AIM: To shed some light on the relationship between anti-apoptotic serum Bcl-2 concentrations and metabolic status, anthropometric parameters, inflammation indi- ces, and non-alcoholic fatty liver disease severity we...AIM: To shed some light on the relationship between anti-apoptotic serum Bcl-2 concentrations and metabolic status, anthropometric parameters, inflammation indi- ces, and non-alcoholic fatty liver disease severity were investigated in 43 young individuals with fatty liver (FL) and 41 with nonalcoholic steatohepatitis (NASH). METHODS: Circulating levels of Bcl-2 were detected in 84 patients with ultrasonographic findings of "bright liver" and/or hyper-transaminasemia of unknown origin and/or increase in T-glutamyl-transpeptidase (T-GT) strictly in the absence of other acute or chronic liver disease, whose age was not advanced, who gave consent to liver biopsy and were then divided on the basis of the histological results into two groups (43 with FL and 41 with NASH). Twenty lean subjects, apparently healthy and young, were chosen as controls.RESULTS: Serum Bcl-2 concentrations were significantly higher in the FL group than in the NASH group. Insulin resistance and γ-GT activity were significantly higher in NASH subjects. Apoptotic hepatocytes were significantly more numerous in NASH patients. NASH patients presented with larger spleens and augmented C-reactive protein (CRP) concentrations than healthy subjects. Steatosis grade at histology was similar in both NASH and FL populations. The number of apoptotic cells was significantly related to anti-apoptotic Bcl-2 protein values in FL patients. Bcl-2 serum levels positively correlated to body mass index (BMI) values (P ~ 0.0001) but not to age of the population. Triglycerides/HDL ratio correlated well to waist circumference in males (P = 0.0008). γ-GT activity was associated with homeostatic metabolic assessment (HOMA) (P = 0.0003) and with serum ferritin (P = 0.02). Bcl-2 concentrations were not related to either spleen size or CRP values. NASH patients pre- sented a weak negative correlation between Iobular inflammation and Bcl-2 levels. A prediction by low values of serum Bcl-2 towards a greater presence of metabolically unhealthy overweight/obese patients (MUOs) was evidenced. HOMA, BMI and uric acid, in that sequence, best predicted serum Bcl-2 concentrations. CONCLUSION: IvlUOs could be detected by Bcl-2 levels. By favoring the life span of hepatocytes, and enhancing triglyceride formation, the anti-apoptotic process inhibits free fatty acids toxicity in FL.展开更多
The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of dige...The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of nonalcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.展开更多
Non-alcoholic fatty liver disease(NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome(Met S). Importantly, NAFLD is one of its most dangerous complications because it can l...Non-alcoholic fatty liver disease(NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome(Met S). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of Met S. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease(CVD), diabetes mellitus type 2(T2DM) and chronic kidney disease(CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with Met S, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2 DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both(sub-) specialists and primary care physicians.展开更多
AIM To determine the clinical effectiveness of nutritional counseling on reduction of non-alcoholic fatty liver disease(NAFLD) severity, weight loss, metabolic and anthropometric indexes and liver enzymes.METHODS Fort...AIM To determine the clinical effectiveness of nutritional counseling on reduction of non-alcoholic fatty liver disease(NAFLD) severity, weight loss, metabolic and anthropometric indexes and liver enzymes.METHODS Forty-six adults with NAFLD received a 6-mo clinical and a dietary intervention(based on Mediterranean diet) carried out respectively by a gastroenterologist and a nutritionist with counseling license. The counseling process consisted of monthly meeting(about 45 min each). The effect of the treatment was evaluated monitoring liver enzymes, metabolic parameters, cardiovascular risk indexes, NAFLD severity [assessed by ultrasound(US)] and related indexes. All parameters were assessed at baseline. Biochemistry was also assessed at mid-and end-interventions and US was repeated at end-intervention.RESULTS The percentage of patients with steatosis grade equal or higher than 2 was reduced from 93% to 48% and steatosis regressed in 9 patients(20%). At the end of the treatment the end-point concerning the weight(i.e., a 7% weight reduction or achievement/maintenance of normal weight) was accomplished by 25 out of 46 patients(i.e., 54.3%). As far as the liver enzymes is concerned, all three liver enzymes significantly decrease during the treatment the normalization was particularly evident for the ALT enzyme(altered values reduced from 67% down to 11%). Several parameters, i.e., BMI, waist circumference, waist-to-hip ratio, AST, ALT, GGT, HDL, serum glucose, Tot-Chol/HDL, LDL/HDL, TG/HDL, AIP, HOMA, FLI, Kotronen index, VAI, NAFLD liver fat score and LAP, showed a significant improvement(P < 0.01) between baseline and end-treatment.CONCLUSION Outcomes of this study further strengthen the hypothesis that Med Diet and more active lifestyle can be considered a safe therapeutic approach for reducing risk and severity of NAFLD and related disease states. The proposed approach may be proposed as a valid and recommended approach for improving the clinical profile of NAFLD patients.展开更多
