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Many patients with hepatocellular carcinoma (HCC) do not respond to the first-line immune checkpoint inhibitor treatment. Immunization with effective cancer vaccines is an attractive alternative approach to immunotherapy. However, its efficacy remains insufficiently evaluated in preclinical studies. Here, we investigated HCC-associated self/tumor antigen, α-fetoprotein-based (AFP-based) vaccine immunization for treating AFP (+) HCC mouse models. We found that AFP immunization effectively induced AFP-specific CD8+ T cells in vivo. However, these CD8+ T cells expressed exhaustion markers, including PD1, LAG3, and Tim3. Furthermore, the AFP vaccine effectively prevented c-MYC/Mcl1 HCC initiation when administered before tumor formation, while it was ineffective against full-blown c-MYC/Mcl1 tumors. Similarly, anti-PD1 and anti-PD-L1 monotherapy showed no efficacy in this murine HCC model. In striking contrast, AFP immunization combined with anti-PD-L1 treatment triggered significant inhibition of HCC progression in most liver tumor nodules, while in combination with anti-PD1, it induced slower tumor progression. Mechanistically, we demonstrated that HCC-intrinsic PD-L1 expression was the primary target of anti-PD-L1 in this combination therapy. Notably, the combination therapy had a similar therapeutic effect in the cMet/β-catenin mouse HCC model. These findings suggest that combining the AFP vaccine and immune checkpoint inhibitors may be effective for AFP (+) HCC treatment.

Abstract Alcohol-associated liver disease is currently the leading cause of liver transplantation and liver deaths both in Europe and the United States. Efficacious treatments exist for alcohol use disorder, but they are seldomly prescribed for patients who need them. Besides, the presence of liver cirrhosis can complicate pharmacological treatment choices. In this review, we discuss established and innovative treatment strategies to treat unhealthy alcohol use in patients with alcohol-associated liver disease. We also describe the experience of our own institutions, Hospital Universitari Germans Trias i Pujol in Badalona (Spain) and Yale-New Haven Health and Yale Medicine (Connecticut. United States of America).

Functional constipation (FC) is a common condition in childhood in the United Kingdom and worldwide. Various radiological approaches have been established for diagnostic purposes. The radiopaque marker study (ROMS) is universally accepted and used to assess colonic transit time (CTT) in children with FC. Despite being widely used, there is a lack of standardization with various technical protocols, reproducibility of different populations, the purpose for using investigation, variance in the number of markers used, the amount of study days and calculations, the need to empty the colon before performing the test, and whether to perform on medication or off, or the use of specific diets. As part of the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) motility working group (MWG), we decided to explore further into the evidence, in order to provide guidance regarding the use of ROMS in dealing with FC in the pediatric population. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease affects millions of people worldwide. Progress towards a definitive cure has been incremental and treatment is currently limited to lifestyle modification. Hepatocyte-specific lipid accumulation is the main trigger of lipotoxic events, driving inflammation and fibrosis. The underlying pathology is extraordinarily heterogenous, and the manifestations of steatohepatitis are markedly influenced by metabolic communications across non-hepatic organs. Synthetic human tissue models have emerged as powerful platforms to better capture the mechanistic diversity in disease progression, while preserving person-specific genetic traits. In this review, we will outline current research efforts focused on integrating multiple synthetic tissue models of key metabolic organs, with an emphasis on organoid-based systems. By combining functional genomics and population-scale en masse profiling methodologies, human tissues derived from patients can provide insights into personalised genetic, transcriptional, biochemical, and metabolic states. These collective efforts will advance our understanding of steatohepatitis and guide the development of rational solutions for mechanism-directed diagnostic and therapeutic investigation. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusions Transjugular intrahepatic portosystemic shunt (TIPS) is an important therapy for complications of portal hypertension but remains underutilised in regional settings.The aim of this study is to explore the demographics, indications, outcomes and complications in patients undergoing TIPS in two regional hepatology centres.Retrospective analysis was undertaken of all patients undergoing TIPS at two regional centres between January 2017 and March 2023. The primary outcome measures were efficacy and complications of TIPS. Patient demographics (such as age, baseline liver severity scores and aetiology of liver disease) and indications for TIPS are detailed.Forty‐eight patients underwent TIPS. Median age was 56 years (interquartile range (IQR): 46–65). The most common indications for TIPS were refractory ascites (n = 17) and failure of secondary prophylaxis of variceal bleeding (n = 13). Cumulative survival at 3 months and 1 year was 93% and 77% respectively. There was no significant difference in outcomes based on TIPS indication. The median number of paracenteses in patients undergoing TIPS for refractory ascites 1 year pre‐ and post‐TIPS were 10 (IQR: 4.5–16) and 2 (IQR: 0–4) respectively (P < 0.001). There were no procedure‐related deaths. Inpatient management of liver disease complications had a mean cost of $32 874.67 (SEM: 7779) in 1 year pre‐TIPS compared with $12 304.70 (SEM: 3531.1) in 1 year post‐TIPS (P < 0.001).TIPS is a safe and effective treatment to reduce complications of portal hypertension and can be performed successfully in the regional setting. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common liver disease worldwide in recent years. MASLD commonly presents as simple hepatic steatosis, but ~25% of patients develop liver inflammation, progressive fibrosis, liver cirrhosis and related hepatocellular carcinoma. Liver inflammation and the degree of fibrosis are key determinants of the prognosis. The pathophysiology of liver inflammation is incompletely understood and involves diverse factors and specifically innate and adaptive immune responses. More specifically, diverse mediators of innate immunity such as proinflammatory cytokines, adipokines, inflammasomes and various cell types like mononuclear cells, macrophages and natural killer cells are involved in directing the inflammatory process in MASLD. The activation of innate immunity is driven by various factors including excess lipids and lipotoxicity, insulin resistance and molecular patterns derived from gut commensals. Targeting pathways of innate immunity might therefore appear as an attractive therapeutic strategy in the future management of MASLD and possibly its complications. [ABSTRACT FROM AUTHOR]

Rhythmic intraorgan communication coordinates environmental signals and the cell-intrinsic clock to maintain organ homeostasis. Hepatocyte-specific KO of core components of the molecular clock Rev-erbα and -β (Reverb-hDKO) alters cholesterol and lipid metabolism in hepatocytes as well as rhythmic gene expression in nonparenchymal cells (NPCs) of the liver. Here, we report that in fatty liver caused by diet-induced obesity (DIO), hepatocyte SREBP cleavage-activating protein (SCAP) was required for Reverb-hDKO-induced diurnal rhythmic remodeling and epigenomic reprogramming in liver macrophages (LMs). Integrative analyses of isolated hepatocytes and LMs revealed that SCAP-dependent lipidomic changes in REV-ERB-depleted hepatocytes led to the enhancement of LM metabolic rhythms. Hepatocytic loss of REV-ERBα and β (REV-ERBs) also attenuated LM rhythms via SCAP-independent polypeptide secretion. These results shed light on the signaling mechanisms by which hepatocytes regulate diurnal rhythms in NPCs in fatty liver disease caused by DIO.

