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Microbiome Oct 2017Alcohol abuse has deleterious effects on human health by disrupting the functions of many organs and systems. Gut microbiota has been implicated in the pathogenesis of...
BACKGROUND
Alcohol abuse has deleterious effects on human health by disrupting the functions of many organs and systems. Gut microbiota has been implicated in the pathogenesis of alcohol-related liver diseases, with its composition manifesting expressed dysbiosis in patients suffering from alcoholic dependence. Due to its inherent plasticity, gut microbiota is an important target for prevention and treatment of these diseases. Identification of the impact of alcohol abuse with associated psychiatric symptoms on the gut community structure is confounded by the liver dysfunction. In order to differentiate the effects of these two factors, we conducted a comparative "shotgun" metagenomic survey of 99 patients with the alcohol dependence syndrome represented by two cohorts-with and without liver cirrhosis. The taxonomic and functional composition of the gut microbiota was subjected to a multifactor analysis including comparison with the external control group.
RESULTS
Alcoholic dependence and liver cirrhosis were associated with profound shifts in gut community structures and metabolic potential across the patients. The specific effects on species-level community composition were remarkably different between cohorts with and without liver cirrhosis. In both cases, the commensal microbiota was found to be depleted. Alcoholic dependence was inversely associated with the levels of butyrate-producing species from the Clostridiales order, while the cirrhosis-with multiple members of the Bacteroidales order. The opportunist pathogens linked to alcoholic dependence included pro-inflammatory Enterobacteriaceae, while the hallmarks of cirrhosis included an increase of oral microbes in the gut and more frequent occurrence of abnormal community structures. Interestingly, each of the two factors was associated with the expressed enrichment in many Bifidobacterium and Lactobacillus-but the exact set of the species was different between alcoholic dependence and liver cirrhosis. At the level of functional potential, the patients showed different patterns of increase in functions related to alcohol metabolism and virulence factors, as well as pathways related to inflammation.
CONCLUSIONS
Multiple shifts in the community structure and metabolic potential suggest strong negative influence of alcohol dependence and associated liver dysfunction on gut microbiota. The identified differences in patterns of impact between these two factors are important for planning of personalized treatment and prevention of these pathologies via microbiota modulation. Particularly, the expansion of Bifidobacterium and Lactobacillus suggests that probiotic interventions for patients with alcohol-related disorders using representatives of the same taxa should be considered with caution. Taxonomic and functional analysis shows an increased propensity of the gut microbiota to synthesis of the toxic acetaldehyde, suggesting higher risk of colorectal cancer and other pathologies in alcoholics.
Topics: Adult; Alcoholism; Bifidobacterium; Dysbiosis; Enterobacteriaceae; Ethanol; Feces; Female; Gastrointestinal Microbiome; Humans; Inflammation; Lactobacillus; Liver; Liver Cirrhosis; Liver Diseases, Alcoholic; Male; Metagenomics; Middle Aged; Probiotics; Symbiosis; Virulence Factors; Young Adult
PubMed: 29041989
DOI: 10.1186/s40168-017-0359-2 -
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 -
European Journal of Gastroenterology &... Mar 2021On 12 March 2020, the WHO declared that the coronavirus disease 2019 (COVID-19) constitutes a pandemic. Cases of liver damage or dysfunction (mainly characterized by... (Review)
Review
On 12 March 2020, the WHO declared that the coronavirus disease 2019 (COVID-19) constitutes a pandemic. Cases of liver damage or dysfunction (mainly characterized by moderately elevated serum aspartate aminotransferase levels) have been reported among patients with COVID-19. However, it is currently uncertain whether the COVID-19 related liver damage/dysfunction is due mainly to the viral infection by itself or other coexisting conditions, such as the use of potentially hepatotoxic medications and the coexistence of systemic inflammatory response, respiratory distress syndrome-induced hypoxia, and multiple organ dysfunction. Individuals at high risk for severe COVID-19 are typical of older age and/or present with comorbid conditions such as diabetes, cardiovascular disease, and hypertension. This is also the same profile for those at increased risk for unrecognized underlying liver disease, especially nonalcoholic fatty liver disease. This could make them more susceptible to liver injury from the virus, medications used in supportive management, or hypoxia. So the aim of this review was to illustrate the clinical implications of COVID-19 on the liver in healthy and diseased states as well as the implications of common liver disorders on the outcome of COVID-19.
