Seminars In Liver Disease[JOURNAL]
Sun
200 papers
Big Data Analytics in Large Cohorts: Opportunities and Challenges for Research in Hepatology.
Huang HYR, Schneider KM, Schneider C
Semin Liver Dis · 2025 Sep · PMID 40398671 · Full text
Advances in big data analytics, precision medicine, and artificial intelligence are transforming hepatology, offering new insights into disease mechanisms, risk stratification, and therapeutic interventions. In this revi...
Advances in big data analytics, precision medicine, and artificial intelligence are transforming hepatology, offering new insights into disease mechanisms, risk stratification, and therapeutic interventions. In this review, we explore how the integration of genetic studies, multi-omics data, and large-scale population cohorts has reshaped our understanding of liver disease, using steatotic liver disease as a prototype for data-driven discoveries in hepatology. We highlight the role of artificial intelligence in identifying patient subgroups, optimizing treatment strategies, and uncovering novel therapeutic targets. Furthermore, we discuss the importance of collaborative networks, open data initiatives, and implementation science in translating these findings into clinical practice. Although data-driven precision medicine holds great promise, its impact depends on structured approaches that ensure real-world adoption.
IgG4-Related Cholangitis.
Beuers U, Trampert DC
Semin Liver Dis · 2025 Sep · PMID 40342085 · Full text
IgG4-related cholangitis (IRC) is a rare fibroinflammatory disease of the biliary tree and liver and presents the major hepatobiliary manifestation of IgG4-related systemic disease (IgG4-RD). IRC also includes the IgG4-r...
IgG4-related cholangitis (IRC) is a rare fibroinflammatory disease of the biliary tree and liver and presents the major hepatobiliary manifestation of IgG4-related systemic disease (IgG4-RD). IRC also includes the IgG4-related inflammatory pseudotumor of the liver and IgG4-related cholecystitis. IRC mimics other cholangiopathies such as primary sclerosing cholangitis or cholangiocarcinoma. IRC may be found in 30 to 60% of cases with type 1 autoimmune pancreatitis, the most frequent manifestation of IgG4-RD. The pathogenesis of IRC (and IgG4-RD) is incompletely understood. Genetic predisposition, environmental factors, oligoclonal glucocorticosteroid-sensitive expansion of IgG4 B cells/plasmablasts in blood and affected tissue and blocking autoantibody formation against protective IgG4-specific autoantigens such as annexin A11 and laminin 511-E8 with impaired protection of biliary epithelia against toxic bile acids have been described in IRC. Specific T cell subtypes are involved in the inflammatory process. The diagnosis of IRC is made according to HISORt criteria comprising histopathology, imaging, serology, other organ manifestations, and response to therapy. Treatment of IRC aiming to prevent organ failure and improve symptoms includes remission induction with highly effective glucocorticosteroids and long-term maintenance of remission with immunomodulators such as glucocorticosteroid sparing additives or B cell depleting approaches.
Intestinal Microbes, Metabolites, and Hormones in Alcohol-Associated Liver Disease.
Wang R, Ma F, Yin D … +2 more , Wang H, Wei X
Semin Liver Dis · 2025 Sep · PMID 40334703 · Publisher ↗
Alcohol-associated liver disease (ALD)-encompassing conditions including steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma-refers to hepatic damage arising from excessive or hazardous alcohol consumption, and...
Alcohol-associated liver disease (ALD)-encompassing conditions including steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma-refers to hepatic damage arising from excessive or hazardous alcohol consumption, and is now recognized as a significant global health burden. Although the mechanisms underlying ALD remain incompletely understood, several pathways have been substantiated over the last five decades, notably the involvement of intestinal microorganisms and the involvement of the gut-liver axis in alcohol metabolism and ALD pathogenesis. Ethanol intake disrupts the intestinal microbial balance and compromises the gut barrier, resulting in increased permeability to microbial products. The subsequent translocation of microbial metabolites and other antigenic substances to the liver activates hepatic immune responses, thereby contributing to liver injury. In addition, gastrointestinal hormones are also implicated in ALD progression through various mechanisms. Although no therapies for ALD have been approved by the Food and Drug Administration, various therapeutic strategies targeting the intestinal microbiota and gut barrier have been identified. In conclusion, this review discusses the role of the gut-liver axis in alcohol metabolism and ALD pathogenesis and explores the emerging therapeutic strategies.
