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109 Primary Alterations in Hepatic Lipid Metabolism Do Not Affect Liver Regeneration Following Partial Hepatectomy
was equally protective suggesting a role for the MyD88-dependent TLR4 pathway activation in the pathogenesis of NASH and associated liver fibrosis in this model.
(viral hepatitis, excessive alcohol use etc.) have been excluded and liver biopsies read in a systematic fashion for NAFLD (age at biopsy 50.1±14.5, male 39.7%, Caucasians 80.4%, type II Diabetes 28.7% and hyperlipidemia 48.5%). NAFLD patients were categorized as NASH, Simple Steatosis (SS) or steatosis with non-specific changes [Non-NASH NAFLD (NNN)]. Mortality data and causes of death were obtained from National Death Index Plus. Univariate and multivariate analyses were performed comparing different NAFLD subtypes and to identify predictors of mortality. Results: A total of 174 NAFLD patients were included (NASH= 66, SS= 75, NNN= 32). The median follow up from the time of biopsy to the time of death or the last NDI follow up was 11.13 years with longest follow up being 28.55 years. Over this period, 78 NAFLD patients had died with the most common causes of death being coronary artery disease (13%), malignancy (8%) and liver death (7%). Although overall mortality was not different between the NAFLD subtypes, liver related mortality was higher in NASH (16%) as compared to SS (2%) or NNN (0%), p-values<0.05. Kaplan Meir survival estimates confirmed the increase in liver-related mortality in NASH as compared to SS and NNN (p=0.0043). In multivariate analysis, independent predictors of liver related mortality included histologic NASH [Hazard Ratio (HR) of 8.647, p=0.0056], presence of diabetes (HR of 5.137, p=0.0108) and age of biopsy (HR of 1.1 per year, p=0.0037). Conclusions: This long term follow up of patients with NAFLD confirms that NASH patients have higher liver related mortality than non-NASH patients with NAFLD. Additionally, patients with NAFLD and diabetes are especially at risk for liver related mortality.
108
AASLD Abstracts
NRF2 Prevents Alcohol Induced Fulminant Liver Injury Jutta Lamlé, Silke Marhenke, Jürgen Borlak, Masayuki Yamamoto, Michael P. Manns, Arndt Vogel The transcription factor Nrf2 is essential for protecting cells against xenobiotic and oxidative stress. To clarify the role of Nrf2 in ethanol induced liver injury, WT and Nrf2-/- mice were treated with an alcohol-containing liquid diet. With doses of ethanol that were tolerated by WT mice, Nrf2-/- mice died of liver failure. Livers of critically sick Nrf2-/- mice exhibited severe macrovesicular steatosis, multiple Tunel-positive hepatocytes and focal inflammation. Following ingestion ethanol is oxidized by cytosolic alcohol dehydrogenases to acetaldehyde, which is oxidized by aldehyde dehydrogenases to produce non-toxic acetate. Loss of Nrf2 did not impair the expression of genes involved in the oxidation of alcohol to acetaldehyde. However, Nrf2-/- mice displayed a reduced expression of Aldh enzymes leading to significantly lower Aldh activity in Nrf2-/- mice. After ethanol administration, toxic acetaldehyde levels were accordingly significantly higher in livers of Nrf2-/- mice that likely contribute to the increased mortality of Nrf2-/- mice. Ethanol feeding induced a severe steatosis in Nrf2-/- mice, which is reflected by a gene expression profile that governs lipid homeostasis in the liver. Pathway analysis identified Srebp-1 as a likely candidate contributing to the early adaptations in Nrf2-/- mice. Furthermore, ethanol consumption led to a progressive depletion of total and mitochondrial GSH, which was associated with more pronounced structural and functional changes to mitochondria of Nrf2-/- mice. Progression of alcoholic liver disease beyond steatosis does not occur in the absence of a second hit that promotes inflammation and cell death. Accumulating evidence indicates that ethanol increases the susceptibility to toxic effects of endotoxins released from the gut. Here, ethanol treatment elicits an aggravated inflammatory response in Nrf2-/- mice. High Tnf-α/ Il-6 levels occurred simultaneously with the onset of the severe steatosis shortly before Nrf2-/- mice died, suggesting that the overwhelming immune response mediated by Kupffer cells is directly related to the increased mortality of ethanol-fed Nrf2-/- mice. Taken together, our data establish a central role for Nrf2 in the protection against ethanol-induced liver injury. Detoxification of acetaldehyde was significantly impaired in Nrf2-/- mice, leading to an accumulation of toxic acetaldehyde. Disruption of Nrf2 further aggravated ethanol-induced liver damage by eliciting an aggravated inflammatory response in ethanol-fed Nrf2-/- mice. Together this changes lead to a vicious cycle of accumulating hepatocellular damage, ultimately leading to liver failure and death of Nrf2-/- mice.
