Retos y estrategias en el manejo de la trombosis de la vena porta / Challenges and strategies in the management of portal vein thrombosis

La trombosis de la vena porta (TVP) en pacientes con o sin cirrosis hepática (CH) se define como una obstrucción de la vena porta debido a la formación de un trombo que puede extenderse a las venas mesentéricas superiores y esplénica. Esta es una complicación común de la enfermedad hepática avanzada. Se creía que la TVP se producía predominantemente debido al potencial protrombótico del paciente con CH, ya que se observaba una mayor incidencia de TVP en CH con una puntuación MELD y Child-Pugh más altas, con una prevalencia informada del 10 % al 25%.

Portal vein thrombosis (PVT) in patients with or without hepatic cirrhosis (CH) is defined as an obstruction of the portal vein due to the formation of a thrombus that may extend to the superior mesenteric and splenic veins. This is a common complication of advanced liver disease. It was believed that PVT predominantly occurred due to the prothrombotic potential of the patient with CH, as a higher incidence of PVT was observed in CH with higher MELD and Child-Pugh scores, with a reported prevalence of 10% to 25%.

Interaction between coagulation and inflammatory system in liver disease: re-focus on hematological markers.

Aim: This study uses blood routine, coagulation and biochemical indicators to explore the relationship between the hematological parameters of patients with various types of liver diseases.Methods: The Kruskal-Wallis, Chi-squared and Fisher exact tests were used to compare the hematological parameters and clinical characteristics of three groups of patients with different degrees of liver disease. Spearman correlation analysis is used to analyze the correlation between two continuous variables. The logistic regression model evaluated the odds ratio between variables and disease changes. Receiver operating characteristic curve analysis was used to understand the predictive value of each index in relation to the progress of liver disease.Results: There are differences in inflammation and coagulation profiles among different types of liver diseases and there is a correlation between them. In addition to the traditional marker α-fetoprotein, the inflammatory marker c-reactive protein and the coagulation marker D-dimer also have good diagnostic value for liver injury.Conclusion: The coagulation and inflammation systems interact, are connected and play essential roles in the liver.

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Hepatic recompensation according to the Baveno VII criteria via a transjugular intrahepatic portosystemic shunt: Is this true?

Hepatic recompensation is firstly described in the Baveno VII criteria, which requires the fulfillment of strict criteria. First, a primary cause of cirrhosis must be addressed, suppressed, or cured. Second, complications of liver cirrhosis, including ascites, encephalopathy, and variceal hemorrhage, must disappear without any intervention. Finally, liver function indicators must be improved. Moreover, without addressing/suppressing/curing cirrhosis and improvement in liver synthetic function, complications, including ascites and variceal hemorrhage can be improved by a transjugular intrahepatic portosystemic shunt (TIPS), which is not evidence of hepatic recompensation. Therefore, on the basis of the definition of hepatic recompensation, TIPS does not achieve hepatic recompensation.

Strategy and Outcomes of Cardiac Surgery in Patients With Cirrhosis: Comprehensive Approach With Liver Transplant Program.

