AIM: The pathogenesis of occurrence of liver inflammation and fibrosis in patients with nonalcoholic steatohepatitis (NASH) is not completely understood. Other than insulin resistance, iron abnormalities have been tho...AIM: The pathogenesis of occurrence of liver inflammation and fibrosis in patients with nonalcoholic steatohepatitis (NASH) is not completely understood. Other than insulin resistance, iron abnormalities have been thought to be one of the triggering factors. Therefore, our aim was to study the role of iron abnormalities and HFE gene mutations in patients with NASH. METHODS: Thirty-one patients of NASH diagnosed on the basis of clinical examination biochemistry, ultrasonography and liver biopsy (n = 14) were included in the study. Serum iron parameters (n = 23) (iron, ferritin, total iron-binding capacity and transferrin saturation), Perls' iron staining on liver biopsies (n = 14) and HFE gene mutations (C282Y and H63D) (n = 16) were studied in these patients. The association between iron staining, necroinflammatory activity and fibrosis stage on liver biopsies was also determined. RESULTS: Elevated serum iron, ferritin and transferrin saturation above 55% were observed in 4.3% of patients. On histology, 71% of the patients had negative iron staining, 21.4% had 1+ staining, 7.2% had 2+ staining and none had 3+ or 4+ staining. There was no association between the degree of iron staining and necroinflammatory activity (P=0.55) and fibrosis stage (P= 0.09) on histology. None of the patients had C282Y HFE gene mutation and four patients (25%) were found to be heterozygotes for H63D gene mutation. CONCLUSION: Our study does not favor iron overload and HFE gene mutations as major factors in the pathogenesis of NASH in Asian Indians.展开更多
AIM:To identify the frequency of iron overload and study the three mutations in the HFE gene (C282Y,H63D,and S65C) in patients with chronic liver disorders (CLD) and controls. METHODS:To identify patients with iron ov...AIM:To identify the frequency of iron overload and study the three mutations in the HFE gene (C282Y,H63D,and S65C) in patients with chronic liver disorders (CLD) and controls. METHODS:To identify patients with iron overload (transferrin saturation > 45% in females and > 50% in males and serum ferritin > 1000 ng/mL) we evaluated 236 patients with CLD,including 59 with non-alcoholic steatohepatitis (NASH),22 with alcoholic liver disease (ALD),19 of cirrhosis due to viruses (HBV,HCV),and 136 with cryptogenic cirrhosis. Mutations of the HFE gene were analyzed by PCR-RE. hundred controls were screened for iron status and the mutations. RESULTS:Seventeen patients with CLD showed evidence of iron overload. Fifteen cases of iron overload had cryptogenic cirrhosis and two had ALD. None of the controls showed iron overload. We did not find any individual with 282Y or 65C either in the cases or in the controls. The prevalence of H63D heterozygosity was 12% in normal individuals,14.8% in 236 patients (16.9% in NASH,13.6% in ALD,26.3% in viral and 12.5% in cryptogenic cirrhosis) and the overall prevalence was 13.98%. Only two of the 17 patients with primary iron overload were heterozygous for H63D. One patient with NASH and one normal individual who were homozygous for H63D showed no iron overload.CONCLUSION:Primary iron overload in Indians is nonHFE type,which is different from that in Europeans and further molecular studies are required to determine the defect in various iron regulatory genes.展开更多
We read with great interest the article, ＂Non-alcoholic fatty liver disease may not be a severe disease at presentation among Asian Indians＂ by Madan et at in the recent issue of WJG. Twenty-eight （55%） out of 51 ...We read with great interest the article, ＂Non-alcoholic fatty liver disease may not be a severe disease at presentation among Asian Indians＂ by Madan et at in the recent issue of WJG. Twenty-eight （55%） out of 51 patients with nonalcoholic fatty liver disease （NAFLD） who presented with abnormal transaminases had histological evidence of nonalcoholic steatohepatitis （NASH）. The majority of patients had grade 1 [32 （63%）] or grade 2 [16 （31%）] inflammation and either had no [23 （45%）] fibrosis or stage I [19 （37%）] fibrosis. None of the patients had cirrhosisf11. We agree with Madan et al that Asian Indians with NAFLD who present with unexplained increase in transaminases may have mild disease at presentation on the basis of similar observations made by us. NAFLD has a spectrum which includes patients with only steatosis and NASH that can progress to cirrhotic and hepatocellular carcinoma.展开更多
