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Introduction: Fibrosing interstitial lung diseases (ILDs) often progress despite treatment and become life-threatening, with lung transplant (LTx) remaining the only curative option. Six-minute walk distance (6MWD) is increasingly recognized as reliable predictor of clinical course, especially when longitudinally considered. The use of reference equations to express 6MWD as percent predicted (6MWD%) has not been previously studied in fibrosing ILDs. We sought to investigate whether the prognostic power of 6MWD% is superior to that of 6MWD expressed in meters (6MWD-m). Methods: A retrospective, multicenter cohort analysis was conducted on both idiopathic pulmonary (IPF) and non-IPF fibrosing ILD patients. Patients were divided into a discovery (n = 211) and a validation (n = 260) cohort. Longitudinal changes of 6MWD% and lung function parameters were simultaneously considered. LTx-free survival at 3 years from baseline was the endpoint. Competing risks of death and LTx were considered. Results: Baseline 6MWD% and its longitudinal changes were significant predictors of LTx-free survival and independent from lung function variables. In both cohorts, on multivariate cox proportional hazard regression analysis, receiver operating characteristics analysis and Kaplan–Meier estimates, 6MWD% was consistently, but only slightly superior to 6MWD-m as a predictor of LTx-free survival. Conclusion: 6MWD% has only a slight, yet detectable advantage over 6MWD-m as a predictor of survival in fibrosing ILDs. Utilizing 6MWD% may aid in risk stratification, treatment monitoring, and LTx timing optimization. However, available reference equations do have predicting limitations. Refined predictive equations and standardizing reporting practices are therefore needed to further enhance the clinical utility of 6MWD% in fibrosing ILDs. [ABSTRACT FROM AUTHOR]

Background and Aim: Plasma exchange (PLEX) improves survival in patients with rodenticidal hepatotoxicity. However, predictors of treatment response are unknown. We aimed at assessing predictors of response to PLEX treatment in these patients. Methods: Patients with rodenticidal hepatotoxicity from 2014 to 2023 managed in our department were included in this study. Kochi criteria (model for end-stage liver disease [MELD] score ≥ 36 or international normalized ratio [INR] ≥ 6 with hepatic encephalopathy [HE]) derived specifically for rodenticidal hepatotoxicity (PubMed IDentifier [PMID]: 26310868) were used to assess need for liver transplantation. We analyzed predictors of survival at one month. ∆Bilirubin, ∆MELD score and ∆INR were calculated as percentage change of the parameter after third PLEX session (or after last PLEX if < 3 PLEX sessions done) from baseline pre-PLEX value. Results: Of 200 patients with rodenticidal hepatotoxicity, 114 patients were treated with low-volume PLEX (PLEX-LV). No patient had liver transplantation. Of 78 patients who fulfilled Kochi criteria, 32 patients were PLEX-LV eligible and underwent PLEX-LV (M: 10; age: 20.5, 7–70 years; median, range; acute liver failure: 24). Twenty-two (69%; acute liver failure: 14) of the 32 patients were alive at one month. Presence of HE (p = 0.03) and ∆MELD (p < 0.001) were significant predictors on univariate analysis, while ∆MELD (aOR = 0.88, 95% CI: 0.79–0.98, p = 0.01) was the only significant independent predictor of one-month transplant-free survival. Area under receiver operating characteristic (ROC) for ∆MELD was 0.93 (95% CI:0.85–1.00) and a decrease of ≥ 20% in MELD score while on PLEX-LV had 90% sensitivity and 90% specificity in predicting one-month survival. Conclusions: Decline in MELD while on PLEX-LV independently predicted one-month transplant-free survival in rodenticidal hepatotoxicity patients. This may help guide decision on stopping PLEX-LV in patients predicted to respond to treatment and to consider alternate treatment options in non-responders. [ABSTRACT FROM AUTHOR]

Background: There is growing recognition of natural history, complications, and outcomes of patients who develop non-acetaminophen (APAP) drug-induced acute liver failure (ALF). To clarify high-risk factors and develop a nomogram model to predict transplant-free survival (TFS) in patients with non-APAP drug-induced ALF. Methods: Patients with non-APAP drug-induced ALF from 5 participating centers were retrospectively analyzed. The primary endpoint was 21-day TFS. Total sample size was 482 patients. Results: Regarding causative agents, the most common implicated drugs were herbal and dietary supplements (HDS) (57.0%). The hepatocellular type (R ≥ 5) was the main liver injury pattern (69.0%). International normalized ratio, hepatic encephalopathy grades, the use of vasopressor, N-acetylcysteine, or artificial liver support system were associated with TFS and incorporated to construct a nomogram model (drug-induced acute liver failure-5, DIALF-5). The AUROC of DIALF-5 for 7-day, 21-day, 60-day, and 90-day TFS in the internal cohort were 0.886, 0.915, 0.920, and 0.912, respectively. Moreover, the AUROC of DIALF-5 for 21-day TFS had the highest AUROC, which was significantly higher than 0.725 of MELD and 0.519 of KCC (p < 0.05), numerically higher than 0.905 of ALFSG-PI but without statistical difference (p > 0.05). These results were successfully validated in the external cohort (147 patients). Conclusions: Based on easily identifiable clinical data, the novel DIALF-5 model was developed to predict transplant-free survival in non-APAP drug-induced ALF, which was superior to KCC, MELD and had a similar prediction performance to ALFSG-PI but is more convenient, which can directly calculate TFS at multiple time points. [ABSTRACT FROM AUTHOR]

Abstract Background Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial lung disease. Clinical models to accurately evaluate the prognosis of IPF are currently lacking. This study aimed to construct an easy-to-use and robust prediction model for transplant-free survival (TFS) of IPF based on clinical and radiological information. Methods A multicenter prognostic study was conducted involving 166 IPF patients who were followed up for 3 years. The end point of follow-up was death or lung transplantation. Clinical information, lung function tests, and chest computed tomography (CT) scans were collected. Body composition quantification on CT was performed using 3D Slicer software. Risk factors in blood routine examination-radiology-pulmonary function (BRP) were identified by Cox regression and utilized to construct the “BRP Prognosis Model”. The performance of the BRP model and the gender-age-physiology variables (GAP) model was compared using time-ROC curves, calibration curves, and decision curve analysis (DCA). Furthermore, histopathology fibrosis scores in clinical specimens were compared between the different risk stratifications identified by the BRP model. The correlations among body composition, lung function, serum inflammatory factors, and profibrotic factors were analyzed. Results Neutrophil percentage > 68.3%, pericardial adipose tissue (PAT) > 94.91 cm3, pectoralis muscle radiodensity (PMD) ≤ 36.24 HU, diffusing capacity of the lung for carbon monoxide/alveolar ventilation (DLCO/VA) ≤ 56.03%, and maximum vital capacity (VCmax) 3 years; intermediate risk: TFS = 2–3 years; high risk: TFS ≈ 1 year). Patients with a high-risk stratification according to the BRP model had a higher fibrosis score on histopathology. Additionally, serum proinflammatory markers were positively correlated with visceral fat volume and infiltration. Conclusions In this study, the BRP prognostic model of IPF was successfully constructed and validated. Compared with the commonly used GAP model, the BRP model had better performance and generalization with easily obtainable indicators. The BRP model is suitable for clinical promotion.

