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Goals To develop an encounter decision aid [Barrett's esophagus Choice (BE-Choice)] for patients and clinicians to engage in shared decision making (SDM) for management of BE with low-grade dysplasia (BE-LGD) and assess its impact on patient-important outcomes. Background Currently, there are 2 strategies for management of BE-LGD-endoscopic surveillance and ablation. SDM can help patients decide on their preferred management option. Study Phase-I: Patients and clinicians were engaged in a user-centered design approach to develop BE-Choice. Phase-I included review of evidence on BE-LGD management, observation of usual care (UC), creation, field-testing, and iterative development of BE-Choice in clinical settings. Phase-II: Impact of BE-Choice on patient-important outcomes (patient knowledge, decisional conflict, and patient involvement in decision making) was assessed using a controlled before-after study design (UC vs. BE-Choice). Results Phase-I: Initial prototype was designed with observation of 8 clinical encounters. With field-testing, 3 successive iterations were made before finalizing BE-Choice. BE-Choice was paper based and fulfilled the qualifying criteria of International patient decision aid standards. Phase II: 29 patients were enrolled, 8 to UC and 21 to BE-Choice. Compared with UC, use of BE-Choice improved patient knowledge (90.4% vs. 70.5%; P=0.03), decisional comfort (89.6 vs. 71.9; P=0.01), and patient involvement (OPTION score: 27.1 vs. 19.2; P=0.01). Conclusions BE-Choice is a feasible and effective decision aid to promote SDM in the management of BE-LGD. On pilot testing, BE-Choice had promising impact on patient-important outcomes. A larger multicenter trial is needed to confirm our results and promote widespread use of BE-Choice.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing. The health care burden resulting from the multidisciplinary management of this complex disease is unknown. We assessed the total health care cost and resource utilization associated with a new NAFLD diagnosis, compared with controls with similar comorbidities. We used OptumLabs Data Warehouse, a large national administrative claims database with longitudinal health data of over 100 million individuals enrolled in private and Medicare Advantage health plans. We identified 152,064 adults with a first claim for NAFLD between 2010 and 2014, of which 108,420 were matched 1:1 by age, sex, metabolic comorbidities, length of follow-up, year of diagnosis, race, geographic region, and insurance type to non-NAFLD contemporary controls from the OptumLabs Data Warehouse database. Median follow-up time was 2.6 (range 1-6.5) years. The final study cohort consisted of 216,840 people with median age 55 (range 18-86) years, 53% female, 78% white. The total annual cost of care per NAFLD patient with private insurance was $7,804 (interquartile range [IQR] $3,068-$18,688) for a new diagnosis and $3,789 (IQR $1,176-$10,539) for long-term management. These costs are significantly higher than the total annual costs of $2,298 (IQR $681-$6,580) per matched control with similar metabolic comorbidities but without NAFLD. The largest increases in health care utilization that may account for the increased costs in NAFLD compared with controls are represented by liver biopsies (relative risk [RR] = 55.00, 95% confidence interval [CI] 24.48-123.59), imaging (RR = 3.95, 95% CI 3.77-4.15), and hospitalizations (RR = 1.87, 95% CI 1.73-2.02). Conclusion: The costs associated with the care for NAFLD independent of its metabolic comorbidities are very high, especially at first diagnosis. Research efforts shouldfocus on identification of underlying determinants of use, sources of excess cost, and development of cost-effective diagnostic tests.

BACKGROUND AND AIM Optimal rectal cancer (RC) outcomes depend on accurate locoregional staging. The study sought to describe the impact of endoscopic ultrasound (EUS) on RC treatment patterns and survival. METHODS Using the Surveillance, Epidemiology, and End Results-Medicare database, the study identified patients with RC between 2005 and 2007. The study excluded patients with stage IV disease, those not enrolled in Medicare parts A and B, those enrolled in managed care, and those staged with pelvic magnetic resonance imaging (because of low numbers). The study then compared outcomes between patients who received EUS and computed tomography of the abdomen and pelvis (CTAP) to those staged with CTAP alone after propensity score matching. RESULTS Between 2005 and 2007, we identified 3,408 nonmetastatic RC patients. Compared with patients staged with CTAP alone, those who received EUS and CTAP were younger (median age: 75 vs 76 years, P

