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656 Dietary Fat Rich in Linoleic Acid Exacerbates Ethanol-Induced Inflammasome Activation and Liver Injury in a Mouse Model of Alcoholic Liver Disease
AASLD Abstracts
654
656
Baclofen Treatment for Alcohol Dependence in Patients With Chronic HCV Liver Disease: A Multicenter Randomized Clinical Trial Peter Hauser, Bret Fuller, Eric Dieperink, Shira Kern, Juan Miranda, Samuel B. Ho
Dietary Fat Rich in Linoleic Acid Exacerbates Ethanol-Induced Inflammasome Activation and Liver Injury in a Mouse Model of Alcoholic Liver Disease Irina Kirpich, Wenke Feng, Craig J. McClain
Objectives: Alcohol Use Disorders (AUD) are a major cause of chronic liver disease, and can accelerate fibrosis in patients with chronic hepatitis C virus (HCV). Additional medication options for AUD treatment are needed. Prior studies have suggested that baclofen may be effective in reducing alcohol use in patients with chronic liver disease. The primary objective of this study is to determine if baclofen, a gamma-aminobutyric acid (GABA) beta-receptor agonist metabolized primarily through the kidneys, reduces alcohol use in a large sample of HCV-infected Veterans with co-morbid AUD and ongoing heavy alcohol consumption. Methods: The study is a12-week, double-blind, placebo-controlled randomized trial of 180 Veterans older than 18 years with HCV and current alcohol use, conducted from 2010 through 2014 at hepatology clinics in four separate Veteran Affairs Medical Centers. Oral baclofen 30 mg/day (n=88) or placebo (n=92) was given during the 12 week study. Rates of abstinence and no heavy drinking (primary) from study weeks 4-12, and standardized measures of alcohol craving and anxiety (secondary), over the 12 week trial were compared between groups. Results: After subjects who dropped out during initial 4 weeks were removed, 8.9% (15/168) of all subjects became abstinent between 4 and 12 weeks; there were no differences between groups with 10.1 % (9/80) in the placebo group and 7.6% (6/ 79) in the baclofen group achieving abstinence ( C2 = 0.33(1), p=0.568). Similarly, the rate of no heavy drinking for all subjects between week 4 and 12 increased from baseline to 20.6% (34/165) but no statistically significant differences were found between placebo 16.3% (14/72) and baclofen 25.3% (20/59), ( C2 = 2.06(1), p=0.152). There were significant reductions for all subjects in all secondary variables over the course of the study but no differences between groups. There was a significant decrease in alcohol craving (F (169.87) = 68.23, p<0.0001) as measured by the Obsessive Compulsive Drinking Scale (OCDS), but no significant group by time effect (F (120.17) = 0.489, p=0.485). Specifically OCDS alcohol craving decreased from 19.50 (95%CI 17.51-21.49) to 9.52 (95%CI 7.51- 11.54) in the placebo group and from 20.55 (95%CI 18.51-22.58) to 8.79 (95%CI 6.71-10.86) in the baclofen group. Measures of various alcohol biomarkers did not change significantly over time for either the baclofen or placebo groups. Conclusions: Baclofen at a dosage of 30 mg/ day was not superior to placebo in reducing various measures of alcohol use in Veterans with HCV and current alcohol use. It is possible that higher dose baclofen may prove effective; but at this time clinicians are encouraged to use other medications to reduce alcohol use in patients with chronic liver disease.