PurposeThe purpose of this study was to investigate factors impacting transplant-free survival among infants with biliary atresia.MethodsA multi-institutional, retrospective cohort study was performed at nine tertiary-level children's hospitals in the United States. Infants who underwent Kasai portoenterostomy (KP) from January 2009 to May 2017 were identified. Clinical characteristics included age at time of KP, steroid use, surgical approach, liver pathology, and surgeon experience. Likelihood of transplant-free survival (TFS) was evaluated using logistic regression, adjusting for patient and surgeon-level factors. Secondary outcomes at 1 year included readmission, cholangitis, reoperation, mortality, and biliary clearance.ResultsOverall, 223 infants underwent KP, and 91 (40.8%) survived with their native liver. Mean age at surgery was 63.9 days (± 24.7 days). At 1 year, 78.5% experienced readmission, 56.9% developed cholangitis, 3.8% had a surgical revision, and 5 died. Biliary clearance at 3 months was achieved in 76.6%. Controlling for patient and surgeon-level factors, each additional day of age toward operation was associated with a 2% decrease in likelihood of TFS (OR 0.98, 95% CI 0.97-0.99).ConclusionEarlier surgical intervention by Kasai portoenterostomy at tertiary-level centers significantly increases likelihood for TFS. Policy-level interventions to facilitate early screening and surgical referral for infants with biliary atresia are warranted to improve outcomes.

Background: Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial lung disease. Clinical models to accurately evaluate the prognosis of IPF are currently lacking. This study aimed to construct an easy-to-use and robust prediction model for transplant-free survival (TFS) of IPF based on clinical and radiological information. Methods: A multicenter prognostic study was conducted involving 166 IPF patients who were followed up for 3 years. The end point of follow-up was death or lung transplantation. Clinical information, lung function tests, and chest computed tomography (CT) scans were collected. Body composition quantification on CT was performed using 3D Slicer software. Risk factors in blood routine examination-radiology-pulmonary function (BRP) were identified by Cox regression and utilized to construct the "BRP Prognosis Model". The performance of the BRP model and the gender-age-physiology variables (GAP) model was compared using time-ROC curves, calibration curves, and decision curve analysis (DCA). Furthermore, histopathology fibrosis scores in clinical specimens were compared between the different risk stratifications identified by the BRP model. The correlations among body composition, lung function, serum inflammatory factors, and profibrotic factors were analyzed. Results: Neutrophil percentage > 68.3%, pericardial adipose tissue (PAT) > 94.91 cm3, pectoralis muscle radiodensity (PMD) ≤ 36.24 HU, diffusing capacity of the lung for carbon monoxide/alveolar ventilation (DLCO/VA) ≤ 56.03%, and maximum vital capacity (VCmax) < 90.5% were identified as independent risk factors for poor TFS among patients with IPF. We constructed a BRP model, which showed superior accuracy, discrimination, and clinical practicability to the GAP model. Median TFS differed significantly among patients at different risk levels identified by the BRP model (low risk: TFS > 3 years; intermediate risk: TFS = 2–3 years; high risk: TFS ≈ 1 year). Patients with a high-risk stratification according to the BRP model had a higher fibrosis score on histopathology. Additionally, serum proinflammatory markers were positively correlated with visceral fat volume and infiltration. Conclusions: In this study, the BRP prognostic model of IPF was successfully constructed and validated. Compared with the commonly used GAP model, the BRP model had better performance and generalization with easily obtainable indicators. The BRP model is suitable for clinical promotion. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is a risk factor for mortality in patients with sarcoidosis. Severe PH in chronic lung disease has previously been defined as mean pulmonary arterial pressure (mPAP) ≥ 35 mmHg or mPAP 25 ≥ mmHg with cardiac index (CI) ≤ 2 L/min/m2. However, there is no clear definition denoting severity of sarcoidosis-associated PH (SAPH). We aimed to determine pulmonary hemodynamic cut-off values where transplant-free survival was worse among patients with SAPH. This was a retrospective cohort analysis of the Registry of SAPH database focusing on pulmonary hemodynamic predictors of transplant-free survival among patients with precapillary SAPH. Cox regression was performed to determine which pulmonary hemodynamic values predicted death or lung transplantation. Kaplan--Meier survival analysis was performed on statistically significant predictors to determine pulmonary hemodynamic cut-off values where transplant-free survival was decreased. Decreased transplant-free survival occurred among SAPH patients with mPAP ≥ 40 mmHg and SAPH patients with pulmonary vascular resistance (PVR) ≥ 5 Woods units (WU). Transplantfree survival was not decreased in patients who fulfilled prior criteria of severe PH in chronic lung disease. We identified new cut-offs with decreased transplant-free survival in the SAPH population. Neither cut-off of mPAP ≥ 40 mmHg nor PVR ≥ 5 WU has previously been shown to be associated with decreased transplant-free survival in SAPH. These values could suggest a new definition of severe SAPH. Our PVR findings are in line with the most recent European Society of Cardiology/European Respiratory Society guideline definition of severe PH in chronic lung disease. [ABSTRACT FROM AUTHOR]

Abstract Pulmonary hypertension (PH) is a risk factor for mortality in patients with sarcoidosis. Severe PH in chronic lung disease has previously been defined as mean pulmonary arterial pressure (mPAP) ≥ 35 mmHg or mPAP 25 ≥ mmHg with cardiac index (CI) ≤ 2 L/min/m2. However, there is no clear definition denoting severity of sarcoidosis‐associated PH (SAPH). We aimed to determine pulmonary hemodynamic cut‐off values where transplant‐free survival was worse among patients with SAPH. This was a retrospective cohort analysis of the Registry of SAPH database focusing on pulmonary hemodynamic predictors of transplant‐free survival among patients with precapillary SAPH. Cox regression was performed to determine which pulmonary hemodynamic values predicted death or lung transplantation. Kaplan−Meier survival analysis was performed on statistically significant predictors to determine pulmonary hemodynamic cut‐off values where transplant‐free survival was decreased. Decreased transplant‐free survival occurred among SAPH patients with mPAP ≥ 40 mmHg and SAPH patients with pulmonary vascular resistance (PVR) ≥ 5 Woods units (WU). Transplant‐free survival was not decreased in patients who fulfilled prior criteria of severe PH in chronic lung disease. We identified new cut‐offs with decreased transplant‐free survival in the SAPH population. Neither cut‐off of mPAP ≥ 40 mmHg nor PVR ≥ 5 WU has previously been shown to be associated with decreased transplant‐free survival in SAPH. These values could suggest a new definition of severe SAPH. Our PVR findings are in line with the most recent European Society of Cardiology/European Respiratory Society guideline definition of severe PH in chronic lung disease.

IntroductionChildren with restrictive cardiomyopathy (RCM) traditionally have a poor prognosis, with most patients either dying or requiring heart transplantation within 2 years of diagnosis. The development of symptoms in RCM suggests advanced disease. However, as screening practices evolve and lead to diagnosis of early disease, identifying appropriate timing of transplant listing becomes increasingly important. In this context we compared outcomes of children with RCM presenting with clinical symptoms to those asymptomatic at initial presentation.MethodsThis retrospective cohort study included 25 patients with RCM presenting to a quaternary care center between 2001 and 2018. Times to transplantation, death, and a composite outcome of adverse cardiac events (CPR, cardioversion, inotropic support, mechanical ventilation, mechanical support, or heart transplant) were compared between those symptomatic and asymptomatic at presentation.ResultsAt 2 years following diagnosis, patients asymptomatic at presentation had a significantly better transplant-free survival at 57% compared to 17% for symptomatic patients (p = 0.03). Those asymptomatic at diagnosis also had significantly improved cardiac event-free survival at 71% compared to symptomatic patients at 25% (p = 0.01). In multivariable analysis, cardiac symptoms at presentation remained an independent risk factor for heart-transplant or death [hazard ratio 5.17 (1.28–20.85), p = 0.02].ConclusionPatients with RCM who are symptomatic at time of diagnosis have significantly worse transplant-free survival and cardiac event-free survival. Given current practice variability in timing of transplant listing, the presence of any cardiac symptoms is an important negative prognostic marker and should prompt urgent transplant listing.

