The novel SALT-M score predicts 1-year post-transplant mortality in patients with severe acute-on-chronic liver failure.

BACKGROUND & AIMS: Twenty-eight-day mortality ranges from 30-90% in patients with acute-on-chronic liver failure grades 2/3 (severe ACLF). Though liver transplantation (LT) has demonstrated a survival benefit, the scarcity of donor organs and uncertainty regarding post-LT mortality among patients with severe ACLF may cause hesitancy. We developed and externally validated a model to predict 1-year post-LT mortality in severe ACLF, called the Sundaram ACLF-LT-Mortality (SALT-M) score, and estimated the median length of stay (LoS) after LT (ACLF-LT-LoS). METHODS: In 15 LT centers in the US, we retrospectively identified a cohort of patients with severe ACLF transplanted between 2014-2019, followed up to Jan'2022. Candidate predictors included demographics, clinical and laboratory values, and organ failures. We selected predictors in the final model using clinical criteria and externally validated them in two French cohorts. We provided measures of overall performance, discrimination, and calibration. We used multivariable median regression to estimate LoS after adjusting for clinically relevant factors. RESULTS: We included 735 patients, of whom 521 (70.8%) had severe ACLF (120 ACLF-3, external cohort). The median age was 55 years, and 104 with severe ACLF (19.9%) died within 1-year post-LT. Our final model included age >50 years, use of 1/≥2 inotropes, presence of respiratory failure, diabetes mellitus, and BMI (continuous). The c-statistic was 0.72 (derivation) and 0.80 (validation), indicating adequate discrimination and calibration based on the observed/expected probability plots. Age, respiratory failure, BMI, and presence of infection independently predicted median LoS. CONCLUSIONS: The SALT-M score predicts mortality within 1-year after LT in patients with ACLF. The ACLF-LT-LoS score predicted median post-LT stay. Future studies using these scores could assist in determining transplant benefits. IMPACT AND IMPLICATIONS: Liver transplantation (LT) may be the only life-saving procedure available to patients with acute-on-chronic liver failure (ACLF), but clinically instability can augment the perceived risk of post-transplant mortality at 1 year. We developed a parsimonious score with clinically and readily available parameters to objectively assess 1-year post-LT survival and predict median length of stay after LT. We developed and externally validated a clinical model called the Sundaram ACLF-LT-Mortality score in 521 US patients with ACLF with 2 or ≥3 organ failure(s) and 120 French patients with ACLF grade 3. The c-statistic was 0.72 in the development cohort and 0.80 in the validation cohort. We also provided an estimation of the median length of stay after LT in these patients. Our models can be used in discussions on the risks/benefits of LT in patients listed with severe ACLF. Nevertheless, the score is far from perfect and other factors, such as patient's preference and center-specific factors, need to be considered when using these tools.

Patients With Acute-on-Chronic Liver Failure Have Greater Healthcare Resource Utilization After Liver Transplantation.

BACKGROUND & AIMS: Although liver transplantation (LT) has been demonstrated to provide survival benefit for patients with acute-on-chronic liver failure (ACLF), data are lacking regarding resource utilization for this population after LT. METHODS: We retrospectively reviewed data from 10 centers in North America of patients transplanted between 2018 and 2019. ACLF was identified by using the European Association for the Study of the Liver-Chronic Liver Failure criteria. RESULTS: We studied 318 patients of whom 106 patients (33.3%) had no ACLF, 61 (19.1%) had ACLF-1, 74 (23.2%) had ACLF-2, and 77 (24.2%) had ACLF-3 at transplantation. Healthcare resource utilization after LT was greater among recipients with ACLF compared with patients without ACLF regarding median post-LT length of hospital stay (LOS) (P < .001), length of post-LT dialysis (P < .001), discharge to a rehabilitation center (P < .001), and 30-day readmission rates (P = .042). Multivariable negative binomial regression analysis demonstrated a significantly longer LOS for patients with ACLF-1 (1.9 days; 95% confidence interval [CI], 0.82-7.51), ACLF-2 (6.7 days; 95% CI, 2.5-24.3), and ACLF-3 (19.3 days; 95% CI, 1.2-39.7), compared with recipients without ACLF. Presence of ACLF-3 at LT was also associated with longer length of dialysis after LT (9.7 days; 95% CI, 4.6-48.8) relative to lower grades. Multivariable logistic regression analysis revealed greater likelihood of discharge to a rehabilitation center among recipients with ACLF-1 (odds ratio [OR], 1.79; 95% CI, 1.09-4.54), ACLF-2 (OR, 2.23; 95% CI, 1.12-5.01), and ACLF-3 (OR, 2.23; 95% CI, 1.40-5.73). Development of bacterial infection after LT also predicted LOS (20.9 days; 95% CI, 6.1-38.5) and 30-day readmissions (OR, 1.39; 95% CI, 1.17-2.25). CONCLUSIONS: Patients with ACLF at LT, particularly ACLF-3, have greater post-transplant healthcare resource utilization.

