Methionine adenosyltransferases(MATs)are essential enzymes for life as they produce S-adenosylmethionine(SAMe),the biological methyl donor required for a plethora of reactions within the cell.Mammalian systems express...Methionine adenosyltransferases(MATs)are essential enzymes for life as they produce S-adenosylmethionine(SAMe),the biological methyl donor required for a plethora of reactions within the cell.Mammalian systems express two genes,MAT1A and MAT2A,which encode for MATα1 and MATα2,the catalytic subunits of the MAT isoenzymes,respectively.A third gene MAT2B,encodes a regulatory subunit known as MATβwhich controls the activity of MATα2.MAT1A,which is mainly expressed in hepatocytes,maintains the differentiated state of these cells,whilst MAT2A and MAT2B are expressed in extrahepatic tissues as well as non-parenchymal cells of the liver(e.g.,hepatic stellate and Kupffer cells).The biosynthesis of SAMe is impaired in patients with chronic liver disease and liver cancer due to decreased expression and inactivation of MATα1.A switch from MAT1A to MAT2A/MAT2B occurs in multiple liver diseases and during liver growth and dedifferentiation,but this change in the expression pattern of MATs results in reduced hepatic SAMe level.Decades of study have utilized the Mat1a-knockout(KO)mouse that spontaneously develops non-alcoholic steatohepatitis(NASH)and hepatocellular carcinoma(HCC)to elucidate a variety of mechanisms by which MAT proteins dysregulation contributes to liver carcinogenesis.An increasing volume of work indicates that MATs have SAMe-independent functions,distinct interactomes and multiple subcellular localizations.Here we aim to provide an overview of MAT biology including genes,isoenzymes and their regulation to provide the context for understanding consequences of their dysregulation.We will highlight recent breakthroughs in the field and underscore the importance of MAT’s in liver tumorigenesis as well as their potential as targets for cancer therapy.展开更多
Pancreatic cysts are identified at an increasing frequency.Although mucinous cystic neoplasms represent a pre-malignant condition,the majority of these lesions do not progress to cancer.Over the last 10 years several ...Pancreatic cysts are identified at an increasing frequency.Although mucinous cystic neoplasms represent a pre-malignant condition,the majority of these lesions do not progress to cancer.Over the last 10 years several societies have established guidelines for the diagnosis,initial evaluation and surveillance of these lesions.Here we provide an overview of five commonly used guidelines:2015 American Gastroenterological Association,2017 International Association of Pancreatology,American College of Gastroenterology 2018,European Study Group and American College of Radiology.We describe the similarities and differences between the methods used to formulate these guidelines,the population they target and their approaches towards initial evaluation and surveillance of cystic lesions.展开更多
Hepatitis B virus (HBV) infection affects a large part of the world population. Within the different virological HBV categories that have been identified, patients with occult HBV infection represent a peculiar group....Hepatitis B virus (HBV) infection affects a large part of the world population. Within the different virological HBV categories that have been identified, patients with occult HBV infection represent a peculiar group. These individuals harbor a replication competent virus, inhibited in its replicative function. Accordingly, cases of reactivations have been observed in immunosuppressed individuals who lose immunological control over the infection. Patients with hematological malignancies (HM) are treated with intense myeloand immunosuppres-sive chemotherapy regimens which favor HBV reactivation. This event can have severe consequences, such as hepatitis flare, hepatic failure and even death. In addition, it can lead to delays or interruptions of curative treatments, resulting in a decreased disease free and overall survival. In this review, we will examine the event of HBV reactivation in patients with signs of resolved HBV infection undergoing treatment for HM and propose possible management strategies.展开更多
While antimicrobials are clinically effective in preventing post-operative recurrence,the role for antibiotics in primary therapy for Crohn's disease(CD) remains unclear.The recent multicenter phase 2 trial by Pra...While antimicrobials are clinically effective in preventing post-operative recurrence,the role for antibiotics in primary therapy for Crohn's disease(CD) remains unclear.The recent multicenter phase 2 trial by Prantera et al received wide attention because it demonstrated an increase in the week 12 remission rate in patients with moderately active CD treated with rifaximin and renewed interest in microbial manipulation as primary therapy for CD.In this commentary,we discuss aspects of durability,immune cell polarization,and safety of microbial manipulation as primary therapy for CD.展开更多
