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The frequency of liver diseases in the intensive care unit has increased significantly in recent years and is now observed in up to 20% of critically ill patients. The occurrence of liver disease is associated with significantly increased morbidity and mortality. Two groups of liver diseases in the intensive care unit can be distinguished. First, the group of "primary hepatic dysfunctions", which includes primary acute liver failure as well as acute-on-chronic liver failure in patients with pre-existing liver cirrhosis. The second group of "secondary or acquired liver diseases" includes cholestatic liver diseases, as well as hypoxic liver injury and mixed forms, as well as other rarer liver diseases. Due to the diversity of liver diseases and the very different triggers, sufficient knowledge of the underlying changes (including hemodynamic changes, inflammatory states or drug-related) is essential. Early recognition, diagnosis, and treatment of the underlying disease are essential for all liver dysfunction in critically ill patients in the intensive care unit. This review article aims to take a closer look at liver diseases in the intensive care unit and provides insight into diagnostics and treatment options., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Lactate is a byproduct of glycolysis, and before the Warburg effect was revealed (in which glucose can be fermented in the presence of oxygen to produce lactate) it was considered a metabolic waste product. At present, lactate is not only recognized as a metabolic substrate that provides energy, but also as a signaling molecule that regulates cellular functions under pathophysiological conditions. Lactylation, a post‑translational modification, is involved in the development of various diseases, including inflammation and tumors. Liver disease is a major health challenge worldwide. In normal liver, there is a net lactate uptake caused by gluconeogenesis, exhibiting a higher net lactate clearance rate compared with any other organ. Therefore, abnormalities of lactate and lactate metabolism lead to the development of liver disease, and lactate and lactate metabolism‑related genes can be used for predicting the prognosis of liver disease. Targeting lactate production, regulating lactate transport and modulating lactylation may be potential treatment approaches for liver disease. However, currently there is not a systematic review that summarizes the role of lactate and lactate metabolism in liver diseases. In the present review, the role of lactate and lactate metabolism in liver diseases including liver fibrosis, non‑alcoholic fatty liver disease, acute liver failure and hepatocellular carcinoma was summarized with the aim to provide insights for future research.

In liver disease, there is derangement of appetite, digestion, absorption, assimilation, storage and metabolism of both macro and micronutrients. These derangements have an impact on mortality and morbidity associated with liver diseases. In infants, breast feeds should not be stopped unless there are compelling reasons such as underlying metabolic problem. Parenteral nutrition should be considered only if, oral or nasogastric feeding is not possible. The effect of malnutrition on liver disease and impact of liver failure on nutrition is vicious and nutritional intervention has to be done at the earliest to break that vicious cycle. This chapter gives an overview of nutritional management in acute and chronic liver diseases in children and also its impact on specific clinical scenarios including liver transplantation., (© 2024. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Orthotopic liver transplantation (OLT) is the current standard of care for both chronic and acute terminal liver disease. However, a major limitation of this treatment is the shortage of healthy donor organs and the need for life-long immunosuppression to prevent graft rejection. Hepatocyte transplantation (HTx) has emerged as a promising, alternative therapeutic approach to either replace OLT or to act as a bridge until a donor liver becomes available thus reducing waiting list mortality. HTx involves the infusion and engraftment of human hepatocytes, typically isolated from organs unsuitable for OLT, into recipient liver parenchyma to carry out the missing hepatic function of the native cells. HTx is less invasive than OLT and can be performed repeatedly if required. The safety of clinical HTx has been shown and treatment results are promising, especially in patients with liver-based metabolic disorders. Nevertheless, HTx has failed to become the standard of care treatment for such disorders. This review aims to evaluate the progress that has been made within the field of HTx over the last 30 years and identify potential shortcomings within the approach which may be hindering its routine clinical application., (© The Author(s) 2023. Published by Oxford University Press.)

Autosomal dominant polycystic kidney disease (ADPKD) often involves polycystic liver disease (PLD). In severe cases, PLD can develop various complications. However, fatal acute portal vein thrombosis (APVT) associated with PLD has not been reported. A 64-year-old male reported mild consciousness disorder. He had been under maintenance hemodialysis for end-stage renal disease due to ADPKD with PLD. Because of recurring hepatic cyst infections, he had sustained high levels of C-reactive protein. Regarding the mild consciousness disorder, a diagnosis of hepatic encephalopathy was made based on an elevation of serum ammonia without any other abnormal liver function tests. Several days after his admission, hepatobiliary enzymes elevated, and acute liver failure progressed. Enhanced abdominal computed tomography suggested the possibility of complete occlusion of the portal vein by a thrombus. Based on an absence of obvious portosystemic collaterals, a diagnosis of APVT was made. The patient died 19 days after admission. Patients with PLD with repeated cystic infections have been seen to develop liver failure, and APVT formation may be one cause of the rapid progression of fatal liver failure. In conclusion, this is the first paper to report on the involvement of APVT in patients with PLD., (© 2023. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

There is little information on the differential diagnosis and prognosis of hospitalized patients with hyperbilirubinemia. Here, we hypothesized that hyperbilirubinemia in hospitalized patients is associated with specific diseases and outcomes. This retrospective cohort analysis included patients admitted to the Medical University of South Carolina with a total bilirubin >3 mg/dL from January 9, 2015 to August 25, 2017. Collected clinical data included demographics, primary diagnosis, Charlson Comorbidity Index (CCI), laboratory data, and clinical outcomes. We separated and analyzed the cohort into seven primary diagnostic groups. We identified 1693 patients with a bilirubin level >3 mg/dL. The cohort was 42% female, had an average age of 54, average CCI of 4.8, and average length of stay of 13 days. The causes of hyperbilirubinemia included the following: primary liver disease (868/1693; 51%) with cirrhosis being most common (385/1693; 23%), benign biliary obstruction (252/1693; 15%), hemolytic anemia (149/1693; 9%), malignant biliary obstruction (121/1693; 7%), unknown etiology (108/1693; 6%), primary liver cancer (74/1693; 4%), and metastatic cancer to the liver (57/1693; 3%). Overall, the mortality/discharge to hospice rate in patients with a bilirubin >3 mg/dL was 30%, and was proportional to the severity of hyperbilirubinemia, including when controlling for the underlying severity of illness. Mortality was highest in patients with primary liver disease and malignancy and was lowest in patients with non-cancerous obstruction or hemolytic jaundice. Hyperbilirubinemia in hospitalized patients is most often due to primary liver disease, and identifies patients with a poor prognosis, particularly when caused by primary liver disease or cancer., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The liver is a vital organ responsible for metabolic and digestive functions, protein synthesis, detoxification, and numerous other necessary functions. Various acute, chronic, and neoplastic disorders affect the liver and hamper its biological functions. Most of the untreated liver diseases lead to inflammation and fibrosis which develop into cirrhosis. The human amniotic membrane (hAM), the innermost layer of the fetal placenta, is composed of multiple layers that include growth-factor rich basement membrane, epithelial and mesenchymal stromal cell layers. hAM possesses distinct beneficial anti-fibrotic, anti-inflammatory and pro-regenerative properties via the secretion of multiple potent trophic factors and/or direct differentiation into hepatic cells which place hAM-based therapies as potential therapeutic strategies for the treatment of chronic liver diseases. Decellularized hAM is also an ideal scaffold for liver tissue engineering as this biocompatible niche provides an excellent milieu for cell proliferation and hepatocytic differentiation. Therefore, the current review discusses the therapeutic potential of hAM and its derivatives in providing therapeutic solutions for liver pathologies including acute liver failure, metabolic disorders, liver fibrosis as well as its application in liver tissue engineering.