Bi-directional Relationship Between Celiac Disease and Liver Chemistries: A Systematic Review and Meta-Analysis.

AIMS: Previous studies have reported conflicting results regarding prevalence of elevated LC (2-70%) in celiac disease (CD). This systematic review and meta-analysis assessed the prevalence of elevated LC at time of CD diagnosis and associated response to GFD. We also report the prevalence of CD in patients with unexplained elevation of LC. METHODS: Studies assessing LC (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) in CD patients were eligible. Studies with < 50 cases or in pediatric populations were excluded. RESULTS: In total, 20 studies assessing prevalence of elevated LC in 4,265 participants with newly diagnosed CD (mean age = 35.6 ± 6.5 years, 69.8% female) were included. Pooled prevalence of elevated LC was 18.7% (95% CI 13.8-24.8; I2 = 95%). Normalization of elevated LC was seen in 83.1% (95% CI 73.4-89.7; I2 = 79%, 11 studies) of patients after GFD. On meta-regression, age at CD diagnosis, gender, and Marsh grading were not associated with elevated LC. Among 979 participants (7 studies) with unexplained elevation of LC, pooled seroprevalence and biopsy-proven CD was 6.4% (95% CI 2.9-10.3, I2 = 71%) and 4.5% (95% CI 2.6-7.7, I2 = 67%), respectively. CONCLUSION: Elevated LC are seen in approximately one-fifth of patients at CD diagnosis with majority normalizing after GFD. Age, gender, and degree of intestinal damage are not predictive of elevated LC. In the appropriate clinical scenario, liver tests should be serially monitored in CD reserving workup for additional causes after a trial of GFD. Patients with unexplained elevation of liver tests should be screened for celiac disease.

Provider Attitudes Toward Risk-Based Hepatocellular Carcinoma Surveillance in Patients With Cirrhosis in the United States.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) surveillance rates are suboptimal in clinical practice. We aimed to elicit providers' opinions on the following aspects of HCC surveillance: preferred strategies, barriers and facilitators, and the impact of a patient's HCC risk on the choice of surveillance modality. METHODS: We conducted a web-based survey among gastroenterology and hepatology providers (40% faculty physicians, 21% advanced practice providers, 39% fellow-trainees) from 26 US medical centers in 17 states. RESULTS: Of 654 eligible providers, 305 (47%) completed the survey. Nearly all (98.4%) of the providers endorsed semi-annual HCC surveillance in patients with cirrhosis, with 84.2% recommending ultrasound ± alpha fetoprotein (AFP) and 15.4% recommending computed tomography (CT) or magnetic resonance imaging (MRI). Barriers to surveillance included limited HCC treatment options, screening test effectiveness to reduce mortality, access to transportation, and high out-of-pocket costs. Facilitators of surveillance included professional society guidelines. Most providers (72.1%) would perform surveillance even if HCC risk was low (≤0.5% per year), while 98.7% would perform surveillance if HCC risk was ≥1% per year. As a patient's HCC risk increased from 1% to 3% to 5% per year, providers reported they would be less likely to order ultrasound ± AFP (83.6% to 68.9% to 57.4%; P < .001) and more likely to order CT or MRI ± AFP (3.9% to 26.2% to 36.1%; P < .001). CONCLUSIONS: Providers recommend HCC surveillance even when HCC risk is much lower than the threshold suggested by professional societies. Many appear receptive to risk-based HCC surveillance strategies that depend on patients' estimated HCC risk, instead of our current "one-size-fits all" strategy.