We examined risks for first hospitalization and the rate, risk factors, costs, and 1-year outcome of 30-day readmission among patients admitted for complications of cirrhosis. Data were retrospectively analyzed for adult patients with cirrhosis residing in Minnesota, Iowa, or Wisconsin and admitted from 2010 through 2013 at both campuses of the Mayo Clinic Hospital in Rochester, MN. Readmission was captured at the two hospitals as well as at community hospitals in the tristate area within the Mayo Clinic Health System. The incidence of hospitalization for complications of cirrhosis was 100/100,000 population, with increasing age and male sex being the strongest risks for hospitalization. For the 2,048 hospitalized study patients, the overall 30-day readmission rate was 32%; 498 (24.3%) patients were readmitted to Mayo Clinic hospitals and 157 (7.7%) to community hospitals, mainly for complications of portal hypertension (52%) and infections (30%). Readmission could not be predicted accurately. There were 146 deaths during readmission and an additional 105 deaths up to 1 year of follow-up (50.4% total mortality). Annual postindex hospitalization costs for those with a 30-day readmission were substantially higher ($73,252) than those readmitted beyond 30 days ($62,053) or those not readmitted ($5,719). At 1-year follow-up, only 20.4% of patients readmitted within 30 days were at home. In conclusion, patients with cirrhosis have high rates of hospitalization, especially among men over 65 years, and of unscheduled 30-day readmission. Readmission cannot be accurately predicted. Postindex hospitalization costs are high; nationally, the annual costs are estimated to be more than $4.45 billion. Only 20% of patients readmitted within 30 days are home at 1 year. (Hepatology Communications 2018;2:188-198).

Purpose To evaluate the diagnostic performance and examination success rate of magnetic resonance (MR) elastography and vibration-controlled transient elastography (VCTE) in the detection of hepatic fibrosis in patients with severe to morbid obesity. Materials and Methods This prospective and HIPAA-compliant study was approved by the institutional review board. A total of 111 patients (71 women, 40 men) participated. Written informed consent was obtained from all patients. Patients underwent MR elastography with two readers and VCTE with three observers to acquire liver stiffness measurements for liver fibrosis assessment. The results were compared with those from liver biopsy. Each pathology specimen was evaluated by two hepatopathologists according to the METAVIR scoring system or Brunt classification when appropriate. All imaging observers were blinded to the biopsy results, and all hepatopathologists were blinded to the imaging results. Examination success rate, interobserver agreement, and diagnostic accuracy for fibrosis detection were assessed. Results In this obese patient population (mean body mass index = 40.3 kg/m2; 95% confidence interval [CI]: 38.7 kg/m2, 41.8 kg/m2]), the examination success rate was 95.8% (92 of 96 patients) for MR elastography and 81.3% (78 of 96 patients) or 88.5% (85 of 96 patients) for VCTE. Interobserver agreement was higher with MR elastography than with biopsy (intraclass correlation coefficient, 0.95 vs 0.89). In patients with successful MR elastography and VCTE examinations (excluding unreliable VCTE examinations), both MR elastography and VCTE had excellent diagnostic accuracy in the detection of clinically significant hepatic fibrosis (stage F2-F4) (mean area under the curve: 0.93 [95% CI: 0.85, 0.97] vs 0.91 [95% CI: 0.83, 0.96]; P = .551). Conclusion In this obese patient population, both MR elastography and VCTE had excellent diagnostic performance for assessing hepatic fibrosis; MR elastography was more technically reliable than VCTE and had a higher interobserver agreement than liver biopsy. © RSNA, 2016 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on January 25, 2017.

Background: Gastrointestinal tract cancers account for a significant proportion of the national cancer burden. Aim: We sought to explore patient- and hospital-level determinants of palliative care utilization among patients hospitalized with metastatic gastrointestinal tract cancers using a national database. Methods: An analysis of the 2012 National Inpatient Sample was performed. International Classification of Diseases, Ninth Revision codes were used to identify hospital discharges associated with metastatic digestive tract cancers and patient/hospital covariates for inclusion in a logistic regression model. Total charges and length of stay were analyzed in a linear regression model. Results: Compared to males, females were more likely to receive inpatient palliative care (adjusted odds ratio [OR] 1.12, P = .002). No difference was seen between white and Asian patients (adjusted OR 1.2, P = .11) or Native Americans patients (adjusted OR 1.4, P = .22). However, relative to white patients, African Americans (adjusted OR 1.13, P = .02) and Hispanics (adjusted OR 1.25, P = .001) had significantly higher odds of inpatient palliative care. Medicare patients were least likely to receive palliative care compared to those with Medicaid or commercial payers. Length of stay during these hospitalizations was longer in African Americans ( P = .0001), Asians ( P = .0001), and Native Americans ( P = .03) compared to white patients. No difference was seen when total charges were compared between white and African American patients ( P = .08). Conversely, total charges were higher in Hispanics ( P = .005) and Asians ( P = .001) relative to white patients. Conclusion: Gender and racial differences exist in utilization of inpatient palliative care among patients hospitalized with metastatic gastrointestinal tract cancers.

