Stroop test, Quickstroop, and the 1-min animal naming test for minimal hepatic encephalopathy diagnosis: A multicenter study in Mexico.

INTRODUCTION AND OBJECTIVES: Although the Psychometric Hepatic Encephalopathy Score (PHES) remains the gold standard in diagnosing minimal hepatic encephalopathy (MHE), its complexity limits its application in clinical practice. While more convenient tests, such as the Stroop test, Quickstroop, and the 1-min animal naming test (ANT-1), have emerged, they haven't been validated in our setting. Our objective was to validate these tests in our population. PATIENTS AND METHODS: This multicenter, observational, descriptive, and cross-sectional study was conducted in three hospitals in northeastern Mexico. MHE was defined as a PHES <-4. We included patients with cirrhosis aged >15 years without a history of overt hepatic encephalopathy. Data regarding sex, age, education, Child-Pugh/MELD-Na scores, etiology of cirrhosis, diabetes, hypertension, obesity, ascites, and clinically significant portal hypertension was collected. Fisher's exact test, Mann-Whitney U test, and receiver operating characteristic (ROC) curves were used for statistical analysis. RESULTS: Of the 121 patients included, 35.5 % were diagnosed with MHE. The presence of MHE was significantly associated with education level, years of study, and scores in the Stroop test, Quickstroop, and ANT-1. The AUROC curves were 77.9 %, 74.6 %, and 72.7 % for the Stroop test, Quickstroop, and ANT-1, respectively. The resulting cut-off points were 218.398 (sensitivity: 74 %; specificity: 74 %), 40.535 (sensitivity: 77 %; specificity: 68 %), and <16 animals (sensitivity: 58 %; specificity: 79 %), respectively. CONCLUSIONS: These tests are valid diagnostic tools for detecting MHE in our population. Their simpler use and applicability could increase the early diagnosis of MHE and prompt primary prophylaxis initiation for overt hepatic encephalopathy.

Chinese consensus on the management of liver cirrhosis.

Liver cirrhosis, characterized by diffuse necrosis, insufficient regeneration of hepatocytes, angiogenesis, severe fibrosis, and the formation of pseudolobules, is a progressive, chronic liver disease induced by a variety of causes. It is clinically characterized by liver function damage and portal hypertension, and many complications may occur in its late stage. Based on the updated practice guidelines, expert consensuses, and research advances on the diagnosis and treatment of cirrhosis, the Chinese Society of Gastroenterology of Chinese Medical Association established the current consensus to standardize the clinical diagnosis and management of liver cirrhosis and guide clinical practice. This consensus contains 43 statements on the etiology, pathology and pathogenesis, clinical manifestations, major complications, diagnosis, treatment, prognosis, and chronic disease control of liver cirrhosis. Since several practice guidelines and expert consensuses on the complications of liver cirrhosis have been published, this consensus emphasizes the research progress of liver cirrhosis itself.

Chronic liver disease after allogeneic hematopoietic cell transplantation.

BACKGROUND AIMS: There are few descriptions of the epidemiology of chronic liver disease (CLD) after allogeneic hematopoietic stem cell transplantation (allo-HCT). Among those transplanted before 2000, viral hepatitis was the dominant cause of CLD. Recently, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD, previously known as nonalcoholic fatty liver disease) is increasing in the general population. In addition, survivors of allo-HCT are known to be at increased risk of metabolic syndrome. We set out to describe the epidemiology of CLD in a modern cohort of allo-HCT recipients. We hypothesized that MASLD would be the most common cause of CLD in the cohort. METHODS: We undertook a retrospective cohort and nested case-control study of 2-year survivors of allo-HCT in Alberta transplanted between 2008 and 2018. RESULTS: Among 392 2-year survivors of allo-HCT between 2008 and 2018, the prevalence of CLD was 41.8% and MASLD was identified in 56% of those with CLD, followed by iron overload in 47% of those with CLD. The prevalence of MASLD among the entire cohort was 46%. Although most patients developed CLD before 2 years post-transplant, there was a 13% cumulative incidence of new CLD after 2 years posttransplant. Grade 2-4 acute graft-versus-host disease and/or moderate-to-severe chronic graft-versus-host disease and pretransplant CLD were strongly associated with CLD. In the case-control study examining the association between cardiovascular risk factors and CLD, type 2 diabetes was associated with CLD. Cirrhosis developed in 1.5% of survivors, and MASLD was an underlying etiology in one half of these cases. There was no difference in overall survival and non-relapse mortality between those who did and did not develop CLD. CONCLUSIONS: MASLD is the main cause of CLD in recent long-term survivors of allo-HCT and may be associated with post-transplant corticosteroid exposure and type 2 diabetes. We note a shift in the underlying etiology of CLD post-HCT: previous studies describe viral hepatitis as the most common cause of CLD. The high prevalence of MASLD in allo-HCT recipients has important implications for survivorship care.