BackgroundUsual interstitial pneumonia (UIP) is a pattern of interstitial pneumonia that is caused by different etiologies. This study aimed to investigate the transplant-free survival (TFS) and the decline in forced vital capacity (FVC) of the patients with UIP and probable UIP patterns on CT caused by various underlying conditions.MethodsA retrospective cohort study was conducted, enrolling patients with interstitial lung disease exhibiting a CT pattern consistent with UIP or probable UIP. Clinical and prognostic data of patients categorized by the etiology were compared.ResultsA total of 591 patients were included and classified into the following groups: idiopathic pulmonary fibrosis (IPF) (n = 320), connective tissue disease (CTD)-UIP (n = 229), asbestosis-UIP (n = 28), and hypersensitivity pneumonitis (HP)-UIP (n = 14). Advanced age, elevated levels of serum cytokeratin fraction 21-1 and percentage of neutrophils in bronchoalveolar lavage were observed in all groups. IPF patients showed a more rapid decline in FVC (133.9 mL/year) compared to CTD-UIP (24.5 mL/year, p = 0.001) and asbestosis-UIP (61.0 mL/year, p = 0.008) respectively. Sub-analysis of CTD-UIP revealed that patients with rheumatoid arthritis (RA)-UIP (88.1 mL/year) or antineutrophil cytoplasmic antibody-associated vasculitis (AAV)-UIP (72.9 mL/year) experienced a faster deterioration in FVC compared to those with primary Sjögren’s syndrome (pSS)-UIP (25.9 mL/year, p

Rationale: To date, it remains unclear whether recent changes in the management of patients with systemic sclerosis-associated pulmonary hypertension (SSc-PH) have improved survival. Objectives: To describe a cohort of SSc-PH patients and compare their characteristics and survival between the last two decades. Methods: SSc-PH patients prospectively enrolled in the Johns Hopkins PH Center Registry were grouped into two cohorts based on the date of diagnostic right heart catheterization: cohort A included patients diagnosed between 1999 and 2010, and cohort B included those diagnosed between 2010 and 2021. Patients' characteristics were compared between the two cohorts. Measurements and Main Results: Of 504 SSc-PH patients distributed almost equally between the two cohorts, 308 (61%) had World Symposium on Pulmonary Hypertension (WSPH) Group 1, 43 (9%) had Group 2, and 151 (30%) had Group 3. Patients with Group 1 disease in cohort B had significantly better clinical and hemodynamic characteristics at diagnosis, were more likely to receive upfront combination pulmonary arterial hypertension therapy, and had a nearly 4-year increase in median transplant-free survival in univariable analysis compared to those in cohort A (P<0.01). Improved transplant-free survival was still observed after adjusting for patients' baseline characteristics. In contrast, for Group 2 or 3 SSc-PH patients, there were no differences in baseline clinical, hemodynamic, or survival characteristics between the two cohorts. Conclusions: This is the largest single-center study that compares clinical characteristics of SSc-PH patients between the last two decades. Transplant-free survival has improved significantly for those with Group 1 disease over the last decade, possibly secondary to earlier detection and better therapeutic management. Conversely, those with Group 2 or 3 disease continue to have dismal prognosis. [ABSTRACT FROM AUTHOR]

Background and Aims: Acute liver failure (ALF) is a rare but serious disease with challenging clinical decisions, including the possibility of liver transplantation. Although there is interest in predicting who will need a transplant, that outcome is difficult to define as the decision to transplant includes many extraneous factors. The majority of research in this setting focuses on identifying factors that can provide guidance on a patient’s likelihood of survival without a liver transplant. The question that arises is whether death and transplant should be combined as a poor outcome or should alternative approaches be used to account for transplant in this setting. Furthermore, does the approach to incorporating transplant information impact the accuracy of predicting survival. We aim to compare alternative analytic methods for the ALF setting to provide guidance to the clinical research community on how to handle transplant when the outcome of interest is survival without a transplant. Methods: Five analysis approaches are compared based on model performance using existing registry data from 2100 ALF patients: logistic regression with transplant as part of the outcome, logistic regression with transplant as a covariate, inverse probability weighting, survival analysis, and multiple imputation. Results: The various models exhibit comparable model fit with each providing advantages and challenges in implementation. Conclusion: There are alternative modeling approaches in the ALF setting, leaving researchers with multiple valid options for how to include transplant when examining factors that may influence transplant-free survival.

Background: It is impossible to predict which patients with biliary atresia (BA) will fail after Kasai portoenterostomy (KPE). We evaluated the predictive nature of pre-KPE clinical and histological factors on transplant-free survival (TFS) and jaundice clearance. Methods: A retrospective review of patients who received a KPE at our institution (1997–2018) was performed. Primary outcomes were two-year TFS, five-year TFS, and jaundice clearance 3 months after KPE. p < 0.05 was considered significant. Results: Fifty-four patients were included in this study. The two-year TFS was 35.1%, five-year TFS was 24.5%, and 37% patients reached a direct bilirubin (DB) ≤ 2.0 mg/dL 3 months post KPE. The median age at biopsy was younger in the five-year TFS (39.0 (24.5–55.5) vs. 56.0 days (51.0–67.0), p = 0.011). Patients with DB ≤ 1.0 mg/dL 3 months after KPE were statistically younger at biopsy (DB ≤ 1.0 44.0 (26.0–56.0) vs. DB > 1.0 56.0 days (51.0–69.0), p = 0.016). Ductal plate malformation was less frequent in the five-year TFS (16/17, 94.1%, vs. 1/17, 5.9%, p = 0.037). Portal fibrosis (19/23, 82.6%, vs. 4/23, 17.4%, p = 0.028) and acute cholangitis (6/7, 85.7%, vs. 1/7, 14.3%, p = 0.047) occurred less frequently in two-year TFS. Conclusion: Older age at biopsy, acute cholangitis, portal fibrosis, and ductal plate malformation were associated with lower native liver survival. Evaluation in a larger study population is needed to validate these results. [ABSTRACT FROM AUTHOR]

Background and aims: Little is known regarding the epidemiology and outcomes of patients with primary sclerosing cholangitis (PSC) in Australia. We, therefore, evaluated the epidemiology and clinical outcomes of PSC in a large cohort of Australian patients and compared these to the general population. Methods: We conducted a multicentre, retrospective cohort study of PSC patients at nine tertiary liver centers across three Australian states, including two liver transplant centers. Results: A total of 413 PSC patients with 3,285 person-years of follow-up were included. Three hundred and seventy-one (90%) patients had large duct PSC and 294 (71%) had associated inflammatory bowel disease. A total of 168 (41%) patients developed cirrhosis (including 34 at the time of PSC diagnosis) after a median of 15.8 (95% CI 12.4, NA) years. The composite endpoint of death or liver transplantation occurred in 49 (12%) and 78 (19%) patients, respectively, with a median transplant-free survival of 13.4 (95% CI 12.2–15) years. Compared to the general population, PSC accounted for a 240-fold increased risk of development of cholangiocarcinoma (CCA) and CCA-related death. CCA risk was increased with older age of PSC diagnosis, presence of dominant stricture and colectomy. Compared to same-aged counterparts in the general population, PSC patients who were diagnosed at an older age or with longer disease duration had reduced relative survival. Conclusion: In this large retrospective cohort study of PSC patients in Australia, increased age and time from diagnosis was associated with increased mortality and morbidity particularly from CCA and development of cirrhosis, necessitating need for liver transplant. [ABSTRACT FROM AUTHOR]

