AIM: To examine whether visceral fat is associated with non-alcoholic steatohepatitis (NASH), to assess for parameters associated with visceral adiposity and to investigate for factors associated with fibrotic seve...AIM: To examine whether visceral fat is associated with non-alcoholic steatohepatitis (NASH), to assess for parameters associated with visceral adiposity and to investigate for factors associated with fibrotic severity in NASH. METHODS: Thirty NASH and 30 control subjects underwent biochemical tests, anthropometric assessment, bioelectrical impedance, dual energy X-ray absorptiometry and abdominal fat study by CT scan. Liver biopsies were graded according to the Brunt criteria. RESULTS: NASH subjects had elevated blood pressure, body mass index, waist circumference and waist-to-hip ratio. A greater number of diabetes rnellitus, impaired glucose tolerance test and HOMA-IR 〉 3.5 were found in NASH patients. HOMA-IR 〉 2.8 (OR 20.98, 95% CI 3.22-136.62; P 〈 0.001) and visceral fat area 〉 158 cm^2 (OR 18.55, 95% CI 1.60-214.67; P = 0.019) were independent predictors for NASH. Advanced stage of NASH was found in 15 (50%) patients. HOMA-IR 〉 3.5 (OR 23.12, 95% CI 2.00-266.23; P = 0.012) and grading of portal inflammation (OR 7.15, 95% CI 1.63-31.20; P = 0.009) were determined as independent risk factors for advanced stage of NASH. CONCLUSION: Obesity (especially central obesity) and metabolic syndrome are common in Thai NASH. Insulin resistance and elevated visceral fat are risk factors for the presence of NASH. The advanced stage of thedisease is related to insulin resistance.展开更多
A 56-year-old man was found to have a pancreatic tail tumor. His blood chemistry showed no infection with hepatitis B or C virus and no elevations of tumor markers or pancreatic hormones. Abdominal ultrasound showed a...A 56-year-old man was found to have a pancreatic tail tumor. His blood chemistry showed no infection with hepatitis B or C virus and no elevations of tumor markers or pancreatic hormones. Abdominal ultrasound showed an encapsulated, rather heterogeneous, hypoechoic tumor, 6.5 cm in maximum diameter, with a beak sign. Helical dynamic CT revealed an irregularly enhanced tumor with pooling of contrast medium in the delayed phase. Abdominal angiography showed a hypervascular tumor. With a tentative diagnosis of non-functional islet-cell tumor, the patient underwent resection of the pancreatic body and tail with splenectomy. The contour of the liver and its surface were normal. In microscopic examination, tumor cells arranged in a trabecular pattern with focal bile pigment resembling hepatocellular carcinoma (HCC). Immunohistochemically, these tumor cells were positivefor HEPPAR-1, CAM5.2, cytokeratin 18 and COX-2, but negative for MUC-1, and cytokeratins 7, 20 and 8. These results supported a diagnosis of HCC without any adenocarcinoma component. The patient is currently doing well without any signs of recurrence in either the remaining pancreas or liver three years after surgery. We report the rare case with ectopic HCC in the pancreas with a review of the literature.展开更多
A variety of hepatic and biliary tract disorders may complicate the clinical course of celiac disease. Some of these have been hypothesized to share common genetic factors or have a common immunopathogenesis, such as ...A variety of hepatic and biliary tract disorders may complicate the clinical course of celiac disease. Some of these have been hypothesized to share common genetic factors or have a common immunopathogenesis, such as primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune forms of hepatitis or cholangitis. Other hepatic changes in celiac disease may be associated with malnutrition resulting from impaired nutrient absorption, including hepatic steatosis. In addition, celiac disease may be associated with rare hepatic complications, such as hepatic T-cell lymphoma. Finally, pancreatic exocrine function may be impaired in celiac disease and represent a cause of treatment failure.展开更多
