This review provides an overview of the current state of the art of magnetic resonance spectroscopy (MRS) in in vivo investigations of diffuse liver disease. So far, MRS of the human liver in vivo has mainly been used...This review provides an overview of the current state of the art of magnetic resonance spectroscopy (MRS) in in vivo investigations of diffuse liver disease. So far, MRS of the human liver in vivo has mainly been used as a research tool rather than a clinical tool. The liver is particularly suitable for static and dynamic metabolic studies due to its high metabolic activity. Furthermore, its relatively superfi cial position allows excellent MRS localization, while its large volume allows detection of signals with relatively low intensity. This review describes the application of MRS to study the metabolic consequences of different conditions including diffuse and chronic liver diseases, congenital diseases, diabetes, and the presence of a distant malignancy on hepatic metabolism. In addition, future prospects of MRS are discussed. It is anticipated that future technical developments such as clinical MRS magnets with higher fi eld strength (3 T) and improved delineation of multicomponent signals such as phosphomonoester and phosphodiester using proton decoupling, especially if combined with price reductions for stable isotope tracers, will lead to intensifi ed research into metabolic syndrome, cardiovascular disease, hepato-biliary diseases, as well as non-metastatic liver metabolism in patients with a distant malignant tumor.展开更多
Diabetes mellitus(DM) that occurs because of chronic liver disease(CLD) is known as hepatogenous diabetes(HD). Although the association of diabetes and liver cirrhosis was described forty years ago, it was scarcely st...Diabetes mellitus(DM) that occurs because of chronic liver disease(CLD) is known as hepatogenous diabetes(HD). Although the association of diabetes and liver cirrhosis was described forty years ago, it was scarcely studied for long time. Patients suffering from this condition have low frequency of risk factors of type 2 DM. Its incidence is higher in CLD of viral, alcoholic and cryptogenic etiology. Its pathophysiology relates to liver damage, pancreatic dysfunction, interactions between hepatitis C virus(HCV) and glucose metabolism mechanisms and genetic susceptibility. It associates with increased rate of liver complications and hepatocellular carcinoma, and decreased 5-year survival rate. It reduces sustained virological response in HCV infected patients. In spite of these evidences, the American Diabetes Association does not recognize HD. In addition, the impact of glucose control on clinical outcomes of patients has not been evaluated. Treatment of diabetes may be difficult due to liver insufficiency and hepatotoxicity of antidiabetic drugs. Notwithstanding, no therapeutic guidelines have been implemented up to date. In this editorial, authors discuss the reasons why they think that HD may be a neglected pathological condition and call attention to the necessity for more clinical research on different fields of this disease.展开更多
Hepatic glycogenosis(HG) is characterized by excessive glycogen accumulation in hepatocytes and represents a hepatic complication of diabetes that particularly occurs in patients with longstanding poorly controlled ty...Hepatic glycogenosis(HG) is characterized by excessive glycogen accumulation in hepatocytes and represents a hepatic complication of diabetes that particularly occurs in patients with longstanding poorly controlled type 1 diabetes(T1D). HG has been reported to be a very rare disease, although it is believed to be extremely underdiagnosed because it is not possible to distinguish it from non-alcoholic fatty liver disease(NAFLD) unless a liver biopsy is performed. In contrast to HG, NAFLD is characterized by liver fat accumulation and is the more likely diagnosis for patients with type 2 diabetes and metabolic syndrome. The pathogenesis of HG involves the concomitant presence of insulin and excess glucose, which increases glycogen storage in the liver. HG is characterized by a transient elevation in liver transaminases and hepatomegaly. Differentiating between these two conditions is of the utmost importance because HG is a benign disease that is potentially reversible by improving glycemic control, whereas NAFLD can progress to cirrhosis. Therefore, HG should be suspected when liver dysfunction occurs in patients with poorly controlled T1 D. The aim of this article is to review the epidemiology, clinical characteristics, pathogenesis and histology of HG.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a common comorbidity with type 2 diabetes.The existing therapeutic options for NAFLD are not adequate.Hypocaloric diet and exercise is the cornerstone of therapy i...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a common comorbidity with type 2 diabetes.The existing therapeutic options for NAFLD are not adequate.Hypocaloric diet and exercise is the cornerstone of therapy in NAFLD.Pioglitazone is the only drug recommended in diabetes patients with biopsy proven non-alcoholic steatohepatitis.The frequent coexistence of NAFLD and type 2 diabetes with their combined adverse health consequences and inadequate therapeutic options makes it necessary to search for newer alternatives.AIM To assess the effect of sodium glucose cotransporter-2(SGLT-2)inhibitors on liver enzymes in type 2 diabetes patients with NAFLD.METHODS We searched PubMed/MEDLINE,Cochrane library,Google scholar,and Clinicaltrials.gov for the relevant articles to be included in this systematic review.Human studies done in type 2 diabetes patients with NAFLD treated with SGLT-2 inhibitors for at least 12 wk were included.Data from eight studies(four randomised controlled trials and four observational studies)were extracted and a narrative synthesis was done.A total of 214 patients were treated with SGLT-2 inhibitors in these studies(94 in randomised controlled trials and 120 in observational studies).RESULTS The primary outcome measure was change in serum alanine aminotransferase level.Out of eight studies,seven studies showed a significant decrease in serum alanine aminotransferase level.Most of the studies revealed reduction in serum level of other liver enzymes like aspartate aminotransferase and gamma glutamyl transferase.Five studies that reported a change in hepatic fat exhibited a significant reduction in hepatic fat content in those treated with SGLT-2 inhibitors.Likewise,among the three studies that evaluated a change in indices of hepatic fibrosis,two studies revealed a significant improvement in liver fibrosis.Moreover,there was an improvement in obesity,insulin resistance,glycaemia,and lipid parameters in those subjects taking SGLT-2 inhibitors.The studies disclosed that about 17%(30/176)of the subjects taking SGLT-2 inhibitors developed adverse events and more than 40%(10/23)of them had genitourinary tract infections.CONCLUSION Based on low to moderate quality of evidence,SGLT-2 inhibitors improve the serum level of liver enzymes,decrease liver fat,and fibrosis with additional beneficial effects on various metabolic parameters in type 2 diabetes patients with NAFLD.展开更多