Introduction/Aim: A critical issue in the development of alcoholic liver disease (ALD) is the progression from simple steatosis to the more advanced stage, alcoholic steatohepatitis. However, the exact mechanism(s) driving/underlying hepatic inflammation during the transition from steatosis to steatohepatitis are not well defined. Inflammasome activation with subsequent IL-1b release appears to be an important pro-inflammatory response in both experimental and clinical ALD. The aim of the present study was to examine the role of different types of dietary fat in EtOH-mediated liver injury and inflammasome activation in an animal model of ALD. Materials and Methods: C57BL/6N male mice were fed either an unsaturated fat (USF, corn oil/linoleic acid enriched) or a saturated fat (SF, medium chain triglycerides enriched [MCT]) Lieber-DeCarli diet (5% EtOH [vol/vol], 40%E from fat) for 8 weeks. Control mice were pair-fed on an isocaloric basis. Liver injury was evaluated by plasma ALT activity. Liver triglyceride accumulation was assessed by biochemical assay and Oil Red O staining. Plasma LPS levels were measured as a marker of endotoxemia. Chloroacetate esterase staining was used to evaluate necroinflammatory changes. Macrophage infiltration was determined by F4/80 staining. Hepatic pro-inflammatory cytokine/chemokine, and TLR expression was assessed by qRT-PCR. Plasma IL-1 b (ELISA), and hepatic NLRP3, ASC, caspase-1, and IL-1b mRNA (qRT-PCR) and protein (WB) levels were measured as markers of inflammasome activation. Results: Compared to SF+EtOH, chronic USF+EtOH feeding resulted in an early stage of ALD characterized by hepatic steatosis, liver injury with increased plasma ALT levels (44.91+2.81 IU/L vs 27.27+1.92 IU/L), and endotoxemia (a 4.5-fold increase in plasma LPS levels compared to control animals). Compared to control animals, hepatic TLR (TLR 1, 2, 3, 4, 7, 8, 9) mRNA expression was significantly increased in USF+EtOH, but not in SF+EtOH group. USF+EtOH-induced liver steatosis and injury were accompanied by neutrophil and macrophage infiltration, and increased hepatic inflammation with elevated levels of pro-inflammatory cytokine mRNA, including TNF- a, MCP1, MIP-2, PAI-1. Compared to SF+EtOH, chronic USF+EtOH feeding resulted in up- regulation of hepatic markers of NLRP3 inflammasome activation, including NLRP3, ASC, caspase1, and IL-1b mRNA. Conclusion: The data suggest that dietary USF, specifically rich in linoleic acid, contributes to EtOH-mediated hepatic inflammation via inflammasome activation. USF+EtOH inflammasome activation represents one of the mechanisms underlying the deleterious effects of dietary USF on EtOH-mediated liver inflammation and injury. The detailed mechanisms need to be further investigated.
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Grainyhead-Like 2, a Novel Hepatic Transcription Factor, Promotes Alcoholinduced Liver Injury, Steatosis and Inflammation via miR-122 Down-regulation Abhishek Satishchandran, Aditya Ambade, Sitara Rao, Ying-Chao Hsueh, Benedek Gyongyosi, Patrick Lowe, Nicita Mehta, James Zatsiorsky, Arvin Iracheta-Vellve, Jia Li, Jun Xie, Li Zhong, Donna Catalano, Banishree Saha, Karen Kodys, Shashi Bala, Guangping Gao, Gyongyi Szabo
Coffee Drinking and Risk of Chronic Liver Disease by Underlying Cause: The Multiethnic Cohort (MEC) Veronica W. Setiawan, Pengxiao C Wei, Shelly C. Lu, Mazen Noureddin Background: Chronic liver disease (CLD) is a major source of morbidity and mortality in the United States. Coffee consumption has been proposed to reduce CLD risk, but few data are available from prospective, US multiethnic populations. We evaluated the association of coffee drinking with CLD by underlying etiology in African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites in the Multiethnic Cohort (MEC). Methods: We used exposure information on the baseline questionnaire to identify coffee consumption and other lifestyle factors. CLD cases were identified using Medicare claim files among the MEC fee-for-service participants with complete coffee and other risk factor data (n=95,197). We used ICD-9 codes and body mass index (BMI) and history of diabetes mellitus (DM) from questionnaire to identify underlying etiologies and classified CLD cases into four major etiologic groups: alcoholic liver disease (ALD, n=933), non-alcoholic fatty liver disease related (NAFLD, n=2,865), hepatitis C related (HCV, n=433), and hepatitis B related (HBV, n= 155). Associations of regular coffee, decaffeinated coffee and caffeine with CLD for each etiologic group were estimated by relative risks (RRs) and 95% confidence intervals (CIs) using log linear proportional hazard models stratified by risk set and adjusted for confounders. Results: Regular coffee was associated with reduced risks of NAFLD-related CLD (p trend= 0.0002) and ALD-related CLD (p trend=0.0005) with dose dependent manners. Compared to non-coffee drinkers, participants who reported drinking 2-3 cups and ‡4 cups per day had a 14% (RR=0.86; 95% CI: 0.77, 0.96) and a 34% (RR=0.66; 95% CI: 0.53, 0.82) reduction in risk for NAFLD-related CLD, respectively. Compared to non-coffee drinkers, participants who reported drinking 2-3 cups and ‡4 cups per day had a 26% (RR=0.74; 95% CI: 0.59, 0.92) and a 37% (RR=0.63; 95% CI: 0.43, 0.91) reduction in risk for ALDrelated CLD, respectively. Only high consumption of ‡4 cups per day of regular coffee (RR= 0.53; 95% CI: 0.29, 0.99) was associated with HCV-related CLD. Regular coffee was not associated with HBV-related CLD (p trend=0.63). Decaffeinated coffee and caffeine intakes were not associated with CLD risk. Conclusions: Coffee drinking is significantly associated with reduced CLD risk, particularly for the NAFLD-related and ALD-related diseases. Caffeine does not seem to contribute to this protective mechanism, and thus, other coffee components need to be investigated further.