Amyloid A and lactic acid as a predictor in patients with sepsis in patients with liver cirrhosis.

BACKGROUND: Sepsis is triggered by pathogenic microorganisms, resulting in a systemic inflammatory response. Liver cirrhosis and sepsis create a vicious cycle: cirrhosis weakens immune function, raising infection risk and hindering pathogen clearance. Optimal treatment outcomes depend on understanding liver cirrhosis patients' sepsis risk factors. Thus, preventing sepsis involves addressing these risk factors. Therefore, early identification and understanding of clinical characteristics in liver cirrhosis patients with sepsis are crucial for selecting appropriate antibiotics. A case-control study using logistic regression was conducted to examine the prognostic value of amyloid A/lactate level monitoring in identifying sepsis risk factors in liver cirrhosis patients. METHODS: From March 2020 to March 2022, 136 liver cirrhosis patients treated at our hospital were divided into a sepsis group (n = 35) and a non-sepsis group (n = 101) based on sepsis complications. General clinical data were collected. Univariate analysis screened for liver cirrhosis patients' sepsis risk factors. Multivariate logistic analysis was subsequently employed to evaluate the risk factors. Sepsis patients were followed up for a month. Based on prognosis, patients were categorized into a poor prognosis group (n = 16) and a good prognosis group (n = 19). Serum amyloid A (SAA) and blood lactic acid (BLA) levels were compared between the two groups. The receiver operating characteristic (ROC) curve was used to evaluate the prognostic value of both individual and combined SAA/BLA monitoring. RESULTS: Patient data, including age, diabetes history, liver cancer, hepatic artery embolization, recent antibiotic use, invasive procedures within two weeks, APACHE II Scoring, ALB and SAA and BLA levels, were compared between the sepsis and non-sepsis groups, showing significant differences (P < 0.05). Logistic regression identified factors such as age ≥ 70, recent antibiotic use, recent invasive procedures, history of liver cancer, hepatic artery embolization history, high APACHE II scores, decreased albumin, and elevated SAA and BLA levels as independent sepsis risk factors in liver cirrhosis patients (P < 0.05). Among the 35 sepsis patients, 16 had a poor prognosis, representing an incidence rate of 45.71%. Serum SAA and BLA levels were significantly higher in the poor prognosis group than in the good prognosis group (P < 0.05). The AUC for serum SAA and BLA was 0.831 (95%CI: 0.738-0.924), 0.720 (95%CI: 0.600-0.840), and 0.909 (95%CI: 0.847-0.972), respectively. The combined diagnostic AUC was significantly higher than that of single factor predictions (P < 0.05). The predictive value ranked as follows: joint detection > SAA > BLA. CONCLUSION: In treating liver cirrhosis, prioritize patients with advanced age, a history of hepatic artery embolization, recent invasive operations, history of liver cancer, recent antibiotic exposure, high APACHE II scores and low albumin. Closely monitoring serum SAA and BLA levels in these patients can offer valuable insights for early clinical prevention and treatment.

Palliative care and end stage liver disease: A survey study comparing perspectives of hepatology and palliative care physicians and clinical scenarios that could require palliative care intervention.

BACKGROUND AND AIMS: The prevalence and mortality of chronic liver disease has risen significantly. In end stage liver disease (ESLD) the survival of patients is approximately 2 years. Despite the poor prognosis and high symptom burden of these patients, integration of palliative care is reduced. We aim to analyze the agreement between palliative care and hepatology physicians of clinical scenarios that could require palliative care intervention. METHODS: A cross-sectional study was conducted. Palliative care and hepatology physicians were surveyed. Using a five-point Likert scale, their perceptions of palliative care in ESLD were rated. Their agreement in clinical scenarios that could require palliative care intervention were evaluated. Analyses were conducted to assess any differences by primary role (hepatology vs. palliative care) and length of practice (<10 years vs. 10 years). RESULTS: A total of 123 responses were obtained: 52% from palliative care and 48% from hepatology. The majority (66.7%) work in the field for up to ten years. There was a great consensus in 4 of the 8 clinical scenarios. In scenarios with less consensus, the area of activity and length of practice influence the reliance of physicians on palliative care. Involvement of palliative care in ESLD was considered "rare" by 30% and 61% consider difficult to predict the prognosis. More than 90% support medical training in both areas of activity. CONCLUSION: The current involvement of palliative care is considered low, but there are clinical conditions that reveal a clear consensus and there's a unanimous view of the relevance of training.

