Nursing care for patients with cirrhosis.

Cirrhosis represents a major cause of morbidity and mortality, leading to a marked impairment in the quality of life of patients and their caregivers, and resulting in a major burden on healthcare systems. Currently, in most countries, nurses still play a limited role in the care of patients with cirrhosis, which is mainly restricted to the care of patients hospitalised for acute complications of the disease. The current manuscript reviews the established and potential new and innovative roles that nurses can play in the care of patients with cirrhosis. In the hospital setting, specialised nurses should become an integral part of interprofessional teams, helping to improve the quality of care and outcomes of patients with cirrhosis. In the primary care setting, nurses should play an important role in the care of patients with compensated cirrhosis and also facilitate early diagnosis of cirrhosis in those at risk of liver diseases. This review calls for an improved global liver disease education programme for nurses and increased awareness among all healthcare providers and policymakers of the positive impacts of advanced or specialist nursing practice in this domain.

Specificity Proteins (SP) and Krüppel-like Factors (KLF) in Liver Physiology and Pathology.

The liver acts as a central hub that controls several essential physiological processes ranging from metabolism to detoxification of xenobiotics. At the cellular level, these pleiotropic functions are facilitated through transcriptional regulation in hepatocytes. Defects in hepatocyte function and its transcriptional regulatory mechanisms have a detrimental influence on liver function leading to the development of hepatic diseases. In recent years, increased intake of alcohol and western diet also resulted in a significantly increasing number of people predisposed to the incidence of hepatic diseases. Liver diseases constitute one of the serious contributors to global deaths, constituting the cause of approximately two million deaths worldwide. Understanding hepatocyte transcriptional mechanisms and gene regulation is essential to delineate pathophysiology during disease progression. The current review summarizes the contribution of a family of zinc finger family transcription factors, named specificity protein (SP) and Krüppel-like factors (KLF), in physiological hepatocyte functions, as well as how they are involved in the onset and development of hepatic diseases.

Acid-base abnormalities and liver dysfunction.

In addition to the kidneys and lungs, the liver also plays an important role in the regulation of the Acid-Base Equilibrium (ABE). The involvement of the liver in the regulation of ABE is crucial because of its role in lactic acid metabolism, urea production and in protein homeostasis. The main acid-base imbalance that occurs in patients with liver cirrhosis is Respiratory Alkalosis (RAlk). Due to the fact that in these patients additional pathophysiological mechanisms that affect the ABE are present, other disorders may appear which compensate or enhance the primary disorder. Conventional ABE reading models fail to identify and assess the underlying disorders in patients with liver cirrhosis. This weakness of the classical models led to the creation of new physicochemical mathematical models that take into account all the known parameters that develop and affect the ABE. In addition to the RAlk, in patients with liver cirrhosis, metabolic alkalosis (due to hypoalbuminemia), hyponatremic metabolic acidosis, hyperchloremic metabolic acidosis, lactic acidosis and metabolic alkalosis due to urea metabolism are some of the pathophysiological mechanisms that affect the ABE.

Routes of Stem Cell Administration.

Stem cells are very promising for the treatment of a plethora of human diseases. Numerous clinical studies have been conducted to assess the safety and efficacy of various stem cell types. Factors that ensure successful therapeutic outcomes in patients are cell-based parameters such as source, viability, and number, as well as frequency and timing of intervention and disease stage. Stem cell administration routes should be appropriately chosen as these can affect homing and engraftment of the cells and hence reduce therapeutic effects, or compromise safety, resulting in serious adverse events. In this chapter, we will describe the use of stem cells in organ repair and regeneration, in particular, the liver and the available routes of cell delivery in the clinic for end-stage liver diseases. Factors affecting homing and engraftment of stem cells for each administration route will be discussed.

Excess liver-related mortality among people with AIDS compared to the general population: an Italian nationwide cohort study using multiple causes of death.