After the Patient Protection and Affordable Care Act or "Obamacare" was signed into law in 2010, the problem of readmission has taken on a new sense of urgency. Hospitals with excess readmissions receive reduced reimbursement because readmission is considered to represent a poor quality measure in the healthcare delivery system. Cirrhosis places a major burden on the healthcare economy. Patients with cirrhosis frequently require hospitalization, and annual admission rates have doubled within 10 years. The costs of hospitalization associated with cirrhosis have also markedly increased. Readmissions create negative consequences for the patient and the family. Several strategies have been proposed to reduce the number of readmissions, but the efficacy of these strategies is questionable. Although the Model for End-Stage of Liver Disease (MELD) score can be a tool for risk stratification, many other factors are also independent risks for readmission. Studies aimed at the reduction of readmission in patients with cirrhosis are very limited, and much research is required before specific recommendations can be made to reduce readmissions.

We sought to characterize the relationship between hospital inpatient racial diversity and outcomes for African-American patients including rates of major complications or mortality during hospitalization for five common gastrointestinal diagnoses.Using the 2012 National Inpatient Sample database, hospital inpatient racial diversity was defined as the percentage of African-American patients discharged from each hospital. Logistic regression was used to predict major complication rates or death, long length of stay, and high total charges. Control variables included age, gender, payer type, patient location, area-associated income quartile, hospital characteristics including size, urban vs. rural, teaching vs. nonteaching, region, and the interaction of the percentage of African Americans with patient race.There were 848,395 discharges across 3,392 hospitals. The patient population was on average 27% minority (s.d.±21%) with African Americans accounting for 14% of all patients. Overall, African-American patients had higher rates of major complications or death relative to white patients (adjusted odds ratio (aOR) 1.19; 95% confidence interval (CI) 1.16-1.23). However, when treated in hospitals with higher patient racial diversity, African-American patients experienced significantly lower rates of major complications or mortality (aOR 0.80; 95% CI 0.74-0.86).African Americans have better outcomes for five common gastrointestinal diagnoses when treated in hospitals with higher inpatient racial diversity. This has major ramifications on total hospital charges.

Patients with cirrhosis are at risk for several complications that require readmission. Readmissions are a direct burden on the patient and the family and are associated with negative outcomes to the patient, family, and health care system. Several recent studies have shown a high rate of readmission in patients with cirrhosis and a trend towards an increase in cost of health care delivery. Physicians and hospitals should recognize the patient at high risk for readmission not only at dismissal from hospital but also at admission. The Model for End-Stage Liver Disease (MELD) score may be used as a tool for risk stratification for readmission among patient with cirrhosis. Frailty, comorbidity, socioeconomic status, and type of health care delivery system are probable independent risk factors. Strategies to prevent readmission should target the high-risk patient.

Secondary analysis of large datasets involves the utilization of existing data that has typically been collected for other purposes to advance scientific knowledge. This is an established methodology applied in health services research with the unique advantage of efficiently identifying relationships between predictor and outcome variables but which has been underutilized for hepatology research. Our review of 1431 abstracts published in the 2013 European Association for the Study of Liver (EASL) abstract book showed that less than 0.5% of published abstracts utilized secondary analysis of large database methodologies. This review paper describes existing large datasets that can be exploited for secondary analyses in liver disease research. It also suggests potential questions that could be addressed using these data warehouses and highlights the strengths and limitations of each dataset as described by authors that have previously used them. The overall goal is to bring these datasets to the attention of readers and ultimately encourage the consideration of secondary analysis of large database methodologies for the advancement of hepatology.

Antimitochondrial antibodies (AMA) are a sensitive and specific marker for primary biliary cirrhosis (PBC). AMAs are present in 95% of patients with PBC. However, 5% do not have AMAs and data on these patients is scarce. We aim to evaluate the long-term outcomes of patients with AMA negative PBC.A retrospective chart review of 71 AMA negative PBC patients. Disease presentation, laboratory results, and clinical endpoints were recorded. AMA negative patients were matched on year of diagnosis to a control group of 71 AMA positive patients.Ninety-six percent of the AMA negative patients were of female gender with a median age at diagnosis of 55 years and a length of follow-up of 7.5 years vs. 86% females, a median age of 56 and a follow-up of 8.3 years in the control group. Mean total bilirubin and alkaline phosphatase levels were 0.7 mg/dL vs. 0.6 and 570 U/L vs 341, in AMA negative vs. AMA positive patients at presentation, respectively (p = NS). AMA negative patients did not differ in terms of age, serum IgM levels, ANA status, or length of follow-up. Notably, AMA negative patients had a significantly reduced survival free of liver-related complications including transplantation and death compared to AMA positive patients (p = 0.0182).In this large experience, AMA negative PBC patients had a significantly worse prognosis compared to AMA positive PBC patients. The reason for the difference in prognosis is unclear, as it may be true difference or reflect delays in case detection among AMA negative patients.