Application of a virtual ruler in predicting postoperative rebleeding from esophageal varices in patients with liver cirrhosis.

BACKGROUND: Esophageal variceal diameter (EVD) is one of the most important predictors of variceal bleeding, as well as an important predictor of the effectiveness of endoscopic esophageal varices (EV) treatments. EVD is currently determined using visual inspection by endoscopic operators, meaning that results can vary widely between operators. This approach also means that cases unsuitable for endoscopic variceal ligation (EVL) can be complicated by postoperative hemorrhage. Thus, the purpose of this study was to explore the value of a virtual ruler (VR) in predicting rebleeding after the endoscopic treatment of EV in patients with cirrhosis. METHODS: We enrolled 588 patients with cirrhosis and EV (with and without gastric varices), who were treated with EVL or endoscopic injection sclerotherapy across 3 hospitals. We categorized participants into 2 groups, a nonbleeding group and a rebleeding group, according to whether they bled again after surgery. We compared basic demographic and clinical data, laboratory tests, EVD, and treatment modalities between the 2 groups. Potential risk factors for rebleeding after EV operations were analyzed using univariate and multivariable regression analyses. Correlations between esophageal variceal rebleeding and EVD were also analyzed, as was the consistency between visual EVD estimates and EVD measured using a VR. RESULTS: Child-Pugh class, albumin (ALB) levels, prothrombin time (PT), EVD (visual value), EVD (VR value), red sign, and the number of laps used for EVL showed statistically significant differences between the rebleeding and nonbleeding groups. Univariate regression analysis showed that Child-Pugh classification, ALB levels, PT, EVD (VR value), and red sign were strongly associated with rebleeding after endoscopic treatment of EV, whereas multivariable regression analysis showed that Child-Pugh classification, ALB levels, and EVD (VR value) were predictive factors for rebleeding after endoscopic treatment of EV. Differences between visual EVD estimates and VR EVD measurements were large. (Kappa value: 0.391, P < .001). However, the 2 methods showed high agreement for EVD >1 cm (87/95) CONCLUSION: EVD (VR value) can more accurately predict rebleeding rates. It can also provide a basis for selecting appropriate endoscopic treatment modalities for EV and effectively circumvent postoperative EV rebleeding.

Investigating the Relationship between Chronic Liver Cirrhosis and Parkinsonism: A Comparative Analysis and a Suggested Diagnostic Scheme.

Aim: Neurological manifestations are common in patients with chronic liver diseases. This study aimed to depict the association between liver cirrhosis and Parkinson's disease (PD) and propose a clinically relevant diagnostic scheme. Methods: We examined patients' medical records with PD and chronic liver impairment secondary to cirrhosis or liver metastases for temporal correlations between liver insult and Parkinsonian signs. Results: Thirty-five individuals with PD and chronic liver impairment were included due to either cirrhosis or liver metastases. In all 22 patients with PD and liver metastases, the diagnosis of PD preceded the diagnosis of cancer. Conversely, patients with cirrhosis were often diagnosed with liver impairment before diagnosing PD. Age at diagnosis did not account for this difference. Conclusions: This study reinforces the potential clinical association between cirrhosis and PD. We also provide a diagnostic scheme that may guide therapeutic interventions and prognostic assessments.

Bedside assessment of sarcopenia in hospitalized patients with liver cirrhosis: Magnitude and clinical implications.

BACKGROUND: Sarcopenia is associated with many adverse outcomes in patients with cirrhosis. The tools currently in use for assessing sarcopenia have numerous flaws. We evaluated the utility of portable ultrasonography and a dynamometer for the bedside assessment of sarcopenia and its implications in hospitalized cirrhosis patients. METHODS: A dynamometer was used to test the hand-grip strength (HGS) and ultrasound was used to measure the thickness of the forearm and quadriceps muscles. HGS value < 27 kg for men and < 16 kg for women was taken as significant according to the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria. The lower normal limit of muscle mass (5th percentile) was determined on 100 matched healthy controls. RESULTS: According to the EWGSOP2 criteria and HGS values, the prevalence of sarcopenia and probable sarcopenia among 300 cirrhosis patients were 56% and 62.3%, respectively. HGS alone identified sarcopenia in 88.9% of patients, while overestimated it in 6.3% of cases. The prevalence rate of sarcopenic obesity was 11%. Compared to patients without sarcopenia, sarcopenic patients had more complications of cirrhosis such as ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, sepsis, hepatorenal syndrome and refractory ascites. In-hospital (p = 0.037), three-month (p < 0.001), and six-month (p < 0.001) mortality rates were all higher among sarcopenic patients. On cox regression survival analysis, overall six-month mortality was significantly higher in sarcopenic patients compared to patients without sarcopenia (hazard ratio, 6.37; 95% confidence interval, 3.15-12.8, p < 0.001). CONCLUSION: Bedside assessment of sarcopenia using a portable ultrasound machine and a dynamometer detects liver cirrhosis patients with high risk of complications and mortality.