BACKGROUND Only one case of liver transplantation for hepatic adenoma has previously been reported for patients with rupture and uncontrolled hemorrhage.We present the case of a massive ruptured hepatic adenoma with p...BACKGROUND Only one case of liver transplantation for hepatic adenoma has previously been reported for patients with rupture and uncontrolled hemorrhage.We present the case of a massive ruptured hepatic adenoma with persistent hemorrhagic shock and toxic liver syndrome which resulted in a two-stage liver transplantation.This is the first case of a two-stage liver transplantation performed for a ruptured hepatic adenoma.CASE SUMMARY A 23 years old African American female with a history of pre-diabetes and oral contraceptive presented to an outside facility complaining of right-sided chest pain and emesis for one day.She was found to be in hemorrhagic shock due to a massive ruptured hepatic hepatic adenoma.She underwent repeated embolizations with interventional radiology with ongoing hemorrhage and the development of renal failure,hepatic failure,and hemodynamic instability,known as toxic liver syndrome.In the setting of uncontrolled hemorrhage and toxic liver syndrome,a hepatectomy with porto-caval anastomosis was performed with liver transplantation 15 h later.She tolerated the anhepatic stage well,and has done well over one year later.CONCLUSION When toxic liver syndrome is recognized,liver transplantation with or withouthepatectomy should be considered before the patient becomes unstable.展开更多
Heavy alcohol use is the cause of alcoholic liver disease(ALD).The ALD spectrum ranges from alcoholic steatosis to steatohepatitis,fibrosis,and cirrhosis.In Western countries,approximately 50%of cirrhosis-related deat...Heavy alcohol use is the cause of alcoholic liver disease(ALD).The ALD spectrum ranges from alcoholic steatosis to steatohepatitis,fibrosis,and cirrhosis.In Western countries,approximately 50%of cirrhosis-related deaths are due to alcohol use.While alcoholic cirrhosis is no longer considered a completely irreversible condition,no effective anti-fibrotic therapies are currently available.Another significant clinical aspect of ALD is alcoholic hepatitis(AH).AH is an acute inflammatory condition that is often comorbid with cirrhosis,and severe AH has a high mortality rate.Therapeutic options for ALD are limited.The established treatment for AH is corticosteroids,which improve short-term survival but do not affect long-term survival.Liver transplantation is a curative treatment option for alcoholic cirrhosis and AH,but patients must abstain from alcohol use for 6 months to qualify.Additional effective therapies are needed.The molecular mechanisms underlying ALD are complex and have not been fully elucidated.Various molecules,signaling pathways,and crosstalk between multiple hepatic and extrahepatic cells contribute to ALD progression.This review highlights established and emerging concepts in ALD clin-icopathology,their underlying molecular mechanisms,and current and future ALD treatment options.展开更多
Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA)constitute the main subtypes of primary liver cancers(PLCs)as a major cause of cancer-related mortality and incidence.They emerge from varying quan...Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA)constitute the main subtypes of primary liver cancers(PLCs)as a major cause of cancer-related mortality and incidence.They emerge from varying quantities and levels of differentiation among major liver cells,comprising hepatocytes,mucin-or non-mucin-producing cholangiocytes,and hepatic progenitor cells(HPCs)with the capability to differentiate into either hepatocytes or cholangiocytes.展开更多
Background:Bariatric surgery represents an important treatment option for severely obese patients with nonalcoholic fatty liver disease(NAFLD).However,there remains inadequate data regarding the effects of different b...Background:Bariatric surgery represents an important treatment option for severely obese patients with nonalcoholic fatty liver disease(NAFLD).However,there remains inadequate data regarding the effects of different bariatric procedures on various NAFLD parameters,especially for histological outcomes.Thus,this meta-analysis aimed to compare the effects of restrictive bariatric procedures and foregut bypass on the metabolic,biochemical,and histological parameters for patients with NAFLD.Methods:Medline and Embase were searched for articles relating to bariatric