- Email: [email protected]
Genetic polymorphism in cluster of differentiation 14 (CD14) gene C(-159) t is associated with nonalcoholic fatty liver disease (NAFLD)
of Pre and post liver biopsy was the limitation. A large control trial needs to validate.
Swastik Agrawal, Ajay Duseja, Radha K. Dhiman, Yogesh K. Chawla
Corresponding Author. Patrick Basu. E-mail: [email protected]
Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
ANALYSIS OF RISK FACTORS FOR FIBROSIS IN BIOPSY PROVEN NAFLD Kaumudee Pattnaik,1 Pallavi Bhuyan,1 Sitaram Mahapatra,1 Bijay Mishra,2 Sanjib Kar,2 S. P. Singh2 1
Department of Pathology, SCB Medical College, Cuttack, India, Department of Gastroenterology, SCB Medical College, Cuttack, India
2
Background: Nonalcoholic fatty liver disease (NAFLD) is fast becoming one of the top concerns for clinicians due to the obesity epidemic and it's potential to progress to chronic liver disease which has significant impact on liver-related morbidity and mortality. Advanced fibrosis that accompanies NAFLD leads to the development of Cirrhosis and hepatocellular carcinoma. Objectives: There is a need to identify patients who are likely to have fibrosis. Methods: Two hundred and sixteen cases were selected for liver biopsies taking into account the clinical parameters and or Ultrasonography findings of fatty liver. Formalin fixed paraffin embedded tissue sections were stained with Haematoxylin and Eosin, Reticulin and Masson's Trichrome. Histopathologic scoring was done as per Brunt et al scoring system. Result: Out of 216 biopsy proven NAFLD patients, 183 were male and 33 female. On histopathological study, fibrosis was found in 48.216 (22%) cases. On evaluation of metabolic profile, two third (59%) were obese (BMI > 23), 75% had transaminitis, 93% had dyslipidemia, 23% were diabetic and 20% were hypertensive. Inspite of these metabolic derangements, only 36% had moderate fatty change on ultrasonography and rests were mild. Metabolic syndrome was present in only 45% of patients. Conclusion: At present, liver biopsy is the only diagnostic method to detect progression to fibrosis stage in NAFLD cases. Early detection of fibrosis can reverse the pathogenetic mechanism with prompt institution of therapy. Factors associated with fibrosis in our study were higher age i.e, age >40 years, female gender, high BMI >23 and moderate fatty change on ultrasonography. Corresponding Author. Kaumudee Pattnaik. E-mail: [email protected]
PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) WITH AND WITHOUT METABOLIC SYNDROME HAVE SIMILAR INCREASE IN BODY FAT
Background and Objectives: Obesity predisposes to both nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS). However, body fat content has not been characterized in Indian patients with NAFLD and MS. Methods: Thirty consecutive patients (M:F 19:11, mean age 39 years) of NAFLD over a period of 1 year were evaluated for the presence of metabolic syndrome (using modified ATP III criteria) and body fat (using bioelectrical impedance analysis). Comparison of body fat was made between obese (BMI$25 Kg/m2) and non-obese patients and between patients with and without MS using independent sample ttest or Mann-Whitney U test as appropriate. A P value of <0.05 was considered significant. Results: Twenty four (80%) of patients were obese with a mean body mass index (BMI) of 29 4 Kg/m2. MS was present in 20 (67%) of patients. As expected, total body fat mass, percentage of body fat and increase in body fat mass and fat percentage from the predicted values were significantly higher in obese than in non-obese patients (299 vs. 173 Kg, 379 vs. 255%, 97 vs. 02 Kg and 75 vs. 35%, P values 0.005, 0.007, 0.050 and <0.001 respectively). However, there was no difference in BMI, total body fat mass, percentage of body fat or increase in body fat mass and fat percentage from the predicted values between patients with and without MS (294 vs. 285 Kg/m2, 279 vs. 259 Kg, 359 vs. 3311%, 88 vs. 68 Kg and 65 vs. 66%, P values 0.429, 0.559, 0.502, 0.448 and 0.880 respectively). Conclusions: Body fat content is significantly higher in obese in comparison to non-obese patients with NAFLD. There is no difference in body fat content between patients with and without MS, suggesting that body fat content is equally increased in these two groups of patients with NAFLD. Corresponding Author. Ajay Duseja. E-mail: [email protected]
