Therapeutic Plasma Exchange in Children With Acute and Acuteon-Chronic Liver Failure: A Single-Center Experience.

OBJECTIVES: Acute liver failure is a life-threatening condition that may result in death if liver transplant is not performed. The aim of our study was to evaluate patients with acute liver failure or acute-on-chronic liver failure who were followed and treated with therapeutic plasma exchange in a pediatric intensive care unit until they achieved clinical recovery or underwent liver transplant. MATERIALS AND METHODS: In this retrospective, singlecenter study, we included patients with acute liver failure or acute-on-chronic liver failure who received therapeutic plasma exchange between April 2020 and December 2021. Clinical findings, laboratory findings, extracorporeal therapies, Pediatric Risk of Mortality III and liver injury unit scores and pretherapy and posttherapy hepatic encephalopathy scores, Model for End-Stage Liver Disease score, and Pediatric End-Stage Liver Disease score were retrospectively analyzed. RESULTS: Nineteen patients were included in the study. One patient was excluded because of positivity for COVID-19. The mean age of children was 62.06 months, ranging from 5 months to 16 years (12 boys, 6 girls). Thirteen patients (72.2%) had acute liver failure, and 5 patients (27.8%) had acute-on-chronic liver failure. No significant difference was shown for mean liver injury unit score (P = .673) and Pediatric Logistic Organ Dysfunction score (P = .168) between patients who died and patients who received treatment at the inpatient clinic and transplant center. However, Pediatric Risk of Mortality score and the mean Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease scores before therapeutic plasma exchange and after therapeutic plasma exchange (after 3 consecutive days of treatment) were statistically significant (P = .001 and P = .004). CONCLUSIONS: Therapeutic plasma exchange may assist bridge to liver transplant or assist with spontaneous recovery of liver failure in pediatric patients with acute liver failure or acute-on-chronic liver failure.

Assessing resuscitation in burn patients with varying degrees of liver disease.

We find minimal literature and lack of consensus among burn practitioners over how to resuscitate thermally injured patients with pre-existing liver disease. Our objective was to assess burn severity in patients with a previous history of liver disease. We attempted to stratify resuscitation therapy utilised, using it as an indicator of burn shock severity. We hypothesized that as severity of liver disease increased, more fluid therapy is needed. We retrospectively studied adult patients with a total body surface area (TBSA) of burn greater than or equal to 20% (n = 314). We determined the severity of liver disease by calculating admission Model for End-Stage Liver Disease (MELD) scores and measured resuscitation adequacy via urine output within the first 24 h. We performed stepwise, multivariable linear regression with backward selection to test our hypothesis with α = 0.05 defined a priori. After controlling for important confounders including age, TBSA, baseline serum albumin, total crystalloids, colloids, blood products, diuretics, and steroids given in first 24 h, we found a statistically significant reduction in urine output as MELD score increased (p < 0.000). In our study, severity of liver disease correlated with declining urine output during first 24-hour resuscitation more so than burn size or burn depth. While resuscitation is standardized for all patients, lack of urine output with increased liver disease suggests a new strategy is of benefit. This may involve investigation of alternate markers of adequacy of resuscitation, or developing modified resuscitation protocols for use in patients with liver disease. More investigation is necessary into how resuscitation protocols may best be modified.

Recent Trends in Palliative Care Utilization in Patients With Decompensated Liver Disease: 2016-2020 National Analysis.