Background: Following liver transplantation (LT), allograft liver failure can be developed by various causes and requires re-LT. Hence, this study aimed to clarify the characteristics and prognostic factors of patients with allograft liver failure awaiting deceased donor LT (DDLT) in Japan. Methods: Of the 2686 DDLT candidates in Japan between 2007 and 2016, 192 adult patients listed for re-LT were retrospectively enrolled in this study. Factors associated with waitlist mortality were assessed using the Cox proportional hazards model. The transplant-free survival probabilities were evaluated using the Kaplan–Meier analysis and log-rank test. Results: The median period from the previous LT to listing for re-LT was 1548 days (range, 4–8449 days). Primary sclerosing cholangitis (PSC), which was a primary indication, showed a higher listing probability for re-LT as compared with other primary etiologies. Recurrent liver disease was a leading cause of allograft failure and was more frequently observed in the primary indication of hepatitis C virus (HCV) infection and PSC in contrast with other etiologies. Multivariate analysis identified the following independent risk factors associated with waitlist mortality: age, Child–Turcotte–Pugh (CTP) score, mode for end-stage liver disease (MELD) score, alanine aminotransferase (ALT), and causes of allograft failure. Conclusions: Recurrent HCV and PSC were major causes of allograft liver failure in Japan. In addition to CTP and MELD scores, either serum ALT levels or causes of allograft failure should be considered as graft liver allocation measures. [ABSTRACT FROM AUTHOR]

Hepatorenal syndrome (HRS) is a life-threatening complication of cirrhosis with a poor prognosis. To develop novel and effective nomograms which could numerically predict both the hospital survival and transplant-free survival of HRS, we retrospectively enrolled a cohort of 149 patients. A backward stepwise method based on the smallest Akaike information criterion value was applied to select the covariates to be included in the Cox proportional hazards models. The Harrell C-index, area under the receiver operating characteristic curve (AUC), Brier score, and Kaplan–Meier curves with the log-rank test were used to assess nomograms. The bootstrapping method with 1000 resamples was performed for internal validation. The nomogram predicting hospital survival included prothrombin activity, HRS clinical pattern, Child–Pugh class, and baseline serum creatinine. The C-index was 0.72 (95% confidence interval (CI), 0.65–0.78), and the adjusted C-index was 0.72 (95% CI, 0.66–0.79). The nomogram predicting transplant-free survival included sex, prothrombin activity, HRS clinical pattern, model for end-stage liver disease–Na score, and peak serum creatinine. The C-index of the nomogram was 0.74 (95% CI, 0.69–0.79), and the adjusted C-index was 0.74 (95% CI, 0.68–0.79). The AUC and Brier score at 15, 30, and 45 days calculated from the hospital survival nomogram and those at 6, 12, and 18 months calculated from the transplant-free survival nomogram revealed good predictive ability. The two models can be used to identify patients at high risk of HRS and promote early intervention treatment. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of transjugular intrahepatic portosystemic shunt (TIPS) creation using Fluency versus Viatorr stent-grafts on the long-term clinical outcomes.Materials and Methods: This was a single-center retrospective study from January 2010 to October 2021 in 213 patients receiving TIPS with Fluency (Fluency group, n = 154) versus Viatorr (Viatorr group, n = 59) stent-grafts. Inclusion criteria were: age > 18 years old and TIPS creation for variceal hemorrhage. Exclusion criteria were: age > 80 years old, concomitant chronic heart or lung disease, active tuberculosis or human immunodeficiency virus infection, extrahepatic malignancy, alcohol dependence, TIPS created outside of our hospital, without any follow-up data, or decline to participate. The primary outcome was primary patency rate and its associated risk factors.Results: The 5-year cumulative primary patency rate was significantly higher in Viatorr group than in Fluency group (89.0% vs. 19.6%, p < 0.001), whereas the 5-year cumulative transplant-free survival rate (62.3% vs. 62.2%, p = 0.636) was comparable between two groups. Cox-regression models revealed that group (hazard ratio [HR]4.029, 95% confidence interval [CI] 1.486-10.927, p = 0.006), use of bare stents (HR 3.307, 95% CI 1.903-5.747, p < 0.001), and baseline portal vein thrombosis (HR 0.248, 95% CI 0.149-0.412, p < 0.001) were significantly associated with shunt patency. Incidences of adverse events were not significantly different between two groups (p > 0.05).Conclusions: TIPS creation using Viatorr stent-grafts is superior to using Fluency stent-grafts in terms of higher long-term primary patency rate but similar transplant-free survival rate. [ABSTRACT FROM AUTHOR]

Abstract Research question There is no widely accepted grading system for IPF disease severity, although physiologic impairment based on pulmonary function testing is frequently employed. We sought to describe clinical and functional characteristics as well as outcomes of patients with severe physiologic impairment. Patients and methods IPF patients with severe physiologic impairment defined by FVC ≤ 50% and/or DLco ≤ 30% predicted evaluated in the Inova Advanced Lung Disease Program between 2011 and 2019 were included. Demographic, physiologic, functional treatment and outcome data were collated. Results There were 531 patients with IPF evaluated of whom 242 (46%) had severe physiologic impairment. Mean age was 72 ± 8 years; baseline FVC was 53 ± 17% and DLCO 28 ± 9% of predicted. The mean 6 min walks test (6MWT) distance was 304 ± 121 m with 59% of the patients requiring supplemental oxygen ( $${\text{6MWT}}_{{{\text{O}}_{{2}} }}$$ 6MWT O 2 group). There was a poor correlation between the 6MWT distance and both FVC% and DLco%. Patients in the 6MWTRA group had a better transplant-free survival than the $${\text{6MWT}}_{{{\text{O}}_{{2}} }}$$ 6MWT O 2 group (p = 0.002). Patients managed before October 2014 and not receiving antifibrotic therapy had worse outcomes with reduced transplant-free survival compared with patients presenting after this date who did receive antifibrotic therapy (n = 113) (log rank p

Abstract Background The role of artificial and bioartificial liver support systems in acute-on-chronic liver failure (ACLF) is still controversial. We aimed to perform the first network meta-analysis comparing and ranking different liver support systems and standard medical therapy (SMT) in patients with ACLF. Methods The study protocol was registered with PROSPERO (CRD42020155850). A systematic search was conducted in five databases. We conducted a Bayesian network meta-analysis of randomized controlled trials assessing the effect of artificial or bioartificial liver support systems on survival in patients with ACLF. Ranking was performed by calculating the surface under cumulative ranking (SUCRA) curve values. The RoB2 tool and a modified GRADE approach were used for the assessment of the risk of bias and quality of evidence (QE). Results In the quantitative synthesis 16 trials were included, using MARS®, Prometheus®, ELAD®, plasma exchange (PE) and BioLogic-DT®. Overall (OS) and transplant-free (TFS) survival were assessed at 1 and 3 months. PE significantly improved 3-month OS compared to SMT (RR 0.74, CrI: 0.6–0.94) and ranked first on the cumulative ranking curves for both OS outcomes (SUCRA: 86% at 3 months; 77% at 1 month) and 3-month TFS (SUCRA: 87%) and second after ELAD for 1-month TFS (SUCRA: 76%). Other comparisons did not reach statistical significance. QE was moderate for PE concerning 1-month OS and both TFS outcomes. Other results were of very low certainty. Conclusion PE seems to be the best currently available liver support therapy in ACLF regarding 3-month OS. Based on the low QE, randomized trials are needed to confirm our findings for already existing options and to introduce new devices.