Topics: COVID-19; Host-Pathogen Interactions; Humans; Liver; Liver Diseases; Prognosis; Risk Assessment; Risk Factors; SARS-CoV-2
PubMed: 32558697
DOI: 10.1097/MEG.0000000000001808 -
Clinics and Research in Hepatology and... Feb 2022Currently, there have been more than one hundred million confirmed cases of coronavirus disease 2019 (COVID-19), with two million deaths worldwide. This has caused a... (Review)
Review
Currently, there have been more than one hundred million confirmed cases of coronavirus disease 2019 (COVID-19), with two million deaths worldwide. This has caused a huge medical burden. Severe COVID-19 patients can experience multi-organ damage, including cardiac injury, kidney injury, and liver injury. About 2.0%-4.9% of COVID-19 cases involve patients with preexisting liver diseases. Additionally, preexisting liver diseases were reported and associated with severity (odds ratio (OR) or risk ratio (RR) = 1.48-1.70) and mortality (OR or RR = 1.08-2.65) among COVID-19 patients. Furthermore, the prevalence of liver injury was 16%-29% in COVID-19 patients. Higher prevalence of liver injury may worsen prognosis in patients (severity: OR or RR = 1.9-2.6; mortality: OR or RR = 1.1-4.0). The mechanisms of this association between liver injury and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection are complex, including direct cholangiocyte damage induced by SARS-COV-2, cytokine storm, and drug-induced liver injury. In particular, drug-induced liver injury may be the most important reason. This review discusses the epidemiology of COVID-19 and liver dysfunction as well as potential mechanisms underlying the association between COVID-19 and liver dysfunction or other preexisting liver diseases. However, the association between preexisting liver diseases and COVID-19 prognosis and potential mechanisms underlying these associations require further prospective studies.
Topics: COVID-19; Chemical and Drug Induced Liver Injury; Humans; Liver Diseases; Risk Factors; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34428501
DOI: 10.1016/j.clinre.2021.101793 -
World Journal of Gastroenterology Mar 2022Coronavirus disease 2019 (COVID-19) is, at present, one of the most relevant global health problems. In the literature hepatic alterations have been described in... (Review)
Review
Coronavirus disease 2019 (COVID-19) is, at present, one of the most relevant global health problems. In the literature hepatic alterations have been described in COVID-19 patients, and they are mainly represented by worsening of underlying chronic liver disease leading to hepatic decompensation and liver failure with higher mortality. Several potential mechanisms used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to cause liver damage have been hypothesized. COVID-19 primary liver injury is less common than secondary liver injury. Most of the available data demonstrate how liver damage in SARS-CoV-2 infection is likely due to systemic inflammation, and it is less likely mediated by a cytopathic effect directed on liver cells. Moreover, liver alterations could be caused by hypoxic injury and drugs (antibiotics and non-steroidal anti-inflammatory drugs, remdesivir, tocilizumab, tofacitinib and dexamethasone). SARS-CoV-2 infection can induce multiple vascular district atherothrombosis by affecting simultaneously cerebral, coronary and peripheral vascular beds. Data in the literature highlight how the virus triggers an exaggerated immune response, which added to the cytopathic effect of the virus can induce endothelial damage and a prothrombotic dysregulation of hemostasis. This leads to a higher incidence of symptomatic and confirmed venous thrombosis and of pulmonary embolisms, especially in central, lobar or segmental pulmonary arteries, in COVID-19. There are currently fewer data for arterial thrombosis, while myocardial injury was identified in 7%-17% of patients hospitalized with SARS-CoV-2 infection and 22%-31% in the intensive care unit setting. Available data also revealed a higher occurrence of stroke and more serious forms of peripheral arterial disease in COVID-19 patients. Hemostasis dysregulation is observed during the COVID-19 course. Lower platelet count, mildly increased prothrombin time and increased D-dimer are typical laboratory features of patients with severe SARS-CoV-2 infection, described as "COVID-19 associated coagulopathy." These alterations are correlated to poor outcomes. Moreover, patients with severe SARS-CoV-2 infection are characterized by high levels of von Willebrand factor with subsequent ADAMTS13 deficiency and impaired fibrinolysis. Platelet hyperreactivity, hypercoagulability and hypofibrinolysis during SARS-CoV-2 infection induce a pathological state named as "immuno-thromboinflammation." Finally, liver dysfunction and coagulopathy are often observed at the same time in patients with COVID-19. The hypothesis that liver dysfunction could be mediated by microvascular thrombosis has been supported by post-mortem findings and extensive vascular portal and sinusoidal thrombosis observation. Other evidence has shown a correlation between coagulation and liver damage in COVID-19, underlined by the transaminase association with coagulopathy, identified through laboratory markers such as prothrombin time, international normalized ratio, fibrinogen, D-dimer, fibrin/fibrinogen degradation products and platelet count. Other possible mechanisms like immunogenesis of COVID-19 damage or massive pericyte activation with consequent vessel wall fibrosis have been suggested.
