[The predictive value of dynamic changes of neutrophil/lymphocyte ratio (NLR) combined with the model of end-stage liver disease (MELD) score in patients with acute-on-chronic hepatitis B liver failure].

Objective: To determine the predictive value of dynamic changes of neutrophil/lymphocyte ratio (NLR) combined with the model of end-stage liver disease (MELD) score in patients with acute-on-chronic hepatitis B liver failure. Methods: Patients with acute-on-chronic hepatitis B liver failure who were hospitalized in the Department of Hepatology of Qilu Hospital of Shandong University from January 2010 to July 2023 were retrospectively enrolled. According to the clinical outcomes of patients within 30 days of admission, they were divided into the survival group and the death group. The dynamic changes in NLR and initial values on day 3, 5, 8, and 12 in two groups were analyzed for the diagnostic value of 30-day prognosis in patients with acute-on-chronic hepatitis B liver failure. Logistic regression analysis and machine learning XGBoost algorithm were used to evaluate the risk factors influencing the prognosis of patients at 30 days. Receiver operating characteristic(ROC) curve was used to evaluate the diagnostic value of NLR and initial value change combined with MELD score on day 12 of admission in patients with chronic acute hepatitis B liver failure. Results: A total of 243 patients were enrolled in the study, including 145 patients in the survival group [115 males, 30 females, aged 25-74 (47±11)] and 98 patients in the death group [80 males, 18 females, aged 22-80 (49±13) ]. The median initial NLR of survival group and death group were 3.5 (2.1, 5.3) and 4.9 (2.9, 8.3), respectively, and the difference was statistically significant (P=0.003). The variation of NLR from the initial value on day 3, 5, 8, and 12 in the survival group [1.6 (0, 4.3), 1.9 (-0.2, 4.1), 2.0 (-0.1, 4.3) and 2.9 (0.3, 7.0), respectively] were lower than that in the death group [3.2 (0.9, 7.5), 5.1 (1.8, 7.6), 5.8 (2.0, 10.6) and 9.6 (3.5, 16.4), respectively] (all P<0.001). Logistic regression multivariate analysis showed that the changes in NLR on the 12th day and initial value (OR=1.07,95%CI:1.01-1.14, P=0.014), the changes in NLR on the 3rd day and initial value (OR=2.71, 95%CI: 1.32-5.55, P=0.007), the initial value of NLR (OR=1.18,95%CI:1.01-1.37,P=0.035) and fibrinogen (OR=0.21,95%CI:0.05-0.96,P=0.044) were related factors for death within 30 days. Machine learning XGBoost algorithm showed that the weight of the change between the NLR on the 12th day and the initial value was the highest. The area under the ROC curve of the combined MELD score was 0.812 (95%CI: 0.728-0.895), the specificity was 67.78%, and the sensitivity was 82.35%. Conclusion: Dynamic change of NLR combined with MELD score has high predictive value for the short-term prognosis of patients with acute-on-chronic hepatitis B liver failure.

Silymarin Synergizes with Antiviral Therapy in Hepatitis B Virus-Related Liver Cirrhosis: A Propensity Score Matching Multi-Institutional Study.

Hepatitis B virus (HBV)-related liver cirrhosis (HBV-LC) presents a substantial mortality and hepatocellular carcinoma (HCC) risk. While antiviral therapy (AVT) is the standard, complete HBV clearance remains elusive and may not reduce the risk of death in patients with decompensated cirrhosis. Silymarin, a centuries-old herbal remedy, has shown promise against HBV infection and as an antifibrosis therapy. This study explores the potential of silymarin combined with AVT to reduce mortality and HCC incidence in patients with HBV-LC. This research, spanning from 2001 to 2019, entailed a multi-institutional retrospective cohort study which included 8447 HBV-LC patients all undergoing AVT. After applying inclusion and exclusion criteria, the study comprised two cohorts: a case cohort receiving silymarin alongside AVT for at least 30 days, and a control cohort on AVT alone. Propensity score matching, based on baseline parameters including HBV-DNA levels, comorbidity, and an important LC medication, namely, non-selective ß-blockers, was employed to ensure balanced groups, resulting in 319 patients in each cohort for subsequent analyses. Overall mortality was the primary outcome, with HCC occurrence as a secondary outcome. Among 319 patients in both cohorts, the case cohort exhibited significant improvements in the international normalized ratio (INR), model for end-stage liver disease (MELD) score and the Charlson comorbidity index (CCI) one year after the index date. A competing risk survival analysis demonstrated superior one-year and two-year mortality outcomes in the case cohort. However, no significant impact on one-year and two-year HCC occurrence was observed in either cohort. The combination of silymarin and AVT in HBV-LC patients demonstrated a synergistic effect, leading to decreased overall mortality and an improved comorbidity index. While the incidence of HCC remained unchanged, our results suggested promising potential for further clinical trials investigating the synergistic role of silymarin in the treatment of HBV-LC.

