Dynamic analysis of acute deterioration in chronic liver disease patients using modified quick sequential organ failure assessment.

BACKGROUND/AIMS: Quick sequential organ failure assessment (qSOFA) is believed to identify patients at risk of poor outcomes in those with suspected infection. We aimed to evaluate the ability of modified qSOFA (m-qSOFA) to identify high-risk patients among those with acutely deteriorated chronic liver disease (CLD), especially those with acute-onchronic liver failure (ACLF). METHODS: We used data from both the Korean Acute-on-Chronic Liver Failure (KACLiF) and the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) cohorts. qSOFA was modified by replacing the Glasgow Coma Scale with hepatic encephalopathy, and an m-qSOFA ≥2 was considered high. RESULTS: Patients with high m-qSOFA had a significantly lower 1-month transplant-free survival (TFS) in both cohorts and higher organ failure development in KACLiF than those with low m-qSOFA (Ps<0.05). Subgroup analysis by ACLF showed that patients with high m-qSOFA had lower TFS than those with low m-qSOFA. m-qSOFA was an independent prognostic factor (hazard ratios, HR=2.604, 95% confidence interval, CI 1.353-5.013, P=0.004 in KACLiF and HR=1.904, 95% CI 1.484- 2.442, P<0.001 in AARC). The patients with low m-qSOFA at baseline but high m-qSOFA on day 7 had a significantly lower 1-month TFS than those with high m-qSOFA at baseline but low m-qSOFA on day 7 (52.6% vs. 89.4%, P<0.001 in KACLiF and 26.9% vs. 61.5%, P<0.001 in AARC). CONCLUSION: Baseline and dynamic changes in m-qSOFA may identify patients with a high risk of developing organ failure and short-term mortality among CLD patients with acute deterioration.

The Health Care Burden of Hepatic Encephalopathy.

Hepatic encephalopathy-a common and debilitating complication of cirrhosis-results in major health care burden on both patients and caregivers through direct and indirect costs. In addition to risk of falls, inability to work and drive, patients with hepatic encephalopathy often require hospital admission (and often readmission), and many require subacute care following hospitalization. The costs and psychological impact of liver transplantation often ensue. As the prevalence of chronic liver disease increases throughout the United States, the health care burden of hepatic encephalopathy will continue to grow.

The assessment and management of cirrhotic patients with encephalopathy.

Hepatic encephalopathy (HE) is a debilitating complication associated with both acute and chronic liver injury. It is associated with a greater risk of death than any other significant hepatic decompensation event. It manifests as a wide spectrum of neuropsychological abnormalities ranging from subtle impairments in higher cognitive function, to confusion and coma. The pathophysiological role of ammonia in the development of HE is well known, but there is increasing recognition that the gut microbiome, gut-derived systemic inflammation and development of infection can serve as drivers of HE in patients with cirrhosis. The development of HE portents to the severity of cirrhosis and the prognosis is poor without liver transplantation. A referral for liver transplantation should therefore be considered early in those who are eligible. This review covers the pragmatic assessment of HE in patients with cirrhosis, as well as the current evidence base for the best practice management of HE in such patients.

TCD assessment in fulminant hepatic failure: Improvements in cerebral autoregulation after liver transplantation.

INTRODUCTION AND OBJECTIVES: Acute liver failure, also known as fulminant hepatic failure (FHF), includes a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction and hepatic encephalopathy. The objective of this study was to assess cerebral autoregulation (CA) in 25 patients (19 female) with FHF and to follow up with seventeen of these patients before and after liver transplantation. PATIENTS AND METHODS: The mean age was 33.8 years (range 14-56, SD 13.1 years). Cerebral hemodynamics was assessed by transcranial Doppler (TCD) bilateral recordings of cerebral blood velocity (CBv) in the middle cerebral arteries (MCA). RESULTS: CA was assessed based on the static CA index (SCAI), reflecting the effects of a 20-30 mmHg increase in mean arterial blood pressure on CBv induced with norepinephrine infusion. SCAI was estimated at four time points: pretransplant and on the 1st, 2nd and 3rd posttransplant days, showing a significant difference between pre- and posttransplant SCAI (p = 0.005). SCAI peaked on the third posttransplant day (p = 0.006). Categorical analysis of SCAI showed that for most patients, CA was reestablished on the second day posttransplant (SCAI > 0.6). CONCLUSIONS: These results suggest that CA impairment pretransplant and on the 1st day posttransplant was re-established at 48-72 h after transplantation. These findings can help to improve the management of this patient group during these specific phases, thereby avoiding neurological complications, such as brain swelling and intracranial hypertension.