BACKGROUND: Cardiac surgery is considered a contraindication in patients with advanced liver cirrhosis (LC) due to increased mortality and morbidity. There are limited data on the treatment strategy and management of this population. We aimed to present our strategy and evaluate the clinical outcome of cardiac surgery in patients with LC. METHODS: Our strategy was (i) to list patients for liver transplant (LT) at the time of cardiac surgery; (ii) to maintain high cardiopulmonary bypass (CPB) flow (index up to 3.0 L/min/m2) based on hyper-dynamic states due to LC; and (iii) to proceed to LT if patients' liver function deteriorated with an increasing model for end-stage liver disease Na (MELD-Na) score after cardiac surgery. Thirteen patients (12 male and 1 female [mean age, 63.0]) with LC who underwent cardiac surgery between 2017 and 2024 were retrospectively analyzed. RESULTS: Six patients were listed for LT. Indications for cardiac surgery included coronary artery disease (N = 7), endocarditis (N = 2), and tricuspid regurgitation (N = 1), tricuspid stenosis (N = 1), mitral regurgitation (N = 1), and hypertrophic obstructive cardiomyopathy (N = 1). The Child-Pugh score was A in five, B in six, and C in one patient. The procedure included coronary artery bypass grafting (N = 6), single valve surgery (mitral valve [N = 2] and tricuspid valve [N = 1]), concomitant aortic and tricuspid valve surgery (N = 2), and septal myectomy (N = 1). Two patients had a history of previous sternotomy. The perfusion index during CPB was 3.1 ± 0.5 L/min/m2. Postoperative complications include pleural effusion (N = 6), bleeding events (N = 3), acute kidney injury (N = 1), respiratory failure requiring tracheostomy (N = 2), tamponade (N = 1), and sternal infection (N = 1). There was no in-hospital death. There was one remote death due to COVID-19 complication. Preoperative and postoperative highest MELD-Na score among listed patients was 15.8 ± 5.1 and 19.3 ± 5.3, respectively. Five patients underwent LT (1, 5, 8, 16, and 24 months following cardiac surgery) and one patient remains on the list. Survival rates at 1 and 3 years are 100% and 75.0%, respectively. CONCLUSION: Cardiac surgery maintaining high CPB flow with LT backup is a feasible strategy in an otherwise inoperable patient population with an acceptable early and midterm survival when performed in a center with an experienced cardiac surgery and LT program.

Recompensation after TIPS reduces the incidence of hepatocellular carcinoma and increases survival in patients with cirrhosis.

BACKGROUND AND AIMS: It has been described that recompensation can improve prognosis in patients with cirrhosis. However, recompensation after transjugular intrahepatic portosystemic shunt (TIPS) has not been studied. We evaluated the impact of recompensation after TIPS on the risk of hepatocellular carcinoma (HCC) and death, and we compared it with compensated cirrhosis patients. METHODS: An observational study of consecutive patients with cirrhosis undergoing TIPS between 2008 and 2022 was performed. Baveno VII definition of recompensation was used including patients with or without diuretics/Hepatic encephalopathy prophylaxis. A prospective cohort of consecutive compensated cirrhosis patients was used for comparison. RESULTS: Overall, 208 patients with cirrhosis were included, 92 compensated and 116 decompensated who underwent TIPS. After 1 year, 24% achieved recompensation. Liver function (MELD 12 ± 5 vs. 15 ± 6; p = .049), LDL-cholesterol (97 mg/dL vs. 76 mg/dL, p = .018), white cell count (7.96 × 109/dL vs. 6.24 × 109/dL, p = .039) and platelets (129 × 109/dL vs. 101 × 109/dL, p = .039) were associated with recompensation. Recompensation was associated with a reduction in the risk of HCC (p = .020). Multivariable analysis showed that this risk was significantly higher in non-recompensated patients (p = .003) but no differences were observed in recompensated compared with compensated patients (p = .816). Similarly, decompensated patients presented lower survival rates (p = .011), while no differences were observed between recompensated and compensated patients (p = .677). CONCLUSIONS: Recompensation after TIPS has a clear impact on the incidence of HCC and death, with a similar prognosis than patients with compensated cirrhosis. Liver function is associated with recompensation, suggesting the importance of considering early TIPS in patients with indication.

Burden of alcohol use disorder and its consequences in Iran from 1990 to 2019: Findings from the global burden of disease study.