Risk of Cerebral Aneurysm Rupture After Liver Transplantation: Development and Validation of a Hemorrhagic Stroke Scoring Model.

BACKGROUND: Liver transplantation (LT) patients appear to be more prone to neurological events compared to individuals undergoing other types of solid-organ transplantation. The aims of the present study were to analyze the prevalence of unruptured intracranial aneurysms (UIAs) in patients undergoing liver transplantation (LT) and to examine the perioperative occurrence of subarachnoid hemorrhage (SAH). Also, it intended to systematically identify the risk factors of SAH and hemorrhagic stroke (HS) within a year after LT and to develop a scoring system which involves distinct clinical features of LT patients. METHODS: Patients who underwent LT from January 2012 to March 2022 were analyzed. All included patients underwent neurovascular imaging within 6 months before LT. We conducted an analysis of prevalence and radiological features of UIA and SAH. The clinical factors that may have an impact on HS within one year of LT were also reviewed. RESULTS: Total of 3,487 patients were enrolled in our study after applying inclusion and exclusion criteria. The prevalence of UIA was 5.4%. The incidence of SAH and HS within one year following LT was 0.5% and 1.6%, respectively. We developed a scoring system based on multivariable analysis to predict the HS within 1-year after LT. The variables were a poor admission mental status, the diagnosis of UIA, serum ammonia levels, and Model for End-stage Liver Disease (MELD) scores. Our model showed good discrimination among the development (C index, 0.727; 95% confidence interval [CI], 0.635-0.820) and validation (C index, 0.719; 95% CI, 0.598-0.801) cohorts. CONCLUSION: The incidence of UIA and SAH was very low in LT patients. A poor admission mental status, diagnosis of UIA, serum ammonia levels, and MELD scores were significantly associated with the risk of HS within one year after LT. Our scoring system showed a good discrimination to predict the HS in LT patients.

Red cell distribution width/platelet ratio estimates the 3-year risk of decompensation in Metabolic Dysfunction-Associated Steatotic Liver Disease-induced cirrhosis.

BACKGROUND: For compensated advanced chronic liver disease (cACLD) patients, the first decompensation represents a dramatically worsening prognostic event. Based on the first decompensation event (DE), the transition to decompensated advanced chronic liver disease (dACLD) can occur through two modalities referred to as acute decompensation (AD) and non-AD (NAD), respectively. Clinically Significant Portal Hypertension (CSPH) is considered the strongest predictor of decompensation in these patients. However, due to its invasiveness and costs, CSPH is almost never evaluated in clinical practice. Therefore, recognizing non-invasively predicting tools still have more appeal across healthcare systems. The red cell distribution width to platelet ratio (RPR) has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). However, its predictive role for the decompensation has never been explored. AIM: In this observational study, we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients. METHODS: Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up (FUP) semiannually for 3 years. At baseline, biochemical, clinical, and Liver Stiffness Measurement (LSM), Child-Pugh (CP), Model for End-Stage Liver Disease (MELD), aspartate aminotransferase/platelet count ratio index (APRI), Fibrosis-4 (FIB-4), Albumin-Bilirubin (ALBI), ALBI-FIB-4, and RPR were collected. During FUP, DEs (timing and modaities) were recorded. CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines. RESULTS: Of 150 MASLD-related cACLD patients, 43 (28.6%) progressed to dACLD at a median time of 28.9 months (29 NAD and 14 AD). Baseline RPR values were significantly higher in cACLD in comparison to controls, as well as MELD, CP, APRI, FIB-4, ALBI, ALBI-FIB-4, and LSM in dACLD-progressing compared to cACLD individuals [all P < 0.0001, except for FIB-4 (P: 0.007) and ALBI (P: 0.011)]. Receiving operator curve analysis revealed RPR > 0.472 and > 0.894 as the best cut-offs in the prediction respectively of 3-year first DE, as well as its superiority compared to the other non-invasive tools examined. RPR (P: 0.02) and the presence of baseline-CSPH (P: 0.04) were significantly and independently associated with the DE. Patients presenting baseline-CSPH and RPR > 0.472 showed higher risk of decompensation (P: 0.0023). CONCLUSION: Altogether these findings suggest the RPR as a valid and potentially applicable non-invasive tool in the prediction of timing and modalities of decompensation in MASLD-related cACLD patients.

Low Mean Perfusion Pressure Indexed to Body Surface Area is a Powerful Predictor of Poor Outcomes After Heart Transplantation in Patients With High Pre-Transplant Venous Pressure: A Clinical Study With Physiological Insights From Mathematical Modelling of Biventricular Heart Failure.