Topics: Blood Coagulation Disorders; COVID-19; Fibrinogen; Humans; Liver Diseases; SARS-CoV-2; Thrombosis
PubMed: 35431501
DOI: 10.3748/wjg.v28.i11.1102 -
World Journal of Gastroenterology Feb 2022The intra and extracellular pathways of hepatic injury by coronavirus disease 2019 (COVID-19) are still being studied. Understanding them is important to treat this...
The intra and extracellular pathways of hepatic injury by coronavirus disease 2019 (COVID-19) are still being studied. Understanding them is important to treat this viral disease and other liver and biliary tract disorders. Thus, this paper aims to present three hypotheses about liver injury caused by COVID-19: (1) The interactions between severe acute respiratory syndrome coronavirus 2 spike protein and membrane receptors in the hepatocyte; (2) The dysbiosis and "gut-liver axis" disruption in patients with serious clinical presentations of COVID-19; and (3) The inflammatory response exacerbated through the production of interleukins such as interleukin-6. However, despite these new perspectives, the pathophysiological process of liver injury caused by COVID-19 is still complex and multifactorial. Thus, understanding all these variables is a challenge to science but also the key to propose individualized and effective patient therapies.
Topics: COVID-19; Dysbiosis; Humans; Liver Diseases; Spike Glycoprotein, Coronavirus
PubMed: 35317425
DOI: 10.3748/wjg.v28.i6.683 -
World Journal of Gastroenterology May 2017The biosynthesis of prostaglandins and thromboxanes has been a focus of interest in the management of many liver diseases. Cyclooxygenases are the enzymes involved in...
The biosynthesis of prostaglandins and thromboxanes has been a focus of interest in the management of many liver diseases. Cyclooxygenases are the enzymes involved in the first step of the biosynthesis of these lipid mediators and selective inhibitors for these isoenzymes as well as pharmacological analogues of prostaglandins have been developed and are currently applied therapeutically. Here we discuss the implications of these enzymes in the onset of metabolic and lipid disorders in the liver and their potential role in the progression of the diseases towards fibrosis and hepatocellular carcinogenesis.
Topics: Animals; Carcinogenesis; Carcinoma, Hepatocellular; Catalysis; Cell Proliferation; Cyclooxygenase 2; Disease Progression; Fibrosis; Hepatocytes; Humans; Hydroxyprostaglandin Dehydrogenases; Lipids; Liver; Liver Cirrhosis; Liver Neoplasms; Mice; Non-alcoholic Fatty Liver Disease; Oxygen; Transgenes; Treatment Outcome
PubMed: 28611510
DOI: 10.3748/wjg.v23.i20.3572 -
BioMed Research International 2018Psoriasis is a chronic inflammatory disease of the skin affecting approximately 2% of the world's population. Systemic treatments, including methotrexate and... (Review)
Review
Psoriasis is a chronic inflammatory disease of the skin affecting approximately 2% of the world's population. Systemic treatments, including methotrexate and cyclosporin, are associated with potential hepatotoxicity, due to either direct liver damage or immunosuppression or both immunomediated and a direct liver injury; therefore, treatment of patients with psoriasis poses a therapeutic challenge. The aim of this minireview is to help clinicians in the management of psoriatic patients who develop signs of liver dysfunction. To find relevant articles, a comprehensive search was performed on PubMed, EMBASE, and Cochrane with appropriate combinations of the following keywords being considered: viral hepatitis, nonalcoholic fatty liver disease, psoriasis, hepatotoxicity, drug toxicity, cholestasis, and autoimmune liver diseases.
