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Patients are prioritized for liver transplantation (LT) under an "urgency-based" system using the Model for End-Stage Liver Disease score. This system focuses solely on waitlist mortality, without considerations of posttransplant morbidity, mortality, and health care use. We sought to develop and internally validate a continuous posttransplant risk score during 5-year and 10-year time horizons. This retrospective cohort study used national registry data of adult deceased donor LT (DDLT) recipients with ≥90 days of pretransplant waiting time from February 27, 2002 to December 31, 2018. We fit Cox regression models at 5 and 10 years to estimate beta coefficients for a risk score using manual variable selection and calculated the absolute predicted survival time. Among 21,103 adult DDLT recipients, 11 variables were selected for the final model. The area under the curves at 5 and 10 years were 0.63 (95% confidence interval [CI], 0.60-0.66) and 0.67 (95% CI, 0.64-0.70), respectively. The group with the highest ("best") scores had 5-year and 10-year survivals of 89.4% and 85.4%, respectively, compared with 45.9% and 22.2% for those with the lowest ("worst") scores. Our score was significantly better at predicting long-term survival compared with the existing scores. We developed and validated a risk score using nearly 17 years of data to prioritize patients with end-stage liver disease based on projected posttransplant survival. This score can serve as the building block by which the transplant field can change the entire approach to prioritizing patients to an approach that is based on considerations of maximizing benefits (ie, survival benefit-based allocation) rather than simply waitlist mortality.

Colorectal cancer (CRC) screening is underused in the US. Tailored message interventions have shown benefit for increasing screening uptake of mammography and Papanicolaou testing, but their role in CRC screening is less clear.To evaluate the effectiveness of a tailored message telephone intervention prior to scheduling of a screening or surveillance colonoscopy and its effect on CRC screening completion rates.This randomized clinical trial was conducted from July 2017 through August 2018 at the University of Pennsylvania Health System (UPHS), an urban academic medical center. Participants were asymptomatic patients aged 50 to 75 years who were eligible for CRC screening or surveillance, had been referred for colonoscopy, and did not have a scheduled colonoscopy appointment. Data analysis was conducted from January to September 2019.Patients underwent block randomization in a 1:1:1 ratio to 1 of 3 study arms. Participants in the usual care group were contacted via a mailed letter and instructed to call to schedule a colonoscopy. In the generic message group, participants were contacted by telephone, completed an assessment, and received a uniform, nontailored message encouraging colonoscopy scheduling. Participants in the tailored message group were contacted by telephone, completed an assessment, and received a tailored message encouraging colonoscopy scheduling based on their identified assessment cohort.The primary outcome was colonoscopy completion rate within 120 days of enrollment. The secondary outcome was colonoscopy scheduling rate appointment within 120 days of enrollment.A total of 600 participants (median [IQR] age, 56 [51-63] years; 373 women [62.2%]) were enrolled, including 200 participants randomized to usual care, 200 participants randomized to the generic message, and 200 participants randomized to the tailored message. The total sample included 12 Asian participants (2.0%), 324 Black participants (54.0%), and 227 White participants (37.8%), and 9 participants (1.5%) were of Latino or Hispanic ethnicity. Colonoscopy completion was significantly higher for both the tailored message group (69 participants [34.5%]) and the generic message group (64 participants [32.0%]) compared with the usual care group (37 participants [18.5%]) (P .001 and P = .002, respectively). Scheduling rates were also significantly higher in both groups, with 106 participants (53.0%) in the tailored message group and 105 participants (52.5%) in the generic message group scheduling appointments, compared with 54 participants (27.0%) in the usual care arm (P .001 for both).In this randomized clinical trial among individuals whose CRC screening was not up to date, both a tailored message intervention and a generic message intervention were significantly more effective at increasing colonoscopy scheduling and completion rates compared with usual care. These findings suggest that individualized health communications can increase individual motivation to obtain CRC screening.ClinicalTrials.gov Identifier: NCT03310892.

Background and Aims: Portopulmonary hypertension (POPH) was previously associated with a single-nucleotide polymorphism (SNP) rs7175922 in aromatase (cytochrome P450 family 19 subfamily A member 1 [CYP19A1]). We sought to determine whether genetic variants and metabolites in the estrogen signaling pathway are associated with POPH. Approach and Results: We performed a multicenter case-control study. POPH patients had mean pulmonary artery pressure >25 mm Hg, pulmonary vascular resistance >240 dyn-sec/cm −5, and pulmonary artery wedge pressure ≤15 mm Hg without another cause of pulmonary hypertension. Controls had advanced liver disease, right ventricular (RV) systolic pressure

BackgroundHepatopulmonary syndrome affects 10–30% of patients with cirrhosis and portal hypertension. We evaluated the serum angiogenic profile of hepatopulmonary syndrome and assessed the clinical impact of hepatopulmonary syndrome in patients evaluated for liver transplantation.MethodsThe Pulmonary Vascular Complications of Liver Disease 2 study was a multicentre, prospective cohort study of adults undergoing their first liver transplantation evaluation. Hepatopulmonary syndrome was defined as an alveolar–arterial oxygen gradient ≥15 mmHg (≥20 mmHg if age >64 years), positive contrast-enhanced transthoracic echocardiography and absence of lung disease.ResultsWe included 85 patients with hepatopulmonary syndrome and 146 patients without hepatopulmonary syndrome. Patients with hepatopulmonary syndrome had more complications of portal hypertension and slightly higher Model for End-Stage Liver Disease-Na score compared to those without hepatopulmonary syndrome (median (interquartile range) 15 (12–19) versus 14 (10–17), p=0.006). Hepatopulmonary syndrome patients had significantly lower 6-min walk distance and worse functional class. Hepatopulmonary syndrome patients had higher circulating angiopoietin 2, Tie2, tenascin C, tyrosine protein kinase Kit (c-Kit), vascular cell adhesion molecule 1 and von Willebrand factor levels, and lower E-selectin levels. Patients with hepatopulmonary syndrome had an increased risk of death (hazard ratio 1.80, 95% CI 1.03–3.16, p=0.04), which persisted despite adjustment for covariates (hazard ratio 1.79, 95% CI 1.02–3.15, p=0.04). This association did not vary based on levels of oxygenation, reflecting the severity of hepatopulmonary syndrome.ConclusionHepatopulmonary syndrome was associated with a profile of abnormal systemic angiogenesis, worse exercise and functional capacity, and an overall increased risk of death.

Background Non-alcoholic steatohepatitis has emerged as a leading cause of cirrhosis, and obesity-associated comorbidities, including renal disease have increased in prevalence. Obesity predisposes the kidney to hyperfiltration injury, potentially impairing acute kidney injury recovery. Identification of patients at risk for renal dysfunction is impeded by poor performance of renal function estimating equations among cirrhotics. To better understand obesity among cirrhotics and renal disease progression, we examined likelihood of kidney transplantation (KT) waitlisting after liver transplant alone (LTA) by obesity class. Methods 68,607 LTA recipients were identified in SRTR (2005-2018). Fine and Gray competing risks models were used to analyze likelihood of KT waitlisting. Results 27.4% of recipients were obese (BMI>30kg/m2) and were 10% more likely to require KT waitlisting (aHR: 1.10, 95%CI: 1.01-1.20). Risk was highest among recipients with Classes II and III obesity (BMI: >35kg/m2 ) (aHR: 1.37, 95%CI: 1.17-1.56). Moreover, recipients with Classes II and III obesity were 57% more likely to require KT waitlisting within one year post-LTA (aHR: 1.57, 95%CI: 1.18-2.10) compared to non-obese recipients. Discussion These findings suggest obesity was a risk factor for renal recovery failure and/or renal disease progression post-LTA and may confound identification of renal dysfunction and/or prediction of renal recovery among cirrhotics.