GENETIC POLYMORPHISM IN CLUSTER OF DIFFERENTIATION 14 (CD14) GENE C(-159) T IS ASSOCIATED WITH NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) Shweta Kapil,1 Ajay Duseja,1 Pallab Ray,2 Ashim Das,3 Anuradha Chakraborti,4 Radha K Dhiman,1 Yogesh K Chawla1 1
Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India, 2Department of Microbiology, Postgraduate Institute of Medical Education and
Journal of Clinical and Experimental Hepatology | March 2013 | Vol. 3 | No. 1S | S24–S32
S27
Non-alcoholic Fatty Liver Disease
JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY
ABSTRACTS
Research, Chandigarh, India, 3Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India, 4Department of Experimental Medicine & Biotechnology Postgraduate Institute of Medical Education and Research, Chandigarh, India
Non-alcoholic Fatty Liver Disease
Introduction: Nonalcoholic Fatty Liver Disease (NAFLD) is a multifactorial disease. Genetic factors including polymorphisms of Toll like receptor (TLR) and its co-receptor CD14 (Cluster of differentiation 14) may be involved in the pathogenesis of NAFLD. Aim: To study the role of genetic variants of CD14 gene [C (-159) T and C (-550) T] in the pathogenesis of NAFLD. Methodology: In a prospective study, 130 patients with NAFLD (M:F =78:52, mean age 38.4710.6 years) and 50 age and gender matched healthy volunteers(HVs) (M:F=38:12,mean age 36.56 4.2) were included in the study. Genotyping of C(-159)T and C(-55)T polymorphism in the promoter region of CD14 gene was done using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results were confirmed by DNA sequencing. Recessive and dominant models were applied to determine the association of these polymorphisms with the recessive and dominant allele. Results: Among C(-550)T polymorphism, CC genotype was equally common genotype amongst patients with NAFLD and HVs (77/130 [59.2%] vs.34/50 [68%] OR 0.68, 95% CI = 0.34-1.36, P=0.27). On applying recessive model (TT vs. CC+TC), [TT, 16(7.44%) vs.CC+TC,199(92.56%),OR=1.6,95% CI=0.53-5.07, P =0.37] and dominant model (TT+TC vs.CC) [TT+TC, 61 (28.37% vs. CC,154 (71.63%) OR=1.49, 95% CI=0.82-2.72, P =0.18] we did not find any association of C(-550)T polymorphism with NAFLD. In case of C(-159)T polymorphism TT genotype was higher among patients with NAFLD than HVs [59/130(45.38%)vs.10/50(20%) OR 3.32, 95% CI = 1.53-7.20, P =0.001]. On applying recessive model [TT vs. CC+TC], C (-159) T polymorphism was found to be associated with NAFLD [TT, 118(56.46%) vs. CC+TC, 91(43.54%) OR=3.24, 95%CI=1.8-5.8, P =.0001]. However when we applied dominant model (TT+ TCvs.CC) [TT+TC, 169(80.86%), CC, 40 (19.14%), OR=1.69, 95% CI=0.9-3.14, P =0.09] we did not find any association of C (-159) T polymorphism with NAFLD. Conclusion: C (-159) T polymorphism of TLR co-receptor CD14 is associated with NAFLD. Corresponding Author. Ajay Duseja. E-mail: [email protected]
LIVER DISEASE STRUCTURE EXPLORED IN RUSSIAN FEDRATION NATIONAL – WIDE DIREG-L-01903 STUDY FOR NON ALCOHOLIC FATTY LIVER DISEASE SCREENING Elena Zyatenkova, Vladimir Ivashkin, Oxana Drapkina
S28
21ST ANNUAL CONFERENCE—2013
I.M. Sechenov First Moscow State Medical University.V.H,Vasilenko Clinic of Propedeutics, Gastroenterology, and Hepatology, Russia