Background: This study aimed to provide an up-to-date evaluation of the burden of alcohol use disorder and its consequences in Iran from 1990 to 2019. Methods: We assessed the burden of alcohol use disorder and its three subsequent disorders, including cirrhosis and other chronic liver diseases, liver cancer, and cardiomyopathy using Global Burden of Disease (GBD) data. We retrieved data on incidence, prevalence, death, Years of Life Lost from mortality (YLL), Years of healthy life Lost due to Disability (YLD), and Disability-Adjusted Life Year (DALY), which is calculated by summing YLL and YLD values, indices, as well as sociodemographic index (SDI) values. Results: Age-standardized DALY rate of alcohol use disorder reduced from 55.5 in 1990 to 41.8 per 100,000 in 2019 (-24.1 %). Similarly, age-standardized DALY rates of cirrhosis due to alcohol use (-28.7 %), liver cancer due to alcohol use (-20.9 %), and alcoholic cardiomyopathy (-36.3 %) decreased in Iran from 1990 to 2019. In 2019, alcohol use disorder had the highest DALY rate among individuals younger than 55 years, while cirrhosis due to alcohol use imposed the greatest burden on those older than 55. After adjusting for the year, SDI was negatively associated with the age-standardized DALY rate of liver cancer due to alcohol use (p < 0.001), positively associated with that of alcoholic cardiomyopathy (p = 0.002), and not significantly associated with the burden of other conditions (p > 0.05). Conclusions: Despite reductions in the age-standardized DALY rate of alcohol use disorders and related consequences among Iranians, they remain a serious public health concern in Iran.

Fibrosis, biomarkers and liver biopsy in AAT deficiency and relation to liver Z protein polymer accumulation.

BACKGROUND AND AIMS: The course of adults with ZZ alpha-1-antitrypsin deficiency (AATD) liver disease is unpredictable. The utility of markers, including liver biopsy, is undefined. METHODS: A prospective cohort, including protocol liver biopsies, was enrolled to address these questions. RESULTS: We enrolled 96 homozygous ZZ AATD adults prospectively at three US sites with standardized clinical evaluations, and protocol liver biopsies. Fibrosis was scored using Ishak (stages 0-6). Also, 51% of the 96 subjects had Ishak score >1 fibrosis (49% Ishak 0-1, 36% Ishak 2-3 and 15% ≥4). Elevated aspartate aminotransferase (AST) more than alanine aminotransferase (ALT), high body mass index (BMI), obesity, AST platelet ratio index and elevated serum Z alpha 1 antitrypsin (AAT) polymer levels were associated with increased fibrosis. Steatosis did not correlate to fibrosis. Increased fibrosis was associated with increased mutant Z polymer globular inclusions (p = .002) and increased diffuse cytoplasmic Z polymer on biopsy (p = .0029) in a direct relationship. Increased globule Z polymer was associated with increased serum AST (p = .007) and increased periportal inflammation on histopathology (p = .004), but there was no relationship of Z polymer hepatocellular accumulation with ALT, gamma glutamine transferase, inflammation in other parts of the lobule, necrosis or steatosis. Serum Z polymer levels were directly correlated to hepatic Z protein polymer content. Lung function, smoking and alcohol consumption patterns were not associated with fibrosis. CONCLUSION: In AATD high BMI, obesity and elevated AST are associated with increased fibrosis. Liver biopsy features are correlated to some serum tests. Serum Z AAT polymer levels could be a future biomarker to detect fibrosis early and is directly correlated to liver Z content.

Liver-secreted FGF21 induces sarcopenia by inhibiting satellite cell myogenesis via klotho beta in decompensated cirrhosis.