Osteoclast-like giant cell tumors (OGCT) are rare abdominal tumors, which mainly occur in the pancreas. The neoplasms are composed of two distinct cell populations and frequently show an inhomogenous appearance with...Osteoclast-like giant cell tumors (OGCT) are rare abdominal tumors, which mainly occur in the pancreas. The neoplasms are composed of two distinct cell populations and frequently show an inhomogenous appearance with cystic structures. However, due to the rarity of these tumors, only very limited clinical data are available. Imaging features and sonographic appearance have hardly been characterized. Here we report on two cases of osteoclast-like giant cell tumors, one located within the pancreas, the other within the liver, in which OGCTs are extremely rare. Both patients were investigated by contrast sonography, which demonstrated a complex, partly cystic and strongly vascularized tumor within the head of the pancreas in the first patient and a large, hypervascularized neoplasm with calcifications within the liver in the second patient. The liver OGCT responded well to a combination of carboplatin, etoposide and paclitaxel. With a combination of surgical resection, radiofrequency ablation and chemotherapy, the patient's survival is currently more than 15 too, making him the longest survivor with an OGCT of the liver to date.展开更多
Combined en bloc liver/pancreas transplantation (CLPT) was used primarily in the treal^nent of otherwise non- resectable upper abdominal malignancy. In fact, a more appropriate indication is in patients with liver d...Combined en bloc liver/pancreas transplantation (CLPT) was used primarily in the treal^nent of otherwise non- resectable upper abdominal malignancy. In fact, a more appropriate indication is in patients with liver disease and insulin-dependent diabetes mellitus (IDDM). Here, we report on two successful cases of CLPT at our hospital. One was a patient with non-resectable advanced liver cancer. The recipient survived for 23 mo and finally died of recurrent tumor. The other was a patient with severe biliary complication after orthotopic liver transplantation and preoperative IDDM. We performed CLPT with a modified surgical technique of preserving the native pancreas. He is currently liver-disease- and insulin-free more than 27 mo post-transplant. Based on our experience in two cases of abdominal cluster transplantation, we describe the technical details of CLPT and a modification of the surgical procedure.展开更多
AIM To test the hypothesis that K8/K18 variants predispose humans to non-alcoholic fatty liver disease(NAFLD) progression and its metabolic phenotypes. METHODS We selected a total of 373 unrelated adult subjects from ...AIM To test the hypothesis that K8/K18 variants predispose humans to non-alcoholic fatty liver disease(NAFLD) progression and its metabolic phenotypes. METHODS We selected a total of 373 unrelated adult subjects from our Physical Examination Department, including 200 unrelated NAFLD patients and 173 controls of both genders and different ages. Diagnoses of NAFLD were established according to ultrasonic signs of fatty liver. All subjects were tested for population characteristics, lipid profile, liver tests, as well as glucose tests. Genomic DNA was obtained from peripheral blood with a DNeasy Tissue Kit. K8/K18 coding regions were analyzed, including 15 exons and exon-intron boundaries. RESULTS Among 200 NAFLD patients, 10(5%) heterozygouscarriers of keratin variants were identified. There were 5 amino-acid-altering heterozygous variants and 6 non-coding heterozygous variants. One novel aminoacid-altering heterozygous variant(K18 N193S) and three novel non-coding variants were observed(K8 IVS5-9A→G, K8 IVS6+19G→A, K18 T195T). A total of 9 patients had a single variant and 1 patient had compound variants(K18 N193S+K8 IVS3-15C→G). Only one R341 H variant was found in the control group(1 of 173, 0.58%). The frequency of keratin variants in NAFLD patients was significantly higher than that in the control group(5% vs 0.58%, P = 0.015). Notably, the keratin variants were significantly associated with insulin resistance(IR) in NAFLD patients(8.86% in NAFLD patients with IR vs 2.5% in NAFLD patients without IR, P = 0.043).CONCLUSION K8/K18 variants are overrepresented in Chinese NAFLD patients and might accelerate liver fat storage through IR.展开更多
Nonalcoholic fatty liver disease(NAFLD) is one of the most common liver diseases and its prevalence is likely to reach epidemic proportions.According to the"two-stage hypothesis"proposed for the pathophysiol...Nonalcoholic fatty liver disease(NAFLD) is one of the most common liver diseases and its prevalence is likely to reach epidemic proportions.According to the"two-stage hypothesis"proposed for the pathophysiology of NAFLD,insulin resistance,oxidative stress and pro-inflammatory cytokines are among the key promoters of the disease. Here,ginger has been hypothesized to prevent NAFLD or blunt its progression via several mechanisms,such as sensitizing insulin effects,activating peroxisome proliferator-activated receptorγwhich induces adiponectin and down-regulates pro-inflammatory cytokines,changing the balance between adiponectin and tumor necrosis factor-αin favor of adiponectin,promoting considerable antioxidant effects and antidyslipidemic properties,and reducing hepatic triglyceride content which can prevent steatosis.The aforementioned mechanisms imply that ginger possesses interesting potentials for serving as a natural supplement for the prevention and treatment of NAFLD.Therefore,conducting trials to explore its benefits in clinical practice is greatly recommended.展开更多
