Alcoholic Liver Research Articles

Ultrasound Assessment of Sarcopenia in Alcoholic Liver Disease.

Malnutrition frequently affects patients with alcoholic liver disease (ALD), with important impacts on disease prognosis. Sarcopenia, the clinical phenotype of malnutrition characterized by skeletal muscle loss, is the major component responsible for adverse events in this population. The aim of this study is to assess the use of ultrasound (US) skeletal muscle performance in stratifying ALD disease severity. We recruited 43 patients with ALD and divided them into two groups: alcoholic hepatitis (AH) and alcoholic cirrhosis (AC). We evaluated disease-specific clinical and biological parameters and their relation to US Rectus Femoris muscle (RFM) measurements, including RFM thickness, stiffness (RFMS) and echogenicity (RFE). A thirty-seconds chairs stand test (30sCST) was used as the sarcopenia surrogate test. RMF thickness correlated with platelet count and serum albumin (p < 0.001). Both RFM and RFMS correlated with disease severity (p < 0.001) and 30sCST (p < 0.001, p = 0.002). Patients with AH had more severe US muscle abnormalities compared to AC (RFMS 1.78 m/s vs. 1.35 m/s, p = 0.001) and the highest prevalence of RFE (χ2 = 8.652, p = 0.003). Rectus Femoris US assessment could represent a reliable tool in the diagnosis and severity stratification of ALD-induced sarcopenia.

Prevalence of Non-alcoholic Fatty Liver Disease - A Population Based Study

Background: Non alcoholic fatty liver disease (NAFLD) is defined as the accumulation of excess fat in the liver in the absence of significant alcohol consumption. NAFLD is a common cause of chronic liver disease. The overall prevalence of NAFLD in western countries varies from 15-40% and in Asian 9-40%. Its prevalence has not been determined in population based study in Bangladesh. The objective of the study was to determine the prevalence and risk factors of NAFLD in adult rural population. Methods: This cross-sectional study was performed among adult population of two villages of Comilla district, Bangladesh from January to December 2015. Persons with alcohol consumption and other liver diseases were excluded. Individuals were undergone anthropometric, blood pressure measurements, thorough medical history and physical examinations. Laboratory measurements included were fasting blood sugar (FBS), fasting lipid profile, and liver function tests. NAFLD was diagnosed by transabdominal ultrasonography. Statistical analyses were performed using the SPSS software, version16.0. Results: Among 665 subjects, 213 were males (32%) and 452 were females (68%) with the mean age of 42.2 ± 15.04 years. NAFLD was diagnosed in 33% subjects. NAFLD were high in 41-60 age group (48.7%) and in female gender (P=&lt;0.175). Subjects with NAFLD had higher BMI (P&lt;0.001), higher prevalence of hypertension (P&lt;0.001), high FBS (P&lt;0.001), high cholesterol (P=0.026), high triglyceride (P&lt;0.001) and high waist circumference (P&lt;0.001). Subjects with NAFLD had significantly higher prevalence of metabolic syndrome when compared to healthy subjects (P&lt;0.001). Conclusion: The prevalence of NAFLD in rural adult population of Bangladesh is 33% and is associated with female gender, obesity and features of metabolic syndrome. J Com Med Col Teachers Asso Jan 2024; 28(1): 27-32

From NAFLD to MAFLD and MASLD: a tale of alcohol, stigma and metabolic dysfunction