OBJECTIVES: Liver diseases have become a leading cause of death among people with AIDS (PWA). This study aimed to investigate whether PWA experienced excess mortality related to liver diseases as compared to the general population (non-PWA), using a multiple cause of death (MCoD; i.e. all conditions reported on death certificates) approach. METHODS: A population-based, nationwide, retrospective cohort study was conducted among Italian people, aged 15-74 years, who had been diagnosed with AIDS since 2006. Date of death and MCoD data were retrieved, up to December 2015, by individual record linkage with national mortality data. Sex- and age-standardized mortality ratios (SMRs), with 95% confidence intervals (CIs), were estimated by dividing the observed number of deaths related to a specific condition among PWA to the expected number, based on non-PWA mortality rates. RESULTS: Among 7912 PWA (34 184 person-years), 2076 deaths occurred. The number of death certificates reporting liver diseases among MCoDs was 583 (28.1%), including 382 (18.4%) reporting viral hepatitis, 370 (17.8%) reporting nonviral liver diseases, and 41 (2.0%) reporting liver cancers. The corresponding SMRs were 40.4 (95% CI 37.2-43.8) for all liver diseases, 131.1 (95% CI 118.3-145.0) for viral hepatitis, 29.9 (95% CI 27.0-33.1) for nonviral liver diseases, and 11.2 (95% CI 8.1-15.3) for liver cancers. Particularly elevated SMRs emerged among PWA aged 15-49 years and those infected by injecting drug use. CONCLUSIONS: The high excess liver-related mortality observed among PWA warrants preventive actions to limit the burden of viral hepatitis coinfections, alcohol abuse, and metabolic disorders, especially among younger PWA and injecting drug users.

Delivery of mRNA Therapeutics for the Treatment of Hepatic Diseases.

Promising improvements in the field of transcript therapeutics have clearly enhanced the potential of mRNA as a new pillar for protein replacement therapies. Synthetic mRNAs are engineered to replace mutated mRNAs and to be immunologically inconspicuous and highly stable while maximizing protein expression. Approaches to deliver mRNA into the cellular cytoplasm safely and efficiently have been further developed so that two mRNA-based approaches replacing vascular endothelial growth factor (VEGF) and cystic fibrosis transmembrane conductance regulator (CFTR) have now made it into clinical trials. These studies bring mRNA therapeutics for protein replacement therapy closer to clinical realization. Herein, we provide an overview of preclinical and clinical developments of mRNA therapeutics for liver diseases.

Systemic delivery of factor IX messenger RNA for protein replacement therapy.

Safe and efficient delivery of messenger RNAs for protein replacement therapies offers great promise but remains challenging. In this report, we demonstrate systemic, in vivo, nonviral mRNA delivery through lipid nanoparticles (LNPs) to treat a Factor IX (FIX)-deficient mouse model of hemophilia B. Delivery of human FIX (hFIX) mRNA encapsulated in our LUNAR LNPs results in a rapid pulse of FIX protein (within 4-6 h) that remains stable for up to 4-6 d and is therapeutically effective, like the recombinant human factor IX protein (rhFIX) that is the current standard of care. Extensive cytokine and liver enzyme profiling showed that repeated administration of the mRNA-LUNAR complex does not cause any adverse innate or adaptive immune responses in immune-competent, hemophilic mice. The levels of hFIX protein that were produced also remained consistent during repeated administrations. These results suggest that delivery of long mRNAs is a viable therapeutic alternative for many clotting disorders and for other hepatic diseases where recombinant proteins may be unaffordable or unsuitable.

Investigation of a Medical Plant for Hepatic Diseases with Secoiridoids Using HPLC and FT-IR Spectroscopy for a Case of Gentiana rigescens.

Secoiridoids could be used as a potential new drug for the treatment of hepatic disease. The content of secoiridoids of G. rigescens varied in different geographical origins and parts. In this study, a total of 783 samples collected from different parts of G. rigescens in Yunnan, Sichuan, and Guizhou Provinces. The content of secoiridoids including gentiopicroside, swertiamarin, and sweroside were determined by using HPLC and analyzed by one-way analysis of variance. Two selected variables including direct selected and variable importance in projection combined with partial least squares regression have been used to establish a method for the determination of secoiridoids using FT-IR spectroscopy. In addition, different pretreatments including multiplicative scatter correction (MSC), standard normal variate (SNV), first derivative and second derivative (SD), and orthogonal signal correction (OSC) were compared. The results indicated that the sample (root, stem, and leaf) with total secoiridoids, gentiopicroside, swertiamarin, and sweroside from west Yunnan had higher content than samples from the other regions. The sample from Baoshan had more total secoiridoids than other samples for the whole medicinal plant. The best performance using FT-IR for the total secoiridoid was with the direct selected variable method involving pretreatment of MSC+OSC+SD in the root and stem, while in leaf, of the best method involved using original data with MSC+OSC+SD. This method could be used to determine the bioactive compounds quickly for herbal medicines.