Rationale & Objective Hepatitis C virus (HCV) infection is common among maintenance dialysis patients. Few studies have examined both dialysis survival and transplantation outcomes for HCV-seropositive patients because registry data sets lack information for HCV serostatus. Study Design Retrospective cohort study. Setting & Participants Adult long-term dialysis patients treated by a US national dialysis provider between January 1, 2004, and December 31, 2014. Exposure HCV antibody serostatus obtained as part of clinical data from a national dialysis provider. Outcomes Mortality on dialysis therapy, entry onto the kidney transplant waiting list, kidney transplantation, and estimated survival benefit from kidney transplantation versus remaining on the waitlist. Analytical Approach After linking clinical data with data from the Organ Procurement and Transplantation Network, Cox and cause-specific hazards regression were implemented to estimate the associations between HCV seropositivity and mortality, as well as entry onto the kidney transplant waitlist. Cox regression was also used to estimate the survival benefit from transplantation versus dialysis among HCV-seropositive individuals. Results Among 442,171 dialysis patients, 31,624 (7.2%) were HCV seropositive. HCV seropositivity was associated with a small elevation in the rate of death (adjusted HR [aHR], 1.09; 95% CI, 1.07-1.11) and a substantially lower rate of entry onto the kidney transplant waitlist (subdistribution HR [sHR], 0.67; 95% CI, 0.61-0.74). Once wait-listed, the kidney transplantation rate was not different for HCV-seropositive (sHR 1.10; 95% CI, 0.96-1.27) versus HCV-seronegative patients. HCV-seropositive patients lived longer with transplantation (aHR at 3 years, 0.42; 95% CI, 0.27-0.63). Receiving an HCV-seropositive donor kidney provided a survival advantage at the 2-year posttransplantation time point compared to remaining on dialysis therapy waiting for an HCV-negative kidney. Limitations No data for HCV viral load or liver biopsy. Conclusions HCV-seropositive patients experience reduced access to the kidney transplantation waitlist despite deriving a substantial survival benefit from transplantation. HCV-seropositive patients should consider foregoing HCV treatment while accepting kidneys from HCV-infected donors to facilitate transplantation and prolong survival.

Background and objectives The 2016 ISHLT guidelines recommend that patients listed for orthotopic heart transplantation (OHT) undergo periodic surveillance right heart catheterization (RHC) to re-assess hemodynamics (Class I, level of evidence C). However, the impact of RHC on management remains unclear. The aim of this study was to determine the utility of both surveillance and clinically prompted RHCs in patients listed for OHT. Methods A retrospective study was conducted in adult patients listed for OHT at our hospital from 2006 through 2014. Each patient included had at least one RHC after being listed for OHT. The primary outcome was management change: hospitalization, surgery (OHT or mechanical circulatory support [MCS]), change in United Network for Organ Sharing (UNOS) status, or initiation/modification of vasoactive drugs, diuretics or neurohormonal blockade. Results Of the 194 patients included, 85 (43%) patients had more than one RHC. The median time between listing and transplantation was 115 days. Of the 376 RHCs performed, 187 (50%) were prompted by a clinical change; 189 (50%) were performed for surveillance. In 90.4% of clinically prompted RHCs and 42.9% of surveillance RHCs, a clinically important management change was implemented. Initiation/modification of vasoactive drugs, placement of MCS and/or change in UNOS transplant status occurred in 61 (33%) of the clinically prompted RHCs and 26 (14%) of the surveillance RHCs. Patients who underwent management change were more likely to receive a heart transplant (HR 1.58; CI 1.15-2.18) without an increased rate of death over the study period compared to those who did not have a management change. Multivariable analysis revealed that a hemoglobin level 0.9 mg/dL (OR 5.07; CI 2.09-12.3) were predictors of management change. Conclusions In patients awaiting OHT, RHCs prompted by clinical instability or routine surveillance resulted in frequent management changes, including earlier heart transplant and MCS implant. Our study supports the Class I recommendation to perform surveillance RHC in patients listed for OHT and suggests that centers should consider maintaining a low threshold for repeat RHC during the formal waiting time.

INTRODUCTION: Post-transplant diabetes mellitus (PTDM), an increasingly recognized complication of solid organ transplantation, is associated with increased morbidity and mortality following liver transplantation. Hepatitis C virus (HCV) infection is a consistent and modifiable risk factor for PTDM. Prior studies have demonstrated improvement in glucose metabolism following sustained virologic response (SVR). However, the effect of SVR on the incidence of PTDM has not been previously investigated in a large cohort of liver transplant (LT) recipients. METHODS: We performed a single center retrospective cohort study of LT recipients with HCV from 1/1/2010 to 6/30/2015 to compare the risk of sustained PTDM (s-PTDM) prior to and following SVR. SVR was treated as a discrete time varying exposure. s-PTDM was defined as de novo diabetes mellitus following LT of greater than 6-months duration. Univariable and multivariable Cox proportional hazards model were used to compare crude and adjusted time to s-PTDM, prior to and following SVR. RESULTS: 256 eligible LT recipients were analyzed. Median follow up was 41.2 months. Overall, 31 (12.1%) and 178 (69.5%) patients achieved SVR prior to LT and following LT respectively. During follow up, 71 (27.7%) patients developed s-PTDM. The incidence of s-PTDM was greatest in the first year after LT. After adjustment for potential confounders, SVR was associated with a significantly reduced risk of s-PTDM (HR 0.40, p=0.048). CONCLUSIONS: Eradication of HCV is independently associated with a reduced incidence of s-PTDM. This benefit appears to be most influenced by pre-LT SVR and persists throughout the post-LT period. Given the association between PTDM and post-transplant morbidity and mortality, these data provide another motivator for pre- or early post-LT treatment of HCV.

Disconnected pancreatic duct syndrome (DPDS) is a recognized complication of necrotizing pancreatitis (NP). Manifestations include recurrent peripancreatic fluid collections (R-PFC) and pancreatocutaneous fistulae (PC-Fistulae). Pancreatitis of the disconnected pancreatic segment (DPDS-P) and its relationship to new-onset diabetes after pancreatitis (NODAP) are not well characterized.We performed a retrospective cohort study of consecutive patients with NP admitted to University of California, San Francisco from January 2011 to June 2019. A diagnosis of a disconnected pancreatic duct (PD) was confirmed using computed tomography and magnetic resonance cholangiopancreatography/endoscopic retrograde cholangiopancreatography. DPDS was defined as a disconnected PD presenting with R-PFC, PC-Fistulae, or DPDS-P. The primary outcome was NODAP, defined as diabetes mellitus (DM) occurring3 months after NP. Cox proportional hazards regression was used to evaluate the relationship between DPDS and NODAP.Of 171 patients with NP in this study, the mean clinical follow-up was 46 ± 18 months and the imaging follow-up was 38 ± 20 months. Twenty-seven patients (16%) developed DPDS-P at a median of 28 months. New-onset DM occurred in 54 of the 148 patients (36%), with 22% developing DM within 3 months of NP and 14% developing NODAP at a median of 31 months after AP. DPDS-P was associated with NODAP when compared with non-DPDS patients (adjusted hazard ratio 5.63 95% confidence interval: 1.69-18.74, P = 0.005) while R-PFCs and PC-Fistulae were not.DPDS and NODAP occurred in 28% and 14% of the patients, respectively. Pancreatitis of the disconnected pancreas occurred in 16% of the patients and was associated with higher rates of NODAP when compared with patients with other manifestations of DPDS and patients without DPDS.

Most patients with hepatitis C virus (HCV) infection perceive some degree of disease-related stigma. Misunderstandings about diseases may contribute to disease-related stigma. The objective of this study was to evaluate patient-level knowledge about HCV infection transmission and natural history and its association with HCV-related stigma among HCV-infected patients. We conducted a cross-sectional survey study among 265 patients with HCV in Philadelphia using the HCV Stigma Scale and the National Health and Nutrition Examination Survey (NHANES) Hepatitis C Follow-up Survey (2001–2008). The association between HCV knowledge and HCV-related stigma was evaluated via linear regression. Overall knowledge about HCV transmission and natural history was high, with >80% of participants answering ≥9 of 11 items correctly (median number of correct responses, 9 [82%]), HCV-related knowledge was similar between HIV/HCV-coinfected and HCV-monoinfected participants (p = 0.30). A higher level of HCV-related knowledge was associated with greater perceived HCV-related stigma (β, 2.34 ([95% CI, 0.51–4.17]; p = 0.013). Results were similar after adjusting for age, race, ethnicity, HIV status, education level, stage of HCV management, time since diagnosis, and history of injection drug use. In this study, increased HCV-related knowledge was associated with greater perceptions of HCV stigma. Clinicians may consider allotting time to address common misconceptions about HCV when educating patients about HCV infection, which may counterbalance the stigmatizing impact of greater HCV-related knowledge.

There has been an increase in hepatitis B (HBV) detection during pregnancy in the United States and an emphasis on measures to decrease mother-to-child transmission of HBV. We performed a multicentre retrospective study (2015-2018) evaluating care among all women with HBV during pregnancy. We determined rates and predictors of adherence to key maternal care measures including: (1) referral to HBV specialty care, (2) assessment of HBV DNA, and (3) initiation of antiviral therapy, and (4) rates of HBIG and HBV vaccine completion in infants. We evaluated two interventions to improve HBV care: (1) clinical decision support with best practice alert and (2) co-location of HBV care in obstetrics department. We identified 372 women with HBV during pregnancy. Patients had a median age of 33 (IQR 29, 36), were mostly of Asian (49%) or Black (36%) race, HBeAg-negative (83%) with HBV DNA ≤2000 IU/mL (65%) and maximum ALT ≤25 (66%). Regarding care measures, 62% were referred to an HBV specialist, 85% had HBV DNA checked during pregnancy and 68% with HBV DNA ≥200,000 were initiated on antiviral therapy. Co-located obstetric-liver diseases clinics appeared to improve adherence to maternal care measures. All infants received HBIG and the first HBV vaccine dose, 106 (81%) received the second, 94 (74%) received the 3rd dose, but fewer at the recommended time intervals. We identified clear gaps in adherence to HBV care measures for both mothers and infants. Co-location of HBV care in the obstetrics department shows promise in improving adherence to maternal care measures.