Metabolic syndrome is a cluster of several clinical conditions characterized by insulin-resistance and high cardiovascular risk. Non-alcoholic fatty liver disease is the liver expression of the metabolic syndrome, and...Metabolic syndrome is a cluster of several clinical conditions characterized by insulin-resistance and high cardiovascular risk. Non-alcoholic fatty liver disease is the liver expression of the metabolic syndrome, and insulin resistance can be a frequent comorbidity in several chronic liver diseases, in particular hepatitis C virus infection and/or cirrhosis. Several studies have demonstrated that insulin action is not only relevant for glucose control, but also for vascular homeostasis. Insulin regulates nitric oxide production, which mediates to a large degree the vasodilating, antiinflammatory and antithrombotic properties of a healthy endothelium, guaranteeing organ perfusion. The effects of insulin on the liver microvasculature and the effects of IR on sinusoidal endothelial cells have been studied in animal models of non-alcoholic fatty liver disease. The hypotheses derived from these studies and the potential translation of these results into humans are critically discussed in this review.展开更多
AIM:To investigate the effectiveness of insulin on decreasing serum potassium concentration during anhepatic stage of orthotopic liver transplantation. METHODS:Sixteen patients with serum potassium concentrations grea...AIM:To investigate the effectiveness of insulin on decreasing serum potassium concentration during anhepatic stage of orthotopic liver transplantation. METHODS:Sixteen patients with serum potassium concentrations greater than 4.0 mmol/L at the onset of anhepatic stage were randomized into two groups.The patients in control group (n=8) received no treatment, while those in treatment group (n=8) received an intravenous bolus injection of regular insulin (20U) 10 min into the anhepatic stage,followed by a glucose infusion (500mL 50g/L dextrose) over 15 min. RESULTS:In control group,potassium concentration underwent no changes whereas in treatment group,it decreased from 4.8±0.48 mmol/L to 4.19±0.55 mmol/L (mean±SD) within 15 min and to 3.62±0.45 mmol/L 60 min after the therapy.The potassium concentration was lower in treatment group than in control group within 30 min of treatment (3.94±0.57 vs 4.47±0.42 mmol/L, respectively;P<0.05),and increased similarly 30 s after graft reperfusion in both groups of patients,but remained lower in treatment group (5.81±2.78 vs 7.44±1.75 mmol/L, respectively;P<0.05).The potassium concentration returned to pre-reperfusion levels within 5 min after graft reperfusion. CONCLUSION:In patients undergoing orthotopic liver transplantation,the administration of insulin rapidly decreases serum potassium concentration even in the absence of the liver,suggesting an important contribution by extrahepatic tissues in insulin-stimulated uptake of potassium.展开更多
AIM: To investigate a possible role for a recently identified polymorphism in the gene of cytochrome P450 2E1, the presence of which is associated with high activity of the enzyme. METHODS: Two hundred and thirty-nine...AIM: To investigate a possible role for a recently identified polymorphism in the gene of cytochrome P450 2E1, the presence of which is associated with high activity of the enzyme. METHODS: Two hundred and thirty-nine alcohol consumers, ICD 10.1/.2 (ALC), and 208 normal controls were studied. PCR amplification of the CYP2E1 gene region was performed to assess polymorphic variation. Fisher's exact test was used to assess the data.RESULTS: Twelve normal controls (5.8%) possessed the insertion. Five ALC (2.1%) had the insertion; of these 2 of 144 with,alcohol induced chronic pancreatitis, none of 28 with alcoholic liver disease and 3 of 67 without endorgan disease had the polymorphism. A significantly Lower frequency of subjects possessed the insertion than normal controls [P = 0.049 (genotype