Omar E Hegazi,1,2 Samer O Alalalmeh,1,2 Moyad Shahwan,1,2 Ammar Abdulrahman Jairoun,3,4 Mansour M Alourfi,5,6 Ghfran Abdulrahman Bokhari,6 Abdullah Alkhattabi,6 Saeed Alsharif,7 Mohannad Abdulrahman Aljehani,8 Abdulmalik Mohammed Alsabban,9 Mohammad Almtrafi,9 Ysear Abdulaziz Zakri,9 Abdullah AlMahmoud,10 Khalid Mohammed Alghamdi,10 Ahmed M Ashour,11 Nasser M Alorfi11 1Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates; 2Department of Clinical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman, United Arab Emirates; 3Health and Safety Department, Dubai, United Arab Emirates; 4School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia; 5Internal medicine Department, King Faisal Medical City for Southern Region, Abha, Saudi Arabia; 6Department of gastroenterology, East Jeddah hospital, Jeddah, Saudi Arabia; 7Gastroenterology Department, Armed force Hospital of southern region, Khamis Mushait, Saudi Arabia; 8Division of Gastroenterology, Department of Medicine, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia; 9Gastroenterology Section, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia; 10Gastroenterology Section, Internal Medicine Department, King Fahad Hospital, Jeddah, Saudi Arabia; 11Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi ArabiaCorrespondence: Nasser M Alorfi, Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia, Email Nmorfi@uqu.edu.saBackground: Non-alcoholic fatty liver disease (NAFLD) is a common disease and has been increasing in recent years. To date, no FDA-approved drug specifically targets NAFLD.Methods: The terms “Non-alcoholic Fatty Liver Disease” and “NAFLD” were used in a search of ClinicalTrials.gov on August 24, 2023. Two evaluators independently examined the trials using predetermined eligibility criteria. Studies had to be interventional, NAFLD focused, in Phase IV, and completed to be eligible for this review.Results: The ClinicalTrials.gov database was searched for trials examining pharmacotherapeutics in NAFLD. The search revealed 1364 trials, with 31 meeting the inclusion criteria. Out of these, 19 were finalized for evaluation. The dominant intervention model was Parallel. The most prevalent studies were in Korea (26.3%) and China (21.1%). The most common intervention was metformin (12.1%), with others like Exenatide and Pioglitazone accounting for 9.1%.Conclusion: Therapeutics used to manage NAFLD are limited. However, various medications offer potential benefits. Further investigations are definitely warranted.Keywords: NAFLD, hepatology, clinical trials, therapeutics, metabolic disorder

Abstract Background Unhealthy alcohol use (UAU) is particularly dangerous for people with chronic liver disease. Liver clinics may be an important setting in which to provide effective alcohol-related care by integrating evidence-based strategies, such as brief intervention and medications for alcohol use disorder. We conducted qualitative interviews with clinical stakeholders and patients at liver clinics in four Veterans Health Administration (VA) medical centers to understand barriers and facilitators of integrating alcohol-related care and to support tailoring of a practice facilitation implementation intervention. Methods Data collection and analysis were guided by the Consolidated Framework for Implementation Research (CFIR). Interviews were transcribed and qualitatively analyzed using a Rapid Assessment Process (RAP) guided by the CFIR. Results We interviewed 46 clinical stakeholders and 41 patient participants and analyzed findings based on the CFIR. Clinical stakeholders described barriers and facilitators that ranged from operations/clinic resource-based (e.g., time and capacity, desire for additional provider types, referral processes) to individual perspective and preference-based (e.g., supportiveness of leadership, individual experiences/beliefs). Patient participants shared barriers and facilitators that ranged from relationship-based (e.g., trusting the provider and feeling judged) to resource and education-based (e.g., connection to a range of treatment options, education about impact of alcohol). Many barriers and facilitators to integrating alcohol-related care in liver clinics were similar to those identified in other clinical settings (e.g., time, resources, role clarity, stigmatizing beliefs). However, some barriers (e.g., fellow-led care and lack of integration of liver clinics with addictions specialists) and facilitators (e.g., presence of quality improvement staff in clinics and integrated pharmacists and behavioral health specialists) were more unique to liver clinics. Conclusions These findings support the possibility of integrating alcohol-related care into liver clinics but highlight the importance of tailoring efforts to account for variation in provider beliefs and experiences and clinic resources. The barriers and facilitators identified in these interviews were used to tailor a practice facilitation implementation intervention in each clinic setting.

The issues of changes in clinical, laboratory and instrumental parameters in cats with hepatocardial syndrome formed against the background of hypertrophic cardiomyopathy were studied. It is known that in high-bred cats with congestive heart failure, secondary hepatopathy can develop and progress. It was shown that hepatocardial syndrome occurs in 33.7 % of cats, out of the total number of patients with hypertrophic cardiomyopathy (n = 83). It has been established that hepatocardial complications in cats are a risk factor for a more severe course of hypertrophic cardiomyopathy. Hepatocardial syndrome in cats with hypertrophic cardiomyopathy is characterized by severe hypothermia, circulatory and respiratory failure. In sick animals, an increase in frequency of breathing during sleep was recorded (33.39.3 versus 17.91.8 times/min; p 0.001). Domestic cats with hepatocardial syndrome had a decrease in mean arterial blood pressure (100.219.3 versus 107.219.1 mm Hg; p 0.05), sinus tachycardia (200.319.6 17.8 times/min; p 0.001), which leads to a significant decrease in PQ intervals (57.99.9 versus 64.99.9 ms; p 0.001) and QT intervals (168.917, 2 vs 157.518.6 ms; p 0.001). Sick cats had a significant increase in the time of refilling of capillaries with blood, slowdown in intraventricular conduction, increase in voltage of ventricular and atrial complex on electrocardiograms, expansion of pulmonary vein, significant dilatation of left atrium, extreme concentric hypertrophy of left ventricle, increase in transverse contractility of myocardium of left ventricle and decrease in longitudinal contractility myocardium of left and right ventricles, cardiomyocyte cytolysis syndrome, cholestasis, and hypoalbuminemia

BackgroundStudies have reported that the COVID-19 pandemic has led to an increase in alcohol consumption and alcohol-associated health problems in the general population. Our previous study documented a rise in severe alcohol-related hepatitis cases requiring inpatient admission in our hospital system in the early pandemic (2019 vs. 2020). This study assesses the rates of severe alcohol-related hepatitis in the latter part of the pandemic (2021).MethodsWe performed a retrospective chart review via an electronic medical record to evaluate the number of cases of alcohol-related hepatitis in patients presenting to three community hospitals in Fresno, California, between 2019 (pre-pandemic) and 2021. A total of 547 patients were included in the study. We compared the demographics, clinical course, and outcomes of patients with alcohol-related hepatitis pre-pandemic (2019), early pandemic (2020), and during the later phase of the pandemic (2021).ResultsThe number of cases increased from 131 in 2019 to 201 in 2020 and 215 in 2021 (53% and 64% increase, respectively). The number of young patients (age

Although glycogen synthase kinase β (Gsk3β) has been shown to regulate tissue inflammation, whether and how it regulates inflammation resolution versus inflammation activation is unclear. In a murine liver, partial warm ischemia/reperfusion injury (IRI) model, we found that Gsk3β inhibitory phosphorylation increased at both the early-activation and late-resolution stages of the disease. Myeloid Gsk3β deficiency not only alleviated liver injuries, it also facilitated the restoration of liver homeostasis. Depletion of Kupffer cells prior to the onset of liver ischemia diminished the differences between the WT and Gsk3β-KO mice in the activation of liver IRI. However, the resolution of liver IRI remained accelerated in Gsk3β-KO mice. In CD11b-DTR mice, Gsk3β-deficient BM-derived macrophages (BMMs) facilitated the resolution of liver IRI as compared with WT cells. Furthermore, Gsk3β deficiency promoted the reparative phenotype differentiation in vivo in liver-infiltrating macrophages and in vitro in BMMs. Gsk3 pharmacological inhibition promoted the resolution of liver IRI in WT, but not myeloid MerTK-deficient, mice. Thus, Gsk3β regulates liver IRI at both activation and resolution stages of the disease. Gsk3 inactivation enhances the proresolving function of liver-infiltrating macrophages in an MerTK-dependent manner.