This review aims to evaluate the current preclinical state of liver bioengineering, the clinical context for liver cell therapies, the cell sources, the delivery routes, and the results of clinical trials for end-stage liver disease. Different clinical settings, such as inborn errors of metabolism, acute liver failure, chronic liver disease, liver cirrhosis, and acute-on-chronic liver failure, as well as multiple cellular sources were analyzed; namely, hepatocytes, hepatic progenitor cells, biliary tree stem/progenitor cells, mesenchymal stromal cells, and macrophages. The highly heterogeneous clinical scenario of liver disease and the availability of multiple cellular sources endowed with different biological properties make this a multidisciplinary translational research challenge. Data on each individual liver disease and more accurate endpoints are urgently needed, together with a characterization of the regenerative pathways leading to potential therapeutic benefit. Here, we critically review these topics and identify related research needs and perspectives in preclinical and clinical settings., Competing Interests: Conflict of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Idiosyncratic drug-induced liver injury (DILI) is an infrequent but important cause of liver disease. Newly identified causes of DILI include the COVID vaccines, turmeric, green tea extract, and immune checkpoint inhibitors. DILI is largely a clinical diagnosis of exclusion that requires evaluation for more common causes of liver injury and a compatible temporal association with the suspect drug. Recent progress in DILI causality assessment includes the development of the semi-automated revised electronic causality assessment method (RECAM) instrument. In addition, several drug-specific HLA associations have been identified that can help with the confirmation or exclusion of DILI in individual patients. Various prognostic models can help identify the 5%-10% of patients at highest risk of death. Following suspect drug cessation, 80% of patients with DILI fully recover, whereas 10%-15% have persistently abnormal laboratory studies at 6 months of follow-up. Hospitalized patients with DILI with an elevated international normalized ratio or mental status changes should be considered for N-acetylcysteine therapy and urgent liver transplant evaluation. Selected patients with moderate to severe drug reaction with eosinophilia and systemic symptoms or autoimmune features on liver biopsy may benefit from short-term corticosteroids. However, prospective studies are needed to determine the optimal patients and dose and duration of steroids to use. LiverTox is a comprehensive, freely accessible Web site with important information regarding the hepatotoxicity profile of more than 1000 approved medications and 60 herbal and dietary supplement products. It is hoped that ongoing "omics" studies will lead to additional insight into DILI pathogenesis, improved diagnostic and prognostic biomarkers, and mechanism-based treatments., (Copyright © 2023 AGA Institute. All rights reserved.)

Background: SARS-CoV-2-induced severe inflammatory response can be associated with severe medical consequences leading to multi-organ failure, including the liver. The main mechanism behind this assault is the aggressive cytokine storm that induces cytotoxicity in various organs. Of interest, hepatic stellate cells (HSC) respond acutely to liver injury through several molecular mechanisms, hence furthering the perpetuation of the cytokine storm and its resultant tissue damage. In addition, hepatocytes undergo apoptosis or necrosis resulting in the release of pro-inflammatory and pro-fibrogenic mediators that lead to chronic liver inflammation., Aims: The aim of this review is to summarize available data on SARS-CoV-2-induced liver inflammation in addition to evaluate the potential effect of anti-inflammatory drugs in attenuating SARS-CoV-2-induced liver inflammation., Methods: Thorough PubMed search was done to gather and summarize published data on SARS-CoV-2-induced liver inflammation. Additionally, various anti-inflammatory potential treatments were also documented., Results: Published data documented SARS-CoV-2 infection of liver tissues and is prominent in most liver cells. Also, histological analysis showed various features of tissues damage, e.g., hepatocellular necrosis, mitosis, cellular infiltration, and fatty degeneration in addition to microvesicular steatosis and inflammation. Finally, the efficacy of the different drugs used to treat SARS-CoV-2-induced liver injury, in particular the anti-inflammatory remedies, are likely to have some beneficial effect to treat liver injury in COVID-19., Conclusion: SARS-CoV-2-induced liver inflammation is a serious condition, and drugs with potent anti-inflammatory effect can play a major role in preventing irreversible liver damage in COVID-19., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Organ dysfunction or overt failure is a commonplace event in the critically ill affecting up to 70% of patients during their stay in the ICU. The outcome depends on the resolution of impaired organ function, while a domino-like deterioration of organs other than the primarily affected ones paves the way for increased mortality. "Acute Liver Failure" was defined in the 1970s as a rare and potentially reversible severe liver injury in the absence of prior liver disease with hepatic encephalopathy occurring within 8 weeks. Dysfunction of the liver in general reflects a critical event in "Multiple Organ Dysfunction Syndrome" due to immunologic, regulatory and metabolic functions of liver parenchymal and non-parenchymal cells. Dysregulation of the inflammatory response, persistent microcirculatory (hypoxic) impairment or drug-induced liver injury are leading problems that result in "secondary liver failure," i.e., acquired liver injury without underlying liver disease or deterioration of preexisting (chronic) liver disease ("Acute-on-Chronic Liver Failure"). Conventional laboratory markers, such as transaminases or bilirubin, are limited to provide insight into the complex facets of metabolic and immunologic liver dysfunction. Furthermore, inhomogeneous definitions of these entities lead to widely ranging estimates of incidence. In the present work, we review the different definitions to improve the understanding of liver dysfunction as a perpetrator (and therapeutic target) of multiple organ dysfunction syndrome in critical care., (© 2022. The Author(s).)