Cation-exchange high-performance liquid chromatography(CE-HPLC) is a widely used laboratory test to detect variant hemoglobins as well as quantify hemoglobins F and A2 for the diagnosis of thalassemia syndromes. It...Cation-exchange high-performance liquid chromatography(CE-HPLC) is a widely used laboratory test to detect variant hemoglobins as well as quantify hemoglobins F and A2 for the diagnosis of thalassemia syndromes. It's versatility, speed, reproducibility and convenience have made CE-HPLC the method of choice to initially screen for hemoglobin disorders. Despite its popularity, several methodological aspects of the technology remain obscure to pathologists and this may have consequences in specific situations. This paper discusses the basic principles of the technique, the initial quality control steps and the interpretation of various controls and variables that are available on the instrument output. Subsequent sections are devoted to methodological considerations that arise during reporting of cases. For instance, common problems of misidentified peaks, totals crossing 100%, causes of total area being above or below acceptable limits and the importance of pre-integration region peaks are dealt with. Ultimately, CE-HPLC remains an investigation, the reporting of which combines in-depth knowledge of the biological basics with more than a working knowledge of the technological aspects of the technique.展开更多
Introduction: Right ventricular (RV) dysfunction can occur early and late in patients after intracardiac repair (ICR) for Tetralogy of Fallots (TOF). This study focuses on early RV dysfunction as there is limited data...Introduction: Right ventricular (RV) dysfunction can occur early and late in patients after intracardiac repair (ICR) for Tetralogy of Fallots (TOF). This study focuses on early RV dysfunction as there is limited data on it. Aims & Objective: RV function was studied with respect to its incidence, course over 3 months, co-relation with peri operative factors and serum iron levels. Material & Method: All patients of TOF undergoing ICR during July 2007-October 2008, done by single surgeon at a single centre, were prospectively studied. Patients were divided into group A (with RV dysfunction) and group B (without RV dysfunction). All patients underwent pre operative & post operative clinical assessment, biochemical evaluation (serum iron profile & CK MB) and 2D echocardiography (pulse Doppler & tissue Doppler). Echocardiography was done at 24 hours, 4 weeks & 12 weeks of ICR. Patients were also assessed for intra operative parameters including cross clamp time, by pass time, acidosis, RV and PA pressures. Results: 24 patients underwent ICR (transannular patch repair) with mean age of 7.31 ± 4.74 years. RV dysfunction was present in 13 patients (54.2%) but was persistent only in 15.3% (2/13) at 12 weeks. Presence of cyanotic spell (p = 0.006), recurrent chest infection (p = 0.002), raised heamatocrit (p = 0.02), and rise in serum iron level (p = 0.002) were significantly associated with post operative RV dysfunction. It resulted in prolong ICU stay and slower recovery. Pre operative RV dysfunction was associated with difficult weaning from bypass and poor post operative outcome (p < 0.001). Conclusion: RV dysfunction is commonly present even after satisfactory ICR. Its aetiology remains unclear in such setting. In our study, pre operative clinical profile and serum iron fluctuations were important determinants of post operative outcome.展开更多
文摘AIM: The pathogenesis of occurrence of liver inflammation and fibrosis in patients with nonalcoholic steatohepatitis (NASH) is not completely understood. Other than insulin resistance, iron abnormalities have been thought to be one of the triggering factors. Therefore, our aim was to study the role of iron abnormalities and HFE gene mutations in patients with NASH. METHODS: Thirty-one patients of NASH diagnosed on the basis of clinical examination biochemistry, ultrasonography and liver biopsy (n = 14) were included in the study. Serum iron parameters (n = 23) (iron, ferritin, total iron-binding capacity and transferrin saturation), Perls' iron staining on liver biopsies (n = 14) and HFE gene mutations (C282Y and H63D) (n = 16) were studied in these patients. The association between iron staining, necroinflammatory activity and fibrosis stage on liver biopsies was also determined. RESULTS: Elevated serum iron, ferritin and transferrin saturation above 55% were observed in 4.3% of patients. On histology, 71% of the patients had negative iron staining, 21.4% had 1+ staining, 7.2% had 2+ staining and none had 3+ or 4+ staining. There was no association between the degree of iron staining and necroinflammatory activity (P=0.55) and fibrosis stage (P= 0.09) on histology. None of the patients had C282Y HFE gene mutation and four patients (25%) were found to be heterozygotes for H63D gene mutation. CONCLUSION: Our study does not favor iron overload and HFE gene mutations as major factors in the pathogenesis of NASH in Asian Indians.