Liver Neurobiology: Regulation of Liver Functions by the Nervous System.
Mravec B, Szantova M
Semin Liver Dis · 2025 Sep · PMID 40239709 · Publisher ↗
The nervous system plays an important role in the regulation of liver functions during physiological as well as pathological conditions. This regulatory effect is based on the processing of signals transmitted to the bra...
The nervous system plays an important role in the regulation of liver functions during physiological as well as pathological conditions. This regulatory effect is based on the processing of signals transmitted to the brain by sensory nerves innervating the liver tissue and other visceral organs and by humoral pathways transmitting signals from peripheral tissues and organs. Based on these signals, the brain modulates metabolism, detoxification, regeneration, repair, inflammation, and other processes occurring in the liver. The nervous system thus determines the functional and morphological characteristics of the liver. Liver innervation also mediates the influence of psychosocial factors on liver functions. The aim of this review is to describe complexity of bidirectional interactions between the brain and liver and to characterize the mechanisms and pathways through which the nervous system influences liver function during physiological conditions and maintains liver and systemic homeostasis.
The Molecular Pathogenesis of Sarcopenia/Frailty in Cirrhosis.
Jiao H, Wang H, Li J … +2 more , Yang Z, Sun C
Semin Liver Dis · 2025 Sep · PMID 40239708 · Publisher ↗
Cirrhosis is an important cause of morbidity and death in patients with chronic liver disease. It can be divided into compensatory and decompensated stages. During the decompensation period, complications such as esophag...
Cirrhosis is an important cause of morbidity and death in patients with chronic liver disease. It can be divided into compensatory and decompensated stages. During the decompensation period, complications such as esophageal and gastric varices hemorrhage, hepatic encephalopathy, infection, and hepatorenal syndrome are often incurred, which has a high mortality rate and leverages huge economic burden on society, healthcare resources, and individuals. Sarcopenia and frailty are common in patients with cirrhosis. The pathogenesis of sarcopenia and frailty in the context of cirrhosis is complicated and multifactorial, including overwhelming systemic inflammation, imbalance of muscle protein metabolism, malnutrition, endocrine and metabolic dysfunctions, intestinal microecological disorders, lack of physical exercise, and other aspects. Notably, accumulating evidence implicates that many patients experience sarcopenia/frailty even before the onset of liver cirrhosis. In this regard, the magnitude of liver fibrosis is closely linked to the progression of sarcopenia with reciprocal impact. In conclusion, this review article will shed light on the pathogenesis of cirrhosis complicated with sarcopenia/frailty, aimed at facilitating early diagnosis and effective management.
The Ways to Die: Cell Death in Liver Pathophysiology.
Cao P, Jaeschke H, Ni HM … +1 more , Ding WX
Semin Liver Dis · 2025 Sep · PMID 40199509 · Publisher ↗
Liver diseases are closely associated with various cell death mechanisms, including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis. Each process contributes uniquely to the pathophysiology of liver injury...
Liver diseases are closely associated with various cell death mechanisms, including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis. Each process contributes uniquely to the pathophysiology of liver injury and repair. Importantly, these mechanisms are not limited to hepatocytes; they also significantly involve nonparenchymal cells. This review examines the molecular pathways and regulatory mechanisms underlying these forms of cell death in hepatocytes, emphasizing their roles in several liver diseases, such as ischemia-reperfusion injury, metabolic dysfunction-associated steatotic liver disease, drug-induced liver injury, and alcohol-associated liver disease. Recent insights into ferroptosis and pyroptosis may reveal novel therapeutic targets for managing liver diseases. This review aims to provide a comprehensive overview of these cell death mechanisms in the context of liver diseases, detailing their molecular signaling pathways and implications for potential treatment strategies.
Recompensation in Cirrhosis: Biomarkers and Strategies.
Ramírez-Quesada W, Alvarado-Tapias E, Shalaby S … +1 more , Hernández-Gea V
Semin Liver Dis · 2025 Mar · PMID 40179966 · Publisher ↗
The onset of decompensation in advanced chronic liver disease (ACLD) is a hallmark in natural history, with a poor prognosis and a significantly increased liver-related mortality. Etiological treatments for viral hepatit...