Risk Factors for Posttransplantation Mortality in Recipients With Grade 3 Acute-on-Chronic Liver Failure: Analysis of a North American Consortium.

Although liver transplantation (LT) yields survival benefit for patients with acute-on-chronic liver failure grade 3 (ACLF-3), knowledge gaps remain regarding risk factors for post-LT mortality. We retrospectively reviewed data from 10 centers in the United States and Canada for patients transplanted between 2018 and 2019 and who required care in the intensive care unit prior to LT. ACLF was identified using the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) criteria. A total of 318 patients were studied, of whom 106 (33.3%) had no ACLF, 61 (19.1%) had ACLF-1, 74 (23.2%) had ACLF-2, and 77 (24.2%) had ACLF-3 at transplantation. Survival probability 1 year after LT was significantly higher in patients without ACLF (94.3%) compared with patients with ACLF (87.3%; P = 0.02), but similar between ACLF-1 (88.5%), ACLF-2 (87.8%), and ACLF-3 (85.7%; P = 0.26). Recipients with ACLF-3 and circulatory failure (n = 29) had similar 1-year post-LT survival (82.3%) compared with patients with ACLF-3 without circulatory failure (89.6%; P = 0.32), including those requiring multiple vasopressors. For patients transplanted with ACLF-3 including respiratory failure (n = 20), there was a trend toward significantly lower post-LT survival (P =  0.07) among those with respiratory failure (74.1%) compared with those without (91.0%). The presence of portal vein thrombosis (PVT) at LT for patients with ACLF-3 (n = 15), however, yielded significantly lower survival (91.9% versus 57.1%; P < 0.001). Multivariable logistic regression analysis revealed that PVT was significantly associated with post-LT mortality within 1 year (odds ratio, 7.3; 95% confidence interval, 1.9-28.3). No correlation was found between survival after LT and the location or extent of PVT, presence of transjugular intrahepatic portosystemic shunt, or anticoagulation. LT in patients with ACLF-3 requiring vasopressors yields excellent 1-year survival. LT should be approached cautiously among candidates with ACLF-3 and PVT.

Hepatitis C Virus NAT-Positive Solid Organ Allografts Transplanted Into Hepatitis C Virus-Negative Recipients: A Real-World Experience.

BACKGROUND AND AIMS: Hepatitis C virus (HCV)-viremic organs are underutilized, and there is limited real-world experience on the transplantation of HCV-viremic solid organs into recipients who are HCV negative. APPROACH AND RESULTS: Patients listed or being evaluated for solid organ transplant after January 26, 2018, were educated and consented by protocol on the transplantation of HCV-viremic organs. All recipients were HCV nucleic acid test and anti-HCV antibody negative at the time of transplant and received an HCV-viremic organ. The primary outcome was sustained virological response (SVR) at 12 weeks after completion of direct-acting antiviral (DAA) therapy (SVR12 ). Seventy-seven patients who were HCV negative underwent solid organ transplantation from a donor who was HCV viremic. No patients had evidence of advanced hepatic fibrosis. Treatment regimen and duration were at the discretion of the hepatologist. Sixty-four patients underwent kidney transplant (KT), and 58 KT recipients had either started or completed DAA therapy. Forty-one achieved SVR12 , 10 had undetectable viral loads but are not eligible for SVR12 , and 7 remain on treatment. One KT recipient was a nonresponder because of nonstructural protein 5A resistance. Four patients underwent liver transplant and 2 underwent liver-kidney transplant. Three patients achieved SVR12 , 1 has completed DAA therapy, and 2 remain on treatment. Six patients underwent heart transplant and 1 underwent heart-kidney transplant. Six patients achieved SVR12 and 1 patient remains on treatment. CONCLUSIONS: Limited data exist on the transplantation of HCV-viremic organs into recipients who are HCV negative. Our study is the largest to describe a real-world experience of the transplantation of HCV-viremic organs into recipients who are aviremic. In carefully selected patients, the use of HCV-viremic grafts in the DAA era appears to be efficacious and well tolerated.

Treatment of Severe Acute on Chronic Liver Failure: Management of Organ Failures, Investigational Therapeutics, and the Role of Liver Transplantation.