Liver steatosis is a frequent finding in clinical practice and it is estimated to affect 30% of the general adult population worldwide. It became one of the leading causes of end-stage liver disease and hepatocellular carcinoma. From its first description, a diagnosis of nonalcoholic fatty liver disease (NAFLD) required the exclusion of excessive alcohol consumption and concomitant chronic liver diseases of different origins, making it a diagnosis of exclusion. In recent years, the need to stress the strict association between liver steatosis and metabolic dysfunction (i.e., insulin resistance, overweight/obesity, type 2 diabetes, and metabolic syndrome), as well as the desire to define a condition in a positive rather than negative way, led to new definitions and new diagnostic criteria. Metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed by Eslam et al. in 2020. More recently, a Delphi consensus endorsed by several international hepatologic societies proposed a new terminology [metabolic dysfunction-associated steatotic liver disease (MASLD)] and a new set of diagnostic criteria. The MAFLD and MASLD definitions have a good degree of concordance. They mainly differ in the number of metabolic derangements needed to define “metabolic dysfunction” in normal-weight individuals and in alcohol consumption. Indeed, while MAFLD does not exclude patients with significant alcohol consumption, the recent Delphi consensus included the metabolic dysfunction and alcohol-related liver disease (MetALD) disease entity, a condition in which steatosis, metabolic dysfunction, and moderate alcohol intake coexist. In the present narrative review, we underline the strengths and possible limitations of each definition and summarize available evidence from epidemiologic studies evaluating the clinical usefulness of each set of diagnostic criteria.

Treatment engagement in comorbid alcohol use disorder and alcohol-related liver disease: A qualitative exploration of barriers and facilitators with service users.

Effective interventions to improve patient outcomes in comorbid alcohol use disorder (AUD) and alcohol-related liver disease (ARLD) remain a clinical unmet need. While the choice of abstinence is the cornerstone for the prevention of disease progression and mortality, evidence suggests a suboptimal engagement with treatment supporting recovery. This qualitative investigation aims to understand barriers and facilitators to treatment as experienced by this clinical population by applying a multidimensional adherence model proposed by the World Health Organization. Twenty-four participants with comorbid AUD and ARLD were recruited from an inpatient clinical setting. Data for this study were collected through semistructured, in-depth interviews. Deductive analysis was organized by the Framework method, and theory-driven themes were identified according to the multidimensional adherence model. This included factors across the social and economic, patient, condition, treatment, and healthcare system levels. The findings in this study indicate systematic challenges in maintaining continuity between primary, secondary, and community care. Aspects related to social and economic context, treatment, and healthcare systems were found to hinder engagement. Identified facilitators to engagement included the participatory role of family, shared lived experience of addiction/recovery, and therapeutic alliance with healthcare providers. The understanding of these barriers and facilitators from a service user's perspective can bridge the treatment gap for this clinical population. This can provide an opportunity for the implementation of effective interventions and inform the development of policies promoting accessible care. Government and public health bodies have fundamental roles in shifting treatment paradigms in comorbid AUDand ARLD.

Trends in the burden of hospitalised patients with cirrhosis in Switzerland: a cross-sectional study of cirrhosis-related hospitalisations between 1998 and 2020

ObjectiveLiver cirrhosis is an increasing cause of morbidity and mortality worldwide with a heavy load on healthcare systems. We analysed the trends in hospitalisations for cirrhosis in Switzerland.DesignCross-sectional study.SettingLarge nationwide...

Cost-Effectiveness Analysis of Deep Brain Stimulation for the Treatment of Alcohol Use Disorder and Alcoholic Liver Disease.

Alcohol use disorder (AUD) is a major public health concern and cause of mortality and morbidity. Alcohol-associated liver disease (ALD) is a debilitating complication of AUD, mitigated by abstinence from alcohol use. Deep brain stimulation (DBS) is emerging as a potential treatment for AUD. However, its cost-effectiveness compared to the standard medical treatment is unclear. To estimate the cost-effectiveness of DBS compared to medical management for patients with AUD and ALD. We utilized a decision analytic model based on published literature to conduct a cost-effectiveness analysis of costs and health outcomes for DBS and medical management in patients with AUD and ALD. We also carried out a threshold analysis to determine the probability of success necessary for DBS to be cost-effective. Costs were measured in 2024 US dollars and effectiveness in quality-adjusted life years (QALYs). We used a time horizon of 1-2 years and adopted a societal perspective. Our results show that for AUD patients in general, DBS is not cost-effective at any DBS success rate. However, for advanced ALD patients, defined as fibrosis stage 3 or beyond DBS becomes cost-effective. For these patients, DBS is cost-effective over a two-year period at a $100,000 willingness-to-pay threshold at DBS success rates greater than 53%. For advanced decompensated ALD patients, DBS is cost-effective over a one-year period at DBS success rate greater than 35%. Should it prove efficacious, DBS may be cost-effective for patients with AUD and ALD. Thus, future randomized controlled trials to evaluate its efficacy are warranted.