文摘AIM: To shed some light on the relationship between anti-apoptotic serum Bcl-2 concentrations and metabolic status, anthropometric parameters, inflammation indi- ces, and non-alcoholic fatty liver disease severity were investigated in 43 young individuals with fatty liver (FL) and 41 with nonalcoholic steatohepatitis (NASH). METHODS: Circulating levels of Bcl-2 were detected in 84 patients with ultrasonographic findings of "bright liver" and/or hyper-transaminasemia of unknown origin and/or increase in T-glutamyl-transpeptidase (T-GT) strictly in the absence of other acute or chronic liver disease, whose age was not advanced, who gave consent to liver biopsy and were then divided on the basis of the histological results into two groups (43 with FL and 41 with NASH). Twenty lean subjects, apparently healthy and young, were chosen as controls.RESULTS: Serum Bcl-2 concentrations were significantly higher in the FL group than in the NASH group. Insulin resistance and γ-GT activity were significantly higher in NASH subjects. Apoptotic hepatocytes were significantly more numerous in NASH patients. NASH patients presented with larger spleens and augmented C-reactive protein (CRP) concentrations than healthy subjects. Steatosis grade at histology was similar in both NASH and FL populations. The number of apoptotic cells was significantly related to anti-apoptotic Bcl-2 protein values in FL patients. Bcl-2 serum levels positively correlated to body mass index (BMI) values (P ~ 0.0001) but not to age of the population. Triglycerides/HDL ratio correlated well to waist circumference in males (P = 0.0008). γ-GT activity was associated with homeostatic metabolic assessment (HOMA) (P = 0.0003) and with serum ferritin (P = 0.02). Bcl-2 concentrations were not related to either spleen size or CRP values. NASH patients pre- sented a weak negative correlation between Iobular inflammation and Bcl-2 levels. A prediction by low values of serum Bcl-2 towards a greater presence of metabolically unhealthy overweight/obese patients (MUOs) was evidenced. HOMA, BMI and uric acid, in that sequence, best predicted serum Bcl-2 concentrations. CONCLUSION: IvlUOs could be detected by Bcl-2 levels. By favoring the life span of hepatocytes, and enhancing triglyceride formation, the anti-apoptotic process inhibits free fatty acids toxicity in FL.
文摘The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of nonalcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.
文摘Non-alcoholic fatty liver disease(NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome(Met S). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of Met S. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease(CVD), diabetes mellitus type 2(T2DM) and chronic kidney disease(CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with Met S, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2 DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both(sub-) specialists and primary care physicians.
基金Supported by Fondo per gli Investimenti della Ricerca di Base,No.RBAP10MY35_002Ente Cassa di Risparmio di FirenzeFior Gen ONLUS to Galli A
文摘AIM To determine the clinical effectiveness of nutritional counseling on reduction of non-alcoholic fatty liver disease(NAFLD) severity, weight loss, metabolic and anthropometric indexes and liver enzymes.METHODS Forty-six adults with NAFLD received a 6-mo clinical and a dietary intervention(based on Mediterranean diet) carried out respectively by a gastroenterologist and a nutritionist with counseling license. The counseling process consisted of monthly meeting(about 45 min each). The effect of the treatment was evaluated monitoring liver enzymes, metabolic parameters, cardiovascular risk indexes, NAFLD severity [assessed by ultrasound(US)] and related indexes. All parameters were assessed at baseline. Biochemistry was also assessed at mid-and end-interventions and US was repeated at end-intervention.RESULTS The percentage of patients with steatosis grade equal or higher than 2 was reduced from 93% to 48% and steatosis regressed in 9 patients(20%). At the end of the treatment the end-point concerning the weight(i.e., a 7% weight reduction or achievement/maintenance of normal weight) was accomplished by 25 out of 46 patients(i.e., 54.3%). As far as the liver enzymes is concerned, all three liver enzymes significantly decrease during the treatment the normalization was particularly evident for the ALT enzyme(altered values reduced from 67% down to 11%). Several parameters, i.e., BMI, waist circumference, waist-to-hip ratio, AST, ALT, GGT, HDL, serum glucose, Tot-Chol/HDL, LDL/HDL, TG/HDL, AIP, HOMA, FLI, Kotronen index, VAI, NAFLD liver fat score and LAP, showed a significant improvement(P < 0.01) between baseline and end-treatment.CONCLUSION Outcomes of this study further strengthen the hypothesis that Med Diet and more active lifestyle can be considered a safe therapeutic approach for reducing risk and severity of NAFLD and related disease states. The proposed approach may be proposed as a valid and recommended approach for improving the clinical profile of NAFLD patients.