Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The intestinal and hepatobiliary tract exhibits host-specific commensal colonization. The resident microbiota has emerged as a key player in intestinal and hepatic diseases. Alcoholic and nonalcoholic fatty liver diseases (ALD/NAFLD), primary sclerosing cholangitis (PSC), liver cirrhosis, and some of their clinical complications, such as hepatic encephalopathy (HE), have been linked to a microbial signature, as also observed for severe liver inflammation in alcoholic hepatitis. In turn, the liver impacts, and communicates with, the microbiota through hepatic mediators, such as bile acids or inflammatory signals. Therefore, a liver-microbiome bidirectional crosstalk appears to be critical in health and various liver diseases and could be therapeutically targeted, such as by fecal microbiota transplantation.
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PMID:Liver-Microbiome Axis in Health and Disease. 2984 59

Early and differential diagnosis of intrahepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC) by noninvasive methods represents a current clinical challenge. The analysis of low-molecular-weight metabolites by new high-throughput techniques is a strategy for identifying biomarkers. Here, we have investigated whether serum metabolome can provide useful biomarkers in the diagnosis of iCCA and HCC and could discriminate iCCA from HCC. Because primary sclerosing cholangitis (PSC) is a risk factor for CCA, serum metabolic profiles of PSC and CCA have also been compared. The analysis of the levels of lipids and amino acids in the serum of patients with iCCA, HCC, and PSC and healthy individuals (n = 20/group) showed differential profiles. Several metabolites presented high diagnostic value for iCCA versus control, HCC versus control, and PSC versus control, with areas under the receiver operating characteristic curve (AUC) greater than those found in serum for the nonspecific tumor markers carbohydrate antigen 19-9 (CA 19-9) and alpha-fetoprotein (AFP), commonly used to help in the diagnosis of iCCA and HCC, respectively. The development of an algorithm combining glycine, aspartic acid, SM(42:3), and SM(43:2) permitted to accurately differentiate in the diagnosis of both types of tumors (biopsy-proven). The proposed model yielded 0.890 AUC, 75% sensitivity, and 90% specificity. Another algorithm by combination of PC(34:3) and histidine accurately permitted to differentiate PSC from iCCA, with an AUC of 0.990, 100% sensitivity, and 70% specificity. These results were validated in independent cohorts of 14-15 patients per group and compared with profiles found in patients with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Conclusion: Specific changes in serum concentrations of certain metabolites are useful to differentiate iCCA from HCC or PSC, and could help in the early diagnosis of these diseases.
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PMID:Serum Metabolites as Diagnostic Biomarkers for Cholangiocarcinoma, Hepatocellular Carcinoma, and Primary Sclerosing Cholangitis. 3032 40

The prevalence of hepatocellular carcinoma (HCC) is still high worldwide because liver diseases could develop into HCC. Recent reports indicate nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NAFLD&NASH) and primary biliary cirrhosis and primary sclerosing cholangitis (PBC&PSC) are significant of HCC. Therefore, understanding the cellular mechanisms of the pathogenesis and hepatocarcinogenesis from normal liver cells to HCC through NAFLD&NASH or PBC&PSC is a priority to prevent the progression of liver damage and reduce the risk of further complications. By the genetic and epigenetic data mining and the system identification through next-generation sequencing data and its corresponding DNA methylation profiles of liver cells in normal, NAFLD&NASH, PBC&PSC, and HCC patients, we identified the genome-wide real genetic and epigenetic networks (GENs) of normal, NAFLD&NASH, PBC&PSC, and HCC patients. In order to get valuable insight into these identified genome-wide GENs, we then applied a principal network projection method to extract the corresponding core GENs for normal liver cells, NAFLD&NASH, PBC&PSC, and HCC. By comparing the signal transduction pathways involved in the identified core GENs, we found that the hepatocarcinogenesis through NAFLD&NASH was induced through DNA methylation of HIST2H2BE, HSPB1, RPL30, and ALDOB and the regulation of miR-21 and miR-122, and the hepatocarcinogenesis through PBC&PSC was induced through DNA methylation of RPL23A, HIST2H2BE, TIMP1, IGF2, RPL30, and ALDOB and the regulation of miR-29a, miR-21, and miR-122. The genetic and epigenetic changes in the pathogenesis and hepatocarcinogenesis potentially serve as potential diagnostic biomarkers and/or therapeutic targets.
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PMID:Investigating Pathogenic and Hepatocarcinogenic Mechanisms from Normal Liver to HCC by Constructing Genetic and Epigenetic Networks via Big Genetic and Epigenetic Data Mining and Genome-Wide NGS Data Identification. 3034 96

