Evaluating a Novel, Portable, Self-Administrable Device ("Beacon") That Measures Critical Flicker Frequency as a Test for Hepatic Encephalopathy.

INTRODUCTION: We compared critical flicker frequency (CFF) thresholds obtained using a novel portable device "Beacon" with thresholds from the commercially available Lafayette Flicker Fusion System (Lafayette-FFS) in patients with cirrhosis. METHODS: One hundred fifty-three participants with chronic liver disease underwent CFF testing using Beacon and Lafayette-FFS with a method-of-limits and/or forced-choice protocol. RESULTS: Beacon demonstrated excellent test-retest reliability (intraclass correlation 0.91-0.97) and good correlation with the Lafayette-FFS values (intraclass correlation 0.77-0.84). Forced-choice CFF were on average 4.1 Hz higher than method-of-limits descending CFFs. DISCUSSION: Beacon can be self-administered by patients with chronic liver disease and cirrhosis to measure CFF, a validated screening test for minimal hepatic encephalopathy.

Temporal Trends and Evolving Outcomes After Simultaneous Liver-Kidney Transplantation: Results from the US SLKT Consortium.

We aimed to understand the contemporary changes in the characteristics and the determinants of outcomes among simultaneous liver-kidney transplantation (SLKT) recipients at 6 liver transplantation centers in the United States. We retrospectively enrolled SLKT recipients between 2002 and 2017 in the US Multicenter SLKT Consortium. We analyzed time-related trends in recipient characteristics and outcomes with linear regression and nonparametric methods. Clustered Cox regression determined the factors associated with 1-year and overall survival. We enrolled 572 patients. We found significant changes in the clinical characteristics of SLKT recipients: as compared with 2002, recipients in 2017 were older (59 versus 52 years; P < 0.001) and more likely to have chronic kidney disease (71% versus 33%; P < 0.001). There was a marked improvement in 1-year survival during the study period: 89% in 2002 versus 96% in 2017 (P < 0.001). We found that the drivers of 1-year mortality were SLKT year, hemodialysis at listing, donor distance, and delayed kidney allograft function. The drivers of overall mortality were an indication of acute kidney dysfunction, body mass index, hypertension, creatinine at SLKT, ventilation at SLKT, and donor quality. In this contemporary cohort of SLKT recipients, we highlight changes in the clinical characteristics of recipients. Further, we identify the determinants of 1-year and overall survival to highlight the variables that require the greatest attention to optimize outcomes.

Renal Outcomes After Simultaneous Liver-Kidney Transplantation: Results from the US Multicenter Simultaneous Liver-Kidney Transplantation Consortium.

Simultaneous liver-kidney transplantation (SLKT) is increasingly common in the United States. However, little is known about the renal-related outcomes following SLKT, which are essential to maximize the health of these allografts. We examined the factors impacting renal function following SLKT. This is an observational multicenter cohort study from the US Multicenter SLKT Consortium consisting of recipients of SLKT aged ≥18 years of transplantations performed between February 2002 and June 2017 at 6 large US centers in 6 different United Network for Organ Sharing regions. The primary outcome was incident post-SLKT stage 4-5 chronic kidney disease (CKD) defined as <30 mL/minute/1.73 m2 or listing for kidney transplant. The median age of the recipients (n = 570) was 58 years (interquartile range, 51-64 years), and 37% were women, 76% were White, 33% had hepatitis C virus infection, 20% had nonalcoholic steatohepatitis (NASH), and 23% had alcohol-related liver disease; 68% developed ≥ stage 3 CKD at the end of follow-up. The 1-year, 3-year, and 5-year incidence rates of post-SLKT stage 4-5 CKD were 10%, 12%, and 16%, respectively. Pre-SLKT diabetes mellitus (hazard ratio [HR], 1.45; 95% CI, 1.00-2.15), NASH (HR, 1.58; 95% CI, 1.01-2.45), and delayed kidney graft function (HR, 1.72; 95% CI, 1.10-2.71) were the recipient factors independently associated with high risk, whereas the use of tacrolimus (HR, 0.44; 95% CI, 0.22-0.89) reduced the risk. Women (ß = -6.22 ± 2.16 mL/minute/1.73 m2 ; P = 0.004), NASH (ß = -7.27 ± 3.27 mL/minute/1.73 m2 ; P = 0.027), and delayed kidney graft function (ß = -7.25 ± 2.26 mL/minute/1.73 m2 ; P = 0.007) were independently associated with low estimated glomerular filtration rate at last follow-up. Stage 4-5 CKD is common after SLKT. There remains an unmet need for personalized renal protective strategies, specifically stratified by sex, diabetes mellitus, and liver disease, to preserve renal function among SLKT recipients.

Assessment of the spectrum of hepatic encephalopathy: A multicenter study.