Colorectal stents are increasingly employed as a bridge to surgery or for palliative relief of malignant large bowel obstruction.To explore determinants of inpatient colorectal stent utilization (CRSU).An analysis of the 2012 National Inpatient Sample was performed. International Classification of Diseases, 9th revision, codes were used to identify discharges associated with CRSU and patient/hospital factors for inclusion in a logistic regression model.We identified 217,055 inpatient colonoscopies, approximating 1.1 million inpatient colonoscopies nationwide. Colorectal stents were placed in 1.4 % of all procedures. Across all racial groups, Medicare was the most common payer. Patients with commercial insurance had lower CRSU compared with Medicare patients [adjusted odds ratio (OR) 0.83, 95 % confidence interval (CI) 0.75-0.92]. No gender disparities were identified (OR 0.96, 95 % CI 0.89-1.03). In addition, no racial differences in CRSU existed between Caucasians versus African-Americans (OR 0.94, 95 % CI 0.83-1.06) and Caucasians versus Hispanics (OR 0.96, 95 % CI 0.83-1.1). Compared with patients living in less affluent neighborhoods, those residing in more affluent areas had higher CRSU (OR 1.65, 95 % CI 1.46-1.86). This displayed a linear relationship with the odds of CRSU increasing as household income increased. Less affluent patients also had the highest total charges and longest wait time to CRSU. CRSU was highest among patients treated in larger medical centers (OR 1.7, 95 % CI 1.51-1.93) and teaching hospitals (OR 3.9, 95 % CI 3.2-4.8).Individuals from less affluent neighborhoods have lower colorectal stent utilization. This disparity is independent of race and likely related to poorer access to healthcare resources.

In a population-based study, we examined time trends in chronic liver disease (CLD)-related hospitalizations in a large and diverse metroplex. 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). 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%). 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.

Elastography evaluates the intrinsic mechanical viscoelastic properties of liver parenchyma and allow for estimation of liver stiffness (LS), whereby elevated stiffness is associated with presence of advanced fibrosis. Measurement of liver stiffness by magnetic resonance elastography (MRE) has been tested for staging of liver disease in a variety of patients, providing convincing data especially among those with non-alcoholic fatty liver disease. Beyond diagnosis, non-invasive measures may have a prognostic role. Measurement of LS by MRE may serve as a complementary tool to monitor progression of disease. However, clinical algorithms are needed whereby MRE and other non-invasive markers can seamlessly be incorporated in care of patients with CLD, keeping in mind the cost, accessibility and incremental clinical utility offered above and beyond that which may be gained by simple bedside clinical assessment.

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.

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.

Approximately half the US adult population consumes herbals and dietary supplements (HDS),(1,2) with recent reports showing their use to be increasing.(3,4) Supplement users are more commonly women, non-Hispanic whites, over age 40, and have higher levels of education than non-users.(4-7) NHANES III data indicate that multivitamins and minerals are the most common supplements used, followed by calcium and fish oils.(5) However, the range of HDS is far broader and includes numerous commercial products. Although dietary supplements are perceived as safe (8), the current regulatory framework established by the Dietary Supplement Health and Education Act of 1994 (9) requires less evidence of safety prior to marketing as assessed by the Food and Drug Administration (FDA) than is required for pharmaceuticals. The FDA and other regulatory bodies can take action against a manufacturer only if there is proven adulteration or injury from its supplement. Recent cases of life-threatening hepatotoxicity from the dietary supplement OxyElite Pro (10) underscore the potential adverse consequences of this oversight process. The Drug-Induced Liver Injury Network (DILIN), supported by the National Institutes of Diabetes and Digestive and Kidney Diseases, was established in 2003 to identify, enroll, and characterize cases of drug-induced liver injury attributable to medications (excluding acetaminophen) and HDS (ClinicalTrials.gov Identifier:NCT00345930).(11) The original DILIN report identified HDS as the second most common cause for liver injury. (12) Since that report, many more cases have been accrued by the DILIN. Thus, we examined the burden and characteristics of liver injury attributable to HDS in the DILIN, and compared this injury with that due to conventional medications.