Liver transplantation is the gold standard for the treatment of pediatric end-stage liver disease and liver based metabolic disorders. Although liver transplant is successful, its wider application is limited by shortage of donor organs, surgical complications, need for life long immunosuppressive medication and its associated complications. Cellular therapies such as hepatocytes and mesenchymal stromal cells (MSCs) are currently emerging as an attractive alternative to liver transplantation. The aim of this review is to present the existing world experience in hepatocyte and MSC transplantation and the potential for future effective applications of these modalities of treatment.

Mitochondrial hepatopathies are a subset of mitochondrial diseases defined by primary dysfunction of hepatocyte mitochondria leading to a phenotype of hepatocyte cell injury, steatosis, or liver failure. Increasingly, the diagnosis is established by new sequencing approaches that combine analysis of both nuclear DNA and mitochondrial DNA and allow for timely diagnosis in most patients. Despite advances in diagnostics, for most affected children their disorders are relentlessly progressive, and result in substantial morbidity and mortality. Treatment remains mainly supportive; however, novel therapeutics and a more definitive role for liver transplantation hold promise for affected children., Competing Interests: Disclosure M. Ayers: Nothing to disclose. S.P. Horslen: Nothing to disclose. A.M. Gómez: Nothing to disclose. J.E. Squires: Nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The hepatic compartment syndrome (HCS) corresponds to compression of the intraparenchymal liver tissue (intrahepatic pressure greater than the portal vein pressure, i.e. >10-15mmHg) caused by a subcapsular or intraparenchymal hematoma of the liver. It can lead to reversal of portal flow and hepatic parenchymal necrosis. We report the case of a patient who underwent a right radical nephrectomy by laparoscopy and who presented with HCS due to a subcapsular hematoma of the liver. Emergency decompression of the liver via laparotomy was performed, which allowed rapid clinical and laboratory improvement., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Introduction: Acute liver injury and progression to acute liver failure can be life-threatening conditions that require prompt careful clinical assessment and therapeutic management., Areas Covered: The aim of this article is to review the safety and side effect profile of pharmacological therapies used in the treatment of acute liver injury with specific focus on hepatic toxicity. We performed an extensive literature search with the terms 'acute liver injury,' 'acute liver failure,' 'therapy,' 'safety,' 'adverse reactions' and 'drug induced liver injury.' A thorough discussion of the main drugs and devices used in patients with acute liver injury and acute liver failure, its safety profile and the management of complications associated to therapy of these conditions is presented., Expert Opinion: Several pharmacological approaches are used in acute liver injury and acute liver failure in an empirical basis. Whilst steroids are frequently tried in serious drug-induced liver injury there is concern on a potential harmful effect of these agents because of the higher mortality in patients receiving the drug; hence, statistical approaches such as propensity score matching might help resolve this clinical dilemma. Likewise, properly designed clinical trials using old and new drugs for subjects with serious drug-induced liver injury are clearly needed.

Recently, probiotics have been widely used as an adjuvant therapy to cure, prevent, or improve certain diseases. However, no research has been carried out into the dose of probiotics, especially the maximum dose. Therefore, the effective and safe dosage of probiotics needs to be studied. Recently, L. Yang, X. Bian, W. Wu, L. Lv, et al. (Microb Biotechnol 13:1860-1876, 2020, https://doi.org/10.1111/1751-7915.13629) discovered that Lactobacillus salivarius Li01 had a protective effect on thioacetamide-induced acute liver injury and hyperammonemia, and a fixed concentration (3 × 10 9 CFU/mL) of L. salivarius Li01 was applied in their study. However, the most effective treatment concentration of L. salivarius Li01 remains unknown. Therefore, four concentration gradients of L. salivarius Li01 suspension were prepared for groups of mice to have different levels of bacterial colonization by gavage. Then, acute liver injury and hyperammonemia were induced via thioacetamide administration. By observation and detection, an inverted U-shaped protective effect from L. salivarius Li01 existed in thioacetamide-induced acute liver injury and hyperammonemia. Of note, significant deterioration was confirmed within the group that was orally administered with an excessive concentration of L. salivarius Li01 suspension, and this was attributed to endotoxemia that resulted from compromised immunity, a damaged intestinal barrier, and bacterial translocation. IMPORTANCE This research investigated the relationship between the concentration of Lactobacillus salivarius Li01 and its impact on mice that had a thioacetamide-induced acute liver injury and hyperammonemia. These findings could provide new insights into the effective, proper, and safe use of probiotics.

This working group of the International Society of Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) was commissioned to summarize and update current efforts in the development and characterization of animal models of hepatic encephalopathy (HE). As defined in humans, HE in animal models is based on the underlying degree and severity of liver pathology. Although hyperammonemia remains the key focus in the pathogenesis of HE, other factors associated with HE have been identified, together with recommended animal models, to help explore the pathogenesis and pathophysiological mechanisms of HE. While numerous methods to induce liver failure and disease exist, less have been characterized with neurological and neurobehavioural impairments. Moreover, there still remains a paucity of adequate animal models of Type C HE induced by alcohol, viruses and non-alcoholic fatty liver disease; the most common etiologies of chronic liver disease., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The Practical guideline is based on the current scientific ESPEN guideline on Clinical Nutrition in Liver Disease., Methods: It has been shortened and transformed into flow charts for easier use in clinical practice. The guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with chronic liver disease., Results: A total of 103 statements and recommendations are presented with short commentaries for the nutritional and metabolic management of patients with (i) acute liver failure, (ii) alcoholic steatohepatitis, (iii) non-alcoholic fatty liver disease, (iv) liver cirrhosis, and (v) liver surgery/transplantation. The disease-related recommendations are preceded by general recommendations on the diagnostics of nutritional status in liver patients and on liver complications associated with medical nutrition., Conclusion: This practical guideline gives guidance to health care providers involved in the management of liver disease to offer optimal nutritional care., Competing Interests: Conflict of interest The expert members of the working group were accredited by the ESPEN Guidelines Group, the ESPEN Education and Clinical Practice Committee, and the ESPEN executive. All expert members have declared their individual conflicts of interest according to the rules of the International Committee of Medical Journal Editors (ICMJE). If potential conflicts were indicated, they were reviewed by the ESPEN guideline officers and, in cases of doubts, by the ESPEN executive. None of the expert panel had to be excluded from the working group or from co-authorship because of serious conflicts. The conflict of interest forms are stored at the ESPEN guideline office and can be reviewed by ESPEN members with legitimate interest upon request to the ESPEN executive., (Copyright © 2020 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd.. All rights reserved.)