BACKGROUND & AIMS: Sarcopenia, a prevalent condition, significantly impacts the prognosis of patients with decompensated cirrhosis (DC). Serum fibroblast growth factor 21 (FGF21) levels are significantly higher in DC patients with sarcopenia. Satellite cells (SCs) play a role in aging- and cancer-induced sarcopenia. Here, we investigated the roles of FGF21 and SCs in DC-related sarcopenia as well as the underlying mechanisms. METHODS: We developed two DC mouse models and performed in vivo and in vitro experiments. Klotho beta (KLB) knockout mice in SCs were constructed to investigate the role of KLB downstream of FGF21. In addition, biological samples were collected from patients with DC and control patients to validate the results. RESULTS: Muscle wasting and impaired SC myogenesis were observed in the DC mouse model and patients with DC. Elevated circulating levels of liver-derived FGF21 were observed, which were significantly negatively correlated with skeletal muscle mass/skeletal muscle index. Liver-secreted FGF21 induces SC dysfunction, contributing to sarcopenia. Mechanistically, FGF21 in the DC state exhibits enhanced interactions with KLB on SC surfaces, leading to downstream phosphatase and tensin homolog upregulation. This inhibits the protein kinase B (PI3K/Akt) pathway, hampering SC proliferation and differentiation, and blocking new myotube formation to repair atrophy. Neutralizing circulating FGF21 using neutralizing antibodies, knockdown of hepatic FGF21 by adeno-associated virus, or knockout of KLB in SCs effectively improved or reversed DC-related sarcopenia. CONCLUSIONS: Hepatocyte-derived FGF21 mediates liver-muscle crosstalk, which impairs muscle regeneration via the inhibition of the PI3K/Akt pathway, thereby demonstrating a novel therapeutic strategy for DC-related sarcopenia.

The effectiveness of exercise prehabilitation on aerobic capacity, muscle strength and body composition in patients with cirrhosis awaiting liver transplantation: a systematic review and meta-analysis protocol.

INTRODUCTION: Cirrhosis is the main cause of morbidity and mortality globally, accounting for approximately 1.2 million deaths annually. Impaired aerobic capacity, muscle wasting and reduced muscle strength are significant complications in patients with cirrhosis. Preoperative exercise intervention "prehabilitation" has been recognised as a potential approach to optimise muscle strength, aerobic capacity and body composition as well as quality of life in patients awaiting abdominal surgery. However, there is little evidence on the effects of preoperative exercise on older adults with cirrhosis and awaiting liver transplant. Thus, the primary objective of this systematic review and meta-analysis will be to assess the effects of exercise interventions in improving aerobic capacity, muscle strength and body composition of older adults with cirrhosis and awaiting liver transplant. METHODS AND ANALYSIS: This systematic review and metaanalysis protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review will include all peer-reviewed randomised controlled trials (RCTs), including cluster RCTs, controlled (non-controlled), complex clinical trials (CCTs) or cluster trials, cohort, observational studies published in English from inception until July 2024. The following electronic databases will be searched: MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO) and Scopus (Elsevier) and supplemented by a secondary screening of the reference lists of all included articles. Searches will involve studies with both male and female participants aged ≥ 18 years with cirrhosis and awaiting liver transplant. Primary outcomes will include muscle strength, and aerobic capacity. The secondary outcomes include body composition (e.g. body mass index, and thigh circumference). The Cochrane Collaboration Risk of Bias Tool will be used to evaluate quality of the studies and Review Manager (RevMan) V.5.3 (Copenhagen, Denmark: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Effect sizes will be expressed as a standardised mean difference, and their 95% confidence intervals will be calculated and presented as a forest plot. The standard χ2 and I2 tests will be used to test heterogeneity. CONCLUSION: This systematic review and meta-analysis is anticipated to provide meaningful and contemporary evidence on the effects of preoperative exercise in older adults living with cirrhosis and awaiting liver transplant. In addition, the findings will help clinicians with developing safe and effective preoperative exercise regimens for these patients.

Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities.

A consistent feature of chronic liver diseases and the hallmark of pathologic repair is the so-called ductular reaction. This is a histological abnormality characterized by an expansion of dysmorphic cholangiocytes inside and around portal spaces infiltrated by inflammatory, mesenchymal, and vascular cells. The ductular reaction is a highly regulated response based on the reactivation of morphogenetic signaling mechanisms and a complex crosstalk among a multitude of cell types. The nature and mechanism of these exchanges determine the difference between healthy regenerative liver repair and pathological repair. An orchestrated signaling among cell types directs mesenchymal cells to deposit a specific extracellular matrix with distinct physical and biochemical properties defined as portal fibrosis. Progression of fibrosis leads to vast architectural and vascular changes known as liver cirrhosis. The signals regulating the ecology of this microenvironment are just beginning to be addressed. Contrary to the tumor microenvironment, immune modulation inside this "benign" microenvironment is scarcely known. One of the reasons is that both the ductular reaction and portal fibrosis have been primarily considered a manifestation of cholestatic liver disease, whereas this phenomenon is also present, albeit with distinctive features, in all chronic human liver diseases. Novel human-derived cellular models and progress in "omics" technologies are increasing our knowledge at a fast pace. Most importantly, this knowledge is on the edge of generating new diagnostic and therapeutic advances. Here, we will critically review the latest advances, in terms of mechanisms, pathophysiology, and treatment prospects. In addition, we will delineate future avenues of research including innovative translational opportunities.