PURPOSE To compare patients treated with large-volume paracentesis (LVP), transjugular intrahepatic portosystemic shunt (TIPS), and peritoneovenous shunt (PVS) for ascites. MATERIALS AND METHODS A retrospective study of 192 patients treated with LVP (94), TIPS (75), or PVS (23) was performed. Records were reviewed for patient characteristics and outcomes. The patients' age differed (LVP, 59.5 years; TIPS, 58.8 years; and PVS, 65.6 years; P = .003). Nonalcoholic steatohepatitis was the most common etiology in the PVS cohort (11/23, 47%), and hepatitis C in the TIPS (27/75, 36%), and LVP cohorts (43/94, 46%) (P = .032). The model for end-stage liver disease score was significantly different (LVP, 14; TIPS, 13; and PVS, 8; P = .035). Hepatocellular carcinoma was higher in the PVS cohort (6/23 patients, 25%) than in the TIPS (4/75, 5%), and LVP (12/94, 12%) cohorts (P = .03). RESULTS Emergency department visits and hospital readmissions were the highest in the LVP cohort (40%, ≥2 readmissions, P < .001). Patients required fewer LVPs after TIPS (1.5 to 0.14, P < .001) or PVS (2.1 to 0.5, P = .019). In an unadjusted Cox model, patients in the TIPS cohort were found to have a 58% reduction in the risk of death compared with patients in the LVP cohort (P = .003). Transplant-free survival (PVS, 44 days; TIPS, 155 days; and LVP, 213 days) differed (log rank = 0.001). CONCLUSIONS The survival in the PVS and TIPS cohorts was similar, with less healthcare utilization than the LVP cohort. PVS is a satisfactory alternative to LVP.

Importance Differences in local organ supply and demand have introduced geographic inequities in the Model for End-stage Liver Disease (MELD) score–based liver allocation system, prompting national debate and patient-initiated lawsuits. No study to our knowledge has quantified the sex disparities in allocation associated with clinical vs geographic characteristics. Objective To estimate the proportion of sex disparity in wait list mortality and deceased donor liver transplant (DDLT) associated with clinical and geographic characteristics. Design, Setting, and Participants This retrospective cohort study used adult (age ≥18 years) liver-only transplant listings reported to the Organ Procurement and Transplantation Network from June 18, 2013, through March 1, 2018. Exposure Liver transplant waiting list. Main Outcomes and Measures Primary outcomes included wait list mortality and DDLT. Multivariate Cox proportional hazards regression models were constructed, and inverse odds ratio weighting was used to estimate the proportion of disparity across geographic location, MELD score, and candidate anthropometric and liver measurements. Results Among 81 357 adults wait-listed for liver transplant only, 36.1% were women (mean [SD] age, 54.7 [11.3] years; interquartile range, 49.0-63.0 years) and 63.9% were men (mean [SD] age, 55.7 [10.1] years; interquartile range, 51.0-63.0 years). Compared with men, women were 8.6% more likely to die while on the waiting list (adjusted hazard ratio [aHR], 1.11; 95% CI, 1.04-1.18) and were 14.4% less likely to receive a DDLT (aHR, 0.86; 95% CI, 0.84-0.88). In the geographic domain, organ procurement organization was the only variable that was significantly associated with increased disparity between female sex and wait list mortality (22.1% increase; aHR, 1.22; 95% CI, 1.09-1.30); no measure of the geographic domain was associated with DDLT. Laboratory and allocation MELD scores were associated with increases in disparities in wait list mortality: 1.14 (95% CI, 1.09-1.19; 50.1% increase among women) and DDLT: 0.87 (95% CI, 0.86-0.88; 10.3% increase among women). Candidate anthropometric and liver measurements had the strongest association with disparities between men and women in wait list mortality (125.8% increase among women) and DDLT (49.0% increase among women). Conclusions and Relevance Our findings suggest that addressing geographic disparities alone may not mitigate sex-based disparities, which were associated with the inability of the MELD score to accurately estimate disease severity in women and to account for candidate anthropometric and liver measurements in this study.

We investigated the prevalence of spirometric restriction in liver transplantation (LT) candidates and the clinical impacts of restriction. We performed a cross-sectional study within the Pulmonary Vascular Complications of Liver Disease 2 (PVCLD2) study, a multicenter prospective cohort study of patients being evaluated for LT. Patients with obstructive lung disease or missing spirometry or chest imaging were excluded. Patients with and without restriction, defined as a forced vital capacity (FVC)

Cardiovascular disease is a leading cause of death among liver transplant (LT) recipients. With a rising burden of posttransplantation metabolic disease, increases in cardiovascular-related morbidity and mortality may reduce life expectancy after LT. It is unknown if the risk of long-term major cardiovascular events (MCEs) differs among LT recipients with varying diabetic states. We performed a retrospective cohort study of LT recipients from 2003 through 2013 to compare the incidence of MCEs among patients (1) without diabetes, (2) with pretransplantation diabetes, (3) with de novo transient posttransplantation diabetes, and (4) with de novo sustained posttransplantation diabetes. We analyzed 994 eligible patients (39% without diabetes, 24% with pretransplantation diabetes, 16% with transient posttransplantation diabetes, and 20% with sustained posttransplantation diabetes). Median follow-up was 54.7 months. Overall, 12% of patients experienced a MCE. After adjustment for demographic and clinical variables, sustained posttransplantation diabetes was the only state associated with a significantly increased risk of MCEs (subdistribution hazard ratio 1.95, 95% confidence interval 1.20-3.18). Patients with sustained posttransplantation diabetes mellitus had a 13% and 27% cumulative incidence of MCEs at 5 and 10 years, respectively. While pretransplantation diabetes has traditionally been associated with cardiovascular disease, the long-term risk of MCEs is greatest in LT recipients with sustained posttransplantation diabetes mellitus.

Background & Aims Biliary complications occur in up to 25% of patient following liver transplantation and are often managed by endoscopic retrograde cholangiopancreatography (ERCP). Pancreatitis is the most common adverse event after ERCP (PEP). Tacrolimus and rectal indomethacin have each been reported to reduce risk of PEP. We investigated the incidence of PEP in patients who have undergone ERCP after liver transplantation and the effectiveness of tacrolimus and/or indomethacin in reducing risk of PEP. Methods We performed a retrospective study of 337 patients who underwent ERCP (n = 937 procedures) for biliary complications after liver transplantation from June 1, 2007 through December 1, 2015. After June 1, 2012, rectal indomethacin (100 mg) was routinely administered at the conclusion of the ERCP unless patients had contraindications. Indomethacin was given after 286 ERCP procedures. After excluding patients with acute/chronic rejection, 323 patients were maintained on a stable dose of tacrolimus prior to ERCP (901 procedures). We collected data on demographic and clinical variables, pre-procedural tacrolimus trough levels, and development of PEP. We calculated adjusted odds ratios (ORs) for the association between tacrolimus and indomethacin use and risk of PEP using mixed-effects multivariable logistic regression. The primary outcome was development of PEP; secondary outcomes included the development moderate-to-severe PEP, cholangitis and bleeding. Results PEP occurred after 2.2% of ERCP procedures. A trough level of tacrolimus above 2.5 ng/mL was associated with 79% lower odds of PEP (OR, 0.21; 95% CI, 0.06–0.72; P = .01). Indomethacin was associated with a 91% reduction in risk of PEP (OR, 0.09; 95% CI, 0.01–0.85; P = .03). Indomethacin use did not affect rates of bleeding or cholangitis or decrease in glomerular filtration rate. In patients with trough levels of tacrolimus above 2.5 ng/mL, addition of indomethacin reduced the odds of PEP by 93% compared with patients who were unexposed to indomethacin. (OR, 0.07; 95% CI, 0.01–0.90; P = .04). Conclusions In a retrospective study of patients who underwent ERCP for biliary complications after liver transplantation, we found trough levels of tacrolimus above 2.5 ng/mL to significantly reduce risk for PEP. Rectal administration of indomethacin after ERCP significantly decreased rates of pancreatitis, and reduced risk further in patients given tacrolimus. Administration of both drugs prevented patients from developing moderate or severe pancreatitis. Indomethacin did not worsen renal function in patients with chronic kidney disease.