BACKGROUND & AIM: The deleterious consequences of chronically elevated venous pressure in patients with profound right ventricular or biventricular dysfunction are well known, including renal and hepatic dysfunction, and volume overload. The only option for these patients, if they fail optimal medical treatment, is a heart transplant, as they are not candidates for left ventricular assist device therapy. Mean perfusion pressure (MPP) is important in the outcomes of critically ill patients with high venous pressure. The question arises whether MPP is important for the outcomes of heart transplants in patients with elevated pre-transplant venous pressure. Medical management of heart failure patients with reduced ejection fraction involves lowering the systemic afterload with vasodilators while awaiting a transplant. We hypothesised that when venous pressure is elevated prior to transplant, a substantial reduction in systemic arterial elastance (Ea) through vasodilation may significantly decrease MPP, resulting in compromised end-organ function and consequent unfavourable outcomes after heart transplantation. This study aims to investigate whether a low MPP serves as a risk factor for adverse outcomes in heart transplant recipients with high venous pressure. METHOD: A retrospective analysis was conducted on 250 heart transplant recipients undergoing isolated heart transplantation at a single institution from October 2012 to March 2020. Right atrial pressure (RAP) of more than 15 mmHg was considered high. Additionally, Ea calculated as the ratio of end-systolic pressure to stroke volume, and MPP calculated as the difference between mean arterial pressure and RAP were considered in our analysis. The outcomes of transplantation were measured in terms of 90-day mortality and survival up to 7 years. RESULTS: High RAP was a significant risk factor for short-term and medium-term survival if Ea was low (<2.7 mmHg/mL, the median value). This group had 39.39% in-hospital mortality compared to 14.49% for RAP<15 mmHg (p∼0.005). When Ea was high, this difference in survival was not evident: 8% for RAP<15 mmHg vs 4.8% for RAP>15 mmHg (p∼0.550). This effect was mediated through a lower MPP, and the mortality due to lower MPP increased strikingly with higher body surface area (BSA). A negative correlation was observed between MPP indexed to BSA (MPPI) and the Model for End-Stage Liver Disease score (r∼-0.3580, p<0.0001) as well as creatinine (r∼-0.3551, p<0.0001). MPPI less than 40 mmHg/m2 was associated with poorer short-term (23.2% for MPPI<40 mmHg/m2 vs 7.1% for MPPI>40 mmHg/m2, p∼0.001) and medium-term survival. The impact of high RAP and low Ea on survival was evident even on medium-term follow-up; only 30% survival at 7 years follow-up for high RAP and low Ea vs 75% for RAP<15 mmHg (p∼0.0033). CONCLUSION: The acceptable blood pressure during vasodilator therapy in patients with high RAP needs to be higher, especially in those with higher BSA. MPPI less than 40 mmHg/m2 is a risk factor for survival, in the short and medium-term, after heart transplantation.

[Epidemiological characteristics of inpatients with liver failure at the Beijing You'an Hospital from 2012 to 2021].

Objective: To elucidate the epidemiological characteristics and changing trends of liver failure in order to provide evidence-based strategies for prevention and treatment. Methods: The epidemiological information of inpatients with liver failure admitted and treated at Beijing You'an Hospital from 2012 to 2021 was retrospectively collected. The trend test was used to analyze age, gender, as well as the year-by-year changes in the underlying acute and chronic etiology of acute liver failure (ALF), sub-acute liver failure (SALF), acute-on-chronic liver failure (ACLF), and chronic liver failure (CLF). Results: During the study period, information on a total of 8512 inpatients, aged 51.3±13.5 years and mainly male (71.9%) with liver failure, was collected. The highest to lowest proportions of liver failure types were ACLF 4 023 (47.3%), CLF 3 571(42.0%), SALF 670 (7.9%), and ALF 248 (2.9%). The top five causes of liver failure in the overall population, accounting for 87.6% of the total, were hepatitis B 3 199 (37.58%), alcoholic liver disease 2 237 (26.28%), cryptogenic liver disease 906(10.61%), hepatitis B + alcoholic liver disease 603 (7.08%), drugs 488 (5.73%), The top three etiologies of patients with different types of liver failure were acute etiologies for acute liver failure (ALF), followed by drugs 107 (43.1%), hepatitis B 47(19.0%), and unknown etiology 36 (14.5%); sub-acute liver failure (SALF), followed by drugs 381(56.9%), unknown etiology 106 (15.8%), and sepsis 56 (8.4%); and acute-on-chronic liver failure (ACLF), followed by drugs 2 092(52.0%), alcoholic liver disease 813(20.2%), and cryptogenic liver disease 398(9.9%); and chronic etiologies for chronic liver failure (CLF), followed by alcoholic liver disease 1 410(39.5%), hepatitis B 1 028(28.8%), and cryptogenic liver disease 364(10.2%). Longitudinal analysis showed that the average age of patients with liver failure increased year by year, but the sex ratio trend did not change significantly, with male patients predominating throughout. The proportion of drug-induced liver failure in patients with ALF and SALF increased year by year, and the difference in the trend test was statistically significant (P < 0.05). The proportion of patients with chronic etiologies of ACLF and CLF decreased year by year among hepatitis B, while the proportion of alcoholic liver disease, autoimmune liver disease, and cryptogenic liver disease increased year by year (the difference was statistically significant, P < 0.05). Conclusion: The etiological spectrum of liver failure is changing in our country. Although hepatitis B is still the main cause of liver failure, its proportion shows a decreasing trend year by year, with the exception of ACLF, which is no longer the primary etiology of other types of liver failure, while drug-induced liver disease, alcoholic liver disease, autoimmune liver disease, and cryptogenic liver disease are increasing year by year and will become the focus of liver disease prevention and treatment in the future.

