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Advances in Clinical and Experimental... Apr 2018Despite continuous progress in medicine, sepsis remains the main cause of deaths in the intensive care unit. Liver failure complicating sepsis/septic shock has a... (Review)
Review
Despite continuous progress in medicine, sepsis remains the main cause of deaths in the intensive care unit. Liver failure complicating sepsis/septic shock has a significant impact on mortality in this group of patients. The pathophysiology of sepsis-associated liver dysfunction is very complicated and still not well understood. According to the Surviving Sepsis Campaign (SSC) Guidelines, the diagnosis of liver dysfunction during sepsis is based on the increase in bilirubin concentration >2 mg/dL and the occurrence of coagulation disorders with INR > 1.5. The lack of specificity and ability to distinguish acute liver failure from previous liver dysfunction disqualifies bilirubin as a single parameter reflecting the complex liver function. Clinical manifestations of sepsis-associated liver dysfunction include hypoxic hepatitis, sepsis-induced cholestasis and dysfunction of protein synthesis manifesting with, e.g., coagulopathies. Detoxifying liver dysfunction, which is associated with an increase in serum ammonia concentration, manifesting with e.g., confusion, loss of consciousness and hepatic encephalopathy, may be disguised by analgosedation used in the intensive care unit. To determine a liver dysfunction in a critically ill patient, the concept of shock liver may be used. It is a complex syndrome of hemodynamic, cellular, molecular and immunologic changes leading to severe liver hypoxia. In clinical practice, there is no standardized diagnostic panel that would allow for an early, clear diagnosis of acute liver dysfunction, and there is no therapeutic panel enabling the full restoration of damaged liver function. The aim of the article is to present the pathophysiology and clinical manifestations of sepsis-associated liver dysfunction.
Topics: Critical Illness; Humans; Intensive Care Units; Liver; Liver Failure; Sepsis; Shock, Septic
PubMed: 29558045
DOI: 10.17219/acem/68363 -
Molecules (Basel, Switzerland) Jan 2017Silymarin is the extract of , or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver... (Review)
Review
Silymarin is the extract of , or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver disorders, particularly chronic liver diseases, cirrhosis and hepatocellular carcinoma, because of its antioxidant, anti-inflammatory and antifibrotic power. Indeed, the anti-oxidant and anti-inflammatory effect of silymarin is oriented towards the reduction of virus-related liver damages through inflammatory cascade softening and immune system modulation. It also has a direct antiviral effect associated with its intravenous administration in hepatitis C virus infection. With respect to alcohol abuse, silymarin is able to increase cellular vitality and to reduce both lipid peroxidation and cellular necrosis. Furthermore, silymarin/silybin use has important biological effects in non-alcoholic fatty liver disease. These substances antagonize the progression of non-alcoholic fatty liver disease, by intervening in various therapeutic targets: oxidative stress, insulin resistance, liver fat accumulation and mitochondrial dysfunction. Silymarin is also used in liver cirrhosis and hepatocellular carcinoma that represent common end stages of different hepatopathies by modulating different molecular patterns. Therefore, the aim of this review is to examine scientific studies concerning the effects derived from silymarin/silybin use in chronic liver diseases, cirrhosis and hepatocellular carcinoma.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Antiviral Agents; Chronic Disease; Humans; Liver Diseases; Silybin; Silymarin
PubMed: 28125040
DOI: 10.3390/molecules22020191 -
The Korean Journal of Gastroenterology... Apr 2020Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. During sepsis, the liver has essential roles, such as... (Review)
Review
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. During sepsis, the liver has essential roles, such as immune defense and metabolic adaptation to inflammation. In addition, it is a target for sepsis-related injury, including hypoxic hepatitis, cholestasis, drug-induced liver injury, and secondary sclerosing cholangitis in critically ill patients. In particular, the mortality rate due to sepsis is four times higher in patients with cirrhosis, warranting a high index of suspicion for infection, appropriate diagnosis, and prompt antimicrobial treatment. The most recent definition of sepsis (Sepsis-3) no longer uses systemic inflammatory response syndrome (SIRS) and is based on the signs of organ dysfunction, which can be assessed by the Sequential Organ Failure Assessment (SOFA) and quick SOFA (qSOFA) scores. The qSOFA score can be applied at the bedside before any tests and is believed to be suggestive of sepsis when at least two of the following criteria are met: altered consciousness, respiratory rate ≥22/min, and systolic blood pressure ≤100 mmHg. While the qSOFA score performs well in the general population, its role in cirrhotic patients is unclear. This paper briefly reviews the current knowledge of the pathogenesis, definition of sepsis, and sepsis-related liver dysfunction. Furthermore, this review summarizes the clinical applicability of Sepsis-3 in cirrhotic patients.