Nonalcoholic fatty liver disease(NAFLD)is the most prevalent chronic liver disease in the world and represents a clinical-histopathologic entity where the steatosis component may vary in degree and may or may not have...Nonalcoholic fatty liver disease(NAFLD)is the most prevalent chronic liver disease in the world and represents a clinical-histopathologic entity where the steatosis component may vary in degree and may or may not have fibrotic progression.The key concept of NAFLD pathogenesis is excessive triglyceride hepatic accumulation because of an imbalance between free fatty acid influx and efflux.Strong epidemiological,biochemical,and therapeutic evidence supports the premise that the primary pathophysiological derangement in most patients with NAFLD is insulin resistance;thus the association between diabetes and NAFLD is widely recognized in the literature.Since NAFLD is the hepatic manifestation of a metabolic disease,it is also associated with a higher cardiovascular risk.Conventional B-mode ultrasound is widely adopted as a first-line imaging modality for hepatic steatosis,although magnetic resonance imaging represents the gold standard noninvasive modality for quantifying the amount of fat in these patients.Treatment of NAFLD patients depends on the disease severity,ranging from a more benign condition of nonalcoholic fatty liver to nonalcoholic steatohepatitis.Abstinence from alcohol,a Mediterranean diet,and modification of risk factors are recommended for patients suffering from NAFLD to avoid major cardiovascular events,as per all diabetic patients.In addition,weight loss induced by bariatric surgery seems to also be effective in improving liver features,together with the benefits for diabetes control or resolution,dyslipidemia,and hypertension.Finally,liver transplantation represents the ultimate treatment for severe nonalcoholic fatty liver disease and is growing rapidly as a main indication in Western countries.This review offers a comprehensive multidisciplinary approach to NAFLD,highlighting its connection with diabetes.展开更多
BACKGROUND Non-alcoholic fatty liver disease has become the most common chronic liver disease worldwide,which originates from the accumulation of triglyceride(TG)in the liver.Patients with type 2 diabetes mellitus(T2D...BACKGROUND Non-alcoholic fatty liver disease has become the most common chronic liver disease worldwide,which originates from the accumulation of triglyceride(TG)in the liver.Patients with type 2 diabetes mellitus(T2DM)are considered to have a predisposition to hepatic steatosis.However,the influencing factors for hepatic fat accumulation in T2DM patients remain unclear.AIM To investigate the influencing factors for hepatic fat accumulation in T2DM patients.METHODS We enrolled 329 T2DM patients admitted to the Endocrinology Department of the First Affiliated Hospital of Soochow University,who underwent MR mDIXONQuant examination to quantify the hepatic fat fraction(HFF).According to body mass index(BMI),the patients were divided into normal weight,overweight,and obese groups.The differences in general statistics,biochemical parameters,islet function,and HFF were compared among the three groups.The associations between HFF and other parameters and the influences of various parameters on the severity of hepatic fat accumulation were analyzed.RESULTS The HFF of T2DM patients gradually increased in the normal weight,overweight,and obese groups(P<0.05).Spearman correlation analysis showed that in T2DM patients,HFF was negatively correlated with age and high-density lipoprotein cholesterol(P<0.05),whereas it was positively correlated with BMI,waist-hip ratio,fasting plasma glucose,alanine aminotransferase(ALT),aspartate aminotransferase,bilirubin,glutamyl transpeptidase,lactate dehydrogenase,albumin(ALB),uric acid(UA),total cholesterol,TG,low-density lipoprotein cholesterol(LDL-C),C-reactive protein,free triiodothyronine,fasting insulin,fasting C-peptide,and homeostasis model assessment of insulin resistance(P<0.05).Multiple linear regression analysis showed significant positive influences of BMI,ALT,LDL-C,UA,and ALB on HFF in T2DM patients(P<0.05).Binary logistic regression analysis showed that BMI,ALT,ALB,and LDL-C were independent risk factors for moderate to severe fatty liver in T2DM patients,and obesity increased the risk of being complicated with moderate to severe fatty liver by 4.03 times(P<0.05).CONCLUSION The HFF of T2DM patients increases with BMI.Higher BMI,ALT,ALB,and LDLC are independent risk factors for moderate to severe fatty liver in T2DM patients.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in people with diabetes with no available treatment.AIM To explore the effect of testosterone treatment on liver.Testosterone therapy improves ins...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in people with diabetes with no available treatment.AIM To explore the effect of testosterone treatment on liver.Testosterone therapy improves insulin resistance and reduces total body fat,but its impact on the liver remains poorly studied.METHODS This secondary analysis of a 40 wk,randomised,double-blinded,placebocontrolled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone concentrations evaluated the change in hepatic steatosis as measured by liver fat fraction on magnetic resonance imaging(MRI).RESULTS Of 88 patients enrolled in the index study,39 had liver MRIs of whom 20 received testosterone therapy and 19 received placebo.All patients had>5%hepatic steatosis at baseline and 38 of 39 patients met diagnostic criteria for NAFLD.Median liver fat at baseline was 15.0%(IQR 11.5%-21.1%)in the testosterone and 18.4%(15.0%-28.9%)in the placebo group.Median ALT was 34units/L(26-38)in the testosterone and 32units/L(25-52)in the placebo group.At week 40,patients receiving testosterone had a median reduction in absolute liver fat of 3.5%(IQR 2.9%-6.4%)compared with an increase of 1.2%in the placebo arm(between-group difference 4.7%P<0.001).After controlling for baseline liver fat,testosterone therapy was associated with a relative reduction in liver fat of 38.3%(95%confidence interval 25.4%-49.0%,P<0.001).CONCLUSION Testosterone therapy was associated with a reduction in hepatic steatosis in men with diabetes and low serum testosterone.Future randomised studies of testosterone therapy in men with NAFLD focusing on liver-related endpoints are therefore justified.展开更多