Predictors and Outcomes of Post-transjugular Intrahepatic Portosystemic Shunt Liver Failure in Patients with Cirrhosis.

BACKGROUND: Post-transjugular intrahepatic portosystemic shunt (TIPS) liver failure (PTLF) is a serious complication of TIPS procedure with poor patient prognosis. This study tried to investigate the incidence of PTLF following elective TIPS procedure and evaluated possible predictive factors for the same. METHODS: A retrospective analysis of patients who underwent elective TIPS placement between 2012 and 2022 and was conducted to determine development of PTLF (≥ 3-fold bilirubin and/or ≥ 2-fold INR elevation from the baseline) within 30 days following TIPS procedure. Medical record review was done and factors predicting development of PTLF and the 90-day transplant-free survival was determined. RESULTS: Thirty of 352 (8.5%) patients developed PTLF within 30 days of TIPS (mean age 54.2 ± 9.8 years, 83% male). The etiology of cirrhosis was related to non-alcoholic steatohepatitis (NASH) in 50%, alcohol in 33.3%, and hepatitis B/C virus infection in 16.7% of the patients. The mean Child-Turcotte-Pugh (CTP) score was 9.5 ± 1.2 and mean model for end stage liver disease (MELD) score was 14.6 ± 4.5 at the time of admission in patients who developed PTLF. The indication for TIPS was recurrent variceal bleed in 50% (15 of 30) and refractory ascites in 46.7% (14 of 30) patients with PTLF. Multivariate analysis identified prior HE (OR 6.1; CI 2.57-14.5, p < 0.0001) and higher baseline CTP score (OR 1.47; CI 1.07-2.04; p = 0.018) as predictors of PTLF. PTLF was associated with significantly lower 90-day transplant-free survival, as compared to patients without PTLF (40% versus 96%, p < 0.001). CONCLUSION: Almost 10% of patients with cirrhosis develop post-TIPS liver failure and is associated with significant early mortality and morbidity. Higher baseline CTP score and prior HE were identified as predictors for PTLF.

'Effects of a home-based bimodal lifestyle intervention in frail patients with end-stage liver disease awaiting orthotopic liver transplantation': study protocol of a non-randomised clinical trial.

INTRODUCTION: Patients with end-stage liver disease awaiting orthotopic liver transplantation (OLT) are generally classified as frail due to disease-related malnutrition and a progressive decline in musculoskeletal and aerobic fitness, which is associated with poor pre-OLT, peri-OLT and post-OLT outcomes. However, frailty in these patients may be reversable with adequate exercise and nutritional interventions. METHODS AND ANALYSIS: Non-randomised clinical trial evaluating the effect of a home-based bimodal lifestyle programme in unfit patients with a preoperative oxygen uptake (VO2) at the ventilatory anaerobic threshold ≤13 mL/kg/min and/or VO2 at peak exercise ≤18 mL/kg/min listed for OLT at the University Medical Center Groningen (UMCG). The programme is patient tailored and comprises high-intensity interval and endurance training, and functional exercises three times per week, combined with nutritional support. Patients will go through two training periods, each lasting 6 weeks.The primary outcome of this study is the impact of the programme on patients' aerobic fitness after the first study period. Secondary outcomes include aerobic capacity after the second study period, changes in sarcopenia, anthropometry, functional mobility, perceived quality of life and fatigue, incidence of hepatic encephalopathy and microbiome composition. Moreover, number and reasons of intercurrent hospitalisations during the study and postoperative outcomes up to 12 months post OLT will be recorded. Finally, feasibility of the programme will be assessed by monitoring the participation rate and reasons for non-participation, number and severity of adverse events, and dropout rate and reasons for dropout. ETHICS AND DISSEMINATION: This study was approved by the Medical Research Ethics Committee of the UMCG (registration number NL83612.042.23, August 2023) and is registered in the Clinicaltrials.gov register (NCT05853484). Good Clinical Practice guidelines and the principles of the Declaration of Helsinki will be applied. Results of this study will be submitted for presentation at (inter)national congresses and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05853484.