Background & Aims Non-invasive predictors identifying subjects with compensated liver disease at highest risk for transitioning to a decompensated state are lacking. We hypothesized that liver shear stiffness as measured by magnetic resonance elastography is an important non-invasive predictor of hepatic decompensation. Methods Among patients with advanced fibrosis undergoing magnetic resonance elastography (2007–2011), a baseline cohort and follow up cohort (compensated liver disease) were established. Cause specific cox proportional hazards analysis adjusting for competing risks was utilized to determine the association between elevated liver shear stiffness and development of decompensation (hepatic encephalopathy, ascites, variceal bleeding). Results In the baseline cohort (n=430), subjects with decompensated liver disease had a significantly higher mean liver shear stiffness (6.8kPa, IQR 4.9–8.5) as compared to subjects with compensated liver disease (5.2kPa, IQR 4.1–6.8). After adjustment for Model for End Stage Liver Disease score, hepatitis C, age, gender, albumin, and platelet count, the mean liver shear stiffness (OR=1.13, 95% CI 1.03–1.27) was independently associated with decompensated cirrhosis at baseline. Over a median follow up of 27months (n=167), 7.2% of subjects with compensated disease experienced hepatic decompensation. In the follow up cohort, the hazard of hepatic decompensation was 1.42 (95% CI 1.16–1.75) per unit increase in liver shear stiffness over time. The hazard of hepatic decompensation was 4.96 (95% CI 1.4–17.0, p =0.019) for a subject with compensated disease and mean LSS value ⩾5.8kPa as compared to an individual with compensated disease and lower mean LSS values. Conclusion Baseline liver shear stiffness assessed by magnetic resonance elastography is independently associated with decompensated liver disease.

The care of the patient with cholestasis hinges on identifying the etiology, treating reversible causes, and managing chronic cholestatic processes. PBC and PSC are important causes of chronic cholestasis, and are the most common causes of cholestatic liver disease. Effective therapy is available for patients with PBC, whereas none exists for patients with PSC. Awareness of the complications that may be associated with cholestasis and implementing the appropriate management are essential.

Drug-induced liver injury (DILI) is considered to be a diagnosis of exclusion. Liver biopsy may contribute to diagnostic accuracy, but the histological features of DILI and their relationship to biochemical parameters and outcomes are not well defined. We have classified the pathological pattern of liver injury and systematically evaluated histological changes in liver biopsies obtained from 249 patients with suspected DILI enrolled in the prospective, observational study conducted by the Drug Induced Liver Injury Network. Histological features were analyzed for their frequency within different clinical phenotypes of liver injury and to identify associations between clinical and laboratory findings and histological features. The most common histological patterns were acute (21%) and chronic hepatitis (14%), acute (9%) and chronic cholestasis (10%), and cholestatic hepatitis (29%). Liver histology from 128 patients presenting with hepatocellular injury had more severe inflammation, necrosis, and apoptosis and more frequently demonstrated lobular disarray, rosette formation, and hemorrhage than those with cholestasis. Conversely, histology of the 73 patients with cholestatic injury more often demonstrated bile plugs and duct paucity. Severe or fatal hepatic injury in 46 patients was associated with higher degrees of necrosis, fibrosis stage, microvesicular steatosis, and ductular reaction among other findings, whereas eosinophils and granulomas were found more often in those with milder injury. Conclusion: We describe an approach for evaluating liver histology in DILI and demonstrate numerous associations between pathological findings and clinical presentations that may serve as a foundation for future studies correlating DILI pathology with its causality and outcome. (Hepatology 2014;59:661–670)

Patients with primary sclerosing cholangitis (PSC) and associated inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC). We estimated the pooled incidence of CRC after liver transplantation (LT) in patients with PSC as well as in a subset of patients with associated IBD (PSC-IBD). Through a systematic review of major bibliographic databases up to April 1, 2013, we identified cohort studies reporting the incidence of de novo CRC after LT for PSC. The main outcome measure was CRC incidence rate (IR) per 1000 person-years after LT in all patients with PSC and in a subset of patients with PSC-IBD with an intact colon. According to a meta-analysis of 18 independent cohorts (69 cases of CRC among 1987 patients), the pooled IR of de novo CRC in patients with PSC after LT was 5.8 per 1000 person-years [95% confidence interval (CI) = 3.8-7.8]. According to a meta-analysis of 16 independent cohort studies (66 cases of CRC among 1017 patients), the IR of CRC in patients with PSC-IBD and an intact colon at the time of LT was 13.5 per 1000 person-years (95% CI = 8.7-18.2). A long duration of IBD and extensive colitis were identified as risk factors for CRC. Specific transplant-related factors that can increase the risk of CRC have not been identified. In conclusion, the risk of CRC remains high for patients who undergo LT for PSC, particularly in the subset of patients with associated IBD and an intact colon at the time of LT. Aggressive colonoscopic surveillance for CRC would be prudent for patients with PSC-IBD even after LT.

