Six-Minute walk distance predicts outcomes in liver transplant candidates.

A 6-minute walk test is a simple tool for assessing submaximal exercise capacity. We sought to determine whether a 6-minute walk distance (6MWD) predicts outcomes in patients with cirrhosis. The Pulmonary Vascular Complications of Liver Disease 2 study is a multicenter, prospective cohort study that enrolled adults with portal hypertension during liver transplantation evaluation. We excluded subjects with an incident or prevalent portopulmonary hypertension. The 6-minute walk test was performed using standardized methods. Cox proportional hazards modeling and multivariable linear regression analysis were performed to determine the relationship between baseline 6MWD and outcomes. The study sample included 352 subjects. The mean 6MWD was 391±101 m. For each 50-meter decrease in 6MWD, there was a 25% increase in the risk of death (HR 1.25, 95% CI [1.11, 1.41], p < 0.001) after adjustment for age, gender, body mass index, MELD-Na, and liver transplant as a time-varying covariate. In a multistate model, each 50-meter decrease in 6MWD was associated with an increased risk of death before the liver transplant ( p < 0.001) but not after the transplant. 6MWD was similar to MELD-Na in discriminating mortality. Each 50-meter decrease in 6MWD was associated with an increase in all-cause ( p < 0.001) and transplant-free hospitalizations ( p < 0.001) in multivariable models for time-to-recurrent events. Shorter 6MWD was associated with worse Short Form-36 physical ( p < 0.001) and mental component scores ( p = 0.05). In conclusion, shorter 6MWD is associated with an increased risk of death, hospitalizations, and worse quality of life in patients evaluated for liver transplantation. The 6-minute walk distance may be a useful adjunct for risk assessment in patients undergoing liver transplant evaluation.

The Hepatitis C Care Cascade During the Direct-Acting Antiviral Era in a United States Commercially Insured Population.

Background: Periodic surveillance of the hepatitis C virus (HCV) care cascade is important for tracking progress toward HCV elimination goals, identifying gaps in care, and prioritizing resource allocation. In the pre-direct-acting antiviral (DAA) era, it was estimated that 50% of HCV-infected individuals were diagnosed and that 16% had been prescribed interferon-based therapy. Since then, few studies utilizing nationally representative data from the DAA era have been conducted in the United States. Methods: We performed a cross-sectional study to describe the HCV care cascade in the United States using the Optum de-identified Clinformatics® Data Mart Database to identify a nationally representative sample of commercially insured beneficiaries between January 1, 2014 and December 31, 2019. We estimated the number of HCV-viremic individuals in Optum based on national HCV prevalence estimates and determined the proportion who had: (1) recorded diagnosis of HCV infection, (2) recorded HCV diagnosis and underwent HCV RNA testing, (3) DAA treatment dispensed, and (4) assessment for cure. Results: Among 120,311 individuals estimated to have HCV viremia in Optum during the study period, 109,233 (90.8%; 95% CI, 90.6%-91.0%) had a recorded diagnosis of HCV infection, 75,549 (62.8%; 95% CI, 62.5%-63.1%) had a recorded diagnosis of HCV infection and underwent HCV RNA testing, 41,102 (34.2%; 95% CI, 33.9%-34.4%) were dispensed DAA treatment, and 25,760 (21.4%; 95% CI, 21.2%-21.6%) were assessed for cure. Conclusions: Gaps remain between the delivery of HCV-related care and national treatment goals among commercially insured adults. Efforts are needed to increase HCV treatment among people diagnosed with chronic HCV infection to achieve national elimination goals.

Gastrointestinal Features of 22q11.2 Deletion Syndrome Include Chronic Motility Problems From Childhood to Adulthood.

OBJECTIVES: 22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion syndrome and has a multisystemic presentation including gastrointestinal features that have not yet been fully described. Our aim was to examine lifetime gastrointestinal problems in a large cohort of patients with 22q11.2DS. METHODS: All patients followed in the 22q and You Center at the Children's Hospital of Philadelphia (n = 1421) were retrospectively screened for: 1) age ≥ 17 years, 2) documented chromosomal microdeletion within the 22q11.2 LCR22A-LCR22D region, and 3) sufficient clinical data to characterize the adult gastrointestinal phenotype. Gastrointestinal problems in childhood, adolescence, and adulthood were summarized. Statistical association testing of symptoms against other patient characteristics was performed. RESULTS: Included patients (n = 206; 46% female; mean age, 27 years; median follow-up, 21 years) had similar clinical characteristics to the overall cohort. Genetic distribution was also similar, with 96% having deletions including the critical LCR22A-LCR22B segment (95% in the overall cohort). Most patients experienced chronic gastrointestinal symptoms in their lifetime (91%), but congenital gastrointestinal malformations (3.5%) and gastrointestinal autoimmune diseases (1.5%) were uncommon. Chronic symptoms without anatomic or pathologic abnormalities represented the vast burden of illness. Chronic symptoms in adulthood are associated with other chronic gastrointestinal symptoms and psychiatric comorbidities ( P < 0.01) but not with deletion size or physiologic comorbidities ( P > 0.05). One exception was increased nausea/vomiting in hypothyroidism ( P = 0.002). CONCLUSIONS: Functional gastrointestinal disorders (FGIDs) are a common cause of ill health in children and adults with 22q11.2DS. Providers should consider screening for the deletion in patients presenting with FGIDs and associated comorbidities such as neuropsychiatric illness, congenital heart disease, and palatal abnormalities.