The onset of decompensation in advanced chronic liver disease (ACLD) is a hallmark in natural history, with a poor prognosis and a significantly increased liver-related mortality. Etiological treatments for viral hepatitis or abstinence in cirrhosis due to alcohol abuse have demonstrated that some patients experience partial to complete clinical and analytical improvement, a stage termed "recompensation." Although recompensation is primarily defined clinically based on treatable etiologies, it is still evolving for conditions like metabolic dysfunction-associated steatotic liver disease (MASLD). Despite the need for specific biomarkers in hepatic recompensation, no biomarkers have been thoroughly studied in this context. Biomarkers identified in compensated ACLD (cACLD) following etiological treatment might be explored for recompensation. Although the pathophysiology mechanisms underlying the hepatic recompensation remain unclear, understanding the mechanism involved in cirrhosis decompensation could help identify potential targets for recompensation. This review provides an update on the hepatic recompensation concept, examines the existing data on invasive and non-invasive biomarkers, mainly in cACLD after cure, that could be raised in recompensation, and explores future therapeutic targets for the hepatic recompensation process.
Understanding and Treating Hepatorenal Syndrome: Insights from Recent Research.
Song Y, Yang X, Yu C
Semin Liver Dis · 2025 Sep · PMID 40169136 · Publisher ↗
Acute kidney injury (AKI) is a critical and often fatal complication in decompensated cirrhosis, significantly affecting inpatient survival rates. Hepatorenal syndrome (HRS), a distinct subtype of AKI, develops in indivi...
Acute kidney injury (AKI) is a critical and often fatal complication in decompensated cirrhosis, significantly affecting inpatient survival rates. Hepatorenal syndrome (HRS), a distinct subtype of AKI, develops in individuals with advanced cirrhosis and portal hypertension. It is marked by progressive kidney dysfunction, poor prognosis, and frequently causes death before liver transplantation. The pathogenesis of HRS involves vasodilation of the splanchnic vessels, leading to overactivation of the endogenous vasoactive systems, circulatory dysfunction, and reduced renal perfusion, which ultimately impairs glomerular filtration. Recent studies have highlighted the role of systemic inflammation in exacerbating renal damage. Despite these changes, renal histology in HRS usually shows no significant abnormalities, and there is typically no hematuria, proteinuria, or abnormal findings on ultrasound. Common risk factors for HRS include spontaneous bacterial peritonitis, infections, and large-volume paracentesis without albumin infusion. Diagnosing HRS is challenging, particularly in distinguishing it from acute tubular necrosis, due to the absence of specific biomarkers. Treatment primarily involves vasoconstrictors such as terlipressin and albumin, with liver transplantation being the definitive therapeutic option. This review provides an updated understanding of HRS, addressing its pathophysiology, diagnosis, management, and future challenges, based on recent expert consensus.
Alcohol-Metabolizing Enzymes, Liver Diseases and Cancer.
Liu T, Zhang F, Feng Y … +2 more , Han P, Gao Y
Semin Liver Dis · 2025 Mar · PMID 40157374 · Full text
Alcohol is generally believed to be metabolized in the liver by alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and to a much lesser extent cytochrome P450 2E1 (CYP2E1) and other enzymes. Recent studies sugge...
Alcohol is generally believed to be metabolized in the liver by alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and to a much lesser extent cytochrome P450 2E1 (CYP2E1) and other enzymes. Recent studies suggest that gut also play important roles in the promotion of alcohol metabolism. ADH, ALDH, and CYP2E1 have several polymorphisms that markedly impact alcohol metabolism. These alcohol-metabolizing enzymes not only affect alcohol-associated liver disease (ALD), but may also modulate the pathogenesis of other liver diseases and cancer in the absence of alcohol consumption. In this review, we discuss alcohol metabolism and the roles of alcohol-metabolizing enzymes in the pathogenesis of ALD, metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction and alcohol-associated liver disease, viral hepatitis, and liver cancer. We also discuss how alcohol-metabolizing enzymes may affect endogenous ethanol production, and how ethanol metabolism in the gut affects liver disease and cancer. Directions for future research on the roles of alcohol-metabolizing enzymes in liver disease and cancer are also elaborated.