Intestinal microbiota homeostasis analysis in riboflavin-treated alcoholic liver disease

Alcoholic liver disease (ALD) is a disease with high incidence, limited therapies, and poor prognosis. The present study aims to investigate the effect of riboflavin on ALD and explore its potential therapeutic mechanisms. C57BL/6 mice were divided into the control, alcohol, and alcohol+ riboflavin groups. 16S rRNA-seq and RNA-seq analysis were utilized to analyze the polymorphism of intestinal microbiota and the transcriptome heterogeneity respectively. KEGG and GO enrichment analysis were performed. CIBERSORTx was applied to evaluate the immune cell infiltration level. Publicly available transcriptome data of ALD was enrolled and combined with the RNA-seq data to identify the immune subtypes of ALD. Pathological and histology analysis demonstrated that riboflavin reversed the progression of ALD. 16S rRNA-seq results showed that riboflavin could regulate alcohol-induced intestinal microbiota alteration. Intestinal microbiota polymorphism analysis indicated that VLIDP may contribute to the progression of ALD. Based on the VLIDP pathway, two subtypes were identified. Immune microenvironment analysis indicated that the upregulated inflammatory factors may be important regulators of ALD. In conclusion, intestinal microbiota homeostasis was associated with the protective effect of riboflavin against ALD, which was likely mediated by modulating inflammatory cell infiltration. Riboflavin emerges as a promising therapeutic candidate for the management of ALD.

The Role of Tripartite Motif Family Proteins in Chronic Liver Diseases: Molecular Mechanisms and Therapeutic Potential.

The worldwide impact of liver diseases is increasing steadily, with a consistent upswing evidenced in incidence and mortality rates. Chronic liver diseases (CLDs) refer to the liver function's progressive deterioration exceeding six months, which includes abnormal clotting factors, detoxification failure, and hepatic cholestasis. The most common etiologies of CLDs are mainly composed of chronic viral hepatitis, MAFLD/MASH, alcoholic liver disease, and genetic factors, which induce inflammation and harm to the liver, ultimately resulting in cirrhosis, the irreversible final stage of CLDs. The latest research has shown that tripartite motif family proteins (TRIMs) function as E3 ligases, which participate in the progression of CLDs by regulating gene and protein expression levels through post-translational modification. In this review, our objective is to clarify the molecular mechanisms and potential therapeutic targets of TRIMs in CLDs and provide insights for therapy guidelines and future research.

Trilobatin, a Novel Naturally Occurring Food Additive, Ameliorates Alcoholic Liver Disease in Mice: Involvement of Microbiota-Gut-Liver Axis and Yap/Nrf2 Signaling Pathway.

Trilobatin, a novel natural food additive, exerts a protective effect on acute liver injury. However, whether Trilobatin can protect against alcoholic liver disease (ALD) has not been elucidated. This research is intended to ascertain the impact of Trilobatin on ALD in mice and decipher the potential underlying mechanisms. Lieber-DeCarli liquid alcohol diet was used to induce ALD in mice, followed by administration of Trilobatin (10, 20, 40 mg·kg-1·d-1) for 15 days. The results suggested that Trilobatin significantly alleviated ethanol-induced hepatic injury in mice. Furthermore, RNA-Seq analysis revealed that yes-associated protein (YAP) downregulation occurred in the liver after Trilobatin treatment. Mechanistically, Trilobatin directly bound to YAP and hindered its nuclear translocation, which activated the Nrf2 pathway to reduce pro-inflammatory cytokines and oxidative stress. Intriguingly, 16S rDNA analysis results revealed that Trilobatin reshaped the gut microbiota, reducing harmful bacteria and increasing beneficial bacteria. It also enhanced tight junction proteins, defending against damage to the intestinal barrier. These findings not only highlight the microbiota-gut-liver axis and YAP/Nrf2 pathway as crucial potential targets to treat ALD but also reveal that Trilobatin effectively protects against ALD, at least partly, through modulating the microbiota-gut-liver axis and YAP/Nrf2 pathway.