Association of non-selective ß blockers with the development of renal dysfunction in liver cirrhosis: a systematic review and meta-analysis.

BACKGROUND & AIMS: Non-selective ß blockers (NSBBs) may negatively influence renal function through decreasing heart rate and cardiac output. This study aimed to systematically investigate their association. METHODS: PubMed, EMBASE, and Cochrane library databases were searched to identify all relevant studies evaluating the association of NSBBs with renal dysfunction in cirrhotic patients. Unadjusted and adjusted data were separately extracted. Odds ratios (ORs) and hazard ratios (HRs) were pooled. Subgroup meta-analyses were performed according to the proportions of ascites and Child-Pugh class B/C and the mean model for end-stage liver disease (MELD) score. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework. RESULTS: Fourteen studies were finally included. Based on unadjusted data, NSBBs significantly increased the risk of developing renal dysfunction (OR = 1.49; p = 0.03), and this association remained significant in subgroup analyses of studies where the proportions of ascites was >70% and Child-Pugh class B/C was 100%. Based on adjusted data with propensity score matching (adjusted OR = 0.61; p = 0.08) and multivariable regression modelling (adjusted HR = 0.86; p = 0.713), NSBBs did not increase the risk of developing renal dysfunction, and this association remained not significant in subgroup analyses of studies where the proportions of ascites was >70% and <70%, the proportion of Child-Pugh class B/C was <100%, and the mean MELD score was <15. The quality of evidence was very low for all meta-analyses. CONCLUSIONS: NSBBs may not be associated with the development of renal dysfunction in liver cirrhosis. However, more evidence is required to clarify their association in specific populations.

Non-selective ß blockers (NSBBs) may negatively influence renal function through decreasing heart rate and cardiac output in liver cirrhosis.Our meta-analysis failed to support the association of NSBBs with an increased risk of developing renal dysfunction after covariate adjustment.

Effects of Psychological Nursing Combined with Comprehensive Nursing on Gastrointestinal Bleeding and Nutritional Status in Cirrhosis.

Objective: Cirrhosis of the upper GIB is a surgical emergency, PN and CN can reduce the risk of gastrointestinal bleeding, but there is a lack of analysis on PN combined with CN in Cirrhotic patients. This work explored the effects of psychological nursing (PN) combined with comprehensive nursing (CN) on gastrointestinal bleeding (GIB) and nutritional status of patients with cirrhosis. Methods: Total 80 patients with GIB and cirrhosis who received emergency treatment in the Affiliated Hospital of Shaoxing University from October 2019 to October 2022 were randomly rolled into two groups. Patients in the control group (Ctrl group) received CN (n = 40 cases), and those in the experimental group (Exp group) received PN combined CN (n = 40 cases). The Model for end-stage liver disease (MELD) score, self-rating anxiety scale (SAS), self-rating depression scale (SDS), SCL-90, complication rate, and nursing satisfaction of patients from different groups were analyzed and compared. MELD score effectively predicts short - and medium-term mortality in end-stage liver disease. SAS consisted of 20 questions related to anxiety symptoms, four-level scoring method was adopted. The SCL-90 scale included four aspects: somatic symptoms, interpersonal relationships, psychological emotions, and psychological needs. Results: The results disclosed that after nursing intervention, SAS, SDS, and MELD scores in the Exp group were remarkably lower than those in the Ctrl group (P < .05). The scores of SCL-90 somatic symptoms, interpersonal relationships, psychological emotion, and psychological needs of participants in the Exp group were much lower than those in the Ctrl group (P < .05). The complication rate was significantly lower in the Exp (30.0%) than in the Ctrl groups (72.5%) (P < .05). The total nursing satisfaction was increased, and it is significan higher in the Exp group (97.5%) than control group (87.5% ) (P < .05). Conclusions: In conclusion, PN combined with CN could effectively reduce the incidence of complications in patients with GIB and cirrhosis and improve nursing satisfaction. Therefore, such a method was worth promoting, which provides a reference for the clinical diagnosis and treatment of patients with GIB and cirrhosis.

Perioperative proximal splenic artery embolization in cirrhotic patients with splenomegaly.

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

Clinical characteristics and prognosis of hospitalized patients with moderate alcohol-associated hepatitis.