Primary Cilia in Hepatic Biliary Hyperplasia: Implications for Liver Diseases.
Pant K, Peixoto E, Gradilone SA
Semin Liver Dis · 2025 Sep · PMID 40118103 · Full text
Primary cilia, hair-like projections on the surface of various cell types, play crucial roles in sensing and regulating environmental cues within the liver, particularly among cholangiocytes. These structures detect chan...
Primary cilia, hair-like projections on the surface of various cell types, play crucial roles in sensing and regulating environmental cues within the liver, particularly among cholangiocytes. These structures detect changes in bile composition, flow, and other biochemical signals, integrating this information to modulate cellular processes. Dysfunction in cholangiocyte cilia-whether due to structural abnormalities or genetic mutations-has been linked to an array of cholangiopathies and ciliopathies. These include conditions such as biliary atresia, cholangiocarcinoma, primary sclerosing cholangitis, and polycystic liver diseases, each with distinct clinical phenotypes influenced by impaired ciliary function. Given the complexity of the ciliary proteome and its role in cellular signaling, including the Hedgehog, Wnt, and TGR5 pathways, ciliary dysfunction disrupts essential signaling cascades, thus driving disease progression. While over 40 gene mutations are associated with ciliopathic features, there may be additional contributors within the expansive ciliary proteome. This study synthesizes current knowledge on cholangiocyte cilia, emphasizing their mechanistic role in liver disease, and highlights emerging therapeutic strategies aimed at restoring ciliary function. In conclusion, ciliotherapies are proposed as a promising approach for addressing cholangiopathies, with the potential to shift the current therapeutic landscape.
Environmental Pollutants, Occupational Exposures, and Liver Disease.
Beier JI, Luo J, Vanderpuye CM … +11 more , Brizendine P, Muddasani P, Bolatimi O, Heinig SA, Ekuban FA, Siddiqui H, Ekuban A, Gripshover TC, Wahlang B, Watson WH, Cave MC
Semin Liver Dis · 2025 Jun · PMID 40118102 · Full text
Environmental pollutants significantly impact liver disease development, progression, and outcomes. This review examines the complex relationship between environmental exposures and liver pathology, from malignant condit...
Environmental pollutants significantly impact liver disease development, progression, and outcomes. This review examines the complex relationship between environmental exposures and liver pathology, from malignant conditions like hepatocellular carcinoma to steatotic and cholestatic liver diseases. Key environmental factors include air pollutants, volatile organic compounds, persistent organic pollutants, heavy metals, and per- and polyfluoroalkyl substances. These compounds can act through multiple mechanisms, including endocrine disruption, metabolic perturbation, oxidative stress, and direct hepatotoxicity. The impact of these exposures is often modified by factors such as sex, diet, and genetic predisposition. Recent research has revealed that even low-level exposures to certain chemicals can significantly affect liver health, particularly when combined with other risk factors. The emergence of exposomics as a research tool promises to enhance our understanding of how environmental factors influence liver disease. Importantly, exposure effects can vary by demographic and socioeconomic factors, highlighting environmental justice concerns. Implementation of this knowledge in clinical practice requires new diagnostic approaches, healthcare system adaptations, and increased awareness among medical professionals. In conclusion, this review provides a comprehensive examination of current evidence linking environmental exposures to liver disease and discusses implications for clinical practice and public health policy.
Fontan-Associated Liver Disease.
Hilscher MB, Johnson JN
Semin Liver Dis · 2025 Mar · PMID 40081822 · Full text
Fontan-associated liver disease (FALD) occurs in all patients who have undergone Fontan palliation for functional single ventricle congenital heart defects. While liver fibrosis is universal in patients who have undergon...
Fontan-associated liver disease (FALD) occurs in all patients who have undergone Fontan palliation for functional single ventricle congenital heart defects. While liver fibrosis is universal in patients who have undergone Fontan palliation, FALD may lead to more serious consequences including portal hypertension, cirrhosis, and hepatocellular carcinoma. Scientific studies of the pathophysiology and clinical management of FALD have been limited to date by the heterogeneous nature of the disease, relatively small population of patients with Fontan physiology, and inaccuracy of noninvasive staging tests. As survival after the Fontan procedure improves, the population of adults with Fontan physiology is growing, leading to more severe extracardiac complications related to the Fontan circulation and growing demand for heart and liver transplantation. The accurate evaluation, staging, and management of FALD comprises a clinical challenge which requires expert multidisciplinary input.