Introduction: The fundamental changes to hepatocytes caused by chronic alcohol abuse result in accelerated liver injury, leading to cirrhosis and hepatocellular carcinoma (HCC). However, understanding of an underlying pathway leading to increased carcinogenesis remains elusive in alcoholic liver disease (ALD). Knockout models of miRNA-122, the most abundant miRNA in hepatocytes, have demonstrated its role as an oncogene and essential regulator of hepatocyte function. In humans, miR-122 expression inversely correlates with HCC survival and metastasis. Recent studies have pointed to Grainy-head-like 2 (GRHL2), a transcriptional regulator, as an inhibitor of miR-122 expression and correlated with increased HCC invasiveness. We hypothesized that the loss of miR-122 is a central mediator of alcohol-induced liver injury, and that chronic alcohol inhibits miR-122 expression though GRHL2. Methods: Livers from 10 patients with alcoholic liver disease were assessed, healthy donors were used as controls. Eight-week-old, C57Bl/6 mice were injected intravenously with hepatocyte-tropic AAV (AAV8) containing anti-miR-122 TuD (TuD), or scrambled (Scr) vector 14 days prior to Lieber-DeCarli (LDC) alcohol diet (Et) or control diet (PF) for 4 weeks. Results: We have observed that chronic alcoholic patients, free of neoplastic changes, had a reduction of miR-122 and its primary transcript, pri-miR-122, in the liver. This was associated with increased mRNA expression of GRHL2 in human ALD livers. MiR-122 was also significantly decreased in livers of mice after chronic alcohol feeding. In vivo knockdown of miR-122 in mice resulted in increased liver injury (ALT), steatosis, inflammation in PF mice while combination of miR-122 knockdown and alcohol were synergistic in increasing liver injury, inflammation and fibrosis. Interestingly, alcohol further suppressed miR-122 expression in livers with miR-122 knockdown indicating that alcohol specifically inhibits expression of the precursor miR-122, pri-miR-122, at the transcriptional level. We also discovered that alcohol increased GRHL2 expression in the livers of alcohol-fed mice that was similar to increased GRHL2 in human livers with ALD. Of note, we found that in these patients, alcohol specifically increased the dominant negative form of GRHL2, GRHL2DN, an isoform that contains only the DNA binding and not the transactivation domain. Conclusions: miR-122 inhibition mimics the steatosis, inflammation and early fibrosis seen in ALD. We discovered that alcohol regulates the transcription of miR-122 by upregulating the dominant negative form of GRHL2, an inhibitor of miR-122 transcription. Our findings dissect a novel mechanistic regulatory axis of miR-122 and indicate a potential target for restoration of miR-122 in early ALD.