Objective: This study aimed to evaluate outcomes in cirrhotic patients diagnosed with spontaneous bacterial empyema (SBE) compared with those without this complication. Methods: We performed a retrospective cohort study of cirrhotic patients from a tertiary care center. The primary outcome was time to death or liver transplantation (LT) within one year after diagnosis of infection. We integrated three groups: patients with SBE (group A), patients with spontaneous bacterial peritonitis (SBP; group B), and cirrhotic patients without SBP or SBE (group C), matched by age, model for end‐stage liver disease‐sodium (MELD‐Na) score and year of infection. Outcomes were analyzed using a Cox regression model adjusted for cardiovascular risk factors and MELD‐Na score. Results: Between January 1999 and February 2019, 4829 cirrhotic patients were identified. Among them, 73 (1.5%) had hepatic hydrotorax, of whom 22 (30.1%) were diagnosed with SBE. Median age in group A was 58 years, 50% were men, and median MELD‐Na was 21.5. Compared with group C, the hazard ratio of death or LT during the first year after infection was 2.98 (95% confidence interval [CI] 1.43‐6.22, P = 0.004) for group A and 1.23 (95% CI 0.65‐2.32, P = 0.522) for group B. Conclusions: Our results suggest that patients with SBE have a worse outcome during the first year after infection is diagnosed. Patients who develop SBE should be promptly referred for transplant evaluation. SBE may emerge as new indication that could benefit from MELD exception points. [ABSTRACT FROM AUTHOR]

Abstract Background Acute liver failure is a rare syndrome with significant morbidity and mortality, particularly in absence of transplantation as a rescue therapy. An important mechanism contributing to mortality is hyperammonemia which drives cerebral edema and raised intracranial pressure. Multiple therapies for managing hyperammonemia have been trialed. Continuous renal replacement therapy is effective in treating hyperammonemia in other disease states (notably inborn errors of metabolism). Its efficacy in acute liver failure has been suggested but further investigation is required to prove this. The objective of this systematic review will be to determine the efficacy of continuous renal replacement therapy in patients with acute liver failure and its effect on mortality and transplant-free survival. Methods MEDLINE, EMBASE, Web of Science, and Cochrane Database will be searched. Identified studies will include all patients with acute liver failure in a critical care unit treated with continuous renal replacement therapy. Primary outcome will be effectiveness of ammonia clearance and mortality. Patients treated with any other modality of ammonia lowering therapy (such as plasma exchange or Molecular Adsorbent Recirculating System) will be excluded. Narrative synthesis of the identified studies will occur and if clinical homogeneity is identified, data will be pooled for meta-analysis using a DerSimonian-Laird random effects model. Discussion We present a protocol for a systematic review seeking to establish a link between transplant-free survival in acute liver failure and the use of continuous renal replacement therapy. Given the anticipated paucity of literature on this subject, both narrative and quantitative syntheses are planned. Systematic review registration (PROSPERO) CRD42019122520 , registered April 16, 2019.

Background and objective: Antifibrotic therapy with nintedanib or pirfenidone slows disease progression and reduces mortality in patients with idiopathic pulmonary fibrosis (IPF). However, patients with advanced IPF, as defined by forced vital capacity (FVC) < 50% and/or diffusion capacity for carbon monoxide (DLCO) < 30% of predicted, have not been included in randomized trials, and the outcomes of such patients who initiate treatment are not well understood. We determined lung function, disease progression and mortality outcomes following initiation of antifibrotic therapy in patients with advanced IPF at the time of treatment initiation compared to those with mild-moderate IPF. Methods: We included 502 patients enrolled in IPF registries from four Nordic countries. Linear mixed models were used to assess change in FVC and DLCO over time. Cox proportional hazards models were used to assess transplant-free survival and progression- and transplant-free survival. Results: Of 502 patients, 66 (13%) had advanced IPF. Annual change in FVC was -125 ml (95% CI -163, -87) among patients with mild-moderate IPF, and +28 ml (95% CI -96, +152) among those with advanced IPF. Advanced IPF at treatment initiation was associated with poorer transplant-free survival (hazard ratio [HR] 2.39 [95% CI 1.66, 3.43]) and progression- and transplant-free survival (HR 1.60 [95% CI 1.15, 2.23]). Conclusion: In a broadly representative IPF population, patients with advanced IPF at the initiation of antifibrotic therapy did not have greater lung function decline over time compared with those with mild-moderate IPF, but had substantially higher mortality. Prospective studies are needed to determine the effect of antifibrotic therapy in patients with advanced IPF. [ABSTRACT FROM AUTHOR]

Background/Aims: Primary sclerosing cholangitis (PSC) is a chronic, progressive, fibrotic bile duct disease. Resultant complications include infection, progressive liver disease and cancer. While diagnosis relies extensively on imaging, the role of imaging in determining prognosis is unclear. The aim of this study was to systematically review existing imaging indices and features that predict PSC progression. Materials and Methods: We performed a systematic review of imaging features that predict PSC progression. PubMed, EMBASE, MEDLINE, Clinicaltrials.gov and the Cochrane Library were searched from inception to November 2018 for relevant studies. Pertinent data were extracted and assessed. Study quality was evaluated using the Newcastle-Ottawa scale (NOS). Results: The search returned 2504 results. Nine studies were included in the final review. Four studies evaluated the prognostic value of imaging features and five evaluated prognostic algorithms. The mean NOS score was 4.44 ± 0.98 on a scale of 0 to 9. Imaging features that were of prognostic value were degree of intrahepatic duct narrowing, the presence of a dominant biliary duct stricture and percentage of narrowed intraheptic ducts. Three imaging indices (one endoscopic retrograde cholangiopancreatography (ERCP)-based and two magnetic resonance-based) had been derived. The ERCP index was validated in a second cohort and subsequently updated to improve its predictive ability. The magnetic resonance cholangiopancreatography (MRCP) index was validated in two studies and was found to be predicative of transplant-free survival. A modified MRCP index (MRCP-risk score) was evaluated in a prospective multicenter study and was found to be predicative of PSC-related disease progression. Conclusion: In conclusion, ERCP and MRCP-based indices have short-term prognostic value in PSC. However, more studies are required to validate their predictability of disease-related progression, such as liver decompensation, ascending cholangitis, cholangiocarcinoma and liver transplantation.

Hepatorenal syndrome (HRS) is a life-threatening complication of cirrhosis with a poor prognosis. To develop novel and effective nomograms which could numerically predict both the hospital survival and transplant-free survival of HRS, we retrospectively enrolled a cohort of 149 patients. A backward stepwise method based on the smallest Akaike information criterion value was applied to select the covariates to be included in the Cox proportional hazards models. The Harrell C-index, area under the receiver operating characteristic curve (AUC), Brier score, and Kaplan–Meier curves with the log-rank test were used to assess nomograms. The bootstrapping method with 1000 resamples was performed for internal validation. The nomogram predicting hospital survival included prothrombin activity, HRS clinical pattern, Child–Pugh class, and baseline serum creatinine. The C-index was 0.72 (95% confidence interval (CI), 0.65–0.78), and the adjusted C-index was 0.72 (95% CI, 0.66–0.79). The nomogram predicting transplant-free survival included sex, prothrombin activity, HRS clinical pattern, model for end-stage liver disease–Na score, and peak serum creatinine. The C-index of the nomogram was 0.74 (95% CI, 0.69–0.79), and the adjusted C-index was 0.74 (95% CI, 0.68–0.79). The AUC and Brier score at 15, 30, and 45 days calculated from the hospital survival nomogram and those at 6, 12, and 18 months calculated from the transplant-free survival nomogram revealed good predictive ability. The two models can be used to identify patients at high risk of HRS and promote early intervention treatment.