Evaluating outcomes of transjugular intrahepatic portosystemic shunt procedure among Native Americans

BackgroundThis study aims to explore racial disparities in immediate outcomes of Transjugular Intrahepatic Portosystemic Shunt (TIPS) among Native Americans, a group that have higher prevalence of liver cirrhosis but were the “invisible group” in previous TIPS studies due to their small population size. MethodsThe study identified Native Americans and Caucasians who underwent TIPS in National/Nationwide Inpatient Sample (NIS) database from Q4 2015–2020. Preoperative factors, including demographics, indications for TIPS, comorbidities, etiologies for liver disease, primary payer status, and hospital characteristics, were matched by 1:5 propensity score matching. In-hospital post-TIPS outcomes were then compared between the two cohorts. ResultsThere were 6,658 patients who underwent TIPS, where 101 (1.52 %) were Native Americans and 4,574 (68.70 %) were Caucasians. Native Americans presented as younger, with a lower socioeconomic status, and displayed higher rates of alcohol abuse and related liver diseases. After propensity-score matching, Native Americans had comparable in-hospital post-TIPS outcomes including mortality (8.33% vs 9.09 %, p = 1.00), hepatic encephalopathy (18.75% vs 25.84 %, p = 0.19), acute kidney injury (28.13% vs 30.62 %, p = 0.71), and other adverse events. Native Americans also had similar wait from admission to operation (2.15 ± 0.30 vs 2.87 ± 0.21 days, p = 0.13), hospital length of stay (7.43 ± 0.63 vs 8.62 ± 0.47 days, p = 0.13), and total costs (158,299 ± 14,218.2 vs 169,425 ± 8,600.7 dollars, p = 0.50). ConclusionNative Americans had similar immediate outcomes after TIPS compared to their propensity-matched Caucasians. While these results underscore effective healthcare delivery of TIPS to Native Americans, it is imperative to pursue further research for long-term post-procedure outcomes.

Lipopolysaccharide, arbiter of the gut-liver axis, modulates hepatic cell pathophysiology in alcoholism.

Over the last four decades, clinical research and experimental studies have established that lipopolysaccharide (LPS)-a component of the outer membrane of gram-negative bacteria-is a potent hepatotoxic molecule in humans and animals. Alcohol abuse is commonly associated with LPS endotoxemia. This review highlights LPS molecular structures and modes of release from bacteria, plasma LPS concentrations, induction of microbiota dysbiosis, disruption of gut epithelial barrier, and translocation of LPS into the portal circulation impacting the pathophysiology of hepatic cells via the gut-liver axis. We describe and illustrate the portal vein circulation and its distributaries draining the gastrointestinal tract. We also elaborate on the gut-liver axis coupled with enterohepatic circulation that represents a bidirectional communication between the gut and liver. The review also updates the data on how circulating LPS is cleared in a coordinated effort between Kupffer cells, hepatocytes, and liver sinusoidal endothelial cells. Significantly, the article reviews and updates the modes/mechanisms of action by which LPS mediates the diverse pathophysiology of Kupffer cells, hepatocytes, sinusoidal endothelial cells, and hepatic stellate cells primarily in association with alcohol consumption. Specifically, we review the intricate linkages between ethanol, microbiota dysbiosis, LPS production, gut-liver axis, and pathophysiology of various hepatic cells. The maintenance of the gut barrier structural and functional integrity and microbiome homeostasis is essential in mitigating alcoholic liver disease and improving liver health.

Chronic binge drinking-induced susceptibility to colonic inflammation is microbiome-dependent

