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1.
Direct or Collateral Liver Damage in SARS-CoV-2-Infected Patients.
Lizardo-Thiebaud, MJ, Cervantes-Alvarez, E, Limon-de la Rosa, N, Tejeda-Dominguez, F, Palacios-Jimenez, M, Méndez-Guerrero, O, Delaye-Martinez, M, Rodriguez-Alvarez, F, Romero-Morales, B, Liu, WH, et al
Seminars in liver disease. 2020;(3):321-330
Abstract
Liver injury can result from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with more than one-third of COVID-19 patients exhibiting elevated liver enzymes. Microvesicular steatosis, inflammation, vascular congestion, and thrombosis in the liver have been described in autopsy samples from COVID-19 patients. Several factors, including direct cytopathic effect of the virus, immune-mediated collateral damage, or an exacerbation of preexisting liver disease may contribute to liver pathology in COVID-19. Due to its immunological functions, the liver is an organ likely to participate in the viral response against SARS-CoV-2 and this may predispose it to injury. A better understanding of the mechanism contributing to liver injury is needed to develop and implement early measures to prevent serious liver damage in patients suffering from COVID-19. This review summarizes current reports of SARS-CoV-2 with an emphasis on how direct infection and subsequent severe inflammatory response may contribute to liver injury in patients with and without preexisting liver disease.
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2.
The effect of vitamin D supplementation on the progression of fibrosis in patients with chronic liver disease: A protocol for a systematic review and meta-analysis.
Chen, T, Zuo, X, Wang, S, Yu, P, Yuan, J, Wei, S, Chen, J, Sun, Y, Gao, Y, Li, X
Medicine. 2020;(19):e20296
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Abstract
BACKGROUND Hepatic fibrosis (HF) is the common pathological basis of chronic liver disease (CLD). Many data indicate that serum vitamin D (VD) levels in patients with liver fibrosis are significantly lower than those without liver fibrosis, and lower level of serum 1,25(OH)2D3 is also an independent risk factor for patients with liver fibrosis combined with other diseases. VD has the functions of anti-fibrosis, regulating cell proliferation and differentiation, anti-inflammatory, and immune regulation, Therefore, serum 1,25(OH)2D3 level may be negatively correlated with the progression of liver fibrosis. But there is absent convincing evidence-based medicine to confirm the efficacy of VD supplementation for CLD. Thus, we aimed to conduct this meta-analysis to summarize the efficacy of VD supplementation on the progression of fibrosis in patients with CLD. METHODS The study only selects clinical randomized controlled trials of VD supplementation for CLD. We will search each database from the built-in until September 2020. The English literature mainly searches Cochrane Library, Pubmed, EMBASE, and Web of Science. While the Chinese literature comes from CNKI, CBM, VIP, and Wangfang database. Meanwhile, we will retrieve clinical trial registries and gray literature. Two researchers worked independently on literature selection, data extraction and quality assessment. The dichotomous data is represented by relative risk (RR), and the continuous is expressed by mean difference (MD) or standard mean difference (SMD), eventually the data is synthesized using a fixed effect model (FEM) or a random effect model (REM) depending on the heterogeneity. The serum VD level, hepatic function and serological indexes of hepatic fibrosis were evaluated as the main outcomes. While several secondary outcomes were also evaluated in this study. The statistical analysis of this Meta-analysis was conducted by RevMan software version 5.3. RESULTS This meta-analysis will further determine the beneficial efficacy of VD supplementation on the progression of fibrosis in patients with CLD. CONCLUSION This study determines the positive efficacy of VD supplementation for CLD. ETHICS AND DISSEMINATION This review is based solely on a secondary study of published literatures and does not require ethics committee approval. Its conclusion will be disseminated in conference papers, magazines or peer-reviewed journals. REGISTRATION NUMBER INPLASY202040054.
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Alpha-1 Antitrypsin Deficiency Liver Disease, Mutational Homogeneity Modulated by Epigenetic Heterogeneity With Links to Obesity.