analysis P = 0.03)]. To further assess, if there was a relationship to alcohol problems per se or end-organ disease, we compared patients with alcohol induced end-organ disease vs alcoholic controls without end-organ disease vs normal controls which again showed a significant difference [P = 0.045 (genotype analysis,P = 0.011)], further sub-group analysis did not identify which group(s) accounted for these differences.CONCLUSION: We have shown the frequencies of this high-activity polymorphism in alcohol related patient groups for the first time. The frequency is significantly less in alcoholics than normal controls, as with high activity polymorphisms of alcohol dehydrogenase. The biological significance, and whether the relevance is solely for alcoholism or is there a relationship to end-organ disease,would benefit from the assessment in the populations with a greater frequency of this polymorphism.展开更多
Nonalcoholic fatty liver disease(NAFLD) is the commonest chronic liver disease and its prevalence is increasing driven by the pandemic of obesity and type 2 diabetes mellitus. NAFLD can progress to cirrhosis and is as...Nonalcoholic fatty liver disease(NAFLD) is the commonest chronic liver disease and its prevalence is increasing driven by the pandemic of obesity and type 2 diabetes mellitus. NAFLD can progress to cirrhosis and is associated with increased risk for cardiovascular disease and hepatocellular cancer. Diet and exercise are limited by suboptimal long-term adherence in patients with NAFLD. On the other hand, current pharmacological treatment of NAFLD has limited efficacy and unfavorable safety profile. In this context, obeticholic acid(OCA), a selective agonist of the farnesoid X receptors, might represent a useful option in these patients. Preclinical studies suggest that OCA improves hepatic steatosis, inflammation and fibrosis. A proof-of-concept study and the randomized, placebo-controlled Farnesoid X Receptor Ligand Obeticholic Acid in non-alcoholic steatohepatitis Treatment(FLINT) trial also showed improvements in liver histology in patients with NAFLD who received OCA. Weight loss and reduction in blood pressure were also observed. However, the effects of OCA on insulin resistance are conflicting and the lipid profile is adversely affected by this agent. In addition, pruritus is frequently observed during treatment with OCA and might lead to treatment discontinuation. However, given the limitations of existing treatments for NAFLD, OCA might represent a useful therapeutic option in selected patients with NAFLD.展开更多
The red blood cell distribution width(RDW) is a routinely measured and automatically reported blood parameter,which reflects the degree of anisocytosis. Recently,the baseline RDW was found to have clinical significanc...The red blood cell distribution width(RDW) is a routinely measured and automatically reported blood parameter,which reflects the degree of anisocytosis. Recently,the baseline RDW was found to have clinical significance for assessing clinical outcome and severity of various pathological conditions including cardiovascular diseases,sepsis,cancers,leukemia,renal dysfunction and respiratory diseases. A myriad of factors,most of which ill-defined,have an impact on the red cell population dynamics(i.e.,production,maturation and turnover). A delay in the red blood cell clearance in pathological conditions represents one of the leading determinants of increased anisocytosis. Further study of RDW may reveal new insight into inflammation mechanisms. In this review,we specifically discuss the current literature about the association of RDW in various disease conditions involving the gastrointestinal and hepatobiliary systems. We also present some of the related measurements for their value in predicting clinical outcomes in such conditions. According to our data,RDW was found to be a valuable prognostic index in gastrointestinal disorders along with additional inflammatory biomarkers(i.e.,C reactive protein,erythrocyte sedimentation rate,and platelet count) and current disease severity indices used in clinical practice.展开更多