Background: Patients with end-stage liver disease (ESLD) have a poor quality of life, which often worsens as disease severity increases. Palliative care (PC) has emerged as a management option in ESLD patients, especially for those who are not candidates for a liver transplant. Objective: To assess the associated factors and trends in PC utilization in recent years. Design: We used the 2016-2020 National Inpatient Sample (NIS) database of the United States to identify patients with decompensated cirrhosis who suffered in-hospital mortality. Information regarding patient demographics, hospital characteristics, etiology and decompensations, Elixhauser comorbidities, and interventions was collected. The multivariate regression model was used to identify factors associated with PC use. Results: Out of 98,160 patients, 52,645 patients (53.6%) received PC consultations. PC utilization increased from 49.11% in 2016 to 56.85% in 2019, with a slight decrease to 54.47% in 2020. Patients with PC use had decreased incidence of blood transfusions (28.85% vs. 36.53%, p < 0.001), endoscopy (18% vs. 20.26%, p 0.0001), liver transplantation (0.28% vs. 0.69%, p < 0.001), and mechanical ventilation (46.22% vs. 56.37%, p < 0.001). African American, Hispanic, and Asian/Pacific Islander patients had 29%, 27%, and 23% lower odds of receiving PC than White patients. Patients in the two lowest income quartiles had 12% and 22% lower odds of receiving PC compared with the highest quartile. Conclusions: PC utilization in patients with ESLD is associated with decreased invasive procedures, shorter lengths of stay, and lower hospitalization charges. Minorities, as well as patients in the lower income quartiles, were less likely to receive PC.

Extracorporeal Immunomodulation Therapy in Acute Chronic Liver Failure With Multiorgan Failure: First in Human Use.

Two patients presented with acute on chronic liver failure and multiorgan failure and, as typical for this disorder, they presented with hyperinflammation and anticipated high mortality rates. Both cases were diagnosed with hepatorenal syndrome (HRS). Under a FDA approved Investigational Device Exemption clinical trial, they underwent treatment with an extracorporeal cell-directed immunomodulatory device, called selective cytopheretic device. Both patients showed rapid clinical improvement associated with a decline in elevated blood cytokine concentrations and diminution of activation levels of circulating leukocytes. On follow-up, one patient was alive at day 90 after treatment and undergoing liver transplantation evaluation and the other patient had a successful liver transplantation 6 days after selective cytopheretic device therapy ended. These cases represent the first in human evaluation of extracorporeal cell-directed immunomodulation therapy in acute on chronic liver failure with successful clinical outcomes in a disorder with dismal prognosis.

Perioperative proximal splenic artery embolization in cirrhotic patients with splenomegaly.

INTRODUCTION: The purpose of this study was to determine the effect of proximal splenic artery embolization (SAE) in cirrhotic patients with splenomegaly who underwent surgical laparotomy. MATERIAL AND METHODS: This retrospective observational study included 8 cirrhotic patients with splenomegaly. They underwent proximal SAE before- (n = 6) or after (n = 2) laparotomy. Vascular plugs or coils were placed in the proximal splenic artery. The diameter of the portal vein and the splenic volume were recorded. Clinical outcome assessments included platelet counts, the model for end-stage liver disease (MELD) score, and complications. RESULTS: After embolization, the portal venous diameter was significantly smaller (pre: 13.6 ± 2.7 mm, post: 12.5 ± 2.3 mm, p = 0.023), the splenic volume was significantly decreased (pre: 463.2 ± 145.7 ml, post: 373.3 ± 108.5 ml, p = 0.008) and the platelet count was significantly higher (pre: 69.6 ± 30.8 × 103/µl, post: 86.8 ± 27.7 × 103/µl, p = 0.035). Before embolization, the median MELD score was 12; after embolization, it was 11 (p = 0.026). No patient developed post-treatment complications after embolization. CONCLUSIONS: The reduction of hypersplenism by perioperative proximal SAE may be safe and reduce the surgical risk in cirrhotic patients with splenomegaly.

Early palliative care referral may improve end-of-life care in end-stage liver disease patients: A retrospective analysis from a non-transplant center.