Screening for hepatopulmonary syndrome (HPS) using pulse oximetry is recommended in liver transplant (LT) candidates because mortality is increased, independently of the severity of the oxygenation defect. LT exception points may be afforded to those with HPS and severe hypoxemia. We assessed the screening characteristics of pulse oximetry for HPS. The Pulmonary Vascular Complications of Liver Disease 2 study is a multicenter, prospective cohort study of adults undergoing their first LT evaluation. Patients underwent protocolized assessment of oxygen saturation by pulse oximetry (SpO2 ), arterial blood gas, spirometry, and contrast-enhanced echocardiography (CE). HPS was defined as an alveolar-arterial gradient ≥15 mm Hg (≥20 mm Hg if age >64 years), intrapulmonary vascular dilatation on CE, and absence of lung disease. The study sample included 363 patients. Of these, 75 (20.7%; 95% confidence interval [CI], 16.6%-25.2%) met the criteria for HPS. The area under the receiver operating characteristic curve (or c-statistic) for SpO2 in discriminating HPS was 0.59 (95% CI, 0.51-0.66). An SpO2

Objective Low muscle mass is associated with reduced survival in HIV, possibly mediated by systemic inflammation. Viral hepatitis coinfection can induce additional inflammation and hepatic dysfunction that may exacerbate low muscle mass. We determined the prevalence of and risk factors for low muscle mass in HIV/viral hepatitis coinfection. Design and methods A cross-sectional study of participants in the Multicenter AIDS Cohort Study and Women's Interagency HIV Study with anthropometry performed after 1 January 2000. Viral hepatitis defined by positive hepatitis B virus surface antigen and/or hepatitis C virus RNA. Low muscle mass defined as less than 10th percentile of age-matched and sex-matched reference values for mid-upper arm circumference. Using multivariable logistic regression, we determined adjusted odds ratios with 95% confidence intervals (CIs) of the association of HIV/viral hepatitis coinfection with low muscle mass and factors associated with low muscle mass in coinfected persons. Analyses adjusted for age, race, BMI, alcohol use, and IDU (also, nadir CD4 cell count and HIV RNA where appropriate). Results Among 3518 participants (164 HIV/viral hepatitis, 223 viral hepatitis alone, 1070 HIV alone, and 2061 uninfected), HIV/viral hepatitis-coinfected persons had a 3.50-fold (95% CI, 1.51-8.09), 1.93-fold (1.17-3.20), and 2.65-fold (1.62-4.35) higher odds of low muscle mass than viral hepatitis-monoinfected, HIV-monoinfected, and uninfected persons, respectively. Lack of HIV RNA suppression [odds ratio, 2.26 (95% CI, 1.10-4.63)] was the only factor associated with low muscle mass in coinfected persons. Conclusion HIV/viral hepatitis-coinfected persons have a higher likelihood of low muscle mass than those with viral hepatitis monoinfection, HIV monoinfection, or neither infection. HIV viremia is an important risk factor for low muscle mass among coinfected persons.

The direct-acting antivirals (DAAs) constitute an emerging group of small molecule inhibitors that effectively treat hepatitis C virus (HCV) infection, a common comorbidity in end-stage renal disease patients. To date, there are no data to guide use of these agents in kidney transplant patients. The authors collected data from 20 consecutive kidney recipients treated with interferon-free treatment regimens for HCV at their center: 88% were infected with genotype 1; 50% had biopsy-proved advanced hepatic fibrosis on their most recent liver biopsy preceding treatment (Metavir stage 3 fibrosis [F3] or F4); and 60% had failed treatment pretransplantation with interferon-based therapy. DAA treatment was initiated a median of 888 days after renal transplantation. All patients cleared the virus while on therapy, and 100% have achieved a sustained virologic response at 12 weeks after completion of DAA therapy. The most commonly used regimen was sofosbuvir 400 mg daily in combination with simeprevir 150 mg daily. However, four different treatment approaches were used, with comparable results. The DAAs were well tolerated, and less than half of patients required calcineurin inhibitor dose adjustment during treatment. Eradication of HCV infection with DAAs is feasible after kidney transplantation with few treatment-related side effects.

Background & Aims Few studies have evaluated the ability of laboratory tests to predict risk of acute liver failure (ALF) among patients with drug-induced liver injury (DILI). We aimed to develop a highly sensitive model to identify DILI patients at increased risk of ALF. We compared its performance with that of Hy's Law, which predicts severity of DILI based on levels of alanine aminotransferase or aspartate aminotransferase and total bilirubin, and validated the model in a separate sample. Methods We conducted a retrospective cohort study of 15,353 Kaiser Permanente Northern California members diagnosed with DILI from 2004 through 2010, liver aminotransferase levels above the upper limit of normal, and no pre-existing liver disease. Thirty ALF events were confirmed by medical record review. Logistic regression was used to develop prognostic models for ALF based on laboratory results measured at DILI diagnosis. External validation was performed in a sample of 76 patients with DILI at the University of Pennsylvania. Results Hy's Law identified patients that developed ALF with a high level of specificity (0.92) and negative predictive value (0.99), but low level of sensitivity (0.68) and positive predictive value (0.02). The model we developed, comprising data on platelet count and total bilirubin level, identified patients with ALF with a C statistic of 0.87 (95% confidence interval [CI], 0.76–0.96) and enabled calculation of a risk score (Drug-Induced Liver Toxicity ALF Score). We found a cut-off score that identified patients at high risk patients for ALF with a sensitivity value of 0.91 (95% CI, 0.71–0.99) and a specificity value of 0.76 (95% CI, 0.75–0.77). This cut-off score identified patients at high risk for ALF with a high level of sensitivity (0.89; 95% CI, 0.52–1.00) in the validation analysis. Conclusions Hy's Law identifies patients with DILI at high risk for ALF with low sensitivity but high specificity. We developed a model (the Drug-Induced Liver Toxicity ALF Score) based on platelet count and total bilirubin level that identifies patients at increased risk for ALF with high sensitivity.

Background Despite a survival benefit from transplantation and acceptable outcomes, patients with human immunodeficiency virus (HIV+) face barriers to kidney transplantation. Little is known about the acceptance or decline of organ offers on their behalf because waitlist registry data do not include HIV serostatus. Methods We performed a retrospective cohort study using match run data from the Organ Procurement and Transplantation Network, including every kidney offer from May 1, 2007, to July 3, 2013. HIV and hepatitis C virus (HCV) serostatus were obtained by merging the match run with clinical data from a large dialysis provider. We used Cox proportional hazards modeling to evaluate differences in time to the first organ offer and to transplantation. A total of 35 646 uninfected, 2213 HCV+, 418 HIV+, and 71 HIV+/HCV+ candidates received organ offers during the study period. Results Compared to uninfected candidates, HIV+ candidates had a significantly lower likelihood of receiving a first offer (adjusted hazard ratio [aHR] 0.88, 95% confidence interval [CI] 0.79-0.99) and undergoing transplantation (aHR 0.82, 95% CI: 0.68-0.98) after receiving a first offer; HCV+ candidates had a similar likelihood of receiving a first offer (aHR 0.98, 95% CI: 0.92-1.03) and greater likelihood of transplantation after receiving a first offer (aHR 1.23, 95% CI: 1.12-1.36). Conclusions HIV+ candidates had a significantly longer wait until their first organ offer and to transplantation. Efforts to increase their access to transplantation are needed.

Early liver transplantation for alcoholic hepatitis is a potentially life-saving treatment. As this practice becomes increasingly common, however, the liver transplant community is taking a fresh look at a familiar challenge: best stewardship of donor organs. Herein, we examine a few basic, necessary ethical and practical concerns relevant to this indication.

