The liver involvement in alcoholic liver disease(ALD) classically ranges from alcoholic steatosis, alcoholic hepatitis or steatohepatitis, alcoholic cirrhosis and even hepatocellular carcinoma. The more commonly seen ...The liver involvement in alcoholic liver disease(ALD) classically ranges from alcoholic steatosis, alcoholic hepatitis or steatohepatitis, alcoholic cirrhosis and even hepatocellular carcinoma. The more commonly seen histologic features include macrovesicular steatosis, neutrophilic lobular inflammation, ballooning degeneration, Mallory-Denk bodies, portal and pericellular fibrosis. Nonalcoholic steatohepatitis(NASH) is a condition with similar histology in the absence of a history of alcohol intake. Although the distinction is essentially based on presence or absence of a history of significant alcohol intake, certain histologic features favour one or the other diagnosis. This review aims at describing the histologic spectrum of alcoholic liver disease and at highlighting the histologic differences between ALD and NASH.展开更多
Red cell distribution width (RDW) may play an important role in predicting steatohepatitis and liver fibrosis. In the original study, it was aimed to determine whether RDW could be used for this purpose or not. There ...Red cell distribution width (RDW) may play an important role in predicting steatohepatitis and liver fibrosis. In the original study, it was aimed to determine whether RDW could be used for this purpose or not. There are studies indicating that higher RDW is correlated well with components of metabolic syndrome. Because nonalcoholic fatty liver disease is now recognized as the hepatic manifestation of metabolic syndrome, possible impact of the accompanying confounders on the study findings should have been detailed. There may be a patient selection bias due to use of improper cut-off values for alcohol consumption and inclusion of only subjects with normal aminotransferase levels and normal abdominal ultrasonography. Patients without hepatosteatosis on ultrasonography and with any restriction of aminotransferase levels should have been included in the control group, because isolated aminotransferase elevation is not decisive in the diagnosis of hepatosteatosis. Although iron, vitamin B<sub>12</sub> and folic acid deficiencies were included in exclusion criteria, functional forms of these molecules like methylmalonic acid, homocysteine, ferritin levels and total iron binding capacity, which are more sensitive and specific parameters for vitamin B<sub>12</sub> and folic acid deficiencies, were not mentioned. Consequently, RDW, an inexpensive, non-invasive, but powerful indicator overlooked on whole blood analysis, itself without other inflammatory markers may not accurately provide information about progression of nonalcoholic steatohepatitis and fibrosis.展开更多
AIM: To study the significance and clinical implication of hepatic lipogranuloma in chronic liver diseases, including fatty liver disease and hepatitis C. METHODS: A total of 376 sequential, archival liver biopsy spec...AIM: To study the significance and clinical implication of hepatic lipogranuloma in chronic liver diseases, including fatty liver disease and hepatitis C. METHODS: A total of 376 sequential, archival liver biopsy specimens were reviewed. Lipogranuloma, steatosis and steato-fibrosis were evaluated with combined hematoxylin and eosin and Masson’s trichrome staining. RESULTS: Fifty-eight (15.4%) patients had lipogranuloma, including 46 patients with hepatitis C, 14 patients with fatty liver disease, and 5 patients with other diseases. Hepatic lipogranuloma was more frequently seen in patients with hepatitis C (21%) and fatty liver disease (18%), and its incidence was significantly higher than that in control group (P < 0.0002 and P < 0.007, respectively). In addition, 39 