Association of Statin Usage and the Development of Diabetes Mellitus after Acute Pancreatitis.

BACKGROUND: Patients with acute pancreatitis (AP) have at least a 2-fold higher risk for developing postpancreatitis diabetes mellitus (PPDM). No therapies have prevented PPDM. Statins were demonstrated to possibly lower the incidence and severity of AP but have not been studied to prevent PPDM. METHODS: Data from a commercial insurance claim database (Optum Clinformatics) were used to assess the impact of statins on patients without pre-existing DM admitted for a first episode of AP in 118,479 patients. Regular statin usage was defined as filled statin prescriptions for at least 80% of the year prior to AP. The primary outcome was defined as PPDM. We constructed a propensity score and applied inverse probability of treatment weighting to balance baseline characteristics between groups. Using Cox proportional hazards regression modeling, we estimated the risk of PPDM, accounting for competing events. RESULTS: With a median of 3.5 years of follow-up, the 5-year cumulative incidence of PPDM was 7.5% (95% confidence interval [CI], 6.9% to 8.0%) among regular statin users and 12.7% (95% CI, 12.4% to 12.9%) among nonusers. Regular statin users had a 42% lower risk of developing PPDM compared with nonusers (hazard ratio, 0.58; 95% CI, 0.52 to 0.65; P < .001). Irregular statin users had a 15% lower risk of PPDM (hazard ratio, 0.85; 95% CI, 0.81 to 0.89; P < .001). Similar benefits were seen with low, moderate, and high statin doses. CONCLUSIONS: In a large database-based study, statin usage reduced the risk of developing DM after acute pancreatitis. Further prospective studies with long-term follow-up are needed to study the impact of statins on acute pancreatitis and prevention of PPDM.

A Prospective Cohort Study Evaluating PAN-PROMISE, a Patient-reported Outcome Measure to Detect Post-ERCP Morbidity.

BACKGROUND & AIMS: The Cotton Consensus (CC) criteria for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) may not capture post-ERCP morbidity. PAN-PROMISE, a patient-reported outcome measure (PROM), was developed to quantify acute pancreatitis-related morbidity. This study aims to determine the value of PAN-PROMISE in independently defining ERCP-related morbidity. METHODS: We conducted a prospective cohort study of patients undergoing ERCP at 2 academic centers from September 2021 to August 2022. We administered PAN-PROMISE and assessed quality of life and work productivity at baseline, 48 to 72 hours, 7 days, and 30 days following ERCP. PEP was defined by a 3-physician committee using the CC criteria. We defined high morbidity following ERCP (elevated PROM) by an increase of PAN-PROMISE score of >7 at 7 days post-procedure. The McNemar test assessed discordance between PEP and elevated-PROM. RESULTS: A total of 679 patients were enrolled. Choledocholithiasis (30%) and malignant biliary obstruction (29%) were the main indications for ERCP. Thirty-two patients (4.7%) developed PEP. One hundred forty-seven patients (21.6%) had an elevated PROM, whereas only 20 of them (13.4%) had PEP by the CC criteria (P < .001 for discordance). An elevated PROM strongly correlated with lower physical quality of life and increased direct and indirect health care costs ($80 and $25 per point increase in PAN-PROMISE, respectively). Patients with pancreatic cancer (odds ratio, 4.52; 95% confidence interval, 1.68-10.74) and primary sclerosing cholangitis (odds ratio, 1.79; 95% confidence interval, 1.29-2.45) had the highest odds of elevated PROM. CONCLUSIONS: A substantial number of patients experience significant morbidity after ERCP despite not developing PEP or other adverse events. Future studies are needed to characterize better the reasons behind this increase in symptoms and potential interventions to reduce the symptom burden post-ERCP. CLINICALTRIALS: gov number, NCT05310409.

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.

Cardiac index and hepatopulmonary syndrome in liver transplantation candidates: The pulmonary vascular complications of liver disease study.

BACKGROUND AND AIMS: Hepatopulmonary syndrome (HPS) and a hyperdynamic circulation are common complications of advanced liver disease, but the relationship between HPS and cardiac index (CI) is poorly understood. We sought to compare CI in patients with and without HPS and to assess the relationship between CI and symptoms, quality of life, gas exchange, and exercise capacity among liver transplantation (LT) candidates. We performed a cross-sectional analysis within the Pulmonary Vascular Complications of Liver Disease 2 study, a multicenter prospective cohort study of patients being evaluated for LT. We excluded patients with obstructive or restrictive lung disease, intracardiac shunting, and portopulmonary hypertension. We included 214 patients (81 with HPS and 133 controls without HPS). Compared with controls, patients with HPS had a higher CI (least square mean 3.2 L/min/m 2 , 95% CI 3.1-3.4 vs. 2.8 L/min/m 2 , 95% CI 2.7-3.0, p < 0.001) after adjustment for age, sex, Model for End-stage Liver Disease-Sodium (MELD-Na) score and beta-blocker use, and a lower systemic vascular resistance. Among all LT candidates, CI was correlated with oxygenation (Alveolar-arterial oxygen gradient r =0.27, p < 0.001), intrapulmonary vasodilatation severity ( p < 0.001), and biomarkers of angiogenesis. Higher CI was independently associated with dyspnea and worse functional class and physical quality of life after adjusting for age, sex, MELD-Na, beta-blocker use, and HPS status. HPS was associated with a higher CI among LT candidates. Independent of HPS, higher CI was associated with increased dyspnea and worse functional class, quality of life, and arterial oxygenation.

