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To improve the management of cirrhotic patients diagnosed with new renal masses, we used a nationally representative cohort to assess the perioperative outcomes of nephrectomy in the setting of liver disease. The incidences of liver disease and renal masses are both rising in the US. Delaying liver transplantation to address other health concerns may have life changing consequences in these patients, thus these results help to guide treatment decisions at this critical junction in care.A retrospective study of the 2016-2019 Nationwide Readmissions Database was performed in adults undergoing nephrectomy for non-emergent indications. Outcomes were compared between three cohorts: no chronic liver disease (no CLD), chronic liver disease (CLD), and decompensated cirrhosis (DC). Mixed regression models were used to evaluate the association between CLD and DC with outcomes of interest including morbidity, mortality, readmission rates, non-home discharges, length of stay, and costs.A total of 183,362 patients were evaluated. The mortality rate in the DC cohort (7%) was higher than with CLD (0.4%) and no CLD (0.3%), (p0.001). DC was associated with higher mortality (OR 8.29, 95% CI 4.07 - 16.88), post-operative bleeding requiring transfusion (OR 5.55, 95% CI 3.72 - 8.26), non-home discharge (OR 5.12, 95% CI 3.16 - 8.30) and readmission (OR 1.79, 95% CI 1.09 - 2.94) compared to no CLD. The DC cohort had the greatest length of stay and costs.Patients undergoing nephrectomy with DC have increased morbidity, mortality, readmission rates, non-home discharges, LOS and costs. Alternative management strategies may be considered in these patients.

Early cancer detection by cell-free DNA faces multiple challenges: low fraction of tumor cell-free DNA, molecular heterogeneity of cancer, and sample sizes that are not sufficient to reflect diverse patient populations. Here, we develop a cancer detection approach to address these challenges. It consists of an assay, cfMethyl-Seq, for cost-effective sequencing of the cell-free DNA methylome (with > 12-fold enrichment over whole genome bisulfite sequencing in CpG islands), and a computational method to extract methylation information and diagnose patients. Applying our approach to 408 colon, liver, lung, and stomach cancer patients and controls, at 97.9% specificity we achieve 80.7% and 74.5% sensitivity in detecting all-stage and early-stage cancer, and 89.1% and 85.0% accuracy for locating tissue-of-origin of all-stage and early-stage cancer, respectively. Our approach cost-effectively retains methylome profiles of cancer abnormalities, allowing us to learn new features and expand to other cancer types as training cohorts grow.

Liver transplantation (LT) is an effective strategy for patients with unresectable hepatocellular carcinoma (HCC). To qualify for standardized LT model for end-stage liver disease exception points, the United Network for Organ Sharing National Liver Review Board (NLRB) requires that the presenting and final HCC tumor burden be within the University of California San Francisco criteria, which were recently expanded (within expanded UCSF [W-eUCSF]). Current NLRB criteria may be too restrictive because it has been shown previously that the initial burden does not predict LT failure when tumors downstage to UCSF. This study aims to assess LT outcomes for HCC initially presenting beyond expanded UCSF (B-eUCSF) criteria in a large multicenter collaboration.Comparisons of B-eUCSF and W-eUCSF candidates undergoing LT at seven academic institutions between 2001 and 2017 were made from a multi-institutional database. Survival outcomes were compared by Kaplan-Meier and Cox regression analyses.Of 1,846 LT recipients with HCC, 86 (5%) met B-eUCSF criteria at initial presentation, with the remainder meeting W-eUCSF criteria. Despite differences in tumor burden, B-eUCSF candidates achieved comparable 1-, 5- and 10-year overall (89%, 70%, and 55% vs 91%, 74%, and 60%, respectively; p = 0.2) and disease-free (82%, 60%, and 53% vs 89%, 71%, and 59%, respectively; p = 0.07) survival to patients meeting W-eUCSF criteria after LT. Despite increased tumor recurrence in B-eUCSF vs W-eUCSF patients (24% vs 10%, p = 0.0002), post-recurrence survival was similar in both groups (p = 0.69).Transplantation for patients initially presenting with HCC B-eUSCF criteria offers a survival advantage similar to those with tumors meeting W-eUCSF criteria at presentation. The current NLRB policy is too stringent, and considerations to expand criteria should be discussed.