基金a grant from the Department of Biotechnology, India
文摘AIM:To identify the frequency of iron overload and study the three mutations in the HFE gene (C282Y,H63D,and S65C) in patients with chronic liver disorders (CLD) and controls. METHODS:To identify patients with iron overload (transferrin saturation > 45% in females and > 50% in males and serum ferritin > 1000 ng/mL) we evaluated 236 patients with CLD,including 59 with non-alcoholic steatohepatitis (NASH),22 with alcoholic liver disease (ALD),19 of cirrhosis due to viruses (HBV,HCV),and 136 with cryptogenic cirrhosis. Mutations of the HFE gene were analyzed by PCR-RE. hundred controls were screened for iron status and the mutations. RESULTS:Seventeen patients with CLD showed evidence of iron overload. Fifteen cases of iron overload had cryptogenic cirrhosis and two had ALD. None of the controls showed iron overload. We did not find any individual with 282Y or 65C either in the cases or in the controls. The prevalence of H63D heterozygosity was 12% in normal individuals,14.8% in 236 patients (16.9% in NASH,13.6% in ALD,26.3% in viral and 12.5% in cryptogenic cirrhosis) and the overall prevalence was 13.98%. Only two of the 17 patients with primary iron overload were heterozygous for H63D. One patient with NASH and one normal individual who were homozygous for H63D showed no iron overload.CONCLUSION:Primary iron overload in Indians is nonHFE type,which is different from that in Europeans and further molecular studies are required to determine the defect in various iron regulatory genes.
文摘We read with great interest the article, ＂Non-alcoholic fatty liver disease may not be a severe disease at presentation among Asian Indians＂ by Madan et at in the recent issue of WJG. Twenty-eight （55%） out of 51 patients with nonalcoholic fatty liver disease （NAFLD） who presented with abnormal transaminases had histological evidence of nonalcoholic steatohepatitis （NASH）. The majority of patients had grade 1 [32 （63%）] or grade 2 [16 （31%）] inflammation and either had no [23 （45%）] fibrosis or stage I [19 （37%）] fibrosis. None of the patients had cirrhosisf11. We agree with Madan et al that Asian Indians with NAFLD who present with unexplained increase in transaminases may have mild disease at presentation on the basis of similar observations made by us. NAFLD has a spectrum which includes patients with only steatosis and NASH that can progress to cirrhotic and hepatocellular carcinoma.
文摘Cation-exchange high-performance liquid chromatography(CE-HPLC) is a widely used laboratory test to detect variant hemoglobins as well as quantify hemoglobins F and A2 for the diagnosis of thalassemia syndromes. It's versatility, speed, reproducibility and convenience have made CE-HPLC the method of choice to initially screen for hemoglobin disorders. Despite its popularity, several methodological aspects of the technology remain obscure to pathologists and this may have consequences in specific situations. This paper discusses the basic principles of the technique, the initial quality control steps and the interpretation of various controls and variables that are available on the instrument output. Subsequent sections are devoted to methodological considerations that arise during reporting of cases. For instance, common problems of misidentified peaks, totals crossing 100%, causes of total area being above or below acceptable limits and the importance of pre-integration region peaks are dealt with. Ultimately, CE-HPLC remains an investigation, the reporting of which combines in-depth knowledge of the biological basics with more than a working knowledge of the technological aspects of the technique.
文摘Introduction: Right ventricular (RV) dysfunction can occur early and late in patients after intracardiac repair (ICR) for Tetralogy of Fallots (TOF). This study focuses on early RV dysfunction as there is limited data on it. Aims & Objective: RV function was studied with respect to its incidence, course over 3 months, co-relation with peri operative factors and serum iron levels. Material & Method: All patients of TOF undergoing ICR during July 2007-October 2008, done by single surgeon at a single centre, were prospectively studied. Patients were divided into group A (with RV dysfunction) and group B (without RV dysfunction). All patients underwent pre operative & post operative clinical assessment, biochemical evaluation (serum iron profile & CK MB) and 2D echocardiography (pulse Doppler & tissue Doppler). Echocardiography was done at 24 hours, 4 weeks & 12 weeks of ICR. Patients were also assessed for intra operative parameters including cross clamp time, by pass time, acidosis, RV and PA pressures. Results: 24 patients underwent ICR (transannular patch repair) with mean age of 7.31 ± 4.74 years. RV dysfunction was present in 13 patients (54.2%) but was persistent only in 15.3% (2/13) at 12 weeks. Presence of cyanotic spell (p = 0.006), recurrent chest infection (p = 0.002), raised heamatocrit (p = 0.02), and rise in serum iron level (p = 0.002) were significantly associated with post operative RV dysfunction. It resulted in prolong ICU stay and slower recovery. Pre operative RV dysfunction was associated with difficult weaning from bypass and poor post operative outcome (p < 0.001). Conclusion: RV dysfunction is commonly present even after satisfactory ICR. Its aetiology remains unclear in such setting. In our study, pre operative clinical profile and serum iron fluctuations were important determinants of post operative outcome.