Acute on chronic liver failure (ACLF) is a unique syndrome that afflicts patients with chronic liver disease and results in high short-term mortality, in the setting of organ system failures. Given this prognosis, there is an urgent need to understand risk factors for this condition, for appropriate medical management of organ failures, and for selection criteria for patients who may benefit from liver transplantation (LT). Although several definitions exist to identify ACLF, all of them are designed to identify patients with uniquely high mortality. Currently, management of severe ACLF relies on best supportive care for specific organ failures. Thromboelastography should guide the evaluation of coagulation pathways and hyperfibrinolysis in ACLF; prophylactic blood product transfusions and thrombopoetin agonists are not recommended. Combination therapy with terlipressin and albumin has been shown to be efficacious in the management of the hepatorenal syndrome but should be administered with caution in patients with ACLF-3. Recent data have characterized the role of beta-blockers and transjugular intrahepatic portosystemic shunt placement in the management of ACLF. Investigational therapies such as extracorporeal liver support and hepatocyte stem cell therapies have shown promise; larger scale studies may better define the subpopulations of patients with ACLF mostly likely to benefit from these evolving therapeutics. Regarding LT in ACLF, data suggest that even patients with 3 or more organ system failures may have a 1-year survival >80%. However, further efforts are needed to understand the predictors of post-LT survival to facilitate LT criteria for this condition.

Provider Attitudes and Practice Patterns for Direct-Acting Antiviral Therapy for Patients With Hepatocellular Carcinoma.

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are effective against hepatitis C virus and sustained virologic response is associated with reduced incidence of hepatocellular carcinoma (HCC). However, there is controversy over the use of DAAs in patients with active or treated HCC and uncertainty about optimal management of these patients. We aimed to characterize attitudes and practice patterns of hepatology practitioners in the United States regarding the use of DAAs in patients with HCC. METHODS: We conducted a survey of hepatology providers at 47 tertiary care centers in 25 states. Surveys were sent to 476 providers and we received 279 responses (58.6%). RESULTS: Provider beliefs about risk of HCC recurrence after DAA therapy varied: 48% responded that DAAs reduce risk, 36% responded that DAAs do not change risk, and 16% responded that DAAs increase risk of HCC recurrence. However, most providers believed DAAs to be beneficial to and reduce mortality of patients with complete response to HCC treatment. Accordingly, nearly all providers (94.9%) reported recommending DAA therapy to patients with early-stage HCC who received curative treatment. However, fewer providers recommended DAA therapy for patients with intermediate (72.9%) or advanced (57.5%) HCC undergoing palliative therapies. Timing of DAA initiation varied among providers based on HCC treatment modality: 49.1% of providers reported they would initiate DAA therapy within 3 months of surgical resection whereas 45.9% and 5.0% would delay DAA initiation for 3-12 months and >1 year post-surgery, respectively. For patients undergoing transarterial chemoembolization (TACE), 42.0% of providers would provide DAAs within 3 months of the procedure, 46.7% would delay DAAs until 3-12 months afterward, and 11.3% would delay DAAs more than 1 year after TACE. CONCLUSIONS: Based on a survey sent to hepatology providers, there is variation in provider attitudes and practice patterns regarding use and timing of DAAs for patients with HCC. Further studies are needed to characterize the risks and benefits of DAA therapy in this patient population.

The EMALT Score: An Improved Model for Prediction of Early Mortality in Liver Transplant Recipients.

PURPOSE: Needs, risks, and outcomes of patients admitted to a post liver transplant intensive care unit (POLTICU) differ in important ways from those admitted to pretransplant intensive care units (ICUs). The aim of this study was to create the optimal model to risk stratify POLTICU patients. METHODS: Consecutive patients who underwent first deceased donor liver transplantation (LT) at a large United States center between 2008 and 2014 were followed from admission to LT and to discharge or death. Receiver-operating characteristic analysis was performed to assess the value of various scores in predicting in-hospital mortality. A predictive model was developed using logistic regression analysis. RESULTS: A total of 697 patients underwent LT, and 3.2% died without leaving the hospital. A model for in-hospital mortality was derived from variables available within 24 hours of admission to the POLTICU. Key variables best predicting survival were white blood cell count, 24-hour urine output, and serum glucose. A model using these variables performed with an area under the curve (AUC) of 0.88, compared to the Acute Physiology and Chronic Health Evaluation III and Model for End-Stage Liver Disease, which performed with AUCs of 0.74 and 0.60, respectively. CONCLUSION: An improved model, the early mortality after LT (EMALT) score, performs better than conventional models in predicting in-hospital mortality after LT.