The recently proposed nomenclature change from non-alcoholic fatty liver disease to metabolic dysfunction-associated fatty liver disease(MAFLD)has resulted in the reappraisal of epidemiological trends and associations...The recently proposed nomenclature change from non-alcoholic fatty liver disease to metabolic dysfunction-associated fatty liver disease(MAFLD)has resulted in the reappraisal of epidemiological trends and associations with other chronic diseases.In this context,MAFLD appears to be tightly linked to incident chronic kidney disease(CKD).This association may be attributed to multiple shared risk factors including type 2 diabetes mellitus,arterial hypertension,obesity,dyslipidemia,and insulin resistance.Moreover,similarities in their molecular pathophysiologic mechanisms can be detected,since inflammation,oxidative stress,fibrosis,and gut dysbiosis are highly prevalent in these pathologic states.At the same time,lines of evidence suggest a genetic predisposition to MAFLD due to gene polymorphisms,such as the PNPLA3 rs738409 G allele polymorphism,which may also propagate renal dysfunction.Concerning their management,available treatment considerations for obesity(bariatric surgery)and novel antidiabetic agents(glucagon-like peptide 1 receptor agonists,sodiumglucose co-transporter 2 inhibitors)appear beneficial in preclinical and clinical studies of MAFLD and CKD modeling.Moreover,alternative approaches such as melatonin supplementation,farnesoid X receptor agonists,and gut microbiota modulation may represent attractive options in the future.With a look to the future,additional adequately sized studies are required,focusing on preventing renal complications in patients with MAFLD and the appropriate management of individuals with concomitant MAFLD and CKD.展开更多
Helicobacter pylori(H. pylori) is an ancient microorganism that has co-evolved with humans for over 60000 years. This bacterium typically colonizes the human stomach and it is currently recognized as the most common i...Helicobacter pylori(H. pylori) is an ancient microorganism that has co-evolved with humans for over 60000 years. This bacterium typically colonizes the human stomach and it is currently recognized as the most common infectious pathogen of the gastroduodenal tract. Although its chronic infection is associated with gastritis, peptic ulcer, dysplasia, neoplasia, MALT lymphoma and gastric adenocarcinoma, it has been suggested the possible association of H. pylori infection with several extragastric effects including hepatobiliary and pancreatic diseases. Since a microorganism resembling H. pylori was detected in samples from patients with hepatobiliary disorders, several reports have been discussed the possible role of bacteria in hepatic diseases as hepatocellular carcinoma, cirrhosis and hepatic encephalopathy, nonalcoholic fatty liver disease and fibrosis. Additionally, studies have reported the possible association between H. pylori infection and pancreatic diseases, especially because it has been suggested that this infection could change the pancreatic physiology. Some of them have related a possible association between the microorganism and pancreatic cancer. H. pylori infection has also been suggested to play a role in the acute and chronic pancreatitis pathogenesis, autoimmune pancreatitis, diabetes mellitus and metabolic syndrome. Considering that association of H. pylori to liver and pancreas diseases needs further clarification, our work offers a review about the results of some investigations related to the potential pathogenicity of H. pylori in these extragastric diseases.展开更多
Due to the energy-dense but nutrient-deficient diets,sedentary lifestyle and lack of exercise as well as an aging population,the prevalence and incidence of overweight/obesity/sarcopenic obesity,type 2 diabetes mellit...Due to the energy-dense but nutrient-deficient diets,sedentary lifestyle and lack of exercise as well as an aging population,the prevalence and incidence of overweight/obesity/sarcopenic obesity,type 2 diabetes mellitus(T2DM),metabolic syndrome and their related non-alcoholic fatty liver disease(NAFLD)have been increasing globally in the last two decades.In Europe and the United States,NAFLD has become the second leading cause of end-stage liver disease and liver transplantation(1).Worse still,the onset age of NAFLD is becoming younger tendency.Although the new nomenclature of metabolic dysfunction-associated fatty liver disease(MAFLD)has been proposed for 3 years,MAFLD is not equivalent to NAFLD,and few epidemiologic investigations on MAFLD to date.Therefore,this invited editorial is focus on the global epidemiology of NAFLD and the major impact on China.展开更多
Long-term nucleos(t)ide analogue therapy in chronic hepatitis B virus(HBV)infection is effective in suppressing viral replication and reducing liver-related complications. However, HBV-related liver events can still o...Long-term nucleos(t)ide analogue therapy in chronic hepatitis B virus(HBV)infection is effective in suppressing viral replication and reducing liver-related complications. However, HBV-related liver events can still occur in different patient sub-groups. There is emerging evidence that, similar to chronic hepatitis C virus infection, metabolic risk factors may play a role in the disease process of chronic HBV. While the mechanistic nature of metabolic-HBV interactions remains uncertain, studies in different HBV-infected populations have demonstrated that hepatic steatosis, increased body-mass index, diabetes, or a combination of different metabolic risk factors are associated with an increased risk of hepatocellular carcinoma and cirrhosis. The impact of metabolic risk factors is especially prominent in patients with quiescent virological activity,including on-treatment patients with effective viral suppression. As the proportion of on-treatment chronic HBV patients increases worldwide,longitudinal studies determining the relative risks of different metabolic parameters with respect to clinical outcomes are needed. Future studies should also determine if metabolic-directed interventions can improve disease outcomes in chronic HBV.展开更多