BACKGROUND AND OBJECTIVE: Over the years, telemedicine has played a prominent role in delivering healthcare to patients. Due to its flexibility and many benefits, telemedicine confers physicians the ability to guide and promote medical care remotely. The advent of the coronavirus disease 2019 (COVID-19) pandemic has changed the landscape of medicine and has accelerated the usage of digital and remote healthcare systems for clinical care. Herein, we provide an overview of telemedicine, its applications in managing inflammatory bowel disease (IBD), celiac disease (CD), and liver diseases, its advantages and limitations, and its use in educating the next generation of gastroenterologists. METHODS: We conducted a review of scientific articles published in PubMed and Google Scholar. Articles were selected based on the search terms included in the search strategy summary. The language of the articles was restricted to English only. KEY CONTENT AND FINDINGS: We report that telemedicine has the potential to streamline and improve patient care in gastroenterology (GI) and hepatology while also limiting health care expenses. Additionally, we noted the importance of tele-education for training the next generation of physicians who intend on practicing in rural settings. Furthermore, we identified barriers to telemedicine care that exacerbate health inequities and potential solutions to achieving digital health equity. Lastly, we briefly discuss the role of artificial intelligence (AI) in remote patient monitoring. CONCLUSIONS: Although telemedicine has existed for many decades, over the past decade there have been many advancements in telemedicine applications in GI and hepatology. Despite its broad benefits, further research needs to be done to alleviate barriers to telemedicine care.

Background & aimsNon-invasive tests (NITs) offer a practical solution for advanced fibrosis identification in non-alcoholic fatty liver disease (NAFLD). Despite increasing implementation, their use is not standardised, which can lead to inconsistent interpretation and risk stratification. We aimed to assess the types of NITs and the corresponding cut-offs used in a range of healthcare settings.MethodsA survey was distributed to a convenience sample of liver health experts who participated in a global NAFLD consensus statement. Respondents provided information on the NITs used in their clinic with the corresponding cut-offs and those used in established care pathways in their areas.ResultsThere were 35 respondents from 24 countries, 89% of whom practised in tertiary level settings. A total of 14 different NITs were used, and each respondent reported using at least one (median = 3). Of the respondents, 80% reported using FIB-4 and liver stiffness by vibration-controlled transient elastography (Fibroscan®), followed by the NAFLD fibrosis score (49%). For FIB-4, 71% of respondents used a low cut-off of 7.5 to >20 kPa, respectively).ConclusionsThe cut-offs used for the same NITs for NAFLD risk stratification vary between clinicians. As cut-offs impact test performance, these findings underscore the heterogeneity in risk-assessment and support the importance of establishing consistent guidelines on the standardised use of NITs in NAFLD management.Lay summaryOwing to the high prevalence of non-alcoholic fatty liver disease (NAFLD) in the general population it is important to identify those who have more advanced stages of liver fibrosis, so that they can be properly treated. Non-invasive tests (NITs) provide a practical way to assess fibrosis risk in patients. However, we found that the cut-offs used for the same NITs vary between clinicians. As cut-offs impact test performance, these findings highlight the importance of establishing consistent guidelines on the standardised use of NITs to optimise clinical management of NAFLD.

IntroductionImplementation strategies supporting the translation of evidence into practice need to be tailored and adapted for maximum effectiveness, yet the field of adapting implementation strategies remains nascent. We aimed to adapt "Getting To Outcomes"® (GTO), a 10-step implementation playbook designed to help community-based organizations plan and evaluate behavioral health programs, into "Getting To Implementation" (GTI) to support the selection, tailoring, and use of implementation strategies in health care settings.MethodsOur embedded evaluation team partnered with operations, external facilitators, and site implementers to employ participatory methods to co-design and adapt GTO for Veterans Health Administration (VA) outpatient cirrhosis care improvement. The Framework for Reporting Adaptations and Modifications to Evidenced-based Implementation Strategies (FRAME-IS) guided documentation and analysis of changes made pre- and post-implementation of GTI at 12 VA medical centers. Data from multiple sources (interviews, observation, content analysis, and fidelity tracking) were triangulated and analyzed using rapid techniques over a 3-year period.ResultsAdaptations during pre-implementation were planned, proactive, and focused on context and content to improve acceptability, appropriateness, and feasibility of the GTI playbook. Modifications during and after implementation were unplanned and reactive, concentrating on adoption, fidelity, and sustainability. All changes were collaboratively developed, fidelity consistent at the level of the facilitator and/or implementer.ConclusionGTO was initially adapted to GTI to support health care teams' selection and use of implementation strategies for improving guideline-concordant medical care. GTI required ongoing modification, particularly in steps regarding team building, context assessment, strategy selection, and sustainability due to difficulties with step clarity and progression. This work also highlights the challenges in pragmatic approaches to collecting and synthesizing implementation, fidelity, and adaptation data.Trial registrationThis study was registered on ClinicalTrials.gov (Identifier: NCT04178096).

Glutamine synthetase (GS) catalyzes de novo synthesis of glutamine that facilitates cancer cell growth. In the liver, GS functions next to the urea cycle to remove ammonia waste. As a dysregulated urea cycle is implicated in cancer development, the impact of GS's ammonia clearance function has not been explored in cancer. Here, we show that oncogenic activation of β-catenin (encoded by CTNNB1) led to a decreased urea cycle and elevated ammonia waste burden. While β-catenin induced the expression of GS, which is thought to be cancer promoting, surprisingly, genetic ablation of hepatic GS accelerated the onset of liver tumors in several mouse models that involved β-catenin activation. Mechanistically, GS ablation exacerbated hyperammonemia and facilitated the production of glutamate-derived nonessential amino acids, which subsequently stimulated mechanistic target of rapamycin complex 1 (mTORC1). Pharmacological and genetic inhibition of mTORC1 and glutamic transaminases suppressed tumorigenesis facilitated by GS ablation. While patients with hepatocellular carcinoma, especially those with CTNNB1 mutations, have an overall defective urea cycle and increased expression of GS, there exists a subset of patients with low GS expression that is associated with mTORC1 hyperactivation. Therefore, GS-mediated ammonia clearance serves as a tumor-suppressing mechanism in livers that harbor β-catenin activation mutations and a compromised urea cycle.