BACKGROUND: Patients with end-stage liver disease (ESLD) who are not transplant candidates often have a trajectory of rapid decline and death similar to patients with stage IV cancer. Palliative care (PC) services have been shown to be underutilized for such patients. Most studies examining the role of PC in ESLD have been done at transplant centers. Thus, determining the utilization and benefit of PC at a non-transplant tertiary center may help establish a standard of care in the management of patients with ESLD not eligible for transplant. METHODS: We conducted a retrospective analysis of adult (>18 years) patients with ESLD admitted to Rochester Regional Health (RRH) system hospitals from 2012 to 2021. Patients were divided into groups based on the presence or absence of PC involvement. Baseline characteristics were recorded. The impact of PC was assessed by comparing the number of hospitalizations before and after the involvement of PC, comparing code status changes, health care proxy (HCP) assignments, Aspira catheter placements, and frequency of repeated paracentesis. RESULTS: In our analysis of 576 patients, 41.1% (237 patients) received a PC consult (PC group), while 58.9% (339 patients) did not (no-PC group). Baseline characteristics were comparable. However, their mean number of admissions significantly decreased (15.66 vs. 3.49, p < 0.001) after PC involvement. Full code status was more prevalent in the no-PC group (67.8% vs. 18.6%, p < 0.001), while comfort care code status was more common in the PC group (59.9% vs. 20.6%, p < 0.001). Changes in code status were significantly higher in the PC group (77.6% vs. 29.2%, p < 0.001). The PC group had a significantly higher mortality rate (83.1% vs. 46.4%, p < 0.01). Patients in the PC group had a higher likelihood of having an assigned HCP (63.7% vs. 37.5%, p < 0.001). PC referral was associated with more frequent use of an Aspira catheter (5.9% vs. 0.9%, p < 0.001) and more frequent paracentesis (30.8% vs. 16.8%, p < 0.001). CONCLUSIONS: In conclusion, our study provides compelling evidence of the diverse advantages of palliative care for patients with end-stage liver disease, including reduced admissions, improved goals of care, code status modifications, enhanced healthcare proxy assignments, and targeted interventions. These findings highlight the potential significance of early integration of palliative care in the disease trajectory to provide comprehensive, patient-centered care that addresses the unique needs and preferences of individuals with advanced liver disease.

A single center retrospective study: Comparison between centrifugal separation plasma exchange with ACD-A and membrane separation plasma exchange with heparin on acute liver failure and acute on chronic liver failure.

The purpose of this retrospective study is to compare the efficacy and safety of the centrifugal separation therapeutic plasma exchange (TPE) using citrate anticoagulant (cTPEc) with membrane separation TPE using heparin anticoagulant (mTPEh) in liver failure patients. The patients treated by cTPEc were defined as cTPEc group and those treated by mTPEh were defined as mTPEh group, respectively. Clinical characteristics were compared between the two groups. Survival analyses of two groups and subgroups classified by the model for end-stage liver disease (MELD) score were performed by Kaplan-Meier method and were compared by the log-rank test. In this study, there were 51 patients in cTPEc group and 18 patients in mTPEh group, respectively. The overall 28-day survival rate was 76% (39/51) in cTPEc group and 61% (11/18) in mTPEh group (P > .05). The 90-day survival rate was 69% (35/51) in cTPEc group and 50% (9/18) in mTPEh group (P > .05). MELD score = 30 was the best cut-off value to predict the prognosis of patients with liver failure treated with TPE, in mTPEh group as well as cTPEc group. The median of total calcium/ionized calcium ratio (2.84, range from 2.20 to 3.71) after cTPEc was significantly higher than the ratio (1.97, range from 1.73 to 3.19) before cTPEc (P < .001). However, there was no significant difference between the mean concentrations of total calcium before cTPEc and at 48 h after cTPEc. Our study concludes that there was no statistically significant difference in survival rate and complications between cTPEc and mTPEh groups. The liver failure patients tolerated cTPEc treatment via peripheral vascular access with the prognosis similar to mTPEh. The prognosis in patients with MELD score < 30 was better than in patients with MELD score ≥ 30 in both groups. In this study, the patients with acute liver failure (ALF) and acute on chronic liver failure (ACLF) treated with cTPEc tolerated the TPE frequency of every other day without significant clinical adverse event of hypocalcemia with similar outcomes to the mTPEh treatment. For liver failure patients treated with cTPEc, close clinical observation and monitoring ionized calcium are necessary to ensure the patients' safety.

Frailty in end-stage liver disease: Understanding pathophysiology, tools for assessment, and strategies for management.