Persistent pleural effusions (PPEf) represent a known complication of orthotopic liver transplant (OLT). However, their clinical relevance is not well described. We evaluated the clinical, biochemical, and cellular characteristics of post-OLT PPEf and assessed their relationship with longitudinal outcomes. We performed a retrospective cohort study of OLT recipients between 2006 and 2015. Included patients had post-OLT PPEf, defined by effusion persisting >30 days after OLT and available pleural fluid analysis. PPEf were classified as transudates or exudates (ExudLight) by Light’s criteria. Exudates were subclassified as those with elevated lactate dehydrogenase (ExudLDH) or elevated protein (ExudProt). Cellular composition was classified as neutrophil- or lymphocyte-predominant. Of 1602 OLT patients, 124 (7.7%) had PPEf, of which 90.2% were ExudLight. Compared to all OLT recipients, PPEf patients had lower two-year survival (HR 1.63; p = 0.002). Among PPEf patients, one-year mortality was associated with pleural fluid RBC count (p = 0.03). While ExudLight and ExudProt showed no association with outcomes, ExudLDH were associated with increased ventilator dependence (p = 0.03) and postoperative length of stay (p = 0.03). Neutrophil-predominant effusions were associated with increased postoperative ventilator dependence (p = 0.03), vasopressor dependence (p = 0.02), and surgical pleural intervention (p = 0.02). In summary, post-OLT PPEf were associated with increased mortality. Ninety percent of these effusions were exudates by Light’s criteria. Defining exudates using LDH only and incorporating cellular analysis, including neutrophils and RBCs, was useful in predicting morbidity.

Aim Cirrhosis is a leading cause of death worldwide, yet there are no well‐established risk stratifying tools for lethal complications, including hepatocellular carcinoma (HCC). Patients with liver cirrhosis undergo routine endoscopic surveillance, providing ready access to duodenal aspirate samples that could be a source for identifying novel biomarkers. The aim of this study was to characterize the microbiome and bile acid profiles in duodenal aspirates from patients with liver cirrhosis to assess the feasibility of developing biomarkers for HCC risk stratification. Methods Thirty patients with liver cirrhosis were enrolled in the Microbiome, Microbial Markers, and Liver Disease study between May 2015 and March 2017. Detailed clinical and epidemiological data were collected at baseline and at 6‐monthly follow‐up visits. Duodenal aspirate fluid was collected at baseline for microbial characterization using 16S ribosomal RNA sequencing and bile acid quantification using mass spectroscopy. Results Alcohol‐related cirrhosis was associated with reductions in the Bacteroidetes phylum, particularly Prevotella (13‐fold reduction), and expansion of Staphylococcus (13‐fold increase), compared to hepatitis C virus‐related cirrhosis. Participants with hepatic encephalopathy (HE) had less microbial diversity compared to patients without HE (P

Elevated liver function tests (eLFTs) are a major cause of unplanned readmissions (UR) after orthotopic liver transplantation. Diagnostic workup for eLFTs requires multiple invasive and noninvasive procedures, often done in the inpatient setting to expedite diagnosis, yet consequently resulting in increased costs. In this study, we evaluated eLFT readmissions at a single institution with respect to resource utilization. From 3/2013 to 12/2015, 388 patients underwent orthotopic liver transplantation, resulting in 463 UR totaling 5833 bed days; 87 (18.8%) UR and 929 (15.9%) bed days were for eLFTs. During eLFT-UR all patients underwent repeat laboratory testing, 75 (86.2%) liver ultrasound, 66 (75.8%) liver biopsy, and 17 (19.5%) endoscopic retrograde cholangiopancreatography. Discharge diagnoses were acute cellular rejection (40.2%), transaminitis not otherwise specified (17.2%), biliary complications (16.1%), recurrent hepatitis (11.5%), vascular complications (5.8%), viral hepatitis (5.8%), and steatohepatitis (3.5%). The greatest bed-day utilization was secondary to acute cellular rejection (60.8%) and biliary complications (13.7%). More than 35 per cent of eLFT-UR were due to transaminitis not otherwise specified, steatohepatitis, recurrent or viral hepatitis, none of which necessitate inpatient treatment. In addition,25 per cent of eLFT-UR bed days were attributed to diagnostic workup. Identifying patients who can undergo expedited outpatient workup and require only outpatient management will result in significantly decreased readmissions, bed days, and hospital costs.

Background: Orthotopic liver transplantation (LT) is the only curative treatment for end-stage liver disease, and is a resource-intense, high-risk surgery. While cardiovascular events are the second highest cause of post-LT morbidity, data regarding the development of post-LT cardiomyopathy (CMY)