- Risk of endoscopic biliary interventions in primary sclerosing cholangitis is similar between patients with and without cirrhosis. [Journal Article]
- PlosPLoS One 2018; 13(8):e0202686
- CONCLUSIONS: In patients with PSC, cirrhosis was not a risk factor for post-ERC complications. Therefore, cirrhosis should not preclude endoscopic intervention in patients with clear clinical indication.
- Identification of Specific MicroRNA Biomarkers in Early Stages of Hepatocellular Injury, Cholestasis, and Steatosis in Rats. [Journal Article]
- TSToxicol Sci 2018 Aug 17
- Recently, studies on circulating microRNAs (miRNAs) as potential biomarkers of drug-induced liver injury (DILI) have received increasing attention. It has been demonstrated that miR-122 and miR-192, ...
Recently, studies on circulating microRNAs (miRNAs) as potential biomarkers of drug-induced liver injury (DILI) have received increasing attention. It has been demonstrated that miR-122 and miR-192, which are liver enriched, could be potential biomarkers of DILI; however, these miRNAs cannot discern types of injuries.In the present study, we comprehensively analyzed time-dependent plasma miRNA profiles in rats with drug- or chemical-induced hepatocellular injury, cholestasis, and steatosis with high-throughput miRNA sequencing. To enable the comparison of miRNA expression levels between DILI models with different severity and peak time of injuries, the stages of injury were defined as early, middle and late, according to cluster patterns of miRNA expression profiles. Through differential analysis, we characterized miRNAs that were specifically up- or down-regulated in each DILI model. Several miRNAs were dramatically changed earlier than traditional biomarkers such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST). For example, in an acetaminophen (APAP)-induced hepatocellular injury model, plasma let-7b-5p was up-regulated as early as 3 h after dosing, whereas a significant change in ALT level was observed at 12 h. We then focused on the DILI type-specific miRNAs in plasma that were up-regulated at the early stage of injury. RT-qPCR analysis validated that let-7b-5p and miR-1-3p for hepatocellular injury, miR-143-3p and miR-218a-5p for cholestasis, and miR-320-3p for steatosis models showed significant increases in the early stage of the injuries. The present study suggests the utility of miRNAs as specific biomarkers for the early detection of DILI.
- Developmental regulation of the gut-liver (FGF19-CYP7A1) axis in neonates. [Journal Article]
- JMJ Matern Fetal Neonatal Med 2018 Aug 19; :1-181
- CONCLUSIONS: The activity of CYP7A1, the rate-limiting BA synthetic enzyme in adults, is developmentally regulated and undetectable in newborns less than 30 weeks' gestation. FGF19 concentrations do not correlate with CYP7A1 activity, suggesting that the gut-liver axis is not functional in infants. High FGF19 concentrations at birth in infants less than 37 weeks' gestation is a novel finding, and its source and role in preterm infants warrants further investigation.
- Liver complications following treatment of hematologic malignancy with anti-cd22-calicheamicin (Inotuzumab Ozogamicin). [Journal Article]
- HepHepatology 2018 Aug 18
- CONCLUSIONS: The frequencies of SOS and DILI after inotuzumab ozogamicin treatment were 1.5% and 7.9%, respectively, compared to none and 1% among controls who received standard chemotherapy. These data suggest that ADCs that do not target antigens present in the normal liver have a relatively low frequency of SOS but a relatively high frequency of DILI. This article is protected by copyright. All rights reserved.
- Serum Level of D-Lactate in Patients with Cystic Fibrosis: Preliminary Data. [Journal Article]
- DMDis Markers 2018; 2018:5940893
- D-Lactate is produced by the intestinal biota and later absorbed into circulation. Some patients with cystic fibrosis (CF) develop exocrine pancreatic insufficiency that may disturb the gut microbiom...
D-Lactate is produced by the intestinal biota and later absorbed into circulation. Some patients with cystic fibrosis (CF) develop exocrine pancreatic insufficiency that may disturb the gut microbiome and enhance the production of D-lactate. However, this concept has not been studied yet. The aim of the study was to assess D-lactate concentration in relation to the occurrence of clinical features, activity of CF, and diet composition in paediatric patients. Patients and Method. Serum concentrations of D-lactate were measured in 38 CF patients (19 girls and 19 boys) from 6 months to 18 years of age. The analysis included age, sex, clinical symptoms, diet (the variety and calorie needs), the laboratory tests for pancreatic efficiency (serum levels of albumin and glucose, faecal elastase activity, and faecal fat index) and faecal calprotectin (the marker of intestinal inflammation), and parameters of liver damage and of cholestasis (the activity of aminotransferases, γ-glutamyltransferase, level of bilirubin, and international normalized ratio). Results. The median level of D-lactate was 0.86 μg/ml (1Q-3Q: 0.48-2.03) and correlated with the CF severity in the Schwachman-Kulczycki score, parameters of pancreatic insufficiency, and the presence of intestinal inflammation. An increased level of D-lactate was observed in the subgroup with pancreas insufficiency (1.05 versus 0.73; p < 0.05), parallel with an elevated level of calprotectin (0.948 versus 0.755; p = 0.08). There was no relationship between energy consumption and diet composition and serum D-lactates. Conclusion. Serum D-lactate concentration in CF patients is a promising new marker of exocrine pancreatic insufficiency probably related to intestinal flora dysbiosis/overgrowth.