Wang, L, Marek, GW, Hlady, RA, Wagner, RT, Zhao, X, Clark, VC, Fan, AX, Liu, C, Brantly, M, Robertson, KD
Hepatology (Baltimore, Md.). 2019;(1):51-66
Abstract
Alpha-1 antitrypsin deficiency (AATD) liver disease is characterized by marked heterogeneity in presentation and progression, despite a common underlying gene mutation, strongly suggesting the involvement of other genetic and/or epigenetic modifiers. Variation in clinical phenotype has added to the challenge of detection, diagnosis, and testing of new therapies in patients with AATD. We examined the contribution of DNA methylation (5-methylcytosine [5mC]) to AATD liver disease heterogeneity because 5mC responds to environmental and genetic cues and its deregulation is a major driver of liver disease. Using liver biopsies from adults with early-stage AATD and the ZZ genotype, genome-wide 5mC patterns were interrogated. We compared DNA methylation among patients with early AATD, and among patients with normal liver, cirrhosis, and hepatocellular carcinoma derived from multiple etiologic exposures, and linked patient clinical/demographic features. Global analysis revealed significant genomic hypomethylation in AATD liver-impacting genes related to liver cancer, cell cycle, and fibrosis, as well as key regulatory molecules influencing growth, migration, and immune function. Further analysis indicated that 5mC changes are localized, with hypermethylation occurring within a background of genome-wide 5mC loss and with patients with AATD manifesting distinct epigenetic landscapes despite their mutational homogeneity. By integrating clinical data with 5mC landscapes, we observed that CpGs differentially methylated among patients with AATD disease are linked to hallmark clinical features of AATD (e.g., hepatocyte degeneration and polymer accumulation) and further reveal links to well-known sex-specific effects of liver disease progression. Conclusion: Our data reveal molecular epigenetic signatures within this mutationally homogeneous group that point to ways to stratify patients for liver disease risk.
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REVIEW- Contemporary evidence on the dynamic role of probiotics in liver diseases.
Ahmed, B, Rasul, A, Tareen, KZ, Hamid Akash, MS, Muhammad, SA, Irfan, M, Abbas, K, Qadir, MI
Pakistan journal of pharmaceutical sciences. 2019;(6):2765-2770
Abstract
Currently probiotics are considered as an emerging therapeutic strategy in the treatment of many liver disorders. The use of probiotics beyond infection of intestinal flora is a very helpful approach. The optimistic effect of probiotics has been observed in treating the hepatic cirrhosis, hepatic encephalopathy, viral hepatitis, irritable bowel syndrome, non-alcoholic fatty liver and alcoholic liver disease. The characterize mechanisms of probiotics are still unknown but may involve in, maintaining a microbial barrier against potential pathogens, reducing the production of bacterial toxins, modulating the immune system, intestinal permeability, and the inflammatory response. Its safety issues, effectiveness, food supplements as its source are still to be studied. However, studies revealed that probiotic therapy in hepatocellular carcinoma and in portal hypertension are still weak. Larger clinical studies are required before probiotics can be recommended as a treatment modality in liver diseases.
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5.
Liver-associated immune abnormalities.
Grunebaum, E, Avitzur, Y
Autoimmunity reviews. 2019;(1):15-20
Abstract
In recent years, the cross talk between the liver and the immune system is being uncovered, in part by studying liver involvement in primary immune deficiencies (PID) and in part by investigating the alterations of the immune system following orthotopic liver transplantation (OLT). Here we review some of the reciprocal interactions between the liver and the immune system. Patients with PID, particularly those involving inherited defects in T and B cells or innate immunity are prone to infections and inflammatory responses that often involve the liver. Omenn's syndrome, familial hemophagocytic lymphohistiocytosis, AIRE, FOXP3 and CD25 deficiencies, common variable immunodeficiency, CD40 ligand deficiency, chronic granulomatous disease and autoimmune lymphoproliferative syndrome are some of the notable PID associated with typical hepatobiliary abnormalities. Knowledge gained from studying these PID together with laboratory and histological evaluations can assist in managing PID-associated liver dysfunction. The liver itself also has important effects on the immune system, as evident from the growing experience with patients surviving OLT. Up to 40% of pediatric patients who receive OLT suffer from post transplantation allergy, autoimmunity, and immune-mediated disorders (PTAA). PTAA is more common after liver and heart transplantations than kidney transplantations. Potential contributing factors for the increased frequency of PTAA after OLT include the age of the patients, the prolonged use of tacrolimus and the reduced regulatory immune function with a shift towards a TH2 immune response. Better understanding of the mechanisms leading to the development of PTAA after OLT will also improve the management of these conditions.
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6.
Theanine: the unique amino acid in the tea plant as an oral hepatoprotective agent.
Wang, D, Gao, Q, Wang, T, Qian, F, Wang, Y
Asia Pacific journal of clinical nutrition. 2017;(3):384-391
Abstract
For thousands of years, humans have consumed tea made from leaves of Camellia sinensis, first as a medicinal herb and then as a widely popular beverage. In the past 10 years, theanine, a tea-derived, unique, nonproteinic amino acid, has been extensively studied for its health benefits. Recently, multiple lines of evidence have proven its beneficial effects on hepatic and immune functions. One possible mechanism for its biological activity involves the downregulation of the inflammatory response through the induction of nitric oxide production and glutathione synthesis. In this review, we summarize published results describing the potential mechanisms for these beneficial health effects and provide new insight into how theanine can be therapeutic for liver injury and chronic liver disease.
