End-stage Liver Disease Research Articles

Management of Incidentally Detected Urinary Tract Calculus in Patients Awaiting Living Donor Liver Transplantation: A Protocol-Based Approach

BackgroundUrinary tract calculi (UTC) in patients awaiting living donor liver transplant (LDLT) requires proper management due to increased risk of infections in the post-liver transplant (LT) period. Materials and MethodsA retrospective analysis of records of LDLT recipients with UTC was conducted between July 2019 and July 2023. No prisoners or paid participants were included. ResultsThirty patients (25 women and 5 men) with a mean age of 44.45 ± 9.67 years, model of end stage liver disease with sodium (MELD-Na) of 20.5 ± 12.2 were diagnosed to have a UTC during pre-LT evaluation. Twenty-five patients had renal stones, whereas five patients had ureteric calculus (22 were unilateral and 8 were bilateral calculi). Fifteen patients underwent double J (DJ)-stenting prior to LT. The mean stone size in patients who underwent DJ stenting was 13.6 (±9.83) mm vs 4.78 (±5.3) mm in whom stenting was not done. Patients with preoperative DJ stenting had a significantly reduced hospital stay (18.5 ± 2.1 days), lower mortality rates (0%), and lower rates of hematuria (6.66%) vs (23.4 ± 12.8 days, 13.33% and 13.3%, respectively). Patients with preoperative DJ stenting underwent post-transplant definitive procedure for UTC without any complications.Our Protocol for Incidentally Detected Ureteric Stones in LT Recipients:a. Proximal-ureteric calculi: Preoperative DJ stenting (2-3 days prior/ on day of LT) → LT → ESWL/URS 2-3 weeks later → DJ stent removal after 2-3 weeks.b. Distal-ureteric calculi: Preoperative DJ stenting ± URS (2-3 days prior/ day of LT) → LT → DJ stent removal after 2-3 weeks.Our protocol for incidentally detected renal stones in LT recipients:a. Stone size (< 5 mm) and nonobstructive calculi with no active UTI:No surgical intervention → Liver transplant under antibiotics cover → medical management of stone.b. Multiple calculi sized < 5 mm or single stone 5-10 mm:DJ stent placement → LT → ESWL/RIRS after 4-6 weeks → DJ stent removal after 3 weeks.c. Single stone size > 10 mm or multiple calculi > 5 mm:DJ stent placement → LT → RIRS/PCNL after 4-6 weeks→DJ stent removal after 3-4 weeks. ConclusionA systemic minimally invasive approach is needed for pre-LT management of UTC for better patient outcomes.

Brief Report: Unmet Need for Solid Organ Transplantation Among People With HIV and End-Stage Kidney or Liver Disease: A Brief Report From the HIV Outpatient Study, 2009–2023

Background: Persons with HIV (PWH) with end-stage kidney disease (ESKD) who are eligible for kidney transplantation have post-transplantation outcomes similar to those without HIV infection. However, barriers to referral for care, evaluation, and receipt of transplants remain for PWH. We sought to identify PWH with ESKD or end-stage liver disease (ESLD) who would be candidates for organ transplant and to review their clinical outcomes. Methods: We analyzed data from participants in the HIV Outpatient Study (HOPS) between January 1, 2009, and June 30, 2023, with a diagnosis of ESKD or ESLD. We identified a subset of PWH who would otherwise meet the general criteria for kidney or liver transplantation. Targeted clinical outcomes included dialysis, transplantation, and death. Results: Among 5215 PWH in the HOPS, 258 with ESKD and 23 with ESLD would otherwise meet the criteria for transplant. However, only 9 kidney and 2 liver transplants were performed. Conclusions: Low transplantation rates among eligible PWH suggest that timely referral for care and evaluation for kidney and liver transplantation often does not occur. Expanding access for PWH with ESKD to both deceased and living donor kidney allografts is needed. Kidney and liver transplant centers also need to seek ways to broaden access for eligible PWH with ESKD or ESLD.

Myosteatosis Is Associated With Frailty and Poor Physical Function in Patients Undergoing Liver Transplant Evaluation: A Cohort Study.