111 Hepatic Lipid Partitioning and Liver Damage in NAFLD: Role of Stearoyl-CoA Desaturase Zhengzheng Li, Michael P. Berk, Ariel E. Feldstein Hepatic lipid overloading mainly in the form of triglycerides (TG) is considered a prerequisite for the development of NAFLD. However, TG accumulation in the liver in response to lipid overflow may represent a protective mechanism against lipotoxicity. Our aims were to assess the fundamental cellular mechanisms that link lipid partitioning to liver injury by using both In Vivo dietary models of NAFLD and In Vitro cell models of lipid overloading. METHODS: Primary mouse hepatocytes, HepG2 and McNtcp.24 cells were treated with varied concentrations of free fatty acids (FFA) with different degrees of saturation, alone or in combination for up to 24 hrs. Apoptosis was assessed morphologically and biochemically. TG accumulation was assessed by Oil Red O staining. Activity of Stearoyl-CoA Desaturase (SCD)-1, the enzyme that catalysis the rate limiting step in TG formation, was suppressed by genetic (siRNA) or pharmacological approaches. SCD-1 knock out and wildtype mice were placed on either a high fat(HSAT), a methionine-choline deficient (MCD), or a control chow diet (n = 6 in each group) for 6 wks. Liver injury was assessed by TUNEL assay, active caspase 3 staining, WB for cytosolic cytochrome c, histopathology, and serum ALT. Hepatic lipids were quantified by capillary gas chromatography. SCD-1 expression was assessed by WB analysis. RESULTS: Exposure of liver cells to unsaturated FFA (oleate) resulted in significant accumulation of TG without changes in cell viability. In contrast, cells incubated with saturated FFA (palmitate or stearate) showed significant decrease in cell viability as a result of increase apoptotic cell death in conjunction with absence of TG accumulation above the baseline levels. Moreover, blocking TG synthesis by either genetic or pharmacological inhibition of SCD-1 resulted in a significant increased sensitivity to FFA induced apoptotic cell death. Hepatic SCD-1 expression was increased in HSAT fed and decreased in MCD fed wildtype animals compared to those mice on the control diet. SCD1-/- mice showed decreased in hepatic TG content on both HSAT and MCD diet compared to the SCD-1+/+ on the respective diets. However SCD-/- mice on the MCD diet showed significant increase in hepatic saturated FFA levels, and marked increased in hepatocellular apoptosis, inflammation and liver injury. CONCLUSIONS: These data strongly suggest that lipid partitioning in the liver and in particular excessive accumulation of saturated FFA may play an important role in disease progression from fatty liver to steatohepatitis. This concept has important implications for the development of novel treatment strategies for patients with this condition.
109 Primary Alterations in Hepatic Lipid Metabolism Do Not Affect Liver Regeneration Following Partial Hepatectomy Elizabeth P. Newberry, Susan Kennedy, Yan Xie, Jianyang Luo, Nicholas O. Davidson A marked, but transient hepatic steatosis occurs after 70% partial hepatectomy (PH) in mice, with hepatic triglyceride (TG) levels peaking 18-24h after PH, returning to baseline after ~72h. Studies have shown that genetic or pharmacologic modifications that alter whole body lipid metabolism prevent PH-induced hepatic lipid accumulation and abrogate liver regeneration, leading to the suggestion that hepatic steatosis is required for normal liver regeneration. We have reexamined this issue using a range of genetically manipulated mice with primary alterations in hepatic lipid metabolism in order to modulate hepatic TG accumulation following PH and then examined liver regeneration. L-Fabp-/- mice exhibit reduced (50-80%) hepatic TG content compared to WT mice at 6, 12, 24, and 48h after PH, with no effect on liver regeneration or hepatocyte proliferation. This phenotype correlates with the absence of L-Fabp in liver, since WT mice treated with L-Fabp antisense oligonucleotide (ASO), which manifest decreased hepatic but not intestinal L-Fabp mRNA and protein, had a 50% reduction in hepatic TG 24h after PH compared to control ASO mice. BrdU incorporation 48h after PH is similar in control and L-Fabp ASO treated mice (27.6 ± 6.7 vs 32.2 ± 13.0% positive nuclei, respectively). Mice with intestine-specific deletion of microsomal