- ACR Appropriateness Criteria® Jaundice. [Journal Article]
- JAJ Am Coll Radiol 2019; 16(5S):S126-S140
- Jaundice is the end result of myriad causes, which makes the role of imaging in this setting particularly challenging. In the United States, the most common causes of all types of jaundice fall into …
Jaundice is the end result of myriad causes, which makes the role of imaging in this setting particularly challenging. In the United States, the most common causes of all types of jaundice fall into four categories including hepatitis, alcoholic liver disease, blockage of the common bile duct by a gallstone or tumor, and toxic reaction to a drug or medicinal herb. Clinically, differentiating between the various potential etiologies of jaundice requires a detailed history, targeted physical examination, and pertinent laboratory studies, the results of which allow the physician to categorize the type of jaundice into mechanical or nonmechanical causes. Imaging modalities used to evaluate the jaundiced patient (all etiologies) include abdominal ultrasound (US), CT, MR cholangiopancreatography, endoscopic retrograde cholangiopancreatography and endoscopic US. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
- Efficacy of Ozone and Selenium Therapy for Alcoholic Liver Injury: An Experimental Model. [Journal Article]
- VIn Vivo 2019 May-Jun; 33(3):763-769
- CONCLUSIONS: Through ozone and/or selenium therapies, less damage was observed histopathologically compared to the alcohol group. It is thought that the results of our study can be used in individual treatments following confirmation of liver damage in alcoholic patients.
- Mono-2-ethylhexyl phthalate induces the expression of genes involved in fatty acid synthesis in HepG2 cells. [Journal Article]
- ETEnviron Toxicol Pharmacol 2019 Apr 09; 69:104-111
- Mono-2-ethylhexyl phthalate (MEHP) is a major bioactive metabolite in the widely used industrial plasticizer diethylhexyl phthalate (DEHP) that has been found to be toxic to the liver. The aim of thi…
Mono-2-ethylhexyl phthalate (MEHP) is a major bioactive metabolite in the widely used industrial plasticizer diethylhexyl phthalate (DEHP) that has been found to be toxic to the liver. The aim of this study is to determine whether MEHP exposure can change the expression of fatty acid metabolism-related genes in HepG2 cells, which might be related to non-alcoholic fatty liver disease (NAFLD). The results revealed that exposure to MEHP promoted lipid accumulation in HepG2 cells. The levels of intracellular triglycerides in the hepatocytes increased after exposure to 0.8-100 μM MEHP for 24 h and 48 h. The genetic expressions of SREBP-1c, ChREBP, ACC1, FASN, and SCD significantly increased at 6 h after exposure to MEHP. At 24 h, the expression of the SREBP-1c and ChREBP genes remained increased, while the expression of the FASN and SCD genes decreased. At 48 h, the expression of SREBP-1c, ChREBP, ACC1, FASN, and SCD decreased. Furthermore, the levels of proteins including ACC1, FASN, SCD, and ChREBP (except SREBP-1c) increased at 24 h. These findings suggest that MEHP exposure can promote fatty acid synthesis in hepatocytes by regulating the expression of relevant genes and proteins, contributing to NAFLD.
- [Alcoholic liver disease: the roles of genetic-epigenetic factors and the effect of abstinence]. [Journal Article]
- OHOrv Hetil 2019; 160(14):524-532
- The pathogenesis of alcoholic liver disease depends not only on the toxic effects of alcohol, but also on the complex interaction of host's and environmental factors. Thus, the genetic pre-dispositio…
The pathogenesis of alcoholic liver disease depends not only on the toxic effects of alcohol, but also on the complex interaction of host's and environmental factors. Thus, the genetic pre-disposition, co-morbidities and behavioral factors all play a role in the individual variations in the disease outcomes. On the other hand, the essential part of the therapeutic strategy is the complete withdrawal of the harmful etiological agent. The present paper is devoted to overview the genetics, the environmental factors and the effects of abstinence in alcoholic liver disease. Genetic variants in two enzymes involved in the metabolism of ethanol, alcohol-dehydrogenase ADH1B *2 and aldehyde-dehydrogenase ALDH2 *2 through increasing the blood level of acetaldehyde, may play a "protective" role against alcoholism. The P450 CYP2E1 *5 c2, an inducible microsomal oxidase, upregulated by ethanol and by formation of acetaldehyde and reactive oxygen species, increases liver toxicity. Three novel gene polymorphisms - such as the patatin-like phospholipase domain-containing 3 (PNPLA3 I148M C>G), the transmembrane 6 superfamily member 2 (TM6SF2 E167K), and the membrane-bound O-acyltransferase domain-containing 7 (MB0AT7 rs641738 C>T) - have been proven as risk factors of steatosis, fibrosis and even hepatocellular carcinoma in both alcoholic and non-alcoholic fatty liver disease patients. Alcohol-induced epigenetic effects, reversible but inheritable gene expression alterations - as histon modulations, DNA methylation and micro-RNA-s - are of importance in the pathogenesis as well, and in the future, they may serve as diagnostic markers and therapeutic targets. Women are at greater risk of developing alcoholic cirrhosis, furthermore, malnutrition, obesity, diabetes, smoking, and hepatitis virus infections are also risk factors. Alcoholic liver disease should be regarded as a preventable disease. Several clinical studies revealed that abstinence may result in the regression of steatohepatitis and fibrosis, compensation of cirrhosis, improving disease outcome and increasing survival even in patients with advanced stages. Early diagnosis and multidisciplinary interventions are highly required to achieve long-term abstinence and to prevent alcoholic cirrhosis. Orv Hetil. 2019; 160(14): 524-532.