Myosteatosis is fat infiltration within skeletal muscle. The impact of myosteatosis on physical function and clinical outcomes in patients referred for liver transplantation (LT) is unclear. We explored associations between myosteatosis and sarcopenia, frailty, physical function, and pre- and early post-LT outcomes. Myosteatosis was assessed by computed tomography (CT) in 237 patients referred for LT (March 2018 to September 2022). Chi-square/Fishers exact tests and multivariable regression compared myosteatosis and sarcopenia, frailty (liver frailty index), physical function (short physical performance battery, SPPB); and associations with pre-LT unplanned hospitalizations, post-LT surgical complications (Clavien-Dindo grade≥3), and LT admission length of stay (LOS). Kaplan-Meier and Cox-proportional hazards models explored myosteatosis and time to LT and unplanned admission. Fine-Gray model evaluated the competing risks of receiving an LT. Myosteatosis was present in 74 (31%) patients. Patients with myosteatosis were 2.5 times (95% confidence interval [CI] 1.1-5.7, p=0.03) more likely to be frail, and 3.0 times (95% CI 1.6-5.6, p<0.001) more likely to have a poor physical function (SPPB≤9/12) than those without myosteatosis. Patients with myosteatosis versus those without were more likely to have a pre-LT unplanned hospitalization (51% vs. 36%, p=0.03), but significance was lost after adjusting for age, sex, Model for End-stage Liver Disease (MELD), and the presence of hepatocellular carcinoma. Myosteatosis did not impact the likelihood of receiving an LT (p=0.39), post-LT complications (p=0.93), or LOS in intensive care unit (ICU) (p=0.66) or hospital (p=0.34). Myosteatosis is prevalent in patients referred for LT and is associated with impaired physical function. Using existing CTs to assess myosteatosis in practice may help identify physically compromised patients.

Post-Liver Transplant Outcomes: A Comparative Study of 6 Predictive Models.

We compared the performance of the Liver Transplant Risk Score (LTRS) with the survival outcomes following liver transplantation (SOFT), pretransplant SOFT (P-SOFT), Balance of Risk Score (BAR), donor-age and model for end-stage liver disease (D-MELD), and Organ Procurement and Transplantation Network Risk Prediction Score (ORPS) for the prediction of 90-d mortality, 1-y mortality, and 5-y survival after first-time liver transplantation (LT). A retrospective analysis of the Scientific Registry of Transplant Recipients was conducted using data collected between 2002 and 2021. A total of 82 696 adult LT recipients with a median age of 56 y were included. The area under the curve for 90-d mortality were 0.61, 0.66, 0.65, 0.61, 0.58, and 0.56 for the LTRS, SOFT, P-SOFT, BAR, D-MELD, and ORPS, respectively (all pairwise comparisons: P < 0.05). The area under the curve for 1-y mortality were 0.60, 0.63, 0.62, 0.59, 0.60, 0.57, and 0.59 for the LTRS, SOFT, P-SOFT, BAR, D-MELD, and ORPS, respectively (all pairwise comparisons: P < 0.05). The c-statistics for 5-y survival were not statistically significant among the models. For 90-d mortality, 1-y mortality, and 5-y survival, the correlation coefficients between the LTRS and P-SOFT (the 2 models requiring only preoperative parameters) were 0.90. 0.91, and 0.81, respectively (P < 0.01). None of the predictive models demonstrated sufficient precision to reliably identify LT recipients who died within 90 d and 1 y after LT. However, all models exhibited strong capabilities in perioperative risk stratification. Notably, the P-SOFT and LTRS models, the 2 models that can be calculated using only preoperative data, proved to be valuable tools for identifying candidates at a significant risk of poor outcomes.