Renoportal anastomosis in liver transplantation and its impact on patient outcomes: a systematic literature review.

Portal vein thrombosis (PVT) is commonly encountered during liver transplantation (LT). Depending on the grade of thrombosis, varied management strategies are indicated. The aims of this study are to clarify the contemporary role of renoportal anastomosis (RPA) in patients with splanchnic vein thrombosis (SVT) undergoing LT and to systematically analyze all reported cases of RPA. A systematic literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta- Analyses statement guidelines. The study was limited to studies reported in English between January 1997 and May 2017. Only retrospective single center studies were included in the analysis. A total of 66 patients with SVT were reported to have undergone RPA during LT. Transient renal dysfunction was reported in 12 patients (18.1%), variceal hemorrhage in 2 patients (3%), early portal vein (PV) re-thrombosis in 2 patients (3%), chronic renal dysfunction in 2 patients (3%), and late PV re-thrombosis in 1 patient (1.5%). The overall patient and graft survival were each 80%. This analysis illustrates the decades-long evolution of a technique practiced across the field of transplantation. Postoperative complications and graft survival appear to be encouraging, even in the setting of SVT.

A Clinical Decision Rule Based on the AST-to-Platelet Ratio Index Improves Adherence to Published Guidelines on the Management of Acute Variceal Bleeding.

BACKGROUND: Optimal management of acute upper gastrointestinal bleeding (UGIB) depends on identifying a variceal versus nonvariceal etiology. An objective measure predicting etiology could guide early management pending endoscopy. The AST-to-platelet ratio index (APRI) score has been studied as a marker of cirrhosis and portal hypertension, but has not been evaluated in the setting of acute UGIB. METHODS: In this single-center retrospective cohort study, we reviewed endoscopy reports and other data for patients with acute UGIB, and classified episodes as variceal bleeds or other. We assessed the diagnostic utility of the APRI score relative to other objective measures by Area Under the Receiver Operating Characteristic (AUROC) curve analysis. We constructed a clinical decision rule based on the APRI score, and assessed how it would have changed management. RESULTS: The APRI score performed well in predicting a variceal etiology of acute UGIB, with AUROC 0.89. We developed a clinical decision rule using an APRI score of 0.4 to guide early management of acute UGIB patients. Retroactively applying this to our cohort, adherence to published guidelines for administration of octreotide and antibiotics would have increased from 56% to 91%. CONCLUSIONS: The APRI score is an objective metric that helps predict a variceal etiology of acute UGIB. Using our proposed decision rule could improve adherence to guidelines on management of acute variceal bleeding. Although we were unable to demonstrate a survival benefit, improved adherence to evidence-based guidelines serves as a metric related to this most important outcome measure. Prospective study to validate these findings is indicated.

Molecular Adsorbent Recirculating System in Acute Liver Failure.

Acetaminophen (APAP) overdose is the most common cause of acute liver failure (ALF) in the United States. Liver transplantation (LT) is potentially lifesaving for patients with ALF, but its feasibility in clinical practice is limited. Liver assist devices, such as the Molecular Adsorbent Recirculating System (MARS), are used in some centers as a "bridge" to liver transplantation or as a means of liver recovery, but their role in the treatment of ALF is not well-defined. We present the case of a 44-year-old man with APAP-associated ALF who experienced hepatic recovery after treatment with MARS.

Comparison of fungal vs bacterial infections in the medical intensive liver unit: Cause or corollary for high mortality?