BACKGROUND AND AIMS: Little is known about the clinical characteristics and prognosis of hospitalized patients with moderate alcohol-associated hepatitis (mAH) as compared to severe alcohol-associated hepatitis (sAH). Therefore, we aimed to describe the clinical characteristics and risk factors associated with mortality in hospitalized mAH patients. METHODS: Patients hospitalized with alcohol-associated hepatitis (AH) from 1 January 2010 to 31 December 2020 at a large US healthcare system [11 hospitals, one liver transplant centre] were retrospectively analysed for outcomes. Primary outcome was 90-day mortality. AH and mAH were defined according to NIAAA Alcoholic Hepatitis Consortia and Model for End-stage Liver Disease Score ≤ 20 respectively. Multivariable Cox regression analysis was performed to identify independent risk factors associated with 90-day mortality. RESULTS: 1504 AH patients were hospitalized during the study period, of whom 39% (n = 590) had mAH. Compared to sAH patients, mAH patients were older (50 vs. 48 years, p < 0.001) and less likely to have underlying cirrhosis (74% vs. 83%, p < 0.001). There were no differences between the two groups for median alcohol intake g/day (mAH 140.0 vs. sAH 112.0, p = 0.071). The cumulative proportion surviving at 90 days was 88% in mAH versus 62% in sAH (p < 0.001). On multivariable analysis, older age [HR 1.03 (95% CI 1.00-1.06), p = 0.020], corticosteroid use [HR 1.80 (95% CI 1.06-3.06), p = 0.030] and acute kidney injury (AKI) [HR 2.43 (95% CI 1.33-4.47), p = 0.004] were independently associated with 90-day mortality. CONCLUSIONS: mAH carries a 12% mortality rate at 90 days. Age, AKI and corticosteroid use were associated with an increased risk for 90-day mortality. Avoidance of corticosteroids and strategies to reduce the risk of AKI could improve outcomes in mAH patients.

Underrecognition and Suboptimal Quality of Care for Nonalcoholic Fatty Liver Disease Cirrhosis in Primary Care Patients with Diabetes Mellitus.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of cirrhosis but is underrecognized in primary care. Cirrhosis management requires complex monitoring, and the quality of care (QoC) for NAFLD cirrhosis patients in primary care may be inadequate. METHODS: In this retrospective-prospective cohort study of primary care patients with diabetes mellitus, we identified patients with NAFLD cirrhosis by 1) evidence of cirrhosis from abdominal imaging identified by natural language processing, or 2) existence of International Classification of Diseases code for cirrhosis. A finding of either was followed by manual chart review for confirmation of both cirrhosis and NAFLD. We then determined if cirrhosis care measures were up-to-date, including hepatitis A and B vaccination, Model for End-Stage Liver Disease score components, esophagogastroduodenoscopy, and hepatocellular carcinoma screening. We created a composite score quantifying overall QoC (scale 0-8), with high QoC defined as ≥6 points. RESULTS: Among 3,028 primary care patients with diabetes mellitus, we identified 51 (1.7%) with NAFLD cirrhosis. Although 78% had ≥3 average primary care visits/year, only 24% completed hepatocellular carcinoma screening at least annually in at least 75% of years since diagnosis. The average QoC composite score was 4.9 (SD 2.4), and less than one-third had high QoC. CONCLUSIONS: NAFLD cirrhosis is prevalent but underdiagnosed in primary care, and receipt of comprehensive QoC was suboptimal. Given the rising incidence of NAFLD cirrhosis, primary care providers need improved awareness and mechanisms to ensure high QoC for this population.

Liver transplantation for pediatric patients with congenital heart disease: A single-center study in mainland China.

BACKGROUND: Liver transplantation (LT) is a serious cardiovascular stressor for patients with end-stage liver disease (ESLD). Data on the effects of cardiovascular diseases on pediatric LT is limited. No study on LT for pediatric patients with ESLD combined with congenital heart disease (CHD) has been reported from mainland China. METHODS: A total of 1005 patients were included in this study. The Kaplan-Meier method with log-rank testing was used to evaluate survival outcomes between groups. Univariable and multivariable Cox regression models were used to determine the risk factors for patient and graft survival. RESULTS: The most common indication for LT was biliary atresia (BA 90.3%). The prevalence of CHD was 3.8% (38). 42 CHD were found in 38 patients. The incidence of death and graft loss was more common in the CHD group than in the no-CHD group (13.2% vs. 5.0%, p = .045 and 15.8% vs. 6.2%, p = .019, respectively). The 5-year patient survival and graft survival in the CHD group versus the no-CHD group was 86.8% versus 94.7% (log-rank p = .022) and 84.2% versus 93.5% (log-rank p = .015), respectively. No significant differences were observed in re-transplantation, hepatic artery thrombosis (HAT), and portal vein thrombosis (PVT). After adjusting for age, BMI, etiology of LT, and other confounding factors, we can still find that the presence of CHD was associated with patient and graft survival after LT. CONCLUSION: The presence of CHD was associated with higher mortality and lower graft survival after LT. If possible, the cardiac defects should be addressed prior to LT.

AGA Clinical Practice Update on the Use of Vasoactive Drugs and Intravenous Albumin in Cirrhosis: Expert Review.