Outcomes of Patients with Hepatocellular Carcinoma Undergoing Liver Transplantation Utilizing Extended Criteria Donor Grafts

Background: The deceased donor shortage in the United States has led to increased utilization extended criteria donor (ECD) liver grafts. Centers often utilize ECD grafts in patients with low Model for End-Stage Liver Disease scores, like patients with hepatocellular carcinoma (HCC). However, few studies have directly examined outcomes of using ECD grafts in HCC patients. Methods: Adults receiving liver transplantation (LT) for HCC between 2010-2020 were identified in the Organ Procurement and Transplantation Network database. Recipients were categorized according to donor type: standard criteria (SCD), extended criteria, donation after brain death (ECD-DBD), and donation after circulatory death (DCD). Multivariable Cox regression analysis identified variables associated with overall or graft survival at 3 years post-LT. Results: Most patients received ECD-DBD grafts (51.4%); only 8.3% received DCD grafts. Time on waitlist was similar for ECD and SCD recipients (p=0.79). SCD recipients had higher 5-year overall survival post-LT than ECD-DBD or DCD recipients (79.1%, 77.1%, and 76.8%, respectively, p<0.001). Similarly, 5-year graft survival was also highest in SCD recipients (SCD, 77.8%; ECD-DBD, 75.7%; DCD, 72,.2%; p<0.001). In multivariable analysis, DCD grafts increased mortality risk (HR, 1.33; 95% CI, 1.12-1.57; p=0.001), but ECD-DBD grafts did not (HR, 1.10; 95% CI, 1.00-1.22; p=0.052). Conclusions: DCD and ECD-DBD recipients had significantly lower overall and graft survival. However, the survival benefit of liver transplantation for HCC patients greatly outweighs the small differences in patient and graft survival from using ECD grafts. Further research should investigate whether treatment of ECD grafts with machine perfusion may ameliorate this discrepancy.

Outcomes of Liver Transplantation in Infants: A Retrospective Cohort Study

ObjectiveLiver transplantation (LT) is a crucial treatment for infants with end-stage liver disease, yet specific data on LT outcomes in infants under 12 months old remain limited. This study aims to present the clinical course and outcomes of infants who underwent LT, assessing the impact of demographic and etiological differences on mortality and survival. MethodsA retrospective analysis was conducted on 64 infants (<12 months) who underwent LT between January 2019 and March 2024. Demographic, clinical, and laboratory data were collected from medical records. LT-specific details, postoperative complications, and survival data were analyzed. ResultsThe median age of the infants was 157 days, with 37 males (57.8%) and 27 females (42.2%). Biliary atresia was the most common diagnosis (85.9%), and seven infants had undergone a previous Kasai procedure. The median PELD score was 15.5. Left lateral segmentectomy was the predominant graft type (60.9%). The median PICU and hospital stays were 5 and 21 days, respectively. Complications occurred in 20 infants (31.3%), with vascular and biliary complication rates both at 12.5%. The overall mortality rate was 17.2%, with early (30-day) and late mortality rates of 6.3% and 10.9%, respectively. The median OS was 204.5 days, and the one-year survival rate was 32.8%. Kaplan-Meier and Log Rank analyses showed no significant impact of sex, age, diagnostic groups, graft type, or surgical complications on OS (p>0.05). ConclusionLT in infants can be performed with acceptable morbidity and mortality rates, particularly with increased experience and standardized protocols.

Comparisons of efficacy and safety of 400 or 800 ml bacterial count fecal microbiota transplantation in the treatment of recurrent hepatic encephalopathy: a multicenter prospective randomized controlled trial in China

BackgroundHepatic encephalopathy (HE) represents a critical complications of end-stage liver disease, serving as an independent predictor of mortality among patients with cirrhosis. Despite effective treatment with rifaximin, some patients with HE still progress to recurrent episodes, posing a significant therapeutic challenge. Recurrent HE is defined as experiencing two or more episodes within a 6-month period. Previous research has suggested that FMT may emerge as a promising treatment for recurrent HE. However, there remains a critical need to explore the optimal dosage. This trial aims to abscess the efficacy and safety of two FMT dosages: 800 ml or 400 ml total bacterial count, including mortality and quality of life.MethodsThis multicenter, prospective, randomized controlled trial will enroll 100 eligible patients from 31 hospitals in China. Participants will be randomly assigned in a 1:1 ratio to either the high-dose group (800 ml total bacterial count) or the low-dose group (400 ml total bacterial count). The primary objective is to assess the efficacy and safety of both dosages on outcomes at 24 and 48 weeks, including mortality and quality of life.DiscussionIf either or both dosages of FMT demonstrate safe and effective treatment of recurrent HE, leading to improve quality of life and survival at 24 and 48 weeks, this trial would address a significant gap in the management of recurrent HE, carrying innovative and clinically significant implications.Trial registrationNCT05669651 on ClinicalTrials.gov. Registered on 29 December 2022. CHiCTR2200067135 on China Registered Clinical Trial Registration Center. Registered on 27 December 2022.