Topics: Cholangitis, Sclerosing; Cholestasis; Cytokines; Humans; Liver; Liver Cirrhosis; Liver Diseases; Sepsis
PubMed: 32326684
DOI: 10.4166/kjg.2020.75.4.182 -
JACC. Heart Failure Feb 2019Heart failure (HF) and liver disease often co-exist. This is because systemic disorders and diseases affect both organs (alcohol abuse, drugs, inflammation,... (Review)
Review
Heart failure (HF) and liver disease often co-exist. This is because systemic disorders and diseases affect both organs (alcohol abuse, drugs, inflammation, autoimmunity, infections) and because of complex cardiohepatic interactions. The latter, which are the focus of this review, include the development of acute cardiogenic liver injury and congestive hepatopathy in HF as well as cardiac dysfunction and failure in the setting of liver cirrhosis, nonalcoholic fatty liver disease, and sequelae following liver transplantation. The emerging role of altered liver X receptor signaling in the pathogenesis of HF comorbidities as well as of the intestinal microbiome and its metabolites in HF and liver disease are fruitful areas for future research.
Topics: Comorbidity; Gastrointestinal Microbiome; Heart Failure; Humans; Liver Diseases
PubMed: 30553904
DOI: 10.1016/j.jchf.2018.10.007 -
The Journal of Clinical Investigation Feb 2024Alcohol-associated liver disease (ALD) is a major cause of chronic liver disease worldwide, and comprises a spectrum of several different disorders, including simple... (Review)
Review
Alcohol-associated liver disease (ALD) is a major cause of chronic liver disease worldwide, and comprises a spectrum of several different disorders, including simple steatosis, steatohepatitis, cirrhosis, and superimposed hepatocellular carcinoma. Although tremendous progress has been made in the field of ALD over the last 20 years, the pathogenesis of ALD remains obscure, and there are currently no FDA-approved drugs for the treatment of ALD. In this Review, we discuss new insights into the pathogenesis and therapeutic targets of ALD, utilizing the study of multiomics and other cutting-edge approaches. The potential translation of these studies into clinical practice and therapy is deliberated. We also discuss preclinical models of ALD, interplay of ALD and metabolic dysfunction, alcohol-associated liver cancer, the heterogeneity of ALD, and some potential translational research prospects for ALD.
Topics: Humans; Liver Diseases, Alcoholic; Ethanol; Fatty Liver; Liver Cirrhosis; Carcinoma, Hepatocellular; Liver Neoplasms; Liver
PubMed: 38299591
DOI: 10.1172/JCI176345 -
World Journal of Gastroenterology Jun 2022Systemic rheumatic diseases (SRDs) are chronic, inflammatory, autoimmune disorders with the presence of autoantibodies that may affect any organ or system. Liver... (Review)
Review
Systemic rheumatic diseases (SRDs) are chronic, inflammatory, autoimmune disorders with the presence of autoantibodies that may affect any organ or system. Liver dysfunction in SRDs can be associated with prescribed drugs, viral hepatitis, alternative hepatic comorbidities and coexisting autoimmune liver diseases (AILDs), requiring an exclusion of secondary conditions before considering liver involvement. The patterns of overlap diseases depend predominantly on genetic determinants with common susceptible loci widely distributing in both disorders. In AILDs, it is important to identify the overlapping SRDs at an early stage since such a coexistence may influence the disease course and prognosis. Commonly co-occurring SRDs in AILDs are Sjögren syndrome (SS), rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) in autoimmune hepatitis (AIH), and SS, RA or systemic sclerosis in primary biliary cholangitis. Owing to different disease complications and therapies, it is imperative to differentiate between SLE liver involvement and SLE-AIH overlap disease. Therapeutic options can be personalized to control coexisting conditions of liver autoimmunity and rheumatic manifestations in AILD-SRD overlap diseases. The collaboration between hepatologists and rheumatologists can lead to significant advances in managing such a complex scenario. In this review, we provide a comprehensive overview on coexisting AILDs in different SRDs and the therapeutic approach in managing these overlap diseases.