Frailty and sarcopenia are frequently observed in patients with end-stage liver disease. Frailty is a complex condition that arises from deteriorations across various physiological systems, including the musculoskeletal, cardiovascular, and immune systems, resulting in a reduced ability of the body to withstand stressors. This condition is associated with declined resilience and increased vulnerability to negative outcomes, including disability, hospitalization, and mortality. In cirrhotic patients, frailty is influenced by multiple factors, such as hyperammonemia, hormonal imbalance, malnutrition, ascites, hepatic encephalopathy, and alcohol intake. Assessing frailty is crucial in predicting morbidity and mortality in cirrhotic patients. It can aid in making critical decisions regarding patients' eligibility for critical care and transplantation. This, in turn, can guide the development of an individualized treatment plan for each patient with cirrhosis, with a focus on prioritizing exercise, proper nutrition, and appropriate treatment of hepatic complications as the primary lines of treatment. In this review, we aim to explore the topic of frailty in liver diseases, with a particular emphasis on pathophysiology, clinical assessment, and discuss strategies for preventing frailty through effective treatment of hepatic complications. Furthermore, we explore novel assessment and management strategies that have emerged in recent years, including the use of wearable technology and telemedicine.

Stem cell therapy for hepatocellular carcinoma and end-stage liver disease.

Hepatocellular carcinoma (HCC) is a major health problem worldwide, especially for patients who are suffering from end-stage liver disease (ESLD). The ESLD is considered a great challenge for clinicians due to the limited chance for liver transplantation, which is the only curative treatment for those patients. Stem cell-based therapy as a part of regenerative medicine represents a promising application for ESLD patients. Many clinical trials were performed to assess the utility of bone marrow-derived stem cells as a potential therapy for patients with liver diseases. The aim of the present study is to present and review the various types of stem cell-based therapy, including the mesenchymal stem cells (MSCs), BM-derived mononuclear cells (BM-MNCs), CD34 + hematopoietic stem cells (HSCs), induced pluripotent stem cells (iPSCs), and cancer stem cells.Though this type of therapy achieved promising results for the treatment of ESLD, however still there is a confounding data regarding its clinical application. A large body of evidence is highly required to evaluate the stem cell-based therapy after long-term follow-up, with respect to the incidence of toxicity, immunogenicity, and tumorigenesis that developed in many patients.

Effectiveness of adding a defibrillator with cardiac resynchronization therapy in heart failure according to the modified Model for End-stage Liver Disease-Albumin score.

Current guidelines lack clear recommendations between the implantation of cardiac resynchronization therapy (CRT) with defibrillator (CRT-D) and CRT with pacemaker (CRT-P). We hypothesized that modified model for end-stage liver disease score including albumin (MELD-Albumin score), could be used to select patients who may not benefit from CRT-D. We consecutively included patients with CRT-P or CRT-D implantation between 2010 and 2022. The primary endpoint was the composite of all-cause mortality or worsening heart failure. We performed multivariable-adjusted Cox proportional hazard regression. We assessed the interaction between the MELD-Albumin score and the effect of adding a defibrillator with CRT.A total of 752 patients were included in this study, with 291 implanted CRT-P. During a median follow-up of 880 days, 205 patients reached the primary endpoint. MELD-Albumin score was significantly associated with the primary endpoint in the CRT-D group [HR 1.16 (1.09-1.24); P < 0.001] but not in the CRT-P group [HR 1.03 (0.95-1.12); P = 0.49]. There was a significant interaction between the MELD-Albumin score and the effect of CRTD (P = 0.013). The optimal cut-off value of the MELD-Albumin score was 12. For patients with MELD-Albumin ≥ 12, CRT-D was associated with a higher occurrence of the primary endpoint [HR 1.99 (1.10-3.58); P = 0.02], whereas not in patients with MELD-Albumin < 12 [HR 1.19 (0.83-1.70); P = 0.35). Our findings suggest that CRT-D is associated with an excess risk of composite clinical endpoints in HF patients with higher MELD-Albumin score.

[A clinical study of high dependency units to reduce ICU readmission rates in patients with severe liver disease].