Background and Aims: To assess liver disease nosologic structure in patients enrolled into the national population-based DIREG-L-01903 study for non-alcoholic fatty liver disease (NAFLD) screening. Methods: In total of 30,787 primary care patients (56% females, mean age 47.816 yrs) were enrolled into open multicenter national-wide prospective study. Careful clinical examination, serum biochemistry (including ALT, AST, g-GT, lipid spectrum and hepatitis screening) and abdominal ultrasound diagnostics with precise liver, spleen and pancreas assessment and waist circumstence were performed in 30,754 patients. Results: NAFLD was found in 8215 (27&)of included patients. Within group with confirmed NAFLD liver steatosis was diagnosed in 80.3%, steatohepatitisin 16.8 %, and cirrhosis in 2.9% of patients. AST was increased $ 1.5 N in 2816 (9.2%), ALT was increased $ 1.5 N in 3144 (10.2%) of patients. In total, liver ultrasound examination revealed liver enlargement in 16.3%, portal hypertension in 0.5 %, signs of liver steatosis in 24.2 %, signs of liver fibrosis in 2.3%, signs of liver cirrhosis in 0.8% of total patients. Corresponding Author. Elena Zyatenkova. E-mail: [email protected]
THE ROLE OF CORRECTION OF DISBACTERIOSIS IN TREATMENT OF ATHEROGENIC DISLIPOPROTEINEMIA IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE Elizaveta Cherkashova, Larisa Zvenigorodskaja, Tamara Nilova Central Scientific Research Institute of Gastroenterology, Moscow, Russia
Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is one of the important factors of cardiovascular risk. However the diagnosis of NAFLD is frequently late. The aim of the study was to devise noninvasive method to diagnose NAFLD. Methods: One hundred and eight patients were examined in the age of 35-70 years. All patients before and after treatment were examined by several points: biochemical blood analysis (lipids, parameters of liver function), endotoxin and nitric oxide in blood, analysis of short chain fat acids (SFA) in feces Liber biopsy was also performed for all the patients. We also made biopsy of liver. Patients have been divided into 2 groups depending on activity of hepatitis: 1)steatosis 2)steatohepatitis, and into 3 groups according to the therapy: 1)statin 10mg; 2)probiotic; 3)probiotic in combination with statin. © 2013, INASL
Swastik Agrawal, Ajay Duseja, Radha K. Dhiman, Yogesh K. Chawla
Corresponding Author. Patrick Basu. E-mail: [email protected]
Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
ANALYSIS OF RISK FACTORS FOR FIBROSIS IN BIOPSY PROVEN NAFLD Kaumudee Pattnaik,1 Pallavi Bhuyan,1 Sitaram Mahapatra,1 Bijay Mishra,2 Sanjib Kar,2 S. P. Singh2 1
Department of Pathology, SCB Medical College, Cuttack, India, Department of Gastroenterology, SCB Medical College, Cuttack, India
2
Background: Nonalcoholic fatty liver disease (NAFLD) is fast becoming one of the top concerns for clinicians due to the obesity epidemic and it's potential to progress to chronic liver disease which has significant impact on liver-related morbidity and mortality. Advanced fibrosis that accompanies NAFLD leads to the development of Cirrhosis and hepatocellular carcinoma. Objectives: There is a need to identify patients who are likely to have fibrosis. Methods: Two hundred and sixteen cases were selected for liver biopsies taking into account the clinical parameters and or Ultrasonography findings of fatty liver. Formalin fixed paraffin embedded tissue sections were stained with Haematoxylin and Eosin, Reticulin and Masson's Trichrome. Histopathologic scoring was done as per Brunt et al scoring system. Result: Out of 216 biopsy proven NAFLD patients, 183 were male and 33 female. On histopathological study, fibrosis was found in 48.216 (22%) cases. On evaluation of metabolic profile, two third (59%) were obese (BMI > 23), 75% had transaminitis, 93% had dyslipidemia, 23% were diabetic and 20% were hypertensive. Inspite of these metabolic derangements, only 36% had moderate fatty change on ultrasonography and rests were mild. Metabolic syndrome was present in only 45% of patients. Conclusion: At present, liver biopsy is the only diagnostic method to detect progression to fibrosis stage in NAFLD cases. Early detection of fibrosis can reverse the pathogenetic mechanism with prompt institution of therapy. Factors associated with fibrosis in our study were higher age i.e, age >40 years, female gender, high BMI >23 and moderate fatty change on ultrasonography. Corresponding Author. Kaumudee Pattnaik. E-mail: [email protected]
PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) WITH AND WITHOUT METABOLIC SYNDROME HAVE SIMILAR INCREASE IN BODY FAT
Background and Objectives: Obesity predisposes to both nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS). However, body fat content has not been characterized in Indian patients with NAFLD and MS. Methods: Thirty consecutive patients (M:F 19:11, mean age 39 years) of NAFLD over a period of 1 year were evaluated for the presence of metabolic syndrome (using modified ATP III criteria) and body fat (using bioelectrical impedance analysis). Comparison of body fat was made between obese (BMI$25 Kg/m2) and non-obese patients and between patients with and without MS using independent sample ttest or Mann-Whitney U test as appropriate. A P value of <0.05 was considered significant. Results: Twenty four (80%) of patients were obese with a mean body mass index (BMI) of 29 4 Kg/m2. MS was present in 20 (67%) of patients. As expected, total body fat mass, percentage of body fat and increase in body fat mass and fat percentage from the predicted values were significantly higher in obese than in non-obese patients (299 vs. 173 Kg, 379 vs. 255%, 97 vs. 02 Kg and 75 vs. 35%, P values 0.005, 0.007, 0.050 and <0.001 respectively). However, there was no difference in BMI, total body fat mass, percentage of body fat or increase in body fat mass and fat percentage from the predicted values between patients with and without MS (294 vs. 285 Kg/m2, 279 vs. 259 Kg, 359 vs. 3311%, 88 vs. 68 Kg and 65 vs. 66%, P values 0.429, 0.559, 0.502, 0.448 and 0.880 respectively). Conclusions: Body fat content is significantly higher in obese in comparison to non-obese patients with NAFLD. There is no difference in body fat content between patients with and without MS, suggesting that body fat content is equally increased in these two groups of patients with NAFLD. Corresponding Author. Ajay Duseja. E-mail: [email protected]
GENETIC POLYMORPHISM IN CLUSTER OF DIFFERENTIATION 14 (CD14) GENE C(-159) T IS ASSOCIATED WITH NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) Shweta Kapil,1 Ajay Duseja,1 Pallab Ray,2 Ashim Das,3 Anuradha Chakraborti,4 Radha K Dhiman,1 Yogesh K Chawla1 1
Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India, 2Department of Microbiology, Postgraduate Institute of Medical Education and
Journal of Clinical and Experimental Hepatology | March 2013 | Vol. 3 | No. 1S | S24–S32
S27
Non-alcoholic Fatty Liver Disease
JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY
ABSTRACTS
Research, Chandigarh, India, 3Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India, 4Department of Experimental Medicine & Biotechnology Postgraduate Institute of Medical Education and Research, Chandigarh, India
Non-alcoholic Fatty Liver Disease
Introduction: Nonalcoholic Fatty Liver Disease (NAFLD) is a multifactorial disease. Genetic factors including polymorphisms of Toll like receptor (TLR) and its co-receptor CD14 (Cluster of differentiation 14) may be involved in the pathogenesis of NAFLD. Aim: To study the role of genetic variants of CD14 gene [C (-159) T and C (-550) T] in the pathogenesis of NAFLD. Methodology: In a prospective study, 130 patients with NAFLD (M:F =78:52, mean age 38.4710.6 years) and 50 age and gender matched healthy volunteers(HVs) (M:F=38:12,mean age 36.56 4.2) were included in the study. Genotyping of C(-159)T and C(-55)T polymorphism in the promoter region of CD14 gene was done using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results were confirmed by DNA sequencing. Recessive and dominant