The negative effect of preexisting cirrhosis on blunt liver trauma patients: a multifaceted approach from the trauma quality improvement program database.

PURPOSE: To assess the impact of pre-existing cirrhosis on the outcomes of non-operatively managed blunt liver trauma within the Trauma Quality Improvement Program (TQIP) database. METHODS: A study of non-operatively managed blunt liver injury patients from 2016 to 2019 was conducted. Propensity score matching analyzed mortality, complications, and hospital length of stay (LOS) for patients with and without cirrhosis. The effect of transcatheter arterial embolization (TAE) was determined using multivariate logistic regression. RESULTS: Out of 63,946 patients, 767 (1.2%) had pre-existing cirrhosis. Following 1:1 matching, those with cirrhosis experienced more hemorrhage (TAE need: 5.7% vs. 2.7%; transfusion volume: 639.1 vs. 259.3 ml), complications (acute kidney injury: 5.1% vs. 2.8%; sepsis: 2.4% vs. 1.0%), and poorer outcomes (mortality: 19.5% vs. 10.2%; hospital LOS: 11.6 vs. 8.4 days; ICU LOS: 12.1 vs. 7.4 days; ventilator days: 7.6 vs. 1.6). Notably, TAE was associated with increased mortality in cirrhotic patients (odds ratio: 4.093) but did not significantly affect mortality in patients without cirrhosis. CONCLUSIONS: Within TQIP, pre-existing cirrhosis is a significant negative determinant for outcomes in blunt liver trauma. Cirrhotic patients undergoing TAE for hemostasis face greater mortality risk than non-cirrhotic counterparts.

Frailty and risk of metabolic dysfunction-associated steatotic liver disease and other chronic liver diseases.

BACKGROUND & AIMS: Frailty is associated with multiple morbidities. However, its effect on chronic liver diseases remains largely unexplored. This study evaluated the association of frailty with the risk of incident metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and liver-related mortality. METHODS: A total of 339,298 participants without prior liver diseases from the UK Biobank were included. Baseline frailty was assessed by using physical frailty and the frailty index, categorizing participants as nonfrail, prefrail, or frail. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, liver cancer, and liver-related mortality, confirmed through hospital admission records and death registries. RESULTS: During a median follow-up of 11.6 years, 4,667 MASLD, 1,636 cirrhosis, 257 liver cancer, and 646 liver-related mortality cases were identified. After multivariable adjustment, the risk of MASLD was found to be higher in participants with prefrailty (physical frailty: HR = 1.66, 95% CI = 1.40-1.97; frailty index: HR = 2.01, 95% CI = 1.67-2.42) and frailty (physical frailty: HR = 3.32, 95% CI = 2.54-4.34; frailty index: HR = 4.54, 95% CI = 3.65-5.66) than in those with nonfrailty. Similar results were also observed for cirrhosis, liver cancer, and liver-related mortality. Additionally, the frail groups had a higher risk of MASLD, which was defined as magnetic resonance imaging-derived liver proton density fat fraction > 5%, than the nonfrail group (physical frailty: OR = 1.64, 95% CI = 1.32-2.04; frailty index: OR = 1.48, 95% CI = 1.30-1.68). CONCLUSIONS: Frailty was associated with an increased risk of chronic liver diseases. Public health strategies should target reducing chronic liver disease risk in frail individuals. IMPACT AND IMPLICATIONS: While frailty is common and associated with a poor prognosis in people with MASLD and advanced chronic liver diseases, its impact on the subsequent risk of these outcomes remains largely unexplored. Our study showed that frailty was associated with the increased risks of MASLD, cirrhosis, liver cancer, and liver-related mortality. This finding suggests that assessing frailty may help identify a high-risk population vulnerable to developing chronic liver diseases. Implementing strategies that target frailty could have major public health benefits for liver-related disease prevention.