Sex differences in patient-reported outcomes and perception of ascites burden amongst outpatients with decompensated cirrhosis and ascites.: Sex Differences in Ascites Burden Perception.

Perception of the ascites burden and its effects on quality of life may be different between sexes. This study assessed sex differences in perception of ascites burden and its impact on health related QoL (HRQoL) in patients with recurrent or refractory ascites. The North American Consortium for the Study of End-stage Liver Disease prospectively enrolled outpatients with cirrhosis and large ascites requiring repeat large volume paracenteses. Demographics, laboratory results, co-morbidities, medications, frailty measurements, self-reported questionnaires related to functional status, physical activities, and HRQoL (generic = SF36 & ascites specific = ascites Q) were compared between sexes. 392 men (59.6±10.7yrs) and 184 women (59.5±11.1yrs) with predominantly alcohol related liver disease 51% and 43% respectively), median MELD-Na: 13, were enrolled. Both groups had similar co-morbidities and cirrhosis complications, ascites duration and severity, and frailty scores (p=0.94). Women had more symptoms related to their ascites (Ascites Q score =66±21 vs. 60±21 in men, p=0.001) (higher value = feeling worse). 35% of women felt depressed versus 22% of men (p=0.0009), with lower mental but not physical functioning components of SF36 (p=0.019). Women continued to conduct their daily activities as adequately as men as indicated by Duke Status Activity index (p=0.27) and Godin Leisure Activity Index (p=0.47). Women with cirrhosis and ascites experienced worse emotional HRQoL than men without difference in daily function. Our analyses underscore the differences in the lived experience of women versus men with cirrhosis and highlight the need for patient-reported metrics to provide patient-centered care.

Celiac disease is common in adults with cryptogenic cirrhosis and responds favourably to gluten-free diet

Introduction: Liver involvement is common in celiac disease (CeD), and upto 4.6% of patients with cryptogenic cirrhosis have CeD. We investigated the prevalence of CeD in patients with cryptogenic cirrhosis and assessed liver-related outcomes in them on GFD when compared to a propensity-score matched (PSM) cohort of patients with cryptogenic cirrhosis without CeD. Methods: Consecutive patients with cryptogenic cirrhosis were screened for CeD using IgA anti-tissue-transglutaminase antibody(anti-tTG) followed by anti-endomysial antibody (AEA) and duodenal and liver biopsies, on which IgA/anti-tTG colocalization studies were performed. These patients and a cohort of patients with cryptogenic cirrhosis without CeD [1:4 CeD: no CeD matched using PSM for age, sex, Child-Turcotte-Pugh(CTP) and model for end-stage-liver-disease(MELD)] were initiated on GFD plus standard of care (SOC) and SOC, respectively and followed up for liver-related outcomes for one year. Results: Of 232 patients with cryptogenic cirrhosis, 14 had high anti-tTG Ab (16.9±10.5 fold rise), with 9 AEA positive and 11(4.7%) biopsy-proven CeD. IgA/ anti-tTG-Ab colocalization was demonstrated in 7/8 liver and 10/11 duodenal biopsies. Patients with cryptogenic cirrhosis with definite CeD (n=11) and matched cohort without CeD (n=44) were similar at baseline [age:31.3±7.7 vs 31.8±9.3 years; 5(45.5%) vs 15(34.1%) females; MELDNa 9 (interquartile-range[IQR]: 8-15.5) vs 12(9-15); CTP 7(6-7.5) vs 6(5.75-7)]. Patients with CeD on GFD improved significantly on follow-up compared to those without CeD [follow-up MELDNa:9 (7.5-10.5) vs 18.5 (12-20);p=0.001 and follow-up CTP: 5 (5-5) vs 8(7-9);p&lt;0.001] with less frequent further decompensations and similar mortality (9.1% vs 18.2%;p=0.67). Conclusion: Approximately 4.7% of patients with cryptogenic cirrhosis have biopsy-proven CeD and their liver-related outcomes improve with GFD.