Objective: To investigate the real-world difference in the ICU readmission rate between the high-dependency unit (HDU) and the general ward so as to reflect the role of HDU in the diagnosis and management of patients with SLD. Methods: Patients with severe liver disease who were consecutively enrolled were step-downed to HDU and general wards in the ICU of the Fifth Medical Center of the People's Liberation Army General Hospital between July 2017 and December 2021. The main liver function indicators, MELD scores, and other were compared between the two groups. SLD severity, ICU readmission rates, and others differences were analyzed among the patients transferred to different wards. The HDU role was clarified for SLD patients' grade management. The area under the curve of the receiver operating characteristic curve (AUROC) was used to calculate and explore the feasibility of a baseline Model for End-Stage Liver Disease (MELD) score to define the treatment scope of HDU. Results: The SLD group of patients who were transferred to HDU had significantly higher levels of the international normalized ratio, bilirubin, alanine aminotransferase, MELD score, and other factors compared to those in the general ward (P < 0.05). 70.7% of SLD patients in the HDU group had a MELD score > 17, while 61.9% of SLD patients in the general ward group had a MELD score ≤ 17. The overall ICU readmission rate in this cohort was 11.4%. The ICU readmission rate was significantly higher with a MELD score of > 23 (20.0%) than that with a MELD score of ≤ 23 (8.6%) in patients with SLD, according to the MELD score quartile P75 (P = 0.020). The ICU readmission rate was 8.2% when MELD score ≤ 23, and 9.1% when MELD score>23 in the HDU group, with no statistically significant difference (P = 1.000). However, in the general ward group, the ICU readmission rate in patients with a MELD score ≤ 23 was 8.8%, and when the MELD score was >23, the ICU readmission rate significantly increased to 36.4% (P = 0.001). The optimal cut-off value of the MELD score for predicting ICU readmission in patients with SLD in the general ward group was 23.5. Conclusion: The high-dependency unit can better undertake ICU step-down patients with SLD and significantly reduce the ICU readmission rate with MELD scores > 23 in practice. Additionally, ICU step-down SLD patients with a MELD score > 23 are suitable for transfer to HDU treatment.

Cell therapy in end-stage liver disease: replace and remodel.

Liver disease is prevalent worldwide. When it reaches the end stage, mortality rises to 50% or more. Although liver transplantation has emerged as the most efficient treatment for end-stage liver disease, its application has been limited by the scarcity of donor livers. The lack of acceptable donor organs implies that patients are at high risk while waiting for suitable livers. In this scenario, cell therapy has emerged as a promising treatment approach. Most of the time, transplanted cells can replace host hepatocytes and remodel the hepatic microenvironment. For instance, hepatocytes derived from donor livers or stem cells colonize and proliferate in the liver, can replace host hepatocytes, and restore liver function. Other cellular therapy candidates, such as macrophages and mesenchymal stem cells, can remodel the hepatic microenvironment, thereby repairing the damaged liver. In recent years, cell therapy has transitioned from animal research to early human studies. In this review, we will discuss cell therapy in end-stage liver disease treatment, especially focusing on various cell types utilized for cell transplantation, and elucidate the processes involved. Furthermore, we will also summarize the practical obstacles of cell therapy and offer potential solutions.

Cell and cell-derivative-based therapy for liver diseases: current approaches and future promises.

INTRODUCTION: According to the recent updates from World Health Organization, liver diseases are the 12th most common cause of mortality. Currently, orthotopic liver transplantation (OLT) is the most effective and the only treatment for end-stage liver diseases. Owing to several shortcomings like finite numbers of healthy organ donors, lifelong immunosuppression, and complexity of the procedure, cell and cell-derivatives therapies have emerged as a potential therapeutic alternative for liver diseases. Various cell types and therapies have been proposed and their therapeutic effects evaluated in preclinical or clinical studies, including hepatocytes, hepatocyte-like cells (HLCs) derived from stem cells, human liver stem cells (HLSCs), combination therapies with various types of cells, organoids, and implantable cell-biomaterial constructs with synthetic and natural polymers or even decellularized extracellular matrix (ECM). AREAS COVERED: In this review, we highlighted the current status of cell and cell-derivative-based therapies for liver diseases. Furthermore, we discussed future prospects of using HLCs, liver organoids, and their combination therapies. EXPERT OPINION: Promising application of stem cell-based techniques including iPSC technology has been integrated into novel techniques such as gene editing, directed differentiation, and organoid technology. iPSCs offer promising prospects to represent novel therapeutic strategies and modeling liver diseases.