Hepatobiliary disorders are commonly encountered in patients with inflammatory bowel disease (IBD). Although primary sclerosing cholangitis is the stereotypical hepatobiliary disorder associated with IBD, other diseases, including autoimmune hepatitis and nonalcoholic fatty liver disease, also are encountered in this population. Several agents used for treatment of IBD may cause drug-induced liver injury, although severe hepatotoxicity occurs infrequently. Furthermore, reactivation of hepatitis B virus infection may occur in patients with IBD treated with systemic corticosteroids and biologic agents.
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PMID:Hepatic Complications of Inflammatory Bowel Disease. 3094 71

The hepatobiliary system is one of the most common sites of extraintestinal manifestation in patients with inflammatory bowel disease (IBD). The progression of IBD can lead to a primary hepatobiliary manifestation and can occur secondary to multiple drugs or accompanying viral infections. Primary sclerosing cholangitis is the representative hepatobiliary manifestation of IBD, particularly in ulcerative colitis. Although most agents used in the treatment of IBD are potentially hepatotoxic, the risk of serious hepatitis or liver failure is low. The prevalence of HBV and HCV in IBD is similar to the general population, but the clinical concern is HBV reactivation associated with immunosuppressive therapy. Patients undergoing cytotoxic chemotherapy or immunosuppressive therapy with a moderate to high risk of HBV reactivation require prophylactic antiviral therapy. On the other hand, HCV has little risk of reactivation. Patients with IBD are more likely to have nonalcoholic fatty liver disease than the general population and tend to occur at younger ages. IBD and cholelithiasis are closely related, especially in Crohn's disease.
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PMID:[Hepatobiliary Manifestation of Inflammatory Bowel Disease]. 3113 31

Gut microbiota has been demonstrated to have a significant impact on the initiation, progression and development of complications associated with multiple liver diseases. Notably, nonalcoholic fatty liver diseases, including nonalcoholic steatohepatitis and cirrhosis, severe alcoholic hepatitis, primary sclerosing cholangitis and hepatic encephalopathy, have strong links to dysbiosis - or a pathobiological change in the microbiota. In this review, we provide clear and concise discussions on the human gut microbiota, methods of identifying gut microbiota and its functionality, liver diseases that are affected by the gut microbiota, including novel associations under research, and provide current evidence on the modulation of gut microbiota and its effects on specific liver disease conditions.
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PMID:Modulating the Intestinal Microbiota: Therapeutic Opportunities in Liver Disease. 3227 49

In deceased donor liver transplantation, a donor liver with moderate (>30%) macrosteatosis used to be considered inappropriate for grafting. We examined the outcomes of children who underwent living donor liver transplantation (LDLT) at the National Center for Child Health and Development whose donor livers had moderate-to-severe macrosteatosis. Twelve children were enrolled who had received a moderate-to-severe macrosteatotic liver graft and underwent liver biopsy soon after LDLT. The primary diseases were biliary atresia in 7 patients, acute liver failure in 3 patients, glycogen storage disease type 1 in 1 patient, and primary sclerosing cholangitis in 1 patient. Median age was 11 months. There were 4 recipients who received grafts from their fathers, and 8 received grafts from their mothers. Median donor age was 35.5 years. We compared the degree of donor liver steatosis with the results of graft liver biopsies that were collected 4-105 days after LDLT. The levels of donor liver macrovesicular steatosis were moderate (34%-66%) in 9 patients and severe (>66%) in 3 patients. The nonalcoholic fatty liver disease activity score was 3 in 7 patients and 4 in 5 patients. Shortly after LDLT, 11 of 12 patients showed improvement in steatosis compared with the donor livers. One biopsy specimen taken 22 days after LDLT showed 60% macrosteatosis, which was the same as that in the donor liver. However, this patient was alive and well 6 years after LDLT. One patient died after LDLT because of infection and respiratory failure. The levels of steatosis of the donor liver grafts improved soon after LDLT in children, and the outcomes of children receiving a moderate-to-severe macrosteatotic liver from their parents were excellent.
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PMID:Outcome for Pediatric Recipients of Macrosteatotic Liver Grafts From Living Donors. 3231 85