The American Association for the Study of Liver Diseases (AASLD) practice guidelines provide recommendations in diagnosing and managing patients with liver disease from available scientific evidence in combination with expert consensus opinions. The aim was to systematically review the evolution of recommendations from AASLD guidelines and identify gaps limiting the evidence-based foundations of these guidelines. Initial and current AASLD guidelines published from January 1998 to August 2012 were reviewed. The AGREE II instrument was used to evaluate rigor and transparency of guideline development. The number of recommendations, distribution of grades (strength or certainty), classes (benefit versus risk), and types of recommendations were evaluated. Whenever possible, multiple versions were evaluated for evolving scientific evidence. A total of 991 recommendations from 28 guidelines on 17 topics were evaluated. From initial to current guidelines, the total number of recommendations increased by 36% (512 to 699). The largest increases were from chronic hepatitis B virus (HBV) (+71), liver transplantation (+53), and autoimmune hepatitis (AIH) (+27). Most current recommendations are grade II (44%) and less than 20% are grade I. The AGREE II evaluation showed global improvement in guideline quality. Both HBV and chronic hepatitis C guidelines had greatest increases in grade I recommendations (+383% and +67%, respectively). The greatest increases in treatment recommendations were from HBV (grade I, +1,150%), liver transplantation (grade II, +112%), and AIH (grade III, +105%). Conclusion: Despite significant increases in the numbers of recommendations within AASLD practice guidelines over time, only a minority are supported by grade I evidence, highlighting the need for developing well-designed investigations to provide evidence for areas of uncertainty and improving the quality of future guidelines in hepatobiliary diseases. (Hepatology 2013; 58:2142–2152)

The course of inflammatory bowel disease (IBD) after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is complex, with several IBD-, PSC-, and transplant-related factors interplaying with each other. Approximately one-third of patients with known IBD improve, and one-third paradoxically worsen, after LT for PSC. Active IBD, discontinuation of 5-aminosalicylates (5-ASA) at time of LT and tacrolimus-based immunosuppression may be associated with an unfavorable course of IBD after LT. Approximately 14-30% patients with PSC may develop de novo IBD 10 years after LT. LT confers a high risk of pouchitis after ileal pouch-anal anastomosis, although it may not be higher than baseline rates for PSC patients. The risk of colorectal cancer continues to be high after LT for PSC, and is higher in this cohort of patients with PSC-IBD, compared with patients undergoing LT for other indications. IBD does not adversely affect patient survival after LT, although the risk of recurrent PSC in the allograft may be higher in patients with IBD and an intact colon at time of LT. Standard therapy with 5-ASA and/or azathioprine may be appropriate for treatment of active IBD after LT and maintenance of remission. Anti-tumor necrosis factor-α agents are effective, but should be used with caution because of high risk of adverse events. The management of IBD after LT requires close coordination between transplant hepatologists and IBD experts.

BACKGROUND Patients diagnosed with primary sclerosing cholangitis (PSC) and dominant strictures often undergo endoscopic retrograde cholangiopancreatography with brush cytology to exclude or confirm the development of malignancy. Equivocal (atypical or suspicious) routine cytologic results may confound patient management decisions, especially in the absence of a mass on imaging. The objective of the current study was to identify independent predictors of malignancy in patients with PSC with an equivocal cytology diagnosis. METHODS Patients with PSC underwent brush cytology for routine cytology and fluorescence in situ hybridization (FISH) during endoscopy as per standard care. FISH slides were classified as polysomy if at least 5 cells displayed a gain of ≥ 2 probes. A retrospective search identified 102 patients without a mass lesion noted on initial imaging studies, an equivocal routine cytology, and ≥ 2 years of follow-up. RESULTS Of 102 patients, 30 (29%) with an equivocal cytology result developed cancer within 2 years. Serum carbohydrate antigen 19-9 (CA 19-9) levels ≥ 129 U/mL (hazard ratio [HR] 3.19; P = .001) and polysomy (HR 8.70; P

Secondary sclerosing cholangitis (SSC) is an aggressive and rare disease with intricate pathogenesis and multiple causes. Understanding the specific cause underlying each case of SSC is crucial in the clinical management of the disease. Radiologic imaging can help diagnose SSC and hence institute management in a timely manner. Management may encompass simple interventions, such as supportive therapy, antibiotics, and monitoring, or more serious measures, such as surgery, endoscopic intervention, or liver transplantation. Patients with AIDS cholangiopathy have limited therapeutic options and worsened survival. The disease should always be highly suspected in patients with primary sclerosing cholangitis with questionable diagnosis.