- Clinical effect of the extract of TCM Fructus akebiae combined with ursodeoxycholic acid on nonalcoholic fatty liver disease. [Journal Article]
- PJPak J Pharm Sci 2019; 32(1(Special)):433-437
- .Fructus akebiae extract (FAE) is a commonly used drug in the clinical treatment of liver cancer. FAE has many pharmacological activities, such as liver protection, anti-tumor, spasmolysis, pain reli…
.Fructus akebiae extract (FAE) is a commonly used drug in the clinical treatment of liver cancer. FAE has many pharmacological activities, such as liver protection, anti-tumor, spasmolysis, pain relief and antifungal activity. Its clinical application is extensive, so far no toxic reports have been reported, and new drugs can be developed. This study was designed to investigate the therapeutic effect of predictor extract on non-alcoholic fatty liver disease (NAFLD). 180 patients with NAFLD were randomly divided into 2 groups. The control group was treated with ursodeoxycholic acid (UDCA), and the experimental group was treated with Fructus akebiae extract combined with ursodeoxycholic acid. The results showed that the comprehensive clinical efficacy of the treatment group was 95.56%, which was higher than that of the control group (93.33%), and P < 0.01. In the experimental group, 63 cases (70%) were improved after one course of treatment, main symptom score as (5.09 ±3.98), body mass index as (24.65±3.86), and liver CT value increased. It can be seen that the addition of FAE can significantly improve the clinical symptoms and serum biochemical indicators such as ALT, AST, TG and TC in patients with non-alcoholic fatty liver disease, which is supported by some histological evidence. These findings suggest that FAE combined with Ursodeoxycholic Acid is safe and effective in the treatment of fatty liver.
- The Relevance of Toxic AGEs (TAGE) Cytotoxicity to NASH Pathogenesis: A Mini-Review. [Review]
- NNutrients 2019 Feb 22; 11(2)
- Non-alcoholic fatty liver disease (NAFLD) is currently the most common feature of chronic liver disease. Non-alcoholic steatohepatitis (NASH) is a severe form of NAFLD, and one of its risk factors is…
Non-alcoholic fatty liver disease (NAFLD) is currently the most common feature of chronic liver disease. Non-alcoholic steatohepatitis (NASH) is a severe form of NAFLD, and one of its risk factors is hyperglycemia. The chronic ingestion of excessive amounts of high-fructose corn syrup is associated with an increased prevalence of fatty liver. Under hyperglycemic conditions, advanced glycation end-products (AGEs) are generated through a non-enzymatic glycation reaction between the ketone or aldehyde groups of sugars and amino groups of proteins. Glyceraldehyde (GA) is a metabolic intermediate of sugars, and GA-derived AGEs (known as toxic AGEs (TAGE)) have been implicated in the development of NASH. TAGE accumulates more in serum or liver tissue in NASH patients than in healthy controls or patients with simple steatosis. Furthermore, the TAGE precursor, GA, causes cell damage through protein dysfunctions by TAGE modifications and induces necrotic-type hepatocyte death. Intracellular TAGE may leak outside of necrotic-type cells. Extracellular TAGE then induce inflammatory or fibrotic responses related to the pathology of NASH in surrounding cells, including hepatocytes and hepatic stellate cells. This review focuses on the contribution of TAGE to the pathology of NASH, particularly hepatic cell death related to NASH.
- Systemic inactivation of hypoxia-inducible factor prolyl 4-hydroxylase 2 in mice protects from alcohol-induced fatty liver disease. [Journal Article]
- RBRedox Biol 2019; 22:101145
- Alcoholic fatty liver disease (AFLD) is a growing health problem for which no targeted therapy is available. We set out to study whether systemic inactivation of the main hypoxia-inducible factor pro…
Alcoholic fatty liver disease (AFLD) is a growing health problem for which no targeted therapy is available. We set out to study whether systemic inactivation of the main hypoxia-inducible factor prolyl 4-hydroxylase, HIF-P4H-2 (PHD2/EglN1), whose inactivation has been associated with protection against metabolic dysfunction, could ameliorate it. HIF-P4H-2-deficient and wild-type (WT) mice or HIF-P4H inhibitor-treated WT mice were subjected to an ethanol diet for 3-4 weeks and their metabolic health, liver and white adipose tissue (WAT) were analyzed. Primary hepatocytes from the mice were used to study cellular ethanol metabolism. The HIF-P4H-2-deficient mice retained a healthier metabolic profile, including less adiposity, better lipoprotein profile and restored insulin sensitivity, while on the ethanol diet than the WT. They also demonstrated protection from alcohol-induced steatosis and liver damage and had less WAT inflammation. In liver and WAT the expression of the key lipogenic and adipocytokine mRNAs, such as Fas and Ccl2, were downregulated, respectively. The upregulation of metabolic and antioxidant hypoxia-inducible factor (HIF) target genes, such as Slcs 16a1 and 16a3 and Gclc, respectively, and a higher catalytic activity of ALDH2 in the HIF-P4H-2-deficient hepatocytes improved handling of the toxic ethanol metabolites and oxidative stress. Pharmacological HIF-P4H inhibition in the WT mice phenocopied the protection against AFLD. Our data show that global genetic inactivation of HIF-P4H-2 and pharmacological HIF-P4H inhibition can protect mice from alcohol-induced steatosis and liver injury, suggesting that HIF-P4H inhibitors, now in clinical trials for renal anemia, could also be studied in randomized clinical trials for treatment of AFLD.