A large variety of model systems are used in hepatobiliary research. In this review, we aim to provide an overview of established and emerging models for specific research questions. We specifically discuss the value and limitations of these models for research on metabolic associated fatty liver disease (MAFLD), (previously named non-alcoholic fatty liver diseases/non-alcoholic steatohepatitis (NAFLD/NASH)) and cholestasis-related diseases such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). The entire range of models is discussed varying from immortalized cell lines, mature or pluripotent stem cell-based models including organoids/spheroids, to animal models and human ex vivo models such as normothermic machine perfusion of livers and living liver slices. Finally, the pros and cons of each model are discussed as well as the need in the scientific community for continuous innovation in model development to better mimic the human (patho)physiology.
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PMID:From fatty hepatocytes to impaired bile flow: Matching model systems for liver biology and disease. 3271 28

Mast cells are key players in acute immune responses that are evidenced by degranulation leading to a heightened allergic response. Activation of mast cells can trigger a number of different pathways contributing to metabolic conditions and disease progression. Aging results in irreversible physiological changes affecting all organs, including the liver. The liver undergoes senescence, changes in protein expression, and cell signaling phenotypes during aging, which regulate disease progression. Cellular senescence contributes to the age-related changes. Unsurprisingly, mast cells also undergo age-related changes in number, localization, and activation throughout their lifetime, which adversely affects the etiology and progression of many physiological conditions including liver diseases. In this review, we discuss the role of mast cells during aging, including features of aging (e.g., senescence) in the context of biliary diseases such as primary biliary cholangitis and primary sclerosing cholangitis and nonalcoholic fatty liver disease.
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PMID:The Dynamic Interplay Between Mast Cells, Aging/Cellular Senescence, and Liver Disease. 3272 36

Gut microbiota constitute a complicated but manifold ecosystem, in which specific symbiotic relationships are formed among various bacteria. To maintain a steady state, the gastrointestinal tract and the liver form a close anatomical and functional two-way, interconnected network through the portal circulation. "Gut-liver axis" plays a key role in the pathogenesis of liver diseases. Accumulating evidence indicates that gut microbiota can influence the liver pathophysiology directly or indirectly via a variety of signal pathways. In a pathological state where an ecological imbalance occurs at the compositional and functional levels, gut microbes would interact with the host immune system and other type of cells to cause liver steatosis, inflammation and fibrosis, which in turn give rise to the development of such liver diseases as alcoholic liver disease, nonalcoholic fatty liver disease, primary sclerosing cholangitis, and acute liver failure, to name a few. Studies have shown that microorganisms, such as prebiotics and probiotics, can improve the prognosis of certain diseases, which open a new era of treating liver diseases with bacteria. There are many unknowns and hidden values in the gut microbiome. To explore the pathophysiological mechanism of various complex diseases and develop scientific and effective clinical treatment strategies, efforts should be made to obtain insights into how certain intestinal microbiota participates in the occurrence and progression of liver diseases. As the connection between gut microbiota and liver diseases at both the acute and chronic phases was not elaborated in previously published review articles, herein we discuss the association between gut microbiota and both acute and chronic liver injury. The anatomical structure of the liver enables it to form a close network with the gut microbiota, which is an important mediator in the regulation of the hepatic physiological and pathological functions.
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PMID:[Gut microbiota-an important contributor to liver diseases]. 3289 42


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