- Is this the time to reconsider the names for xenobiotic nuclear receptors? [Editorial]
- HepHepatology 2018 Aug 16
- Pregnane X receptor (PXR) has been known as a xenobiotic nuclear receptor and transcriptional factor that is important for inducing the expression of genes involved in drug disposition (1, 2). Recent...
Pregnane X receptor (PXR) has been known as a xenobiotic nuclear receptor and transcriptional factor that is important for inducing the expression of genes involved in drug disposition (1, 2). Recently, PXR has emerged to critically regulate endobiotic metabolism, including the homeostasis of glucose, lipids, steroids, bile acids, bilirubin, retinoids and bone minerals, and maybe implicated in the treatment of cholestasis, inflammatory bowel disease, and nonalcoholic fatty liver diseases (3). PXR activation is also well known to increase liver size and cause liver hypertrophy. However, only a few studies have explored the role of PXR in liver regeneration and regrowth (4, 5), moreover, the exact mechanism by which PXR induces liver growth, especially how PXR interacts with the machinery of cellular proliferation, remains unclear. This article is protected by copyright. All rights reserved.
- Cholestasis induced liver pathology results in dysfunctional immune responses after arenavirus infection. [Journal Article]
- SRSci Rep 2018 Aug 15; 8(1):12179
- Immune responses are critical for defense against pathogens. However, prolonged viral infection can result in defective T cell immunity, leading to chronic viral infection. We studied immune activati...
Immune responses are critical for defense against pathogens. However, prolonged viral infection can result in defective T cell immunity, leading to chronic viral infection. We studied immune activation in response to arenavirus infection during cholestasis using bile duct ligation (BDL). We monitored T cell responses, virus load and liver pathology markers after infection with lymphocytic choriomeningitis virus (LCMV). BDL mice failed to induce protective anti-viral immunity against LCMV and consequently exhibited chronic viral infection. BDL mice exhibited reduced anti-viral T cell immunity as well as reduced type 1 interferon production early after LCMV infection. Consistently, the presence of serum from BDL mice reduced the responsiveness of dendritic cell (DC) and T cell cultures when compared to Sham controls. Following fractionation and mass spectrometry analyses of sera, we identified several serum factors to be upregulated following BDL including bilirubin, bile acids, 78 kDa Glucose regulated protein (GRP78) and liver enzymes. Bilirubin and GRP78 were capable of inhibiting DC and T cell activation. In this work, we demonstrate that liver damage mediated by cholestasis results in defective immune induction following arenavirus infection.
- [Anti-inflammatory mechanism of Dahuang Lidan Pian by network pharmacology]. [Journal Article]
- ZZZhongguo Zhong Yao Za Zhi 2018; 43(13):2770-2776
- Dahuang Lidan Pian contains Rheum palmatum, Gymnadenia conopsea and Phyllanthus emblica, which has a significant effect in the treatment of alcoholic fatty liver, cholestasis and cholecystitis. The e...
Dahuang Lidan Pian contains Rheum palmatum, Gymnadenia conopsea and Phyllanthus emblica, which has a significant effect in the treatment of alcoholic fatty liver, cholestasis and cholecystitis. The efficacy of the formula in traditional Chinese medicine was clearing heat and promoting diuresis, removing dampness, detoxifying and relieving jaundice. These three herbs are widely used in the traditional Chinese medicine, Mongolian medicine and Tibetan medicine. Therefore, the formula was a representative subject in the researches for ethno-drugs. In this research, computer aided drug design methods were used to predict the action targets of the formula. Protein interaction network (PIN) was then constructed, and molecular complex detection (MCODE) clustering algorithm was used to obtain the modules of the formula, so as to analyze the potential action mechanism. The results showed that Rh. palmatum and P. emblica may have a synergistic protective effect on liver function by acting on analogous targets and pathways. G. conopsea regulated metabolic balance of nutrients to strengthen physical fitness. The research explained the liver-protecting mechanism of Dahuang Lidan Pian based on the PIN analysis on molecular network, which provides an reference for the further study of Dahuang Lidan Pian.
- Recent advances in understanding bile duct remodeling and fibrosis. [Review]
- FF1000Res 2018; 7
- Cholestatic liver disease encompasses a detrimental group of diseases that are non-discriminatory in nature. These diseases occur over every age range from infancy (biliary atresia) to geriatrics (he...
Cholestatic liver disease encompasses a detrimental group of diseases that are non-discriminatory in nature. These diseases occur over every age range from infancy (biliary atresia) to geriatrics (hepatitis). They also cover both genders in the form of primary sclerosing cholangitis in men and primary biliary cholangitis in women. Oftentimes, owing to the disease progression and extensive scarring, the treatment of last resort becomes a liver transplant. In this review, we will briefly discuss and explore new avenues of understanding in the progression of cholestatic liver disease and possible therapeutic targets for intervention. The greater our understanding into the idiopathic nature of cholestatic liver disease, the better our chances of discovering treatment options to halt or reverse the progression, reducing or eliminating the need for expensive and risky transplants.
New Search Next
- Duodenal intussusception of the remnant stomach after biliopancreatic diversion: a case report. [Journal Article]
- BSBMC Surg 2018 Aug 14; 18(1):57
- CONCLUSIONS: Bowel obstruction and intussusception after bariatric surgery are a rare but often unrecognized complication. Sonography as well as a CT scan should be performed. The exploratory laparoscopy however is the most valuable diagnostic tool in patients with suspected intussusception, due to the high rate of non-specific symptoms and misinterpreted radiographic investigations.