MEFIB-Index and MAST-Score in the assessment of hepatic decompensation in metabolic dysfunction-associated steatosis liver disease-Individual participant data meta-analyses.

BACKGROUND: There are limited data regarding the longitudinal association between MEFIB-Index (MRE combined with FIB-4) versus MAST-Score (MRI-aspartate aminotransferase) and hepatic decompensation. AIM: To examine the longitudinal association between MEFIB-Index versus MAST-Score in predicting hepatic decompensation in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This was a longitudinal, retrospective analysis of subjects from United States, Japan, and Turkey who underwent a baseline MRE and MRI-PDFF and were followed for hepatic decompensation. Cox-proportional hazard analyses were used to assess the association between MEFIB-Index versus MAST-Score with a composite primary outcome (hepatic decompensation) defined as ascites, hepatic encephalopathy, and varices needing treatment. RESULTS: This meta-analysis of individual participants (IPDMA) included 454 patients (58% women) with a mean (±SD) age of 56.0 (±13.5) years. The MEFIB-Index (MRE ≥3.3 kPa + FIB 4 ≥1.6) and MAST-Score (>0.242) were positive for 34% and 9% of the sample, respectively. At baseline, 23 patients met criteria for hepatic decompensation. Among 297 patients with available longitudinal data with a median (IQR) of 4.2 (5.0) years of follow-up, 25 incident cases met criteria for hepatic decompensation. A positive MEFIB-Index [HR = 49.22 (95% CI: 6.23-388.64, p < 0.001)] and a positive MAST-Score [HR = 3.86 (95% CI: 1.46-10.17, p < 0.001)] were statistically significant predictors of the incident hepatic decompensation. MEFIB-Index (c-statistic: 0.89, standard error (SE) = 0.02) was statistically superior to the MAST-Score (c-statistic: 0.81, SE = 0.03) (p < 0.0001) in predicting hepatic decompensation. CONCLUSION: A combination of MRI-based biomarker and blood tests, MEFIB-Index and MAST-Score can predict the risk of hepatic decompensation in patients with MASLD.

Impact of rifaximin use following an initial overt hepatic encephalopathy hospitalization on rehospitalization and costs.

AIM: To assess the impact of rifaximin (± lactulose) use following discharge of an initial overt hepatic encephalopathy (OHE) hospitalization on OHE rehospitalizations and healthcare costs in a real-world setting. METHODS: Adults (18-64 years) with an OHE hospitalization were identified from MarketScan® Commercial claims (Q4'15-Q2'20), classified into two mutually exclusive treatment cohorts (i.e. rifaximin and no rifaximin treatment), and further stratified into four subgroups based on decreasing quality of care (QoC; i.e. Type 1 - rifaximin without delay post-discharge; Type 2 - rifaximin with delay post-discharge; Type 3 - lactulose only post-discharge; Type 4 - no rifaximin/lactulose treatment post-discharge). The impact of rifaximin use on 30-day and annualized OHE hospitalizations and healthcare costs were assessed between cohorts and by the QoC subgroup. RESULTS: Characteristics were similar between the rifaximin (N = 1,452; Type 1: 1,138, Type 2: 314) and no rifaximin (N = 560; Type 3:337, Type 4: 223) treatment cohorts. The 30-day risk of OHE rehospitalization was lower for the rifaximin vs. no rifaximin treatment cohort (odds ratio 0.56, p < .01) and increased with decreasing QoC. The annual rate of OHE hospitalizations was 59% lower for the rifaximin treatment cohort (incidence rate ratio 0.41, p < .01) and increased with decreasing QoC. Compared to the no rifaximin treatment cohort, the rifaximin treatment cohort had higher pharmacy costs, lower medical costs, and no difference in total healthcare costs. LIMITATIONS: This was a claims-based study subject to common data limitations such as billing inaccuracies or omissions in coded claims. Total healthcare costs were reported from a payer's perspective, which do not capture indirect costs associated with patient burden. CONCLUSIONS: Initiation of rifaximin after an OHE hospitalization was associated with reduced OHE hospitalizations both in the 30-days following and annually. Further, reduced medical costs offset increased pharmacy costs, and no annual cost differences were observed between cohorts.

3D automatic liver and spleen assessment in predicting overt hepatic encephalopathy before TIPS: a multi-center study.