This study was designed to investigate the gut microbiota of patients with non-alcoholic fatty liver disease. The inclusive and exclusive criteria for NAFLD patients and healthy subjects were formulated, and detailed ...This study was designed to investigate the gut microbiota of patients with non-alcoholic fatty liver disease. The inclusive and exclusive criteria for NAFLD patients and healthy subjects were formulated, and detailed clinical data were collected. The genomic DNA of stool samples were extracted for 16 S r DNA sequencing, and the amplified V4-region was sequenced on the Illumina Miseq platform. Metastats analysis was performed to identify the differential taxa between the groups. Redundancy analysis was used to evaluate the association between gut microbial structure and clinical variables. Thirty NAFLD patients and37 healthy controls were involved. The 16 S r DNA sequencing showed that there was a dramatic variability of the fecal microbiota among all the individuals. Metastats analysis identified eight families and 12 genera with significant differences between the two groups. When some clinical parameters, such as waist-to-hip ratio(WHR) and homeostasis model assessment of insulin resistance(HOMA-IR), were enrolled in Redundancy analysis, the distribution of the two group of samples was obviously changed. The compositional shifts in fecal bacterial communities of NAFLD patients from the healthy controls were mainly at family or genus levels. According to our Redundancy analysis, insulin resistance and obesity might be closely related to both NAFLD phenotype and intestinal microecology.展开更多
文摘AIM: To examine whether visceral fat is associated with non-alcoholic steatohepatitis (NASH), to assess for parameters associated with visceral adiposity and to investigate for factors associated with fibrotic severity in NASH. METHODS: Thirty NASH and 30 control subjects underwent biochemical tests, anthropometric assessment, bioelectrical impedance, dual energy X-ray absorptiometry and abdominal fat study by CT scan. Liver biopsies were graded according to the Brunt criteria. RESULTS: NASH subjects had elevated blood pressure, body mass index, waist circumference and waist-to-hip ratio. A greater number of diabetes rnellitus, impaired glucose tolerance test and HOMA-IR 〉 3.5 were found in NASH patients. HOMA-IR 〉 2.8 (OR 20.98, 95% CI 3.22-136.62; P 〈 0.001) and visceral fat area 〉 158 cm^2 (OR 18.55, 95% CI 1.60-214.67; P = 0.019) were independent predictors for NASH. Advanced stage of NASH was found in 15 (50%) patients. HOMA-IR 〉 3.5 (OR 23.12, 95% CI 2.00-266.23; P = 0.012) and grading of portal inflammation (OR 7.15, 95% CI 1.63-31.20; P = 0.009) were determined as independent risk factors for advanced stage of NASH. CONCLUSION: Obesity (especially central obesity) and metabolic syndrome are common in Thai NASH. Insulin resistance and elevated visceral fat are risk factors for the presence of NASH. The advanced stage of thedisease is related to insulin resistance.
文摘A 56-year-old man was found to have a pancreatic tail tumor. His blood chemistry showed no infection with hepatitis B or C virus and no elevations of tumor markers or pancreatic hormones. Abdominal ultrasound showed an encapsulated, rather heterogeneous, hypoechoic tumor, 6.5 cm in maximum diameter, with a beak sign. Helical dynamic CT revealed an irregularly enhanced tumor with pooling of contrast medium in the delayed phase. Abdominal angiography showed a hypervascular tumor. With a tentative diagnosis of non-functional islet-cell tumor, the patient underwent resection of the pancreatic body and tail with splenectomy. The contour of the liver and its surface were normal. In microscopic examination, tumor cells arranged in a trabecular pattern with focal bile pigment resembling hepatocellular carcinoma (HCC). Immunohistochemically, these tumor cells were positivefor HEPPAR-1, CAM5.2, cytokeratin 18 and COX-2, but negative for MUC-1, and cytokeratins 7, 20 and 8. These results supported a diagnosis of HCC without any adenocarcinoma component. The patient is currently doing well without any signs of recurrence in either the remaining pancreas or liver three years after surgery. We report the rare case with ectopic HCC in the pancreas with a review of the literature.
文摘A variety of hepatic and biliary tract disorders may complicate the clinical course of celiac disease. Some of these have been hypothesized to share common genetic factors or have a common immunopathogenesis, such as primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune forms of hepatitis or cholangitis. Other hepatic changes in celiac disease may be associated with malnutrition resulting from impaired nutrient absorption, including hepatic steatosis. In addition, celiac disease may be associated with rare hepatic complications, such as hepatic T-cell lymphoma. Finally, pancreatic exocrine function may be impaired in celiac disease and represent a cause of treatment failure.