Inherited metabolic diseases account for about one third of pediatric patients with hepatomegaly, acute liver failure, cirrhosis or cholestasis. Specifically for pediatric acute liver failure, they account for 10-15% of cases, with a mortality of 22-65%. The percentage of acute liver failure caused by an inherited metabolic disease in children <2-3 years of age is even higher, ranging from a third to half of all cases. Metabolic liver disease accounts for 8-13% of all pediatric liver transplantations. Despite this high burden of disease, underdiagnosis remains common. We reviewed and updated the list of known metabolic etiologies associated with various types of metabolic liver involvement, and found 142 relevant inborn errors of metabolism. This represents the second of a series of articles attempting to create and maintain a comprehensive list of clinical and metabolic differential diagnoses according to system involvement., (Published by Elsevier Inc.)

Hepatocyte growth factor (HGF) is an endogenously expressed bioactive substance that has a strong anti-apoptotic effect. In this study, we biochemically and histologically characterized the effects of rh-HGF on in vitro human hepatocyte injury and mouse acute liver failure (ALF) models, both of which were induced by antibody-mediated Fas signaling. rh-HGF inhibited intracellular caspase-3/7 activation and cytokeratin 18 (CK-18) fragment release in both models. Histologically, rh-HGF dramatically suppressed parenchymal damage and intrahepatic hemorrhage. Among the laboratory parameters, prothrombin time (PT) was strongly preserved by rh-HGF, and PT was well correlated with the degree of intrahepatic hemorrhage. These results showed that the anti-apoptotic effect of rh-HGF on hepatocytes coincided strikingly with the suppression of intrahepatic hemorrhage. PT was considered to be the best parameter that correlated with the intrahepatic hemorrhages associated with hepatocellular damage. The action of rh-HGF might derive not only from its anti-apoptosis effects on liver parenchymal cells but also from its stabilization of structural and vasculature integrity., Competing Interests: Akio Ido has received honoraria from Bristol-Meyers Squibb Co., Ltd., Gilead Sciences Co., Ltd., Abbvie Inc. Those funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Also Akio Ido has received honoraria from Eisai Co., Ltd., and research funding from Eisai Co., Ltd.

This update of evidence-based guidelines (GL) aims to translate current evidence and expert opinion into recommendations for multidisciplinary teams responsible for the optimal nutritional and metabolic management of adult patients with liver disease. The GL was commissioned and financially supported by ESPEN. Members of the guideline group were selected by ESPEN. We searched for meta-analyses, systematic reviews and single clinical trials based on clinical questions according to the PICO format. The evidence was evaluated and used to develop clinical recommendations implementing the SIGN method. A total of 85 recommendations were made for the nutritional and metabolic management of patients with acute liver failure, severe alcoholic steatohepatitis, non-alcoholic fatty liver disease, liver cirrhosis, liver surgery and transplantation as well as nutrition associated liver injury distinct from fatty liver disease. The recommendations are preceded by statements covering current knowledge of the underlying pathophysiology and pathobiochemistry as well as pertinent methods for the assessment of nutritional status and body composition., (Copyright © 2019 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd.. All rights reserved.)

Patients with advanced liver disease have traditionally been considered at risk for bleeding complications. However, although bleeding in patients with cirrhosis frequently occurs due to complications of portal hypertension, research performed within the last 15 years has increasingly shown that hemostasis in patients with liver failure generally achieves a state of "rebalance", whereby compensatory systems restore a relatively neutral or even slightly pro-thrombotic state. Much recent clinical and in vitro research has, in fact, shown over-compensation, such that patients with acute and stable chronic liver failure may have a thrombotic tendency, which may participate in the progression of liver disease and cause systemic and portal thrombosis. Investigators have started to identify differences in hemostasis in patients with unstable cirrhosis, the newly defined syndrome of acute-on-chronic liver failure (ACLF), compared to those with stable cirrhosis. The following discussion will summarize much of the background of rebalanced hemostasis in patients with cirrhosis and acute liver failure (ALF), and suggest management algorithms for coagulation abnormalities before invasive procedures, during active bleeding, and for prophylaxis and treatment of thrombotic complications.

Liver disease in children can present in many ways from the frequently encountered prolonged neonatal jaundice to the comparatively rare acute liver failure. In this article, we will discuss 'red flags' of liver disease, the initial investigations required and when to refer to a specialist liver centre. Across all presentations, the degree of elevation of alanine aminotransferase or aspartate aminotransferase provides only little diagnostic information. Measurement of clotting is vital, and coagulopathy should be followed by a trial of intravenous vitamin K before being repeated., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

This article reviews the Adult-to-Adult Living Donor Liver Transplant Cohort Study (A2ALL). The findings show that the number of adult-to-adult living donor liver transplants is consistently increasing. Living donor liver transplantation has an important benefit for patients with acute liver failure, does not compromise donor safety, and has lower rates of acute cellular rejection in biologically related donor and recipient. The conclusions from the A2ALL consortium have been critical in transplant advancement, supporting increased use to help decrease waitlist death and improve long-term survival of transplant recipients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Pannexins are transmembrane proteins that form communication channels connecting the cytosol of an individual cell with its extracellular environment. A number of studies have documented the presence of pannexin1 in liver as well as its involvement in inflammatory responses. In this study, it was investigated whether pannexin1 plays a role in acute liver failure and non-alcoholic steatohepatitis, being prototypical acute and chronic liver pathologies, respectively, both featured by liver damage, oxidative stress and inflammation. To this end, wild-type and pannexin1 -/- mice were overdosed with acetaminophen for 1, 6, 24 or 48h or were fed a choline-deficient high-fat diet for 8weeks. Evaluation of the effects of genetic pannexin1 deletion was based on a number of clinically relevant read-outs, including markers of liver damage, histopathological analysis, lipid accumulation, protein adduct formation, oxidative stress and inflammation. In parallel, in order to elucidate molecular pathways affected by pannexin1 deletion as well as to mechanistically anchor the clinical observations, whole transcriptome analysis of liver tissue was performed. The results of this study show that pannexin1 -/- diseased mice present less liver damage and oxidative stress, while inflammation was only decreased in pannexin1 -/- mice in which non-alcoholic steatohepatitis was induced. A multitude of genes related to inflammation, oxidative stress and xenobiotic metabolism were differentially modulated in both liver disease models in wild-type and in pannexin1 -/- mice. Overall, the results of this study suggest that pannexin1 may play a role in the pathogenesis of liver disease., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Alongside the kidneys and lungs, the liver has been recognised as an important regulator of acid-base homeostasis. While respiratory alkalosis is the most common acid-base disorder in chronic liver disease, various complex metabolic acid-base disorders may occur with liver dysfunction. While the standard variables of acid-base equilibrium, such as pH and overall base excess, often fail to unmask the underlying cause of acid-base disorders, the physical-chemical acid-base model provides a more in-depth pathophysiological assessment for clinical judgement of acid-base disorders, in patients with liver diseases. Patients with stable chronic liver disease have several offsetting acidifying and alkalinising metabolic acid-base disorders. Hypoalbuminaemic alkalosis is counteracted by hyperchloraemic and dilutional acidosis, resulting in a normal overall base excess. When patients with liver cirrhosis become critically ill (e.g., because of sepsis or bleeding), this fragile equilibrium often tilts towards metabolic acidosis, which is attributed to lactic acidosis and acidosis due to a rise in unmeasured anions. Interestingly, even though patients with acute liver failure show significantly elevated lactate levels, often, no overt acid-base disorder can be found because of the offsetting hypoalbuminaemic alkalosis. In conclusion, patients with liver diseases may have multiple co-existing metabolic acid-base abnormalities. Thus, knowledge of the pathophysiological and diagnostic concepts of acid-base disturbances in patients with liver disease is critical for therapeutic decision making., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Over 20 years ago, sphingosine-1-phosphate (S1P) was discovered to be a bioactive signaling molecule. Subsequent studies later identified two related kinases, sphingosine kinase 1 and 2, which are responsible for the phosphorylation of sphingosine to S1P. Many stimuli increase sphingosine kinase activity and S1P production and secretion. Outside the cell, S1P can bind to and activate five S1P-specific G protein-coupled receptors (S1PR1-5) to regulate many important cellular and physiological processes in an autocrine or paracrine manner. S1P is found in high concentrations in the blood where it functions to control vascular integrity and trafficking of lymphocytes. Obesity increases blood S1P levels in humans and mice. With the world wide increase in obesity linked to consumption of high-fat, high-sugar diets, S1P is emerging as an accomplice in liver pathobiology, including acute liver failure, metabolic syndrome, control of blood lipid and glucose homeostasis, nonalcoholic fatty liver disease, and liver fibrosis. Here, we review recent research on the importance of sphingosine kinases, S1P, and S1PRs in liver pathobiology, with a focus on exciting insights for new therapeutic modalities that target S1P signaling axes for a variety of liver diseases.