745 Inhibition of Hepatic Stellate Cell Activation by Stem Cell Derived Extracellular Vesicles and microRNAs During Cholestatic Liver Injury Kelly McDaniel, Ying Wan, Nan Wu, Julie Venter, Heather L. Francis, Tianhao Zhou, Lindsey Kennedy, Shannon Glaser, Gianfranco Alpini, Fanyin Meng Background: Stem cell-derived extracellular vesicles (EVs) and their related microRNAs mediate genetic changes that promote recovery of liver disorders. The present study aims to characterize the functional role of liver stem cell-derived EVs and specific miRNAs in the regulation of hepatic stellate cell activity during cholestatic-induced liver injury. Methods: microRNA expression was assessed using microarray and real-time PCR assays in isolated microvesicles from human mesenchymal stem cells (MSCs) and liver stem cells (LSCs), in TGF-b/LPS-treated human hepatic stellate cells (HHSCs) and liver specimens from bile duct
AASLD Abstracts
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656
Baclofen Treatment for Alcohol Dependence in Patients With Chronic HCV Liver Disease: A Multicenter Randomized Clinical Trial Peter Hauser, Bret Fuller, Eric Dieperink, Shira Kern, Juan Miranda, Samuel B. Ho
Dietary Fat Rich in Linoleic Acid Exacerbates Ethanol-Induced Inflammasome Activation and Liver Injury in a Mouse Model of Alcoholic Liver Disease Irina Kirpich, Wenke Feng, Craig J. McClain
Objectives: Alcohol Use Disorders (AUD) are a major cause of chronic liver disease, and can accelerate fibrosis in patients with chronic hepatitis C virus (HCV). Additional medication options for AUD treatment are needed. Prior studies have suggested that baclofen may be effective in reducing alcohol use in patients with chronic liver disease. The primary objective of this study is to determine if baclofen, a gamma-aminobutyric acid (GABA) beta-receptor agonist metabolized primarily through the kidneys, reduces alcohol use in a large sample of HCV-infected Veterans with co-morbid AUD and ongoing heavy alcohol consumption. Methods: The study is a12-week, double-blind, placebo-controlled randomized trial of 180 Veterans older than 18 years with HCV and current alcohol use, conducted from 2010 through 2014 at hepatology clinics in four separate Veteran Affairs Medical Centers. Oral baclofen 30 mg/day (n=88) or placebo (n=92) was given during the 12 week study. Rates of abstinence and no heavy drinking (primary) from study weeks 4-12, and standardized measures of alcohol craving and anxiety (secondary), over the 12 week trial were compared between groups. Results: After subjects who dropped out during initial 4 weeks were removed, 8.9% (15/168) of all subjects became abstinent between 4 and 12 weeks; there were no differences between groups with 10.1 % (9/80) in the placebo group and 7.6% (6/ 79) in the baclofen group achieving abstinence ( C2 = 0.33(1), p=0.568). Similarly, the rate of no heavy drinking for all subjects between week 4 and 12 increased from baseline to 20.6% (34/165) but no statistically significant differences were found between placebo 16.3% (14/72) and baclofen 25.3% (20/59), ( C2 = 2.06(1), p=0.152). There were significant reductions for all subjects in all secondary variables over the course of the study but no differences between groups. There was a significant decrease in alcohol craving (F (169.87) = 68.23, p<0.0001) as measured by the Obsessive Compulsive Drinking Scale (OCDS), but no significant group by time effect (F (120.17) = 0.489, p=0.485). Specifically OCDS alcohol craving decreased from 19.50 (95%CI 17.51-21.49) to 9.52 (95%CI 7.51- 11.54) in the placebo group and from 20.55 (95%CI 18.51-22.58) to 8.79 (95%CI 6.71-10.86) in the baclofen group. Measures of various alcohol biomarkers did not change significantly over time for either the baclofen or placebo groups. Conclusions: Baclofen at a dosage of 30 mg/ day was not superior to placebo in reducing various measures of alcohol use in Veterans with HCV and current alcohol use. It is possible that higher dose baclofen may prove effective; but at this time clinicians are encouraged to use other medications to reduce alcohol use in patients with chronic liver disease.