Purpose To investigate the influence of portal pressure on the shear stiffness of the liver and spleen in a well-controlled in vivo porcine model with MR Elastography (MRE). A significant correlation between portal pressure and tissue stiffness could be used to noninvasively assess increased portal venous pressure (portal hypertension), which is a frequent clinical condition caused by cirrhosis of the liver and is responsible for the development of many lethal complications.

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. J. Magn. Reson. Imaging 2013;38:371–379. © 2013 Wiley Periodicals, Inc.

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

A number of new hepatitis C virus (HCV) medications have become available in the United States, but little is known about how these treatments have been adopted into practice and their financial burden on patients. The aim of this study was to examine whether the introduction of new HCV medications was associated with changes in treatment rates and out-of-pocket (OOP) costs.Retrospective analysis of administrative claims data from Optum Labs Data Warehouse.We performed a retrospective analysis using a large, US commercial insurance database to identify 56,116 adults with chronic HCV between January 1, 2010, and December 31, 2014. Logistic regression was performed to calculate patients' predicted probability of being treated before and after the new medications became available.A total of 5436 (9.7%) of patients with HCV received treatment during an average of 1.8 years of follow-up. In the last quarter of 2014, 0.1% of patients with HCV received interferon/ribavirin as the primary treatment; no one received boceprevir or telaprevir, 1.1% received sofosbuvir combined with simeprevir, 1.4% received sofosbuvir or simeprevir alone, and 2.0% received ledipasvir/sofosbuvir. The introduction of new medications was significantly associated with an increased treatment rate, from 5.4% to 6.8% (P.001). The increase was high among elderly patients and patients with liver transplant, liver cancer, and liver disease or cirrhosis. The median OOP costs of patients receiving new regimens were relatively low ($112-$340), but great variations existed.At the end of 2014, patients were almost exclusively using new therapies, which was associated with increased treatment rate, especially among patients who may need urgent treatment but are intolerant or ineligible for interferon-based regimens.

© 2015, European Society of Radiology. Objectives: We conducted an individual participant data (IPD) pooled analysis on diagnostic accuracy of MRE to detect fibrosis stage in patients with non-alcoholic fatty liver disease (NAFLD). Methods: Through a systematic literature search, we identified studies of MRE (at 60–62.5 Hz) for staging fibrosis in patients with NAFLD, using liver biopsy as gold standard, and contacted study authors for IPD. Through pooled analysis, we calculated the cluster-adjusted AUROC, sensitivity and specificity of MRE for any (≥stage 1), significant (≥stage 2) and advanced (≥stage 3) fibrosis and cirrhosis (stage 4). Results: We included nine studies with 232 patients with NAFLD (mean age, 51 ± 13 years; 37.5 % males; mean BMI, 33.5 ± 6.7 kg/m2; interval between MRE and biopsy

United States health care is moving rapidly from volume- to value-based reimbursement. An essential part of this movement will be the development of alternative payment models where a specific bundle of care (colonoscopy), episode of care (a year of care for attributed Crohn’s patients), or ongoing care of a specialty-centric patient population (patients with cirrhosis) are covered within a contract that links health outcomes, quality of care, and payment together. Gastroenterologists are slowly becoming aware of these concepts. Primary care has its patient-centered medical home and now specialists have a patient-centric specialty practice where patient populations are cared for principally by a specialty practice within a well-defined care delivery structure. Previous Road Ahead columns have illustrated these concepts, and this month, Meier and colleagues provide an excellent definition and example of how practices can participate in this new world order.

In the context of clinical medicine, risk stratification is defined as a statistical process to identify detectable characteristics associated with an increased chance of experiencing unwanted clinical outcomes. Over the past two decades, a number of risk stratification models have been created to identify groups of patients at who are likely to develop complications of portal hypertension. The majority of risk models to date use multivariable regression risk score profile approaches to assess the risk for complications such as the formation of esophageal varices, time to decompensation, and death. Emerging techniques to assess established criteria such as validation, discrimination, and calibration have improved our ability to assess the accuracy of new risk models. In addition, a greater understanding of competing risks on predicted outcomes and the economic implications of risk stratification is beginning to influence current work in this area. Future developments in risk stratification for portal hypertension are expected to emphasize greater activity in risk score development and to validate algorithms with prospective study designs including randomized trials.