BACKGROUND: Overt hepatic encephalopathy (HE) should be predicted preoperatively to identify suitable candidates for transjugular intrahepatic portosystemic shunt (TIPS) instead of first-line treatment. This study aimed to construct a 3D assessment-based model to predict post-TIPS overt HE. METHODS: In this multi-center cohort study, 487 patients who underwent TIPS were subdivided into a training dataset (390 cases from three hospitals) and an external validation dataset (97 cases from another two hospitals). Candidate factors included clinical, vascular, and 2D and 3D data. Combining the least absolute shrinkage and operator method, support vector machine, and probability calibration by isotonic regression, we constructed four predictive models: clinical, 2D, 3D, and combined models. Their discrimination and calibration were compared to identify the optimal model, with subgroup analysis performed. RESULTS: The 3D model showed better discrimination than did the 2D model (training: 0.719 vs. 0.691; validation: 0.730 vs. 0.622). The model combining clinical and 3D factors outperformed the clinical and 3D models (training: 0.802 vs. 0.735 vs. 0.719; validation: 0.816 vs. 0.723 vs. 0.730; all p < 0.050). Moreover, the combined model had the best calibration. The performance of the best model was not affected by the total bilirubin level, Child-Pugh score, ammonia level, or the indication for TIPS. CONCLUSION: 3D assessment of the liver and the spleen provided additional information to predict overt HE, improving the chance of TIPS for suitable patients. 3D assessment could also be used in similar studies related to cirrhosis.

High rifaximin out-of-pocket costs are associated with decreased treatment retention among patients with hepatic encephalopathy.

BACKGROUND AND AIMS: Hepatic encephalopathy (HE) is associated with significant morbidity and mortality for those with cirrhosis. Despite the known benefits of rifaximin use for HE, treatment retention remains low. This study aimed to evaluate the impact of out-of-pocket (OOP) rifaximin cost on treatment retention among commercially insured patients in the United States. METHODS: Adult patients with cirrhosis and HE were identified from the IBM MarketScan claims database. Those who began rifaximin treatment between January 1, 2011, and December 1, 2021 were included. Regression models were used to analyze the relationship between patients' 30-day OOP rifaximin cost and rifaximin retention (≥80% eligible days with rifaximin supply) at 180, 360, and 540 days. Models were controlled for patient demographic and clinical characteristics including age, sex, comorbid conditions, Charlson comorbidity index (CCI), and lactulose use. RESULTS: A total of 6839 adult patients were included. Most patients were between 55 and 64 years (57.1%), male (60.4%), and living in urban settings (84.6%). Treatment retention was low for all time periods; retention rates for rifaximin were 42%, 25%, and 16% at 180, 360, and 540 days, respectively. In multivariable analysis, 30-day OOP costs of ≥ $150 were associated with a decreased likelihood of rifaximin retention at 180, 360, and 540 days [relative risk (RR) = 0.67, RR = 0.62, and R = 0.60, respectively]. Younger age was associated with reduced treatment retention for all time periods. Metastatic cancer and depression were associated with reduced treatment retention at 180 days (RR = 0.70 and RR = 0.87, respectively). CONCLUSIONS: Rates of rifaximin treatment retention are low despite the known benefits of rifaximin use for breakthrough HE. High 30-day OOP cost is associated with reduced rifaximin treatment retention.

L-Ornitina L-Aspartato en el tratamiento de la encefalopatía hepática / L-Ornithine L-Aspartate in the treatment of hepatic encephalopathy