Splenic Artery Embolization for Post-Liver Transplant Ascites

AbstractOrthotopic liver transplantation (OLT) is the treatment of choice for end-stage liver disease. However, OLT may be associated with certain postoperative management challenges. Though refractory ascites (RA) is not a common complication post-OLT, it can have a significant impact on patient outcomes and quality of life. RA post-OLT can be caused by portal hyperperfusion. In this article, a systematic review of the literature was pursued to analyze the effectiveness of splenic artery embolization (SAE) with RA after OLT. Data sources included MEDLINE, EMBASE, and CENTRAL from inception to March 2024. Studies reporting on patients treated with SAE for the management of RA following OLT, from inception to March 2024, were included. Morbidity, mortality, and clinical resolution were synthesized through a narrative review. A total of eight articles were identified, including 80 patients. In the majority of the patients, the SAE was performed using a vascular plug. After SAE, no cases associated with mortality were reported. Severe complications (Clavien III) occurred in 2.5% (n = 2) of patients. The success rate, with clinical resolution of symptomatology (ascites), ranged in these articles between 97 and 100%. The approach to the management of RA post-OLT should focus on identifying the underlying cause. If the RA is associated with portal hyperperfusion, it can be managed with SAE. Particularly proximal SAE seems to be highly effective for the resolution of ascites and the procedure is associated with a low complication rate.

Diagnostic performance of procalcitonin for bacterial infection in severe alcoholic hepatitis compared with C-reactive protein

BackgroundSevere alcoholic hepatitis is a catastrophic disease with a mortality rate of up to 35–50% at 30 days. Bacterial infection is an important prognostic factor in patients with severe alcoholic hepatitis, but it is difficult to detect the presence of infection immediately. Procalcitonin (PCT) is a well-known inflammatory marker that can detect bacterial infections in various diseases early. Therefore, we aimed to evaluate the diagnostic accuracy of PCT for bacterial infection in severe alcoholic hepatitis.MethodsWe prospectively enrolled patients with severe alcoholic hepatitis, defined as modified Maddrey’s Discriminant Function ≥ 32, from 10 medical centers. At admission, we performed an initial evaluation including physical examination, laboratory test, radiology, blood and urine culture, PCT, and C-reactive protein (CRP). We compared the receiver operating characteristic (ROC) curves of PCT and CRP for bacterial infection, systemic inflammatory response syndrome (SIRS), and sepsis among total patients.ResultsA total of 108 patients with severe alcoholic hepatitis were enrolled. The number of bacterial infections, SIRS, and sepsis were 31 (28.7%), 41 (38.0%), and 19 (17.6%), respectively. The patients with bacterial infection had significantly higher MELD scores (24.0 vs. 15.0), PCT levels (1.5 vs. 0.4 ng/mL), and CRP levels (4.9 vs. 2.5 mg/dL) compared to those without bacterial infection. The area under the ROC curve (AUROC) of PCT vs. CRP for bacterial infection was 0.752 and 0.655, respectively (P = 0.113). The AUROC of PCT vs. CRP for SIRS was 0.699 and 0.662, respectively (P = 0.490). The AUROC of PCT vs. CRP for sepsis was 0.780 and 0.630, respectively (P = 0.027).ConclusionsAmong patients with severe alcoholic hepatitis, PCT showed a trend of superior diagnostic performance in the early detection of bacterial infection and sepsis compared to CRP. Although PCT might have better potential to diagnose sepsis in the setting of severe alcoholic hepatitis, it is necessary to find more reliable diagnostic markers.

Normothermic machine perfusion of explanted livers: Exploratory study of an alternative translational model forend-stage liver disease.

Normothermic machine perfusion (NMP) is a technique for donor liver preservation and assessment in transplantation. NMP has gained momentum recently by enabling safer use of higher risk organs via organ viability assessment. It also offers a platform for investigating exvivo organ biology. In this exploratory study, we completed a complex vascular reconstruction of explanted, diseased livers from patients undergoing transplantation and then perfused them normothermically on a closed perfusion circuit. We compared these livers to non-diseased donor livers via perfusate samples collected during perfusion. Five hepatectomized grafts and eight donor livers were perfused for 1 h or longer. Four hepatectomized livers cleared lactate, and all consumed glucose; all control livers cleared lactate, and seven utilized glucose. Significantly higher portal vein flows were achieved in the control group. Our findings illustrate the feasibility of using closed-circuit NMP as a platform to study hepatectomized organs, which could reshape the research landscape in mechanisms of disease and applied therapeutics for patients with end-stage liver disease.

