

Context: Medication mismanagement results in 10% of hospitalizations and 50% of therapeutic failures. Little is known about low-income patients' medication knowledge, a group disproportionately affected by chronic disease and often cared for by residents. This study assesses patients' medication knowledge, discrepancies between the patient and chart, and preferences for medication information in the training setting., Design: This cross-sectional study evaluated adults receiving care in two teaching clinics. Patients were asked their medications' names, doses, frequencies, indications, and side effects (SE) and what information they needed to take medications safely. Charts served as a medication reference standard., Results: Most patients were female, nonwhite, had > or = one chronic condition, took a median of five drugs, and saw three different residents in the same clinic. Despite six clinic visits annually, patients could cite only 50% of their medication names, frequencies, and indications, 25% of doses, and 0% of SE, yet they paradoxically responded that SE knowledge was essential for safety. Forty-three percent reported > or = one medication that was undocumented in the chart. There were 84 total discrepant medications of which 63% were prescription only., Conclusion: Low-income patients had poor medication knowledge despite good clinic access. Discontinuity of resident providers may contribute to this phenomenon. Poor global knowledge, the large discrepancy between reported and charted medications, and lack of SE knowledge threaten medication adherence, achievement of treatment goals, and patient safety.

Posterolateral dislocations involve significant injury to the medial structures of the knee, therefore particular attention should be paid to repairing the medial patella stabilizers at the time of open reduction.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the intra- and extra-hepatic bile ducts. Despite the recognition of immunological and genetic alterations cited as factors in its pathogenesis, the exact cause for PSC remains unknown. Observational cohort studies, however, have demonstrated that PSC is a progressive disease culminating in liver failure or death. Natural history assessment in PSC, however, has been complicated by variable rates of disease progression and the impact of clinical symptoms upon initial presentation. The development of mathematical models by multivariable regression techniques (most notably Cox proportional hazards regression) has allowed for an improved description of overall survival on an individual basis among patients with PSC. Additionally, these models have also been employed for determining the optimal selection and timing for liver transplantation when advanced disease is imminent., (Copyright 2001 Harcourt Publishers Ltd.)

Issues in the selection and timing of liver transplantation for primary sclerosing cholangitis (PSC) remain controversial. Although the Child-Pugh classification (CP) score and Mayo PSC model have similar abilities to estimate pretransplantation survival, a comparison of these 2 scores in predicting survival after liver transplantation has not been conducted. The aim of this study is to compare the Mayo PSC model and CP score in predicting patient survival and related economic outcomes after liver transplantation. Data from 128 patients with PSC, identified from the NIDDK database, were used to calculate patient-specific Mayo PSC and CP scores before transplantation. Levels reflecting a poor outcome were defined a priori. Receiver operating characteristic (ROC) curves and regression methods (Cox proportional hazards and linear regression models) were used to assess the relationship between these 2 scores and 5 post liver transplantation outcome measures. CP score was found to be a significantly (P <.05) better predictor of death 4 months or less after liver transplantation than: (a) length of hospital stay >21 days (or death before discharge) and (b) resource utilization >200,000 units (measured by area under the ROC curve). The Cox model identified statistically significant (P <.05) associations between CP score and each outcome after adjusting for the Mayo PSC risk score. Similar results were not observed for the Mayo PSC model when adjusted for CP score. Among patients with PSC undergoing liver transplantation, CP score was a better overall predictor of both survival and economic resource utilization compared with the Mayo PSC model.

We describe a case of prolonged cholestasis temporally associated with the use of itraconazole for onychomycosis. Peak bilirubin level of 32.0 mg/dl was documented approximately 2 months after discontinuation of the patient's itraconazole therapy, with symptoms of cholestasis persisting more than 1 month after the peak in bilirubin. Physicians should be aware of the potential for severe cholestasis associated with itraconazole usage.