Plant polysaccharides (PP) demonstrate a diverse array of biological and pharmacological properties. This comprehensive review aims to compile and present the multifaceted roles and underlying mechanisms of plant polysaccharides in various liver diseases. These diseases include non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), fibrosis, drug-induced liver injury (DILI), and hepatocellular carcinoma (HCC). This study aims to elucidate the intricate mechanisms and therapeutic potential of plant polysaccharides, shedding light on their significance and potential applications in the management and potential prevention of these liver conditions. An exhaustive literature search was conducted for this study, utilizing prominent databases such as PubMed, Web of Science, and CNKI. The search criteria focused on the formula \"(plant polysaccharides liver disease) NOT (review)\" was employed to ensure the inclusion of original research articles up to the year 2023. Relevant literature was extracted and analyzed from these databases. Plant polysaccharides exhibit promising pharmacological properties, particularly in the regulation of glucose and lipid metabolism and their anti-inflammatory and immunomodulatory effects. The ongoing progress of studies on the molecular mechanisms associated with polysaccharides will offer novel therapeutic strategies for the treatment of chronic liver diseases (CLDs).

Background: Acute liver injury occurs most frequently due to trauma, but it can also occur because of sepsis or drug-induced injury. This review aims to analyze artificial intelligence (AI)\'s ability to detect and quantify liver injured areas in adults and pediatric patients. Methods: A literature analysis was performed on the PubMed Dataset. We selected original articles published from 2018 to 2023 and cohorts with ≥10 adults or pediatric patients. Results: Six studies counting 564 patients were collected, including 170 (30%) children and 394 adults. Four (66%) articles reported AI application after liver trauma, one (17%) after sepsis, and one (17%) due to chemotherapy. In five (83%) studies, Computed Tomography was performed, while in one (17%), FAST-UltraSound was performed. The studies reported a high diagnostic performance; in particular, three studies reported a specificity rate > 80%. Conclusions: Radiomics models seem reliable and applicable to clinical practice in patients affected by acute liver injury. Further studies are required to achieve larger validation cohorts.

Humans are continuously exposed to various heavy metals including copper, iron, cadmium, and arsenic, which were specifically selected for the current analysis because they are among the most frequently encountered environmental mankind and industrial pollutants potentially causing human health hazards and liver injury. So far, these issues were poorly assessed and remained a matter of debate, also due to inconsistent results. The aim of the actual report is to thoroughly analyze the positive as well as negative effects of these four heavy metals on human health. Copper and iron are correctly viewed as pollutant elements essential for maintaining human health because they are part of important enzymes and metabolic pathways. Healthy individuals are prepared through various genetically based mechanisms to maintain cellular copper and iron homeostasis, thereby circumventing or reducing hazardous liver and organ injury due to excessive amounts of these metals continuously entering the human body. In a few humans with gene aberration, however, liver and organ injury may develop because excessively accumulated copper can lead to Wilson disease and substantial iron deposition to hemochromatosis. At the molecular level, toxicities of some heavy metals are traced back to the Haber Weiss and Fenton reactions involving reactive oxygen species formed in the course of oxidative stress. On the other hand, cellular homeostasis for cadmium and arsenic cannot be provided, causing their life-long excessive deposition in the liver and other organs. Consequently, cadmium and arsenic represent health hazards leading to higher disability-adjusted life years and increased mortality rates due to cancer and non-cancer diseases. For unknown reasons, however, liver injury in humans exposed to cadmium and arsenic is rarely observed. In sum, copper and iron are good for the human health of most individuals except for those with Wilson disease or hemochromatosis at risk of liver injury through radical formation, while cadmium and arsenic lack any beneficial effects but rather are potentially hazardous to human health with a focus on increased disability potential and risk for cancer. Primary efforts should focus on reducing the industrial emission of hazardous heavy metals.