Extracorporeal liver support systems in patients with acute-on-chronic liver failure: An updated systematic review and meta-analysis.

The utilization of extracorporeal liver support systems is increasingly prevalent for the management of acute-on-chronic liver failure in clinical settings. Yet, the efficacy of these interventions in terms of tangible clinical benefits for patients remains a matter of debate, underscoring the need for meta-analysis. An updated meta-analysis was performed to elucidate the relationship between the application of extracorporeal liver support versus standard pharmacological treatment and the prognostic endpoints of patient survival, specifically assessing 1-month and 3-month mortality rates, as well as the incidence of complications such as hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome. Literature were searched via PubMed, EMBASE, and Web of Science. The meta-analysis revealed the following: the odds ratio for 1-month mortality was 0.63 (95% confidence interval [CIs]: 0.51-0.76), for 3-month mortality was 0.70 (95% CI: 0.61-0.81), for hepatic encephalopathy was 0.81 (95% CI: 0.67-0.97), for spontaneous bacterial peritonitis was 0.66 (95% CI: 0.44-0.99), and for hepatorenal syndrome was 0.68 (95% CI: 0.51-0.92). These results suggest that patients with acute-on-chronic liver failure undergoing extracorporeal liver support system therapy have significantly better survival rates and lower complication incidences compared to those receiving conventional drug therapy. Further subgroup analysis indicated that patients with lower model for end-stage liver disease (MELD) scores and reduced total bilirubin (Tbil) levels demonstrated greater benefits from extracorporeal hepatic support. This study establishes that in the management of acute-on-chronic liver failure, extracorporeal liver support systems confer a survival advantage and reduce complications relative to standard pharmacotherapy.

Development and validation of a novel prognostic nomogram for hepatitis B virus-related acute-on-chronic liver failure patients receiving artificial liver therapy

BackgroundHepatitis B virus-related acute-on-chronic liver failure (HBV–ACLF) is frequently accompanied by short-term morbidity and mortality. However, there have been no studies on the associations between baseline clinicopathologic characteristics at hospital admission and clinical prognosis after receiving artificial liver therapy. Therefore, the current study aimed to develop a prognostic nomogram for predicting the outcomes of patients with HBV–ACLF following artificial liver support.MethodsA retrospective study of 110 consecutive patients who were diagnosed with HBV–ACLF between January 2018 and August 2022 was conducted. First, univariate and multivariate logistic regression analyses were performed to determine the independent prognostic factors significantly associated with patient outcomes. Moreover, a predictive nomogram model underlying the prognostic factors was established and further evaluated. The area under the curve (AUC) was used to gauge the predictive accuracy. The calibration curve and decision curve analysis (DCA) were employed to assess the discriminability and clinical effectiveness, respectively.ResultsIn patients with HBV–ACLF, multivariate logistic analysis revealed that age ≥ 40 years (OR 6.76, p = 0.025), middle-stage liver failure (OR 49.96, p < 0.001), end-stage liver failure (OR 19.27, p = 0.002), hepatic encephalopathy (OR 7.06, p = 0.032), upper gastrointestinal hemorrhage (OR 47.24, p = 0.047), and artificial liver therapy consisting of plasma exchange (PE) + plasma exchange double plasma molecular adsorption system (DPMAS) (OR 0.26, p = 0.04) were identified as prognostic factors. Then, we established and evaluated a predictive nomogram with an AUC of 0.885, which showed better predictive accuracy than the model for end-stage liver disease (MELD) score (AUC of 0.634) and the Child–Pugh score (AUC of 0.611). Moreover, the calibration curve showed good agreement between the ideal and bias-corrected curves. Decision curve analysis confirmed the better clinical utility of this approach.ConclusionsWe developed and evaluated a unique nomogram that was more accurate than conventional prognostic models for predicting the clinical prognosis of HBV–ACLF patients receiving artificial liver therapy. As a result, the nomogram may be a helpful tool in clinical decision-making to predict the outcomes of patients with HBV–ACLF.