procedures and NAFLD.Pairwise meta-analysis was conducted to compare efficacy of bariatric procedures pre-vs.post-procedure with subgroup analysis to further compare restrictive against foregut bypass procedures.Results:Thirty-one articles involving 3,355 patients who underwent restrictive bariatric procedures(n=1,460)and foregut bypass(n=1,895)were included.Both foregut bypass(P<0.01)and restrictive procedures(P=0.03)significantly increased odds of fibrosis resolution.Compared to restrictive procedures,foregut bypass resulted in a borderline non-significant decrease in fibrosis score(P=0.06)and significantly lower steatosis score(P<0.001).For metabolic parameters,foregut bypass significantly lowered body mass index(P=0.003)and low-density lipoprotein(P=0.008)compared to restrictive procedures.No significant differences were observed between both procedures for aspartate aminotransferase(P=0.17)and alkaline phosphatase(P=0.61).However,foregut bypass resulted in significantly lower gamma-glutamyl transferase than restrictive procedures(P=0.01)while restrictive procedures resulted in significantly lower alanine transaminase than foregut bypass(P=0.02).Conclusions:The significant histological and metabolic advantages and comparable improvements in biochemical outcomes support the choice of foregut bypass over restrictive bariatric procedures in NAFLD management.展开更多
Introduction Hepatic sinusoidal obstruction syndrome(HSOS)is a hepatic vascular disease characterized by injury of the endothelial cells in the sinusoidal hepatic and interlobular veins,intra-hepatic congestion,liver ...Introduction Hepatic sinusoidal obstruction syndrome(HSOS)is a hepatic vascular disease characterized by injury of the endothelial cells in the sinusoidal hepatic and interlobular veins,intra-hepatic congestion,liver dysfunction,and portal hypertension[1].In Western countries,HSOS is often associated with myeloablative regimens used for hematopoietic stem-cell transplantation,while,in China,it is often associated with oral intake of Gynura segetum plants that contain pyrrolidine alkaloids[2].In addition,new-onset HSOS after solid-organ transplantation has received increasing attention[3-8].展开更多
Introduction Peritoneal dialysis(PD)is widely used for the treatment of endstage renal disease.Patients treated with PD have similar outcomes to those treated with hemodialysis[1].However,PDrelated infections includin...Introduction Peritoneal dialysis(PD)is widely used for the treatment of endstage renal disease.Patients treated with PD have similar outcomes to those treated with hemodialysis[1].However,PDrelated infections including peritonitis have been reported at 1.66 episodes per patient per year[2].One possible source of peritonitis is gastrointestinal(GI)endoscopic procedures.In 2005,the International Society for Peritoneal Dialysis(ISPD)published guidelines suggesting antibiotics be given to PD patients prior to colonoscopy[3].This suggestion was mostly based on expert opinion and a theoretical concern that patients undergoing colonoscopy are at increased risk for enteric peritonitis from bacterial translocation across the bowel wall.While there is no direct evidence to support this theory,case reports have suggested a risk of transient bacteremia associated with colonoscopy.展开更多
Background and Aims:Hispanic patients with primary bili-ary cholangitis (PBC) have reduced rates of biochemical re-sponse to ursodeoxycholic acid (UDCA) and increased risk of disease progression compared to non-Hispan...Background and Aims:Hispanic patients with primary bili-ary cholangitis (PBC) have reduced rates of biochemical re-sponse to ursodeoxycholic acid (UDCA) and increased risk of disease progression compared to non-Hispanic patients. In this study, we sought to identify differences in demographics, comorbidities, environmental risk factors and socioeconomic status between Hispanic and non-Hispanic patients with PBC. Methods: In a case control study, we analyzed data from Hispanic (n=37 females and 1 male) and non-Hispanic (n=54 females and 4 males) patients with PBC seen at the University of Miami/Jackson Memorial Hospital from January 1998 through January 2013. Data were obtained by filling out a questionnaire either via phone call, mail, or e-mail. Odds ratios were calculated to measure the association between exposure and outcomes.Results: Baseline demographics, environmental risk factors and comorbidities were similar be-tween Hispanic and non-Hispanic patients with PBC. Hispanic patients were less likely to be married and fewer Hispanics had education beyond high school level compared to non-His-panics. Sixty four percent of Hispanic patients had a house-hold income of less than$50000, compared to 19.5% of non-Hispanics. Fewer Hispanic patients with PBC had health insur-ance coverage compared to non-Hispanics (86.5% vs. 98.1%;odds ratio: 0.1, 95% confidence interval: 0-0.9). Conclusions: Differences in disease severity and response to therapy observed in prior studies could not be explained by environmental exposures. In addition to genetic variation, socioeconomic discrepancies (access to care) may further ex-plain these differences.展开更多