Role of Intestinal Barrier Disruption to Acute-on-Chronic Liver Failure.
Pohl J, Aretakis D, Tacke F … +2 more , Engelmann C, Sigal M
Semin Liver Dis · 2025 Mar · PMID 40081417 · Publisher ↗
Acute-on-chronic liver failure (ACLF) is a severe condition in patients with decompensated liver cirrhosis, marked by high short-term mortality. Recent experimental and clinical evidence has linked intestinal dysfunction...
Acute-on-chronic liver failure (ACLF) is a severe condition in patients with decompensated liver cirrhosis, marked by high short-term mortality. Recent experimental and clinical evidence has linked intestinal dysfunction to both the initiation of ACLF as well as disease outcome. This review discusses the significant role of the gut-liver axis in ACLF pathogenesis, highlighting recent advances. Gut mucosal barrier disruption, gut dysbiosis, and bacterial translocation emerge as key factors contributing to systemic inflammation in ACLF. Different approaches of therapeutically targeting the gut-liver axis via farnesoid X receptor agonists, nonselective beta receptor blockers, antibiotics, and probiotics are discussed as potential strategies mitigating ACLF progression. The importance of understanding the distinct pathophysiology of ACLF compared with other stages of liver cirrhosis is highlighted. In conclusion, research findings suggest that disruption of intestinal integrity may be an integral component of ACLF pathogenesis, paving the way for novel diagnostic and therapeutic approaches to manage this syndrome more effectively.
Hepatic Stellate Cells Functional Heterogeneity in Liver Cancer.
Sererols-Viñas L, Garcia-Vicién G, Ruiz-Blázquez P … +7 more , Lee TF, Lee YA, Gonzalez-Sanchez E, Vaquero J, Moles A, Filliol A, Affò S
Semin Liver Dis · 2025 Mar · PMID 40043738 · Full text
Hepatic stellate cells (HSCs) are the liver's pericytes, and play key roles in liver homeostasis, regeneration, fibrosis, and cancer. Upon injury, HSCs activate and are the main origin of myofibroblasts and cancer-associ...
Hepatic stellate cells (HSCs) are the liver's pericytes, and play key roles in liver homeostasis, regeneration, fibrosis, and cancer. Upon injury, HSCs activate and are the main origin of myofibroblasts and cancer-associated fibroblasts (CAFs) in liver fibrosis and cancer. Primary liver cancer has a grim prognosis, ranking as the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) being the predominant type, followed by intrahepatic cholangiocarcinoma (iCCA). Moreover, the liver hosts 35% of all metastatic lesions. The distinct spatial distribution and functional roles of HSCs across these malignancies represent a significant challenge for universal therapeutic strategies, requiring a nuanced and tailored understanding of their contributions. This review examines the heterogeneous roles of HSCs in liver cancer, focusing on their spatial localization, dynamic interactions within the tumor microenvironment (TME), and emerging therapeutic opportunities, including strategies to modulate their activity, and harness their potential as targets for antifibrotic and antitumor interventions.
Pathogenesis and Management of Intestinal Failure-Associated Liver Disease.
Abi-Aad SJ, Lovell M, Khalaf RT … +1 more , Sokol RJ
Semin Liver Dis · 2025 Mar · PMID 40015320 · Full text
Long-term parenteral nutrition (PN) has considerably improved the management of intestinal failure (IF) in children and adults, particularly those with short bowel syndrome; however, it carries a significant risk of hepa...