Cirrhosis is associated with hormonal dysregulation, as evidenced by secondary amenorrhoea in reproductive-aged women, and feminization of cirrhotic men. Whether hormone levels vary by severity of cirrhosis in women is not known. If identified, such changes may have important clinical relevance, particularly, as low sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) are known to promote metabolic and cardiovascular disease in women. In a cohort of post-menopausal women with chronic hepatitis C virus (HCV) infection, we compared comprehensive sex hormone levels by presence of cirrhosis, as well as across Child-Turcotte-Pugh (CTP) class. Results: There were n=18 cirrhotic and n=21 noncirrhotic women with a median age of 57years (interquartile range [IQR] 53-62). Compared to noncirrhotics, cirrhotic women had higher oestradiol (11.0 vs 6.0pg/mL, P=0.05) and oestrone levels (32.0 vs 8.0ng/mL, P&nbsp

Patients with hepatocellular carcinoma (HCC) exceeding Milan criteria on explant pathology are at increased risk of recurrence and death. Discordance between contemporary magnetic resonance imaging (MRI) and explant pathology, and preoperative characteristics predictive of discordance are not well understood.Patients who underwent orthotopic liver transplantation for HCC after preoperative MRI were identified in a prospectively collected institutional database (January 2003 to December 2013). Patients were dichotomized to "within" or "outside" Milan criteria by both imaging and explant pathologic evaluation. Binary logistic regression and Kaplan-Meier methodology were used to identify independent predictors of imaging/pathologic discordance and its impact on posttransplant survival.Of 318 patients with HCC meeting Milan criteria by MRI at the time of orthotopic liver transplantation, 248 (78.0%) remained within a pathological correlate of Milan criteria on explant examination. Understaging was associated with worse median recurrence-free survival (64.0 months vs 140.0 months, P = 0.002) and overall survival (96.0 months vs 143.0 months, P = 0.005), and did not vary between patients exceeding criteria due to tumor explant greater than 5 cm, more than 3 tumor foci, or a tumor greater than 3 cm in the setting of multifocality. Discordance was independently associated with an increasing serum alpha fetal protein level (odds ratio, 2.82; 95% confidence interval, 1.37-5.79; P = 0.005).Underestimating HCC burden before liver transplant remains frequent despite contemporary imaging technologies. Patients with an increasing alpha fetal protein before transplantation may benefit from more frequent testing or novel neoadjuvant therapies.

Continuous-flow left ventricular assist devices (LVADs) for advanced heart failure have been associated with gastrointestinal bleeding (GIB). We examined the association between time of GIB after LVAD implantation and bleeding location (determined by endoscopy), etiology, and patient outcomes.We performed a retrospective study of consecutive patients who underwent implantation of continuous-flow LVADs from 2008 through 2015. We analyzed data on anatomic location of GIB, etiology, length of hospital stay, transfusion requirement, time to endoscopy, and readmission to the hospital within 30 days (30-day readmission).GIB developed in 59 of the 271 patients (22%). Higher proportions of patients with GIB during their index hospitalization for LVAD implantation had upper or lower GIB (86.7%) than patients with GIB during a subsequent hospitalization (50.0%; P = .013). Patients with GIB during their index hospitalization also had lower rates of middle GIB (0 vs 20.5%; P = .052), higher rates of overt GIB (100% vs 63.6%; P = .006), longer hospital stays (24 days vs 11 days; P .001), and more transfusions before endoscopy (7 units vs 4 units; P = .021) than patients with GIB during a subsequent hospitalization. There were no significant differences between groups in time to endoscopy (2 days vs 2.5 days) or 30-day readmission (6.7% vs 9.3%). Angiodysplasias were identified in 100% of patients with middle GIB compared to 48.5% of patients with upper or lower GIB (P.001) in whom a bleeding lesion was identified.In a retrospective study of patients who underwent implantation of continuous-flow LVADs, we found that timing of GIB associates with the location and severity of bleeding. Although patients with LVADs have an overall increase in risk of middle GIB, patients with GIB during their index LVAD hospitalization should undergo initial evaluation by upper endoscopy and colonoscopy, due to insufficient time for development of small bowel angiodysplasias. Patients who later develop GIB should be evaluated early for middle GI bleeding.

There are limited data regarding intermediate-term outcomes in patients with persistent BK viremia. Other viral infections have been implicated in the development of allosensitization through heterologous immunity, but the relationship between BK viremia and donor-specific antibodies (DSAs) is unexplored. In 2008, we initiated routine post-transplant BK viremia and DSA screening at our center; 785 kidney or kidney–pancreas transplant recipients were included in our study. Of these recipients, 132 (17%) recipients developed BK viremia during the study period. The median duration of BK viremia was 140 days (interquartile range=40–393 days), and persistent BK viremia was defined as lasting ≥140 days. Kaplan–Meier curves were generated to assess differences in patient and allograft survival on the basis of BK viremia status; survival was modeled using Cox proportional hazard regression. After a median follow-up of 3 years, there was no significant difference in terms of patient (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.28 to 2.49) or allograft survival (HR, 0.80; 95% CI, 0.37 to 1.73) between patients with and without BK viremia, which was confirmed in a time-varying analysis. In our logistic regression model, persistent BK viremia was strongly associated with the development of class II (HR, 2.55; 95% CI, 1.30 to 4.98) but not class I (HR, 1.13; 95% CI, 0.46 to 2.77) DSAs. These data suggest that persistent BK viremia does not negatively affect intermediate-term patient or allograft survival but is associated with increased risk for de novo DSA, although the exact mechanism is unclear.

Background Intrapulmonary vascular dilatations (IPVD) frequently are detected in patients with liver disease by the delayed appearance of microbubbles at contrast-enhanced echocardiography. IPVD with an elevated alveolar-arterial (A-a) gradient define hepatopulmonary syndrome (HPS); however, the importance of IPVD in the absence of abnormal gas exchange is unknown. We aimed to determine the clinical impact of IPVD in patients with liver disease. Methods We performed a cross-sectional study within the Pulmonary Vascular Complications of Liver Disease 2 Study, a multicenter, prospective cohort study of patients being evaluated for liver transplant. We excluded patients with obstructive or restrictive lung disease, HPS, or intracardiac shunting. We compared patients with and those without IPVD. Results Forty-six patients with IPVD and 81 patients without IPVD were included. Patients with IPVD were more likely to have autoimmune hepatitis and less likely to have cryptogenic cirrhosis and hepatocellular carcinoma. Patients with IPVD had higher Child-Pugh scores (6 [interquartile range (IQR), 5-7] vs 5 [IQR, 4-7]; P = .04), possibly higher Model for End-Stage Liver Disease scores (14.5 [IQR, 11.6-15.8] vs 12.2 [IQR, 9.4-15.5]; P = .06), higher PaO2 levels (97.9 [IQR, 92.0-103.0] vs 89.0 [IQR, 82.0-96.9] mm Hg; P Conclusions Autoimmune hepatitis and increased liver disease severity were associated with the presence of IPVD, which was characterized by higher PaO2 levels. Future studies to better characterize IPVD pathogenesis and the relationship of IPVD to HPS are warranted.

Although tacrolimus is the basis of most maintenance immunosuppression regimens for kidney transplantation, concerns about toxicity have made alternative agents, such as belatacept, attractive to clinicians. However, limited data exist to directly compare outcomes with belatacept-based regimens to tacrolimus.We performed a propensity score matched cohort study of adult kidney transplant recipients transplanted between May 1, 2001, and December 31, 2015, using national transplant registry data to compare patient and allograft survival in patients discharged from their index hospitalization on belatacept-based versus tacrolimus-based regimens.In the primary analysis, we found that belatacept was not associated with a statistically significant difference in risk of patient death (hazard ratio, 0.84; 95% confidence interval [CI], 0.61-1.15, P = 0.28) or allograft loss (hazard ratio, 0.83; 95% CI, 0.62-1.11; P = 0.20) despite an increased risk of acute rejection in the first year posttransplant (odds ratio, 3.12; 95% CI, 2.13-4.57; P0.001). These findings were confirmed in additional sensitivity analyses that accounted for use of belatacept in combination with tacrolimus, transplant center effects, and differing approaches to matching.Belatacept appears to have similar longitudinal risk of mortality and allograft failure compared with tacrolimus-based regimens. These data are encouraging but require confirmation in prospective randomized controlled trials.

Author(s): Byrne, Dana D; Tate, Janet P; Forde, Kimberly A; Lim, Joseph K; Goetz, Matthew Bidwell; Rimland, David; Rodriguez-Barradas, Maria C; Butt, Adeel A; Gibert, Cynthia L; Brown, Sheldon T; Bedimo, Roger; Freiberg, Matthew S; Justice, Amy C; Kostman, Jay R; Roy, Jason A; Lo Re, Vincent | Abstract: BackgroundPatients with human immunodeficiency virus (HIV) and/or chronic hepatitis C virus (HCV) infection may be prescribed statins as treatment for metabolic/cardiovascular disease, but it remains unclear if the risk of acute liver injury (ALI) is increased for statin initiators compared to nonusers in groups classified by HIV/HCV status.MethodsWe conducted a cohort study to compare rates of ALI in statin initiators vs nonusers among 7686 HIV/HCV-coinfected, 8155 HCV-monoinfected, 17739 HIV-monoinfected, and 36604 uninfected persons in the Veterans Aging Cohort Study (2000-2012). We determined development of (1) liver aminotransferases g200 U/L, (2) severe ALI (coagulopathy with hyperbilirubinemia), and (3) death, all within 18 months. Cox regression was used to determine propensity score-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of outcomes in statin initiators compared to nonusers across the groups.ResultsAmong HIV/HCV-coinfected patients, statin initiators had lower risks of aminotransferase levels g200 U/L (HR, 0.66 [95% CI, .53-.83]), severe ALI (HR, 0.23 [95% CI, .12-.46]), and death (HR, 0.36 [95% CI, .28-.46]) compared with statin nonusers. In the setting of chronic HCV alone, statin initiators had reduced risks of aminotransferase elevations (HR, 0.57 [95% CI, .45-.72]), severe ALI (HR, 0.15 [95% CI, .06-.37]), and death (HR, 0.42 [95% CI, .32-.54]) than nonusers. Among HIV-monoinfected patients, statin initiators had lower risks of aminotransferase increases (HR, 0.52 [95% CI, .40-.66]), severe ALI (HR, 0.26 [95% CI, .13-.55]), and death (HR, 0.19 [95% CI, .16-.23]) compared with nonusers. Results were similar among uninfected persons.ConclusionsRegardless of HIV and/or chronic HCV status, statin initiators had a lower risk of ALI and death within 18 months compared with statin nonusers.