Introduction/Aim: A critical issue in the development of alcoholic liver disease (ALD) is the progression from simple steatosis to the more advanced stage, alcoholic steatohepatitis. However, the exact mechanism(s) driving/underlying hepatic inflammation during the transition from steatosis to steatohepatitis are not well defined. Inflammasome activation with subsequent IL-1b release appears to be an important pro-inflammatory response in both experimental and clinical ALD. The aim of the present study was to examine the role of different types of dietary fat in EtOH-mediated liver injury and inflammasome activation in an animal model of ALD. Materials and Methods: C57BL/6N male mice were fed either an unsaturated fat (USF, corn oil/linoleic acid enriched) or a saturated fat (SF, medium chain triglycerides enriched [MCT]) Lieber-DeCarli diet (5% EtOH [vol/vol], 40%E from fat) for 8 weeks. Control mice were pair-fed on an isocaloric basis. Liver injury was evaluated by plasma ALT activity. Liver triglyceride accumulation was assessed by biochemical assay and Oil Red O staining. Plasma LPS levels were measured as a marker of endotoxemia. Chloroacetate esterase staining was used to evaluate necroinflammatory changes. Macrophage infiltration was determined by F4/80 staining. Hepatic pro-inflammatory cytokine/chemokine, and TLR expression was assessed by qRT-PCR. Plasma IL-1 b (ELISA), and hepatic NLRP3, ASC, caspase-1, and IL-1b mRNA (qRT-PCR) and protein (WB) levels were measured as markers of inflammasome activation. Results: Compared to SF+EtOH, chronic USF+EtOH feeding resulted in an early stage of ALD characterized by hepatic steatosis, liver injury with increased plasma ALT levels (44.91+2.81 IU/L vs 27.27+1.92 IU/L), and endotoxemia (a 4.5-fold increase in plasma LPS levels compared to control animals). Compared to control animals, hepatic TLR (TLR 1, 2, 3, 4, 7, 8, 9) mRNA expression was significantly increased in USF+EtOH, but not in SF+EtOH group. USF+EtOH-induced liver steatosis and injury were accompanied by neutrophil and macrophage infiltration, and increased hepatic inflammation with elevated levels of pro-inflammatory cytokine mRNA, including TNF- a, MCP1, MIP-2, PAI-1. Compared to SF+EtOH, chronic USF+EtOH feeding resulted in up- regulation of hepatic markers of NLRP3 inflammasome activation, including NLRP3, ASC, caspase1, and IL-1b mRNA. Conclusion: The data suggest that dietary USF, specifically rich in linoleic acid, contributes to EtOH-mediated hepatic inflammation via inflammasome activation. USF+EtOH inflammasome activation represents one of the mechanisms underlying the deleterious effects of dietary USF on EtOH-mediated liver inflammation and injury. The detailed mechanisms need to be further investigated.
655
657
Grainyhead-Like 2, a Novel Hepatic Transcription Factor, Promotes Alcoholinduced Liver Injury, Steatosis and Inflammation via miR-122 Down-regulation Abhishek Satishchandran, Aditya Ambade, Sitara Rao, Ying-Chao Hsueh, Benedek Gyongyosi, Patrick Lowe, Nicita Mehta, James Zatsiorsky, Arvin Iracheta-Vellve, Jia Li, Jun Xie, Li Zhong, Donna Catalano, Banishree Saha, Karen Kodys, Shashi Bala, Guangping Gao, Gyongyi Szabo
Coffee Drinking and Risk of Chronic Liver Disease by Underlying Cause: The Multiethnic Cohort (MEC) Veronica W. Setiawan, Pengxiao C Wei, Shelly C. Lu, Mazen Noureddin Background: Chronic liver disease (CLD) is a major source of morbidity and mortality in the United States. Coffee consumption has been proposed to reduce CLD risk, but few data are available from prospective, US multiethnic populations. We evaluated the association of coffee drinking with CLD by underlying etiology in African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites in the Multiethnic Cohort (MEC). Methods: We used exposure information on the baseline questionnaire to identify coffee consumption and other lifestyle factors. CLD cases were identified using Medicare claim files among the MEC fee-for-service participants with complete coffee and other risk factor data (n=95,197). We used ICD-9 codes and body mass index (BMI) and history of diabetes mellitus (DM) from questionnaire to identify underlying etiologies and classified CLD cases into four major etiologic groups: alcoholic liver disease (ALD, n=933), non-alcoholic fatty liver disease related (NAFLD, n=2,865), hepatitis C related (HCV, n=433), and hepatitis B related (HBV, n= 155). Associations of regular coffee, decaffeinated coffee and caffeine with CLD for each etiologic group were estimated by relative risks (RRs) and 95% confidence intervals (CIs) using log linear proportional hazard models stratified by risk set and adjusted for confounders. Results: Regular coffee was associated with reduced risks of NAFLD-related CLD (p trend= 0.0002) and ALD-related CLD (p trend=0.0005) with dose dependent manners. Compared to non-coffee drinkers, participants who reported drinking 2-3 cups and ‡4 cups per day had a 14% (RR=0.86; 95% CI: 0.77, 0.96) and a 34% (RR=0.66; 95% CI: 0.53, 0.82) reduction in risk for NAFLD-related CLD, respectively. Compared to non-coffee drinkers, participants who reported drinking 2-3 cups and ‡4 cups per day had a 26% (RR=0.74; 95% CI: 0.59, 0.92) and a 37% (RR=0.63; 95% CI: 0.43, 0.91) reduction in risk for ALDrelated CLD, respectively. Only high consumption of ‡4 cups per day of regular coffee (RR= 0.53; 95% CI: 0.29, 0.99) was associated with HCV-related CLD. Regular coffee was not associated with HBV-related CLD (p trend=0.63). Decaffeinated coffee and caffeine intakes were not associated with CLD risk. Conclusions: Coffee drinking is significantly associated with reduced CLD risk, particularly for the NAFLD-related and ALD-related diseases. Caffeine does not seem to contribute to this protective mechanism, and thus, other coffee components need to be investigated further.