out of the 58 patients with lipogranuloma were associated with steatosis and/or steato-fibrosis. Of the 18 lipogranuloma patients with clinical information available for review, 15 (83%) had risk factors associated with fatty liver disease, such as alcohol use, obesity, hyperlipidemia, and diabetes mellitus. Although the incidence of these risk factors was greater in patients with lipogranuloma than in control group (60%), it did not reach statistical significance. CONCLUSION: Hepatic lipogranuloma is not limited to mineral oil use and commonly associated with hepatic steatosis, hepatitis C and fatty liver disease. With additional histological features of steato-fibrosis, lipogranuloma can also be used as a marker of prior hepatic steatosis.展开更多
目的:观察丹参注射液对非酒精性脂肪性肝炎大鼠脂质代谢、肝组织病理变化及脂肪细胞因子的影响,探讨其防治非酒精性脂肪性肝炎(Non-alcoholic steato-hepatitis,NASH)的可能作用机制。方法:采用高脂饮食16周建立大鼠非酒精性脂肪性肝炎...目的:观察丹参注射液对非酒精性脂肪性肝炎大鼠脂质代谢、肝组织病理变化及脂肪细胞因子的影响,探讨其防治非酒精性脂肪性肝炎(Non-alcoholic steato-hepatitis,NASH)的可能作用机制。方法:采用高脂饮食16周建立大鼠非酒精性脂肪性肝炎模型,并用丹参注射液5 m L/(kg·d)进行干预治疗,观察各组大鼠肝湿质量、肝指数,血清及肝组织匀浆TG、TC含量,HE染色光镜观察肝组织脂肪变和炎症程度,ELISA法检测血清脂联素、TNF-α水平。结果:模型组大鼠肝湿质量、肝指数,血清及肝组织匀浆TG、TC含量升高,血清TNF-α水平升高,脂联素水平下降,肝组织炎症积分升高(P<0.01);丹参治疗后肝组织炎症程度较模型组明显减轻,血清及肝组织匀浆TG、TC含量较模型组明显降低,血清脂联素水平较模型组增高,TNF-α水平较模型组显著下降(P<0.01)。结论:丹参注射液能通过上调脂联素水平、下调TNF-α水平,降低肝脏脂质蓄积,从而抑制肝细胞炎症,防止NASH的进展。展开更多
AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD). METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory...AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD). METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory parameters were assayed after 3 mo of a restricted diet and before silymarin treatment (twice a day orally). The brightness of liver echography texture (hepatorenal ratio brightness) was also defined at same time. These evaluations were repeated after 6 mo of treatment. RESULTS: Serum levels of some metabolic and anti-inflammatory data nonsignificantly lowered after 6 mo of silymarin. On the contrary, Steato test, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase were significantly (P < 0.001) reduced. Instead, the AST/ALT ratio unchanged. Finally, the hepatorenal brightness ratio, as an index of hepatic steatosis, significantly (P < 0.05) dropped. CONCLUSION: The obtained results indicate that silymarin appears to be effective to reduce the biochemical, inflammatory and ultrasonic indices of hepatic steatosis. Some parameters indicative of early stage of atherosclerosis were also lowered.展开更多
AIM: To analyze whether computer-enhanced dynamic analysis of elastography movies is able to better characterize and differentiate between different degrees of liver fibrosis. METHODS: The study design was prospective...AIM: To analyze whether computer-enhanced dynamic analysis of elastography movies is able to better characterize and differentiate between different degrees of liver fibrosis. METHODS: The study design was prospective. A total of 132 consecutive patients with chronic liver diseases and healthy volunteers were examined by transabdominal ultrasound elastography. All examinations were done by two doctors.RESULTS: Due to the limitations of the method, we obtained high-quality elastography information in only 73.48% of the patients. The κ-means clustering method was applied to assess the inter-observer diagnosis varia- bility, which showed good variability values in accordance with the experience of ultrasound examination of every observer. Cohen’sκ test indicated a moderate agreement between the study observers (κ = 0.4728). Furthermore, we compared the way the two observers clustered the patients, using the test for comparing two proportions (t value, two-sided test). There was no statistically significant difference between the two physicians, regardless of the patients’ real status. CONCLUSION: Transabdominal real-time elastography is certainly a very useful method in depicting liver hard- ness, although it is incompletely tested in large multicenter studies.展开更多