Background: The role of artificial and bioartificial liver support systems in acute-on-chronic liver failure (ACLF) is still controversial. We aimed to perform the first network meta-analysis comparing and ranking different liver support systems and standard medical therapy (SMT) in patients with ACLF. Methods: The study protocol was registered with PROSPERO (CRD42020155850). A systematic search was conducted in five databases. We conducted a Bayesian network meta-analysis of randomized controlled trials assessing the effect of artificial or bioartificial liver support systems on survival in patients with ACLF. Ranking was performed by calculating the surface under cumulative ranking (SUCRA) curve values. The RoB2 tool and a modified GRADE approach were used for the assessment of the risk of bias and quality of evidence (QE). Results: In the quantitative synthesis 16 trials were included, using MARS®, Prometheus®, ELAD®, plasma exchange (PE) and BioLogic-DT®. Overall (OS) and transplant-free (TFS) survival were assessed at 1 and 3 months. PE significantly improved 3-month OS compared to SMT (RR 0.74, CrI: 0.6–0.94) and ranked first on the cumulative ranking curves for both OS outcomes (SUCRA: 86% at 3 months; 77% at 1 month) and 3-month TFS (SUCRA: 87%) and second after ELAD for 1-month TFS (SUCRA: 76%). Other comparisons did not reach statistical significance. QE was moderate for PE concerning 1-month OS and both TFS outcomes. Other results were of very low certainty. Conclusion: PE seems to be the best currently available liver support therapy in ACLF regarding 3-month OS. Based on the low QE, randomized trials are needed to confirm our findings for already existing options and to introduce new devices. [ABSTRACT FROM AUTHOR]

Research Question: There is no widely accepted grading system for IPF disease severity, although physiologic impairment based on pulmonary function testing is frequently employed. We sought to describe clinical and functional characteristics as well as outcomes of patients with severe physiologic impairment.Patients and Methods: IPF patients with severe physiologic impairment defined by FVC ≤ 50% and/or DLco ≤ 30% predicted evaluated in the Inova Advanced Lung Disease Program between 2011 and 2019 were included. Demographic, physiologic, functional treatment and outcome data were collated.Results: There were 531 patients with IPF evaluated of whom 242 (46%) had severe physiologic impairment. Mean age was 72 ± 8 years; baseline FVC was 53 ± 17% and DLCO 28 ± 9% of predicted. The mean 6 min walks test (6MWT) distance was 304 ± 121 m with 59% of the patients requiring supplemental oxygen ([Formula: see text] group). There was a poor correlation between the 6MWT distance and both FVC% and DLco%. Patients in the 6MWTRA group had a better transplant-free survival than the [Formula: see text] group (p = 0.002). Patients managed before October 2014 and not receiving antifibrotic therapy had worse outcomes with reduced transplant-free survival compared with patients presenting after this date who did receive antifibrotic therapy (n = 113) (log rank p < 0.0001).Conclusion: IPF patients often present with severe physiologic impairment which may be poorly correlated with their functional status. Assessment of IPF disease severity should not be based on physiologic impairment alone, but should also encompass functional status as well as need for supplemental oxygen. Antifibrotic therapy in patients with severe physiologic impairment is associated with improved outcomes. [ABSTRACT FROM AUTHOR]

Objective: To study the clinico-bacteriological profile of ascitic fluid infection (AFI) and its impact on outcome in childhood chronic liver disease (CLD). Methods: It was a retrospective study on pediatric CLD patients requiring an ascitic tap. Logistic regression was performed to study the predictive factors for AFI. Results: Two hundred and fifty-two (30.9%) of 814 children with CLD underwent ascitic tap on suspicion of AFI of whom 79 (31.3%) had AFI, culture negative neutrocytic ascites being the commonest. Younger age (p = 0.002), male gender (p = 0.007), new onset/rapid increase in ascites (p = 0.032), fever (p = 0.012), and blood total leukocyte count (TLC) (p = 0.001) were found to be independently associated with AFI. Twenty-three children had positive ascitic fluid culture: 15 Gram negative; 11 (52.3%) were multidrug resistant organism. Hepatic encephalopathy (HE) (p = 0.001), Model for End-stage Liver Disease/Pediatric End-stage Liver Disease (MELD/PELD) (p < 0.0005), and difficult-to-treat AFI (p = 0.007) were found to be independently associated with death and or LT. Conclusion: Children with ascites should undergo a diagnostic paracentesis in presence of fever, increasing or new-onset ascites, and/or increased TLC. Death or liver transplant are more likely due to advanced liver disease (high PELD /HE) and in those with difficult-to-treat AFI. [ABSTRACT FROM AUTHOR]

Background and Aims: Improvement in Model for End‐Stage Liver Disease (MELD) score during antiviral treatment is associated with reduced hepatic decompensation and death in patients with chronic hepatitis B (CHB)‐related cirrhosis. We aimed to identify factors associated with transplant‐free survival and on‐treatment MELD score improvement. Methods: We identified patients with CHB‐related cirrhosis and MELD score ≥ 15 at the start of entecavir and/or tenofovir disoproxil fumarate treatment between 2005 and 2017. The primary endpoint was transplant‐free survival at month 6. The secondary endpoints at month 6 were transplant‐free survival with > 5‐point improvement in MELD score and transplant‐free survival with MELD score < 15. Results: Of 999 cirrhotic CHB patients, 605 (60.6%) achieved transplant‐free survival at month 6. Proportion of transplant‐free survival at month 6 stabilized at 10% in patients with high MELD. Patients who achieved transplant‐free survival at month 6 were younger, had lower MELD score, lower alanine aminotransferase (ALT), and higher albumin at baseline. Of 605 patients with transplant‐free survival, 276 (45.6%) achieved > 5‐point improvement in MELD score; 183 (30.2%) had 1‐point to 5‐point improvement in MELD score; 146 (24.1%) had no improvement or a worsened MELD score. Also, 321 (53.1%) patients with transplant‐free survival had a MELD score < 15 at month 6. Conclusion: On top of lower MELD score, patients with CHB‐related cirrhosis who are younger, have higher albumin, and lower ALT are more likely to achieve transplant‐free survival after 6 months of antiviral treatment. [ABSTRACT FROM AUTHOR]

Background: Acute liver failure is a rare syndrome with significant morbidity and mortality, particularly in absence of transplantation as a rescue therapy. An important mechanism contributing to mortality is hyperammonemia which drives cerebral edema and raised intracranial pressure. Multiple therapies for managing hyperammonemia have been trialed. Continuous renal replacement therapy is effective in treating hyperammonemia in other disease states (notably inborn errors of metabolism). Its efficacy in acute liver failure has been suggested but further investigation is required to prove this. The objective of this systematic review will be to determine the efficacy of continuous renal replacement therapy in patients with acute liver failure and its effect on mortality and transplant-free survival. Methods: MEDLINE, EMBASE, Web of Science, and Cochrane Database will be searched. Identified studies will include all patients with acute liver failure in a critical care unit treated with continuous renal replacement therapy. Primary outcome will be effectiveness of ammonia clearance and mortality. Patients treated with any other modality of ammonia lowering therapy (such as plasma exchange or Molecular Adsorbent Recirculating System) will be excluded. Narrative synthesis of the identified studies will occur and if clinical homogeneity is identified, data will be pooled for meta-analysis using a DerSimonian-Laird random effects model. Discussion: We present a protocol for a systematic review seeking to establish a link between transplant-free survival in acute liver failure and the use of continuous renal replacement therapy. Given the anticipated paucity of literature on this subject, both narrative and quantitative syntheses are planned. Systematic review registration: (PROSPERO) CRD42019122520, registered April 16, 2019. [ABSTRACT FROM AUTHOR]