Clinical Scenario A old woman is referred to you for recently identified serum aminotransferase elevations after presenting ith generalized arthralgias and a sense of malaise. Blood test esults include aspartate aminotransferase (AST) of 386 U/L normal, 12– 45 U/L) and alanine aminotransferase (ALT) of 10 U/L (normal, 9 –50 U/L). The alkaline phosphatase level is ildly elevated at 186 U/L (normal, 80 –115 U/L), and the total ilirubin is 0.8 mg/dL (normal, 0.1–1 mg/dL). Additional labratory work revealed negative serologic markers for hepatitis , B, and C. Serum autoantibodies were performed and inluded antinuclear antibody (ANA) of 1:80, positive antimooth muscle antibody (SMA) of 1:40, gamma-globulin level f 3.2 g/dL (normal, 0.8 –1.5 g/dL), negative antimitochondrial ntibody, and negative anti-liver/kidney microsomal (antiKM) antibody titer. There is no history of alcohol use, and the atient uses no hepatotoxic medications. Cross-sectional imaging of the abdomen revealed mild coarsning of the hepatic echotexture without evidence of a hepatic ass, splenomegaly, or lymphadenopathy. A liver biopsy was erformed. Histopathology interpretation revealed moderately ctive interface hepatitis with lobular hepatitis and portalridging necrosis. No significant fibrosis was identified. There ere no biliary lesions or granulomas noted.

Clinical trial design is one of the most important aspects of advancing therapeutic interventions in the management of chronic liver diseases. Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of uncertain etiology and pathogenesis. The natural history of PSC is often assessed through a variety of clinical and histological end points. However, none of the therapeutic options examined in clinical trials for PSC to date has demonstrated benefit in halting or slowing disease progression. Furthermore, the emerging recognition of several subtypes in PSC, coupled with limitations in histological and cholangiographic staging, makes subject stratification and trial design challenging. This article will review approaches that have been used for designing clinical trials for assessing potential therapies for PSC as well as provide recommendations on future clinical trials design and explore the potential use of novel surrogate end points that may improve patient selection and treatment eff...

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.

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.

Introduction: Hepatic magnetic resonance elastography (MRE) allows for noninvasive assessment of liver fibrosis. The purpose of this study was to evaluate the usefulness of MRE in detecting and quantifying liver fibrosis in patients with rheumatoid arthritis (RA) who have received methotrexate (MTX). Methods: The association between mean liver stiffness value as determined by MRE and variables of interest was determined. The decision for a liver biopsy in participants with an abnormal liver stiffness was made based on clinical judgment. Results: Sixty-five RA patients were enrolled. Mean liver stiffness value by MRE was abnormal in 7 patients, suggestive of hepatic injury. As a result of findings from the MRE, biopsies were performed in 5 patients and all correlated with elevated liver stiffness values. Elevated mean liver stiffness values were associated with body mass index (BMI) (OR = 1.18 per 1 kg/m2; 95% CI: 1.03, 1.36; p = 0.017). Neither the total MTX dose nor the duration of MTX treatment was associated with mean liver stiffness value (p = 0.51 and P = 0.20, respectively). Conclusion: MRE provides a reliable, non-invasive assessment of liver fibrosis in patients with RA receiving MTX. Patients with RA receiving MTX who have an elevated BMI may be at increased risk for chronic hepatic injury, regardless of MTX cumulative dose or duration of treatment.

Purpose To conduct a rigorous evaluation of the repeatability of liver stiffness assessed by magnetic resonance elastography (MRE) in healthy and hepatitis-C infected subjects.

OBJECTIVE To create a cohort for cost-effective genetic research, the Mayo Genome Consortia (MayoGC) has been assembled with participants from research studies across Mayo Clinic with high-throughput genetic data and electronic medical record (EMR) data for phenotype extraction. PARTICIPANTS AND METHODS Eligible participants include those who gave general research consent in the contributing studies to share high-throughput genotyping data with other investigators. Herein, we describe the design of the MayoGC, including the current participating cohorts, expansion efforts, data processing, and study management and organization. A genome-wide association study to identify genetic variants associated with total bilirubin levels was conducted to test the genetic research capability of the MayoGC. RESULTS Genome-wide significant results were observed on 2q37 (top single nucleotide polymorphism, rs4148325; P =5.0 × 10 −62 ) and 12p12 (top single nucleotide polymorphism, rs4363657; P =5.1 × 10 −8 ) corresponding to a gene cluster of uridine 5′-diphospho-glucuronosyltransferases (the UGT1A cluster ) and solute carrier organic anion transporter family, member 1B1 ( SLCO1B1 ), respectively. CONCLUSION Genome-wide association studies have identified genetic variants associated with numerous phenotypes but have been historically limited by inadequate sample size due to costly genotyping and phenotyping. Large consortia with harmonized genotype data have been assembled to attain sufficient statistical power, but phenotyping remains a rate-limiting factor in gene discovery research efforts. The EMR consists of an abundance of phenotype data that can be extracted in a relatively quick and systematic manner. The MayoGC provides a model of a unique collaborative effort in the environment of a common EMR for the investigation of genetic determinants of diseases.