Gastrointestinal and hepatic symptoms of tickborne diseases.

While investigating patients with gastrointestinal (GI) and/or hepatic symptoms, tickborne diseases are only rarely considered to be the cause. However, the Czech Republic is an endemic region for several of tickborne diseases and, therefore, they should be a part of differential diagnosis of GI symptoms of unknown origin. This article describes GI and hepatic symptoms of several tickborne diseases - Lyme disease, ehrlichiosis, Rocky mountain spotted fever, tularemia, Colorado tick fever, tickborne relapsing fever, Q fever and babesiosis. GI and hepatic symptoms are quite common in Lyme disease patients. The prognosis is generally favourable with antibiotics treatment, however, serious courses have been described. Lyme disease should be a part of differential diagnosis of liver tests elevation and GI symptoms in patients from endemic regions regardless erythema migrans presence. Ehrlichiosis should be a part of differential diagnosis of acute febrile illness with GI symptoms especially in the presence of leukopenia/thrombocytopenia and/or liver tests elevation. Tularemia should be considered as a rare etiology of cholestatic hepatopathy and a history of a tick bite. In general, the importance of careful patient interviewing, including the history of a tick bite, can be highlighted also as a part of investigation of patients with seemingly unrelated GI and/or hepatic symptoms.

[Research progress of the relationship between von Willebrand factor and hepatic diseases].

Hepatic diseases refer to acute and chronic liver disease linked to all kinds of hepatic pathological changes. Viral hepatitis, bacterial infections, endotoxins and other factors initiate the activation and injury of vascular endothelial cells in patients with liver diseases. Von Willebrand factor (vWF) represents a specific marker of endothelial dysfunction and plays a vital role in the occurrence and development of hepatic diseases. This paper reviews the research progress of the relationship between vWF and hepatic diseases.

Circulating RNA: looking at the liver through a frosted glass.

CONTEXT: The evaluation of the liver condition, based on serum enzymatic activity and biopsies, is insufficient. Therefore, it is a priority to find a correlation between circulating RNAs and liver damage. METHODS: Publications were retrieved by the search terms "circulating RNA AND liver". RESULTS: Although differences exist between studies, a profile of RNAs that repeatedly appeared as indicators of liver damage was identified. DISCUSSION: We highlight those circulating RNAs useful to diagnostic, and discuss the transport mechanisms. CONCLUSION: Several studies have proven that circulating RNAs are useful to establish a diagnostic and a prognosis of liver diseases.

Occult Hepatitis B Virus Infection in Hepatic Diseases and Its Significance for the WHO's Elimination Plan of Viral Hepatitis.

Liver damage can progress through different stages, resulting in cirrhosis or hepatocellular carcinoma (HCC), conditions that are often associated with viral infections. Globally, 42% and 21% of cirrhosis cases correlate with HBV and HCV, respectively. In the Americas, the prevalence ranges from 1% to 44%. The WHO has the goal to eliminate viral hepatitis, but it is important to consider occult HBV infection (OBI), a clinical condition characterized by the presence of HBV genomes despite negative surface antigen tests. This review aims to provide an overview of recent data on OBI, focusing on its role in the development of hepatic diseases and its significance in the WHO Viral Hepatitis Elimination Plan. Specific HBV gene mutations have been linked to HCC and other liver diseases. Factors related to the interactions between OBI and mutated viral proteins, which induce endoplasmic reticulum stress and oxidative DNA damage, and the potential role of HBV integration sites (such as the TERT promoter) have been identified in HCC/OBI patients. Health initiatives for OBI research in Latin American countries are crucial to achieving the WHO's goal of eradicating viral hepatitis by 2030, given the difficulty in diagnosing OBI and its unclear association with hepatic diseases.

Mast cells and the gut-liver Axis: Implications for liver disease progression and therapy.