Hepatitis C virus(HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders in...Hepatitis C virus(HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease.展开更多
BACKGROUND Hereditary hemochromatosis(HH)has an increased risk of hepatocellular cancer(HCC)both due to genetic risks and iron overload as iron overload can be carcinogenic;HH impacts the increasing risk of HCC,not on...BACKGROUND Hereditary hemochromatosis(HH)has an increased risk of hepatocellular cancer(HCC)both due to genetic risks and iron overload as iron overload can be carcinogenic;HH impacts the increasing risk of HCC,not only through the development of cirrhosis but concerning hepatic iron deposition,which has been studied further recently.AIM To evaluate HH yearly trends,patient demographics,symptoms,comorbidities,and hospital outcomes.The secondary aim sheds light on the risk of iron overload for developing HCC in HH patients,independent of liver cirrhosis complications.The study investigated HH(without cirrhosis)as an independent risk factor for HCC.METHODS We analyzed data from National Inpatient Sample(NIS)Database,the largest national inpatient data collection in the United States,and selected HH and HCC cohorts.HH was first defined in 2011 International Classification of Disease-9th edition(ICD-9)as a separate diagnosis;the HH cohort is extracted from January 2011 to December 2019 using 275.01(ICD-9)and E83.110(ICD-10)diagnosis codes of HH.Patients were excluded from the HH cohort if they had a primary or secondary diagnostic code of cirrhosis(alcoholic,non-alcoholic,and biliary),viralhepatitis,alcoholic liver disease,non-alcoholic fatty liver disease(NAFLD),and non-alcoholic steatohepatitis(NASH).We removed these patients from the HH cohort to rule out bias or ICD-10 diagnostic errors.The HCC cohort is selected from January 2011 to December 2019 using the ICD-9 and ICD-10 codes of HCC.We selected a non-HCC cohort with the 1:1 fixed ratio nearest neighbor(greedy)propensity score method using the patients'age,gender,and race.We performed multivariate analysis for the risk factors of HCC in the HCC and non-HCC matched cohort.We further analyzed HH without cirrhosis(removing HH patients with a diagnosis of cirrhosis)as an independent risk factor of HCC after adjusting all known risk factors of HCC in the multivariate model.RESULTS During the 2011-2019 period,a total of 18031 hospitalizations with a primary or secondary diagnosis of HH(excluding liver diseases)were recorded in the NIS database.We analyzed different patients’characteristics,and we found increments in inpatient population trend with a Ptrend<0.001 and total hospital cost of care trend from$42957 in 2011 to$66152 in 2019 with a Ptrend<0.001 despite no change in Length of Stay over the last decade.The multivariate analyses showed that HH without cirrhosis(aOR,28.8;95%CI,10.4–80.1;P<0.0001),biliary cirrhosis(aOR,19.3;95%CI,13.4–27.6;P<0.0001),non-alcoholic cirrhosis(aOR,17.4;95%CI,16.5–18.4;P<0.0001),alcoholic cirrhosis(aOR,16.9;95%CI,15.9–17.9;P<0.0001),hepatitis B(aOR,12.1;95%CI,10.85–13.60;P<0.0001),hepatitis C(aOR,8.58;95%CI,8.20–8.98;P<0.0001),Wilson disease(aOR,4.27;95%CI,1.18–15.41;P<0.0001),NAFLD or NASH(aOR,2.96;95%CI,2.73–3.20;P<0.0001),alpha1-antitrypsin deficiency(aOR,2.10;95%CI,1.21–3.64;P<0.0001),diabetes mellitus without chronic complications(aOR,1.17;95%CI,1.13–1.21;P<0.0001),and blood transfusion(aOR,1.80;95%CI,1.69–1.92;P<0.0001)are independent risk factor for liver cancer.CONCLUSION Our study showed an increasing trend of in-hospital admissions of HH patients in the last decade.These trends were likely related to advances in diagnostic approach,which can lead to increased hospital utilization and cost increments.Still,the length of stay remained the same,likely due to a big part of management being done in outpatient settings.Another vital part of our study is the significant result that HH without cirrhosis is an independent risk factor for HCC with adjusting all known risk factors.More prospective and retrospective large studies are needed to re-evaluate the HH independent risk in developing HCC.展开更多
BACKGROUND Hepatitis B virus is a viral infection that can lead to acute and/or chronic liver disease, and hepatocellular carcinoma(HCC). Hepatitis B vaccination is 95% effective in preventing infection and the develo...BACKGROUND Hepatitis B virus is a viral infection that can lead to acute and/or chronic liver disease, and hepatocellular carcinoma(HCC). Hepatitis B vaccination is 95% effective in preventing infection and the development of chronic liver disease and HCC due to hepatitis B. In 2011, the Centers for Disease Control updated their guidelines recommending that adults at high-risk for hepatitis B infection be vaccinated against hepatitis B including those with diabetes mellitus(DM). We hypothesize that adults at high-risk for hepatitis B infection are not being adequately screened and/or vaccinated for hepatitis B in a large urban healthcare system.AIM To investigate clinical factors associated with Hepatitis B screening and vaccination in patients at high-risk for Hepatitis B infection.METHODS We conducted a retrospective review of 999 patients presenting at a large urban healthcare system from 2012-2017 at high-risk for hepatitis B infection. Patients were considered high-risk for hepatitis B infection based on hepatitis B practice recommendations from the Center for Disease Control. Medical history including hepatitis B serology, concomitant medical diagnoses, demographics, insurance status and social history were extracted from electronic health records.Multivariate logistic regression was used to identify clinical risk factors independently associated with hepatitis B screening and vaccination.RESULTS Among the 999 patients, 556(55.7%) patients were screened for hepatitis B. Of those who were screened, only 242(43.5%) patients were vaccinated against hepatitis B. Multivariate regression analysis revealed end-stage renal disease[odds ratio(OR): 5.122; 2.766-9.483], alcoholic hepatitis(OR: 3.064; 1.020-9.206),and cirrhosis or end-stage liver disease(OR: 1.909; 1.095-3.329); all P < 0.05 were associated with hepatitis B screening, while age(OR: 0.785; 0.680-0.906),insurance status(0.690; 0.558-0.854), history of DM(OR: 0.518; 0.364-0.737), and human immunodeficiency virus(OR: 0.443; 0.273-0.718); all P < 0.05 were instead not associated with hepatitis B screening. Of the adults vaccinated for hepatitis B,multivariate regression analysis revealed age(OR: 0.755; 0.650-0.878) and DM were not associated with hepatitis B vaccination(OR: 0.620; 0.409-0.941) both P <0.05.CONCLUSION Patients at high-risk for hepatitis B are not being adequately screened and/or vaccinated. Improvements in hepatitis B vaccination should be strongly encouraged by all healthcare systems.展开更多