Liver fibrosis is closely linked with metabolic-associated diseases in patients with autoimmune hepatitis.

BACKGROUND: This cross-sectional study aimed to investigate the impact of metabolic-associated diseases (MADs) on patients with autoimmune hepatitis (AIH). METHODS: The study analyzed the clinical characteristics of 283 AIH patients who underwent liver biopsy between January 2016 and February 2022 in Ruijin Hospital, Shanghai, China. RESULTS: Among the identified AIH patients (n = 283), 87.3%, 23.0%, or 43.1% had MADs, non-alcoholic fatty liver disease (NAFLD), or severe fibrosis, respectively. The proportion of diabetes mellitus (DM) was significantly higher in patients with severe liver fibrosis than in those with mild or moderate fibrosis in the AIH cohort (31.1% vs. 18.0%, p < 0.05). Fibrosis was also more severe in patients with NAFLD than in those without (53.8% vs. 39.9%, p < 0.05). Age, Plts, IgG and the presence with MADs were identified as independent predictors of the severity of inflammation in AIH patients. Moreover, severe liver fibrosis (stages 3 to 4) was independently associated with male (OR, 2.855; p = 0.025), γ-GT (OR, 0.997; p = 0.007), and combination with MADs (OR, 4.917; p = 0.006). Furthermore, combination with DM was also an independent predictor of severe liver fibrosis in AIH patients (OR, 2.445, p = 0.038). CONCLUSIONS: Concurrent MADs, common in AIH patients, is an independent risk factor for severe fibrosis or inflammation; of note, combination with DM was also an independent predictor of severe liver fibrosis in AIH patients. While managing with AIH, routine assessment of co-existing MADs, especially DM, is also important.

Mesenchymal stem cell therapy for liver fibrosis need "partner": Results based on a meta-analysis of preclinical studies.

BACKGROUND: The efficacy of mesenchymal stem cells (MSCs) in treating liver fibrosis has been demonstrated in several clinical studies. However, their low survival and liver implantation rates remain problematic. In recent years, a large number of studies in animal models of liver fibrosis have shown that MSCs combined with drugs can improve the efficacy of MSCs in the treatment of liver fibrosis alone and inhibit its progression to end-stage liver disease. This has inspired new ways of thinking about treating liver fibrosis. AIM: To investigate the effectiveness and mechanisms of MSCs combined with drugs in treating liver fibrosis. METHODS: Data sources included four electronic databases and were constructed until January 2024. The subjects, interventions, comparators, outcomes, and study design principle were used to screen the literature, and the quality of the literature was evaluated to assess the risk of bias. Relevant randomised controlled trials were selected, and the final 13 studies were included in the final study. RESULTS: A total of 13 studies were included after screening. Pooled analysis showed that MSCs combined with drug therapy significantly improved liver function, promoted the repair of damaged liver tissues, reduced the level of liver fibrosis-related indexes, and effectively ameliorated hepatic fibrosis by modulating the hepatic inflammatory microenvironment, promoting the homing of MSCs, and regulating the relevant signaling pathways, and the treatment efficacy was superior to MSCs alone. However, the combined treatment statistics showed no ame-lioration in serum albumin levels (standardized mean difference = 0.77, 95% confidence interval: -0.13 to 1.68, P = 0.09). CONCLUSION: In conclusion, MSCs combined with drugs for treating liver fibrosis effectively make up for the shortcomings of MSCs in their therapeutic effects. However, due to the different drugs, the treatment mechanism and effect also differ. Therefore, more randomized controlled trials are needed to compare the therapeutic efficacy of different drugs in combination with MSCs, aiming to select the "best companion" of MSCs in treating hepatic fibrosis.