DESCRIPTION: Cirrhosis is a major cause of morbidity and mortality in the United States and worldwide. It consists of compensated, decompensated, and further decompensated stages; median survival is more than 15 years, 2 years, and 9 months for each stage, respectively. With each stage, there is progressive worsening of portal hypertension and the vasodilatory-hyperdynamic circulatory state, resulting in a progressive decrease in effective arterial blood volume and renal perfusion. Vasoconstrictors reduce portal pressure via splanchnic vasoconstriction and are used in the management of variceal hemorrhage. Intravenous (IV) albumin increases effective arterial blood volume and is used in the prevention of acute kidney injury (AKI) and death after large-volume paracentesis and in patients with spontaneous bacterial peritonitis (SBP). The combination of vasoconstrictors and albumin is used in the reversal of hepatorenal syndrome (HRS-AKI), the most lethal complication of cirrhosis. Because a potent vasoconstrictor, terlipressin, was recently approved by the US Food and Drug Administration, and because recent trials have explored use of IV albumin in other settings, it was considered that a best practice update would be relevant regarding the use of vasoactive drugs and IV albumin in the following 3 specific scenarios: variceal hemorrhage, ascites and SBP, and HRS. METHODS: This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. It underwent internal peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Some of the statements are unchanged from published guidelines because of lack of new evidence in the literature. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality and evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Vasoactive drugs should be initiated as soon as the diagnosis of variceal hemorrhage is suspected or confirmed, preferably before diagnostic and/or therapeutic endoscopy. BEST PRACTICE ADVICE 2: After initial endoscopic hemostasis, vasoactive drugs should be continued for 2-5 days to prevent early rebleeding. BEST PRACTICE ADVICE 3: Octreotide is the vasoactive drug of choice in the management of variceal hemorrhage based on its safety profile. BEST PRACTICE ADVICE 4: IV albumin should be administered at the time of large-volume (>5 L) paracentesis. BEST PRACTICE ADVICE 5: IV albumin may be considered in patients with SBP. BEST PRACTICE ADVICE 6: Albumin should not be used in patients (hospitalized or not) with cirrhosis and uncomplicated ascites. BEST PRACTICE ADVICE 7: Vasoconstrictors should not be used in the management of uncomplicated ascites, after large-volume paracentesis or in patients with SBP. BEST PRACTICE ADVICE 8: IV albumin is the volume expander of choice in hospitalized patients with cirrhosis and ascites presenting with AKI. BEST PRACTICE ADVICE 9: Vasoactive drugs (eg, terlipressin, norepinephrine, and combination of octreotide and midodrine) should be used in the treatment of HRS-AKI, but not in other forms of AKI in cirrhosis. BEST PRACTICE ADVICE 10: Terlipressin is the vasoactive drug of choice in the treatment of HRS-AKI and use of concurrent albumin can be considered when accounting for patient's volume status. BEST PRACTICE ADVICE 11: Terlipressin treatment does not require intensive care unit monitoring and can be administered intravenously through a peripheral line. BEST PRACTICE ADVICE 12: Terlipressin use is contraindicated in patients with hypoxemia and in patients with ongoing coronary, peripheral, or mesenteric ischemia, and should be used with caution in patients with acute-on-chronic liver failure grade 3. The benefits may not outweigh the risks in patients with serum creatinine >5 mg/dL and in patients listed for transplantation with a Model for End-stage Liver Disease ≥35.

Sex-based Disparities in Access to Liver Transplantation for Waitlisted Patients With Model for End-stage Liver Disease Score of 40.

OBJECTIVE: To determine the association of sex with access to liver transplantation among candidates with the highest possible model for end-stage liver disease score (MELD 40). BACKGROUND: Women with end-stage liver disease are less likely than men to receive liver transplantation due in part to MELD's underestimation of renal dysfunction in women. The extent of the sex-based disparity among patients with high disease severity and equally high MELD scores is unclear. METHODS: Using national transplant registry data, we compared liver offer acceptance (offers received at match MELD 40) and waitlist outcomes (transplant vs death/delisting) by sex for 7654 waitlisted liver transplant candidates from 2009 to 2019 who reached MELD 40. Multivariable logistic and competing-risks regression was used to estimate the association of sex with the outcome and adjust for the candidate and donor factors. RESULTS: Women (N = 3019, 39.4%) spent equal time active at MELD 40 (median: 5 vs 5 days, P = 0.28) but had lower offer acceptance (9.2% vs 11.0%, P < 0.01) compared with men (N = 4635, 60.6%). Adjusting for candidate/donor factors, offers to women were less likely accepted (odds ratio = 0.87, P < 0.01). Adjusting for candidate factors, once they reached MELD 40, women were less likely to be transplanted (subdistribution hazard ratio = 0.90, P < 0.01) and more likely to die or be delisted (subdistribution hazard ratio = 1.14, P = 0.02). CONCLUSIONS: Even among candidates with high disease severity and equally high MELD scores, women have reduced access to liver transplantation and worse outcomes compared with men. Policies addressing this disparity should consider factors beyond MELD score adjustments alone.