Background and Aims:Pharmaceutical therapy for NASH is associated with lipid modulation,but the consensus on drug treatment is limited and lacks comparative analysis of effectiveness.A network meta-analysis was conduc...Background and Aims:Pharmaceutical therapy for NASH is associated with lipid modulation,but the consensus on drug treatment is limited and lacks comparative analysis of effectiveness.A network meta-analysis was conducted to compare NASH drug classes in lipid modulation.Methods:Online databases were searched for randomized controlled trails(RCTs)evaluating NASH treatments in biopsy-proven NASH patients.Treatments were classified into four groups:(1)inflammation,(2)energy,(3)bile acids,and(4)fibro-sis based on the mechanism of action.A Bayesian network analysis was conducted with outcome measured by mean difference(MD)with credible intervals(Crl)and surface un-der the cumulative ranking curve(SUCRA).Results:Forty-four RCTs were included in the analysis.Bile acid modulat-ing treatments(MD:0.05,Crl:0.03-0.07)were the best treatment for improvement in high-density lipid(HDL)cho-lesterol,followed by treatments modulating energy(MD:0.03,Crl:0.02-0.04)and fibrosis(MD:0.01,Crl:−0.12 to 0.14)compared with placebo.The top three treatments for reduction in triglycerides were treatments modulating energy(MD:−0.46,Crl:−0.49 to−0.43),bile acids(MD:−0.22,Crl:−0.35 to−0.09),and inflammation(MD:−0.08,Crl:−0.13 to−0.03)compared with placebo.SUCRA found treatment modulating fibrosis(MD:−1.27,Crl:−1.76 to−0.79)was the best treatment for reduction in low-density lipid(LDL)cholesterol followed by treatment modulating in-flammation(MD:−1.03,Crl:−1.09 to−0.97)and energy(MD:−0.37,Crl:−0.39 to−0.34)compared with placebo,but LDL cholesterol was worsened by treatments modulat-ing bile acids.Conclusions:Network analysis comparing the class effects of dyslipidemia modulation in NASH found that treatment targets can include optimization of athero-genic dyslipidemia.Future studies are required to evaluate the cardiovascular outcomes.展开更多
Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide,which affects 25%of the general adult population and 70–80%of individuals with obesity and diabetes(1).
基金National Institutes of Health,NIAAA,No.R01AA026759(Lu)National Institutes of Health,NIDDK,No.R01DK107288(Lu)+4 种基金National Institutes of Health,NCCIH,No.R01AT001576National Institutes of Health,NCI,No.R01CA172086(Lu and Mato)Agencia Estatal de Investigación MINECO,No.SAF 2017-88041-RISCiii PIE14/00031,No.CIBERehdISCiiiSevero Ochoa Excellence Accreditation,No.SEV-2016-0644)(Mato)
文摘Methionine adenosyltransferases(MATs)are essential enzymes for life as they produce S-adenosylmethionine(SAMe),the biological methyl donor required for a plethora of reactions within the cell.Mammalian systems express two genes,MAT1A and MAT2A,which encode for MATα1 and MATα2,the catalytic subunits of the MAT isoenzymes,respectively.A third gene MAT2B,encodes a regulatory subunit known as MATβwhich controls the activity of MATα2.MAT1A,which is mainly expressed in hepatocytes,maintains the differentiated state of these cells,whilst MAT2A and MAT2B are expressed in extrahepatic tissues as well as non-parenchymal cells of the liver(e.g.,hepatic stellate and Kupffer cells).The biosynthesis of SAMe is impaired in patients with chronic liver disease and liver cancer due to decreased expression and inactivation of MATα1.A switch from MAT1A to MAT2A/MAT2B occurs in multiple liver diseases and during liver growth and dedifferentiation,but this change in the expression pattern of MATs results in reduced hepatic SAMe level.Decades of study have utilized the Mat1a-knockout(KO)mouse that spontaneously develops non-alcoholic steatohepatitis(NASH)and hepatocellular carcinoma(HCC)to elucidate a variety of mechanisms by which MAT proteins dysregulation contributes to liver carcinogenesis.An increasing volume of work indicates that MATs have SAMe-independent functions,distinct interactomes and multiple subcellular localizations.Here we aim to provide an overview of MAT biology including genes,isoenzymes and their regulation to provide the context for understanding consequences of their dysregulation.We will highlight recent breakthroughs in the field and underscore the importance of MAT’s in liver tumorigenesis as well as their potential as targets for cancer therapy.