The role of mast cells, traditionally recognized for their involvement in immediate hypersensitivity reactions, has garnered significant attention in liver diseases. Studies have indicated a notable increase in mast cell counts following hepatic injury, underscoring their potential contribution to liver disorder pathogenesis. Predominantly situated in connective tissue that envelops the hepatic veins, bile ducts, and arteries, mast cells are central to both initiating and perpetuating liver disorders. Additionally, they are crucial for maintaining gastrointestinal barrier function. The gut-liver axis emphasizes the complex, two-way communication between the gut microbiome and the liver. Past research has implicated gut microbiota and their metabolites in the progression of hepatic disorders. This review sheds light on how mast cells are activated in various liver conditions such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), viral hepatitis, hepatic fibrogenesis, and hepatocellular carcinoma. It also briefly explores the connection between the gut microbiome and mast cell activation in these hepatic conditions.

Antioxidant therapy for hepatic diseases: a double-edged sword.

Liver diseases are complex conditions, significantly influenced by oxidative stress. This comprehensive review assesses the therapeutic role of antioxidants like l-ascorbic acid and α tocopherol, beta-carotene, various minerals, and plant-based ingredients in mitigating oxidative stress-induced liver diseases. The manuscript delves into the critical influence of genetic and epigenetic factors on disease susceptibility, progression, and response to antioxidant therapy. While animal studies suggest antioxidant efficacy in liver disease treatment, human trials remain inconclusive, and caution is advised due to its possible potential pro-oxidant effects. Moreover, the interactions of antioxidants with other drugs necessitate careful consideration in the management of polypharmacy in liver disease patients. The review underscores the need for further research to establish the clinical benefits of antioxidants with understanding of possible antioxidant toxicities to elucidate the intricate interplay of genetic, epigenetic, and environmental factors in liver diseases. The aim is to foster a better understanding of the knowledge on hepatic disease management with judicial antioxidant therapies.

Biochemical Markers for Liver Injury in Zebrafish Larvae.

Liver plays a crucial role in detoxification processes and metabolism of xenobiotics, and therefore, it is a target organ of toxicity of different classes of chemicals. In this context, some key enzymes present in liver are considered to be good biochemical markers of hepatic damage and can have their activities determined via spectrophotometry. Aspartate and alanine aminotransferases, alkaline phosphatase, lactate dehydrogenase, and glutathione peroxidase are enzymes that have activities often changed in response to hepatotoxic compounds and can be accessed through the larval period of zebrafish (Danio rerio). In this chapter, we described methodologies for analyses of these five biomarkers in pooled zebrafish larvae through spectrophotometry.

Detection of Lymphadenopathy as a Precursor to Autoimmune Liver Diseases Before Clinical Hepatitis Became Apparent: A Report of Two Cases.

Two patients were incidentally diagnosed with intra-abdominal lymphadenopathy on imaging examinations. Although endoscopic ultrasound-guided fine needle aspiration of these areas of lymphadenopathy was performed, their causes remained undetermined. Neither patients had abnormal hepatic enzyme levels at the time lymphadenopathy was detected, but they developed hepatitis 20 months and five months later, respectively. The laboratory data and/or histopathological findings suggested primary biliary cholangitis/cirrhosis (PBC) and autoimmune hepatitis (AIH), respectively. These two patients were each started on appropriate treatment (ursodeoxycholic acid or prednisolone, respectively), their hepatitis ameliorated, and the hepatic enzyme levels recovered to within the normal ranges. These patients' clinical courses suggest that their lymphadenopathy was associated with PBC or AIH and appeared before the causative hepatitis became clinically apparent. We should consider the possibility of latent autoimmune hepatic diseases in cases with cryptogenic intra-abdominal lymphadenopathy even if there is no clinically apparent hepatitis.

mRNA in the Context of Protein Replacement Therapy.

Protein replacement therapy is an umbrella term used for medical treatments that aim to substitute or replenish specific protein deficiencies that result either from the protein being absent or non-functional due to mutations in affected patients. Traditionally, such an approach requires a well characterized but arduous and expensive protein production procedure that employs in vitro expression and translation of the pharmaceutical protein in host cells, followed by extensive purification steps. In the wake of the SARS-CoV-2 pandemic, mRNA-based pharmaceuticals were recruited to achieve rapid in vivo production of antigens, proving that the in vivo translation of exogenously administered mRNA is nowadays a viable therapeutic option. In addition, the urgency of the situation and worldwide demand for mRNA-based medicine has led to an evolution in relevant technologies, such as in vitro transcription and nanolipid carriers. In this review, we present preclinical and clinical applications of mRNA as a tool for protein replacement therapy, alongside with information pertaining to the manufacture of modified mRNA through in vitro transcription, carriers employed for its intracellular delivery and critical quality attributes pertaining to the finished product.