Effect of Patient-Directed Messaging on Colorectal Cancer Screening: A Randomized Clinical Trial.

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Interventions: 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. Main Outcomes and Measures: 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. Results: 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). Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT03310892.

Disconnected Pancreatic Duct Syndrome: Pancreatitis of the Disconnected Pancreas and Its Role in the Development of Diabetes Mellitus.

INTRODUCTION: 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. METHODS: 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) occurring >3 months after NP. Cox proportional hazards regression was used to evaluate the relationship between DPDS and NODAP. RESULTS: 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. DISCUSSION: 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.

Impact of hepatopulmonary syndrome in liver transplantation candidates and the role of angiogenesis.

BACKGROUND: Hepatopulmonary 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. METHODS: The 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. RESULTS: We 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. CONCLUSION: Hepatopulmonary syndrome was associated with a profile of abnormal systemic angiogenesis, worse exercise and functional capacity, and an overall increased risk of death.

The impact of disease-related knowledge on perceptions of stigma among patients with Hepatitis C Virus (HCV) infection.

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 (ß, 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.

Radiologically Placed Peritoneovenous Shunt is an Acceptable Treatment Alternative for Refractory Ascites Due to End-Stage Liver Disease.

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.

Obesity is a risk factor for progression to kidney transplant waitlisting after liver transplantation.

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 ≥ 30 kg/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: ≥35 kg/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.

Predicting survival after liver transplantation in patients with hepatocellular carcinoma using the LiTES-HCC score.

BACKGROUND & AIMS: Liver transplant priority in the US and Europe follows the 'sickest-first' principle. However, for patients with hepatocellular carcinoma (HCC), priority is based on binary tumor criteria to expedite transplant for patients with 'acceptable' post-transplant outcomes. Newer risk scores developed to overcome limitations of these binary criteria are insufficient to be used for waitlist priority as they focus solely on HCC-related pre-transplant variables. We sought to develop a risk score to predict post-transplant survival for patients using HCC- and non-HCC-related variables. METHODS: We performed a retrospective cohort study using national registry data on adult deceased-donor liver transplant (DDLT) recipients with HCC from 2/27/02-12/31/18. We fit Cox regression models focused on 5- and 10-year survival to estimate beta coefficients for a risk score using manual variable selection. We then calculated absolute predicted survival time and compared it to available risk scores. RESULTS: Among 6,502 adult DDLT recipients with HCC, 11 variables were selected in the final model. The AUCs at 5- and 10-years were: 0.62, 95% CI 0.57-0.67 and 0.65, 95% CI 0.58-0.72, which was not statistically significantly different to the Metroticket and HALT-HCC scores. The LiTES-HCC score was able to discriminate patients based on post-transplant survival among those meeting Milan and UCSF criteria. CONCLUSION: We developed and validated a risk score to predict post-transplant survival for patients with HCC. By including HCC- and non-HCC-related variables (e.g., age, chronic kidney disease), this score could allow transplant professionals to prioritize patients with HCC in terms of predicted survival. In the future, this score could be integrated into survival benefit-based models to lead to meaningful improvements in life-years at the population level. LAY SUMMARY: We created a risk score to predict how long patients with liver cancer will live if they get a liver transplant. In the future, this could be used to decide which waitlisted patients should get the next transplant.

Estrogen Signaling and Portopulmonary Hypertension: The Pulmonary Vascular Complications of Liver Disease Study (PVCLD2).

