Performance of race-neutral eGFR equations in patients with decompensated cirrhosis.

The 2021 Chronic Kidney Disease Epidemiology Collaboration equation [CKD-EPI 2021] is a race-neutral equation recently developed and rapidly implemented as a reference standard to estimate glomerular filtration rate(GFR). However, its role in cirrhosis has not been examined especially in low GFR. We analyzed the performance of CKD-EPI 2021 compared to other equations with protocol measured GFR(mGFR) in cirrhosis. We analyzed 2090 unique adult patients with cirrhosis undergoing protocol GFR measurements using iothalamate clearance from 1985-2015 when listed for liver transplantation at Baylor University in Dallas and Fort Worth, Texas. Using mGFR as a reference standard, the CKD-EPI 2021 was compared to CKD-EPI 2012, MDRD-4, MDRD-6, RFH and GRAIL overall and in certain subgroups(ascites, mGFR≤30 mL/min/1.73 m 2 , diagnosis, MELD and gender). We examined bias(difference between eGFR and mGFR), accuracy(p30: eGFR within ±30% of mGFR) and agreement between eGFR and mGFR categories. CKD-EPI 2021 had the 2 nd lowest bias across the entire range of GFR after GRAIL (6.6 vs. 4.6 mL/min/1.73 m 2 , respectively, p <0.001). Accuracy of CKD-EPI 2021 was similar to CKD-EPI 2012 (p30=67.8% vs. 67.9%, respectively) that was higher than the other equations ( p <0.001). It had a similar performance in patients with ascites, by diagnoses, MELD subgroups, by sex and in non-Black patients. However, it had a relatively higher overestimation in mGFR≤30 mL/min/1.73 m 2 than most equations (18.5 mL/min/1.73m 2 , p <0.001). Specifically, 64% of patients with mGFR≤30 mL/min/1.73m 2 were incorrectly classified to a less severe CKD stage by CKD-EPI 2021. In Blacks, CKD-EPI 2021 underestimated eGFR by 17.9 mL/min/1.73 m 2 that was higher than the alternate equations except RFH ( p <0.001). The novel race-neutral eGFR equation, CKD-EPI 2021, improves the GFR estimation overall but may not accurately capture true kidney function in cirrhosis specifically at low GFR. There is an urgent need for a race-neutral equation in liver disease reflecting the complexity of kidney function physiology unique to cirrhosis given implications for organ allocation and dual organ transplant.

Social determinants of health impact mortality from HCC and cholangiocarcinoma: a population-based cohort study.

BACKGROUND AND AIMS: The social determinants of health can pose barriers to accessing cancer screening and treatment and have been associated with cancer mortality. However, it is not clear whether area deprivation is independently associated with mortality in HCC and cholangiocarcinoma when controlling for individual-level social determinants of health. APPROACH AND RESULTS: The cohort included individuals over 18 years old diagnosed with HCC (N=3460) or cholangiocarcinoma (N=781) and reported to the Indiana State Cancer Registry from 2009 to 2017. Area disadvantage was measured using the social deprivation index (SDI). SDI was obtained by linking addresses to the American Community Survey. Individual social determinants of health included race, ethnicity, sex, marital status, and insurance type. The primary outcome was mortality while controlling for SDI and individual social determinants of health by means of Cox proportional hazard modeling. In HCC, living in a neighborhood in the fourth quartile of census-track SDI (most deprived) was associated with higher mortality (HR: 1.14, 95% CI, 1.003-1.30, p=0.04) than living in a first quartile SDI neighborhood. Being uninsured (HR: 1.64, 95% CI, 1.30-2.07, p<0.0001) and never being married (HR: 1.31, 95% CI, 1.15-1.48, p<0.0001) were also associated with mortality in HCC. In cholangiocarcinoma, SDI was not associated with mortality. CONCLUSIONS: Social deprivation was independently associated with mortality in HCC but not cholangiocarcinoma. Further research is needed to better understand how to intervene on both area and individual social determinants of health and develop interventions to address these disparities.

Assessment of Vascular and Valvular Calcification Improves Screening for Coronary Artery Disease Before Liver Transplantation.