Low-dose alcohol exacerbates hyperdynamic circulation and shunting in non-alcoholic cirrhotic rats.

BACKGROUND: Portal hypertension affects hepatic, splanchnic and portosystemic collateral systems. Although alcohol is a well-known risk factor for liver cirrhosis, it also affects vascular contractility. However, the relevant effects on portal hypertension have not been evaluated in non-alcoholic cirrhosis. The present study aimed to investigate the impacts of low-dose alcohol on portal hypertension-related derangements in non-alcoholic cirrhotic rats. METHODS: Sprague-Dawley rats received bile duct ligation to induce cirrhosis or sham operation as controls. The chronic or acute effects of low-dose alcohol (2.4 g/kg/day, oral gavage, approximately 1.3 drinks/day in humans) were evaluated. RESULTS: The chronic administration of low-dose alcohol did not precipitate liver fibrosis in the sham or cirrhotic rats; however, it significantly increased splanchnic blood inflow (P=0.034) and portosystemic collaterals (P=0.001). Mesenteric angiogenesis and pro-angiogenic proteins were up-regulated in the alcohol-treated cirrhotic rats, and poorer collateral vasoresponsiveness to vasoconstrictors (P<0.001) was noted. Consistently, acute alcohol administration reduced splenorenal shunt resistance. Collateral vasoresponsiveness to vasoconstrictors also significantly decreased (P=0.003). CONCLUSIONS: In non-alcoholic cirrhosis rats, a single dose of alcohol adversely affected portosystemic collateral vessels due to vasodilatation. Long-term alcohol use precipitated splanchnic hyperdynamic circulation, in which mesenteric angiogenesis played a role. Further studies are warranted to evaluate the benefits of avoiding low-dose alcohol consumption in patients with non-alcoholic cirrhosis.

Thrombotic Long-Term Consequences of SARS-CoV-2 Infection in Patients with Compensated Cirrhosis: A Propensity Score-Matched Analysis of a U.S. Database.

BACKGROUND: Cirrhosis causes an imbalance in the coagulation pathway and leads to a tendency for both bleeding and clotting. SARS-CoV-2 has been reported to be associated with a hypercoagulable state. This study examines SARS-CoV-2's impact on hemostasis in compensated patients with cirrhosis. METHODS: We analyzed the US Collaborative Network, which comprises 63 HCOs in the U.S.A. Compensated cirrhosis patients were split into two groups: SARS-CoV-2-positive and -negative. Patients' baseline characteristics were used in a 1:1 propensity score-matched module to create comparable cohorts. We compared the risk of portal vein thrombosis (PVT), deep venous thrombosis (DVT), and pulmonary embolism (PE) at 6 months, and 1 and 3 years. RESULTS: Of 330,521 patients, 27% tested positive and 73% remained negative. After PSM, both cohorts included 74,738 patients. Patients with SARS-CoV-2 had a higher rate of PVT compared to those without at 6 months (0.63% vs 0.5%, p < 0.05), 1 year (0.8% vs 0.6%, p < 0.05), and 3 years (1% vs. 0.7%, p < 0.05), a higher rate of DVT at 6 months (0.8% vs. 0.4%, p < 0.05), 1 year (1% vs. 0.5%, p < 0.05), and 3 years (1.4% vs. 0.8%, p < 0.05), and a higher rate of PE at 6 months (0.6% vs. 0.3%, p < 0.05), 1 year (0.7% vs. 0.4%, p < 0.05), and 3 years (1% vs. 0.6%, p < 0.05). CONCLUSIONS: The presence of SARS-CoV-2 infection in patients with compensated cirrhosis was associated with a higher rate of PVT, DVT, and PE at 6 months, and 1 and 3 years.

The Balloon Catheter Method and the End-hole Catheter Method in the Measurement of Hepatic Venous Pressure Gradient: a Comparative Study.