Long-term parenteral nutrition (PN) has considerably improved the management of intestinal failure (IF) in children and adults, particularly those with short bowel syndrome; however, it carries a significant risk of hepatotoxicity, specifically, intestinal failure-associated liver disease (IFALD), also known as PN-associated liver disease. This review provides an update on the latest understanding of IFALD pathogenesis, emerging therapies, and ongoing challenges in the management of this complication. A number of factors are associated with the development of IFALD. PN lipid emulsions, phytosterol exposure, bacterial dysbiosis, an altered gut-liver axis, and episodes of sepsis disrupt bile acid homeostasis and promote liver inflammation in the active phase of IFALD, favoring the development of PN-associated cholestasis (PNAC) and the more chronic form of steatohepatitis with fibrosis. Based on the identification of pathophysiological pathways, potential therapies are being studied in preclinical and clinical trials, including lipid emulsion modifications; targeted therapies such as Farnesoid X receptor (FXR) and liver receptor homolog 1 (LRH-1) agonists, tumor necrosis factor inhibitors, glucagon-like peptide-2 analogs; microbiome modulation; and supplementation with choline and antioxidants. In conclusion, the pathogenesis of IFALD is complex, and PN dependence and liver injury remain challenging, particularly in patients with IF who cannot advance to enteral nutrition and be weaned off PN.
Diagnosis and Management of Early Stages of ALD.
Gratacós-Ginès J, Alvarado-Tapias E, Martí-Aguado D … +3 more , López-Pelayo H, Bataller R, Pose E
Semin Liver Dis · 2025 Jun · PMID 39965759 · Publisher ↗
Early forms of alcohol-associated liver disease (ALD) include different stages in the progression of compensated liver disease ranging from steatosis to steatohepatitis and fibrosis. ALD has been classically diagnosed at...
Early forms of alcohol-associated liver disease (ALD) include different stages in the progression of compensated liver disease ranging from steatosis to steatohepatitis and fibrosis. ALD has been classically diagnosed at advanced stages more frequently than other liver diseases. This fact probably contributed to the scarcity of studies on early forms of ALD. Recent studies have investigated the prevalence of early ALD in the general population and have described the natural history of alcohol-induced steatosis and fibrosis, which have been linked to worse prognosis compared with early stages of other chronic liver diseases. In addition, studies on screening and early diagnosis of ALD in at-risk populations have shown that these strategies allow early detection and intervention. Of note, up to 28% of the United States population has concurrent alcohol use and metabolic syndrome, and estimated prevalence of advanced fibrosis among heavy drinkers with metabolic syndrome has increased from 3% in the 1990s to more than 10% in the 2010s. Therefore, new challenges and treatment opportunities will emerge for patients with ALD. In this review, we provide an overview of the state of the art in early ALD, focusing on natural history, diagnosis, and management, and provide insights into future perspectives.
Influence of Sex in the Development of Liver Diseases.
Zhang JW, Zhang N, Lyu Y … +1 more , Zhang XF
Semin Liver Dis · 2025 Mar · PMID 39809453 · Publisher ↗
The liver is a sexually dimorphic organ. Sex differences in prevalence, progression, prognosis, and treatment prevail in most liver diseases, and the mechanism of how liver diseases act differently among male versus fema...
The liver is a sexually dimorphic organ. Sex differences in prevalence, progression, prognosis, and treatment prevail in most liver diseases, and the mechanism of how liver diseases act differently among male versus female patients has not been fully elucidated. Biological sex differences in normal physiology and disease arise principally from sex hormones and/or sex chromosomes. Sex hormones contribute to the development and progression of most liver diseases, with estrogen- and androgen-mediated signaling pathways mechanistically involved. In addition, genetic factors in sex chromosomes have recently been found to contribute to the sex disparity of many liver diseases, which might explain, to some extent, the difference in gene expression pattern, immune response, and xenobiotic metabolism between men and women. Although increasing evidence suggests that sex is one of the most important modulators of disease prevalence and outcomes, at present, basic and clinical studies have long been sex unbalanced, with female subjects underestimated. As such, this review focuses on sex disparities of liver diseases and summarizes the current understanding of sex-specific mechanisms, including sex hormones, sex chromosomes, etc. We anticipate that understanding sex-specific pathogenesis will aid in promoting personalized therapies for liver disease among male versus female patients.
Current Concepts in Fluid Resuscitation and Vasopressor Use in Cirrhosis.
Premkumar M, Kajal K, Gupta P … +1 more , Reddy KR
Semin Liver Dis · 2025 Jun · PMID 39809452 · Publisher ↗
Critically ill patients with cirrhosis and liver failure do not uncommonly have hypotension due to multifactorial reasons, which include a hyperdynamic state with increased cardiac index (CI), low systemic vascular resis...