文摘Pancreatic cysts are identified at an increasing frequency.Although mucinous cystic neoplasms represent a pre-malignant condition,the majority of these lesions do not progress to cancer.Over the last 10 years several societies have established guidelines for the diagnosis,initial evaluation and surveillance of these lesions.Here we provide an overview of five commonly used guidelines:2015 American Gastroenterological Association,2017 International Association of Pancreatology,American College of Gastroenterology 2018,European Study Group and American College of Radiology.We describe the similarities and differences between the methods used to formulate these guidelines,the population they target and their approaches towards initial evaluation and surveillance of cystic lesions.
文摘Hepatitis B virus (HBV) infection affects a large part of the world population. Within the different virological HBV categories that have been identified, patients with occult HBV infection represent a peculiar group. These individuals harbor a replication competent virus, inhibited in its replicative function. Accordingly, cases of reactivations have been observed in immunosuppressed individuals who lose immunological control over the infection. Patients with hematological malignancies (HM) are treated with intense myeloand immunosuppres-sive chemotherapy regimens which favor HBV reactivation. This event can have severe consequences, such as hepatitis flare, hepatic failure and even death. In addition, it can lead to delays or interruptions of curative treatments, resulting in a decreased disease free and overall survival. In this review, we will examine the event of HBV reactivation in patients with signs of resolved HBV infection undergoing treatment for HM and propose possible management strategies.
文摘While antimicrobials are clinically effective in preventing post-operative recurrence,the role for antibiotics in primary therapy for Crohn's disease(CD) remains unclear.The recent multicenter phase 2 trial by Prantera et al received wide attention because it demonstrated an increase in the week 12 remission rate in patients with moderately active CD treated with rifaximin and renewed interest in microbial manipulation as primary therapy for CD.In this commentary,we discuss aspects of durability,immune cell polarization,and safety of microbial manipulation as primary therapy for CD.
文摘BACKGROUND Only one case of liver transplantation for hepatic adenoma has previously been reported for patients with rupture and uncontrolled hemorrhage.We present the case of a massive ruptured hepatic adenoma with persistent hemorrhagic shock and toxic liver syndrome which resulted in a two-stage liver transplantation.This is the first case of a two-stage liver transplantation performed for a ruptured hepatic adenoma.CASE SUMMARY A 23 years old African American female with a history of pre-diabetes and oral contraceptive presented to an outside facility complaining of right-sided chest pain and emesis for one day.She was found to be in hemorrhagic shock due to a massive ruptured hepatic hepatic adenoma.She underwent repeated embolizations with interventional radiology with ongoing hemorrhage and the development of renal failure,hepatic failure,and hemodynamic instability,known as toxic liver syndrome.In the setting of uncontrolled hemorrhage and toxic liver syndrome,a hepatectomy with porto-caval anastomosis was performed with liver transplantation 15 h later.She tolerated the anhepatic stage well,and has done well over one year later.CONCLUSION When toxic liver syndrome is recognized,liver transplantation with or withouthepatectomy should be considered before the patient becomes unstable.
基金This work was supported by the National Institutes of Health(NIH)grants R01DK085252,R01AA027036,R21AA025841 and a Winnick Research Award from Cedars-Sinai Medical Center.