文摘This review provides an overview of the current state of the art of magnetic resonance spectroscopy (MRS) in in vivo investigations of diffuse liver disease. So far, MRS of the human liver in vivo has mainly been used as a research tool rather than a clinical tool. The liver is particularly suitable for static and dynamic metabolic studies due to its high metabolic activity. Furthermore, its relatively superfi cial position allows excellent MRS localization, while its large volume allows detection of signals with relatively low intensity. This review describes the application of MRS to study the metabolic consequences of different conditions including diffuse and chronic liver diseases, congenital diseases, diabetes, and the presence of a distant malignancy on hepatic metabolism. In addition, future prospects of MRS are discussed. It is anticipated that future technical developments such as clinical MRS magnets with higher fi eld strength (3 T) and improved delineation of multicomponent signals such as phosphomonoester and phosphodiester using proton decoupling, especially if combined with price reductions for stable isotope tracers, will lead to intensifi ed research into metabolic syndrome, cardiovascular disease, hepato-biliary diseases, as well as non-metastatic liver metabolism in patients with a distant malignant tumor.
基金Supported by the Department of Endocrinology and Service of Gastroenterology of the Faculty of MedicineAutonomous University of Nuevo Leon
文摘Diabetes mellitus(DM) that occurs because of chronic liver disease(CLD) is known as hepatogenous diabetes(HD). Although the association of diabetes and liver cirrhosis was described forty years ago, it was scarcely studied for long time. Patients suffering from this condition have low frequency of risk factors of type 2 DM. Its incidence is higher in CLD of viral, alcoholic and cryptogenic etiology. Its pathophysiology relates to liver damage, pancreatic dysfunction, interactions between hepatitis C virus(HCV) and glucose metabolism mechanisms and genetic susceptibility. It associates with increased rate of liver complications and hepatocellular carcinoma, and decreased 5-year survival rate. It reduces sustained virological response in HCV infected patients. In spite of these evidences, the American Diabetes Association does not recognize HD. In addition, the impact of glucose control on clinical outcomes of patients has not been evaluated. Treatment of diabetes may be difficult due to liver insufficiency and hepatotoxicity of antidiabetic drugs. Notwithstanding, no therapeutic guidelines have been implemented up to date. In this editorial, authors discuss the reasons why they think that HD may be a neglected pathological condition and call attention to the necessity for more clinical research on different fields of this disease.
文摘Hepatic glycogenosis(HG) is characterized by excessive glycogen accumulation in hepatocytes and represents a hepatic complication of diabetes that particularly occurs in patients with longstanding poorly controlled type 1 diabetes(T1D). HG has been reported to be a very rare disease, although it is believed to be extremely underdiagnosed because it is not possible to distinguish it from non-alcoholic fatty liver disease(NAFLD) unless a liver biopsy is performed. In contrast to HG, NAFLD is characterized by liver fat accumulation and is the more likely diagnosis for patients with type 2 diabetes and metabolic syndrome. The pathogenesis of HG involves the concomitant presence of insulin and excess glucose, which increases glycogen storage in the liver. HG is characterized by a transient elevation in liver transaminases and hepatomegaly. Differentiating between these two conditions is of the utmost importance because HG is a benign disease that is potentially reversible by improving glycemic control, whereas NAFLD can progress to cirrhosis. Therefore, HG should be suspected when liver dysfunction occurs in patients with poorly controlled T1 D. The aim of this article is to review the epidemiology, clinical characteristics, pathogenesis and histology of HG.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a common comorbidity with type 2 diabetes.The existing therapeutic options for NAFLD are not adequate.Hypocaloric diet and exercise is the cornerstone of therapy in NAFLD.Pioglitazone is the only drug recommended in diabetes patients with biopsy proven non-alcoholic steatohepatitis.The frequent coexistence of NAFLD and type 2 diabetes with their combined adverse health consequences and inadequate therapeutic options makes it necessary to search for newer alternatives.AIM To assess the effect of sodium glucose cotransporter-2(SGLT-2)inhibitors on liver enzymes in type 2 diabetes patients with NAFLD.METHODS We searched PubMed/MEDLINE,Cochrane library,Google scholar,and Clinicaltrials.gov for the relevant articles to be included in this systematic review.Human studies done in type 2 diabetes patients with NAFLD treated with SGLT-2 inhibitors for at least 12 wk were included.Data from eight studies(four randomised controlled trials and four observational studies)were extracted and a narrative synthesis was done.A total of 214 patients were treated with SGLT-2 inhibitors in these studies(94 in randomised controlled trials and 120 in observational studies).RESULTS The primary outcome measure was change in serum alanine aminotransferase level.Out of eight studies,seven studies showed a significant decrease in serum alanine aminotransferase level.Most of the studies revealed reduction in serum level of other liver enzymes like aspartate aminotransferase and gamma glutamyl transferase.Five studies that reported a change in hepatic fat exhibited a significant reduction in hepatic fat content in those treated with SGLT-2 inhibitors.Likewise,among the three studies that evaluated a change in indices of hepatic fibrosis,two studies revealed a significant improvement in liver fibrosis.Moreover,there was an improvement in obesity,insulin resistance,glycaemia,and lipid parameters in those subjects taking SGLT-2 inhibitors.The studies disclosed that about 17%(30/176)of the subjects taking SGLT-2 inhibitors developed adverse events and more than 40%(10/23)of them had genitourinary tract infections.CONCLUSION Based on low to moderate quality of evidence,SGLT-2 inhibitors improve the serum level of liver enzymes,decrease liver fat,and fibrosis with additional beneficial effects on various metabolic parameters in type 2 diabetes patients with NAFLD.