models were applied to determine the association of these polymorphisms with the recessive and dominant allele. Results: Among C(-550)T polymorphism, CC genotype was equally common genotype amongst patients with NAFLD and HVs (77/130 [59.2%] vs.34/50 [68%] OR 0.68, 95% CI = 0.34-1.36, P=0.27). On applying recessive model (TT vs. CC+TC), [TT, 16(7.44%) vs.CC+TC,199(92.56%),OR=1.6,95% CI=0.53-5.07, P =0.37] and dominant model (TT+TC vs.CC) [TT+TC, 61 (28.37% vs. CC,154 (71.63%) OR=1.49, 95% CI=0.82-2.72, P =0.18] we did not find any association of C(-550)T polymorphism with NAFLD. In case of C(-159)T polymorphism TT genotype was higher among patients with NAFLD than HVs [59/130(45.38%)vs.10/50(20%) OR 3.32, 95% CI = 1.53-7.20, P =0.001]. On applying recessive model [TT vs. CC+TC], C (-159) T polymorphism was found to be associated with NAFLD [TT, 118(56.46%) vs. CC+TC, 91(43.54%) OR=3.24, 95%CI=1.8-5.8, P =.0001]. However when we applied dominant model (TT+ TCvs.CC) [TT+TC, 169(80.86%), CC, 40 (19.14%), OR=1.69, 95% CI=0.9-3.14, P =0.09] we did not find any association of C (-159) T polymorphism with NAFLD. Conclusion: C (-159) T polymorphism of TLR co-receptor CD14 is associated with NAFLD. Corresponding Author. Ajay Duseja. E-mail: [email protected]
LIVER DISEASE STRUCTURE EXPLORED IN RUSSIAN FEDRATION NATIONAL – WIDE DIREG-L-01903 STUDY FOR NON ALCOHOLIC FATTY LIVER DISEASE SCREENING Elena Zyatenkova, Vladimir Ivashkin, Oxana Drapkina
S28
21ST ANNUAL CONFERENCE—2013
I.M. Sechenov First Moscow State Medical University.V.H,Vasilenko Clinic of Propedeutics, Gastroenterology, and Hepatology, Russia
Background and Aims: To assess liver disease nosologic structure in patients enrolled into the national population-based DIREG-L-01903 study for non-alcoholic fatty liver disease (NAFLD) screening. Methods: In total of 30,787 primary care patients (56% females, mean age 47.816 yrs) were enrolled into open multicenter national-wide prospective study. Careful clinical examination, serum biochemistry (including ALT, AST, g-GT, lipid spectrum and hepatitis screening) and abdominal ultrasound diagnostics with precise liver, spleen and pancreas assessment and waist circumstence were performed in 30,754 patients. Results: NAFLD was found in 8215 (27&)of included patients. Within group with confirmed NAFLD liver steatosis was diagnosed in 80.3%, steatohepatitisin 16.8 %, and cirrhosis in 2.9% of patients. AST was increased $ 1.5 N in 2816 (9.2%), ALT was increased $ 1.5 N in 3144 (10.2%) of patients. In total, liver ultrasound examination revealed liver enlargement in 16.3%, portal hypertension in 0.5 %, signs of liver steatosis in 24.2 %, signs of liver fibrosis in 2.3%, signs of liver cirrhosis in 0.8% of total patients. Corresponding Author. Elena Zyatenkova. E-mail: [email protected]
THE ROLE OF CORRECTION OF DISBACTERIOSIS IN TREATMENT OF ATHEROGENIC DISLIPOPROTEINEMIA IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE Elizaveta Cherkashova, Larisa Zvenigorodskaja, Tamara Nilova Central Scientific Research Institute of Gastroenterology, Moscow, Russia
Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is one of the important factors of cardiovascular risk. However the diagnosis of NAFLD is frequently late. The aim of the study was to devise noninvasive method to diagnose NAFLD. Methods: One hundred and eight patients were examined in the age of 35-70 years. All patients before and after treatment were examined by several points: biochemical blood analysis (lipids, parameters of liver function), endotoxin and nitric oxide in blood, analysis of short chain fat acids (SFA) in feces Liber biopsy was also performed for all the patients. We also made biopsy of liver. Patients have been divided into 2 groups depending on activity of hepatitis: 1)steatosis 2)steatohepatitis, and into 3 groups according to the therapy: 1)statin 10mg; 2)probiotic; 3)probiotic in combination with statin. © 2013, INASL