Introduction and Objectives: Liver transplant (LT) is a recent option available in the United States (US) to treat those with severe, refractory alcoholic hepatitis (AH). We examined changes in clinical characteristics of patients admitted with AH and tracked hospital outcomes as practice changes involving LT have shifted. Materials and Methods: Using the National Inpatient Sample, we performed a cross-sectional analysis of patients admitted with AH during the years 2016–2020 in the US. Differences in clinical characteristics over time were assessed. To compare outcomes between 2016–2017 (when LT was less common) and 2018–2020 (when LT was more common), we conducted linear and logistic regression. Propensity-score matching was used to compare outcomes between patients with and without LT. Results: From 2016–2017 to 2018–2020, patients admitted with AH tended to have a higher frequency of infection (p = 0.006), hepatorenal syndrome (

Introduction: Stereotactic body radiation therapy (SBRT) is associated with high local control rates in hepatocellular carcinoma (HCC). This study reports the outcomes of SBRT compared to surgical resection (SR) and percutaneous ablation (PA) for treatment‐naïve, solitary HCCs ≤3 cm. Methods: This was a retrospective study of patients with BCLC stage 0/A HCC with a single ≤3 cm lesion, treated with curative intent between 2016 and 2020. SBRT was used for patients considered unsuitable for SR or PA. The co‐primary endpoints were progression‐free survival (PFS) and overall survival (OS). The secondary endpoints were treatment‐related clinical toxicity rates and local control (LC) rates. Results: There were 112 patients included in this study. SBRT was delivered in 36 patients (32.1%), 51 had PA (45.5%) and 25 underwent SR (22.3%). Median follow‐up was 23 months (range, 3–60 months) from diagnosis. The 3‐year PFS and OS were 67% and 69% following SBRT, 55% and 80% following PA, and 85% and 100% following SR, respectively. Patients in the SR cohort had significantly better 3‐year PFS and OS compared to SBRT and PA groups (p = 0.03 and p = 0.04, respectively). There was no significant difference in PFS (p = 0.15) or OS (p = 0.23) between SBRT and PA treated patients. The 3‐year LC rate for the entire cohort was 98%. Conclusions: In patients with treatment‐naïve, early‐stage solitary HCCs ≤3 cm, SBRT was associated with comparable PFS, OS and LC outcomes to PA. SBRT should be considered as a curative intent therapy to avoid treatment stage migration in this favourable prognostic cohort of patients. [ABSTRACT FROM AUTHOR]

The prevention of liver disease has improved significantly in the last few decades, to the point that it can now be considered a true success story. The wide variety of interventions, including comprehensive vaccination strategies, novel medications, lifestyle changes, and even preventive surgeries, have reduced the morbidity and mortality of chronic liver diseases. However, the prevalence of chronic liver diseases is increasing worldwide. Currently, fatty liver disease alone is estimated to be present in as much as 30% of the adult population. Furthermore, there is a trend towards increasing incidences of chronic hepatitis B, and a global lack of success in efforts to eliminate chronic hepatitis C. Thus, improving and efficiently rolling out existing and successful prevention strategies for chronic liver diseases will play an essential role in healthcare throughout the upcoming decades. In this review, we summarize the current options and concepts for preventing chronic liver diseases, highlight their limitations, and provide an outlook on probable future developments to improve awareness, integrated care, and the analysis of big data. [ABSTRACT FROM AUTHOR]

Aim: There has been an increased focus on regulating cell function with Rho family GTPases, including proliferation, migration/invasion, polarity, and adhesion. Due to the challenges involved in targeting Rho family GTPases directly, it may be more effective to target their regulators, such as Rho GTPase‐activating protein 1 (ARHGAP1). This present research was performed to define the clinical significance of ARHGAP1 expression, as well as its regulatory mechanisms in hepatocellular carcinoma. Methods: ARHGAP1 and miR‐101‐3p expression of liver cancer patients, and their relevance with clinicopathological characteristics and prognosis were analyzed by the Cancer Genome Atlas sequencing data, and verified using samples of hepatocellular carcinoma patients. The interactions between miR‐101‐3p and ARHGAP1 or circPIP5K1A were validated by bioinformatic analyses, as well as confirmed by quantitative reverse transcription polymerase chain reaction, western blotting, and dual‐luciferase reporter analysis. Plate clonality assays, cell adhesion and migration experiments, and proliferation experiments were used for assessing the participation of the circPIP5K1A/miR‐101‐3p/ARHGAP1 pathway in cell proliferation and motility. Results: Elevated ARHGAP1 and reduced miR‐101‐3p expression are related to poorer survival. MiR‐101‐3p targets ARHGAP1 to suppress hepatocellular carcinoma cell colony formation and invasion, whereas miR‐101‐3p inhibitor reverses liver cancer proliferation and metastasis suppression caused by ARHGAP1 knockdown. In addition, circPIP5K1A, which is mainly distributed in the cytosol, showed carcinogenic effects by sponging miR‐101‐3p, thus regulating ARHGAP1 expression. Conclusions: ARHGAP1 serves as an oncogenic gene in liver cancer, and the expression thereof is regulated by circPIP5K1A through sponging miR‐101‐3p. [ABSTRACT FROM AUTHOR]

Alanine aminotransferase (ALT) represents the first-level test to detect individuals with hepatocellular damage of any etiology. However, it has been highlighted that the lack of assay harmonization may lead to overdiagnosis and unnecessary further testing if guideline-recommended fixed cut-offs are uncritically employed. To solve the issue of ALT (dis)harmonization and improve the interpretation of its values, a series of urgent actions for documenting and validating metrological traceability of serum ALT measurements, as described in this paper, are no longer postponeable. It is time that all medical laboratory stakeholders (in vitro diagnostic manufacturers, laboratorians, external quality assessment scheme organizers) actively co-operate to implement the ALT standardization in a concerted action following well-established theoretical assumptions and applying experimental approaches described in literature. [ABSTRACT FROM AUTHOR]

We investigated academic developmental trends in emergency medicine (EM) by analyzing the performance of EM journals. Data from the Journal Citation Reports (JCR) database for EM category journals, including journal titles, language, numbers, and impact factors (IFs) from 2000 to 2019 were collected. The aggregate IFs of EM and 11 other categories (cardiac and cardiovascular systems, clinical neurology, critical care medicine, gastroenterology and hepatology, infectious diseases, general and internal medicine, pediatrics, respiratory system, surgery, toxicology, and urology and nephrology) were collected from 2003 to 2019. The slope of the linear regression was used to evaluate the trend in EM journal IFs and the aggregate IFs of all categories. Pearson’s correlation coefficient was used to evaluate the correlation between EM journals’ IF in 2000 and their IF trend from 2000 to 2019. The EM journal number increased from 8 (all in English) in 2000 to 31 (26 in English) in 2019. In total, 28 EM journals had a positive IF trend since their initial enrollment into the JCR database, and the trend was significant for 18 journals. The correlation of the EM journals’ IF in 2000 and IF trends from 2000 to 2019 was 0.75. The increasing trend of aggregate IF for the EM category was significant. In conclusion, the increased number, language diversity, and IF trend for EM journals indicates that the development of academic EM is a continuous international trend. In the past 20 years, the IF trend increased faster for EM journals with a higher initial IF. The overall performance of EM journals was non-inferior to other medical specialties. [ABSTRACT FROM AUTHOR]