Acute liver failure and cirrhosis display sequential and overlapping severe pathogenic processes that include inflammation, hepatocyte necrosis, and fibrosis, carrying a high mortality rate. Mesenchymal stem cells (MSCs) are a heterogeneous subset of stromal stem cells with immunonodulatory characteristics. MSCs are considered to act through multiple mechanisms to coordinate a dynamic, integrated response to liver inflammation and fibrosis, which prevents the progressive distortion of hepatic architecture. Accordingly, MSCs as well as their products have been investigated as a novel therapeutic approach for the treatment of inflammatory and fibrotic liver diseases. In this review, we highlight the current findings on the MSC-based modulation of liver inflammation and fibrosis, and the possible use of MSCs in the therapy of immune-mediated liver pathology. We briefly describe the cellular and molecular mechanisms involved in MSC-dependent modulation of cytokine production, phenotype and function of liver infiltrated inflammatory cells and compare effects of engrafted MSCs versus MSC-generated conditioned medium (MSC-CM) in the therapy of acute liver injury. In order to elucidate therapeutic potential of MSCs and their products in modulation of chronic liver inflammation and fibrosis, we present the current findings regarding pathogenic role of immune cells in liver fibrosis and describe mechanisms involved in MSC-dependent modulation of chronic liver inflammation with the brief overview of on-going and already published clinical trials that used MSCs for the treatment of immune mediated chronic liver diseases. The accumulating evidence shows that MSCs had a significant beneficial effect in the treatment of immune-mediated liver diseases., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Introduction: Ammonia-scavenging drugs, benzoate and phenylacetate (PA)/phenylbutyrate (PB), modulate hepatic nitrogen metabolism mainly by providing alternative pathways for nitrogen disposal. Areas covered: We review the major findings and potential novel applications of ammonia-scavenging drugs, focusing on urea cycle disorders and liver disease. Expert opinion: For over 40 years, ammonia-scavenging drugs have been used in the treatment of urea cycle disorders. Recently, the use of these compounds has been advocated in acute liver failure and cirrhosis for reducing hyperammonemic-induced hepatic encephalopathy. The efficacy and mechanisms underlying the antitumor effects of these ammonia-scavenging drugs in liver cancer are more controversial and are discussed in the review. Overall, as ammonia-scavenging drugs are usually safe and well tolerated among cancer patients, further studies should be instigated to explore the role of these drugs in liver cancer. Considering the relevance of glutamine metabolism to the progression and resolution of liver disease, we propose that ammonia-scavenging drugs might also be used to non-invasively probe liver glutamine metabolism in vivo. Finally, novel derivatives of classical ammonia-scavenging drugs with fewer and less severe adverse effects are currently being developed and used in clinical trials for the treatment of acute liver failure and cirrhosis.

Chronic liver damage is associated with unique changes in the hemostatic system. Patients with liver disease often show a precariously rebalanced hemostatic system, which is easily tipped towards bleeding or thrombotic complications by otherwise benign stimuli. In addition, some clinical studies have shown that hemostatic system components contribute to the progression of liver disease. There is a strong basic science foundation for clinical studies with this particular focus. Chronic and acute liver disease can be modeled in rodents and large animals with a variety of approaches, which span chronic exposure to toxic xenobiotics, diet-induced obesity, and surgical intervention. These experimental approaches have now provided strong evidence that, in addition to perturbations in hemostasis caused by liver disease, elements of the hemostatic system have powerful effects on the progression of experimental liver toxicity and disease. In this review, we cover the basis of the animal models that are most often utilized to assess the impact of the hemostatic system on liver disease, and highlight the role that coagulation proteases and their targets play in experimental liver toxicity and disease, emphasizing key similarities and differences between models. The need to characterize hemostatic changes in existing animal models and to develop novel animal models recapitulating the coagulopathy of chronic liver disease is highlighted. Finally, we emphasize the continued need to translate knowledge derived from highly applicable animal models to improve our understanding of the reciprocal interaction between liver disease and the hemostatic system in patients., (© 2016 International Society on Thrombosis and Haemostasis.)