文摘Heavy alcohol use is the cause of alcoholic liver disease(ALD).The ALD spectrum ranges from alcoholic steatosis to steatohepatitis,fibrosis,and cirrhosis.In Western countries,approximately 50%of cirrhosis-related deaths are due to alcohol use.While alcoholic cirrhosis is no longer considered a completely irreversible condition,no effective anti-fibrotic therapies are currently available.Another significant clinical aspect of ALD is alcoholic hepatitis(AH).AH is an acute inflammatory condition that is often comorbid with cirrhosis,and severe AH has a high mortality rate.Therapeutic options for ALD are limited.The established treatment for AH is corticosteroids,which improve short-term survival but do not affect long-term survival.Liver transplantation is a curative treatment option for alcoholic cirrhosis and AH,but patients must abstain from alcohol use for 6 months to qualify.Additional effective therapies are needed.The molecular mechanisms underlying ALD are complex and have not been fully elucidated.Various molecules,signaling pathways,and crosstalk between multiple hepatic and extrahepatic cells contribute to ALD progression.This review highlights established and emerging concepts in ALD clin-icopathology,their underlying molecular mechanisms,and current and future ALD treatment options.
文摘Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA)constitute the main subtypes of primary liver cancers(PLCs)as a major cause of cancer-related mortality and incidence.They emerge from varying quantities and levels of differentiation among major liver cells,comprising hepatocytes,mucin-or non-mucin-producing cholangiocytes,and hepatic progenitor cells(HPCs)with the capability to differentiate into either hepatocytes or cholangiocytes.
文摘Background:Bariatric surgery represents an important treatment option for severely obese patients with nonalcoholic fatty liver disease(NAFLD).However,there remains inadequate data regarding the effects of different bariatric procedures on various NAFLD parameters,especially for histological outcomes.Thus,this meta-analysis aimed to compare the effects of restrictive bariatric procedures and foregut bypass on the metabolic,biochemical,and histological parameters for patients with NAFLD.Methods:Medline and Embase were searched for articles relating to bariatric procedures and NAFLD.Pairwise meta-analysis was conducted to compare efficacy of bariatric procedures pre-vs.post-procedure with subgroup analysis to further compare restrictive against foregut bypass procedures.Results:Thirty-one articles involving 3,355 patients who underwent restrictive bariatric procedures(n=1,460)and foregut bypass(n=1,895)were included.Both foregut bypass(P<0.01)and restrictive procedures(P=0.03)significantly increased odds of fibrosis resolution.Compared to restrictive procedures,foregut bypass resulted in a borderline non-significant decrease in fibrosis score(P=0.06)and significantly lower steatosis score(P<0.001).For metabolic parameters,foregut bypass significantly lowered body mass index(P=0.003)and low-density lipoprotein(P=0.008)compared to restrictive procedures.No significant differences were observed between both procedures for aspartate aminotransferase(P=0.17)and alkaline phosphatase(P=0.61).However,foregut bypass resulted in significantly lower gamma-glutamyl transferase than restrictive procedures(P=0.01)while restrictive procedures resulted in significantly lower alanine transaminase than foregut bypass(P=0.02).Conclusions:The significant histological and metabolic advantages and comparable improvements in biochemical outcomes support the choice of foregut bypass over restrictive bariatric procedures in NAFLD management.
基金supported by Beijing Municipal Science and Technology Commission Funding Project[Z161100000116058]302 Military Hospital Project[YNKT 2014006].
文摘Introduction Hepatic sinusoidal obstruction syndrome(HSOS)is a hepatic vascular disease characterized by injury of the endothelial cells in the sinusoidal hepatic and interlobular veins,intra-hepatic congestion,liver dysfunction,and portal hypertension[1].In Western countries,HSOS is often associated with myeloablative regimens used for hematopoietic stem-cell transplantation,while,in China,it is often associated with oral intake of Gynura segetum plants that contain pyrrolidine alkaloids[2].In addition,new-onset HSOS after solid-organ transplantation has received increasing attention[3-8].
文摘Introduction Peritoneal dialysis(PD)is widely used for the treatment of endstage renal disease.Patients treated with PD have similar outcomes to those treated with hemodialysis[1].However,PDrelated infections including peritonitis have been reported at 1.66 episodes per patient per year[2].One possible source of peritonitis is gastrointestinal(GI)endoscopic procedures.In 2005,the International Society for Peritoneal Dialysis(ISPD)published guidelines suggesting antibiotics be given to PD patients prior to colonoscopy[3].This suggestion was mostly based on expert opinion and a theoretical concern that patients undergoing colonoscopy are at increased risk for enteric peritonitis from bacterial translocation across the bowel wall.While there is no direct evidence to support this theory,case reports have suggested a risk of transient bacteremia associated with colonoscopy.