DESCRIPCIÓN DEL PROBLEMA DE SALUD: La cirrosis es un trastorno crónico del hígado. Los pacientes con esta afección desarrollan por lo general encefalopatía hepática, una complicación que da lugar a un funcionamiento cerebral deficiente. Algunos pacientes con cirrosis desarrollan características clínicas obvias de una alteración en el funcionamiento cerebral, como dificultades con el habla, el equilibrio y el funcionamiento diario; se dice que presentan encefalopatía hepática evidente; los cambios pueden ser transitorios, recurrentes o pueden persistir durante períodos prolongados. Otros pacientes con cirrosis pueden no mostrar cambios obvios, aunque al realizarles pruebas se pueda encontrar que algunos aspectos clínicos de la función cerebral, como la atención y la capacidad para cumplir tareas complejas, presentan un deterioro; se dice que presentan encefalopatía hepática mínima. La razón por la que los pacientes desarrollan encefalopatía hepática es compleja, pero la acumulación en sangre de toxinas de los intestinos, en particular de un compuesto llamado amoníaco, desempeña una función clave. La L-ornitina L-aspartato reduce los niveles de amoníaco en sangre y, por lo tanto, puede tener efectos beneficiosos en los pacientes con encefalopatía hepática o ayudar a interrumpir su desarrollo. METODOLOGÍA: Se realizó una búsqueda en las principales bases de datos bibliográficas Pubmed: L-ornithine L-aspartate and/or, Dipeptides [adverse effects, *therapeutic use]; Hepatic Encephalopathy [*drug therapy, mortality, *prevention & control]; Liver Cirrhosis [*complications]; Quality of Life; Randomized Controlled Trials as Topic; Branched Chain Amino Acid Supplementation; Probiotics; Lactulose; Placebo; Lactitol; Antibiotic Therapy. Se filtró la búsqueda a Estudios Clínicos fase III, controlados randomizados, Revisiones Sistemáticas, Meta-análisis, Guías de Práctica Clínica, además se limitó la búsqueda estudios en humanos. También se realizó búsqueda manual en otras bases de datos bibliográficas (Cochrane, NIH, TRIP DATABASE), en buscadores genéricos de internet, agencias de evaluación de tecnologías sanitarias y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas, meta-análisis, estudios clínicos aleatorizados y controlados, guías de práctica clínica, evaluaciones de tecnología sanitaria, evaluaciones económicas y políticas de cobertura de otros sistemas de salud. CONCLUSIONES: Eficacia: L-Ornitina-L-Asparato (LOLA) ha sido utilizada como tratamiento para pacientes con hepatopatía crónica con riesgo de encefalopatía hepática. La evaluación de la eficacia de LOLA en esta población se ha basado en estudios clínicos controlados y aleatorizados. En general, la evidencia disponible sugiere que LOLA puede ser eficaz en la prevención y tratamiento de la encefalopatía hepática en pacientes con hepatopatía crónica. En varios estudios clínicos se ha observado que el uso de LOLA se asocia con una reducción significativa en la incidencia de la encefalopatía hepática y una mejora en la calidad de vida de los pacientes. Por ejemplo, un estudio aleatorizado, doble ciego y controlado con placebo realizado en 2011 demostró que LOLA redujo significativamente la incidencia de encefalopatía hepática en pacientes con cirrosis hepática avanzada. Otro estudio aleatorizado y controlado, publicado en 2015, encontró que el uso de LOLA se asoció con una mejora significativa en la calidad de vida de los pacientes con encefalopatía hepática. Sin embargo, es importante tener en cuenta que algunos estudios han reportado resultados contradictorios, y la evidencia global sobre la eficacia de LOLA es limitada y no concluyente. Además, la mayoría de los estudios han sido realizados en poblaciones específicas y pueden no ser generalizables a otras poblaciones. Seguridad: Según la revisión sistemática y metaanálisis analizados, se concluye que la L-Ornitina-L-Asparato es segura en la dosis recomendada para pacientes con cirrosis hepática y encefalopatía hepática. En los estudios revisados, no se reportaron efectos adversos graves asociados con el uso de LOrnitina-L-Asparato, y los efectos secundarios menores (como diarrea y náuseas) se presentaron en una proporción similar entre el grupo de tratamiento y el grupo de control. Además, otros estudios investigados compararon la seguridad de la L-Ornitina-L-Asparato con la lactulosa (un tratamiento convencional para la encefalopatía hepática) en pacientes con cirrosis hepática y encefalopatía hepática. Los resultados indicaron que la L-Ornitina-L-Asparato y la lactulosa fueron igualmente seguras, y que no hubo diferencias significativas en la frecuencia o gravedad de los efectos adversos entre ambos tratamientos. Conveniencia: Las ventajas de utilizar las diferentes opciones terapéuticas dependen de la condición específica del paciente. Tanto la lactulosa como la rifaximina se administran por vía oral, sin embargo, en casos donde la vía oral está comprometida, las ampollas endovenosas de L-ornitina-L-aspartato se convierten en la opción más viable. Costo: Aunque el costo por tratamiento completo puede ser más alto que otras opciones terapéuticas, la eficacia y seguridad de L-Ornitina-L-Asparato lo convierten en una opción atractiva desde el punto de vista costo-efectividad. Además, si se logra prevenir la encefalopatía hepática, los costos a largo plazo para el tratamiento de esta condición serían mucho mayores. Además, considerando los beneficios que se han demostrado en cuanto a la eficacia y seguridad del tratamiento, especialmente en pacientes con encefalopatía hepática de grado leve a moderado, podemos concluir que el uso de L-Ornitina-L-Aspartato es una opción costo-efectiva para el tratamiento de estos pacientes en el contexto del Instituto Salvadoreño del Seguro Social. Es importante tener en cuenta que la evaluación de costo-efectividad no solo se basa en el costo del tratamiento, sino también en la eficacia y los beneficios que se obtienen a través de su uso. En este caso, se ha demostrado que el uso de L-Ornitina-L-Aspartato tiene un impacto positivo en la reducción de los síntomas de encefalopatía hepática y la calidad de vida de los pacientes, lo que puede justificar su uso en términos de costo-efectividad.