Coronary artery disease (CAD) is common in patients with cirrhosis who underwent orthotopic liver transplantation (OLT) evaluation and stress echocardiogram (echo) has a low sensitivity in these patients. This study aimed to assess the impact of vascular and valvular calcification on the ability to identify CAD before OLT. We performed a case-control study of 88 patients with and 97 without obstructive CAD who underwent OLT evaluation. All patients had a preoperative stress echo, abdominal computed tomography, and cardiac catheterization. A series of nested logistic regression models of CAD were fit by adding independent variables of vascular (including coronary) calcification, aortic and mitral valve calcification, age, gender, and history of diabetes mellitus requiring insulin to a baseline model of abnormal stress echo. Compared with stress echo alone, identification of the presence or absence of vascular and valvular calcification on routine preoperative computed tomography and echo improved the diagnostic performance for the detection of CAD based on coronary angiogram when combined with stress echo in patients with cirrhosis who underwent OLT evaluation (area under the curve 0.58 vs 0.73, p <0.001), which is even further improved when age, gender, and history of diabetes mellitus requiring insulin are considered (area under the curve 0.58 vs 0.80, p <0.001). Achieving target heart rate (p = 0.92) or rate-pressure product >25,000 (p = 0.63) did not improve the ability of stress echo to identify CAD. In conclusion, the use of abdominal vascular, coronary artery, and valvular calcification, along with stress echo, improves the ability to identify and rule out obstructive CAD before OLT compared with stress echo alone.

Palliative Care, Patient-Reported Measures, and Outcomes in Hospitalized Patients With Cirrhosis.

CONTEXT: Studies of palliative care (PC) in hospitalized patients with cirrhosis have been retrospective, with limited evaluation of patient-reported measures and outcomes. OBJECTIVES: To examine the relationship between PC, patient-reported measures (quality of life and functional status), and outcomes. METHODS: We performed a prospective cohort study of patients with cirrhosis hospitalized from 2014 to 2019. We recorded PC consultation details, quality of life (chronic liver disease questionnaire), and functional status (functional status questionnaire). Patients were followed for 90 days to assess readmissions, costs, and mortality. RESULTS: Seventy-four of 679 patients saw PC, often later in the hospitalization (median hospital day 8; IQR 4-16). Those who saw PC had greater Charlson comorbidity index (mean 6.8 vs. 5.9), MELD (mean 25 vs. 20), and prior 30-day admission (47% vs. 35%). Compared to those who did not see PC, PC patients had greater impairments in intermediate activities of daily living (83% vs. 72%), social activity (72% vs. 59%), quality of interactions (49% vs. 36%), abdominal symptoms (mean score 3.1 vs. 3.6), activity (mean 3.3 vs. 3.6), and overall quality of life (mean 3.6 vs. 3.8). PC was associated with fewer transfusions and upper endoscopies and with greater completion of advanced directives. After multivariable adjustment, PC was not associated with intensive care, 30-day readmissions, 90-day costs, or mortality. CONCLUSION: PC occurs infrequently and late in those with more severe liver disease and functional impairment. PC may be associated with reduction in utilization and greater completion of advanced directives. Randomized trials are needed to evaluate PC for this population.

Patient-Reported Outcome Measures Modestly Enhance Prediction of Readmission in Patients with Cirrhosis.

BACKGROUND & AIMS: Patients with cirrhosis have high rates of hospital readmission, but prediction models are suboptimal and have not included important patient-reported outcome measures (PROMs). In a large prospective cohort, we examined the impact of PROMs on prediction of 30-day readmissions. METHODS: We performed a prospective cohort study of adults with cirrhosis admitted to a tertiary center between June 2014 and March 2020. We collected clinical information, socioeconomic status, and PROMs addressing functional status and quality of life. We used hierarchical competing risk time-to-event analysis to examine the impact of PROMs on readmission prediction. RESULTS: A total of 654 patients were discharged alive, and 247 (38%) were readmitted within 30 days. Readmission was independently associated with cerebrovascular disease, ascites, prior hospital admission, admission via the emergency department, lower albumin, higher Model for End-Stage Liver Disease, discharge with public transportation, and impaired basic activities of daily living and quality-of-life activity domain. Reduced readmission was associated with cancer, admission for infection, children at home, and impaired emotional function. Compared with a model including only clinical variables, addition of functional status and quality-of-life variables improved the area under the receiver-operating characteristic curve from 0.72 to 0.73 and 0.75, with net reclassification indices of 0.22 and 0.18, respectively. Socioeconomic variables did not significantly improve prediction compared with clinical variables alone. Compared with a model using electronically available variables only, no models improved prediction when examined with integrated discrimination improvement. CONCLUSIONS: PROMs may marginally add to the prediction of 30-day readmissions for patients with cirrhosis. Poor social support and disability are associated with readmissions and may be high-yield targets for future interventions.

Focused Education Increases Hepatocellular Cancer Screening in Patients with Cirrhosis Regardless of Functional Health Literacy.