- Gut microbiota in liver disease: too much is harmful, nothing at all is not helpful either. [Journal Article]
- AJAm J Physiol Gastrointest Liver Physiol 2019 May 01; 316(5):G563-G573
- The intestinal microbiome plays a major role in the pathogenesis of liver disease, with a hallmark event being dysbiosis, or an imbalance of pathobionts and beneficial bacteria with the associated de…
The intestinal microbiome plays a major role in the pathogenesis of liver disease, with a hallmark event being dysbiosis, or an imbalance of pathobionts and beneficial bacteria with the associated deleterious effects on their host. Reducing the number of intestinal bacteria with antibiotic treatment is generally advantageous in experimental liver diseases. Complete absence of intestinal microbiota as in germ-free rodents can be protective in autoimmune hepatitis and hepatic tumors induced by chemicals, or it can exacerbate disease as in acute toxic liver injury and liver fibrosis/cirrhosis. In alcoholic liver disease, nonalcoholic fatty liver disease, and autoimmune cholangiopathies, germ-free status can be associated with worsened or improved hepatic phenotype depending on the experimental model and type of rodent. Some of the unexpected outcomes can be explained by the limitations of rodents raised in a germ-free environment including a deficient immune system and an altered metabolism of lipids, cholesterol, xenobiotics/toxins, and bile acids. Given these limitations and to advance understanding of the interactions between host and intestinal microbiota, simplified model systems such as humanized gnotobiotic mice, or gnotobiotic mice monoassociated with a single bacterial strain or colonized with a defined set of microbes, are unique and useful models for investigation of liver disease in a complex ecosystem.
- Bone Health in Patients With Liver Diseases. [Review]
- JCJ Clin Densitom 2019 Jan 18
- Osteoporosis is the most common bone disease in chronic liver disease (CLD) resulting in frequent fractures and leading to significant morbidity in this population. In addition to patients with cirrh…
Osteoporosis is the most common bone disease in chronic liver disease (CLD) resulting in frequent fractures and leading to significant morbidity in this population. In addition to patients with cirrhosis and chronic cholestasis, patients with CLD from other etiologies may be affected in the absence of cirrhosis. The mechanism of osteoporosis in CLD varies according to etiology, but in cirrhosis and cholestatic liver disease it is driven primarily by decreased bone formation, which differs from the increased bone resorption seen in postmenopausal osteoporosis. Direct toxic effects from iron and alcohol play a role in hemochromatosis and alcoholic liver disease, respectively. Chronic inflammation also has been proposed to mediate bone disease in viral hepatitis and nonalcoholic fatty liver disease. Treatment trials specific to osteoporosis in CLD are small, confined to primary biliary cholangitis and post-transplant patients, and have not consistently demonstrated a benefit in this population. As it stands, prevention of osteoporosis in CLD relies on the mitigation of risk factors such as smoking and alcohol use, treatment of underlying hypogonadism, and encouraging a healthy diet and weight-bearing exercise. The primary medical intervention for the treatment of osteoporosis in CLD remains bisphosphonates though a benefit in terms of fracture reduction has never been shown. This review outlines what is known regarding the pathogenesis of bone disease in CLD and summarizes current and emerging therapies.
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- [The gut microbiome is important in chronic liver disease]. [Journal Article]
- ULUgeskr Laeger 2019 Jan 07; 181(2)
- There is increasing evidence of gut dysbiosis being a significant factor in the development and progression of important chronic liver diseases including non-alcoholic steatohepatitis (NASH), alcohol…
There is increasing evidence of gut dysbiosis being a significant factor in the development and progression of important chronic liver diseases including non-alcoholic steatohepatitis (NASH), alcoholic liver disease, primary sclerosing cholangitis and cirrhosis. Dysbiotic microbiota and their toxic metabolites translocate across the gut epithelium via the portal vein and cause damage to the liver. In NASH, alcohol-producing gut bacteria may be critical for its development. Therapeutic measures to normalise the gut microbiota with diet, probiotics or transplantation of normal microbiota seem to have a beneficial effect.