Quantifying days at home in patients with cirrhosis: A national cohort study.

BACKGROUND AND AIMS: Days at home (DAH) is a patient-centric metric developed by the Medicare Payment Advisory Commission, capturing annual health care use, including and beyond hospitalizations and mortality. We quantified DAH and assessed factors associated with DAH differences among patients with cirrhosis. APPROACH AND RESULTS: Using a national claims database (Optum) between 2014 and 2018, we calculated DAH (365 minus mortality, inpatient, observation, postacute, and emergency department days). Among 20,776,597 patients, 63,477 had cirrhosis (median age, 66, 52% males, and 63% non-Hispanic White). Age-adjusted mean DAH for cirrhosis was 335.1 days (95% CI: 335.0 to 335.2) vs 360.1 (95% CI: 360.1 to 360.1) without cirrhosis. In mixed-effects linear regression, adjusted for demographic and clinical characteristics, patients with decompensated cirrhosis spent 15.2 days (95% CI: 14.4 to 15.8) in postacute, emergency, and observation settings and 13.8 days (95% CI: 13.5 to 14.0) hospitalized. Hepatic encephalopathy (-29.2 d, 95% CI: -30.4 to -28.0), ascites (-34.6 d, 95% CI: -35.3 to -33.9), and combined ascites and hepatic encephalopathy (-63.8 d, 95% CI: -65.0 to -62.6) were associated with decreased DAH. Variceal bleeding was not associated with a change in DAH (-0.2 d, 95% CI: -1.6 to +1.1). Among hospitalized patients, during the 365 days after index hospitalization, patients with cirrhosis had fewer age-adjusted DAH (272.8 d, 95% CI: 271.5 to 274.1) than congestive heart failure (288.0 d, 95% CI: 287.7 to 288.3) and chronic obstructive pulmonary disease (296.6 d, 95% CI: 296.3 to 297.0). CONCLUSIONS: In this national study, we found that patients with cirrhosis spend as many, if not more, cumulative days receiving postacute, emergency, and observational care, as hospitalized care. Ultimately, up to 2 months of DAH are lost annually with the onset of liver decompensation. DAH may be a useful metric for patients and health systems alike.

The trends in cost associated with liver transplantation in the US: Analysis of weighted hospital data.

This study aims to evaluate recent annualized trends in the cost-burden of inpatient hospitalizations associated with liver transplantation (LT) in the US as stratified by patient demographics and medical characteristics. From 2016 to 2019 National Inpatient Sample was used to select patients who underwent LT, from which the weighted charge estimates were derived and converted to admission costs using inflation-adjusted charge-to-cost ratios. The adjusted values were stratified using select patient variables and graphed across the respective years to derive goodness-of-fit for each trend (expressed with R2 and p -values). From 2016 to 2019, the estimated total number of LT-related hospitalizations in the US were 6685, 7075, 7260, and 7815 cases respectively. There was a general increase in the total cost of LT-related hospitalizations over the years: $945.75, $1010.23, $1052.46, and $1143.84 in millions of dollars (0.98, 0.01). Furthermore, positive trends in total cost were observed in the following strata: patients aged 35-49 (0.92, 0.04) and above 65 (0.91, 0.05), Whites (0.99, 0.01), those with congestive heart failure (0.98, 0.01), ≥2 comorbidities (0.97, 0.02), hepatic encephalopathy (0.93, 0.04), and those with private insurance (0.93, 0.04), as well as LT performed in the Northeast (0.94, 0.03), Midwest (0.92, 0.04), and South (0.91, 0.04). Total cost associated with hepatitis C declined significantly (0.94, 0.03). With respect to mean costs, positive trends were observed in the following strata: those with other or cryptogenic liver disease (0.93, 0.03), ≥2 comorbidities (0.96, 0.02), and LT performed in the Northeast region (0.93, 0.04). The number of liver transplants performed in the US, as well as the associated costs, are rising. Given the apparent rising costs in specific patient populations, economic and public health policies must focus on cost containment within these groups to ensure appropriate usage of resources.

Confusion assessment method accurately screens for hepatic encephalopathy and predicts short-term mortality in hospitalized patients with cirrhosis.