OBJECTIVE: This study aims to evaluate the differences between The balloon catheter method and End-hole Catheter Method in measuring hepatic venous pressure gradient (HVPG) among cirrhosis patients. METHODS: From October 2017 to January 2024, patients who underwent HVPG measurements using both methods were consecutively included. HVPGs obtained from both methods were compared with the portal vein pressure gradient (PPG) obtained via transjugular intrahepatic portosystemic shunt (TIPS) using paired comparisons. Additionally, the consistency and predictive ability for bleeding risk of the two methods, as well as the impact of intrahepatic veno-venous shunt (IHVS), were analyzed. RESULTS: The study enrolled 145 patients, each of whom had HVPG measured by both methods. PPG was measured in 61 patients. There was a statistically significant difference between the PPGs and HVPGs measured by both the balloon catheter method and the end-hole catheter method (P < 0.001), with the HVPG mean values obtained by the end-hole catheter method being closer to the PPGs. In the non-IHVS group, no significant statistical difference was found between the two methods (P = 0.071). In contrast, the IHVS group showed a significant difference (P < 0.001), with a mean difference of 2.98 ± 4.03 mmHg. When IHVS was absent, the measurement results from the end-hole catheter method and the balloon catheter method were found to be highly correlated. The end-hole catheter method has a higher screening capability for patients at risk of bleeding compared to the balloon catheter method (75.90% vs. 72.86%). CONCLUSION: HVPG measurements using either the balloon catheter method or end-hole catheter method showed significant difference with the PPG. The end-hole catheter method has a higher screening capability for patients at risk of bleeding, and IHVS could lead to lower HVPG measurements with The balloon catheter method.

Decoding the Role of CYP450 Enzymes in Metabolism and Disease: A Comprehensive Review.

Cytochrome P450 (CYP450) is a group of enzymes that play an essential role in Phase I metabolism, with 57 functional genes classified into 18 families in the human genome, of which the CYP1, CYP2, and CYP3 families are prominent. Beyond drug metabolism, CYP enzymes metabolize endogenous compounds such as lipids, proteins, and hormones to maintain physiological homeostasis. Thus, dysregulation of CYP450 enzymes can lead to different endocrine disorders. Moreover, CYP450 enzymes significantly contribute to fatty acid metabolism, cholesterol synthesis, and bile acid biosynthesis, impacting cellular physiology and disease pathogenesis. Their diverse functions emphasize their therapeutic potential in managing hypercholesterolemia and neurodegenerative diseases. Additionally, CYP450 enzymes are implicated in the onset and development of illnesses such as cancer, influencing chemotherapy outcomes. Assessment of CYP450 enzyme expression and activity aids in evaluating liver health state and differentiating between liver diseases, guiding therapeutic decisions, and optimizing drug efficacy. Understanding the roles of CYP450 enzymes and the clinical effect of their genetic polymorphisms is crucial for developing personalized therapeutic strategies and enhancing drug responses in diverse patient populations.

The TGF-ß1 target WISP1 is highly expressed in liver cirrhosis and cirrhotic HCC microenvironment and involved in pro- and anti-tumorigenic effects.

INTRODUCTION: WNT1-inducible signalling pathway protein 1 (WISP1) promotes progression of several tumor entities often correlating with worse prognosis. Here its expression regulation and role in the progression of chronic liver diseases (CLD) was investigated. METHODS: WISP1 expression was analyzed in human HCC datasets, in biopsies and serum samples and an HCC patient tissue microarray (TMA) including correlation to clinicopathological parameters. Spatial distribution of WISP1 expression was determined using RNAscope analysis. Regulation of WISP1 expression was investigated in cytokine-stimulated primary mouse hepatocytes (PMH) by array analysis and qRT-PCR. Outcome of WISP1 stimulation was analyzed by IncuCyte S3-live cell imaging, qRT-PCR, and immunoblotting in murine AML12 cells. RESULTS: In a TMA, high WISP1 expression was positively correlated with early HCC stages and male sex. Highest WISP1 expression levels were detected in patients with cirrhosis as compared to healthy individuals, patients with early fibrosis, and non-cirrhotic HCC in liver biopsies, expression datasets and serum samples. WISP1 transcripts were predominantly detected in hepatocytes of cirrhotic rather than tumorous liver tissue. High WISP1 expression was associated with better survival. In PMH, AML12 and HepaRG, WISP1 was identified as a specific TGF-ß1 target gene. Accordingly, expression levels of both cytokines positively correlated in human HCC patient samples. WISP1-stimulation induced the expression of Bcl-xL, PCNA and p21 in AML12 cells. CONCLUSIONS: WISP1 expression is induced by TGF-ß1 in hepatocytes and is associated with cirrhotic liver disease. We propose a crucial role of WISP1 in balancing pro- and anti-tumorigenic effects during premalignant stages of CLD.

Monocyte distribution width as a promising biomarker for differential diagnosis of chronic hepatitis, cirrhosis, and hepatocellular carcinoma.