AIM: To analyze the relationship between the serum lectin-like oxidized low-density lipoprotein receptor-1(LOX-1) levels and clinical and histopathological features of biopsy-confirmed nonalcoholic fatty liver disease...AIM: To analyze the relationship between the serum lectin-like oxidized low-density lipoprotein receptor-1(LOX-1) levels and clinical and histopathological features of biopsy-confirmed nonalcoholic fatty liver disease(NAFLD) patients.METHODS: Fifty-three consecutive,biopsy-proven NAFLD patients(31 males and 22 females,mean age 42.5 ± 9.6 years) and 26 age- and gender-matched,healthy controls(14 males and 12 females,mean age 39 ± 10.7 years) were included.The patientswith NAFLD were consecutive patients who had been admitted to the hepatology outpatient clinic within the last year and had been diagnosed with NAFLD as the result of liver biopsy.The healthy controls were individuals who attended the outpatient clinic for routine health control and had no known chronic illnesses.The histological evaluation was conducted according t o t he N AF LD ac t ivi ty scoring syst em recommended by The National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network.The serum LOX-1 levels were measured using an ELISA kit(Life Science Inc.USCN.Wuhan,Catalog No.E1859Hu) in both patients and healthy controls.A receiver operating characteristic(ROC) curve analysis was used to identify the optimal cutoff value of LOX-1 and thereby distinguish between patients with nonalcoholic steatohepatitis(NASH) and healthy controls.A P-value < 0.05 was considered statistically significant.RESULTS: NAFLD and healthy control groups were similar in terms of age and sex.NAFLD patients consisted of 8 patients with simple steatosis(15%),27 with borderline NASH(51%) and 18 with definitive NASH(34%).Metabolic syndrome was found in 62.2% of the patients with NAFLD.The mean serum LOX-1 level in biopsy-proven NAFLD patients was 8.49 ± 6.43 ng/m L compared to 4.08 ± 4.32 ng/m L in healthy controls(P = 0.001).The LOX-1 levels were significantly different between controls,simple steatosis and NASH(borderline+definite) cases(4.08 ± 4.32 ng/m L,6.1 ± 6.16 ng/m L,8.92 ± 6.45 ng/m L,respectively,P = 0.004).When the cut-off value for the serum LOX-1 level was set at 5.35 ng/m L,and a ROC curve analysis was performed to distinguish between steatohepatitis patients and controls; the sensitivity and specificity of the serum LOX-1 level were 69.8% and 69.2%,respectively.CONCLUSION: The serum LOX-1 levels were significantly higher in NAFLD patients than in healthy controls.Additionally,the serum LOX-1 levels could differentiate between steatohepatitis patients and healthy controls.展开更多
目的:观察柴胡疏肝散对非酒精性脂肪性肝炎(NASH)大鼠肝脏内质网应激(ERS)相关IRE-1α/NF-κB通路的影响,探讨其防治NASH的可能作用机制。方法:采用高脂饮食12周建立NASH大鼠模型,同时以6g·kg-1·d-1的柴胡疏肝散干预12周,油红...目的:观察柴胡疏肝散对非酒精性脂肪性肝炎(NASH)大鼠肝脏内质网应激(ERS)相关IRE-1α/NF-κB通路的影响,探讨其防治NASH的可能作用机制。方法:采用高脂饮食12周建立NASH大鼠模型,同时以6g·kg-1·d-1的柴胡疏肝散干预12周,油红O和HE染色光镜观察肝组织脂肪变和炎性反应程度;计算NAFLD活动度(NAS);生化法检测血清ALT、AST和肝组织TG、GHOL;Realtime-PCR和Western blot技术检测肝组织GRP78、IRE-1α、NF-κB m RNA和蛋白或磷酸化水平,ELISA检测血清和肝组织中TNF-α、IL-1β水平。结果:模型组和柴胡疏肝散组大鼠肝组织均出现了脂肪变和炎性坏死。与正常组比较,模型组大鼠NAS显著增高(P<0.01),血清ALT、AST水平和肝组织TG、CHOL含量显著升高(P<0.01),肝组织GRP78、IRE-1α、NF-κB m RNA表达显著增强(P<0.01),GRP78蛋白表达和IRE-1α、NF-κB m RNA磷酸化水平显著上调(P<0.01),血清及肝组织TNF-α、IL-1β含量显著增加(P<0.01)。与模型组比较,柴胡疏肝散组大鼠NAS显著降低(P<0.01),血清ALT、AST水平和肝组织TG、CHOL含量显著降低(P<0.01),肝组织GRP78、IRE-1α、NF-κB m RNA表达显著下降(P<0.05,P<0.01),GRP78蛋白表达和IRE-1α、NF-κB m RNA磷酸化水平显著下调(P<0.05),血清及肝组织TNF-α、IL-1β含量显著下降(P<0.05)。结论:ERS相关的IRE-1α/NF-κB参与高脂饮食诱导的大鼠NASH的发生发展。柴胡疏肝散可能通过调节IRE-1α/NF-κB通路抑制过度的ERS,来调节肝脏脂质代谢紊乱、减轻肝脏炎性反应,防止NASH的进展。展开更多