Critically ill patients with cirrhosis and liver failure do not uncommonly have hypotension due to multifactorial reasons, which include a hyperdynamic state with increased cardiac index (CI), low systemic vascular resistance (SVR) due to portal hypertension, following the use of beta-blocker or diuretic therapy, and severe sepsis. These changes are mediated by microvascular alterations in the liver, systemic inflammation, activation of renin-angiotensin-aldosterone system, and vasodilatation due to endothelial dysfunction. Haemodynamic assessment includes measuring inferior vena cava indices, cardiac output (CO), and SVR using point-of-care ultrasound (POCUS), arterial waveform analysis, pulmonary artery pressures, and lactate clearance to guide fluid resuscitation. Fluid responsiveness reflects the ability of fluid bolus to increase the CO and is assessed effectively by POCUS, passive leg raises manoeuvre, and dynamic tests such as pulse pressure and stroke volume variation in spontaneously breathing and mechanically ventilated patients. Albumin has pleiotropic benefits through anti-inflammatory properties besides its standard action on oncotic pressure and volume expansion in patients with cirrhosis but has the potential for precipitating pulmonary oedema. In conclusion, fluid therapy in critically ill patients with liver disease is a complex and dynamic process that requires individualized management protocols to optimize patient outcomes.
Alcohol Plus Additional Risk Factors: Rodent Model of Liver Injury.
Wu Q, Yang D, Liu C … +1 more , Xu T
Semin Liver Dis · 2025 Mar · PMID 39719149 · Publisher ↗
Alcohol-associated liver disease (ALD), primarily caused by chronic excessive alcohol consumption, is a leading cause of chronic liver disease worldwide. ALD includes alcohol-associated steatotic liver, alcohol-associate...
Alcohol-associated liver disease (ALD), primarily caused by chronic excessive alcohol consumption, is a leading cause of chronic liver disease worldwide. ALD includes alcohol-associated steatotic liver, alcohol-associated hepatitis (AH), fibrosis, cirrhosis, and can even progress to hepatocellular carcinoma (HCC). Existing research indicates that the risk factors of ALD are quite numerous. In addition to drinking patterns, factors such as aldehyde dehydrogenase 2 (ALDH2) deficiency, smoking, medication administration, high-fat diet (HFD), hepatitis virus infection, and disruption of circadian rhythms can also increase susceptibility to ALD. However, there is limited understanding regarding the exacerbation of liver injury by alcohol plus additional risk factors. This review presents rodent models of EtOH + "X," which simulate the synergistic effects of alcohol and additional risk factors in causing liver injury. These models offer a further exploration of the interactions between alcohol and additional risk factors, advancing the simulation of human ALD and providing a more reliable platform for studying disease mechanisms and exploring therapeutic interventions. We summarize the modeling methods, relevant indicators of liver injury, and focus on the targets of the synergistic effects as well as the associated mechanisms.
Extracellular Vesicles and Micro-RNAs in Liver Disease.
Washington AM, Kostallari E
Semin Liver Dis · 2025 Jun · PMID 39626790 · Full text
Progression of liver disease is dependent on intercellular signaling, including those mediated by extracellular vesicles (EVs). Within these EVs, microRNAs (miRNAs) are packaged to selectively silence gene expression in...
Progression of liver disease is dependent on intercellular signaling, including those mediated by extracellular vesicles (EVs). Within these EVs, microRNAs (miRNAs) are packaged to selectively silence gene expression in recipient cells for upregulating or downregulating a specific pathway. Injured hepatocytes secrete EV-associated miRNAs which can be taken up by liver sinusoidal endothelial cells, immune cells, hepatic stellate cells, and other cell types. In addition, these recipient cells will secrete their own EV-associated miRNAs to propagate a response throughout the tissue and the circulation. In this review, we comment on the implications of EV-miRNAs in the progression of alcohol-associated liver disease, metabolic dysfunction-associated steatohepatitis, viral and parasitic infections, liver fibrosis, and liver malignancies. We summarize how circulating miRNAs can be used as biomarkers and the potential of utilizing EVs and miRNAs as therapeutic methods to treat liver disease.
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