TG transfer protein (MTP-IKO) exhibit virtually complete fat malabsorption, resulting in a lack of peripheral fat and manifest a compensatory induction of hepatic lipogenesis. Hepatic TG accumulation following PH is reduced 2-4x in MTP-IKO mice, likely due to decreased availability of FA, yet there is no decrease in hepatocyte proliferation. Mice lacking PPARα exhibit ~4x elevated hepatic TG compared to WT mice 48h after PH, with no difference in liver regeneration (PPARα-/-, 36.2 ± 5.7; C57BL/6, 39.1 ± 6.2% BrdU positive nuclei). This temporary inability to mobilize TG stores likely reflects decreased induction of hepatic MTP expression, which is markedly attenuated in PPARα null mice (increased 70% 24h after PH in both WT and L-Fabp-/- mice vs 0% in PPARα-/- mice) and reduced ketogenesis following PH. Double knockout (L-Fabp-/-, PPARα-/-) mice demonstrated reversal of hepatic TG accumulation at 48h following PH, but again there was no defect in hepatic regeneration. Together these data indicate that hepatic TG accumulation is regulated through MTP-dependent defects in lipid mobilization but is not required for liver regeneration.
112 18β-Glycyrrhetinic Acid Prevents Free Fatty Acids/High Fat Diet-Induced Hepatic Toxicity By Inhibiting Cathepsin B Expression and Enzyme Activities Xudong Wu, Luyong Zhang, Jing Shang, Emily C. Gurley, Elaine Studer, Xuan Wang, Phillip Hylemon, William M. Pandak, Arun J. Sanyal, Huiping Zhou Free fatty acids (FFAs)-induced lipotoxicity plays a pivotal role in the pathogenesis of nonalcoholic fatty liver disease NAFLD. Inhibition of FFAs-associated hepatic toxicity represents a potential therapeutic strategy. Glycyrrhizin (GL), the major bioactive component of licorice root extract, has been used to treat hepatitis to reduce liver inflammation and hepatic injury. However, the underlying mechanism remains unknown. 18β-glycyrrhetinic acid (GA) is the biologically active metabolite of GL. In the present study, we examined whether GA is able to prevent FFAs-induced lipotoxicity both in In Vitro and In Vivo NAFLD models. Methods: HepG2 cells were treated with 1 mM FFAs (oleic acid /palmitic acid, 2;1) in the presence of GA (0 ~ 30 µM) for various time periods. High fat diet (HFD)-induced rat NAFLD models were used for In Vivo studies. Rats were fed HFD and gavaged with GA (25 and 50 mg/kg) for 8-weeks. The apoptotic cells were detected by Annexin V-FITC/PI staining followed by flow cytometry. The lipid accumulation was detected by nile red staining. The lysosomal stability was assessed using the acridine orange (AO)-uptake method. The expression of cathepsin B was detected by western blot analysis and immunofluorescent staining. Serum lipids and liver function enzymes were measured using standard enzymatic techniques. Cathepsin B enzyme activities were measured using specific substrate Z-ArgArg-7-amido-4-methylcourmarin hydrochloride. Liver injury was examined by HE staining. The histopathological score of rat liver was analyzed by Mann-Whitney Rank Sum Test. Results: GA not only significantly inhibited FFAs-induced apoptosis in HepG2 cells, but also protected the HFD-induced lipid accumulation and liver injury in rats. In HepG2 cells, GA (10 µM) markedly inhibited FFAs-induced cathepsin B expression and enzyme activities by 50% and 26%, respectively. In rat NAFLD models, GA (50 mg/kg) also significantly inhibited HFD-induced cathepsin B expression and enzyme activity by 70% and 34%,
110 Over Twenty Five Years of Follow Up for a Non-Alcoholic Fatty Liver Disease (NAFLD) Cohort Nila Rafiq, Chunhong Bai, Yun Fang, Manirath K. Srishord, Arthur J. McCullough, Zobair M. Younossi NAFLD is one of the most common causes of chronic liver disease. From the spectrum of NAFLD, patients with non-alcoholic steatohepatitis (NASH) have a potentially progressive course. Aim: To assess the long term mortality outcomes of patients with NAFLD and its subtypes. Design: From our existing databases, patients with biopsy proven NAFLD with a minimum of 5 years of follow up were included in the study. All other causes of liver disease
AASLD Abstracts
A-754