BACKGROUND: Due to development of an immune-dysregulated phenotype, advanced liver disease in all forms predisposes patients to sepsis acquisition, including by opportunistic pathogens such as fungi. Little data exists on fungal infection within a medical intensive liver unit (MILU), particularly in relation to acute on chronic liver failure. AIM: To investigate the impact of fungal infections among critically ill patients with advanced liver disease, and compare outcomes to those of patients with bacterial infections. METHODS: From our prospective registry of MILU patients from 2018-2022, we included 27 patients with culture-positive fungal infections and 183 with bacterial infections. We compared outcomes between patients admitted to the MILU with fungal infections to bacterial counterparts. Data was extracted through chart review. RESULTS: All fungal infections were due to Candida species, and were most frequently blood isolates. Mortality among patients with fungal infections was significantly worse relative to the bacterial cohort (93% vs 52%, P < 0.001). The majority of the fungal cohort developed grade 2 or 3 acute on chronic liver failure (ACLF) (90% vs 64%, P = 0.02). Patients in the fungal cohort had increased use of vasopressors (96% vs 70%, P = 0.04), mechanical ventilation (96% vs 65%, P < 0.001), and dialysis due to acute kidney injury (78% vs 52%, P = 0.014). On MILU admission, the fungal cohort had significantly higher Acute Physiology and Chronic Health Evaluation (108 vs 91, P = 0.003), Acute Physiology Score (86 vs 65, P = 0.003), and Model for End-Stage Liver Disease-Sodium scores (86 vs 65, P = 0.041). There was no significant difference in the rate of central line use preceding culture (52% vs 40%, P = 0.2). Patients with fungal infection had higher rate of transplant hold placement, and lower rates of transplant; however, differences did not achieve statistical significance. CONCLUSION: Mortality was worse among patients with fungal infections, likely attributable to severe ACLF development. Prospective studies examining empiric antifungals in severe ACLF and associations between fungal infections and transplant outcomes are critical.

Red Blood Cell Transfusion in Critically Ill Adults: An American College of Chest Physicians Clinical Practice Guideline.

BACKGROUND: Blood products frequently are administered to critically ill patients. Considering recent trials and practice variability, a comprehensive review of current evidence was deemed essential to offer pertinent guidance to critical care practitioners. This American College of Chest Physicians (CHEST) guidelines panel examined the literature on RBC transfusions among critically ill patients overall and specific subgroups, including patients with gastrointestinal bleeding, acute coronary syndrome (ACS), cardiac surgery, isolated troponin elevation, and septic shock, to provide evidence-based recommendations. STUDY DESIGN AND METHODS: A panel of experts developed 6 Population, Intervention, Comparator, and Outcome questions addressing RBC transfusions in critically ill patients and performed a comprehensive evidence review. The panel applied the Grading of Recommendations, Assessment, Development, and Evaluations approach to assess the certainty of evidence and to formulate and grade recommendations. A modified Delphi technique was used to reach consensus on the recommendations. RESULTS: The initial search identified a total of 3,082 studies, and after the initial screening, 38 articles were reviewed. Among them, 23 studies met inclusion criteria, comprising 22 randomized controlled trials and 1 cohort study. Based on the analysis of these studies, the panel formulated 2 strong and 4 conditional recommendations. The overall quality of evidence for recommendations ranged from very low to moderate. CONCLUSIONS: In most critically ill patients, a restrictive strategy was preferable to a permissive approach because it does not increase the risk of death or complications, but does decrease RBC use significantly. Data from critically ill subpopulations also supported a restrictive approach, except in patients with ACS, for whom favoring a restrictive approach could increase adverse outcomes.

Evaluation of a protocol for rifaximin discontinuation in critically ill patients with liver disease receiving broad-spectrum antibiotic therapy.