文摘Nonalcoholic fatty liver disease(NAFLD)is the most prevalent chronic liver disease in the world and represents a clinical-histopathologic entity where the steatosis component may vary in degree and may or may not have fibrotic progression.The key concept of NAFLD pathogenesis is excessive triglyceride hepatic accumulation because of an imbalance between free fatty acid influx and efflux.Strong epidemiological,biochemical,and therapeutic evidence supports the premise that the primary pathophysiological derangement in most patients with NAFLD is insulin resistance;thus the association between diabetes and NAFLD is widely recognized in the literature.Since NAFLD is the hepatic manifestation of a metabolic disease,it is also associated with a higher cardiovascular risk.Conventional B-mode ultrasound is widely adopted as a first-line imaging modality for hepatic steatosis,although magnetic resonance imaging represents the gold standard noninvasive modality for quantifying the amount of fat in these patients.Treatment of NAFLD patients depends on the disease severity,ranging from a more benign condition of nonalcoholic fatty liver to nonalcoholic steatohepatitis.Abstinence from alcohol,a Mediterranean diet,and modification of risk factors are recommended for patients suffering from NAFLD to avoid major cardiovascular events,as per all diabetic patients.In addition,weight loss induced by bariatric surgery seems to also be effective in improving liver features,together with the benefits for diabetes control or resolution,dyslipidemia,and hypertension.Finally,liver transplantation represents the ultimate treatment for severe nonalcoholic fatty liver disease and is growing rapidly as a main indication in Western countries.This review offers a comprehensive multidisciplinary approach to NAFLD,highlighting its connection with diabetes.
基金Suzhou Health Committee and Science and Technology Bureau,No.KJXW2019005.
文摘BACKGROUND Non-alcoholic fatty liver disease has become the most common chronic liver disease worldwide,which originates from the accumulation of triglyceride(TG)in the liver.Patients with type 2 diabetes mellitus(T2DM)are considered to have a predisposition to hepatic steatosis.However,the influencing factors for hepatic fat accumulation in T2DM patients remain unclear.AIM To investigate the influencing factors for hepatic fat accumulation in T2DM patients.METHODS We enrolled 329 T2DM patients admitted to the Endocrinology Department of the First Affiliated Hospital of Soochow University,who underwent MR mDIXONQuant examination to quantify the hepatic fat fraction(HFF).According to body mass index(BMI),the patients were divided into normal weight,overweight,and obese groups.The differences in general statistics,biochemical parameters,islet function,and HFF were compared among the three groups.The associations between HFF and other parameters and the influences of various parameters on the severity of hepatic fat accumulation were analyzed.RESULTS The HFF of T2DM patients gradually increased in the normal weight,overweight,and obese groups(P<0.05).Spearman correlation analysis showed that in T2DM patients,HFF was negatively correlated with age and high-density lipoprotein cholesterol(P<0.05),whereas it was positively correlated with BMI,waist-hip ratio,fasting plasma glucose,alanine aminotransferase(ALT),aspartate aminotransferase,bilirubin,glutamyl transpeptidase,lactate dehydrogenase,albumin(ALB),uric acid(UA),total cholesterol,TG,low-density lipoprotein cholesterol(LDL-C),C-reactive protein,free triiodothyronine,fasting insulin,fasting C-peptide,and homeostasis model assessment of insulin resistance(P<0.05).Multiple linear regression analysis showed significant positive influences of BMI,ALT,LDL-C,UA,and ALB on HFF in T2DM patients(P<0.05).Binary logistic regression analysis showed that BMI,ALT,ALB,and LDL-C were independent risk factors for moderate to severe fatty liver in T2DM patients,and obesity increased the risk of being complicated with moderate to severe fatty liver by 4.03 times(P<0.05).CONCLUSION The HFF of T2DM patients increases with BMI.Higher BMI,ALT,ALB,and LDLC are independent risk factors for moderate to severe fatty liver in T2DM patients.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in people with diabetes with no available treatment.AIM To explore the effect of testosterone treatment on liver.Testosterone therapy improves insulin resistance and reduces total body fat,but its impact on the liver remains poorly studied.METHODS This secondary analysis of a 40 wk,randomised,double-blinded,placebocontrolled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone concentrations evaluated the change in hepatic steatosis as measured by liver fat fraction on magnetic resonance imaging(MRI).RESULTS Of 88 patients enrolled in the index study,39 had liver MRIs of whom 20 received testosterone therapy and 19 received placebo.All patients had>5%hepatic steatosis at baseline and 38 of 39 patients met diagnostic criteria for NAFLD.Median liver fat at baseline was 15.0%(IQR 11.5%-21.1%)in the testosterone and 18.4%(15.0%-28.9%)in the placebo group.Median ALT was 34units/L(26-38)in the testosterone and 32units/L(25-52)in the placebo group.At week 40,patients receiving testosterone had a median reduction in absolute liver fat of 3.5%(IQR 2.9%-6.4%)compared with an increase of 1.2%in the placebo arm(between-group difference 4.7%P<0.001).After controlling for baseline liver fat,testosterone therapy was associated with a relative reduction in liver fat of 38.3%(95%confidence interval 25.4%-49.0%,P<0.001).CONCLUSION Testosterone therapy was associated with a reduction in hepatic steatosis in men with diabetes and low serum testosterone.Future randomised studies of testosterone therapy in men with NAFLD focusing on liver-related endpoints are therefore justified.