BACKGROUND: Health education interventions are successful in modifying lifestyle. Functional health literacy (FHL) can determine patient adherence to clinic visits and procedures and may adversely impact the success of these interventions. AIMS: We sought to evaluate the hypothesis that a health education intervention would improve compliance with hepatocellular cancer (HCC) screening and that poor FHL would reduce such compliance. METHODS: We assessed FHL using a short version test of functional health literacy in adults (STOFHLA). Cirrhotic patients free of HCC were prospectively enrolled from clinics and provided an educational intervention consisting of focused physician-led discussion regarding cirrhosis and HCC, along with written material on these topics for the subject to review at home. Patients were subsequently followed for 6 months (prospective time period), and the same cohort's clinic/HCC screening behavior between 6 and 12 months prior to the educational intervention (retrospective time period) was compared. RESULTS: In total, 104 cirrhotic patients (age 60.01 ± 8.58 years, 80% men, MELD 12.70 ± 5.76) were included. Of these, 89 (85.57%) of patients had educational level 12th grade and higher. There were 76% (n = 79) with adequate, while 24% (n = 25) had inadequate/marginal FHL on S-TOHFLA. The number of HCC-related imaging increased from 59 (56.7%) to 86 (82.6%, p < 0.0001) post-education in the prospective compared to prior time period which was similar regardless of FHL. CONCLUSIONS: While the educational intervention was successful in improving compliance with HCC screenings, FHL status did not impact the power of this intervention. Hence, the combination of specific verbal information, along with targeted written material, improved compliance with clinic visits and liver imaging for HCC.

Bleeding After Elective Interventional Endoscopic Procedures in a Large Cohort of Patients With Cirrhosis.

INTRODUCTION: Elective therapeutic endoscopy is an important component of care of cirrhotic patients, but there are concerns regarding the risk of bleeding. This study examined the incidence, risk factors, and outcomes of bleeding after endoscopic variceal ligation (EVL), colonoscopic polypectomy, and endoscopic retrograde cholangiopancreatography with sphincterotomy in cirrhotic patients. METHODS: A cohort study of patients with cirrhosis who underwent the above procedures at a single center between 2012 and 2014 was performed. Patients with active bleeding at the time of procedure were excluded. Patients were followed for 30 days to assess for postprocedural bleeding and for 90 days for mortality. RESULTS: A total of 1,324 procedures were performed in 857 patients (886 upper endoscopies, 358 colonoscopies, and 80 endoscopic retrograde cholangiopancreatograpies). After EVL, bleeding occurred in 2.8%; after polypectomy, bleeding occurred in 2.0%; and after sphincterotomy, bleeding occurred in 3.8%. Independent predictors of bleeding after EVL and polypectomy included younger age and lower hemoglobin. For EVL, bleeding was also associated with infection and model for end-stage liver disease-Na. International normalized ratio was associated with bleeding in univariate analysis only, and platelet count was not associated with bleeding in any procedure. Bleeding after EVL was associated with 29% 90-day mortality, and bleeding after polypectomy was associated with 14% mortality. Of the 3 patients with postsphincterotomy bleeding, none were outliers regarding their baseline characteristics. DISCUSSION: In patients with cirrhosis, bleeding occurs infrequently after elective therapeutic endoscopy and is associated with younger age, lower hemoglobin, and high mortality. Consideration of these risk factors may guide appropriate timing and preprocedural management to optimize outcomes.

Improving Outcomes of Bariatric Surgery in Patients With Cirrhosis in the United States: A Nationwide Assessment.

INTRODUCTION: With increasing burden of obesity and liver disease in the United States, a better understanding of bariatric surgery in context of cirrhosis is needed. We described trends of hospital-based outcomes of bariatric surgery among cirrhotics and determined effect of volume status and type of surgery on these outcomes. METHODS: In this population-based study, admissions for bariatric surgery were extracted from the National Inpatient Sample using International Classification of Diseases, 9th and 10th Revision, Clinical Modification codes from 2004 to 2016 and grouped by cirrhosis status, type of bariatric surgery, and center volume. In-hospital mortality, complications, and their trends were compared between these groups using weighted counts, odds ratios [ORs], and logistic regression. RESULTS: Among 1,679,828 admissions for bariatric surgery, 9,802 (0.58%) had cirrhosis. Cirrhosis admissions were more likely to be in white men, had higher Elixhauser Index, and higher in-hospital complications rates including death (1.81% vs 0.17%), acute kidney injury (4.5% vs 1.2%), bleeding (2.9% vs 1.1%), and operative complications (2% vs 0.6%) (P < 0.001 for all) compared to those without cirrhosis. Overtime, restrictive surgeries have grown in number (12%-71%) and complications rates have trended down in both groups. Cirrhotics undergoing bariatric surgery at low-volume centers (<50 procedures per year) and nonrestrictive surgery had a higher inpatient mortality rate (adjusted OR 4.50, 95% confidence interval 3.14-6.45, adjusted OR 4.00, 95% confidence interval 2.68-5.97, respectively). DISCUSSION: Contemporary data indicate that among admissions for bariatric surgery, there is a shift to restrictive-type surgeries with an improvement in-hospital complications and mortality. However, patients with cirrhosis especially those at low-volume centers have significantly higher risk of worse outcomes (see Visual abstract, Supplementary Digital Content, http://links.lww.com/AJG/B648).