Ethnopharmacological Relevance: Aconitum carmichaelii Debeaux is a well-known Chinese herb that has been used to treat liver diseases for many years in China. We investigated the effects of aqueous extract from Aconitum carmichaelii Debeaux (AEACD) on acute liver failure and identified the possible mechanisms of these effects., Material and Methods: Specific pathogen-free (SPF) male Wistar rats were used to establish acute liver failure model by intraperitoneal injection of D-galactosamine (D-GalN) and treated with Stronger Neo-Minophagen C (SNMC) and AEACD by gavage. Then, the serum biochemical parameters, the pathological scores in the liver tissue, the mRNA expressions of toll- like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), high mobility group box 1 (HMGB1) and caspase-3, the proliferating cell nuclear antigen (PCNA) positive rates were analyzed., Results: The liver function was improved, the pathological scores were decreased, the expressions the TLR4, NF-κB, HMGB1, and caspase-3 were inhibited, and the PCNA positive rates were increased by both SNMC and AEACD, but AEACD induced greater effects., Conclusions: AEACD protected liver function by inhibiting inflammatory reaction, apoptosis and promoting liver tissue regeneration in the acute liver failure rats induced by D-galactosamine., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Background: Delayed postoperative arterial bleeding is rare and may be life-threatening. When the bleeding source is the hepatic artery, complete ligation or embolization from the proximal to the distal area of the ruptured lesion usually results in complete occlusion of hepatic arterial flow., Methods: To evaluate the frequency and severity of ischemic liver injury following complete hepatic artery occlusion, a retrospective study was conducted. Patients who underwent complete hepatic artery occlusion in the treatment of delayed postoperative arterial bleeding between January 2007 and December 2014 in our institution were reviewed. Changes of hepatic function and rates of associated complications and prognosis were analyzed., Results: A total of 24 patients experienced 26 episodes of bleeding. Nineteen experienced transient liver enzyme elevation alone. There were no signs of acute liver failure after complete hepatic artery occlusion. The rates of liver infarction and liver abscess were 23.8 % (5/21) and 19 % (4/21), respectively. The 30-day mortality rate was 8.3 % (2/24)., Conclusion: Complete occlusion of the hepatic artery does not always result in severe hepatic ischemic injury. As a common cause of delayed postoperative bleeding, intra-abdominal infection may be fatal when it is not controlled successfully.

Drug hepatoxicity can be nonidiosyncratic (predictable), as in the case of acetaminophen, or idiosyncratic (unpredictable). This review article focuses primarily on idiosyncratic drug-induced liver injury (DILI). New epidemiologic data suggest that approximately 20 new cases of DILI per 100,000 persons occur each year. Idiosyncratic DILI accounts for 11% of the cases of acute liver failure in the United States. Risk factors for DILI include medication dose, drug lipophilicity, and extent of hepatic metabolism. There is mixed evidence to support the role of host factors such as age, sex, and chronic liver disease in the development of DILI. For specific drugs, a genetic predisposition appears to be a risk factor for DILI. Suspected cases of idiosyncratic DILI should be categorized as hepatitic, cholestatic, or mixed on the basis of the degree/ratio of abnormalities in the alanine aminotransferase and alkaline phosphatase. A careful evaluation for other causes of liver disease should be performed, though a liver biopsy is rarely needed. There is evidence that some patients with DILI may actually have hepatitis E and this diagnosis should be considered. Amoxicillin/clavulanate isoniazid, and nonsteroidal anti-inflammatory drugs are among the most common causes of DILI. Drug discontinuation or dechallenge should lead to an improvement in liver biochemistries in most patients, though a bilirubin value of more than 3 g/dL is associated with mortality of at least 10%. New biomarkers for DILI using proteomics and micro RNA appear promising but require further study. New studies on drugs with potential for causing DILI are reviewed herein, including tumor necrosis factor-alpha antagonists, fluoroquinolones, tyrosine kinase inhibitors, statins, and supplements. PubMed was used with search terms of drug induced liver injury OR DILI with filter settings of "English language" and "humans" and custom date range of "January 1, 2000." The authors also manually searched bibliographies from key references and included seminal references before the year 2000., (Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

The human hemostasis system is complex and poorly understood after decades of intense scientific study. Despite multiple defects in routine coagulation laboratory studies in patients with chronic liver disease, there is growing evidence that these patients are effectively "rebalanced" with regard to procoagulant and anticoagulant activity and that most of these patients remain in a tenuous but balanced state of hemostasis. A major difficulty in the assessment of these patients is that there are no established laboratory tests that accurately reflect the changes in both the procoagulant and anticoagulant systems; therefore, routine laboratory testing is misleading to the clinician and may prompt inappropriate or risky therapies with little real benefit to the patient. The international normalized ratio is an example of this type of misleading test. Although the international normalized ratio is inextricably linked to prognosis and severity of protein synthetic dysfunction in acute and chronic liver disease, it is a very poor marker for bleeding risk and should not be used in isolation for this purpose. Coagulation disorders are critical in the management of frequent clinical scenarios such as esophageal variceal bleeding, invasive and percutaneous procedures, portal vein thrombosis, venous thromboembolism, and acute liver failure. This article summarizes the pathophysiology of hemostasis in liver disease, describes the strengths and weaknesses of various laboratory tests in assessment of these patients, and outlines the optimal management of hemostasis for some common clinical scenarios. Further research is needed for proper understanding of hemostasis in liver disease to optimally and safely manage these complex patients., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: Infections cause considerable morbidity after liver transplantation (LT). Acute liver failure is a rapidly progressing life-threatening condition where pretransplant dental evaluation is not always possible. We investigated how missing pretransplant dental treatment in acute or subacute liver failure correlates with post-transplant infectious complications., Subjects and Methods: Medical and dental data came from hospital records and infection data from the Finnish LT registry. The follow-up was until February 2011. Of 51 patients (LT during 2000-2006), 16 had and 35 did not have dental treatment pretransplant., Results: Univariate Cox regression analysis demonstrated a 2.46-fold (95% CI 1.06-5.69) infection risk among the patients omitted from dental treatment. After adjustment for either pretransplant factors alone or both pre- and post-transplant factors, the corresponding infection risk increased, respectively, to 8.17-fold (95% CI 2.19-30.6) and 8.54-fold (95% CI 1.82-40.1). This increased risk involved a variety of bacterial, viral, and fungal infections of various sources both < 6 and > 6 months after transplantation., Conclusion: High risk of infections was noticed in acute liver failure patients without pretransplant dental treatment, but a more severe medical condition might have influenced the results. We encourage eradication of dental infection foci whenever clinical condition allows., (© 2012 John Wiley & Sons A/S.)