Rescue effect of curcumin against copper toxicity.

Turmeric has long been used not only as an indispensable part of Asian cuisine but as a medicinal herb for dressing wounds, bites, burns, treating eye infections and acne. Curcuminoids are the active substances and their synthetic derivatives (i.e. diacetylcurcumin (DAC) and metal-curcumin complexes) possess an incredibly wide range of medicinal properties that encompass chelation capacity for multiple heavy metals, antioxidant activity, anti-inflammatory properties, cytotoxicity against cancerous cells, antiviral and antibacterial effects, antihypertensive and insulin sensitizing role, and regulatory role on apoptosis. The aforementioned properties have put curcumin on spotlight as a potential treatment for ailments such as, hepatic diseases, neurodegenerative diseases, metabolic syndrome, dyslipidemia, cardiovascular disease, auto-immune diseases, malignancies and conditions associated with metal overload. Copper is essential for major biological functions, however, an excess causes chronic ailments including neurodegenerative disorders. The fascinating approach of curcumin could alleviate such effect by forming a complex. Thus, this review aims to present available data on the effect of copper-curcumin interaction in various in vitro, ex-vivo in vivo, and clinical studies.

A Comprehensive Review on Liver Targeting: Emphasis on Nanotechnology- based Molecular Targets and Receptors Mediated Approaches.

BACKGROUND: The pathogenesis of hepatic diseases involves several cells, which complicates the delivery of pharmaceutical agents. Many severe liver diseases affecting the worldwide population cannot be effectively treated. Major hindrances or challenges are natural physiological barriers and non-specific targeting of drugs administered, leading to inefficient treatment. Hence, there is an earnest need to look for novel therapeutic strategies to overcome these hindrances. A kind of literature has reported that drug safety and efficacy are incredibly raised when a drug is incorporated inside or attached to a polymeric material of either hydrophilic or lipophilic nature. This has driven the dynamic investigation for developing novel biodegradable materials, drug delivery carriers, target-specific drug delivery systems, and many other novel approaches. OBJECTIVE: Present review is devoted to summarizing receptor-based liver cell targeting using different modified novel synthetic drug delivery carriers. It also highlights recent progress in drug targeting to diseased liver mediated by various receptors, including asialoglycoprotein, mannose and galactose receptor, Fc receptor, low-density lipoprotein, glycyrrhetinic, and bile acid receptor. The essential consideration is given to treating liver cancer targeting using nanoparticulate systems, proteins, viral and non-viral vectors, homing peptides and gene delivery. CONCLUSION: Receptors based targeting approach is one such approach that was explored by researchers to develop novel formulations which can ensure site-specific drug delivery. Several receptors are on the surfaces of liver cells, which are highly overexpressed in various disease conditions. They all are helpful for the treatment of liver cancer.

Human Evidence of Perfluorooctanoic Acid (PFOA) Exposure on Hepatic Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Perfluorooctanoic acid (PFOA) is widely used throughout different industries, including the food industry, because it is resistant to heat and prevents water or oil from easily permeating into or contaminating materials coated by PFOA. Although many studies have reported an association between PFOA exposure and the risk of developing hepatic diseases, it is still in debate because they have shown conflicting results. Therefore, this study conducted a systematic review and meta-analysis on the relationship between PFOA exposure and hepatic diseases. METHODS: This study searched studies related to hepatic diseases due to PFOA exposure until 31 December 2021, using PubMed, EMBASE, and Web of Science. This study performed a systematic review and meta-analysis through research question development, literature screening, data extraction, and risk of bias evaluation. This study found 8280 studies after excluding duplicate literature and selected 5 studies in the final stage. Among them, two studies were included in the meta-analysis. RESULTS: The results of the meta-analysis showed that the ALT of people exposed to PFOA was 117% higher than the ALT of those not exposed to PFOA, and it was significantly different (OR = 1.167; 95% CI, 1.086-1.254). CONCLUSION: However, since the number of studies included in the analysis was not large enough to conclude that PFOA exposure was associated with the development of hepatic diseases, more observational studies are needed to confirm its long-term effects.