Context Biliary atresia (BA) remains the most common indication for pediatric liver transplantation worldwide. Ultimately, 50–80% of BA patients will require a liver transplant Thus, much of the research in the field has focused on identifying predictors for transplant and optimizing the efficacy of Kasai portoenterostomy (KPE), in order to decrease the need for transplantation and avoid the risks of lifelong immunosuppression. Aim The aim of this study was to identify perioperative risk factors for the need of liver transplantation following KPE operation for BA. Patients and methods A retrospective analysis of 150 patients undergoing KPE for BA at Hepatobiliary and Pancreatic Surgery Department, National Liver Institute, Menoufia University, from May 2013 to May 2018, was carried out. Patients were divided into two groups: group one included 73 (48.7%) patients who survived without the need for liver transplantation and group two included 77 (51.3%) patients with mortality, listed for liver transplantation or transplanted; thereafter, logistic regression analysis was used to identify the independent predictors of cases needing liver transplantation. Statistical analysis used Continuous variables were expressed as mean±SD and categorical variables as proportions. Univariate analysis for the two groups were carried out using the independent samples t test for continuous variables and χ2 test for categorical variables. Logistic regression analysis was used to identify the independent predictors of cases needing liver transplantation. Receiver operating characteristic analysis was used for the cut-off determination of predictive parameters using MedCalc application, version 18.2.1. Results The mean age at the time of operation was 74.9±14.6 days after birth (range, 31–111 days); there were 70 (46.7%) male babies and 80 (53.3%) female babies. The mean preoperative weight was 4.6±0.6 kg, while the mean preoperative height was 57.3±3.58 cm. Total bilirubin and albumin levels at 1 and 3 months following KPE were associated with death or the need for liver transplantation; however, only a total bilirubin level of more than 6 mg/dl at 3 months is an independent predictor of the need for liver transplantation. Age at the time of KPE and postoperative steroid use were not associated with improved transplant-free survival. Conclusion Total bilirubin level of more than 7.3 mg/dl at 1 month and a level of more than 6 mg/dl at 3 months after KPE are predictive of the need for liver transplantation (P<0.001). Albumin level of less than or equal to 2.5 g/dl at 1 month and a level of less than or equal to 3 g/dl at 3 months after KPE are predictive of the need for liver transplantation (P<0.001); however, only total bilirubin level of more than 6 mg/dl at 3 months is an independent predictor of the need for transplantation (P<0.001). Age at the time of KPE and postoperative steroid use were not associated with improved transplant-free survival. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine perioperative risk factors for need of liver transplantation following hepatoportoenterostomy. A retrospective review of patients undergoing hepatoportoenterostomy for biliary atresia at our institution from 1990 to 2016 was completed. A total of 81 patients were identified with a median age of 51 days (IQR: 33-68) at hepatoportoenterostomy and a median follow-up time of 5.7 years (IQR: 1-11.6). Ten-year overall survival was 93% (95% CI: 84-97). Thirty-six patients (44%) ultimately required transplantation at a median time from hepatoportoenterostomy of 8.9 months (IQR: 5.2-19). The 10-year transplant-free survival was 36% (95%CI: 24-49). Steroid use (N = 42) was not associated with improved 10-yr transplant-free survival (33% vs. 38%, p = 0.690). Age at hepatoportoenterostomy was not significantly associated with the need for transplantation. Multivariable logistic regression analysis demonstrated that total bilirubin > 2mg/dL (OR: 97, p < 0.001) and albumin < 3.5g/dL (OR: 24, p = 0.027) at 3 months after surgery were independent predictors of the need for transplantation, while adjusting for age, sex, prematurity, and steroid use. Overall survival for children with biliary atresia is excellent, although most patients will ultimately require liver transplantation. Total bilirubin and albumin level at 3 months following hepatoportoenterostomy are predictive of the need for transplantation. Steroid use is not associated with improved outcomes. [ABSTRACT FROM AUTHOR]

Background/Aims: Primary sclerosing cholangitis (PSC) is a chronic, progressive, fibrotic bile duct disease. Resultant complications include infection, progressive liver disease and cancer. While diagnosis relies extensively on imaging, the role of imaging in determining prognosis is unclear. The aim of this study was to systematically review existing imaging indices and features that predict PSC progression. Materials and Methods: We performed a systematic review of imaging features that predict PSC progression. PubMed, EMBASE, MEDLINE, Clinicaltrials.gov and the Cochrane Library were searched from inception to November 2018 for relevant studies. Pertinent data were extracted and assessed. Study quality was evaluated using the Newcastle-Ottawa scale (NOS). Results: The search returned 2504 results. Nine studies were included in the final review. Four studies evaluated the prognostic value of imaging features and five evaluated prognostic algorithms. The mean NOS score was 4.44 ± 0.98 on a scale of 0 to 9. Imaging features that were of prognostic value were degree of intrahepatic duct narrowing, the presence of a dominant biliary duct stricture and percentage of narrowed intraheptic ducts. Three imaging indices (one endoscopic retrograde cholangiopancreatography (ERCP)-based and two magnetic resonance-based) had been derived. The ERCP index was validated in a second cohort and subsequently updated to improve its predictive ability. The magnetic resonance cholangiopancreatography (MRCP) index was validated in two studies and was found to be predicative of transplant-free survival. A modified MRCP index (MRCP-risk score) was evaluated in a prospective multicenter study and was found to be predicative of PSC-related disease progression. Conclusion: In conclusion, ERCP and MRCP-based indices have short-term prognostic value in PSC. However, more studies are required to validate their predictability of disease-related progression, such as liver decompensation, ascending cholangitis, cholangiocarcinoma and liver transplantation. [ABSTRACT FROM AUTHOR]

Background: Exogenous growth factor‐mobilized bone marrow (BM) stem cells have shown a differential response in the management of decompensated cirrhosis (DC). This study was designed to evaluate potential clinical benefit of adding Erythropoietin (EPO) in granulocyte‐colony stimulating factor (G‐CSF)‐mobilized stem cell therapy, possible mechanisms of regeneration and predictive factors of regenerative response. Methods: Sixty consecutive DC patients received either G‐CSF with EPO (Group A; n = 30) or G‐CSF and placebo (Group B; n = 30) for 2 months and were carefully followed up for 1 year. Baseline and post‐treatment liver biopsy, BM biopsy and BM aspirate were analysed for fibro‐inflammatory and regenerative response and BM hematopoietic reservoir. Results: Addition of EPO to G‐CSF showed a significant improvement in Child‐Pugh score (P = 0.03) and MELD score (P = 0.003) as compared to G‐CSF alone, with reduction in mortality (16.6% vs 36.7%, P = 0.09). The combination arm also demonstrated a decreased incidence of acute kidney injury (P < 0.001), encephalopathy (P = 0.005) and refilling of ascites (P = 0.03). Compared to monotherapy, it increased CD163+ macrophages (P = 0.013), Ki67+ index (P < 0.001) with decrease in α‐SMA levels (P < 0.001) in liver tissue. The response was better with grade 1 and 2 than with grade 3 ascites; Child B cirrhosis and MELD < 16. Non‐responders had lower hematopoietic stem cells (HSCs) at baseline. On multivariate analysis, the liver disease severity (MELD < 16) and a relatively preserved BM (BM‐HSCs > 0.4) predicted therapeutic response (AUROC = 0.82). Conclusions: Early DC (MELD < 16) patients with mild‐moderate ascites and those with a healthy cellular baseline BM respond better to growth factor therapy. Addition of EPO to G‐CSF provides better regenerative response than G‐CSF monotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Children with restrictive cardiomyopathy (RCM) traditionally have a poor prognosis, with most patients either dying or requiring heart transplantation within 2 years of diagnosis. The development of symptoms in RCM suggests advanced disease. However, as screening practices evolve and lead to diagnosis of early disease, identifying appropriate timing of transplant listing becomes increasingly important. In this context we compared outcomes of children with RCM presenting with clinical symptoms to those asymptomatic at initial presentation., Methods: This retrospective cohort study included 25 patients with RCM presenting to a quaternary care center between 2001 and 2018. Times to transplantation, death, and a composite outcome of adverse cardiac events (CPR, cardioversion, inotropic support, mechanical ventilation, mechanical support, or heart transplant) were compared between those symptomatic and asymptomatic at presentation., Results: At 2 years following diagnosis, patients asymptomatic at presentation had a significantly better transplant-free survival at 57% compared to 17% for symptomatic patients ( p  = 0.03). Those asymptomatic at diagnosis also had significantly improved cardiac event-free survival at 71% compared to symptomatic patients at 25% ( p  = 0.01). In multivariable analysis, cardiac symptoms at presentation remained an independent risk factor for heart-transplant or death [hazard ratio 5.17 (1.28-20.85), p  = 0.02]., Conclusion: Patients with RCM who are symptomatic at time of diagnosis have significantly worse transplant-free survival and cardiac event-free survival. Given current practice variability in timing of transplant listing, the presence of any cardiac symptoms is an important negative prognostic marker and should prompt urgent transplant listing., Competing Interests: AL was supported by a Heart Failure Research Fellowship from Bristol-Myers Squibb, Mitacs, and Myant during this research study. AJ is a medical monitor for the Pumpkin trial and employed as a consultant for Abbott. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Lorenzo, Lynch, Ashkanase, Fazari, George, Arathoon, Minn, Nicolson, Jeewa and Jean-St-Michel.)