Parenteral nutrition (PN) is indicated in alcoholic steatohepatitis (ASH) and in cirrhotic patients with moderate or severe malnutrition. PN should be started immediately when sufficientl oral or enteral feeding is not possible. ASH and cirrhosis patients who can be sufficiently fed either orally or enterally, but who have to abstain from food over a period of more than 12 hours (including nocturnal fasting) should receive basal glucose infusion (2-3 g/kg/d). Total PN is required if such fasting periods last longer than 72 h. PN in patients with higher-grade hepatic encephalopathy (HE); particularly in HE IV degrees with malfunction of swallowing and cough reflexes, and unprotected airways. Cirrhotic patients or patients after liver transplantation should receive early postoperative PN after surgery if they cannot be sufficiently rally or enterally nourished. No recommendation can be made on donor or organ conditioning by parenteral administration of glutamine and arginine, aiming at minimising ischemia/reperfusion damage. In acute liver failure artificial nutrition should be considered irrespective of the nutritional state and should be commenced when oral nutrition cannot be restarted within 5 to 7 days. Whenever feasible, enteral nutrition should be administered via a nasoduodenal feeding tube.

Acute liver failure (ALF), associated with a clinical fatality rate exceeding 80%, is characterized by severe liver damage resulting from various factors in the absence of pre-existing liver disease. The role of microbiota in the progression of diverse liver diseases, including ALF, has been increasingly recognized, with the interactions between the microbiota and the host significantly influencing both disease onset and progression. Despite growing interest in the microbiological aspects of ALF, comprehensive reviews remain limited. This review critically examines the mechanisms and efficacy of microbiota-based treatments for ALF, focusing on their role in prevention, treatment, and prognosis over the past decade. [ABSTRACT FROM AUTHOR]

Liver biopsies have consistently contributed to our understanding of the pathogenesis and aetiologies of acute liver disease. As other diagnostic modalities have been developed and refined, the role of biopsy in the management of patients with acute liver failure (ALF), acute‐on‐chronic liver failure (ACLF) and acute hepatitis, including acute liver injury (ALI), has changed. Liver biopsy remains particularly valuable when first‐line diagnostic algorithms fail to determine aetiology. Despite not being identified as a mandatory diagnostic tool in recent clinical guidelines for the management of ALF or ACLF, many centres continue to undertake biopsies given the relative safety of transjugular biopsy in this setting. Several studies have demonstrated that liver biopsy can provide prognostic information, particularly in the context of so‐called indeterminate hepatitis, and is extremely useful in excluding conditions such as metastatic tumours that would preclude transplantation. In addition, its widespread use of percutaneous biopsies in cases of less severe acute liver injury, for example in the establishment of a diagnosis of acute presentation of autoimmune hepatitis or confirmation of a probable or definite drug‐induced liver injury (DILI), has meant that many centres have seen a shift in the ratio of specimens they are receiving from patients with chronic to acute liver disease. Histopathologists therefore need to be equipped to deal with these challenging specimens. This overview provides an insight into the contemporary role of biopsies (as well as explant and autopsy material) in diagnosing acute liver disease. It outlines up‐to‐date clinical definitions of liver injury and considers recent recommendations for the diagnosis of AIH and drug‐induced, autoimmune‐like hepatitis (DI‐AIH). [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) is an acute liver disease with a high mortality rate in clinical practice, characterized histologically by extensive hepatocellular necrosis and massive neutrophil infiltration. However, the role of these abnormally infiltrating neutrophils during ALF development is unclear. Here, in an ALF mouse model, metabolites were identified that promote the formation of neutrophil extracellular traps (NETs) in the liver, subsequently influencing macrophage differentiation and disease progression. ALF occurs with abnormalities in hepatic and intestinal metabolites. Abnormal metabolites (LTD4 and glutathione) can directly, or indirectly via reactive oxygen species, promote NET formation of infiltrating neutrophils, which subsequently regulate macrophages in a pro‐inflammatory M1‐like state, inducing an amplification of the destructive effects of inflammation. Together, this study provides new insights into the role of NETs in the pathogenesis of ALF. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the clinical and molecular genetic characteristics of ten children with ornithine carbamoyltransferase deficiency (OTCD) in southeastern China, as well as the correlation between the genotype and phenotype of OTCD. Methods: A retrospective analysis was performed on the clinical manifestations, laboratory testing, and genetic test findings of ten children with OTCD admitted between August 2015 and October 2021 at Quanzhou Maternity and Children's Hospital of Fujian Province in China. Results: Five boys presented with early-onset symptoms, including poor appetite, drowsiness, groaning, seizures, and liver failure. In contrast, five patients (one boy and four girls) had late-onset gastrointestinal symptoms as the primary clinical manifestation, all presenting with hepatic impairment, and four with hepatic failure.Nine distinct variants of the OTC gene were identified, including two novel mutations: c.1033del(p.Y345Tfs*50) and c.167T > A(p.M56K). Of seven patients who died, five had early-onset disease despite active treatment. Three patients survived, and two of them underwent liver transplantation. Conclusions: The clinical manifestations of OTCD lack specificity. However, elevated blood ammonia levels serve as a crucial diagnostic clue for OTCD. Genetic testing aids in more accurate diagnosis and prognosis assessment by clinicians. In addition, we identified two novel pathogenic variants and expand the mutational spectrum of the gene OTC, which may contribute to a better understanding of the clinical and genetic characteristics of OTCD patients. [ABSTRACT FROM AUTHOR]

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The von Willebrand factor (vWF) is best known for its role in the hemostatic pathway, aiding platelet adhesion and aggregation, as well as circulating along with coagulation factor VIII, prolonging its half-life. However, vWF is more than a hemostatic protein and is a marker of endothelial dysfunction in patients with cirrhosis. The levels of vWF increase progressively as cirrhosis progresses. Despite its qualitative defects, it can support and carry out its hemostatic role and contribute to a pro-coagulant disbalance. Moreover, it has been shown to be a good noninvasive marker for predicting clinically significant portal hypertension (CSPH). The vWF has been shown to predict decompensation and mortality among cirrhosis patients independently of the stage of liver disease and severity of portal hypertension. Increased vWF levels in the setting of endothelial injury predict bacterial translocation and systemic inflammation. The vWF-to-thrombocyte ratio (VITRO) score adds to the diagnostic ability of vWF alone in detecting CSPH non-invasively. Not only have vWF levels been shown to help predict the risk of hepatocellular carcinoma (HCC) among cirrhosis patients, but they also predict the risk of complications post-resection for HCC and response to systemic therapies. vWF-induced portal microthrombi have been purported to contribute to the pathogenesis of acute liver failure progression as well as non-cirrhotic portal hypertension. The prospect of modulation of vWF levels using drugs such as non-selective beta-blockers, statins, anticoagulants, and non-absorbable antibiotics and its use as a predictive biomarker for the response to these drugs needs to be explored. [ABSTRACT FROM AUTHOR]