ABSTRACT Alterations in intestinal permeability and the gut microbiome caused by alcohol abuse are associated with alcoholic liver disease and with worsening of inflammatory bowel diseases (IBD) symptoms. To resolve the direct effects of chronic ethanol consumption on the colon and its microbiome in the absence of acute or chronic alcohol-induced liver disease, we developed a mouse model of chronic binge drinking that uncovers how alcohol may enhance susceptibility to colitis via the microbiota. Employing daily ethanol gavage, we recapitulate key features of binge ethanol consumption. We found that binge ethanol drinking worsens intestinal infection, colonic injury and inflammation, and this effect persists beyond the drinking period. Using gnotobiotics, we showed that alcohol-driven susceptibility to colitis is microbiota-dependent and transferable to ethanol-naïve mice by microbiome transplantation. Allobaculum spp. expanded in binge drinking mice, and administration of Allobaculum fili was sufficient to enhance colitis in non-drinking mice. Our study provides a model to study binge drinking-microbiota interactions and their effects on host disease and reinforces the pathogenic function of Allobaculum spp. as colitogenic bacteria. Our findings illustrate how chronic binge drinking-induced alterations of the microbiome may affect susceptibility to IBD onset or flares.

Causal effects of smoking, alcohol consumption, and coffee intake on hepatobiliary and pancreatic diseases: A Mendelian randomization study

BackgroundHepatobiliary and pancreatic diseases, such as cirrhosis, hepatocellular carcinoma, cholelithiasis, and pancreatitis, are major global health challenges. Lifestyle factors like smoking, alcohol consumption, and coffee intake are commonly studied for their health impacts. However, observational studies often face issues with confounding factors and reverse causality, making it difficult to establish causal relationships. MethodsThis research uses Mendelian randomization (MR) to investigate the causal effects of smoking, alcohol use, and coffee intake on 10 hepatobiliary and pancreatic diseases. Genetic data from the Sequencing Consortium of Alcohol and Nicotine Use (GSCAN) and self-reported GWAS were used to derive instrumental variables (IVs). The outcomes were obtained from the FinnGen and UK Biobank cohorts. Univariable and multivariable MR analyses were conducted to assess the associations. ResultsGenetic predisposition to tobacco use was associated with increased risks of acute pancreatitis, alcoholic hepatitis, chronic pancreatitis, cirrhosis, gallstones, liver cancer, and pancreatic cancer. Alcohol consumption was linked to acute pancreatitis, chronic pancreatitis, alcoholic liver disease, hepatic cancer, and cholangitis. Coffee intake showed minimal associations, with a slight protective effect against non-alcoholic steatohepatitis. ConclusionsThis study confirms the harmful effects of inhaling tobacco and consuming alcohol on hepatobiliary and pancreatic diseases. It highlights the need for public health strategies to reduce tobacco use and heavy alcohol consumption. Coffee intake showed minimal effects, suggesting further research is needed to understand its relationship with hepatobiliary health.

Metabolic characteristics of patients with MetALD: Caveats of a new definition.

Recently, a new entity was introduced, MetALD, which includes patients with metabolic dysfunction-associated steatotic liver disease (MASLD), who consume moderate amounts of alcohol. However, little is known regarding the metabolic and clinical characteristics of these patients. Data from the National Health and Nutrition Examination Surveys 2017-2020 was used. Participants without valid transient elastography (TE) measurements, incomplete alcohol consumption report, or with alternative etiologies of liver steatosis were excluded. A total of 6901 patients were included in the study, of which 106 (1.5%) had MetALD. Overall, MetALD patients showed a metabolic profile that was more similar to patients with alcohol related liver disease (ALD) than MASLD. Specifically, while patients with MetALD showed values in-between MASLD and ALD for body mass index (BMI), aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyltransferase (GGT) and haemoglobin A1c, they had similar high-density lipoprotein cholesterol (HDL-C), blood pressure, prevalence of diabetes and insulin resistance to ALD patients. Increasing alcohol consumption was associated with lower insulin resistance and A1c and higher triglycerides, HDL-C and blood pressure. Moreover, while AST, ALT and GGT increased with alcohol consumption, this did not translate into worse hepatic steatosis or liver fibrosis by TE. MetALD patients share some characteristics with MASLD, but they resemble ALD patients more, especially after adjusting for BMI. Alcohol consumption produces a dissociation between insulin resistance and some cardiometabolic risk factors (blood pressure and HDL-C), which may make the current classification of patients challenging.