BACKGROUND: Rifaximin is frequently administered to critically ill patients with liver disease and hepatic encephalopathy, but patients currently or recently treated with antibiotics were frequently excluded from studies of rifaximin efficacy. Due to overlapping spectrums of activity, combination therapy with broad-spectrum antibiotics and rifaximin may be unnecessary. A pharmacist-driven protocol was piloted to reduce potentially overlapping therapy in critically ill patients with liver disease. It was hypothesized that withholding rifaximin during broad-spectrum antibiotic therapy would be safe and reduce healthcare costs. AIM: To determine the clinical, safety, and financial impact of discontinuing rifaximin during broad-spectrum antibiotic therapy in critically ill liver patients. METHODS: This was a single-center, quasi-experimental, pre-post study based on a pilot pharmacist-driven protocol. Patients in the protocol group were prospectively identified via the medical intensive care unit (ICU) (MICU) protocol to have rifaximin withheld during broad-spectrum antibiotic treatment. These were compared to a historical cohort who received combination therapy with broad-spectrum antibiotics and rifaximin. All data were collected retrospectively. The primary outcome was days alive and free of delirium and coma (DAFD) to 14 d. Safety outcomes included MICU length of stay, 48-h change in vasopressor dose, and ICU mortality. Secondary outcomes characterized rifaximin cost savings and protocol adherence. Multivariable analysis was utilized to evaluate the association between group assignment and the primary outcome while controlling for potential confounding factors. RESULTS: Each group included 32 patients. The median number of delirium- and coma-free days was similar in the control and protocol groups [3 interquartile range (IQR 0, 8) vs 2 (IQR 0, 9.5), P = 0.93]. In multivariable analysis, group assignment was not associated with a reduced ratio of days alive and free of delirium or coma at 14 d. The protocol resulted in a reduced median duration of rifaximin use during broad-spectrum antibiotic therapy [6 d control (IQR 3, 9.5) vs 1 d protocol (IQR 0, 1); P < 0.001]. Rates of other secondary clinical and safety outcomes were similar including ICU mortality and 48-h change in vasopressor requirements. Overall adherence to the protocol was 91.4%. The median estimated total cost of rifaximin therapy per patient was reduced from $758.40 (IQR $379.20, $1200.80) to $126.40 (IQR $0, $126.40), P < 0.01. CONCLUSION: The novel pharmacist-driven protocol for rifaximin discontinuation was associated with significant cost savings and no differences in safety outcomes including DAFD.

Analysis of Native Kidney Function Recovery With Renal Scintigraphy Following Simultaneous Liver-Kidney Transplantation.

BACKGROUND: Patients undergoing simultaneous liver-kidney transplantation (SLK) have impaired native kidney function. The relative contribution of allograft versus native function after SLK is unknown. We sought to characterize the return of native kidney function following SLK. METHODS: Following SLK, patients underwent technetium-99 m-mercaptoacetyltriglycine renal scintigraphy following serum creatinine nadir. Kidney contributions to estimated glomerular filtration rate (eGFR) were determined. Patients with native kidney function at serum creatinine nadir contributing eGFR ≥30 versus <30 mL/min/1.73 m 2 were compared, and multiple linear regression analysis for native eGFR improvement was performed. RESULTS: Thirty-one patients were included in this analysis. Average native kidney contribution to overall kidney function following SLK was 51.1% corresponding to native kidney eGFR of 44.5 mL/min/1.73 m 2 and native kidney function eGFR improvement of 30.3 mL/min/1.73 m 2 ( P < 0.001). Twenty-six of 31 patients had native kidney contribution of eGFR ≥30 mL/min/1.73 m 2 . Hepatorenal syndrome as the sole primary etiology of kidney dysfunction was 100% specific for native kidney eGFR >30 mL/min/1.73 m 2 and predicted native eGFR improvement ( P = 0.03). CONCLUSIONS: Substantial improvement in native kidney function follows SLK, and hepatorenal syndrome as the sole primary etiology of kidney dysfunction is predictive of improvement. Whether such patients are suitable for liver transplant followed by surveillance with option for subsequent kidney transplants requires investigation.

Cirrhotic coagulopathy: A rebalanced hemostasis.

Cirrhosis has been regarded as a hypocoagulable state associated with an increased risk of bleeding. But patients with cirrhosis also have a high incidence of thrombotic complications, challenging this dogma. We now recognize that in cirrhosis there is a simultaneous decrease in both clotting and anticlotting factors, leading to a new equilibrium. Conventional coagulation tests such as the platelet count and prothrombin time do not assess the reduced anticoagulation factors in cirrhosis and overestimate the bleeding risk, and any intervention based on these test results can lead to thrombotic complications. This article reviews the changes in hemostasis associated with cirrhosis, newer tests for assessing coagulation, and preprocedural minimization of coagulopathy.

Endo-hepatology: The changing paradigm of endoscopic ultrasound in cirrhosis.

Content available: Author Interview and Audio Recording.

Surgical Considerations Regarding Transplantation for the Patient With Acute-on-Chronic Liver Failure.

Content available: Author Audio Recording.