文摘The recently proposed nomenclature change from non-alcoholic fatty liver disease to metabolic dysfunction-associated fatty liver disease(MAFLD)has resulted in the reappraisal of epidemiological trends and associations with other chronic diseases.In this context,MAFLD appears to be tightly linked to incident chronic kidney disease(CKD).This association may be attributed to multiple shared risk factors including type 2 diabetes mellitus,arterial hypertension,obesity,dyslipidemia,and insulin resistance.Moreover,similarities in their molecular pathophysiologic mechanisms can be detected,since inflammation,oxidative stress,fibrosis,and gut dysbiosis are highly prevalent in these pathologic states.At the same time,lines of evidence suggest a genetic predisposition to MAFLD due to gene polymorphisms,such as the PNPLA3 rs738409 G allele polymorphism,which may also propagate renal dysfunction.Concerning their management,available treatment considerations for obesity(bariatric surgery)and novel antidiabetic agents(glucagon-like peptide 1 receptor agonists,sodiumglucose co-transporter 2 inhibitors)appear beneficial in preclinical and clinical studies of MAFLD and CKD modeling.Moreover,alternative approaches such as melatonin supplementation,farnesoid X receptor agonists,and gut microbiota modulation may represent attractive options in the future.With a look to the future,additional adequately sized studies are required,focusing on preventing renal complications in patients with MAFLD and the appropriate management of individuals with concomitant MAFLD and CKD.
文摘Helicobacter pylori(H. pylori) is an ancient microorganism that has co-evolved with humans for over 60000 years. This bacterium typically colonizes the human stomach and it is currently recognized as the most common infectious pathogen of the gastroduodenal tract. Although its chronic infection is associated with gastritis, peptic ulcer, dysplasia, neoplasia, MALT lymphoma and gastric adenocarcinoma, it has been suggested the possible association of H. pylori infection with several extragastric effects including hepatobiliary and pancreatic diseases. Since a microorganism resembling H. pylori was detected in samples from patients with hepatobiliary disorders, several reports have been discussed the possible role of bacteria in hepatic diseases as hepatocellular carcinoma, cirrhosis and hepatic encephalopathy, nonalcoholic fatty liver disease and fibrosis. Additionally, studies have reported the possible association between H. pylori infection and pancreatic diseases, especially because it has been suggested that this infection could change the pancreatic physiology. Some of them have related a possible association between the microorganism and pancreatic cancer. H. pylori infection has also been suggested to play a role in the acute and chronic pancreatitis pathogenesis, autoimmune pancreatitis, diabetes mellitus and metabolic syndrome. Considering that association of H. pylori to liver and pancreas diseases needs further clarification, our work offers a review about the results of some investigations related to the potential pathogenicity of H. pylori in these extragastric diseases.
基金supported by the National Natural Science Foundation of China(Nos.82170593,81900507).
文摘Due to the energy-dense but nutrient-deficient diets,sedentary lifestyle and lack of exercise as well as an aging population,the prevalence and incidence of overweight/obesity/sarcopenic obesity,type 2 diabetes mellitus(T2DM),metabolic syndrome and their related non-alcoholic fatty liver disease(NAFLD)have been increasing globally in the last two decades.In Europe and the United States,NAFLD has become the second leading cause of end-stage liver disease and liver transplantation(1).Worse still,the onset age of NAFLD is becoming younger tendency.Although the new nomenclature of metabolic dysfunction-associated fatty liver disease(MAFLD)has been proposed for 3 years,MAFLD is not equivalent to NAFLD,and few epidemiologic investigations on MAFLD to date.Therefore,this invited editorial is focus on the global epidemiology of NAFLD and the major impact on China.
文摘Long-term nucleos(t)ide analogue therapy in chronic hepatitis B virus(HBV)infection is effective in suppressing viral replication and reducing liver-related complications. However, HBV-related liver events can still occur in different patient sub-groups. There is emerging evidence that, similar to chronic hepatitis C virus infection, metabolic risk factors may play a role in the disease process of chronic HBV. While the mechanistic nature of metabolic-HBV interactions remains uncertain, studies in different HBV-infected populations have demonstrated that hepatic steatosis, increased body-mass index, diabetes, or a combination of different metabolic risk factors are associated with an increased risk of hepatocellular carcinoma and cirrhosis. The impact of metabolic risk factors is especially prominent in patients with quiescent virological activity,including on-treatment patients with effective viral suppression. As the proportion of on-treatment chronic HBV patients increases worldwide,longitudinal studies determining the relative risks of different metabolic parameters with respect to clinical outcomes are needed. Future studies should also determine if metabolic-directed interventions can improve disease outcomes in chronic HBV.
文摘Hepatitis C virus(HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease.
基金Supported by National Science Council,Taiwan,NSC94-2314-B002-272,NSC94-3112-B-002-017,NSC95-3112-B-002-001,and NSC95-2314-B-002-244-M Y3,NSC98-2314-B-002,NSC99-2314-B-002-096,NSC102-2321-B-002-083National Taiwan University Hospital,and Liver Disease prevention and Treatment Research Foundation,NTUH 95M022,NTUH 98M 1227
文摘AIM: To investigate whether hepatitis B virus (HBV) and hepatitis C virus (HCV) increase risk of pancreatic ductal adenocarcinoma (PDAC).