Objective: We aimed to investigate the association and diagnostic value of monocyte distribution width (MDW) for chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Methods: MDW levels were measured in 483 individuals (103 CHB, 77 LC, 153 HCC, and 150 controls). MDW was detected using UniCel Dx900 for specific cell volume parameters and the distribution of cell volumes. Results: Our findings revealed a dynamic upward change in MDW levels across different stages of chronic liver disease, from CHB to LC and HCC. In CHB, MDW levels were highest among HBeAg-positive CHB patients and exhibited a negative correlation with HBV markers while positively correlating with ALT levels. In LC, MDW showed a positive association with the pathological progression of LC, demonstrating consistency with CP scores. MDW proved to be equally effective as traditional detection for diagnosing LC. In HCC, MDW was positively correlated with HCC occurrence and development, with higher levels observed in the high MDW group, which also exhibited elevated AFP levels, MELD scores, and 90-day mortality rates. MDW surpassed predictive models in its effectiveness for diagnosing HCC, as well as CHB and LC, with respective areas under the curve of 0.882, 0.978, and 0.973. Furthermore, MDW emerged as an independent predictor of HCC. Conclusion: MDW holds significant diagnostic efficacy in identifying CHB, LC, and HCC. These findings suggest that MDW could serve as a promising biomarker for predicting the severity of liver diseases and aid in rational clinical treatment strategies.

Durability and on-treatment predictors of recompensation in entecavir-treated patients with hepatitis B and decompensated cirrhosis.

Background & Aims: Hepatic recompensation may be achieved in patients with decompensated cirrhosis due to chronic hepatitis B (CHB) upon effective suppression of viral replication by nucleos(t)ide analogues (NAs). However, the optimal timing and predictors of recompensation and the subsequent clinical course of patients with CHB with vs. without recompensation are not well-defined. Methods: This study was a retrospective extension of a multi-centre prospective cohort, focusing on patients with CHB and decompensated cirrhosis treated with entecavir. We followed patients beyond treatment week 120 until a second decompensation event or June 2023. We identified the optimal timing and predictors of recompensation by week 120, evaluated durability of recompensation in patients fulfilling recompensation criteria by week 120 and examined late recompensation in those who did not fulfil it by week 120. Results: At treatment week 24, serum albumin ≥34 g/L predicted recompensation by week 120. The Brec-PAS model offered good predictive ability for recompensation by week 120. Of the 283 patients who finished 120 weeks of therapy, 175 were followed beyond week 120 (median follow-up: 240 weeks). Among the 106 patients achieving recompensation by week 120, 92 (86.8%) maintained recompensation for another 120 (72-168) weeks. Among the 69 patients without recompensation by week 120, 40.6% attained late recompensation during the subsequent 120 (72-168) weeks. Additionally, hepatocellular carcinoma incidence was lower in the recompensated group (5.0% vs. 16.13%, p = 0.002). Conclusions: A serum albumin ≥34 g/L at treatment week 24 predicted recompensation by week 120. Recompensation achieved by week 120 of NA treatment is maintained in >80% of patients in the long term. Some patients may achieve recompensation only after >120 weeks of NA treatment. The incidence of hepatocellular carcinoma was reduced but not completely abolished after recompensation. Impact and implications: Our research provides a meaningful contribution to understanding the long-term prognosis of recompensation in patients with chronic hepatitis B and decompensated cirrhosis, as well as to evaluating the predictive value of serum albumin levels, offering a comprehensive view of clinical outcomes after recompensation. The significance of early biomarkers in guiding therapeutic decisions is highlighted, shedding light on the continued benefits and possible risks after recompensation. This enhances the capability for more precise prognostic evaluations and informed therapeutic strategies. For healthcare providers, these insights afford a detailed perspective on patient monitoring and intervention planning, underscoring the need for ongoing assessment past the initial recompensation phase.