Background: Usual interstitial pneumonia (UIP) is a pattern of interstitial pneumonia that is caused by different etiologies. This study aimed to investigate the transplant-free survival (TFS) and the decline in forced vital capacity (FVC) of the patients with UIP and probable UIP patterns on CT caused by various underlying conditions., Methods: A retrospective cohort study was conducted, enrolling patients with interstitial lung disease exhibiting a CT pattern consistent with UIP or probable UIP. Clinical and prognostic data of patients categorized by the etiology were compared., Results: A total of 591 patients were included and classified into the following groups: idiopathic pulmonary fibrosis (IPF) ( n  = 320), connective tissue disease (CTD)-UIP ( n  = 229), asbestosis-UIP ( n  = 28), and hypersensitivity pneumonitis (HP)-UIP ( n  = 14). Advanced age, elevated levels of serum cytokeratin fraction 21-1 and percentage of neutrophils in bronchoalveolar lavage were observed in all groups. IPF patients showed a more rapid decline in FVC (133.9 mL/year) compared to CTD-UIP (24.5 mL/year, p  = 0.001) and asbestosis-UIP (61.0 mL/year, p  = 0.008) respectively. Sub-analysis of CTD-UIP revealed that patients with rheumatoid arthritis (RA)-UIP (88.1 mL/year) or antineutrophil cytoplasmic antibody-associated vasculitis (AAV)-UIP (72.9 mL/year) experienced a faster deterioration in FVC compared to those with primary Sjögren's syndrome (pSS)-UIP (25.9 mL/year, p  < 0.05). Kaplan-Meier curves showed that IPF had the poorest TFS (median 55.9 months), followed by HP-UIP (57.5 months), CTD-UIP (66.7 months), and asbestosis-UIP (TFS not reached). RA-UIP or AAV-UIP did not exhibit any prognostic advantages compared to IPF, while asbestosis-UIP and pSS-UIP showed better survival rates., Conclusion: Patients with UIP caused by different underlying conditions share certain common features, but the trajectories of disease progression and survival outcomes differ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Wang, Sun, Wang, Xue and Ye.)

Clinically, it is highly challenging to promote recovery in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Despite recent advances in understanding the underlying mechanisms of ALF and ACLF, standard medical therapy remains the primary therapeutic approach. Liver transplantation (LT) is considered the last option, and in several cases, it is the only intervention that can be lifesaving. Unfortunately, this intervention is limited by organ donation shortage or exclusion criteria such that not all patients in need can receive a transplant. Another option is to restore impaired liver function with artificial extracorporeal blood purification systems. The first such systems were developed at the end of the 20 th century, providing solutions as bridging therapy, either for liver recovery or LT. They enhance the elimination of metabolites and substances that accumulate due to compromised liver function. In addition, they aid in clearance of molecules released during acute liver decompensation, which can initiate an excessive inflammatory response in these patients causing hepatic encephalopathy, multiple-organ failure, and other complications of liver failure. As compared to renal replacement therapies, we have been unsuccessful in using artificial extracorporeal blood purification systems to completely replace liver function despite the outstanding technological evolution of these systems. Extracting middle to high-molecular-weight and hydrophobic/protein-bound molecules remains extremely challenging. The majority of the currently available systems include a combination of methods that cleanse different ranges and types of molecules and toxins. Furthermore, conventional methods such as plasma exchange are being re-evaluated, and novel adsorption filters are increasingly being used for liver indications. These strategies are very promising for the treatment of liver failure. Nevertheless, the best method, system, or device has not been developed yet, and its probability of getting developed in the near future is also low. Furthermore, little is known about the effects of liver support systems on the overall and transplant-free survival of these patients, and further investigation using randomized controlled trials and meta-analyses is needed. This review presents the most popular extracorporeal blood purification techniques for liver replacement therapy. It focuses on general principles of their function, and on evidence regarding their effectiveness in detoxification and in supporting patients with ALF and ACLF. In addition, we have outlined the basic advantages and disadvantages of each system., Competing Interests: Conflict-of-interest statement: The authors declare having no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

The Primary Biliary Cholangitis (PBC) Obeticholic Acid (OCA) International Study of Efficacy (POISE) randomized, double-blind, placebo-controlled trial demonstrated that OCA reduced biomarkers associated with adverse clinical outcomes (ie, alkaline phosphatase, bilirubin, aspartate aminotransferase, and alanine aminotransferase) in patients with PBC. The objective of this study was to evaluate time to first occurrence of liver transplantation or death in patients with OCA in the POISE trial and open-label extension vs comparable non-OCA–treated external controls. Propensity scores were generated for external control patients meeting POISE eligibility criteria from 2 registry studies (Global PBC and UK-PBC) using an index date selected randomly between the first and last date (inclusive) on which eligibility criteria were met. Cox proportional hazards models weighted by inverse probability of treatment assessed time to death or liver transplantation. Additional analyses (Global PBC only) added hepatic decompensation to the composite end point and assessed efficacy in patients with or without cirrhosis. During the 6-year follow-up, there were 5 deaths or liver transplantations in 209 subjects in the POISE cohort (2.4%), 135 of 1381 patients in the Global PBC control (10.0%), and 281 of 2135 patients in the UK-PBC control (13.2%). The hazard ratios (HRs) for the primary outcome were 0.29 (95% CI, 0.10–0.83) for POISE vs Global PBC and 0.30 (95% CI, 0.12–0.75) for POISE vs UK-PBC. In the Global PBC study, HR was 0.20 (95% CI, 0.03–1.22) for patients with cirrhosis and 0.31 (95% CI, 0.09–1.04) for those without cirrhosis; HR was 0.42 (95% CI, 0.21–0.85) including hepatic decompensation. Patients treated with OCA in a trial setting had significantly greater transplant-free survival than comparable external control patients. [Display omitted] Patients with primary biliary cholangitis treated with obeticholic acid in the POISE study had fewer deaths and liver transplants vs comparable patients in the Global PBC and UK-PBC disease registries. [ABSTRACT FROM AUTHOR]