文摘Background and Aims:Hispanic patients with primary bili-ary cholangitis (PBC) have reduced rates of biochemical re-sponse to ursodeoxycholic acid (UDCA) and increased risk of disease progression compared to non-Hispanic patients. In this study, we sought to identify differences in demographics, comorbidities, environmental risk factors and socioeconomic status between Hispanic and non-Hispanic patients with PBC. Methods: In a case control study, we analyzed data from Hispanic (n=37 females and 1 male) and non-Hispanic (n=54 females and 4 males) patients with PBC seen at the University of Miami/Jackson Memorial Hospital from January 1998 through January 2013. Data were obtained by filling out a questionnaire either via phone call, mail, or e-mail. Odds ratios were calculated to measure the association between exposure and outcomes.Results: Baseline demographics, environmental risk factors and comorbidities were similar be-tween Hispanic and non-Hispanic patients with PBC. Hispanic patients were less likely to be married and fewer Hispanics had education beyond high school level compared to non-His-panics. Sixty four percent of Hispanic patients had a house-hold income of less than$50000, compared to 19.5% of non-Hispanics. Fewer Hispanic patients with PBC had health insur-ance coverage compared to non-Hispanics (86.5% vs. 98.1%;odds ratio: 0.1, 95% confidence interval: 0-0.9). Conclusions: Differences in disease severity and response to therapy observed in prior studies could not be explained by environmental exposures. In addition to genetic variation, socioeconomic discrepancies (access to care) may further ex-plain these differences.
文摘Background and Aims:Pharmaceutical therapy for NASH is associated with lipid modulation,but the consensus on drug treatment is limited and lacks comparative analysis of effectiveness.A network meta-analysis was conducted to compare NASH drug classes in lipid modulation.Methods:Online databases were searched for randomized controlled trails(RCTs)evaluating NASH treatments in biopsy-proven NASH patients.Treatments were classified into four groups:(1)inflammation,(2)energy,(3)bile acids,and(4)fibro-sis based on the mechanism of action.A Bayesian network analysis was conducted with outcome measured by mean difference(MD)with credible intervals(Crl)and surface un-der the cumulative ranking curve(SUCRA).Results:Forty-four RCTs were included in the analysis.Bile acid modulat-ing treatments(MD:0.05,Crl:0.03-0.07)were the best treatment for improvement in high-density lipid(HDL)cho-lesterol,followed by treatments modulating energy(MD:0.03,Crl:0.02-0.04)and fibrosis(MD:0.01,Crl:−0.12 to 0.14)compared with placebo.The top three treatments for reduction in triglycerides were treatments modulating energy(MD:−0.46,Crl:−0.49 to−0.43),bile acids(MD:−0.22,Crl:−0.35 to−0.09),and inflammation(MD:−0.08,Crl:−0.13 to−0.03)compared with placebo.SUCRA found treatment modulating fibrosis(MD:−1.27,Crl:−1.76 to−0.79)was the best treatment for reduction in low-density lipid(LDL)cholesterol followed by treatment modulating in-flammation(MD:−1.03,Crl:−1.09 to−0.97)and energy(MD:−0.37,Crl:−0.39 to−0.34)compared with placebo,but LDL cholesterol was worsened by treatments modulat-ing bile acids.Conclusions:Network analysis comparing the class effects of dyslipidemia modulation in NASH found that treatment targets can include optimization of athero-genic dyslipidemia.Future studies are required to evaluate the cardiovascular outcomes.
基金NIH grants R01DK085252 and R21AA025841,and Winnick Research award from Cedars-Sinai Medical CenterQinglan Wang is supported by National Natural Science Foundation of China(81573810,81270053)China Postdoctoral Science Foundation(2015T80445).
文摘Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide,which affects 25%of the general adult population and 70–80%of individuals with obesity and diabetes(1).