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 <40 mm Hg, and normal RV function by echocardiography. We genotyped three SNPs in CYP19A1 and CYP1B1 using TaqMan and imputed SNPs in estrogen receptor 1 using genome-wide markers. Estrogen metabolites were measured in blood and urine samples. There were 37 patients with POPH and 290 controls. Mean age was 57 years, and 36% were female. The risk allele A in rs7175922 (CYP19A1) was significantly associated with higher levels of estradiol (P = 0.02) and an increased risk of POPH (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.12-4.91; P = 0.02) whereas other SNPs were not. Lower urinary 2-hydroxyestrogen/16-α-hydroxyestrone (OR per 1-ln decrease = 2.04; 95% CI, 1.16-3.57; P = 0.01), lower plasma levels of dehydroepiandrosterone-sulfate (OR per 1-ln decrease = 2.38; 95% CI, 1.56-3.85; P < 0.001), and higher plasma levels of 16-α-hydroxyestradiol (OR per 1-ln increase = 2.16; 95% CI, 1.61-2.98; P < 0.001) were associated with POPH. CONCLUSIONS: Genetic variation in aromatase and changes in estrogen metabolites were associated with POPH.

Adherence to pregnancy hepatitis B care guidelines in women and infants in the United States and evaluation of two interventions to improve care: A multicentre hospital-based study.

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.

Quantifying Sex-Based Disparities in Liver Allocation.

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.

One-Year Outcomes of Percutaneous Coronary Intervention in Patients with End-Stage Liver Disease.

BACKGROUND: Patients with cirrhosis and coronary artery disease (CAD) are at high risk for morbidity during surgical revascularization so they are often referred for complex percutaneous coronary intervention (PCI). Percutaneous coronary intervention in the cirrhotic population also has inherent risks; however, quantifiable data on long-term outcomes are lacking. METHODS: Patients with angiographically significant CAD and cirrhosis were identified from the catheterization lab databases of the University of Pennsylvania Health System between 2007 and 2015. Outcomes were obtained from the medical record and telephonic contact with patients/families. RESULTS: Percutaneous coronary intervention was successfully performed in 42 patients (51 PCIs). Twenty-nine patients with significant CAD were managed medically (36 angiograms). The primary outcome (a composite of mortality, subsequent revascularization, and myocardial infarction) was not significantly different between the 2 groups during a follow-up period at 1 year (PCI: 50%, Control: 40%, P = .383). In the PCI group, a composite adverse outcome rate that included acute kidney injury (AKI), severe bleed, and peri-procedural stroke was elevated (40%), with severe bleeding occurring after 23% of PCI events and post-procedural AKI occurring after 26% of events. The medical management group had significantly fewer total matched adverse outcomes (17% vs 40% in the PCI group, P = .03), with severe bleeding occurring after 11% of events and AKI occurring after 6% of events. Increased risk of adverse events following PCI was associated with severity of liver disease by Child-Pugh class. CONCLUSIONS: Percutaneous coronary intervention in patients with cirrhosis is associated with an elevated risk of adverse events, including severe bleeding and AKI.

Clinical utility of surveillance and clinically prompted right heart catheterization in patients listed for heart transplantation.

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 <12.2 g/dL (OR 2.96; CI 1.36-6.42) and a total bilirubin 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.

Tacrolimus and Indomethacin Are Safe and Effective at Reducing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography in Patients Who Have Undergone Liver Transplantation.

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.

Transient elastography reliably estimates liver fibrosis in autoimmune hepatitis.

AIM OF THE STUDY: Autoimmune hepatitis (AIH) may result in liver fibrosis and cirrhosis. While the gold standard for staging fibrosis is biopsy, transient elastography (TE) represents a non-invasive alternative. TE has been validated in several chronic liver diseases, but no data exist to establish an association between histologic fibrosis on biopsy and TE liver stiffness measurements among a United States cohort of AIH patients. MATERIAL AND METHODS: We conducted a retrospective cohort study of 53 AIH patients who received TE assessment and liver biopsy. Histologic fibrosis was classified as advanced (F3-F4) or mild/moderate (F0-F2). Liver stiffness by TE was measured in kilopascals (kPa). We performed a score test for trend to test the association between histologic fibrosis stage and increasing TE kPa categories. Analyses incorporated probe type (medium or extra-large) and body mass index (BMI). Linear regression was used to generate predicted associations between median kPa and histologic fibrosis score with the medium probe. RESULTS: The cohort was primarily female (83%) with median age 56.3 years. Increasing kPa category was associated with worsening fibrosis stage when using the medium probe (p = 0.04), but not the extra-large probe (p = 0.40). BMI, however, differed between these groups (median 25.8 vs. 33.1, respectively, p < 0.001). In adjusted linear regression, increasing median kPa corresponded well to worsening fibrosis stage (p = 0.003). CONCLUSIONS: In a United States AIH cohort, increasing TE kPa measurements are associated with worsening histologic fibrosis staging. While medium probe performance was superior to the extra-large probe, significant variation in BMI between groups may explain this difference.