文摘BACKGROUND Hereditary hemochromatosis(HH)has an increased risk of hepatocellular cancer(HCC)both due to genetic risks and iron overload as iron overload can be carcinogenic;HH impacts the increasing risk of HCC,not only through the development of cirrhosis but concerning hepatic iron deposition,which has been studied further recently.AIM To evaluate HH yearly trends,patient demographics,symptoms,comorbidities,and hospital outcomes.The secondary aim sheds light on the risk of iron overload for developing HCC in HH patients,independent of liver cirrhosis complications.The study investigated HH(without cirrhosis)as an independent risk factor for HCC.METHODS We analyzed data from National Inpatient Sample(NIS)Database,the largest national inpatient data collection in the United States,and selected HH and HCC cohorts.HH was first defined in 2011 International Classification of Disease-9th edition(ICD-9)as a separate diagnosis;the HH cohort is extracted from January 2011 to December 2019 using 275.01(ICD-9)and E83.110(ICD-10)diagnosis codes of HH.Patients were excluded from the HH cohort if they had a primary or secondary diagnostic code of cirrhosis(alcoholic,non-alcoholic,and biliary),viralhepatitis,alcoholic liver disease,non-alcoholic fatty liver disease(NAFLD),and non-alcoholic steatohepatitis(NASH).We removed these patients from the HH cohort to rule out bias or ICD-10 diagnostic errors.The HCC cohort is selected from January 2011 to December 2019 using the ICD-9 and ICD-10 codes of HCC.We selected a non-HCC cohort with the 1:1 fixed ratio nearest neighbor(greedy)propensity score method using the patients'age,gender,and race.We performed multivariate analysis for the risk factors of HCC in the HCC and non-HCC matched cohort.We further analyzed HH without cirrhosis(removing HH patients with a diagnosis of cirrhosis)as an independent risk factor of HCC after adjusting all known risk factors of HCC in the multivariate model.RESULTS During the 2011-2019 period,a total of 18031 hospitalizations with a primary or secondary diagnosis of HH(excluding liver diseases)were recorded in the NIS database.We analyzed different patients’characteristics,and we found increments in inpatient population trend with a Ptrend<0.001 and total hospital cost of care trend from$42957 in 2011 to$66152 in 2019 with a Ptrend<0.001 despite no change in Length of Stay over the last decade.The multivariate analyses showed that HH without cirrhosis(aOR,28.8;95%CI,10.4–80.1;P<0.0001),biliary cirrhosis(aOR,19.3;95%CI,13.4–27.6;P<0.0001),non-alcoholic cirrhosis(aOR,17.4;95%CI,16.5–18.4;P<0.0001),alcoholic cirrhosis(aOR,16.9;95%CI,15.9–17.9;P<0.0001),hepatitis B(aOR,12.1;95%CI,10.85–13.60;P<0.0001),hepatitis C(aOR,8.58;95%CI,8.20–8.98;P<0.0001),Wilson disease(aOR,4.27;95%CI,1.18–15.41;P<0.0001),NAFLD or NASH(aOR,2.96;95%CI,2.73–3.20;P<0.0001),alpha1-antitrypsin deficiency(aOR,2.10;95%CI,1.21–3.64;P<0.0001),diabetes mellitus without chronic complications(aOR,1.17;95%CI,1.13–1.21;P<0.0001),and blood transfusion(aOR,1.80;95%CI,1.69–1.92;P<0.0001)are independent risk factor for liver cancer.CONCLUSION Our study showed an increasing trend of in-hospital admissions of HH patients in the last decade.These trends were likely related to advances in diagnostic approach,which can lead to increased hospital utilization and cost increments.Still,the length of stay remained the same,likely due to a big part of management being done in outpatient settings.Another vital part of our study is the significant result that HH without cirrhosis is an independent risk factor for HCC with adjusting all known risk factors.More prospective and retrospective large studies are needed to re-evaluate the HH independent risk in developing HCC.
文摘BACKGROUND Hepatitis B virus is a viral infection that can lead to acute and/or chronic liver disease, and hepatocellular carcinoma(HCC). Hepatitis B vaccination is 95% effective in preventing infection and the development of chronic liver disease and HCC due to hepatitis B. In 2011, the Centers for Disease Control updated their guidelines recommending that adults at high-risk for hepatitis B infection be vaccinated against hepatitis B including those with diabetes mellitus(DM). We hypothesize that adults at high-risk for hepatitis B infection are not being adequately screened and/or vaccinated for hepatitis B in a large urban healthcare system.AIM To investigate clinical factors associated with Hepatitis B screening and vaccination in patients at high-risk for Hepatitis B infection.METHODS We conducted a retrospective review of 999 patients presenting at a large urban healthcare system from 2012-2017 at high-risk for hepatitis B infection. Patients were considered high-risk for hepatitis B infection based on hepatitis B practice recommendations from the Center for Disease Control. Medical history including hepatitis B serology, concomitant medical diagnoses, demographics, insurance status and social history were extracted from electronic health records.Multivariate logistic regression was used to identify clinical risk factors independently associated with hepatitis B screening and vaccination.RESULTS Among the 999 patients, 556(55.7%) patients were screened for hepatitis B. Of those who were screened, only 242(43.5%) patients were vaccinated against hepatitis B. Multivariate regression analysis revealed end-stage renal disease[odds ratio(OR): 5.122; 2.766-9.483], alcoholic hepatitis(OR: 3.064; 1.020-9.206),and cirrhosis or end-stage liver disease(OR: 1.909; 1.095-3.329); all P < 0.05 were associated with hepatitis B screening, while age(OR: 0.785; 0.680-0.906),insurance status(0.690; 0.558-0.854), history of DM(OR: 0.518; 0.364-0.737), and human immunodeficiency virus(OR: 0.443; 0.273-0.718); all P < 0.05 were instead not associated with hepatitis B screening. Of the adults vaccinated for hepatitis B,multivariate regression analysis revealed age(OR: 0.755; 0.650-0.878) and DM were not associated with hepatitis B vaccination(OR: 0.620; 0.409-0.941) both P <0.05.CONCLUSION Patients at high-risk for hepatitis B are not being adequately screened and/or vaccinated. Improvements in hepatitis B vaccination should be strongly encouraged by all healthcare systems.