Hepatic encephalopathy (HE) is a major cause of morbidity in cirrhosis. However, its severity assessment is often subjective, which needs to be studied systematically. The aim was to determine how accurately trainee and nontrainee practitioners grade and manage HE patients throughout its severity. We performed a survey study using standardized simulated patient videos at 4 US and 3 Canadian centers. Participants were trainees (gastroenterology/hepatology fellows) and nontrainees (faculty, nurse practitioners, physician assistants). We determined the accuracy of HE severity identification and management options between grades <2 or ≥2 HE and trainees/nontrainees. In total, 108 respondents (62 trainees, 46 nontrainees) were included. For patients with grades <2 versus ≥2 HE, a higher percentage of respondents were better at correctly diagnosing grades ≥2 compared with grades <2 (91% versus 64%; P < 0.001). Specialized cognitive testing was checked significantly more often in grades <2, whereas more aggressive investigation for precipitating factors was ordered in HE grades >2. Serum ammonia levels were ordered in almost a third of grade ≥2 patients. For trainees and nontrainees, HE grades were identified similarly between groups. Trainees were less likely to order serum ammonia and low-protein diets, more likely to order rifaximin, and more likely to perform a more thorough workup for precipitating factors compared with nontrainee respondents. There was excellent concordance in the classification of grade ≥2 HE between nontrainees versus trainees, but lower grades showed discordance. Important differences were seen regarding blood ammonia, specialized testing, and nutritional management between trainees and nontrainees. These results have important implications at the patient level, interpreting multicenter clinical trials, and in the education of practitioners. Liver Transplantation 24 587-594 2018 AASLD.

Predictors of Length of Stay and Mortality During Simultaneous Liver-Kidney Transplant Index Admission: Results From the US-Multicenter SLKT Consortium.

Length of stay (LOS) during index solid organ transplant impacts morbidity and healthcare costs. To date, there are no studies evaluating characteristics and outcomes of simultaneous liver-kidney transplant (SLKT) index hospitalization. We examined factors associated with LOS and mortality during index SLKT admission. Methods: Adult SLKT recipients between 2002 and 2017 at 6 transplant centers across 6 UNOS regions were retrospectively enrolled in the US-Multicenter SLKT Consortium. Multivariable regression analyses assessed predictors of SLKT LOS and death during index admission. Results: Median age of cohort (N = 570) was 58 y (interquartile range: 51-64); 63% male, 75% White, 32.3% hepatitis C, 23.3% alcohol-related, 20.1% nonalcoholic steatohepatitis with median MELD-Na at SLKT 28 (23-34). Seventy-one percent were hospitalized at the time of SLKT with median LOS pretransplant of 10 d. Majority of patients were discharged alive (N = 549; 96%)' and 36% were discharged to subacute rehab facility. LOS for index SLKT was 19 d (Q1: 10, Q3: 34 d). Female sex (P = 0.003), Black race (P = 0.02), advanced age (P = 0.007), ICU admission at time of SLKT (P = 0.03), high MELD-Na (P = 0.003), on cyclosporine during index hospitalization (P = 0.03), pre-SLKT dialysis (P < 0.001), and kidney delayed graft function (P < 0.001) were the recipient factors associated with prolonged LOS during index SLKT hospitalization. Prolonged LOS also contributed to overall mortality (HR = 1.007; P = 0.03). Conclusions: Despite excellent survival, index SLKT admission was associated with high-resource utilization with more than half the patients with LOS >2 wk and affected overall patient survival. Further investigation is needed to optimize healthcare resources for these patients in a financially strained healthcare landscape.

Therapeutic dilemma in the management of a patient with the clinical picture of TTP and severe B12 deficiency.

BACKGROUND: Idiopathic thrombotic thrombocytopenic purpura (TTP) is a rare hematological emergency characterized by the pentad of microangiopathic hemolytic anemia, thrombocytopenia, neurological symptoms, renal injury, and fever that is invariably fatal if left untreated. Prompt intervention with plasma exchange minimizes mortality and is the cornerstone of therapy. Rare reports have described "pseudo-TTP" driven by extreme hematologic abnormalities resulting from deficiency of vitamin B12. Distinguishing between these entities can pose a diagnostic and therapeutic challenge. CASE PRESENTATION: A 77 year old female presented with altered mental status, renal insufficiency, thrombocytopenia and evidence of microangiopathic hemolytic anemia, suggesting TTP. Workup demonstrated macrocytosis and reticulocytopenia, and B12 level was unmeasurably low. Other elements of her clinical presentation, including volume loss and bleeding suggested a multifactorial pathogenesis could be contributing to her laboratory abnormalities, reducing the likelihood that she had TTP. The risks and benefits of treating aggressively with therapeutic plasma exchange (TPE) for TTP were considered given the diagnostic possibilities. The patient received TPE initially, with rapid de-escalation after her clinical response suggested "pseudo-TTP" from B12 deficiency was the driving the process. B12 supplementation corrected her hematologic abnormalities and she remains well two years after presenting. CONCLUSIONS: TTP is a rare condition with fatal consequences if left untreated. Guidelines recommend TPE even if there is uncertainty about the diagnosis of TTP. B12 deficiency is common, though not typically associated with severe hematologic abnormalities. We compare the presenting characteristics of all thirteen cases of pseudo-TTP reported in the literature with those from patients in case series of TTP to suggest a set of parameters that can help clinicians distinguish between pseudo-TTP and TTP and guide decision making regarding intervention. Evaluation of all TTP cases should include a B12, methylmalonic acid level and reticulocyte count. Reticulocytopenia suggests B12 deficiency. Finally an LDH level above 2500 IU/L is relatively uncommon in TTP and should suggest consideration of B12 deficiency.