文摘The liver involvement in alcoholic liver disease(ALD) classically ranges from alcoholic steatosis, alcoholic hepatitis or steatohepatitis, alcoholic cirrhosis and even hepatocellular carcinoma. The more commonly seen histologic features include macrovesicular steatosis, neutrophilic lobular inflammation, ballooning degeneration, Mallory-Denk bodies, portal and pericellular fibrosis. Nonalcoholic steatohepatitis(NASH) is a condition with similar histology in the absence of a history of alcohol intake. Although the distinction is essentially based on presence or absence of a history of significant alcohol intake, certain histologic features favour one or the other diagnosis. This review aims at describing the histologic spectrum of alcoholic liver disease and at highlighting the histologic differences between ALD and NASH.
文摘Red cell distribution width (RDW) may play an important role in predicting steatohepatitis and liver fibrosis. In the original study, it was aimed to determine whether RDW could be used for this purpose or not. There are studies indicating that higher RDW is correlated well with components of metabolic syndrome. Because nonalcoholic fatty liver disease is now recognized as the hepatic manifestation of metabolic syndrome, possible impact of the accompanying confounders on the study findings should have been detailed. There may be a patient selection bias due to use of improper cut-off values for alcohol consumption and inclusion of only subjects with normal aminotransferase levels and normal abdominal ultrasonography. Patients without hepatosteatosis on ultrasonography and with any restriction of aminotransferase levels should have been included in the control group, because isolated aminotransferase elevation is not decisive in the diagnosis of hepatosteatosis. Although iron, vitamin B<sub>12</sub> and folic acid deficiencies were included in exclusion criteria, functional forms of these molecules like methylmalonic acid, homocysteine, ferritin levels and total iron binding capacity, which are more sensitive and specific parameters for vitamin B<sub>12</sub> and folic acid deficiencies, were not mentioned. Consequently, RDW, an inexpensive, non-invasive, but powerful indicator overlooked on whole blood analysis, itself without other inflammatory markers may not accurately provide information about progression of nonalcoholic steatohepatitis and fibrosis.
文摘AIM: To study the significance and clinical implication of hepatic lipogranuloma in chronic liver diseases, including fatty liver disease and hepatitis C. METHODS: A total of 376 sequential, archival liver biopsy specimens were reviewed. Lipogranuloma, steatosis and steato-fibrosis were evaluated with combined hematoxylin and eosin and Masson’s trichrome staining. RESULTS: Fifty-eight (15.4%) patients had lipogranuloma, including 46 patients with hepatitis C, 14 patients with fatty liver disease, and 5 patients with other diseases. Hepatic lipogranuloma was more frequently seen in patients with hepatitis C (21%) and fatty liver disease (18%), and its incidence was significantly higher than that in control group (P < 0.0002 and P < 0.007, respectively). In addition, 39 out of the 58 patients with lipogranuloma were associated with steatosis and/or steato-fibrosis. Of the 18 lipogranuloma patients with clinical information available for review, 15 (83%) had risk factors associated with fatty liver disease, such as alcohol use, obesity, hyperlipidemia, and diabetes mellitus. Although the incidence of these risk factors was greater in patients with lipogranuloma than in control group (60%), it did not reach statistical significance. CONCLUSION: Hepatic lipogranuloma is not limited to mineral oil use and commonly associated with hepatic steatosis, hepatitis C and fatty liver disease. With additional histological features of steato-fibrosis, lipogranuloma can also be used as a marker of prior hepatic steatosis.