(viral hepatitis, excessive alcohol use etc.) have been excluded and liver biopsies read in a systematic fashion for NAFLD (age at biopsy 50.1±14.5, male 39.7%, Caucasians 80.4%, type II Diabetes 28.7% and hyperlipidemia 48.5%). NAFLD patients were categorized as NASH, Simple Steatosis (SS) or steatosis with non-specific changes [Non-NASH NAFLD (NNN)]. Mortality data and causes of death were obtained from National Death Index Plus. Univariate and multivariate analyses were performed comparing different NAFLD subtypes and to identify predictors of mortality. Results: A total of 174 NAFLD patients were included (NASH= 66, SS= 75, NNN= 32). The median follow up from the time of biopsy to the time of death or the last NDI follow up was 11.13 years with longest follow up being 28.55 years. Over this period, 78 NAFLD patients had died with the most common causes of death being coronary artery disease (13%), malignancy (8%) and liver death (7%). Although overall mortality was not different between the NAFLD subtypes, liver related mortality was higher in NASH (16%) as compared to SS (2%) or NNN (0%), p-values<0.05. Kaplan Meir survival estimates confirmed the increase in liver-related mortality in NASH as compared to SS and NNN (p=0.0043). In multivariate analysis, independent predictors of liver related mortality included histologic NASH [Hazard Ratio (HR) of 8.647, p=0.0056], presence of diabetes (HR of 5.137, p=0.0108) and age of biopsy (HR of 1.1 per year, p=0.0037). Conclusions: This long term follow up of patients with NAFLD confirms that NASH patients have higher liver related mortality than non-NASH patients with NAFLD. Additionally, patients with NAFLD and diabetes are especially at risk for liver related mortality.
108
AASLD Abstracts
NRF2 Prevents Alcohol Induced Fulminant Liver Injury Jutta Lamlé, Silke Marhenke, Jürgen Borlak, Masayuki Yamamoto, Michael P. Manns, Arndt Vogel The transcription factor Nrf2 is essential for protecting cells against xenobiotic and oxidative stress. To clarify the role of Nrf2 in ethanol induced liver injury, WT and Nrf2-/- mice were treated with an alcohol-containing liquid diet. With doses of ethanol that were tolerated by WT mice, Nrf2-/- mice died of liver failure. Livers of critically sick Nrf2-/- mice exhibited severe macrovesicular steatosis, multiple Tunel-positive hepatocytes and focal inflammation. Following ingestion ethanol is oxidized by cytosolic alcohol dehydrogenases to acetaldehyde, which is oxidized by aldehyde dehydrogenases to produce non-toxic acetate. Loss of Nrf2 did not impair the expression of genes involved in the oxidation of alcohol to acetaldehyde. However, Nrf2-/- mice displayed a reduced expression of Aldh enzymes leading to significantly lower Aldh activity in Nrf2-/- mice. After ethanol administration, toxic acetaldehyde levels were accordingly significantly higher in livers of Nrf2-/- mice that likely contribute to the increased mortality of Nrf2-/- mice. Ethanol feeding induced a severe steatosis in Nrf2-/- mice, which is reflected by a gene expression profile that governs lipid homeostasis in the liver. Pathway analysis identified Srebp-1 as a likely candidate contributing to the early adaptations in Nrf2-/- mice. Furthermore, ethanol consumption led to a progressive depletion of total and mitochondrial GSH, which was associated with more pronounced structural and functional changes to mitochondria of Nrf2-/- mice. Progression of alcoholic liver disease beyond steatosis does not occur in the absence of a second hit that promotes inflammation and cell death. Accumulating evidence indicates that ethanol increases the susceptibility to toxic effects of endotoxins released from the gut. Here, ethanol treatment elicits an aggravated inflammatory response in Nrf2-/- mice. High Tnf-α/ Il-6 levels occurred simultaneously with the onset of the severe steatosis shortly before Nrf2-/- mice died, suggesting that the overwhelming immune response mediated by Kupffer cells is directly related to the increased mortality of ethanol-fed Nrf2-/- mice. Taken together, our data establish a central role for Nrf2 in the protection against ethanol-induced liver injury. Detoxification of acetaldehyde was significantly impaired in Nrf2-/- mice, leading to an accumulation of toxic acetaldehyde. Disruption of Nrf2 further aggravated ethanol-induced liver damage by eliciting an aggravated inflammatory response in ethanol-fed Nrf2-/- mice. Together this changes lead to a vicious cycle of accumulating hepatocellular damage, ultimately leading to liver failure and death of Nrf2-/- mice.