Drug-induced liver disease (DILI) represents one of the main problems in the therapeutic field. There are several non-modifiable risk factors, such as age and sex, and all drugs can cause hepatotoxicity of varying degrees, including those for the treatment of inflammatory bowel diseases (IBD). The aim of this review is to illustrate the adverse effects on the liver of the various drugs used in the treatment of IBD, highlighting which drugs are safest to use based on current knowledge. The mechanism by which drugs cause hepatotoxicity is not fully understood. A possible cause is represented by the formation of toxic metabolites, which in some patients may be increased due to alterations in the enzymatic apparatus involved in drug metabolism. Various studies have shown that the drugs that can most frequently cause hepatotoxicity are immunosuppressants, while mesalazine and biological drugs are, for the most part, less associated with such complications. Therefore, it is possible to assume that in the future, biological therapies could become the first line for the treatment of IBD.

Tuberculosis (TB) remains the second leading cause of death from a single infectious agent and long-term medication could lead to antituberculosis drug-induced liver injury (ATB-DILI). We established a prospective longitudinal cohort of ATB-DILI with multiple timepoint blood sampling and used untargeted metabolomics to analyze the metabolic profiles of 107 plasma samples from healthy controls and newly diagnosed TB patients who either developed ATB-DILI within 2 months of anti-TB treatment (ATB-DILI subjects) or completed their treatment without any adverse drug reaction (ATB-Ctrl subjects). The untargeted metabolome revealed that 77 metabolites (of 895 total) were significantly changed with ATB-DILI progression. Among them, levels of multiple fatty acids and bile acids significantly increased over time in ATB-DILI subjects. Meanwhile, metabolites of the same class were highly correlated with each other and pathway analysis indicated both fatty acids metabolism and bile acids metabolism were up-regulated with ATB-DILI progression. The targeted metabolome further validated that 5 fatty acids had prediction capability at the early stage of the disease and 6 bile acids had a better diagnostic performance when ATB-DILI occurred. These findings provide evidence indicating that fatty acids metabolism and bile acids metabolism play a vital role during ATB-DILI progression. Our report adds a dynamic perspective better to understand the pathological process of ATB-DILI in clinical settings.

With the continued rise of polysubstance use throughout the country, it has been shown to affect a multitude of organ systems. Drug-induced liver injury (DILI) has been widely documented in its association with salicylates or acetaminophen and the utility of using N-acetylcysteine (NAC) for its hepatoprotective effects. However, DILI caused by illicit drug use and guideline-directed management has had little research. We present the case of a 29-year-old female who presented with altered mental status. She was found to have a concomitant liver injury and was treated supportively without the use of NAC, with gradual improvement.

Drug-induced liver injury (DILI) has been significant challenge in drug discovery, often leading to clinical trial failures and necessitating drug withdrawals. The existing suite of in vitro proxy-DILI assays is generally effective at identifying compounds with hepatotoxicity. However, there is considerable interest in enhancing in silico prediction of DILI because it allows for the evaluation of large sets of compounds more quickly and cost-effectively, particularly in the early stages of projects. In this study, we aim to study ML models for DILI prediction that first predicts nine proxy-DILI labels and then uses them as features in addition to chemical structural features to predict DILI. The features include in vitro (e.g., mitochondrial toxicity, bile salt export pump inhibition) data, in vivo (e.g., preclinical rat hepatotoxicity studies) data, pharmacokinetic parameters of maximum concentration, structural fingerprints, and physicochemical parameters. We trained DILI-prediction models on 888 compounds from the DILIst dataset and tested on a held-out external test set of 223 compounds from DILIst dataset. The best model, DILIPredictor, attained an AUC-ROC of 0.79. This model enabled the detection of top 25 toxic compounds compared to models using only structural features (2.68 LR+ score). Using feature interpretation from DILIPredictor, we were able to identify the chemical substructures causing DILI as well as differentiate cases DILI is caused by compounds in animals but not in humans. For example, DILIPredictor correctly recognized 2-butoxyethanol as non-toxic in humans despite its hepatotoxicity in mice models. Overall, the DILIPredictor model improves the detection of compounds causing DILI with an improved differentiation between animal and human sensitivity as well as the potential for mechanism evaluation. DILIPredictor is publicly available at https://broad.io/DILIPredictor for use via web interface and with all code available for download and local implementation via https://pypi.org/project/dilipred/.