Inpatient Outcomes of Cirrhosis-related Cachexia in the United States.

Background and Aims: Cachexia is a metabolic syndrome defined by a loss of more than 5% of body weight in patients with chronic diseases. The goal of this study was to investigate the link between cirrhotic cachexia and hospital mortality and the 30-day risk of all-cause readmission. Methods: The study utilized Nationwide Readmission Database for the years 2016-2019 in which all patients older than 18 year old with a primary diagnosis of cirrhosis were included. We excluded patients with a concurrent diagnosis of Human Immunodeficiency Virus, chronic lung disease, end-stage renal disease, malignancy, heart failure, and certain neurological diseases. We compared baseline characteristics and outcomes between those who were cachectic and those who were not. Survey multivariate logistic regression was used to analyze the independent impact of cachexia on categorical outcomes. Results: The study cohort was 342,030 cases. Cachexia was identified in approximately 17% of the study population (58,509 discharges). The mean age was 56 years. Slightly more female patients noted in cachexia group (41% vs 38%). Inpatient mortality during index hospitalization were higher in patients with cirrhotic cachexia (6.7% vs 3%, P < .01). Inpatient mortality during first all-cause readmission within 30 days of index discharge was also higher in cachexia group (8.6% vs 6.5%, P < .01). Conclusion: Cachexia is an adverse prognosticator for inpatient outcomes in patients with cirrhosis. It is associated with greater readmission rates, inpatient mortality, and prolonged hospital admissions.

Identification of Fast Progressors Among Patients With Nonalcoholic Steatohepatitis Using Machine Learning.

Background and Aims: There is a high unmet need to develop noninvasive tools to identify nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) patients at risk of fast progression to end-stage liver disease (ESLD). This study describes the development of a machine learning (ML) model using data around the first clinical evidence of NAFLD/NASH to identify patients at risk of future fast progression. Methods: Adult patients with ESLD (cirrhosis or hepatocellular carcinoma) due to NAFLD/NASH were identified in Optum electronic health records (2007-2018 period). Patients were stratified into fast (0.5 and 3 years) and standard progressor (6-10 years) cohorts based on retrospectively established progression time between ESLD and the earliest observable disease, and characteristics were reported using descriptive statistics. Two ML models predicting fast progression were created, performance was compared, and top predictive features from the final model were compared between cohorts. Results: Among a total of 4013 NAFLD patients with cirrhosis or hepatocellular carcinoma (mean age 58.6 ± 12.5; 65% female), 24% were fast (n = 951) and 25% standard (n = 992) progressors that were used for modeling. The cohorts were comparable for gender, body mass index, type 2 diabetes, and arterial hypertension, but differed significantly for obesity, hyperlipidemia, and age at index. The final model (NASH FASTmap) is a 44 feature light gradient boosting model which performed better (area under the curve [0.77], F1-score [0.74], accuracy [0.71], and precision [0.71]) than eXtreme gradient boosting model to predict fast progression. Conclusion: Future fast progression to ESLD in NAFLD/NASH patients can be predicted from clinical data using ML. Electronic health record implementation of NASH FASTmap could support clinical assessment for risk stratification and potentially improve disease management.

Sodium-glucose co-transporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors on major liver outcomes in metabolic dysfunction-associated steatotic liver disease.