Barriers to palliative care in hepatocellular carcinoma: A review of the literature.

Hepatocellular carcinoma (HCC) is a deadly and burdensome form of liver cancer with an increasing global prevalence. Its course is unpredictable as it frequently occurs in the context of underlying end-stage liver disease, and the associated symptoms and adverse effects of treatment cause severe suffering for patients. Palliative care (PC) is a medical specialty that addresses the physical, emotional, and spiritual needs of patients and their carers in the context of life-limiting illness. In other cancers, a growing body of evidence has demonstrated that the early introduction of PC at diagnosis improves patient and carer outcomes. Despite this, the integration of palliative care at the diagnosis of HCC remains suboptimal, as patients usually receive PC only at the very terminal phase of their disease, even when diagnosed early. Significant barriers to the uptake of palliative care in the treatment algorithm of hepatocellular carcinoma fall under four main themes: data limitations, disease, clinician, and patient factors. Barriers relating to data limitations mainly encapsulated the risk of bias inherent in published work in the field of PC. Clinician-reported barriers related to negative attitudes towards PC and a lack of time for PC discussions. Barriers related to the disease align with prognostic uncertainty due to the unpredictable course of HCC. Significantly, there exists a paucity of evidence exploring patient-perceived barriers to timely PC implementation in HCC. Given that patients are often the underrepresented stakeholder in the delivery of PC, future research should explore the patient perspective in adequately designed qualitative studies as the first step.

Standardized Criteria Increases Palliative Care Consultation Utilization in Patients With End-Stage Liver Disease: A Pilot Study.

Context: Patients with end-stage liver disease have high symptom burden and high healthcare utilization, which may be improved by palliative care consultation. Objectives: We sought to determine if implementing standardized palliative care consultation criteria in hospitalized patients with end-stage liver disease would increase palliative care utilization and improve patient outcomes. Methods: We conducted a retrospective cohort study of hospitalized patients with end-stage liver disease. Patients under the age of 18, received a previous liver transplant, or admitted for liver transplantation were not included. Patients with end-stage liver disease meeting two or more of the following criteria were included: (i)Child Pugh C cirrhosis, (ii)2 or more liver related hospitalizations within 6 months, (iii) current alcohol use with alcoholic cirrhosis, and (iv) unsuitable for transplantation work up. We compared consults before and after implementation of the criteria, and we compared outcomes in patients who did and did not see palliative care. Results: With implementation, consults increased (2/25 (8%) vs 11/33 (33%), p = .020). Palliative care was associated with higher completion of health care representative documentation (66.7% vs 35.7%, P = .20) and physician orders for scope of treatment forms (16.7% vs 0%, P = 0.13). Patients seen by palliative care had a higher rate of discharges with hospice (30.8% vs 0, P = .002). Conclusions: Implementation of standardized palliative care consultation criteria for patients with end-stage liver disease increased palliative care utilization. Patients seen by palliative care had increased discharges with hospice services and a trend towards higher completion rates of advanced directives.

National frequency, trends, and healthcare burden of care fragmentation in readmissions for end-stage liver disease in the USA.