Drug-induced liver injury (DILI) is a common clinical pharmacogenic disease. In the United States and Europe, DILI is the most common cause of acute liver failure. Drugs can cause hepatic damage either directly through inherent hepatotoxic properties or indirectly by inducing oxidative stress, immune responses, and inflammatory processes. These pathways can culminate in hepatocyte necrosis. The role of the gut microecology in human health and diseases is well recognized. Recent studies have revealed that the imbalance in the gut microecology is closely related to the occurrence and development of DILI. The gut microecology plays an important role in liver injury caused by different drugs. Recent research has revealed significant changes in the composition, relative abundance, and distribution of gut microbiota in both patients and animal models with DILI. Imbalance in the gut microecology causes intestinal barrier destruction and microorganism translocation; the alteration in microbial metabolites may initiate or aggravate DILI, and regulation and control of intestinal microbiota can effectively mitigate drug-induced liver injury. In this paper, we provide an overview on the present knowledge of the mechanisms by which DILI occurs, the common drugs that cause DILI, the gut microbiota and gut barrier composition, and the effects of the gut microbiota and gut barrier on DILI, emphasizing the contribution of the gut microecology to DILI.

Acute liver failure (ALF) exemplifies a rapid decline in liver function among individuals with previously healthy livers, often manifesting through symptoms such as jaundice, confusion, and potentially life-threatening complications. Timely medical intervention, and, in severe instances, liver transplantation, are essential for enhancing outcomes and averting further deterioration. While the causes of ALF are multifaceted, in developed nations, it predominantly arises from drug-induced liver injury. Treatment primarily revolves around supportive measures, with severe cases necessitating liver transplantation. In instances where acute overdose with acetaminophen serves as the instigating factor, N-acetylcysteine (NAC) emerges as a pivotal component of management, as indicated by the Rumack-Matthew nomogram. The Rumack-Matthew nomogram guides treatment for acetaminophen overdose by correlating serum levels with the risk of liver damage. If levels exceed a set threshold, NAC is administered to prevent toxicity by replenishing glutathione. The decision to administer NAC is typically guided by this clinical tool, which aids healthcare providers in determining the appropriate course of action. NAC assumes a critical role in ameliorating the detrimental effects of acetaminophen overdose, particularly in averting liver damage, thus holding significant importance in patient care and recovery. While chronic acetaminophen overdose cases leading to ALF may also benefit from NAC, the supporting evidence remains weak. In this context, we present a case of ALF stemming from chronic acetaminophen ingestion, managed with NAC when liver transplantation was not a viable option.

Huanglian Jiedu Decoction (HJD) is a well-known Traditional Chinese Medicine formula that has been used for liver protection in thousands of years. However, the therapeutic effects and mechanisms of HJD in treating drug-induced liver injury (DILI) remain unknown. In this study, a total of 26 genes related to both HJD and DILI were identified, which are corresponding to a total of 41 potential active compounds in HJD. KEGG analysis revealed that Tryptophan metabolism pathway is particularly important. The overlapped genes from KEGG and GO analysis indicated the significance of CYP1A1, CYP1A2, and CYP1B1. Experimental results confirmed that HJD has a protective effect on DILI through Tryptophan metabolism pathway. In addition, the active ingredients Corymbosin, and Moslosooflavone were found to have relative strong intensity in UPLC-Q-TOF-MS/MS analysis, showing interactions with CYP1A1, CYP1A2, and CYP1B1 through molecule docking. These findings could provide insights into the treatment effects of HJD on DILI.