Liver transplantation (LT) is a life-saving therapeutic modality for patients with various advanced liver diseases. It is crucial to identify that the patient's illness is sufficiently advanced and unlikely to improve with medical management to justify the need for transplantation. At the same time, it is crucial to identify patients with comorbidities and far advanced disease that would result in an unacceptable outcome after LT. Specific care also is required before deciding on LT in the elderly, acute on chronic liver disease, patients with comorbidities, and hepatocellular carcinoma. Transplantation needs to be timed appropriately to avoid unnecessary LT and ensure that the decision is not left too late to avoid losing the patient without a transplant. Also, important is the decision as to when not to transplant. The current review explores some of these issues of contraindications and ineligibility for LT. [ABSTRACT FROM AUTHOR]

Nutrition therapy in critically ill patients with liver disease represents a challenge for Intensive Care Units (ICUs). Nutritional status is correlated with the degree of hepatic dysfunction and the presence of malnutrition worsens outcomes in these patients. The nutritional risk that critically ill patients represent, together with the pathophysiological alterations of liver disease, especially in terms of nutrition intake and protein depletion, leads to malnutrition and sarcopenia. Nutrition therapy improves the survival of these patients; however, this is challenging since they more frequently experience difficulties with nutrition delivery. In consequence, both evaluation of nutritional status and an individualized approach seem mandatory for achieving nutrition objectives. The present narrative review discusses the importance of nutrition therapy, the recommendations of contemporary clinical practice guidelines, and a practical approach to provide the best possible nutrition therapy in patients with liver disease admitted to ICUs. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) is a rare, acute, potentially reversible condition resulting in severe liver impairment and rapid clinical deterioration in patients without preexisting liver disease. Due to the rarity of this condition, published studies are limited by the use of retrospective or prospective cohorts and lack of randomized controlled trials. Current guidelines represent the suggested approach to the identification, treatment, and management of ALF and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence was reviewed using the Grading of Recommendations, Assessment, Development and Evaluation process to develop recommendations. When no robust evidence was available, expert opinions were summarized using Key Concepts. Considering the variety of clinical presentations of ALF, individualization of care should be applied in specific clinical scenarios. [ABSTRACT FROM AUTHOR]

Ferroptosis is an iron-dependently nonapoptotic cell death characterized by excessive accumulation of lipid peroxides and cellular iron metabolism disturbances. Impaired iron homeostasis and dysregulation of metabolic pathways are contributors to ferroptosis. As a major metabolic hub, the liver synthesizes and transports plasma proteins and endogenous fatty acids. Also, it acts as the primary location of iron storage for hepcidin generation and secretion. To date, although the intricate correlation between ferroptosis and liver disorders needs to be better defined, there is no doubt that ferroptosis participates in the pathogenesis of liver diseases. Accordingly, pharmacological induction and inhibition of ferroptosis show significant potential for the treatment of hepatic disorders involved in lipid peroxidation. In this review, we outline the prominent features, molecular mechanisms, and modulatory networks of ferroptosis and its physiopathologic functions in the progression of liver diseases. Further, this review summarizes the underlying mechanisms by which ferroptosis inducers and inhibitors ameliorate liver diseases. It is noteworthy that natural active ingredients show efficacy in preclinical liver disease models by regulating ferroptosis. Finally, we analyze crucial concepts and urgent issues concerning ferroptosis as a novel therapeutic target in the diagnosis and therapy of liver diseases. [ABSTRACT FROM AUTHOR]

Hepatic disease during pregnancy can result in the development of critical illness requiring special attention from a multidisciplinary team with a low threshold for tertiary care transfer to provide access to liver transplantation. Management of this population requires taking into consideration the benefit and risks of both mother and fetus. A myriad of diseases has been recognized, some being unique to pregnancy while others are common to the general population. We present a review of the literature on the diagnosis, management, and prognosis of these diseases to aid in the optimization of care in this special population. [ABSTRACT FROM AUTHOR]

Fifty-four-year old male was admitted to the intensive care unit (ICU) due to impaired consciousness. Past medical history included alcohol dependence, liver cirrhosis, esophageal varices, 2 esophageal varices banding procedures in the past, pathological obesity. Computed tomography (CT) examination of the head performed in the referring hospital was normal. At admission the CT examination of the head was repeated and showed no abnormalities. Urgent esophagogastroduodenoscopy revealed presence of esophageal varices and scarification following previous banding procedures located in the middle and lower part of the esophagus. Gastrointestinal bleeding being the most likely cause of chronic liver decompensation was therefore excluded. Multimodal neurologic diagnostic assessment was negative. Finally magnetic resonance imaging (MRI) of the head was performed. Taking into account clinical picture and the MRI result, the differential diagnosis included chronic liver encephalopathy, exacerbated acquired hepatocerebral degeneration, and acute liver encephalopathy. Due to history of umbilical hernia CT of the abdomen and pelvis was performed and showed intussusception of the ileum, confirming hepatic encephalopathy. In this case report the MRI suggested the diagnosis of hepatic encephalopathy and prompted search for alternative causes of decompensation of chronic liver disease. [ABSTRACT FROM AUTHOR]

Background: Acute liver failure (ALF) is caused by massive hepatocyte death and accompanied by severe coagulation disorder and encephalopathy. It often leads to multiple organ failure and subsequently death. However, the association between ALF and other organ failure remains unclear. Objectives: Here, we evaluated patients with acute liver injury (ALI) and elevated pancreatic enzymes to demonstrate the association between ALI and pancreatic disorder. Methods: We conducted a single-center retrospective study to analyze patients with ALI. Between 2012 and 2017, 163 patients with ALI were treated in our hospital. We stratified patients based on whether serum amylase and lipase were elevated above 1.5 times the upper limit of normal. We compared the baseline characteristics, severity, prognosis, and serum cytokine levels between the two groups. Results: Of the 163 patients, 75 (54.0%) presented elevated pancreatic enzymes above 1.5 times the upper limit of normal. Computed tomography imaging findings associated with pancreatitis were observed in 29 patients (17.8%). The elevation of pancreatic enzymes was associated with ALI severity. High level of serum tumor necrosis factor-alpha (TNF-α) was associated with the elevation of pancreatic enzymes (elevation group Vs. no elevation group: 134.0 ± 177.2 pg/mL Vs. 89.4 ± 159.8 pg/mL). Conclusions: The elevation of pancreatic enzymes was often accompanied by ALI and associated with ALI severity. TNF-α signaling was involved in the elevation of pancreatic enzymes. It is possible that the pancreatic disorder reflected ALI severity, consequently correlated with mortality, and did not directly aggravate ALI pathogenesis. These findings provide novel insights into the pathogenesis of ALF. [ABSTRACT FROM AUTHOR]