111 Hepatic Lipid Partitioning and Liver Damage in NAFLD: Role of Stearoyl-CoA Desaturase Zhengzheng Li, Michael P. Berk, Ariel E. Feldstein Hepatic lipid overloading mainly in the form of triglycerides (TG) is considered a prerequisite for the development of NAFLD. However, TG accumulation in the liver in response to lipid overflow may represent a protective mechanism against lipotoxicity. Our aims were to assess the fundamental cellular mechanisms that link lipid partitioning to liver injury by using both In Vivo dietary models of NAFLD and In Vitro cell models of lipid overloading. METHODS: Primary mouse hepatocytes, HepG2 and McNtcp.24 cells were treated with varied concentrations of free fatty acids (FFA) with different degrees of saturation, alone or in combination for up to 24 hrs. Apoptosis was assessed morphologically and biochemically. TG accumulation was assessed by Oil Red O staining. Activity of Stearoyl-CoA Desaturase (SCD)-1, the enzyme that catalysis the rate limiting step in TG formation, was suppressed by genetic (siRNA) or pharmacological approaches. SCD-1 knock out and wildtype mice were placed on either a high fat(HSAT), a methionine-choline deficient (MCD), or a control chow diet (n = 6 in each group) for 6 wks. Liver injury was assessed by TUNEL assay, active caspase 3 staining, WB for cytosolic cytochrome c, histopathology, and serum ALT. Hepatic lipids were quantified by capillary gas chromatography. SCD-1 expression was assessed by WB analysis. RESULTS: Exposure of liver cells to unsaturated FFA (oleate) resulted in significant accumulation of TG without changes in cell viability. In contrast, cells incubated with saturated FFA (palmitate or stearate) showed significant decrease in cell viability as a result of increase apoptotic cell death in conjunction with absence of TG accumulation above the baseline levels. Moreover, blocking TG synthesis by either genetic or pharmacological inhibition of SCD-1 resulted in a significant increased sensitivity to FFA induced apoptotic cell death. Hepatic SCD-1 expression was increased in HSAT fed and decreased in MCD fed wildtype animals compared to those mice on the control diet. SCD1-/- mice showed decreased in hepatic TG content on both HSAT and MCD diet compared to the SCD-1+/+ on the respective diets. However SCD-/- mice on the MCD diet showed significant increase in hepatic saturated FFA levels, and marked increased in hepatocellular apoptosis, inflammation and liver injury. CONCLUSIONS: These data strongly suggest that lipid partitioning in the liver and in particular excessive accumulation of saturated FFA may play an important role in disease progression from fatty liver to steatohepatitis. This concept has important implications for the development of novel treatment strategies for patients with this condition.
109 Primary Alterations in Hepatic Lipid Metabolism Do Not Affect Liver Regeneration Following Partial Hepatectomy Elizabeth P. Newberry, Susan Kennedy, Yan Xie, Jianyang Luo, Nicholas O. Davidson A marked, but transient hepatic steatosis occurs after 70% partial hepatectomy (PH) in mice, with hepatic triglyceride (TG) levels peaking 18-24h after PH, returning to baseline after ~72h. Studies have shown that genetic or pharmacologic modifications that alter whole body lipid metabolism prevent PH-induced hepatic lipid accumulation and abrogate liver regeneration, leading to the suggestion that hepatic steatosis is required for normal liver regeneration. We have reexamined this issue using a range of genetically manipulated mice with primary alterations in hepatic lipid metabolism in order to modulate hepatic TG accumulation following PH and then examined liver regeneration. L-Fabp-/- mice exhibit reduced (50-80%) hepatic TG content compared to WT mice at 6, 12, 24, and 48h after PH, with no effect on liver regeneration or hepatocyte proliferation. This phenotype correlates with the absence of L-Fabp in liver, since WT mice treated with L-Fabp antisense oligonucleotide (ASO), which manifest decreased hepatic but not intestinal L-Fabp mRNA and protein, had a 50% reduction in hepatic TG 24h after PH compared to control ASO mice. BrdU incorporation 48h after PH is similar in control and L-Fabp ASO treated mice (27.6 ± 6.7 vs 32.2 ± 13.0% positive nuclei, respectively). Mice with intestine-specific deletion of microsomal TG transfer protein (MTP-IKO) exhibit virtually complete fat malabsorption, resulting in a lack of peripheral fat and manifest a compensatory induction of hepatic lipogenesis. Hepatic TG accumulation following PH is reduced 2-4x in MTP-IKO mice, likely due to decreased availability of FA, yet there is no decrease in hepatocyte proliferation. Mice lacking PPARα exhibit ~4x elevated hepatic TG compared to WT mice 48h after PH, with no difference in liver regeneration (PPARα-/-, 36.2 ± 5.7; C57BL/6, 39.1 ± 6.2% BrdU positive nuclei). This temporary inability to mobilize TG stores likely reflects decreased induction of hepatic MTP expression, which is markedly attenuated in PPARα null mice (increased 70% 24h after PH in both WT and L-Fabp-/- mice vs 0% in PPARα-/- mice) and reduced ketogenesis following PH. Double knockout (L-Fabp-/-, PPARα-/-) mice demonstrated reversal of hepatic TG accumulation at 48h following PH, but again there was no defect in hepatic regeneration. Together these data indicate that hepatic TG accumulation is regulated through MTP-dependent defects in lipid mobilization but is not required for liver regeneration.