Use of diabetic donor kidneys has been a necessary response to the donor organ shortage. Recipients of diabetic donor kidneys have higher mortality risk compared with recipients of nondiabetic donor kidneys. However, the survival benefit of transplantation with diabetic donor kidneys over remaining on the waitlist has not been previously evaluated.We performed an observational cohort study of 437,619 kidney transplant candidates from the Organ Procurement and Transplantation Network database, including 8101 recipients of diabetic donor kidneys and 126,560 recipients of nondiabetic donor kidneys. We used time-varying Cox proportional hazards modeling to assess the mortality risk of accepting a diabetic donor kidney compared with remaining on the waitlist or receiving a nondiabetic donor kidney.Among transplant recipients, median follow-up was 8.9 years and mortality rate was 35 deaths per 1000 person-years. Recipients of diabetic donor kidneys had 9% lower mortality compared with remaining on the waitlist or transplantation with a nondiabetic donor kidney (adjusted hazard ratio, 0.91; 95% confidence interval, 0.84 to 0.98). Although recipients of nondiabetic donor kidneys with a Kidney Donor Profile Index score85% had lower mortality risk (adjusted hazard ratio, 0.86; 95% confidence interval, 0.81 to 0.91), recipients of diabetic donor kidneys with an index score85% did not show any difference (adjusted hazard ratio, 1.09; 95% confidence interval, 0.97 to 1.22). Patients aged40 years attained no survival benefit from transplantation with diabetic donor kidneys; diabetic patients at centers with long waitlist times attained the greatest survival benefit.Diabetic donor kidneys appear associated with higher mortality risk compared with nondiabetic donor kidneys, but offer greater survival benefit compared with remaining on the waitlist for many candidates. Patients with high risk of mortality on the waitlist at centers with long wait times appear to benefit most from transplantation with diabetic donor kidneys.

Background & aims There is limited knowledge about hepatitis B virus (HBV) flare among pregnant women. We evaluated the incidence, determinants and outcomes of HBV flare in a multicultural cohort of pregnant HBV-infected women in the United States. Methods We performed a retrospective cohort study of pregnant hepatitis B surface antigen-positive women cared for at hospital-based clinics of 4 medical centres in Southeastern Pennsylvania from 2006 to 2015. The main outcome was incident HBV flare (alanine aminotransferase [ALT] ≥2 times upper limit of normal) during pregnancy or within 6 months after delivery. Among patients with flare, we determined development of jaundice (total bilirubin ≥2.5 mg/dL) and hepatic decompensation. Multivariable logistic regression was used to estimate odds ratios (ORs) of HBV flare for risk factors of interest, including timing of flare (during pregnancy versus post-delivery), nulliparity, younger age, HBV e antigen (HBeAg) status, and lack of anti-HBV therapy. Results Among 310 pregnant predominantly African HBV-infected women with 388 pregnancies, the incidence of HBV flare was 14% (95% CI, 10-18%) during pregnancy and 16% (95% CI, 11-24%) post-delivery. Jaundice developed in 12% and hepatic decompensation in 2%. Positive HBeAg was associated with HBV flare (OR, 2.55; 95% CI, 1.04-6.20). HBV DNA was measured in 55% of patients, and only 50% were referred for HBV specialty care. Conclusions Pregnancy-associated hepatitis B flare occurred in 14% during pregnancy and 16% post-delivery and rarely led to hepatic decompensation. Positive HBeAg was the main risk factor identified. Women did not have adequate HBV monitoring or follow-up during pregnancy.

Individuals with HIV infection are at elevated risk of developing end-stage renal disease. However, their outcomes after starting chronic dialysis in the contemporary era of widespread antiretroviral therapy are not well described. Using detailed data from a national dialysis provider, we determined HIV status by administrative codes and antiretroviral medication prescriptions, with hepatitis C virus (HCV) co-infection status provided by routinely measured serology. The survival on dialysis among 5348 individuals in the HIV

Women are significantly less likely than men to receive a liver transplant and more likely to die on the waitlist. We investigated potential reasons for these disparities, including match run positioning and organ declines caused by small stature of female recipients.We analyzed data from the United Network of Organ Sharing registry of candidates placed on the waitlist from May 10, 2007, through June 17, 2013. Primary outcomes included ranked in first position on a match run, having an organ declined while in first position, declining an organ while in first position because of size mismatch between donor and recipient (body surface area discordance), and death or becoming too sick for liver transplantation.Among 64,995 patients on the waitlist for liver transplantation, 23.1% of men and 15.6% of women received exception points (P.001). Women listed without exception points were less likely than men to be ranked first (odds ratio [OR], 0.93; 95% CI, 0.88-0.99). Women who achieved first position were more likely to decline an organ than men (OR, 1.15; 95% CI, 1.06-1.26); this difference was reduced after we accounted for recipient body surface area (OR, 1.08; 95% CI, 0.98-1.19). Women with a single organ decline were more likely than men with a single organ decline to die or become too sick for transplantation (OR, 1.26; 95% CI, 1.12-1.41). The difference was reduced after we accounted for exception points (OR, 1.16; 95% CI, 1.12-1.21) and recipient body surface area (OR, 1.01; 95% CI, 0.96-1.06).In an analysis of data from the United Network of Organ Sharing registry, we found that women when compared with men on the waitlist for liver transplantation are disadvantaged by an imbalance in exception point allocation and organ declines because of small stature.

Risk factors for hepatocellular carcinoma (HCC) recurrence after liver transplantation have been well described. It has been surmised that longer time on the waitlist may select for tumors with a lower-risk of recurrence posttransplant, as patients with unfavorable tumor characteristics would be delisted due to tumor progression. Utilizing national explant pathology records from transplant recipients waitlisted with T2 HCC exception points, this study explored the correlation between waiting time and the development of pathologic HCC features associated with increased risk of tumor recurrence. Of 1976 explant pathology reports submitted nationally between April 8, 2012 and June 30, 2013, 1453 (73.5%) were from recipients with automatic T2 HCC exception points. There was no association between pretransplant waiting time and the proportion of HCC explants with either: (i) a poorly differentiated tumor; (ii) macrovascular invasion; (iii) HCC beyond Milan or University of California San Francisco criteria; (iv) HCC beyond the "up-to-seven" criteria; or (v) extra-hepatic or lymph node involvement. Though there was a statistically significant increase in microvascular invasion in recipients with pretransplant waiting 6-12 months, this association was not seen when adjusted for United Network for Organ Sharing region. These findings suggest that waiting time alone may not select for tumors with more favorable characteristics.

Nonalcoholic fatty liver disease (NAFLD) is a common cause of hepatic steatosis in patients with inflammatory bowel disease (IBD). Both metabolic syndrome (MetS) and intestinal inflammation are implicated in NAFLD pathogenesis. We performed a retrospective cohort study of patients with IBD and NAFLD seen in our health system from January 1997 to December 2011 to examine associations between IBD severity and phenotype; MetS; and NAFLD fibrosis as estimated by the NAFLD Fibrosis Score (NFS). A total of 84 patients were included in our analysis (24 UC, 60 CD). 23% of patients had MetS. IBD patients with MetS were significantly older at the time of IBD diagnosis (44 vs. 33, p = 0.005) and NAFLD diagnosis (55 vs. 47, p = 0.018). IBD patients with MetS had higher ALT (54 vs. 38 U/L, p = 0.02) and AST (52 vs. 35 U/L, p = 0.004). Comparing MetS patients to non-MetS IBD patients, there was no significant difference between IBD medication use (i.e., steroids, anti-TNFs, and immunomodulators) or NAFLD medication use, other than statins. Both UC and CD patients with concomitant MetS had significantly higher NFS scores than non-MetS patients: UC (−0.4 vs. −2.5, p = 0.02) and CD (−0.8 vs. −2.3, p = 0.03). IBD disease severity, disease location, or IBD medication use was associated with NAFLD severity. To our knowledge, this is the first study to demonstrate that NAFLD severity in both UC and CD IBD patients is associated with the presence of MetS but not with the severity of IBD.