Predictive model of in-hospital mortality in liver cirrhosis patients with hyponatremia: an artificial neural network approach

Hyponatremia can worsen the outcomes of patients with liver cirrhosis. However, it remains unclear about how to predict the risk of death in cirrhotic patients with hyponatremia. Patients with liver cirrhosis and hyponatremia were screened. Eligible patients were randomly divided into the training (n = 472) and validation (n = 471) cohorts. In the training cohort, the independent predictors for in-hospital death were identified by logistic regression analyses. Odds ratios (ORs) were calculated. An artificial neural network (ANN) model was established in the training cohort. Areas under curve (AUCs) of ANN model, Child-Pugh, model for end-stage liver disease (MELD), and MELD-Na scores were calculated by receiver operating characteristic curve analyses. In multivariate logistic regression analyses, ascites (OR = 2.705, P = 0.042), total bilirubin (OR = 1.004, P = 0.003), serum creatinine (OR = 1.004, P = 0.017), and international normalized ratio (OR = 1.457, P = 0.005) were independently associated with in-hospital death. Based on the four variables, an ANN model was established. Its AUC was 0.865 and 0.810 in the training and validation cohorts, respectively, which was significantly larger than those of Child-Pugh (AUC = 0.757), MELD (AUC = 0.765), and MELD-Na (AUC = 0.769) scores. An ANN model has been developed and validated for the prediction of in-hospital death in patients with liver cirrhosis and hyponatremia.

The Research and Application Progress of Heterologous Liver Transplantation

Liver transplantation is an effective treatment for various end-stage liver diseases, and the shortage of donor livers is one of the main obstacles affecting the development of liver transplantation. Xenotransplantation holds promise as a potential solution to the organ shortage. By using gene-editing technology to modify animal genes, their physiological compatibility with humans can be improved. Combining this with new immunosuppressive drugs can reduce the occurrence of rejection, thereby increasing the survival time of the graft. Due to the more complex structure and physiological functions of the liver, inter-species incompatibility is more pronounced in liver xenotransplantation compared to heart or kidney. The molecular mechanisms related to xenograft rejection and coagulation disorders post-operation require further research. This article reviews the latest research progress domestically and internationally, the historical development of liver xenotransplantation, the main current challenges, and clinical applications, aiming to enhance clinicians' understanding of liver xenotransplantation.

Bowel Colonization With Carbapenem-Resistant Bacteria Is Associated With Short-Term Outcomes in Patients With Acute-On-Chronic Liver Failure.

Bowel colonization with antimicrobial-resistant bacteria has been associated with worse clinical outcomes in patients with cirrhosis; however, it has not been studied in patients with acute-on-chronic liver failure (ACLF). We evaluated whether fecal isolation of carbapenem-resistant gram-negative bacteria (CR-GNB) among patients with ACLF affects short-term outcomes. Patients of APASL-ACLF (n = 339) were screened between June 2020 and December 2021, and 150 were included. Stool cultures were carried out at baseline and every 5 days thereafter until discharge or death. All surviving patients were followed until 60 days after discharge. Mean age was 44.8 (8.8) years, with 86% males and alcohol as etiology in 66%. CR-GNB organisms were isolated from stool in 42% of hospitalized ACLF patients, with E. coli and Klebsiella pneumoniae as the most common species. Patients with CR-GNB fecal carriage were associated with higher CTP, MELD, and DF scores but not with recent antibiotics, proton pump inhibitors, or lactulose use. Extraintestinal infections developed in 59.3% overall, most commonly UTI, pneumonia, and SBP. Infectious complications developed in 57.3% and 19.7% with and without CR-GNB in the stool (RR: 5.5; p < 0.001). Peripheral cultures were positive in 60.7% with infections, with species concordant with the fecal isolates found in 90.7%. Isolation of CR-GNB from stool and high bilirubin were independently associated with both in-hospital mortality and 60-day mortality (p = 0.05). Hospitalized ACLF patients with CR-GNB in the stool have a significantly higher risk of extraintestinal infections, in-hospital mortality, and short-term mortality up to 60 days. [NCT04383106].