Cocaine-derived hippuric acid activates mtDNA-STING signaling in alcoholic liver disease: Implications for alcohol and cocaine co-abuse

The simultaneous abuse of alcohol-cocaine is known to cause stronger and more unpredictable cellular damage in the liver, heart, and brain. However, the mechanistic crosstalk between cocaine and alcohol in liver injury remains unclear. The findings revealed cocaine-induced liver injury and inflammation in both marmosets and mice. Of note, co-administration of cocaine and ethanol in mice causes more severe liver damage than individual treatment. The metabolomic analysis confirmed that hippuric acid (HA) is the most abundant metabolite in marmoset serum after cocaine consumption and that is formed in primary marmoset hepatocytes. HA, a metabolite of cocaine, increases mitochondrial DNA leakage and subsequently increases the production of proinflammatory factors via STING signaling in Kupffer cells (KCs). In addition, conditioned media of cocaine-treated KC induced hepatocellular necrosis via alcohol-induced TNFR1. Finally, disruption of STING signaling in vivo ameliorated co-administration of alcohol- and cocaine-induced liver damage and inflammation. These findings postulate intervention of HA-STING-TNFR1 axis as a novel strategy for treatment of alcohol- and cocaine-induced excessive liver damage.Graphical

A research study on the utility of GGT level and AST/ALT ratio in alcoholic liver diseases

A research study on the utility of GGT level and AST/ALT ratio in alcoholic liver diseases

Elucidating hydroxysafflor yellow A's multi-target mechanisms against alcoholic liver disease through integrative pharmacology

BackgroundAlcoholic liver disease (ALD) significantly contributes to global liver-related morbidity and mortality. Natural products play a crucial role in the prevention and treatment of ALD. Hydroxysafflor yellow A (HSYA), a unique and primary component of Safflower (Carthamus tinctorius l.), exhibits diverse pharmacological activities. However, the impact and mechanism of HSYA on ALD have not been fully elucidated. PurposeThe purpose of this study was to employ an integrative pharmacology approach to assess the multi-targeted mechanism of HSYA against ALD. MethodsNetwork pharmacology and molecular docking techniques were used to analyze the potential therapeutic signaling pathways and targets of HSYA against ALD. An ALD model in zebrafish larvae was established. Larvae were pretreated with HSYA and then exposed to ethanol. Liver injury was measured by fluorescence expression analysis in the liver-specific transgenic zebrafish line Tg (fabp10a:DsRed) and liver tissue H&E staining. Liver steatosis was determined by whole-mount oil red O staining and TG level. Additionally, an ethanol-induced hepatocyte injury model was established in vitro to observe hepatocyte damage (cell viability, ALT level), lipid accumulation (oil red O staining, TC and TG), and oxidative stress (ROS, MDA, GPx and SOD) in HepG2 cells treated with or without HSYA. Finally, qRT-PCR combined with network pharmacology and molecular docking was employed to validate the effects of HSYA on targets. ResultsHSYA exhibited a significant, dose-dependent improvement in ethanol-induced liver injury in zebrafish larvae and HepG2 cells. Network pharmacology analysis revealed that HSYA may exert pharmacological effects against ALD through 341 potential targets. These targets are involved in various signaling pathways, including lipid metabolism and atherosclerosis, PI3K-Akt signaling pathway, MAPK signaling pathway, and ALD itself. Molecular docking studies displayed that HSYA had a strong binding affinity toward the domains of IL1B, IL6, TNF, PPARA, PPARG, HMGCR and ADH5. qRT-PCR assays demonstrated that HSYA effectively reversed the ethanol-induced aberrant gene expression of SREBF1, FASN, ACACA, CPT1A, PPARA, IL1B, IL6, TNFα, ADH5, and ALDH2 in vivo and in vitro. ConclusionThis study offers a comprehensive investigation into the anti-ALD mechanisms of HSYA using an integrative pharmacology approach. The potential targets of HSYA may be implicated in enhancing ethanol catabolism, reducing lipid accumulation, mitigating oxidative stress, and inhibiting inflammatory response.