Introduction: The fundamental changes to hepatocytes caused by chronic alcohol abuse result in accelerated liver injury, leading to cirrhosis and hepatocellular carcinoma (HCC). However, understanding of an underlying pathway leading to increased carcinogenesis remains elusive in alcoholic liver disease (ALD). Knockout models of miRNA-122, the most abundant miRNA in hepatocytes, have demonstrated its role as an oncogene and essential regulator of hepatocyte function. In humans, miR-122 expression inversely correlates with HCC survival and metastasis. Recent studies have pointed to Grainy-head-like 2 (GRHL2), a transcriptional regulator, as an inhibitor of miR-122 expression and correlated with increased HCC invasiveness. We hypothesized that the loss of miR-122 is a central mediator of alcohol-induced liver injury, and that chronic alcohol inhibits miR-122 expression though GRHL2. Methods: Livers from 10 patients with alcoholic liver disease were assessed, healthy donors were used as controls. Eight-week-old, C57Bl/6 mice were injected intravenously with hepatocyte-tropic AAV (AAV8) containing anti-miR-122 TuD (TuD), or scrambled (Scr) vector 14 days prior to Lieber-DeCarli (LDC) alcohol diet (Et) or control diet (PF) for 4 weeks. Results: We have observed that chronic alcoholic patients, free of neoplastic changes, had a reduction of miR-122 and its primary transcript, pri-miR-122, in the liver. This was associated with increased mRNA expression of GRHL2 in human ALD livers. MiR-122 was also significantly decreased in livers of mice after chronic alcohol feeding. In vivo knockdown of miR-122 in mice resulted in increased liver injury (ALT), steatosis, inflammation in PF mice while combination of miR-122 knockdown and alcohol were synergistic in increasing liver injury, inflammation and fibrosis. Interestingly, alcohol further suppressed miR-122 expression in livers with miR-122 knockdown indicating that alcohol specifically inhibits expression of the precursor miR-122, pri-miR-122, at the transcriptional level. We also discovered that alcohol increased GRHL2 expression in the livers of alcohol-fed mice that was similar to increased GRHL2 in human livers with ALD. Of note, we found that in these patients, alcohol specifically increased the dominant negative form of GRHL2, GRHL2DN, an isoform that contains only the DNA binding and not the transactivation domain. Conclusions: miR-122 inhibition mimics the steatosis, inflammation and early fibrosis seen in ALD. We discovered that alcohol regulates the transcription of miR-122 by upregulating the dominant negative form of GRHL2, an inhibitor of miR-122 transcription. Our findings dissect a novel mechanistic regulatory axis of miR-122 and indicate a potential target for restoration of miR-122 in early ALD.
745 Inhibition of Hepatic Stellate Cell Activation by Stem Cell Derived Extracellular Vesicles and microRNAs During Cholestatic Liver Injury Kelly McDaniel, Ying Wan, Nan Wu, Julie Venter, Heather L. Francis, Tianhao Zhou, Lindsey Kennedy, Shannon Glaser, Gianfranco Alpini, Fanyin Meng Background: Stem cell-derived extracellular vesicles (EVs) and their related microRNAs mediate genetic changes that promote recovery of liver disorders. The present study aims to characterize the functional role of liver stem cell-derived EVs and specific miRNAs in the regulation of hepatic stellate cell activity during cholestatic-induced liver injury. Methods: microRNA expression was assessed using microarray and real-time PCR assays in isolated microvesicles from human mesenchymal stem cells (MSCs) and liver stem cells (LSCs), in TGF-b/LPS-treated human hepatic stellate cells (HHSCs) and liver specimens from bile duct
AASLD Abstracts
X : 10052$CH02 03-28-16 22:36:37 PDFd : 10052B : e
S-1044
Page 1044