AIM: To compare the effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2is) with dipeptidyl peptidase-4 inhibitors (DPP4is) on major liver outcomes (MLO) in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD). MATERIALS AND METHODS: We included adult patients with T2D and MASLD, using metformin without specific liver conditions or surgeries, from the Merative MarketScan database. Patients initiating SGLT2is or DPP4is from 1 January 2014 to 31 December 2022 were identified. The primary outcome was time to MLO diagnosis. Overlap weighting balanced covariates, integrated with a Cox proportional hazards model for survival analysis. RESULTS: Among 44 651 patients, 22 100 initiated SGLT2is, and 22 551 began DPP4is. After weighting, the incidence rate of MLO in the SGLT2i group was 3.8 per 1000 person-years, and it was 3.9 per 1000 person-years in the DPP4i group, resulting in an adjusted hazard ratio (aHR) of 0.82 (95% CI, 0.60-1.10). SGLT2i initiation was not associated with cirrhosis (aHR: 0.77; 95% CI, 0.55-1.06) or hepatocellular carcinoma (aHR: 0.99; 95% CI, 0.47-1.83) separately. Subgroup and sensitivity analyses did not yield significant results. CONCLUSIONS: In patients with T2D and MASLD, SGLT2is did not show a lower risk of MLO compared with DPP4is. Clinicians should consider the overall patient conditions and the additional benefits of SGLT2is to support the decision to switch from DPP4is.

Whole-liver histogram analysis of hepatocyte-specific contrast-enhanced magnetic resonance imaging for predicting progression in patients with cirrhosis.

Background: Liver cirrhosis, as the terminal phase of chronic liver disease fibrosis, is associated with high morbidity and mortality. Traditional methods for assessing liver function, such as clinical scoring systems, offer only a global evaluation and may not accurately reflect regional liver function variations. This study aimed at evaluating the diagnostic potential of whole-liver histogram analysis of gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance imaging (MRI) for predicting the progression of cirrhosis. Methods: In this retrospective study, 265 consecutive patients with cirrhosis admitted to the Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University from August 2012 to September 2019 were enrolled. After the exclusion criteria were applied, 117 patients (84 males and 33 females) were divided into Child-Pugh A cirrhosis (n=43), Child-Pugh B cirrhosis (n=49), and Child-Pugh C cirrhosis (n=25). After correction for liver signal intensity with the spleen was completed, 19 histogram features of the whole liver were extracted and modeled to evaluate liver function, with the Child-Pugh class being incorporated as a clinical parameter. Receiver operating characteristic (ROC) curves were used to assess the diagnosis capability and determine the optimal cutoffs after a mean follow-up of 42.3±19.1 (range, 8-93) months. The association between significant histogram features and the cumulative incidence of hepatic insufficiency was analyzed with the adjusted Kaplan-Meier curve model. Results: Among 117 patients (12%), 14 developed hepatic insufficiency through a period of follow-up. Five features, including the median (P<0.01), 90th percentile (P<0.01), root mean squared (P<0.01), mean (P<0.01), and 10th percentile (P<0.05), were significantly different between the groups with and without hepatic insufficiency according to the Kruskal-Wallis test; in the ROC curve analysis, the area under the curve (AUC) of these features was 0.723 [95% confidence interval (CI): 0.653-0.793], 0.722 (95% CI: 0.652-0.792), 0.722 (95% CI: 0.652-0.792), 0.721 (95% CI: 0.651-0.791), and 0.674 (95% CI: 0.600-0.748) after correction, respectively (all P values <0.05). Median, 90th percentile, root mean squared, and mean were found to be significant factors in predicting liver insufficiency. The adjusted Kaplan-Meier curves revealed that patients with a feature level less than the cutoff, as compared to those with a level above the cutoff, showed a statistically shorter progression-free survival and higher incidences of hepatic insufficiency for significant features of median (cutoff =26.001; 21.28% versus 5.71%; P=0.02), 90th percentile (cutoff =86.263; 20.41% versus 5.88%; P<0.01), root mean squared (cutoff =1,028.477; 19.15% versus 7.14%; P=0.049), and mean (cutoff =27.484; 19.15% versus 7.14%; P=0.049). Patients with a 10th percentile less than -39.811 also showed a higher cumulative incidence of hepatic insufficiency than did those with a value higher than the cutoff (0.18% versus 7.46%; P=0.22). Conclusions: Whole-liver histogram analysis of Gd-BOPTA-enhanced MRI may serve as a noninvasive analytical method to predict hepatic insufficiency in patients with cirrhosis.