BACKGROUND Acute decompensation in patients with chronic liver disease, resulting from acute kidney injury and infections, leads to significant morbidity and mortality. It is unclear whether patients who develop acute-on-chronic liver failure (ACLF) have poor outcomes after liver transplantation. METHODS We performed a single-center retrospective cohort study of 332 patients to evaluate the effect of ACLF, defined as an acute rise in the Model for End-Stage Liver Disease score of more than 5 within 4 weeks before transplantation, on posttransplant outcomes including stage 4 chronic kidney disease, death, recurrent cirrhosis, or graft failure requiring retransplantation. RESULTS AND CONCLUSIONS One hundred fifty-seven patients in the study had ACLF and 175 patients had no ACLF (non-ACLF) pretransplant. Thirty-four patients in the entire cohort received dual organs, 10 of them (29.4%) had ACLF. Seventy-six percent of the patients with ACLF had acute kidney injury as their reason for decompensation and 23.6% had an infection. Mean Model for End-Stage Liver Disease score at transplant was significantly different between the groups (ACLF 28.77 vs. non-ACLF 21.23, P

In patients with chronic liver disease, race plays a role in the rate of survival after transplantation. It is not known how race and ethnicity influence the presentation, etiology, and outcomes in patients with acute liver failure (ALF).A retrospective cohort study was conducted using the ALF Study Group database to assess differences between racial and ethnic groups in subjects with ALF.In the cohort of 927 subjects (81.8% white, 12.8% black, and 5.4% Asian), enrolled between January 1998 and March 2006, age, sex, and level of education were comparable among the groups. Differences were found in the prevalence of psychiatric illness and the use of medications. Racial groups also differed with respect to etiology of ALF. Whites presented more frequently with acetaminophen toxicity (51% vs 27%; P.001). By day 21, 228 (30%) whites, 46 (39%) blacks, and 11 (22%) Asians had died. There were no significant differences found in the overall mortality rate after adjustment for potential confounders including etiology of ALF, encephalopathy, age, sex, admission laboratory values, and region. The odds of liver transplantation were higher among Asians and Hispanics; however, this finding was attenuated after adjustment for the previously-described confounders (adjusted odds ratio, 1.50; 95% confidence interval, 0.72-3.13; and adjusted odds ratio, 1.89; 95% confidence interval, 1.08-3.30, respectively).In patients with ALF, there were no significant differences in survival or rate of liver transplantation among racial and ethnic groups except for transplantation in Hispanics.

Hepatitis C virus (HCV) infection remains a large-scale and significant health concern. The combination of subcutaneously administered pegylated interferon and oral ribavirin is the FDA-approved regimen for the treatment of chronic HCV infection. Combination therapy may result in a sustained virologic response leading to HCV eradication, with a reduction in risk for cirrhosis, hepatic decompensation, and hepatocellular carcinoma.9,10 However, the combination of PEG-IFN and ribavirin does not universally result in cure in all patients who undergo treatment. In this article, the authors discuss immunomodulatory therapies and clinical trials in the treatment of HCV infection.

Ulcerative colitis (UC) can be treated with surgery or medications. Patients often must choose between long-term immunosuppressant therapy or total colectomy. Whether one of these treatment approaches has a mortality benefit is uncertain.To determine whether patients with advanced UC treated with elective colectomy have improved survival compared with those treated with medical therapy.Retrospective matched cohort study.Data from all 50 states for Medicaid beneficiaries (2000 to 2005), Medicare beneficiaries (2006 to 2011), and dual-eligible persons (2000 to 2011).830 patients with UC pursuing elective colectomy and 7541 matched patients with UC pursuing medical therapy.The primary outcome was time to death. Cox proportional hazards models were used to compare the survival of patients with advanced UC treated with elective colectomy or medical therapy. The models controlled for significant comorbid conditions through matched and adjusted analysis.The mortality rates associated with elective surgery and medical therapy were 34 and 54 deaths per 1000 person-years, respectively. Elective colectomy was associated with improved survival compared with long-term medical therapy (adjusted hazard ratio [HR], 0.67 [95% CI, 0.52 to 0.87]), although this result did not remain statistically significant in all sensitivity analyses. Post hoc analysis by age group showed improved survival with surgery in patients aged 50 years or older with advanced UC (HR, 0.60 [CI, 0.45 to 0.79]; P = 0.032 for age-by-treatment interaction).Retrospective nonrandomized analysis is subject to residual confounding. The source cohort was derived from different databases throughout the study. Sensitivity and secondary analyses had reduced statistical power.Elective colectomy seemed to be associated with improved survival relative to medical therapy among patients aged 50 years or older with advanced UC.National Institutes of Health and Agency for Healthcare Research and Quality.

BACKGROUND The effectiveness of liver transplant (LT) in human immunodeficiency virus (HIV) and HIV/hepatitis C virus (HCV) coinfected recipients in the United States is unknown. We investigated (i) the effect of HIV on US patient and allograft LT outcomes, compared to HCV+ and HIV/HCV uninfected recipients and (ii) whether LT at centers that participated in the National Institutes of Health (NIH) Solid Organ Transplantation in HIV Trial, reflecting experience and a standardized approach to patient selection, impacted outcomes. METHODS A retrospective cohort study of primary LT recipients transplanted 27 February 2002 through 31 December 2013, categorized by serostatus: HCV+ (n = 20 829), HIV+ (n = 72), HIV+/HCV+ (n = 160), and HIV-/HCV- uninfected (n = 22 926) as reference. Survival was determined using Cox regression, stratified according to center NIH trial participation. RESULTS HCV (hazard ratio [HR] 1.46, 95% confidence interval [CI], 1.41-1.52) and HIV/HCV coinfection (HR 2.62, 95% CI, 2.06-3.33) were associated with mortality; HIV monoinfection was not (HR 1.37, 95% CI, .86-2.18). This was unchanged after stratification on NIH trial participation, although mortality was higher in NIH-enrolling (HIV+: HR 1.65, 95% CI, .93-2.92; HIV+/HCV+: HR 3.15, 95% CI, 2.32-4.28) than in non-enrolling centers (HIV+: HR 1.03, 95% CI, .43-2.47, HIV+/HCV+: HR 2.55, 95% CI, 1.64-3.96). Although allograft loss was higher in HIV/HCV coinfected recipients transplanted at enrolling (HR 2.64, 9%% CI, 1.91-3.64) vs nonenrolling centers (HR 2.22, 95% CI, 1.41-3.49), there was no difference in HIV and HCV monoinfected patients. CONCLUSIONS HIV+ LT recipient outcomes were superior to HCV+ or HIV/HCV coinfected recipients. Despite a standardized approach and plausibly more experience with HIV patients, transplantation at NIH study center did not improve outcomes.

UNLABELLED Previous studies have identified gaps in hepatitis B care. The objectives of this study were to evaluate the delivery of care among a national cohort of US veterans with chronic hepatitis B infection and examine risk factors for adverse clinical outcomes. We conducted a retrospective cohort study using the Veterans Health Administration Corporate Data Warehouse from 1999 to 2013 to evaluate (1) care delivery and (2) clinical outcomes such as hepatocellular carcinoma, hepatic decompensation, and mortality among US veterans with hepatitis B. Incidence rates with 95% confidence intervals were calculated and Cox regression models were used to evaluate clinical outcomes. We identified 21,419 veterans with a positive hepatitis B surface antigen, and 97% of patients had alanine aminotransferase and 44% had hepatitis B virus DNA testing; hepatitis B e antigen and hepatitis B e antibody were tested

Living donor liver transplantation (LDLT) is a comparable alternative to deceased donor liver transplantation and can mitigate the risk of dying while waiting for transplant. Although evidence exists of decreased utilization of living donor kidney transplants among racial minorities, little is known about access to LDLT among racial/ethnic minorities. We used Organ Procurement and Transplantation Network/United Network for Organ Sharing data from February 27, 2002 to June 4, 2014 from all adult liver transplant recipients at LDLT-capable transplant centers to evaluate differential utilization of LDLTs based on race/ethnicity. We then used data from 2 major urban transplant centers to analyze donor inquiries and donor rule-outs based on racial/ethnic determination. Nationally, of 35,401 total liver transplant recipients performed at a LDLT-performing transplant center, 2171 (6.1%) received a LDLT. In multivariate generalized estimating equation models, racial/ethnic minorities were significantly less likely to receive LDLTs when compared to white patients. For cholestatic liver disease, the odds ratios of receiving LDLT based on racial/ethnic group for African American, Hispanic, and Asian patients compared to white patients were 0.35 (95% CI, 0.20-0.60), 0.58 (95% CI, 0.34-0.99), and 0.11 (95% CI, 0.02-0.55), respectively. For noncholestatic liver disease, the odds ratios by racial/ethnic group were 0.53 (95% CI, 0.40-0.71), 0.78 (95% CI, 0.64-0.94), and 0.45 (95% CI, 0.33-0.60) respectively. Transplant center-specific data demonstrated that African American patients received fewer per-patient donation inquiries than white patients, whereas fewer African American potential donors were ruled out for obesity. In conclusion, racial/ethnic minorities receive a disproportionately low percentage of LDLTs, due in part to fewer initial inquiries by potential donors. This represents a major inequality in access to a vital health care resource and demands outreach to both patients and potential donors.