Exploring the reasons for liver cancer occurrence still after long-term nucleos(t)ide analogue therapy in patients with chronic hepatitis B

Chronic hepatitis B virus (HBV) infection is the main etiology of viral hepatitis, cirrhosis, and primary hepatocellular carcinoma and is also a major public health problem worldwide. With the progression of chronic infection, HBV DNA continuously integrates into host DNA and brings about integration and insertion mutations within host genes. In the process of repeated chronic inflammatory necrosis and compensatory regeneration, hepatocytes carrying HBV DNA integration have an advantage in proliferation and frequent clonal expansion formation that causes the accumulation of mutations over time and ultimately malignant transformation of hepatocytes. Although nucleos(t)ide analogs (NAs), currently the most widely used, can effectively inhibit viral replication, delay disease progression in patients with chronic hepatitis B, and significantly reduce the occurrence of end-stage liver disease, many patients still progress to liver cancer. Furthermore, even among clinically cured patients with hepatitis B surface antigen clearance, NAs have not significantly reduced the long-term occurrence of liver cancer, suggesting that their impact under previous treatment strategies for reducing the risk of liver cancer is limited. This could be due to antiviral treatment initiation at a time when patients already have numerous integrated cell proliferation colonies. Hence, NAs have not had any therapeutic impact on the expression of integrated HBV DNA fragments and viral proteins, such as hepatitis B surface antigen. In light of this, we suggest initiating antiviral treatment as early as possible to pursue clinical cure and ultimately reduce the risk of liver cancer in patients with chronic HBV infection.

Cell therapy for end-stage liver disease: Current state and clinical challenge.

Liver disease involves a complex interplay of pathological processes, including inflammation, hepatocyte necrosis, and fibrosis. End-stage liver disease (ESLD), such as liver failure and decompensated cirrhosis, has a high mortality rate, and liver transplantation is the only effective treatment. However, to overcome problems such as the shortage of donor livers and complications related to immunosuppression, there is an urgent need for new treatment strategies that need to be developed for patients with ESLD. For instance, hepatocytes derived from donor livers or stem cells can be engrafted and multiplied in the liver, substituting the host hepatocytes and rebuilding the liver parenchyma. Stem cell therapy, especially mesenchymal stem cell therapy, has been widely proved to restore liver function and alleviate liver injury in patients with severe liver disease, which has contributed to the clinical application of cell therapy. In this review, we discussed the types of cells used to treat ESLD and their therapeutic mechanisms. We also summarized the progress of clinical trials around the world and provided a perspective on cell therapy.

Prognostic value of inflammation-related model in hepatitis B acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is characterized by rapid onset, rapid development and a high short-term mortality rate. Systemic inflammation exerts an effect on the disease progression of ACLF. The purposes of this study were to explore the clinical significance that the inflammatory response has on the disease process of hepatitis B virus acute-on-chronic liver failure (HBV-ACLF) patients, to further compare the values of different inflammation-related biomarkers in the prognosis evaluation of HBV-ACLF patients, and to combine inflammatory-related markers to establish a new prediction model. Baseline admission data and 90-day outcomes were collected from 247 patients who met the inclusion criteria. According to the 90-day survival situation, they were divided into a survival group and a death group. The differences in baseline data and inflammation levels between the 2 groups were compared. A regression model was used to analyze the risk factors for 90-day mortality and establish a new model. The study found that the differences between the survival group and the death group were statistically significant in terms of age, total bilirubin (Tbil), prothrombin time (PT), international standardized ratio (INR), inflammation level, and model for end-stage liver disease (MELD) series scores (p < 0.05). The monocyte-to-lymphocyte ratio (MLR)-integrated iMELD model (MLR-iMELD) can effectively predict the 90-day survival rate of HBV-ACLF patients. The area under the receiver operating characteristic (ROC) curve (AUROC) of the new model was 0.792, and the best cutoff for predicting the prognosis of 90 days for patients was -0.33 (sensitivity 0.577 and specificity 0.898). The higher the level of inflammation in patients with HBV-ACLF, the greater the risk of 90-day death. Compared with other inflammation-related markers, the MLR-iMELD model can better predict the 90-day survival rate of HBV-ACLF patients.