BACKGROUND: End-stage liver disease (ESLD) patients have frequent readmissions to the same facility or a different hospital (care fragmentation). Care fragmentation results in care delivery from an unfamiliar clinical team or setting, a potential source of suboptimal clinical outcomes. We examined the occurrence, trends, and association between care fragmentation and outcomes during readmissions for ESLD. METHODS: From the Nationwide Readmissions Database (January to September 2010-2014), we followed adult (age ≥18 years) hospitalizations for ESLD who were discharged alive for 90 days. During 30- and 90-day readmissions, we calculated the frequency, determinants, and clinical outcomes of care fragmentation (SAS 9.4). RESULTS: Of the 67,480 ESLD hospitalizations surviving at discharge from 2010-2014, 35% (23,872) and 52% (35,549) were readmitted in 30- and 90-days respectively. During readmissions, the frequencies of care fragmentation were similar (30-day: 25.4% and 90-day: 25.8%) and remained stable from 2010 to 2014 (P trends>0.5). Similarly, factors associated with care fragmentation were consistent across 30- and 90-day readmissions. These included ages: 18-44 years, liver cancer, receipt of liver transplantation, hepatorenal syndrome, prolonged length of stay, and hospitalization in non-teaching facilities. During 30- and 90-day readmissions, care fragmentation was associated with higher risk of mortality (adjusted mean ratio: 1.13[1.03-1.24] and 1.14 [1.06-1.23]; P values<0.0001), prolonged length of stay (4.6-days vs. 4.1-days and 5.2-days vs. 4.6-days; P values<0.0001), and higher hospital charges ($36,884 vs. $28,932 and $37,354 vs. $30,851; P values<0.0001). CONCLUSIONS: Care fragmentation is high among readmissions for ESLD and is associated with poorer outcomes.

Therapeutic plasma exchange is a safe and effective bridge therapy in patients with alcohol-associated ACLF not having immediate prospects for liver transplantation-A case-control, pilot study.

BACKGROUND: Therapeutic plasma exchange (TPE) is a well-established treatment modality in acute liver failure patients, but its efficacy in treating acute on chronic liver failure (ACLF) patients is yet to be established. AIM: To assess the efficacy and safety of TPE in patients with alcohol-associated ACLF who were nonresponders to standard medical treatment (SMT) and without immediate prospects for liver transplantation. METHODS: Twenty-eight alcohol-related ACLF (grade II) patients (14 cases and 14 controls) were enrolled in the study. Cases underwent standard volume TPE along with SMT while the controls were on SMT alone. The change (baseline to day 10) in laboratory parameters, cytokine concentrations, clinical severity scores along with 30 and 90 day mortality rates were noted and compared between the two groups. The adverse events (AEs) were noted in the groups and analyzed. RESULTS: A total of 51 TPE procedures were performed in 14 patients (average of 3.62 procedures/patient). TPE was effective in reduction of serum bilirubin, ammonia, activated partial thromboplastin time, prothrombin time, international normalized ratio, and severity scores (ACLF Research Consortium, Maddrey's discriminant function, and model for end-stage liver disease) (P < .05). There was no significant difference in the reduction of serum interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α concentrations among cases. Among the cases who received the complete TPE interventions, 30- and 90-day mortality rates were lower in the cases as compared to controls albeit only the 90-day mortality was significantly different. Procedure-related AEs was observed in 2% of procedures. CONCLUSION: TPE is an effective and well-tolerated bridge therapy in patients with alcohol-associated ACLF of moderate severity not improving on SMT and without immediate prospects for liver transplantation.

Adult Stem Cell Therapy as Regenerative Medicine for End-Stage Liver Disease.

The increased incidence of end-stage liver disease (ESLD) causes a major burden on the global health system and population health. Liver transplantation (LT) is one of the most effective treatments for ESLD patients, but its practice is extensively hampered by the scarcity of liver donors, the limited number of transplantation centers, the complexity of the procedure, and postoperative complication. In parallel, vast growing advances in cellular biology and biotechnology have opened new alternatives in clinics, including the transplantation of adult stem cells for chronic diseases such as ESLD. Numerous types of stem cells, such as mesenchymal stem cells, hematopoietic stem cells, endothelial progenitor cells, and other cells, obtained from bone marrow, umbilical cord, adipose tissue, or peripheral blood had been isolated and given to ESLD patients all over the world. Many clinical data had demonstrated promising results, indicating its potential. However, conclusive protocol and agreement on adult stem cell definition and transplantation method are still lacking, and thus further research must still be conducted.