Hepatic encephalopathy (HE), a subtype of delirium, is common in cirrhosis and associated with poor outcomes. Yet, objective bedside screening tools for HE are lacking. We examined the relationship between an established screening tool for delirium, Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and short-term outcomes while comparing its performance with previously established measures of cognitive function such as West Haven criteria (WHC). Prospectively enrolled adults with cirrhosis who completed the CAM-ICU from 6/2014-6/2018 were followed for 90 days. Blinded provider-assigned West Haven Criteria (WHC) and other measures of cognitive function were collected. Logistic regression was used to test associations between CAM-ICU status and outcomes. Mortality prediction by CAM-ICU status was assessed using Area under the Receiver Operating Characteristics curves (AUROC). Of 469 participants, 11% were CAM-ICU( +), 55% were male and 94% were White. Most patients were Childs-Pugh class C (59%). CAM-ICU had excellent agreement with WHC (Kappa = 0.79). CAM-ICU( +) participants had similar demographic features to those CAM-ICU(-), but had higher MELD (25 vs. 19, p < 0.0001), were more often admitted to the ICU (28% vs. 7%, p < 0.0001), and were more likely to be admitted for HE and infection. CAM-ICU( +) participants had higher mortality (inpatient:37% vs. 3%, 30-day:51% vs. 11%, 90-day:63% vs. 23%, p < 0.001). CAM-ICU status predicted mortality with AUROC of 0.85, 0.82 and 0.77 for inpatient, 30-day and 90-day mortality, respectively. CAM-ICU easily screens for delirium/HE, has excellent agreement with WHC, and identifies a hospitalized cirrhosis cohort with high short-term mortality.

WAITING LIST FOR LIVER TRANSPLANTATION: CLINICAL AND ECONOMIC BURDEN.

BACKGROUND: Burden of disease is an indicator that relates to health status. United States and European epidemiological data have shown that the burden of chronic liver disease has increased significantly in recent decades. There are no studies evaluating the impact of complications of chronic liver disease on the waiting list for deceased donor liver transplantation (LTx). OBJECTIVE: To determine the clinical and economic burden of complications of liver disease in wait-listed patients from the perspective of a transplant center. METHODS: The study retrospectively analyzed medical records of 104 patients wait-listed for deceased donor LTx from October 2012 to May 2016 and whose treatment was fully provided at the study transplant center. Clinical data were obtained from electronic medical records, while economic data were collected from a hospital management software. To allocate all direct medical costs, two methods were used: full absorption costing and micro-costing. RESULTS: The most common complication was refractory ascites (20.2%), followed by portosystemic encephalopathy (12.5%). The mean number of admissions per patient was 1.37±3.42. Variceal hemorrhage was the complication with longest median length of stay (18 days), followed by hepatorenal syndrome (13.5 days). Hepatorenal syndrome was the costliest complication (mean cost of $3,565), followed by portosystemic encephalopathy ($2,576) and variceal hemorrhage ($1,530). CONCLUSION: The burden of chronic liver disease includes a great cost for health systems. In addition, it is likely to be even greater as a result of the insidious course of the disease.

The Assessment of Driving Fitness Using an On-Road Evaluation in Patients With Cirrhosis.

INTRODUCTION: The association between cirrhosis and driving performance is of particular clinical relevance because of the life-threatening safety issues both for the driver with cirrhosis and the general public. Study aims were to assess (i) driving competency through the use of an in-office computerized battery and on-road driving assessment (DriveABLE) and (ii) the association between minimal hepatic encephalopathy (MHE), in-office paper-pencil tools, and additional measures (e.g., frailty, depression, cognitive testing) with unsafe driving. METHODS: Patients were prospectively recruited from 2 tertiary care liver clinics. In-office tests and in-office and on-road assessments of driving competence were completed. The χ 2 test and 1-way analysis of variance were used to analyze differences among those with and without MHE. Logistic regression was used to evaluate predictors of an indeterminate/fail result on the in-office computerized driving assessment battery (DriveABLE Cognitive Assessment Tool [DCAT]). RESULTS: Eighty patients participated with a mean age of 57 years, 70% male, 75% Child-Pugh B/C, and 36% with a history of overt hepatic encephalopathy. Thirty percent met MHE criteria on both the psychometric hepatic encephalopathy score and the Stroop app tests. Only 2 patients (3%) were categorized as "unfit to drive" in the on-road driving test, one with MHE and the other without. Fifty-eight percent of the patients were scored as indeterminate/fail on the DCAT. This corresponded to a higher mean number of on-road driving errors (5.3 [SD 2.1] vs 4.2 [SD 1.6] in those who passed the DCAT, P = 0.01). Older age (odds ratio 1.3; confidence interval 1.1, 1.5; P = 0.001) and MHE by Stroop/psychometric hepatic encephalopathy score (odds ratio 11.0; confidence interval 2.3, 51.8; P = 0.002) were independently predictive of worse performance on the DCAT. DISCUSSION: Worse performance in in-office testing was associated with worse scores on a computerized driving assessment battery and more on-road driving errors, but in-office tools were insufficient to predict on-road driving failures. A diagnosis of MHE should not be used alone to restrict driving in patients with cirrhosis. At-risk patients require on-road driving tests under the supervision of driving regulatory agencies. Future studies should continue to refine and evaluate in-office or at-home testing to predict driving performance.