文摘Osteoclast-like giant cell tumors (OGCT) are rare abdominal tumors, which mainly occur in the pancreas. The neoplasms are composed of two distinct cell populations and frequently show an inhomogenous appearance with cystic structures. However, due to the rarity of these tumors, only very limited clinical data are available. Imaging features and sonographic appearance have hardly been characterized. Here we report on two cases of osteoclast-like giant cell tumors, one located within the pancreas, the other within the liver, in which OGCTs are extremely rare. Both patients were investigated by contrast sonography, which demonstrated a complex, partly cystic and strongly vascularized tumor within the head of the pancreas in the first patient and a large, hypervascularized neoplasm with calcifications within the liver in the second patient. The liver OGCT responded well to a combination of carboplatin, etoposide and paclitaxel. With a combination of surgical resection, radiofrequency ablation and chemotherapy, the patient's survival is currently more than 15 too, making him the longest survivor with an OGCT of the liver to date.
基金Supported by The Major Scientific and Technological Project of Hubei Province, No. 2006AA301A06
文摘Combined en bloc liver/pancreas transplantation (CLPT) was used primarily in the treal^nent of otherwise non- resectable upper abdominal malignancy. In fact, a more appropriate indication is in patients with liver disease and insulin-dependent diabetes mellitus (IDDM). Here, we report on two successful cases of CLPT at our hospital. One was a patient with non-resectable advanced liver cancer. The recipient survived for 23 mo and finally died of recurrent tumor. The other was a patient with severe biliary complication after orthotopic liver transplantation and preoperative IDDM. We performed CLPT with a modified surgical technique of preserving the native pancreas. He is currently liver-disease- and insulin-free more than 27 mo post-transplant. Based on our experience in two cases of abdominal cluster transplantation, we describe the technical details of CLPT and a modification of the surgical procedure.
基金Supported by National Natural Science Foundation of China,No.81670518 and No.81170392The Science and Technology Project of Guangdong Province,China,No.2013B021800290 and No.2014A020212118Guangzhou Science and Technology Innovation Commission,China,No.201604020155
文摘AIM To test the hypothesis that K8/K18 variants predispose humans to non-alcoholic fatty liver disease(NAFLD) progression and its metabolic phenotypes. METHODS We selected a total of 373 unrelated adult subjects from our Physical Examination Department, including 200 unrelated NAFLD patients and 173 controls of both genders and different ages. Diagnoses of NAFLD were established according to ultrasonic signs of fatty liver. All subjects were tested for population characteristics, lipid profile, liver tests, as well as glucose tests. Genomic DNA was obtained from peripheral blood with a DNeasy Tissue Kit. K8/K18 coding regions were analyzed, including 15 exons and exon-intron boundaries. RESULTS Among 200 NAFLD patients, 10(5%) heterozygouscarriers of keratin variants were identified. There were 5 amino-acid-altering heterozygous variants and 6 non-coding heterozygous variants. One novel aminoacid-altering heterozygous variant(K18 N193S) and three novel non-coding variants were observed(K8 IVS5-9A→G, K8 IVS6+19G→A, K18 T195T). A total of 9 patients had a single variant and 1 patient had compound variants(K18 N193S+K8 IVS3-15C→G). Only one R341 H variant was found in the control group(1 of 173, 0.58%). The frequency of keratin variants in NAFLD patients was significantly higher than that in the control group(5% vs 0.58%, P = 0.015). Notably, the keratin variants were significantly associated with insulin resistance(IR) in NAFLD patients(8.86% in NAFLD patients with IR vs 2.5% in NAFLD patients without IR, P = 0.043).CONCLUSION K8/K18 variants are overrepresented in Chinese NAFLD patients and might accelerate liver fat storage through IR.