文摘目的:观察丹参注射液对非酒精性脂肪性肝炎大鼠脂质代谢、肝组织病理变化及脂肪细胞因子的影响,探讨其防治非酒精性脂肪性肝炎(Non-alcoholic steato-hepatitis,NASH)的可能作用机制。方法:采用高脂饮食16周建立大鼠非酒精性脂肪性肝炎模型,并用丹参注射液5 m L/(kg·d)进行干预治疗,观察各组大鼠肝湿质量、肝指数,血清及肝组织匀浆TG、TC含量,HE染色光镜观察肝组织脂肪变和炎症程度,ELISA法检测血清脂联素、TNF-α水平。结果:模型组大鼠肝湿质量、肝指数,血清及肝组织匀浆TG、TC含量升高,血清TNF-α水平升高,脂联素水平下降,肝组织炎症积分升高(P<0.01);丹参治疗后肝组织炎症程度较模型组明显减轻,血清及肝组织匀浆TG、TC含量较模型组明显降低,血清脂联素水平较模型组增高,TNF-α水平较模型组显著下降(P<0.01)。结论:丹参注射液能通过上调脂联素水平、下调TNF-α水平,降低肝脏脂质蓄积,从而抑制肝细胞炎症,防止NASH的进展。
文摘AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD). METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory parameters were assayed after 3 mo of a restricted diet and before silymarin treatment (twice a day orally). The brightness of liver echography texture (hepatorenal ratio brightness) was also defined at same time. These evaluations were repeated after 6 mo of treatment. RESULTS: Serum levels of some metabolic and anti-inflammatory data nonsignificantly lowered after 6 mo of silymarin. On the contrary, Steato test, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase were significantly (P < 0.001) reduced. Instead, the AST/ALT ratio unchanged. Finally, the hepatorenal brightness ratio, as an index of hepatic steatosis, significantly (P < 0.05) dropped. CONCLUSION: The obtained results indicate that silymarin appears to be effective to reduce the biochemical, inflammatory and ultrasonic indices of hepatic steatosis. Some parameters indicative of early stage of atherosclerosis were also lowered.
基金Supported by Research Grant, No. 2076/2007, Entitled SONO-FIBROCAST, Financed by the Romanian Ministry of Educationand Research
文摘AIM: To analyze whether computer-enhanced dynamic analysis of elastography movies is able to better characterize and differentiate between different degrees of liver fibrosis. METHODS: The study design was prospective. A total of 132 consecutive patients with chronic liver diseases and healthy volunteers were examined by transabdominal ultrasound elastography. All examinations were done by two doctors.RESULTS: Due to the limitations of the method, we obtained high-quality elastography information in only 73.48% of the patients. The κ-means clustering method was applied to assess the inter-observer diagnosis varia- bility, which showed good variability values in accordance with the experience of ultrasound examination of every observer. Cohen’sκ test indicated a moderate agreement between the study observers (κ = 0.4728). Furthermore, we compared the way the two observers clustered the patients, using the test for comparing two proportions (t value, two-sided test). There was no statistically significant difference between the two physicians, regardless of the patients’ real status. CONCLUSION: Transabdominal real-time elastography is certainly a very useful method in depicting liver hard- ness, although it is incompletely tested in large multicenter studies.