Systemic Complications Secondary to Chronic Liver Disease.

The systemic sequelae of chronic liver disease (CLD) may be due to portal hypertension and shunting, malnutrition, and/or a low grade inflammatory state. This article will focus on the consequences of chronic liver disease affecting extrahepatic organs. Portal hypertension underlies many systemic complications of CLD. Aside from varices and ascites, portal hypertension may cause both hepatopulmonary syndrome and portopulmonary hypertension leading to respiratory compromise. Cardiomyopathy may also occur secondary to end stage liver disease. Hepatorenal syndrome is also well recognised and hepatic encephalopathy is a consequence of the effect of liver dysfunction on the brain. Compromise of the immune system is well described in end-stage liver disease leading to sepsis and its consequences. Bony disease including osteoporosis and hepatic arthropathy may both be seen in children with CLD. CLD may be asymptomatic initially but then complications may present as the disease progresses. Furthermore, systemic effects of end stage liver disease may complicate liver transplant. These complications often present insidiously or at the time of acute decompensation. Thus, it is important that healthcare providers are vigilant when caring for children with CLD. This article outlines the secondary complications of CLD with an overview of the definition and diagnosis, pathophysiology, management and prognosis of each.

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

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

Preoperative low muscle mass and early postoperative outcomes in children undergoing living donor liver transplantation: A retrospective study.

Low skeletal muscle mass may develop in children with end-stage liver disease, affecting postoperative outcomes. We retrospectively investigated whether preoperative low muscle mass was associated with early postoperative outcomes in pediatric patients undergoing living donor liver transplantation (LDLT). Electronic medical records of children (age below 12 y) who underwent LDLT between February 1, 2007, and January 31, 2018, were reviewed. The cross-sectional areas of psoas, quadratus lumborum, and erector spinae muscles at the level of fourth-fifth lumbar intervertebral disks were measured using abdominal CT images, divided by the square of the height and were added to obtain the total skeletal muscle index (TSMI). The patients were divided into two groups according to the median TSMI in the second quintile (1859.1 mm 2 /m 2 ). Complications in the early postoperative period (within 30 d after surgery) classified as Clavien-Dindo grade 3 or higher were considered major complications. Logistic regression analyses were performed to determine the association between preoperative low muscle mass and early postoperative outcomes. In the study population of 123 patients (median age, 14 mo; range, 8-38 mo) who underwent LDLT, 29% and 71% were classified in the low (mean TSMI, 1642.5 ± 187.0 mm 2 /m 2 ) and high (mean TSMI 2188.1 ± 273.5 mm 2 /m 2 ) muscle mass groups, respectively. The rates of major complications, mechanical ventilation >96 hours, intensive care unit stay >14 days, hospital stay >30 days, and in-hospital mortality were not significantly different between the 2 groups. Additionally, adverse outcomes according to pediatric end-stage liver disease scores and sex were not significantly different between the 2 groups. In conclusion, preoperative low muscle mass defined by TSMI was not associated with early postoperative outcomes in pediatric patients undergoing LDLT.

Risk factors for pre-transplantation bacteremia in adults with end-stage liver disease: Effects on outcomes of liver transplantation.

BACKGROUND AND AIM: Limited data are available regarding pre-liver transplantation (LT) bacteremia in adults with end-stage liver disease. In this study, we investigated the risk factors independently associated with pre-LT bacteremia and their effects on clinical outcomes of LT. METHODS: This retrospective study performed between 2010 and 2021 included 1287 LT recipients. The study population was categorized into patients with pre-LT bacteremia and those without pre-LT infection. Pre-LT bacteremia was defined as bacteremia detected within 90 days before LT. RESULTS: Among 1287 LT recipients, 92 (7.1%) developed pre-LT bacteremia. The mean interval between bacteremia and LT was 28.3 ± 19.5 days. Of these 92 patients, seven (7.6%) patients died after LT. Of the 99 microorganisms isolated in this study, gram-negative bacteria were the most common microbes (72.7%). Bacteremia was mainly attributed to spontaneous bacterial peritonitis. The most common pathogen isolated was Escherichia coli (25.2%), followed by Klebsiella pneumoniae (18.2%), and Staphylococcus aureus (15.1%). Multivariate analysis showed that massive ascites (adjusted odds ratio [OR] 1.67, 95% confidence Interval [CI] 1.048-2.687) and a prolonged international normalized ratio for prothrombin time (adjusted OR 1.13, 95% CI 1.074-1.257) were independent risk factors for pre-LT bacteremia in patients with end-stage liver disease. Intensive care unit and in-hospital stay were significantly longer, and in-hospital mortality was significantly higher among LT recipients with pre-LT bacteremia than among those without pre-LT infection. CONCLUSIONS: This study highlights predictors of pre-LT bacteremia in patients with end-stage liver disease. Pre-LT bacteremia increases the post-transplantation mortality risk.