Data are being generated, collected, and aggregated in massive quantities at exponentially increasing rates. This "big data," discussed in depth in the first section of this two-part series, is increasingly important to understand the nuances of the gastrointestinal tract and its complex interactions and networks involving a host of other organ systems and microbes. Creating and using these datasets correctly requires comprehensive training; however, current instruction in the integration, analysis, and interpretation of big data appears to lag far behind data acquisition. While opportunities exist for those interested in acquiring the requisite training, these appear to be underutilized, in part due to widespread ignorance of their existence. Here, to address these gaps in knowledge, we highlight existing big data learning opportunities and propose innovative approaches to attain such training. We offer suggestions at both the undergraduate and graduate medical education levels for prospective clinical and basic investigators. Lastly, we categorize training opportunities that can be selected to fit specific needs and timeframes. [ABSTRACT FROM AUTHOR]

A multitude of federally and industry-funded efforts are underway to generate and collect human, animal, microbial, and other sources of data on an unprecedented scale; the results are commonly referred to as "big data." Often vaguely defined, big data refers to large and complex datasets consisting of myriad datatypes that can be integrated to address complex questions. Big data offers a wealth of information that can be accessed only by those who pose the right questions and have sufficient technical knowhow and analytical skills. The intersection comprised of the gut-brain axis, the intestinal microbiome and multi-ome, and several other interconnected organ systems poses particular challenges and opportunities for those engaged in gastrointestinal and liver research. Unfortunately, there is currently a shortage of clinicians, scientists, and physician-scientists with the training needed to use and analyze big data at the scale necessary for widespread implementation of precision medicine. Here, we review the importance of training in the use of big data, the perils of insufficient training, and potential solutions that exist or can be developed to address the dearth of individuals in GI and hepatology research with the necessary level of big data expertise. [ABSTRACT FROM AUTHOR]

Gastrointestinal endoscopy has long been a reliable backbone in the diagnosis and management of hepatobilary disorders and their complications. However, with evolving non-invasive testing, personalised medicine has reframed the utility and necessity of endoscopic screening. Conversely, the growing interest and use of endoscopic ultrasound (EUS) and advanced endoscopy within gastrointestinal units has also opened novel diagnostic and therapeutic avenues for patients with various hepatobiliary diseases. The integration of "advanced endoscopy" within the practice of hepatology is nowadays referred to as "endo-hepatology". In essence, endo-hepatology consists of two pillars: one focusing primarily on disorders of the liver parenchyma, vascular disorders, and portal hypertension, which is mainly captured via EUS, while the other targets the hepatobiliary tract via endoscopic retrograde cholangiopancreatography and advanced imaging. Applications under the umbrella of endo-hepatology include, amongst others, EUS-guided liver biopsy, EUS-guided portal pressure gradient measurement, coil and glue embolisation of gastric varices as well as cholangioscopy. As such endo-hepatology could become an attractive concept wherein advanced endoscopy might reinforce the medical management of patients with hepatobiliary disorders and their complications after initial basic work-up. In this review, we discuss current trends and future developments within endo-hepatology and the remaining hurdles to overcome. [ABSTRACT FROM AUTHOR]

This study analyzed the results of a transition program in a patient population with a rare liver disease of pediatric onset. Data were collected on the clinical course of an adolescent population with a rare disease of pediatric onset and enrolled in a transition program between 1994 and 2022. A total of 238 adolescents (including 34 having undergone a liver transplant on enrolling in the program) were included. Eight patients were lost to follow-up before the first transition consultation and 16 families requested follow-up in an adult hepatology department closer to their home. Overall, 214 initial transition consultations were carried out; 29 patients were subsequently lost to follow-up and 13 switched center. Overall, 15.4 % of the patients enrolled in our program were lost to follow-up. Five adult patients underwent a liver transplantation during this 28-year period. Overall mortality was 3.2 %, graft survival was 91.5 %, and posttransplant survival was 92 %. In total, the current active file represents 183 patients with a median age of 24.3 years (18–51) and a median follow-up period of 5.8 years (6 months to 28 years). The implementation of a transition program to adult medicine for adolescents with a rare liver disease should follow the recommendations but must be adapted in line with local practice conditions. This process requires close collaboration between the pediatric and adult medicine teams based on a mutual desire to constantly improve practices and enhance knowledge. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, represents a growing health challenge worldwide. The incidence of HCC is rising, which, in turn, has led to a corresponding increase in the associated number of deaths. HCC will become the third leading cause of cancer-related deaths in the United States by 2030. HCC usually develops in the setting of chronic liver disease. Individuals at increased risk of HCC are recommended to undergo surveillance with ultrasound every 6 months along with serum α-fetoprotein testing. Computed tomography (CT) and magnetic resonance imaging (MRI) are considered alternatives based on specific patient factors. Lesions suspicious for HCC are recommended to undergo a diagnostic testing, which includes contrast-enhanced multiphase CT or MRI and liver biopsy when findings are indeterminate. The Barcelona Clinic Liver Cancer prognosis and treatment strategy is the most used assessment for patients with HCC (Fig. 2). Curative therapies include resection, liver transplantation, and ablation. Locoregional therapies, such as transarterial chemoembolization and radioembolization, can be used for patients with intermediate-stage HCC. For patients with advanced-stage HCC, systemic therapy is often used. This review aims to provide an overview of HCC from a hepatologist's perspective, including epidemiology, screening, surveillance, diagnosis, and management. [ABSTRACT FROM AUTHOR]

The document titled "Author Index" is a list of authors published in the Journal of Gastroenterology & Hepatology. It includes the names of various authors along with their corresponding articles. The list is organized alphabetically by last name and provides a comprehensive index of authors who have contributed to the journal. This index can be a valuable resource for library patrons conducting research on specific topics within the field of gastroenterology and hepatology. [Extracted from the article]

The word endo-hepatology evokes many perceptions. Some believe it to be the emerging new interventional branch and some believe it to be an extension of endoscopy. Nonetheless, it has continued to evolve into an exciting area of active work. With the advent of endoscopic ultrasound (EUS) based procedures, new vistas have opened up. EUS-guided liver biopsies, portal hypertension management, and multiple new procedures are being described. EUS also plays a large role in the management of patients in the peritransplant period. With this review, we present an overview of the role of EUS in the field of hepatology as well as during the peritransplant period and its applications. [ABSTRACT FROM AUTHOR]

Lay summaries exist to bridge the gap that separates the scientific community from the general public. To foster improved science communication, this study examined the overall quality and readability of published lay summaries across peer-reviewed journals. We obtained 200 lay summaries published in four science journals: eLife, PLOS Medicine, Proceedings of the National Academy of Science (PNAS), and the Journal of Hepatology. Over 900 students across three semesters participated as raters of each summary using a rubric developed to assess the overall quality, accuracy, and accessibility of lay summaries across these journals. The Flesch Reading Ease formula was used to determine the readability of the highest and lowest scoring summaries from each journal. eLife and the Journal of Hepatology had the highest and lowest mean scores for overall quality of 15.6 and 11.7 out of 20, respectively. There were statistically significant differences in accuracy and accessibility found across all journals (p<0.0001). eLife had the highest scoring lay summary for readability. The differences in and lack of consistent scoring across journals with the rubric indicate that deficits exist in the overall quality and readability of published lay summaries. These findings may support the development of guidelines that incorporate elements of the rubric used to write effective lay summaries. [ABSTRACT FROM AUTHOR]