文摘Nonalcoholic fatty liver disease(NAFLD) is one of the most common liver diseases and its prevalence is likely to reach epidemic proportions.According to the"two-stage hypothesis"proposed for the pathophysiology of NAFLD,insulin resistance,oxidative stress and pro-inflammatory cytokines are among the key promoters of the disease. Here,ginger has been hypothesized to prevent NAFLD or blunt its progression via several mechanisms,such as sensitizing insulin effects,activating peroxisome proliferator-activated receptorγwhich induces adiponectin and down-regulates pro-inflammatory cytokines,changing the balance between adiponectin and tumor necrosis factor-αin favor of adiponectin,promoting considerable antioxidant effects and antidyslipidemic properties,and reducing hepatic triglyceride content which can prevent steatosis.The aforementioned mechanisms imply that ginger possesses interesting potentials for serving as a natural supplement for the prevention and treatment of NAFLD.Therefore,conducting trials to explore its benefits in clinical practice is greatly recommended.
文摘Metabolic syndrome is a cluster of several clinical conditions characterized by insulin-resistance and high cardiovascular risk. Non-alcoholic fatty liver disease is the liver expression of the metabolic syndrome, and insulin resistance can be a frequent comorbidity in several chronic liver diseases, in particular hepatitis C virus infection and/or cirrhosis. Several studies have demonstrated that insulin action is not only relevant for glucose control, but also for vascular homeostasis. Insulin regulates nitric oxide production, which mediates to a large degree the vasodilating, antiinflammatory and antithrombotic properties of a healthy endothelium, guaranteeing organ perfusion. The effects of insulin on the liver microvasculature and the effects of IR on sinusoidal endothelial cells have been studied in animal models of non-alcoholic fatty liver disease. The hypotheses derived from these studies and the potential translation of these results into humans are critically discussed in this review.
基金Supported by the National Natural Science Foundation of China,No.39900140
文摘AIM:To investigate the effectiveness of insulin on decreasing serum potassium concentration during anhepatic stage of orthotopic liver transplantation. METHODS:Sixteen patients with serum potassium concentrations greater than 4.0 mmol/L at the onset of anhepatic stage were randomized into two groups.The patients in control group (n=8) received no treatment, while those in treatment group (n=8) received an intravenous bolus injection of regular insulin (20U) 10 min into the anhepatic stage,followed by a glucose infusion (500mL 50g/L dextrose) over 15 min. RESULTS:In control group,potassium concentration underwent no changes whereas in treatment group,it decreased from 4.8±0.48 mmol/L to 4.19±0.55 mmol/L (mean±SD) within 15 min and to 3.62±0.45 mmol/L 60 min after the therapy.The potassium concentration was lower in treatment group than in control group within 30 min of treatment (3.94±0.57 vs 4.47±0.42 mmol/L, respectively;P<0.05),and increased similarly 30 s after graft reperfusion in both groups of patients,but remained lower in treatment group (5.81±2.78 vs 7.44±1.75 mmol/L, respectively;P<0.05).The potassium concentration returned to pre-reperfusion levels within 5 min after graft reperfusion. CONCLUSION:In patients undergoing orthotopic liver transplantation,the administration of insulin rapidly decreases serum potassium concentration even in the absence of the liver,suggesting an important contribution by extrahepatic tissues in insulin-stimulated uptake of potassium.
文摘AIM: To investigate a possible role for a recently identified polymorphism in the gene of cytochrome P450 2E1, the presence of which is associated with high activity of the enzyme. METHODS: Two hundred and thirty-nine alcohol consumers, ICD 10.1/.2 (ALC), and 208 normal controls were studied. PCR amplification of the CYP2E1 gene region was performed to assess polymorphic variation. Fisher's exact test was used to assess the data.RESULTS: Twelve normal controls (5.8%) possessed the insertion. Five ALC (2.1%) had the insertion; of these 2 of 144 with,alcohol induced chronic pancreatitis, none of 28 with alcoholic liver disease and 3 of 67 without endorgan disease had the polymorphism. A significantly Lower frequency of subjects possessed the insertion than normal controls [P = 0.049 (genotype analysis P = 0.03)]. To further assess, if there was a relationship to alcohol problems per se or end-organ disease, we compared patients with alcohol induced end-organ disease vs alcoholic controls without end-organ disease vs normal controls which again showed a significant difference [P = 0.045 (genotype analysis,P = 0.011)], further sub-group analysis did not identify which group(s) accounted for these differences.CONCLUSION: We have shown the frequencies of this high-activity polymorphism in alcohol related patient groups for the first time. The frequency is significantly less in alcoholics than normal controls, as with high activity polymorphisms of alcohol dehydrogenase. The biological significance, and whether the relevance is solely for alcoholism or is there a relationship to end-organ disease,would benefit from the assessment in the populations with a greater frequency of this polymorphism.