Low Utilization of External Beam Radiation Therapy for Patients With Unresectable Hepatocellular Carcinoma: An Analysis of the United Network for Organ Sharing Database.

PURPOSE: External beam radiation therapy (EBRT) is a safe and emerging bridging liver-directed therapy (LDT) to liver transplant (LT) for patients with hepatocellular carcinoma (HCC). The prevalence and clinical characteristics of patients receiving EBRT as an LDT for LT have not been evaluated. Our aim was to describe the utilization of EBRT in patients with HCC evaluated for LT in the United States. METHODS AND MATERIALS: We analyzed United Network for Organ Sharing data from October 2013 to June 2020 and identified patients with HCC who applied for model for end-stage liver disease (MELD) exceptions for LT wait list prioritization. The primary outcome was the period prevalence of EBRT. We examined associations between clinical variables and EBRT and fit survival models with EBRT as a time-varying predictor. RESULTS: We identified 18,543 patients with HCC with MELD exception applications. EBRT was used in 658 patients (3.5%) either alone (1.2%) or combined with other LDT (2.3%). Transarterial chemoembolization was the most used LDT (59.3%), followed by thermal ablation (27.9%) and radioembolization (15.2%). EBRT prevalence rose by an average of 12.2% per year (P = .001). Use of EBRT differed by geographic region, ranging from 2% to 8% (P < .001). EBRT and no EBRT groups had similar initial MELD score, portal vein thrombosis, tumor diameter, number of tumors, bilirubin, and α-fetoprotein (P > .05). Median time-to-transplant from wait list registration for EBRT versus no EBRT groups was 10 months (95% confidence interval, 9.4-10.9) versus 11.9 months (95% confidence interval, 11.7-12.2; P < .001). Evaluated as a time-varying predictor, EBRT increased the risk of LT by 30% (sub-hazard ratio, 1.30; P < .001), while the effect of EBRT on the risk of wait list removal due to clinical deterioration or death (sub-hazard ratio, 1.07; P = .489) was nonsignificant. CONCLUSIONS: In the United States, EBRT is rarely used compared with other LDTs and exhibits geographic variation. Low EBRT utilization highlights a gap in the treatment armamentarium for HCC.

Prognostic value of decline in model for end-stage liver disease score and hepatic encephalopathy in hepatitis B-related acute-on-chronic liver failure patients treated with plasma exchange.

OBJECTIVE: To investigate the prognostic value of Model for End-Stage Liver Disease (MELD) score and Hepatic Encephalopathy (HE) for short-term prognosis of Hepatitis B virus-related Acute-on-Chronic Liver Failure (HBV-ACLF) patients treated with plasma exchange (PE). METHODS: A total of 108 patients with HBV-ACLF treated with PE were retrospectively enrolled between January 2014 to December 2020. Based on survival at 28 days, patients were divided into survival (N = 87) and death groups (N = 21). Clinical data and laboratory indicators were analyzed. RESULTS: Compared with the survival group, the death group was associated with higher ACLF grade and incidence of HE. The levels of total bilirubin, prothrombin time, creatinine, blood urea nitrogen, MELD score, and Chinese Group on the Study of Severe Hepatitis B-ACLF II (COSSH II) score were significantly higher in the death group than in the survival group (p < .05). Grade 1 ACLF and the MELD score after PE treatment at one week were independent risk factors for 28-day liver transplantation-free mortality (OR = 0.062, 95%CI: 0.005-0.768; OR = 1.328, 95%CI: 1.153-1.531). A MELD score at one week of at least 25.5 was associated with a poor short-term prognosis. Of note, HE was a strong independent risk factor for a decline in MELD score at one week. (OR = 11.815, 95%CI: 3.187-43.796, p < 0.001). CONCLUSION: We found patients with HE at admission and MELD score of at least 25.5 at one week after PE treatment had a poor short-term prognosis and should prompt preparation for liver transplantation. Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04231565). Registered 13 May 2020.