Disparities for Hispanic Adults with metabolic dysfunction-associated steatotic liver disease in the US: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) is reported to be higher in Hispanic adults in the United States (US), though rates vary substantially across studies and have increased given the evolving obesity epidemic. This systematic review and meta-analysis quantifies MASLD disease burden and severity in contemporary cohorts to characterize health disparities experienced by adult Hispanic individuals in the US. METHODS: We searched MEDLINE, Embase and Cochrane databases per the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies from 2010 to December 2023 were included to capture data representative of current populations given the obesity epidemic. Studies from overlapping cohorts were excluded. Meta-analyses were conducted using random-effects models to estimate pooled prevalence and relative risk (RR) with 95% confidence intervals (CIs). RESULTS: We identified 22 studies, comprising 756,088 subjects, of which 62,072 were Hispanic. The pooled prevalence (95% CI) in US Hispanic adults was 41% (95% CI: 30-52%) for MASLD, 61% (95% CI: 39-82%) for metabolic dysfunction-associated steatohepatitis (MASH), 27% (95% CI: 15-39%) for MASH-associated advanced fibrosis (AF), and 5% (95% CI: 1-8%) for MASH cirrhosis. Compared to non-Hispanic adults, Hispanic adults had a RR of 1.50 (95% CI: 1.32-1.69) for MASLD, 1.42 (95% CI: 1.04-1.93) for MASH, 1.37 (95% CI: 0.96-1.96) for MASH-associated AF and 0.93 (95% CI: 0.49-1.77) for MASH cirrhosis. CONCLUSION: Health disparities for US Hispanic adults continue to worsen with significantly higher relative risk of MASLD and MASH compared to non-Hispanic adults. Public health efforts to optimize screening and care delivery for adult Hispanic population are urgently needed.

Alcohol consumption and liver phenotype of individuals with alpha-1 antitrypsin deficiency.

BACKGROUND AND AIMS: Alpha-1 antitrypsin deficiency is an inherited disorder caused by alpha-1 antitrypsin (AAT) mutations. We analysed the association between alcohol intake and liver-related parameters in individuals with the heterozygous/homozygous Pi*Z AAT variant (Pi*MZ/Pi*ZZ genotype) found in the United Kingdom Biobank and the European Alpha1 liver consortium. METHODS: Reported alcohol consumption was evaluated in two cohorts: (i) the community-based United Kingdom Biobank (17 145 Pi*MZ, 141 Pi*ZZ subjects, and 425 002 non-carriers [Pi*MM]); and (ii) the European Alpha1 liver consortium (561 Pi*ZZ individuals). Cohort (ii) included measurements of carbohydrate-deficient transferrin (CDT). RESULTS: In both cohorts, no/low alcohol intake was reported by >80% of individuals, while harmful consumption was rare (~1%). Among Pi*MM and Pi*MZ individuals from cohort (i), moderate alcohol consumption resulted in a <30% increased rate of elevated transaminases and ~50% increase in elevated gamma-glutamyl transferase values, while harmful alcohol intake led to an at least twofold increase in the abnormal levels. In Pi*ZZ individuals from both cohorts, moderate alcohol consumption had no marked impact on serum transaminase levels. Among Pi*ZZ subjects from cohort (ii) who reported no/low alcohol consumption, those with increased CDT levels more often had signs of advanced liver disease. CONCLUSIONS: Pi*MZ/Pi*ZZ genotype does not seem to markedly aggravate the hepatic toxicity of moderate alcohol consumption. CDT values might be helpful to detect alcohol consumption in those with advanced fibrosis. More data are needed to evaluate the impact of harmful alcohol consumption.

Assessment of intestinal inflammation via fecal calprotectin for early prediction of adverse outcomes in advanced chronic liver disease.

BACKGROUND AND AIMS: Intestinal inflammation assessed by fecal calprotectin (F-CAL) in advanced chronic liver disease (ACLD) may represent an early sign of intestinal barrier dysfunction. We aimed to explore the usefulness of F-CAL testing in ACLD in the prediction of adverse outcomes (AO, death, or LT) and refinement of prognostic stratification. PATIENTS AND METHODS: We explored the RH7 cirrhosis registry comprising consecutive hospitalized patients and a control group with data on disease phenotype, demographics, anthropometrics, prognostic indices, and medication. The F-CAL was evaluated on admission and reported in multiples of the upper limit of normal or terciles. Predictive power was tested in the Cox model for AO over 180 days. Additional risk refinement by F-CAL was tested for both groups. RESULTS: We enrolled 263 cases in the study group with a median age of 57.2 years, M/F ratio 167/96, with alcohol, metabolic dysfunction-associated steatotic liver disease, MetALD, and viral etiologies in 72.2%, 9.1, 8.0, 3.4%. The median F-CAL was 3.92 × ULN. The control group comprised 108 cases. The adjusted Cox model confirmed F-CAL (hazard ratio [HR] = 1.05, p < 0.001) and F-CAL terciles (HR = 1.413, p = 0.009) as independent predictors of AO. F-CAL terciles had higher predictive accuracy in CLIF-C-AD<50 (HR = 2.49, p = 0.013) and Child stages A and B (HR = 1.706, p = 0.025), in whom high F-CAL (cut-off >11 × ULN) could identify patients having 2-3 times higher risk of AO. This approach has been validated in the control group. CONCLUSION: Among hospitalized patients with ACLD, F-CAL values were independently proportional to the risk of AO, particularly in early disease stages when high F-CAL values could refine prognostic stratification.