Alcohol-associated liver disease is currently the leading cause of liver transplantation and liver deaths both in Europe and the United States. Efficacious treatments exist for alcohol use disorder, but they are seldomly prescribed for patients who need them. Besides, the presence of liver cirrhosis can complicate pharmacological treatment choices. In this review, we discuss established and innovative treatment strategies to treat unhealthy alcohol use in patients with alcohol-associated liver disease. We also describe the experience of our own institutions, Hospital Universitari Germans Trias i Pujol in Badalona (Spain) and Yale-New Haven Health and Yale Medicine (Connecticut. United States of America). [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Liver transplant (LT) is a recent option available in the United States (US) to treat those with severe, refractory alcoholic hepatitis (AH). We examined changes in clinical characteristics of patients admitted with AH and tracked hospital outcomes as practice changes involving LT have shifted. Materials and Methods: Using the National Inpatient Sample, we performed a cross-sectional analysis of patients admitted with AH during the years 2016-2020 in the US. Differences in clinical characteristics over time were assessed. To compare outcomes between 2016-2017 (when LT was less common) and 2018 -2020 (when LT was more common), we conducted linear and logistic regression. Propensity-score matching was used to compare outcomes between patients with and without LT. Results: From 2016-2017 to 2018-2020, patients admitted with AH tended to have a higher frequency of infection (p = 0.006), hepatorenal syndrome (<0.001), and ascites (<0.001). Hospital costs and length of stay (LOS) were highest in transplant hospitals, and costs rose over time in both non-transplant (NT) teaching and non-teaching hospitals (p < 0.001). Mortality decreased in NT teaching hospitals [aOR 0.7 (95% CI: 0.6-0.8)] and slightly decreased in NT non-teaching hospitals [aOR 0.7 (95% CI: 0.5-1.0)]. In the propensity-matched cohort involving LT versus non-LT patients, there was a 10% absolute reduction in-hospital mortality, but this came at a higher cost (p < 0.001) and length of stay (p < 0.001). Conclusions: The severity of AH has been increasing over time, yet mortality has declined after adjusting for severity of disease. Patients who underwent LT survived; however, the healthcare burden of LT is substantial. [ABSTRACT FROM AUTHOR]

BACKGROUNDA pilot, single-center study showed that first-degree relatives of probands with nonalcoholic fatty liver disease (NAFLD) cirrhosis have a high risk of advanced fibrosis. We aimed to validate these findings using 2 independent cohorts from the US and Europe.METHODSThis prospective study included probands with NAFLD with advanced fibrosis, NAFLD without advanced fibrosis, and non-NAFLD, with at least 1 first-degree relative. A total of 396 first-degree relatives - 220 in a derivation cohort and 176 in a validation cohort - were enrolled in the study, and liver fibrosis was evaluated using magnetic resonance elastography and other noninvasive imaging modalities. The primary outcome was prevalence of advanced fibrosis in first-degree relatives.RESULTSPrevalence of advanced fibrosis in first-degree relatives of probands with NAFLD with advanced fibrosis, NAFLD without advanced fibrosis, and non-NAFLD was 15.6%, 5.9%, and 1.3%, respectively (P = 0.002), in the derivation cohort, and 14.0%, 2.6%, and 1.3%, respectively (P = 0.004), in the validation cohort. In multivariable-adjusted logistic regression models, age of ≥50 years (adjusted OR [aOR]: 2.63, 95% CI 1.0-6.7), male sex (aOR: 3.79, 95% CI 1.6-9.2), diabetes mellitus (aOR: 3.37, 95% CI 1.3-9), and a first-degree relative with NAFLD with advanced fibrosis (aOR: 11.8, 95% CI 2.5-57) were significant predictors of presence of advanced fibrosis (all P < 0.05).CONCLUSIONFirst-degree relatives of probands with NAFLD with advanced fibrosis have significantly increased risk of advanced fibrosis. Routine screening should be done in the first-degree relatives of patients with advanced fibrosis.FUNDINGSupported by NCATS (5UL1TR001442), NIDDK (U01DK061734, U01DK130190, R01DK106419, R01DK121378, R01DK124318, P30DK120515, K23DK119460), NHLBI (P01HL147835), and NIAAA (U01AA029019); Academy of Finland grant 309263; the Novo Nordisk, EVO, and Sigrid Jusélius Foundations; and the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement 777377. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and the EFPIA.

Horses and other equids can be infected with several viruses of the family Flaviviridae, belonging to the genus Flavivirus and Hepacivirus. This consensus statement focuses on viruses with known occurrence in Europe, with the objective to summarize the current literature and formulate clinically relevant evidence-based recommendations regarding clinical disease, diagnosis, treatment, and prevention. The viruses circulating in Europe include West Nile virus, tick-borne encephalitis virus, Usutu virus, Louping ill virus and the equine hepacivirus. West Nile virus and Usutu virus are mosquito-borne, while tick-borne encephalitis virus and Louping ill virus are tick-borne. The natural route of transmission for equine hepacivirus remains speculative. West Nile virus and tick-borne encephalitis virus can induce encephalitis in infected horses. In the British Isle, rare equine cases of encephalitis associated with Louping ill virus are reported. In contrast, equine hepacivirus infections are associated with mild acute hepatitis and possibly chronic hepatitis. Diagnosis of flavivirus infections is made primarily by serology, although cross-reactivity occurs. Virus neutralization testing is considered the gold standard to differentiate between flavivirus infections in horses. Hepacivirus infection is detected by serum or liver RT-PCR. No direct antiviral treatment against flavi- or hepacivirus infections in horses is currently available and thus, treatment is supportive. Three vaccines against West Nile virus are licensed in the European Union. Geographic expansion of flaviviruses pathogenic for equids should always be considered a realistic threat, and it would be beneficial if their detection was included in surveillance programs.

The liver regulates energy partitioning and use in a sex-dependent manner, coupling hepatic substrate availability to female reproductive status. Fibroblast growth factor 21 (FGF21) is a hepatokine produced in response to metabolic stress that adaptively directs systemic metabolism and substrate use to reduce hepatic lipid storage. Here we report that FGF21 altered hepatic transcriptional and metabolic responses, and reduced liver triglycerides, in a sex-dependent manner. FGF21 decreased hepatic triglycerides in obese male mice in a weight loss-independent manner; this was abrogated among female littermates. The effect of FGF21 on hepatosteatosis is thought to derive, in part, from increased adiponectin secretion. Accordingly, plasma adiponectin and its upstream adrenergic receptor → cAMP → exchange protein directly activated by cAMP signaling pathway was stimulated by FGF21 in males and inhibited in females. Both ovariectomized and reproductively senescent old females responded to FGF21 treatment by decreasing body weight, but liver triglycerides and adiponectin remained unchanged. Thus, the benefit of FGF21 treatment for improving hepatosteatosis depends on sex but not on a functional female reproductive system. Because FGF21 provides a downstream mechanism contributing to several metabolic interventions, and given its direct clinical importance, these findings may have broad implications for the targeted application of nutritional and pharmacological treatments for metabolic disease.