Admission plasma uromodulin and the risk of acute kidney injury in hospitalized patients with cirrhosis: a pilot study.

Acute kidney injury (AKI) is a common complication in hospitalized patients with cirrhosis. Uromodulin, a protein uniquely produced by the kidney and released both in the urine and circulation, has been shown to regulate AKI and is linked to tubular reserve. Although low levels of urine uromodulin are associated with AKI after cardiac surgery, it is unclear whether circulating uromodulin can stratify the risk of AKI, particularly in a susceptible population such as hospitalized patients with cirrhosis. Thus, we investigated whether plasma uromodulin measured at the time of admission is associated with subsequent hospital-acquired AKI (defined by a rise in serum creatinine >0.3mg/dL within 48 h or ≥ 1.5 times baseline) in patients with cirrhosis. A total of 98 patients [mean age 54 yr, Model for Endstage Liver Disease Sodium (MELD-Na) score 19, and baseline creatinine of 0.95 mg/dL] were included, of which 13% (n = 13) developed AKI. Median uromodulin levels were significantly lower in patients who developed AKI compared with patients who did not (9.30 vs. 13.35 ng/mL, P = 0.02). After adjusting for age, sex, diabetes, hypertension, albumin, and MELD-Na score as covariates on multivariable logistic regression, uromodulin was independently associated with AKI [odd ratios of 1.19 (95% confidence interval 1.02, 1.37; P = 0.02)]. Lower uromodulin levels on admission are associated with increased odds of subsequent AKI in hospitalized patients with cirrhosis. Further studies are needed to better understand the role of uromodulin in the pathogenesis and as a predictive biomarker of AKI in this population.NEW & NOTEWORTHY In this study, we found that admission plasma uromodulin levels are significantly lower in patients who developed subsequent acute kidney injury (AKI) during their hospital stay compared with patients who did not. Additionally, uromodulin is independently associated with AKI development after adjusting for clinically relevant parameters such as age, sex, diabetes, hypertension, severity of cirrhosis, and kidney function. To our knowledge, this is the first study linking plasma uromodulin with AKI development in patients with cirrhosis.

Performance of non-invasive models of fibrosis in predicting mild to moderate fibrosis in patients with non-alcoholic fatty liver disease.

BACKGROUND & AIMS: In non-alcoholic fatty liver disease, presence of fibrosis is predictive of long-term liver-related complications. Currently, there are no reliable and non-invasive means of quantifying fibrosis in those with non-alcoholic fatty liver disease. Therefore, we aimed to evaluate the performance of a panel of non-invasive models in predicting fibrosis in non-alcoholic fatty liver disease. METHODS: The accuracy of FibroMeter non-alcoholic fatty liver disease, fibrosis 4 and four other non-invasive models in predicting fibrosis in those with biopsy proven non-alcoholic fatty liver disease was compared. These models were constructed post hoc in patients who had necessary clinical information collected within 2 months of a liver biopsy. The areas under receiver operating characteristics curves were compared for each model using Delong analysis. Optimum cut-off for each model and fibrosis stage were calculated using the Youden index. RESULTS: The area under receiver operating characteristics curves for F ≥ 1 fibrosis for fibrosis 4 and FibroMeter non-alcoholic fatty liver disease was 0.821 and 0.801 respectively. For F ≥ 3, the area under receiver operating characteristics curves was 0.866 for fibrosis 4 and 0.862 for FibroMeter non-alcoholic fatty liver disease. Delong analysis showed the area under receiver operating characteristics curves was statistically different for fibrosis 4 and FibroMeter non-alcoholic fatty liver disease compared with BARD, BAAT and aspartate aminotransferase:alanine aminotransferase ratio for F ≥ 1 and F ≥ 3. Area under receiver operating characteristics curves were significantly different for fibrosis 4 and FibroMeter non-alcoholic fatty liver disease for F ≥ 3 compared with non-alcoholic fatty liver disease fibrosis score. At a fixed sensitivity of 90%, FibroMeter non-alcoholic fatty liver disease had the highest specificity for F ≥ 1 (52.4%) and F ≥ 3 (63.8%). In contrast, at a fixed specificity of 90%, fibrosis 4 outperformed other models with a sensitivity of 60.2% for F ≥ 1 and 70.6% for F ≥ 3 fibrosis. CONCLUSION: These non-invasive models of fibrosis can predict varying degrees of fibrosis from routinely collected clinical information in non-alcoholic fatty liver disease.