Topics: Arthritis, Rheumatoid; Autoimmune Diseases; Autoimmunity; Hepatitis, Autoimmune; Humans; Liver Diseases; Lupus Erythematosus, Systemic; Rheumatic Diseases
PubMed: 35949355
DOI: 10.3748/wjg.v28.i23.2527 -
Critical Care (London, England) Sep 2022Organ 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... (Review)
Review
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.
Topics: Bilirubin; Biomarkers; Critical Care; Critical Illness; Gastroenterology; Humans; Incidence; Intensive Care Units; Liver Diseases; Liver Failure; Microcirculation; Multiple Organ Failure; Prognosis; Transaminases
PubMed: 36163253
DOI: 10.1186/s13054-022-04163-1 -
World Journal of Gastroenterology Jul 2021Severe acute respiratory syndrome coronavirus 2 infection is the cause of coronavirus disease 2019 (COVID-19), which predominantly affects the respiratory system; it...
Severe acute respiratory syndrome coronavirus 2 infection is the cause of coronavirus disease 2019 (COVID-19), which predominantly affects the respiratory system; it also causes systemic and multi-organic disease. Liver damage is among the main extrapulmonary manifestations. COVID-19-associated liver injury is defined as any liver damage occurring during the disease course and treatment of COVID-19 in patients with or without pre-existing liver disease, and occurs in approximately one in five patients. Abnormal liver test results have been associated with a more severe course of COVID-19 and other complications, including death. Mechanisms linking COVID-19 to liver injury are diverse. Particular consideration should be made for patients with pre-existing liver disease, such as metabolic dysfunction-associated fatty liver disease, chronic liver disease due to viral or autoimmune disease, liver transplant carriers, or cirrhosis, given the risk for more severe outcomes. This manuscript summarizes the current lines of evidence on COVID-19-associated liver injury regarding pathophysiology, clinical significance, and management in both patients with or without pre-existing liver disease, to facilitate clinicians' access to updated information and patient care. Finally, we mention the ideas and recommendations to be considered for future research.
Topics: COVID-19; Humans; Liver Cirrhosis; Liver Diseases; SARS-CoV-2
PubMed: 34326607
DOI: 10.3748/wjg.v27.i26.3951 -
Annals of Hepatology 2022In 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... (Review)
Review
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.
Topics: Acidosis; Alkalosis; Humans; Liver Cirrhosis; Liver Diseases; Urea
PubMed: 35074477
DOI: 10.1016/j.aohep.2022.100675 -
Frontiers in Public Health 2022Chronic liver diseases (CLDs) are characterized by progressive necrosis of hepatocytes, which leads to liver fibrosis and cirrhosis, and ultimately liver dysfunction.... (Review)
Review
Chronic liver diseases (CLDs) are characterized by progressive necrosis of hepatocytes, which leads to liver fibrosis and cirrhosis, and ultimately liver dysfunction. The statistics of 2020 shows that the number of patients with CLDs, including chronic hepatitis, fatty liver, and cirrhosis, may exceed 447 million in China. The liver is a crucial organ for the metabolism of various substances, including sex hormones and lipids. CLDs frequently result in abnormalities in the metabolism of sex hormones, glucose, and lipids, as well as mental and psychological illnesses, all of which are significant risk factors for erectile dysfunction (ED). It has been reported that the prevalence of ED in male patients with CLDs ranges from 24.6 to 85.0%. According to a survey of Caucasians, liver transplantation may improve the erectile function of CLDs patients with ED. This finding supports the link between CLDs and ED. In addition, ED is often a precursor to a variety of chronic diseases. Given this correlation and the significant prevalence of CLDs, it is important to evaluate the epidemiology, risk factors, etiology, and treatment outcomes of ED in male patients with CLDs, expecting to attract widespread attention.
Topics: Male; Humans; Erectile Dysfunction; Risk Factors; Liver Cirrhosis; Gonadal Steroid Hormones; Lipids
PubMed: 36684968
DOI: 10.3389/fpubh.2022.1092353