Cysteine triggered cascade reaction forming coumarin: Visualization of cysteine fluctuation in alcoholic liver disease by a NIR fluorescent probe

Alcoholic liver disease (ALD) is a chronic toxic liver injury caused by long-term heavy drinking. Due to the increasing incidence, ALD is becoming one of important medical tasks. Many studies have shown that the main mechanism of liver damage caused by large amounts of alcohol may be related to antioxidant stress. As an important antioxidant, cysteine (Cys) is involved in maintaining the normal redox balance and detoxifying metabolic function of the liver, which may be closely related to the pathogenesis of ALD. Therefore, it is necessary to develop a simple non-invasive method for rapid monitoring of Cys in liver. Thus, a near-infrared (NIR) fluorescent probe DCI-Ac-Cys which undergoes Cys triggered cascade reaction to form coumarin fluorophore is developed. Using the DCI-Ac-Cys, decreased Cys was observed in the liver of ALD mice. Importantly, different levels of Cys were monitored in the livers of ALD mice taking silybin and curcumin with the antioxidant effects, indicating the excellent therapeutic effect on ALD. This study provides the important references for the accurate diagnosis of ALD and the pharmacodynamic evaluation of silybin and curcumin in the treatment of ALD, and support new ideas for the pathogenesis of ALD.

Unveiling the multifaceted role of adropin in various diseases (Review).

Adropin is a secreted peptide encoded by the energy homeostasis‑associated gene, which also functions as a membrane‑bound protein facilitating intercellular communication. This peptide has been detected in various tissues and body fluids, including the brain, liver, kidney, heart, pancreas, small intestine, endothelial cells and colostrum. Notably, the amino acid sequences of adropin are identical in humans, mice and rats. Previous studies have demonstrated that adropin levels fluctuate under different physiological and pathological conditions. Adropin plays a role in regulating carbohydrate metabolism, lipid metabolism and intercellular molecular signaling pathways, implicating its involvement in the progression of numerous diseases, such as acute myocardial infarction, lung injury, non‑alcoholic fatty liver disease/non‑alcoholic steatohepatitis, kidney disease, polycystic ovary syndrome, obesity, and diabetes, atherosclerosis, systemic sclerosis and cancer. Despite its significance, the precise role and mechanism of this protein remain inadequately understood and studied. To elucidate the function of adropin and its clinical research status, a systematic review of recent studies on adropin across various diseases was conducted. Additionally, several challenges and limitations associated with adropin research in both animal and clinical contexts were identified, aiming to offer valuable insights for future investigation.

Efficacy and safety of palliative treatment in patients with autoimmune liver disease-associated hepatocellular carcinoma

Introduction and ObjectivesAutoimmune liver diseases (AILD) are rare causes hepatocellular carcinoma (HCC), and data on the efficacy and tolerability of anti-tumor therapies are scarce. This pan-European study aimed to assess outcomes in AILD-HCC patients treated with tyrosine kinase inhibitors (TKIs) or transarterial chemoembolization (TACE) compared with patients with more common HCC etiologies, including viral, alcoholic or non-alcoholic fatty liver disease. Materials and Methods107 patients with HCC-AILD (AIH:55; PBC:52) treated at 13 European centres between 1996 and 2020 were included. 65 received TACE and 28 received TKI therapy. 43 (66 %) were female (median age 73 years) with HCC tumor stage BCLC A (34 %), B (46 %), C (9 %) or D (11 %). For each treatment type, propensity score matching was used to match AILD to non-AILD-HCC on a 1:1 basis, yielding in a final cohort of 130 TACE and 56 TKI patients for comparative analyses of median overall survival (mOS) and treatment tolerability. ResultsHCC-AILD patients showed comparable mOS to controls for both TACE (19.5 vs. 22.1 months, p = 0.9) and TKI (15.4 vs. 15.1 months, p = 0.5). Adverse events were less frequent in AILD-HCC patients than controls (33 % % vs. 62 %, p = 0.003). For TKIs, there were no significant differences in adverse events (73% vs. 86%, p = 0.2) or interruption rates (44% vs. 36 %, p = 0.7). ConclusionsIn summary, this study demonstrates comparable mOS for AILD-HCC patients undergoing local and systemic treatments, with better tolerability than HCC of other causes. TKIs remain important therapeutic options for AILD-HCC patients, particularly given their exclusion from recent immunotherapy trials.