文摘AIM: To analyze the relationship between the serum lectin-like oxidized low-density lipoprotein receptor-1(LOX-1) levels and clinical and histopathological features of biopsy-confirmed nonalcoholic fatty liver disease(NAFLD) patients.METHODS: Fifty-three consecutive,biopsy-proven NAFLD patients(31 males and 22 females,mean age 42.5 ± 9.6 years) and 26 age- and gender-matched,healthy controls(14 males and 12 females,mean age 39 ± 10.7 years) were included.The patientswith NAFLD were consecutive patients who had been admitted to the hepatology outpatient clinic within the last year and had been diagnosed with NAFLD as the result of liver biopsy.The healthy controls were individuals who attended the outpatient clinic for routine health control and had no known chronic illnesses.The histological evaluation was conducted according t o t he N AF LD ac t ivi ty scoring syst em recommended by The National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network.The serum LOX-1 levels were measured using an ELISA kit(Life Science Inc.USCN.Wuhan,Catalog No.E1859Hu) in both patients and healthy controls.A receiver operating characteristic(ROC) curve analysis was used to identify the optimal cutoff value of LOX-1 and thereby distinguish between patients with nonalcoholic steatohepatitis(NASH) and healthy controls.A P-value < 0.05 was considered statistically significant.RESULTS: NAFLD and healthy control groups were similar in terms of age and sex.NAFLD patients consisted of 8 patients with simple steatosis(15%),27 with borderline NASH(51%) and 18 with definitive NASH(34%).Metabolic syndrome was found in 62.2% of the patients with NAFLD.The mean serum LOX-1 level in biopsy-proven NAFLD patients was 8.49 ± 6.43 ng/m L compared to 4.08 ± 4.32 ng/m L in healthy controls(P = 0.001).The LOX-1 levels were significantly different between controls,simple steatosis and NASH(borderline+definite) cases(4.08 ± 4.32 ng/m L,6.1 ± 6.16 ng/m L,8.92 ± 6.45 ng/m L,respectively,P = 0.004).When the cut-off value for the serum LOX-1 level was set at 5.35 ng/m L,and a ROC curve analysis was performed to distinguish between steatohepatitis patients and controls; the sensitivity and specificity of the serum LOX-1 level were 69.8% and 69.2%,respectively.CONCLUSION: The serum LOX-1 levels were significantly higher in NAFLD patients than in healthy controls.Additionally,the serum LOX-1 levels could differentiate between steatohepatitis patients and healthy controls.
文摘目的:观察柴胡疏肝散对非酒精性脂肪性肝炎(NASH)大鼠肝脏内质网应激(ERS)相关IRE-1α/NF-κB通路的影响,探讨其防治NASH的可能作用机制。方法:采用高脂饮食12周建立NASH大鼠模型,同时以6g·kg-1·d-1的柴胡疏肝散干预12周,油红O和HE染色光镜观察肝组织脂肪变和炎性反应程度;计算NAFLD活动度(NAS);生化法检测血清ALT、AST和肝组织TG、GHOL;Realtime-PCR和Western blot技术检测肝组织GRP78、IRE-1α、NF-κB m RNA和蛋白或磷酸化水平,ELISA检测血清和肝组织中TNF-α、IL-1β水平。结果:模型组和柴胡疏肝散组大鼠肝组织均出现了脂肪变和炎性坏死。与正常组比较,模型组大鼠NAS显著增高(P<0.01),血清ALT、AST水平和肝组织TG、CHOL含量显著升高(P<0.01),肝组织GRP78、IRE-1α、NF-κB m RNA表达显著增强(P<0.01),GRP78蛋白表达和IRE-1α、NF-κB m RNA磷酸化水平显著上调(P<0.01),血清及肝组织TNF-α、IL-1β含量显著增加(P<0.01)。与模型组比较,柴胡疏肝散组大鼠NAS显著降低(P<0.01),血清ALT、AST水平和肝组织TG、CHOL含量显著降低(P<0.01),肝组织GRP78、IRE-1α、NF-κB m RNA表达显著下降(P<0.05,P<0.01),GRP78蛋白表达和IRE-1α、NF-κB m RNA磷酸化水平显著下调(P<0.05),血清及肝组织TNF-α、IL-1β含量显著下降(P<0.05)。结论:ERS相关的IRE-1α/NF-κB参与高脂饮食诱导的大鼠NASH的发生发展。柴胡疏肝散可能通过调节IRE-1α/NF-κB通路抑制过度的ERS,来调节肝脏脂质代谢紊乱、减轻肝脏炎性反应,防止NASH的进展。