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7.
Immunity, tolerance and autoimmunity in the liver: A comprehensive review.
Doherty, DG
Journal of autoimmunity. 2016;:60-75
Abstract
The hepatic immune system is constantly exposed to a massive load of harmless dietary and commensal antigens, to which it must remain tolerant. Immune tolerance in the liver is mediated by a number of specialized antigen-presenting cells, including dendritic cells, Kupffer cells, liver sinusoidal endothelial cells and hepatic stellate cells. These cells are capable of presenting antigens to T cells leading to T cell apoptosis, anergy, or differentiation into regulatory T cells. However, the hepatic immune system must also be able to respond to pathogens and tumours and therefore must be equipped with mechanisms to override immune tolerance. The liver is a site of accumulation of a number of innate lymphocyte populations, including natural killer cells, CD56(+) T cells, natural killer T cells, γδ T cells, and mucosal-associated invariant T cells. Innate lymphocytes recognize conserved metabolites derived from microorganisms and host cells and respond by killing target cells or promoting the differentiation and/or activation of other cells of the immune system. Innate lymphocytes can promote the maturation of antigen-presenting cells from their precursors and thereby contribute to the generation of immunogenic T cell responses. These cells may be responsible for overriding hepatic immune tolerance to autoantigens, resulting in the induction and maintenance of autoreactive T cells that mediate liver injury causing autoimmune liver disease. Some innate lymphocyte populations can also directly mediate liver injury by killing hepatocytes or bile duct cells in murine models of hepatitis, whilst other populations may protect against liver disease. It is likely that innate lymphocyte populations can promote or protect against autoimmune liver disease in humans and that these cells can be targeted therapeutically. Here I review the cellular mechanisms by which hepatic antigen-presenting cells and innate lymphocytes control the balance between immunity, tolerance and autoimmunity in the liver.
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8.
Role of the intestinal microbiome in liver disease.
Henao-Mejia, J, Elinav, E, Thaiss, CA, Licona-Limon, P, Flavell, RA
Journal of autoimmunity. 2013;:66-73
Abstract
The liver integrates metabolic outcomes with nutrient intake while preventing harmful signals derived from the gut to spread throughout the body. Direct blood influx from the gastrointestinal tract through the portal vein makes the liver a critical firewall equipped with a broad array of immune cells and innate immune receptors that recognize microbial-derived products, microorganisms, toxins and food antigens that have breached the intestinal barrier. An overwhelming amount of evidence obtained in the last decade indicates that the intestinal microbiota is a key component of a wide variety of physiological processes, and alterations in the delicate balance that represents the intestinal bacterial communities are now considered important determinants of metabolic syndrome and immunopathologies. Moreover, it is now evident that the interaction between the innate immune system and the intestinal microbiota during obesity or autoimmunity promotes chronic liver disease progression and therefore it might lead to novel and individualized therapeutic approaches. In this review, we discuss a growing body of evidence that highlights the central relationship between the immune system, the microbiome, and chronic liver disease initiation and progression.
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9.
Extragastric diseases and Helicobacter pylori.
Roubaud Baudron, C, Franceschi, F, Salles, N, Gasbarrini, A
Helicobacter. 2013;:44-51
Abstract
In the last year, several diseases from outside of the gastrointestinal tract have been associated with Helicobacter pylori infection. Indeed, this bacterium produces a low-grade inflammatory state, induces molecular mimicry mechanisms, and interferes with the absorbance of nutrients and drugs possibly influencing the occurrence or the evolution of many diseases. In addition to its role in some hematologic conditions, such as immune thrombocytopenic purpura, idiopathic sideropenic anemia, and vitamin B12 deficiency, which were included in the current guidelines, several other conditions such as cardiovascular diseases, diabetes mellitus, hepatobiliary diseases, and neurologic disorders have also shown promising results.
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Complications of chronic liver disease.
Tsouka, A, McLin, VA
Clinics and research in hepatology and gastroenterology. 2012;(3):262-7
Abstract
Children with chronic liver disease (CLD) need a head to toe approach and an early suspicion of multi organ involvement. Nutritional assessment and management is the cornerstone of management. Consider immune dysfunction in everyday treatment decisions. Consider early heart-lung-brain involvement in transplant evaluation.