112 18β-Glycyrrhetinic Acid Prevents Free Fatty Acids/High Fat Diet-Induced Hepatic Toxicity By Inhibiting Cathepsin B Expression and Enzyme Activities Xudong Wu, Luyong Zhang, Jing Shang, Emily C. Gurley, Elaine Studer, Xuan Wang, Phillip Hylemon, William M. Pandak, Arun J. Sanyal, Huiping Zhou Free fatty acids (FFAs)-induced lipotoxicity plays a pivotal role in the pathogenesis of nonalcoholic fatty liver disease NAFLD. Inhibition of FFAs-associated hepatic toxicity represents a potential therapeutic strategy. Glycyrrhizin (GL), the major bioactive component of licorice root extract, has been used to treat hepatitis to reduce liver inflammation and hepatic injury. However, the underlying mechanism remains unknown. 18β-glycyrrhetinic acid (GA) is the biologically active metabolite of GL. In the present study, we examined whether GA is able to prevent FFAs-induced lipotoxicity both in In Vitro and In Vivo NAFLD models. Methods: HepG2 cells were treated with 1 mM FFAs (oleic acid /palmitic acid, 2;1) in the presence of GA (0 ~ 30 µM) for various time periods. High fat diet (HFD)-induced rat NAFLD models were used for In Vivo studies. Rats were fed HFD and gavaged with GA (25 and 50 mg/kg) for 8-weeks. The apoptotic cells were detected by Annexin V-FITC/PI staining followed by flow cytometry. The lipid accumulation was detected by nile red staining. The lysosomal stability was assessed using the acridine orange (AO)-uptake method. The expression of cathepsin B was detected by western blot analysis and immunofluorescent staining. Serum lipids and liver function enzymes were measured using standard enzymatic techniques. Cathepsin B enzyme activities were measured using specific substrate Z-ArgArg-7-amido-4-methylcourmarin hydrochloride. Liver injury was examined by HE staining. The histopathological score of rat liver was analyzed by Mann-Whitney Rank Sum Test. Results: GA not only significantly inhibited FFAs-induced apoptosis in HepG2 cells, but also protected the HFD-induced lipid accumulation and liver injury in rats. In HepG2 cells, GA (10 µM) markedly inhibited FFAs-induced cathepsin B expression and enzyme activities by 50% and 26%, respectively. In rat NAFLD models, GA (50 mg/kg) also significantly inhibited HFD-induced cathepsin B expression and enzyme activity by 70% and 34%,
110 Over Twenty Five Years of Follow Up for a Non-Alcoholic Fatty Liver Disease (NAFLD) Cohort Nila Rafiq, Chunhong Bai, Yun Fang, Manirath K. Srishord, Arthur J. McCullough, Zobair M. Younossi NAFLD is one of the most common causes of chronic liver disease. From the spectrum of NAFLD, patients with non-alcoholic steatohepatitis (NASH) have a potentially progressive course. Aim: To assess the long term mortality outcomes of patients with NAFLD and its subtypes. Design: From our existing databases, patients with biopsy proven NAFLD with a minimum of 5 years of follow up were included in the study. All other causes of liver disease
AASLD Abstracts
A-754