文摘Nonalcoholic fatty liver disease(NAFLD) is the commonest chronic liver disease and its prevalence is increasing driven by the pandemic of obesity and type 2 diabetes mellitus. NAFLD can progress to cirrhosis and is associated with increased risk for cardiovascular disease and hepatocellular cancer. Diet and exercise are limited by suboptimal long-term adherence in patients with NAFLD. On the other hand, current pharmacological treatment of NAFLD has limited efficacy and unfavorable safety profile. In this context, obeticholic acid(OCA), a selective agonist of the farnesoid X receptors, might represent a useful option in these patients. Preclinical studies suggest that OCA improves hepatic steatosis, inflammation and fibrosis. A proof-of-concept study and the randomized, placebo-controlled Farnesoid X Receptor Ligand Obeticholic Acid in non-alcoholic steatohepatitis Treatment(FLINT) trial also showed improvements in liver histology in patients with NAFLD who received OCA. Weight loss and reduction in blood pressure were also observed. However, the effects of OCA on insulin resistance are conflicting and the lipid profile is adversely affected by this agent. In addition, pruritus is frequently observed during treatment with OCA and might lead to treatment discontinuation. However, given the limitations of existing treatments for NAFLD, OCA might represent a useful therapeutic option in selected patients with NAFLD.
文摘The red blood cell distribution width(RDW) is a routinely measured and automatically reported blood parameter,which reflects the degree of anisocytosis. Recently,the baseline RDW was found to have clinical significance for assessing clinical outcome and severity of various pathological conditions including cardiovascular diseases,sepsis,cancers,leukemia,renal dysfunction and respiratory diseases. A myriad of factors,most of which ill-defined,have an impact on the red cell population dynamics(i.e.,production,maturation and turnover). A delay in the red blood cell clearance in pathological conditions represents one of the leading determinants of increased anisocytosis. Further study of RDW may reveal new insight into inflammation mechanisms. In this review,we specifically discuss the current literature about the association of RDW in various disease conditions involving the gastrointestinal and hepatobiliary systems. We also present some of the related measurements for their value in predicting clinical outcomes in such conditions. According to our data,RDW was found to be a valuable prognostic index in gastrointestinal disorders along with additional inflammatory biomarkers(i.e.,C reactive protein,erythrocyte sedimentation rate,and platelet count) and current disease severity indices used in clinical practice.
基金supported by National High Technology Research and Development Program of China (2015AA020701)
文摘This study was designed to investigate the gut microbiota of patients with non-alcoholic fatty liver disease. The inclusive and exclusive criteria for NAFLD patients and healthy subjects were formulated, and detailed clinical data were collected. The genomic DNA of stool samples were extracted for 16 S r DNA sequencing, and the amplified V4-region was sequenced on the Illumina Miseq platform. Metastats analysis was performed to identify the differential taxa between the groups. Redundancy analysis was used to evaluate the association between gut microbial structure and clinical variables. Thirty NAFLD patients and37 healthy controls were involved. The 16 S r DNA sequencing showed that there was a dramatic variability of the fecal microbiota among all the individuals. Metastats analysis identified eight families and 12 genera with significant differences between the two groups. When some clinical parameters, such as waist-to-hip ratio(WHR) and homeostasis model assessment of insulin resistance(HOMA-IR), were enrolled in Redundancy analysis, the distribution of the two group of samples was obviously changed. The compositional shifts in fecal bacterial communities of NAFLD patients from the healthy controls were mainly at family or genus levels. According to our Redundancy analysis, insulin resistance and obesity might be closely related to both NAFLD phenotype and intestinal microecology.