Real-world clinical features, health-care utilization, and economic burden in decompensated cirrhosis patients: A national database.

BACKGROUND: Patients with decompensated cirrhosis are well known to experience morbidity and mortality. AIM: We assessed clinical characteristics, health-care utilization, and economic burden according to the type, number, and combination of decompensation-related complications. METHODS: We used recent nationally representative sample data from 2016 to 2018, covering approximately 13% of hospitalized patients in South Korea annually. Decompensation-related complications included ascites, hepatic encephalopathy (HE), gastroesophageal variceal (GEV) bleeding, and hepatorenal syndrome (HRS). RESULTS: Among 14 601 patients with decompensated cirrhosis, 11 201 (76.7%) experienced ≥ 1 decompensation-related complications, and approximately three-quarters underwent hospitalization. The most prevalent decompensation-related complications were ascites (54.8%), GEV bleeding (33.2%), HE (27.4%), and HRS (3.6%). Patients with GEV bleeding exhibited the highest hospitalization rate (95.7%), and patients with HE or HRS underwent hospitalization for 4 weeks/year due to decompensated cirrhosis. Hospitalization costs were 1.9 times higher in patients with HRS than in those with ascites alone ($9022 vs $4673; P < 0.01). Once patients developed decompensation-related complications, 41.3% had ≥ 2 types of decompensation-related complications. As the number of decompensation-related complications increased from 0 to ≥ 3, health-care utilization and economic burden significantly increased in a stepwise manner; patients with ascites, GEV bleeding, and HE visited medical institutions 2.2 times more (11 vs 5/year; P < 0.01) and incurred 6.4 times greater medical expenditure ($11 060 vs $1728/year; P < 0.01) than those with ascites only. CONCLUSION: A substantial proportion of patients had multiple decompensation-related complications and socioeconomic burdens for decompensated cirrhosis considering admission rate, hospital stay, and costs increased markedly, depending on the number of decompensation-related complications.

Racial and ethnic disparities in rifaximin use and subspecialty referrals for patients with hepatic encephalopathy in the United States.

BACKGROUND & AIMS: Rifaximin use in combination with lactulose is associated with a decreased risk of overt hepatic encephalopathy (HE). We sought to determine whether race and ethnicity were associated with rifaximin prescriptions. METHODS: We examined data for a 20% random sample of United States Medicare enrollees with cirrhosis and hepatic encephalopathy treated with outpatient lactulose and Part D prescription coverage from 2011-2019. Beginning at the time of first diagnosis, we evaluated time to first prescription of rifaximin accounting for competing risks (Fine-Gray, yielding subdistribution hazard ratios [sHRs]) and cumulative rifaximin exposure using a gamma hurdle model (yielding exposure length ratios). We aimed to determine the association of race and ethnicity with each outcome, adjusting for demographics, clinical factors, and other features of clinical management. RESULTS: Overall, 29,095 patients were diagnosed with HE and treated with lactulose, of whom 13,272 were prescribed rifaximin. Compared to White patients, Black patients were least likely to receive any prescription for rifaximin (sHR 0.70; 95% CI 0.65-0.76). Asian and Hispanic patients were also less likely to receive rifaximin compared to White patients. Black patients also received fewer doses of rifaximin (exposure length ratio 0.90; 95% CI 0.82-0.98). Hispanic patients also received fewer doses (0.88; 95% CI 0.80-0.98). Out-of-pocket spending on rifaximin per person-year was higher for Black and Hispanic than White patients. Out-of-pocket medication spending was associated with reduced odds of filling a rifaximin prescription. Black and Hispanic patients were least likely to be referred to a gastroenterologist. CONCLUSION: In a national cohort of patients with HE, we observed stark racial and ethnic disparities in the use of rifaximin, an approved therapy for the improvement of HE-specific outcomes. Access to gastroenterologists and cost controls may reduce disparities. LAY SUMMARY: Hepatic encephalopathy is a serious problem that can affect people with cirrhosis. When someone develops hepatic encephalopathy, there are 2 main treatments. The first-line treatment is called lactulose. If episodes of hepatic encephalopathy happen on lactulose, another treatment called rifaximin is recommended. In this study, we found that compared to White patients, Black and Hispanic patients are less likely to be prescribed rifaximin, receive fewer rifaximin refills, spend more on rifaximin, and have less access to subspecialists who are familiar with rifaximin. We conclude that efforts to address the cost of rifaximin and access to gastroenterologists could help improve these disparities.