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.

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.

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.

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.

Development and Validation of a Model to Predict Long-Term Survival After Liver Transplantation.

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.

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.

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.

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.

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.

Prevalence and Impact of Restrictive Lung Disease in Liver Transplant Candidates.

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) <70% predicted, were compared. Restriction prevalence was 18.4% (63/343). Higher Model for End-Stage Liver Disease-sodium score (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02-1.11; P = 0.007), the presence of pleural effusions (OR, 3.59; 95% CI, 1.96-6.58; P < 0.001), and a history of ascites (OR, 2.59; 95% CI, 1.26-5.33; P = 0.01) were associated with the presence of restriction, though one-third with restriction had neither pleural effusions nor ascites. In multivariate analysis, restriction was significantly and independently associated with lower 6-minute walk distances (least squares mean, 342.0 [95% CI, 316.6-367.4] m versus 395.7 [95% CI, 381.2-410.2] m; P < 0.001), dyspnea (OR, 2.69; 95% CI, 1.46-4.95; P = 0.002), and lower physical component summary Short Form 36 scores indicating worse quality of life (least squares mean, 34.1 [95% CI, 31.5-36.7] versus 38.2 [95% CI, 36.6-39.7]; P = 0.004). Lower FVC percent predicted was associated with an increased risk of death (hazard ratio, 1.16; 95% CI, 1.04-1.27 per 10-point decrease in FVC percent predicted; P = 0.01). Restriction and abnormal lung function are common in LT candidates; can be present in the absence of an obvious cause, such as pleural effusions or ascites; and is associated with worse exercise capacity, quality of life, and survival.

Transplantation for Alcoholic Hepatitis: Are We Achieving Justice and Utility?

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.

Pulse Oximetry Is Insensitive for Detection of Hepatopulmonary Syndrome in Patients Evaluated for Liver Transplantation.

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 <96%, recommended by practice guidelines as a threshold to require further testing, had low sensitivity (28%; 95% CI, 18%-28%). The c-statistic of SpO2 in discriminating HPS with a partial pressure of oxygen (PaO2 ) <60 mm Hg (eligible for LT exception points) was 0.76 (95% CI, 0.46-1.00). An SpO2 cutoff of <96% had higher sensitivity for detecting HPS with PaO2 <60 mm Hg (71%; 95% CI, 38%-100%) but was still inadequate. Conclusion: Pulse oximetry is not sufficiently sensitive to screen for HPS in LT candidates. Arterial blood gas and CE are required in LT candidates for diagnosis of HPS.

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.

Timing of Gastrointestinal Bleeding After Implantation of Left Ventricular Assist Devices Associates With Anatomic Location, Presentation, and Management.

BACKGROUND & AIMS: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Mortality and Kidney Transplantation Outcomes Among Hepatitis C Virus-Seropositive Maintenance Dialysis Patients: A Retrospective Cohort Study.

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.

Sex hormone levels by presence and severity of cirrhosis in women with chronic hepatitis C virus infection.

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 57 years (interquartile range [IQR] 53-62). Compared to noncirrhotics, cirrhotic women had higher oestradiol (11.0 vs 6.0 pg/mL, P = 0.05) and oestrone levels (32.0 vs 8.0 ng/mL, P < 0.001), and lower sex hormone binding globulin (SHBG) (69.2 vs 155.6 nmol/L, P = 0.001), and FSH levels (4.9 vs 89.6 mIU/mL, P < 0.001). Among cirrhotic women, there was a progressive decline in FSH and SHBG and concurrent rise in oestrone levels from CTP class A to C (test of trend, P values ≤0.02). Cirrhosis is associated with lower FSH and SHBG levels in cirrhotic compared to noncirrhotic women with HCV infection. In cirrhotic women, these levels demonstrate steady decline by disease severity. Given known associations of low SHBG and FSH with cardio-metabolic disease, the clinical implications of hormonal changes by cirrhosis severity in HCV-infected women warrants investigation.