Nasser M Alorfi, Ahmed M Ashour Pharmacology and Toxicology Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi ArabiaCorrespondence: Nasser M Alorfi, Email Nmorfi@uqu.edu.saBackground: Non-alcoholic fatty liver disease (NAFLD) is a predominant health condition across the world due to its rising prevalence and association with various metabolic disorders. Intermittent fasting (IF) has attracted increasing attention as a dietary approach to addressing weight management and enhancing metabolic well-being, and its potential effects on NAFLD have been a topic of growing research interest.Aim: This review aims to critically evaluate the current evidence on IF’s impact on NAFLD, including the mechanisms underlying the observed effects in older adults (65+).Methods: A comprehensive search of Clinicaltrials.gov was conducted to identify relevant studies that investigated the effects of IF on NAFLD in older adults (65+). Data on study design, sample size, intervention details, and outcomes related to NAFLD were extracted and analyzed.Results: As of April 12th, 2023, there were 1304 clinical trials on NAFLD. Most of these were interventional studies. The investigation focused on completed studies and found that limited clinical trials were identified with limited interventional measures. Only five out of the 1304 studies on NAFLD involved IF. Basic and advanced outcome measures were examined.Conclusion: Although some studies suggest that IF may have potential benefits for NAFLD, the evidence is still limited and inconclusive.Keywords: hepatology, intermittent fasting, metabolic disease, lifestyles, clinical trials

Limited case series describe conflicting results regarding the safety of checkpoint inhibitors (CPI) prior to liver transplantation (LT). We reviewed single-center data on all consecutive patients who underwent LT for hepatocellular carcinoma treated with CPI between January 1, 2018, and January 30, 2021. Time from CPI to LT, immunosuppression, biopsy-proven acute cellular rejection (BPACR), graft loss and death were evaluated. Five patients with a mean age 65 (range 61-71) years underwent LT after CPI with nivolumab. Time from last CPI to LT ranged from 0.3 to 11 months. Two patients with 3 months from the last dose of CPI had BPACR. In conclusion, pretransplant use of CPIs, particularly within 90 days of LT, was associated with BPACR and immune-mediated hepatic necrosis. Future multicenter studies should consider a sufficient interval from the last dose of CPI to LT to mitigate the risk for adverse immune-mediated outcomes and graft loss.

Abstract Introduction Stereotactic body radiation therapy (SBRT) is associated with high local control rates in hepatocellular carcinoma (HCC). This study reports the outcomes of SBRT compared to surgical resection (SR) and percutaneous ablation (PA) for treatment‐naïve, solitary HCCs ≤3 cm. Methods This was a retrospective study of patients with BCLC stage 0/A HCC with a single ≤3 cm lesion, treated with curative intent between 2016 and 2020. SBRT was used for patients considered unsuitable for SR or PA. The co‐primary endpoints were progression‐free survival (PFS) and overall survival (OS). The secondary endpoints were treatment‐related clinical toxicity rates and local control (LC) rates. Results There were 112 patients included in this study. SBRT was delivered in 36 patients (32.1%), 51 had PA (45.5%) and 25 underwent SR (22.3%). Median follow‐up was 23 months (range, 3–60 months) from diagnosis. The 3‐year PFS and OS were 67% and 69% following SBRT, 55% and 80% following PA, and 85% and 100% following SR, respectively. Patients in the SR cohort had significantly better 3‐year PFS and OS compared to SBRT and PA groups (p = 0.03 and p = 0.04, respectively). There was no significant difference in PFS (p = 0.15) or OS (p = 0.23) between SBRT and PA treated patients. The 3‐year LC rate for the entire cohort was 98%. Conclusions In patients with treatment‐naïve, early‐stage solitary HCCs ≤3 cm, SBRT was associated with comparable PFS, OS and LC outcomes to PA. SBRT should be considered as a curative intent therapy to avoid treatment stage migration in this favourable prognostic cohort of patients.

Summary: Cirrhosis is becoming one of the most common diseases worldwide. Abnormal upregulation of transforming growth factor β (TGF-β) signaling plays a pivotal role in the excess activation of hepatic stellate cells. However, an efficient countermeasure against abnormal hepatic stellate cell activation is yet to be established because TGF-β signaling is involved in several biological processes. Herein, we demonstrated the antifibrotic effect of miR-12135, a microRNA with unknown function upregulated by isoflavone. Comprehensive transcriptome assay demonstrated that miR-12135 suppressed Integrin Subunit Alpha 11 (ITGA11) and that ITGA11 expression is correlated with alpha smooth muscle actin expression in patients with cirrhosis. miR-12135 suppressed the expression level of ITGA11 and liver fibrosis. Importantly, ITGA11 is overexpressed in activated hepatic stellate cells, whereas ITGA11 knockout mice are viable and fertile. In conclusions, the miR-12135/ITGA11 axis can be an ideal therapeutic target to suppress fibrosis by precisely targeting abnormally upregulated TGF-β signaling in hepatic stellate cells.

Summary: Liver stage (LS) Plasmodia mature in 2–2.5 days in rodents compared to 5–6 days in humans. Plasmodium-specific CD8+ T cell expansion differs across these varied timespans. To mimic the kinetics of CD8+ T cells of human Plasmodium infection, a two-dose challenge mouse model that achieved 4–5 days of LS antigen exposure was developed. In this model, mice were inoculated with a non-protective, low dose of late-arresting, genetically attenuated sporozoites to initiate T cell activation and then re-inoculated 2–3 days later with wild-type sporozoites. Vaccines that partially protected against traditional challenge completely protected against two-dose challenge. During the challenge period, CD8+ T cell frequencies increased in the livers of two-dose challenged mice but not in traditionally challenged mice, further suggesting that this model better recapitulates kinetics of CD8+ T cell expansion in humans during the P. falciparum LS. Vaccine development and antigen discovery efforts may be aided by using the two-dose challenge strategy.

Summary: Previous research has demonstrated significant differences in intestinal flora between pregnant women with intrahepatic cholestasis of pregnancy (ICP) and healthy pregnant women. The objective of our study is to identify the key bacteria involved in ICP rats and explore the underlying mechanism. We established an ICP rat model and collected rat feces for metagenomic sequencing and found that Roseburia intestinalis (R.I) is the key bacteria in ICP. Transplantation of R.I improved phenotypes associated with ICP through the bile acid/farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) signaling pathway. We used the FXR antagonist Z-Guggulsterone (Z-Gu) to verify the key role of FXR in ICP and found that Z-Gu reversed the benefits of R.I on ICP rats. Our research highlights the important role of intestinal flora in the pathogenesis of ICP and provides a novel approach for its treatment.

For pediatric liver transplant (LT) recipients, an ideal outcome is to survive and thrive into adulthood. However, outcomes reporting for all LT recipients typically rely on much shorter-term outcomes, 1-5 years post-LT. Using Organ Procurement and Transplantation Network (OPTN) registry data from 1990 to 2018, this analysis seeks to determine if long-term follow-up and outcome data are complete for pediatric LT recipients age 0 to 12 years who survive at least 1 year post-LT without graft loss (n = 9309). Of the 7948 pediatric transplant recipients who did not die or require re-LT, 1 in 6 was reported as lost to follow-up by their transplant center during long-term follow-up. Rates of lost to follow-up were highest in those transplanted between 1990 and 1999 and increased in early adulthood for all recipients. Almost 10% of pediatric LT recipients who remained in follow-up required relisting for LT. 8% of children remaining in follow-up had graft failure. Lost to follow-up may bias estimates of long-term outcomes and risk factors for poor outcomes. For those remaining in follow-up, graft failure and death continue to occur in the decades after LT. Continued proactive monitoring, management, and innovations are needed to truly optimize post-LT survival for all children.