Topics: Autoimmune Diseases; Chemical and Drug Induced Liver Injury; Cyclosporine; Humans; Inflammation; Liver; Liver Diseases; Methotrexate; Psoriasis
PubMed: 29546055
DOI: 10.1155/2018/3140983 -
Discovery Medicine 2020Liver injury has been reported as a common complication in Coronavirus disease 2019 (COVID-19). Recently, more and more studies reported that the degree of liver damages... (Review)
Review
Liver injury has been reported as a common complication in Coronavirus disease 2019 (COVID-19). Recently, more and more studies reported that the degree of liver damages was associated with the severity of COVID-19. Although the exact mechanism of liver injury in COVID-19 patients is unknown, recent studies have made some explorations and investigations. In this review, we summarized the potential mechanisms of liver dysfunction in COVID-19 patients gleaned from recently published research reports, which suggested that the progression of pre-existing liver diseases, direct damage of liver by SARS-CoV-2, systemic inflammation caused by SARS-CoV-2 infection, anti-viral drug toxicity, and hypoxia-reperfusion may be associated with liver injury in patients with COVID-19. Hypoxic liver injury due to ischemia and shock, cholestasis-related liver injury due to altered bile metabolism, and hepatocellular injury due to drug toxicity or overwhelming inflammation might occur in severe COVID-19 patients with sepsis. To understand the pathogenesis of liver dysfunction in COVID-19 patients, further research is needed to focus on liver-related comorbidities, the evidence of viral replication in hepatocytes and bile duct cells, histological features of liver injury, and the influence of hepatotoxic antiviral drugs. We also suggested that special attention should be paid to monitoring inflammatory cytokines and hypoxia for the prevention and treatment of liver injury in severe COVID-19 patients. A deep understanding of the mechanism of liver injury is helpful for the management and treatment of COVID-19 patients.
Topics: Antiviral Agents; COVID-19; Humans; Hypoxia; Inflammation; Liver; Liver Diseases; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33382966
DOI: No ID Found -
World Journal of Gastroenterology Jul 2015There are numerous physiologic and biochemical changes in menopause that can affect the function of the liver and mediate the development of liver disease. Menopause... (Review)
Review
There are numerous physiologic and biochemical changes in menopause that can affect the function of the liver and mediate the development of liver disease. Menopause represents a state of growing estrogen deficiency, and this loss of estrogen in the setting of physiologic aging increases the likelihood of mitochondrial dysfunction, cellular senescence, declining immune responses to injury, and disarray in the balance between antioxidant formation and oxidative stress. The sum effect of these changes can contribute to increased susceptibility to development of significant liver pathology, particularly nonalcoholic fatty liver disease and hepatocellular carcinoma, as well as accelerated progression of fibrosis in liver diseases, as has been particularly demonstrated in hepatitis C virus liver disease. Recognition of the unique nature of these mediating factors should raise suspicion for liver disease in perimenopausal and menopausal women and offer an opportunity for implementation of aggressive treatment measures so as to avoid progression of liver disease to cirrhosis, liver cancer and liver failure.
Topics: Age Factors; Animals; Female; Gonadal Steroid Hormones; Humans; Inflammation Mediators; Liver; Liver Diseases; Menopause; Oxidative Stress; Prognosis; Risk Factors; Sex Factors; Signal Transduction
PubMed: 26167064
DOI: 10.3748/wjg.v21.i25.7613