A Prospective, Blinded Assessment of Ammonia Testing Demonstrates Low Utility Among Front-Line Clinicians.

Although ammonia is essential to the pathophysiology of hepatic encephalopathy (HE), its levels cannot diagnose HE, do not correlate with the grade of HE, and are plagued by technical challenges.1 Nevertheless, ammonia levels are routinely obtained in the evaluation of hospitalized patients.2 We have advocated for quality improvement to limit testing.3 However, data are lacking regarding the reasons for, context, and perceived value of ammonia testing among ordering clinicians. Additional data are needed to optimize a quality improvement intervention aiming to curb overuse.

Predictors of 30-day readmission and hospitalization costs of patients with hepatic encephalopathy in the US from 2010 to 2014.

BACKGROUND: Hepatic encephalopathy (HE) is a complex and reversible neuropsychiatric syndrome that is associated with growing, substantial healthcare resource utilization. We aim to examine the predictors of 30-day readmission and hospitalization cost associated with HE. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study using the Nationwide Readmissions Database from 2010 to 2014. We assessed the readmission rates using multivariate logistic regression and established temporal trends of readmission rates and hospitalization cost. Weighted hierarchical logistic regression and generalized linear mixed models were used to identify predictors for nationally representative readmissions and hospitalization costs, respectively. RESULTS: The number of index hospitalizations with HE increased with a significant trend from 34,967 in 2010 to 44,791 in 2014. 16.8% of patients were readmitted within 30 days. Predictors increasing readmission risk included female sex, Elixhauser readmission score < 25, elective admission, patient's state residential status, privately insured, number of diagnoses >13, and length of stay >4 days. CONCLUSIONS: Our results indicate there is a need to implement better management strategies to improve outcomes in patients hospitalized with HE to curb the increase in the economic burden associated with the disease.

Budget impact of optimizing rifaximin-α use for the prevention of recurrent hepatic encephalopathy in The Netherlands.

AIMS: Rifaximin-α as an adjunct to lactulose is reimbursed in the Netherlands for prevention of the third and subsequent episodes of overt Hepatic Encephalopathy (HE) in cirrhotic patients. However, use of rifaximin-α remains limited. This study evaluates the clinical and economic impact of treating all patients eligible under Dutch reimbursement conditions with rifaximin-α as an adjunct to lactulose for the prevention of overt HE in the Netherlands from a hospital and healthcare payer's perspective. MATERIALS AND METHODS: A budget impact analysis was performed following national and international guidelines. Resource use was based on Dutch real-world data. HE-related cost inputs were based on the declaration codes, Dutch cost manual, and actual drug list prices. Several sensitivity and scenario analyses were conducted to assess model robustness. RESULTS: Treating eligible HE patients with rifaximin-α in addition to lactulose saves €4,487 and costs €249 per patient over a 5-year period compared with lactulose monotherapy from hospital and healthcare payer's perspectives, respectively. In the Netherlands, an estimated 38% of the 2,567 eligible patients are currently being treated with rifaximin-α. Optimizing rifaximin-α use by treating all eligible patients with the rifaximin-α + lactulose could save more than 3,000 hospital admissions, almost 15,000 hospital bed days, and 300 deaths over a 5-year period. Despite increased drug costs, treatment is estimated to result in potential cost savings over a 5-year period of 7.2 million euros from a Dutch hospital perspective. The budget impact is 397,770 euros from a healthcare payer's perspective. CONCLUSIONS: Next to a clinical perspective, also from an economic perspective, wider prescription of rifaximin-α adhering to guidelines could be beneficial to reduce costs from a hospital perspective. From a healthcare payer's perspective, costs increase with addition of rifaximin-α due to relative better survival causing relatively higher drug and liver transplantation-related costs.

Hepatic Encephalopathy is Associated With Slow Speech on Objective Assessment.

INTRODUCTION: There are no available low-burden, point-of-care tests to diagnose, grade, and predict hepatic encephalopathy (HE). METHODS: We evaluated speech as a biomarker of HE in 76 English-speaking adults with cirrhosis. RESULTS: Three speech features significantly correlated with the following neuropsychiatric scores: speech rate, word duration, and use of particles. Patients with low neuropsychiatric scores had slower speech (22 words/min, P = 0.01), longer word duration (0.09 seconds/word, P = 0.01), and used fewer particles (0.85% fewer, P = 0.01). Patients with a history of overt HE had slower speech (23 words/min, P = 0.005) and longer word duration (0.09 seconds/word, P = 0.005). DISCUSSION: HE is associated with slower speech.