PurposeThe Liver Disease and Reproductive Ageing (LIVRA) study leverages the infrastructure of the decades-long multicentre prospective Women's Interagency HIV Study (WIHS) to examine the contributions of HIV, hepatitis C virus (HCV) and ageing to liver disease progression in women.ParticipantsFrom 2013 to 2018, LIVRA enrolled 1576 participants (77 HCV-seropositive only, 248 HIV/HCV-seropositive, 868 HIV-seropositive only and 383 HIV/HCV-seronegative) who underwent vibration controlled transient elastography (VCTE). A VCTE quality assurance programme was established to ensure consistency and accuracy for longitudinal assessment of steatosis (fatty liver) via the controlled attenuation parameter (CAP) and fibrosis via liver stiffness (LS). Demographic, lifestyle factors, anthropometry, clinical and medication history, host genetics, immune markers and hormone levels were collected as part of the WIHS.Findings to dateAt baseline, 737 of 1543 women with CAP measurements had steatosis (CAP ≥248 dB/m) and 375 of 1576 women with LS measurements had significant fibrosis (LS ≥7.1 kPa), yielding a prevalence of 48% and 24%, respectively. On multivariable analysis, waist circumference (WC) and insulin resistance were independently associated with higher CAP (17.8 dB/m per 10 cm (95% CI:16.2 to 19.5) and 1.2 dB/m per doubling (95% CI:0.8 to 1.6), respectively). By contrast, HIV/HCV seropositivity and HCV seropositivity alone were associated with less steatosis compared with HIV/HCV-seronegative women, although the latter did not reach statistical significance (-9.2 dB/m (95% CI:-18.2 to -0.3) and -10.4 dB/m (95% CI: -23.8 to 3.1), respectively). Factors independently associated with higher LS were age (4.4% per 10 years (95% CI: 0.4% to 8.4%)), WC (5.0% per 10 cm (95% CI: 3.3% to 6.6%)), CAP steatosis (0.6% per 10 dB/m (95% CI: 0.1% to 1.0%)), HIV/HCV seropositivity (33% (95% CI: 24% to 44%)) and HCV seropositivity alone (43% (95% CI: 28% to 60%)). Excluding scans that were invalid based on traditional criteria for unreliability did not affect the results.Future plansEnrolled women undergo VCTE at 3-year intervals unless LS is ≥9.5 kPa, indicating advanced fibrosis, in which case VCTE is performed annually. Participants also undergo VCTE every 6 months until 18 months after HCV treatment initiation. Analysis of the data collected will provide insights into the impact of ageing/ovarian function, host genetics, immune function and contemporary HIV and HCV treatments on liver disease progression.

A 68-year-old male with a history of end-stage renal disease and latent tuberculosis on isoniazid (INH), and no psychiatric history presented with a five-day history of anorexia, fatigue, and nausea. Physical exam in the emergency department was notable for somnolence, right upper extremity tremor, and diffuse abdominal pain. Initial workup revealed an anion gap metabolic acidosis with elevated lactate, prompting admission to the general ward for empiric IV antibiotics for suspected bacteremia from his permacath. Within a few hours of admission, he became increasingly encephalopathic and had two episodes of copious hematemesis. Repeat studies revealed a cholestatic pattern of liver injury and new-onset coagulopathy. With an overall clinical picture consistent with fulminant hepatic failure, our pharmacy team initiated a comprehensive pill count of all his medications, which established that he had been inadvertently taking up to six times the recommended dose of INH. With INH discontinuation and supportive therapy, he improved and was discharged on hospital day eight. Our experience provides lessons in the timely recognition and management of this rarely reported toxidrome in the United States.

Abstract Twelve 30‐ to 75‐day‐old mixed breed lambs were examined in an intensive system because of sudden recumbency and death. Clinical examination revealed sudden recumbency, visceral pain, and auscultation of respiratory crackles. Lambs died shortly (between 30 minutes and 3 hours) after the onset of clinical signs. The lambs were necropsied, and after routine parasitology, bacteriology and histopathology procedures, the occurrence of acute cysticercosis caused by Cysticercus tenuicollis was confirmed. The use of the suspect infested feed (newly purchased starter concentrate) was discontinued and other lambs of the flock were treated with praziquantel (15 mg/kg, single dose, orally). After these actions, no new cases were observed. The present study showed the importance of preventive measures against cysticercosis in intensive sheep farming systems which include proper storage of feed, preventing feed and environmental access by potential definitive hosts, and implementing consistent parasite control programs in dogs that are in contact with sheep.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common liver disease worldwide in recent years. MASLD commonly presents as simple hepatic steatosis, but ~25% of patients develop liver inflammation, progressive fibrosis, liver cirrhosis and related hepatocellular carcinoma. Liver inflammation and the degree of fibrosis are key determinants of the prognosis. The pathophysiology of liver inflammation is incompletely understood and involves diverse factors and specifically innate and adaptive immune responses. More specifically, diverse mediators of innate immunity such as proinflammatory cytokines, adipokines, inflammasomes and various cell types like mononuclear cells, macrophages and natural killer cells are involved in directing the inflammatory process in MASLD. The activation of innate immunity is driven by various factors including excess lipids and lipotoxicity, insulin resistance and molecular patterns derived from gut commensals. Targeting pathways of innate immunity might therefore appear as an attractive therapeutic strategy in the future management of MASLD and possibly its complications.

Background: Early identification of alcohol use is crucial for informing recommendations of appropriate follow‐up treatment pre‐liver transplant and optimizing post‐liver transplant outcomes. The purpose of the study was to investigate whether there are psychosocial factors associated with a positive PEth test. Methods: All patients who underwent a routine pre‐surgical psychological evaluation for liver transplant listing (all etiologies, including acute liver failure, dual organ, and re‐transplantation) at a single health care system in 2020 were included in a retrospective chart review. Data extraction included results from PEth testing and information from the psychological evaluation (i.e., demographic, psychiatric symptoms, and cognitive functioning). Results: There were 158 patients (73.8%) who had a PEth test, of whom 21.5% had a positive result (n = 34). Younger age was associated with a positive PEth (p <.001). ALD status and type of ALD (hepatitis vs. cirrhosis) were also associated with a positive PEth test. Other demographic characteristics and psychiatric symptoms were not associated with a positive PEth result (p >.05). Conclusion: Younger age was the only significant demographic variable associated with a positive PEth test. Given the difficulty of predicting who may be using alcohol, it may be useful to use PEth testing for all patients during the pre‐liver transplant evaluation and while patients are listed for liver transplant. Early identification of alcohol use through routine PEth testing will help identify patients who are using alcohol and need further treatment for alcohol use to optimize health and post‐transplant outcomes. [ABSTRACT FROM AUTHOR]