Organ transplantation is an acceptable option for human immunodeficiency virus (HIV)-infected patients with end-stage kidney or liver disease. With worse outcomes on the waitlist, HIV-infected patients may actually be disproportionately affected by the organ shortage in the United States. One potential solution is the use of HIV-infected deceased donors (HIVDD), recently legalized by the HIV Organ Policy Equity (HOPE) Act. This is the first analysis of patient-specific data from potential HIVDD, retrospectively examining charts of HIV-infected patients dying in care at six HIV clinics in Philadelphia, Pennsylvania from January 1, 2009 to June 30, 2014. Our data suggest that there are four to five potential HIVDD dying in Philadelphia annually who might yield two to three kidneys and three to five livers for transplant. Extrapolated nationally, this would approximate 356 potential HIVDD yielding 192 kidneys and 247 livers annually. However, several donor risk indices raise concerns about the quality of kidneys that could be recovered from HIVDD as a result of older donor age and comorbidities. On the other hand, livers from these potential HIVDD are of similar quality to HIV-negative donors dying locally, although there is a high prevalence of positive hepatitis C antibody.

In cystic fibrosis (CF) patients, elevations in 1 hr plasma glucose (PG1) during a 75 g oral glucose tolerance test are common, but of unclear long-term clinical relevance. Thus, we examined associations of PG1 with percent-predicted forced expiratory volume in 1 sec (FEV1 % predicted), CF exacerbations, and CF related diabetes (CFRD) development.We conducted a retrospective cohort study of 80 pediatric patients with CF (43 males) followed over 5 years in a single CF center. We considered the association between elevated versus normal PG1 (greater vs. no greater than 160 mg/dl) and linear changes in FEV1 % predicted over time for males and female, as well as the odds of a CF exacerbation and the odds of developing CFRD.No significant difference in FEV1 % predicted between normal versus elevated PG1 was found at baseline, or over time in males or females. However, males with elevated PG1 tended to have worse FEV1 % predicted over time than those with normal PG1 (reduction of 0.9 FEV1 % predicted/year, 95%CI: -2.5, 0.6). Subjects with PG1 160 mg/dl were more likely to develop CFRD (OR 4.5, 95%CI: 1.7, 18.7, P = 0.04) but CF exacerbation risk was similar in both groups.The risk of CFRD increases with PG1 160 mg/dl. No statistically significant evidence of an association between elevated PG1 and pulmonary function was found, yet our results do not exclude the possibility that in males, elevated PG1 may signal adverse changes in FEV1 % predicted over time. This possibility requires further study with a larger sample size.

Identification of acute liver failure (ALF) is important for post-marketing surveillance of medications, but the validity of using ICD-9 diagnoses and laboratory data to identify these events within electronic health records is unknown. We examined positive predictive values (PPVs) of hospital ICD-9 diagnoses and laboratory tests of liver dysfunction for identifying ALF within a large, community-based integrated care organization.We identified Kaiser Permanente Northern California health plan members (2004-2010) with a hospital diagnosis suggesting ALF (ICD-9 570, 572.2, 572.4, 572.8, 573.3, 573.8, or V42.7) plus an inpatient international normalized ratio ≥1.5 (off warfarin) and total bilirubin ≥5.0 mg/dL. Hospital records were reviewed by hepatologists to adjudicate ALF events. PPVs for confirmed outcomes were determined for individual ICD-9 diagnoses, diagnoses plus prescriptions for hepatic encephalopathy treatment, and combinations of diagnoses in the setting of coagulopathy and hyperbilirubinemia.Among 669 members with no pre-existing liver disease, chart review confirmed ALF in 62 (9%). Despite the presence of co-existing coagulopathy and hyperbilirubinemia, individual ICD-9 diagnoses had low PPVs (range, 5-15%); requiring prescriptions for encephalopathy treatment did not increase PPVs of these diagnoses (range, 2-23%). Hospital diagnoses of other liver disorders (ICD-9 573.8) plus hepatic coma (ICD-9 572.2) had high PPV (67%; 95%CI, 9-99%) but only identified two (3%) ALF events.Algorithms comprising relevant hospital diagnoses, laboratory evidence of liver dysfunction, and prescriptions for hepatic encephalopathy treatment had low PPVs for confirmed ALF events. Studies of ALF will need to rely on medical records to confirm this outcome.

Despite the use of administrative data to perform epidemiological and cost-effectiveness research on patients with hepatitis B or C virus (HBV, HCV), there are no data outside of the Veterans Health Administration validating whether International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes can accurately identify cirrhotic patients with HBV or HCV. The validation of such algorithms is necessary for future epidemiological studies.We evaluated the positive predictive value (PPV) of ICD-9-CM codes for identifying chronic HBV or HCV among cirrhotic patients within the University of Pennsylvania Health System, a large network that includes a tertiary care referral center, a community-based hospital, and multiple outpatient practices across southeastern Pennsylvania and southern New Jersey. We reviewed a random sample of 200 cirrhotic patients with ICD-9-CM codes for HCV and 150 cirrhotic patients with ICD-9-CM codes for HBV.The PPV of 1 inpatient or 2 outpatient HCV codes was 88.0% (168/191, 95% CI: 82.5-92.2%), while the PPV of 1 inpatient or 2 outpatient HBV codes was 81.3% (113/139, 95% CI: 73.8-87.4%). Several variations of the primary coding algorithm were evaluated to determine if different combinations of inpatient and/or outpatient ICD-9-CM codes could increase the PPV of the coding algorithm.ICD-9-CM codes can identify chronic HBV or HCV in cirrhotic patients with a high PPV and can be used in future epidemiologic studies to examine disease burden and the proper allocation of resources.

Background & Aims Despite recent attention to differences in access to livers for transplantation, research has focused on patients already on the wait list. We analyzed data from a large administrative database that represents the entire US population, and state Medicaid data, to identify factors associated with differences in access to wait lists for liver transplantation. Methods We performed a retrospective cohort study of transplant-eligible patients with end-stage liver disease using the HealthCore Integrated Research Database (2006–2014; n = 16,824) and Medicaid data from 5 states (2002–2009; California, Florida, New York, Ohio, and Pennsylvania; n = 67,706). Transplant-eligible patients had decompensated cirrhosis, hepatocellular carcinoma (HCC), and/or liver synthetic dysfunction, based on validated International Classification of Diseases, Ninth Revision–based algorithms and data from laboratory studies. Placement on the wait list was determined through linkage with the Organ Procurement and Transplantation Network database. Results In an unadjusted analysis of the HealthCore database, we found that 29% of patients with HCC were placed on the 2-year wait list (95% confidence interval [CI], 25.4%–33.0%) compared with 11.9% of patients with stage 4 cirrhosis (ascites) (95% CI, 11.0%–12.9%) and 12.6% of patients with stage 5 cirrhosis (ascites and variceal bleeding) (95% CI, 9.4%–15.2%). Among patients with each stage of cirrhosis, those with HCC were significantly more likely to be placed on the wait list; adjusted subhazard ratios ranged from 1.7 (for patients with stage 5 cirrhosis and HCC vs those without HCC) to 5.8 (for patients with stage 1 cirrhosis with HCC vs those without HCC). Medicaid beneficiaries with HCC were also more likely to be placed on the transplant wait list, compared with patients with decompensated cirrhosis, with a subhazard ratio of 2.34 (95% CI, 2.20–2.49). Local organ supply and wait list level demand were not associated with placement on the wait list. Conclusions In an analysis of US healthcare databases, we found patients with HCC to be more likely to be placed on liver transplant wait lists than patients with decompensated cirrhosis. Previously reported reductions in access to transplant care for wait-listed patients with decompensated cirrhosis underestimate the magnitude of this difference.