Long-term outcome following liver transplantation of patients with ACLF grade 3.

BACKGROUND AND AIMS: Utility, a major principle for allocation in the context of transplantation, is questioned in patients with acute-on chronic liver failure grade 3 (ACLF-3) who undergo liver transplantation (LT). We aimed to explore long-term outcomes of patients included the three-center retrospective French experience published in 2017. METHOD: All patients with ACLF-3 (n=73) as well as their transplanted matched controlled with ACLF-2 (n=145), 1 (n=119) and no ACLF (n=292) that have participated in the princeps study published in 2017 were included. We explored 5- and 10-year patient and graft survivals, causes of death and their predictive factors. RESULTS: Median follow-up of patients ACLF-3 patients was 7.5 years. At LT, median MELD was 40. In patients with ACLF-3, 2, 1 and no ACLF, 5-year patients' survivals were respectively 72.6% vs. 69.7% vs. 76.4% vs. 77.0% (p=0.31). Ten-year patients' survival ACLF-3 was 56.8% and was not different other groups (p=0.37) Leading causes of death in ACLF-3 patients were infections (33.3%), and cardiovascular events (23.3%). After exclusion of early death, UCLA futility risk score, age-adjusted Charlson comorbidity index and Chronic Liver Failure Consortium ACLF score were independently associated with 10-year patients' survival. Long-term grafts' survivals were not different across the groups. Clinical frailty scale and WHO performance status improved over time in patients alive after 5 years. CONCLUSION: 5- and 10-year patients' and grafts' survivals in ACLF-3 patients were not different from their controls. 5-year patients' survival is higher than that of the 50%-70% threshold defining the utility of liver graft. Efforts should focus on candidates' selection based on comorbidities as well as the prevention of infection and cardiovascular events standing as the main cause of death. IMPACT AND IMPLICATIONS: While short-term outcomes following liver transplantation in the most severely ill cirrhotic patients (ACLF-3) are known, long-term data are limited, raising questions about the utility of graft allocation in the context of scarce medical resources. This study provides a favorable long-term update, confirming no differences in 5- and 10-year patient and graft survival following liver transplantation in ACLF-3 patients compared to matched ACLF-2, ACLF-1, and no-ACLF patients. The study highlights the risk of dying from infection and cardiovascular causes in the long-term and identifies scores including comorbidities evaluation, such as the age-adjusted Charlson Comorbidity Index, as independently associated with long-term survival. Therefore, physicians should consider the cumulative burden of comorbidities when deciding to transplant these patients. Additionally, after transplantation, the study encourages mitigating infectious risk with tailored immunosuppressive regimens and managing tightly cardiovascular risk over time.

Safety of naltrexone in patients with cirrhosis.

Background & Aims: Treatment of alcohol use disorder (AUD) improves survival in patients with alcohol-related cirrhosis. However, medications for alcohol use disorder (MAUD) are underutilized in this population, partially due to concerns regarding drug-induced liver injury (DILI). Our aim was to evaluate the safety of naltrexone in patients with cirrhosis. Methods: This was a retrospective study of patients with cirrhosis who were prescribed naltrexone using the VOCAL (Veterans Outcomes and Costs Associated with Liver Disease) database. Patients with new initiation of naltrexone after diagnosis of cirrhosis who had liver enzymes checked within a 3-month time frame were included. A chart review was performed on patients who developed alanine aminotransferase or alkaline phosphatase elevations to more than 2× or 5× the upper limit of normal, respectively. The RUCAM (Roussel Uclaf causality assessment method) was used to determine if DILI occurred. Results: A total of 3,285 patients with cirrhosis were initiated on naltrexone, of whom 2,940 had laboratory testing during the high-risk DILI period. Only 2% of patients had liver enzyme elevations, and among those, 30 (48%) were classified as "DILI excluded" and 32 (52%) were classified as "DILI unlikely". No patients were classified as possible, probable, or highly probable DILI. No deaths or new decompensations were attributed to naltrexone. Conclusions: Naltrexone in patients with cirrhosis was not associated with development of DILI using RUCAM scoring. Naltrexone appears to be safe in patients with compensated and decompensated cirrhosis. Impact and Implications: Naltrexone is an effective medication for treating alcohol use disorder but is underutilized in patients with underlying liver disease due to historical concerns regarding hepatotoxicity. This retrospective study shows no drug-induced liver injury in a large cohort of patients with cirrhosis with new initiation of naltrexone. This study may encourage providers to prescribe naltrexone to patients with existing liver disease with ongoing alcohol use disorder.