Talat Ayyildiz

Characterization of nonalcoholic fatty liver disease unrelated to the metabolic syndrome

Eur J Clin Invest 2012; 42 (4): 411–418

AST/ALT ratio is not useful in predicting the degree of fibrosis in chronic viral hepatitis patients.

Background and aim Noninvasive tests are primarily used for staging hepatic fibrosis in patients with chronic liver disease. In clinical practice, serum aminotransferase levels, coagulation parameters, and platelet count have been used to predict whether or not a patient has cirrhosis. In addition, several studies have evaluated the accuracy of combinations (or ratios) of these measures. The present study aimed to investigate the relationship between five noninvasive models [AST/ALT ratio (AAR), aspartate aminotransferase to platelet ratio index (APRI), Bonacini cirrhosis discriminant score (CDS), age–platelet index (APind), and King’s score] and the degree of hepatic fibrosis as determined by biopsy in patients with chronic hepatitis B and C. Patients and methods A total of 380 patients with viral hepatitis (237 with chronic hepatitis B and 143 with chronic hepatitis C) who were seen at our clinic between January 2005 and January 2011 were retrospectively analyzed. The degree of fibrosis was determined using the Ishak score. Patients with a fibrosis score of 0–2 were considered to have low fibrosis and those with a score between 3 and 6 were considered to have high fibrosis. Five noninvasive models were compared between the groups with low and high fibrosis. Results There were statistically significant differences between the hepatitis B and C patients with high and low fibrosis with respect to APind (4.49±2.35 vs. 2.41±1.84; P<0.001 in hepatitis B and 4.83±2.25 vs. 2.92±1.88; P<0.001 in hepatitis C), APRI (1.00±1.17 vs. 0.47±0.39; P<0.001 in hepatitis B and 1.01±1.01 vs. 0.41±0.29; P<0.001 in hepatitis C), CDS (4.53±1.90 vs. 3.58±1.30; P<0.001 in hepatitis B and 4.71±2.03 vs. 3.42±1.49; P<0.05 in hepatitis C), and King’s score (24.31±3.14 vs. 7.65±6.70; P<0.001 in hepatitis B and 24.82±2.55 vs. 8.33±7.29; P<0.001 in hepatitis C). There were no significant differences in the AAR between the hepatitis B and C patients with high and low fibrosis (0.78±0.31 vs. 0.74±0.34; P=0.082 in hepatitis B and 0.91±0.40 vs. 0.85±0.27; P=0.25 in hepatitis C). The area under the receiver-operating characteristic curve of the APind, APRI, CDS, and King’s score in the hepatitis B group were 0.767, 0.710, 0.646, and 0.770, respectively; these values were 0.732, 0.763, 0.677, and 0.783, respectively, in the hepatitis C group. Conclusion In conclusion, our data suggest that four of the five noninvasive methods evaluated in this study can be used to predict advanced fibrosis in patients with hepatitis B and C. However, there was no significant relationship between the degree of hepatic fibrosis and the AAR score, indicating that AAR is not useful in estimating the fibrosis stage in hepatitis B and C patients.

The relation between liver histopathology and GGT levels in viral hepatitis: more important in hepatitis B.

BACKGROUND/AIMS To investigate the relationship between gamma-glutamyl transpeptidase (GGT) levels and histopathological status determined by biopsy in patients with chronic hepatitis B and C. MATERIALS AND METHODS Patients with chronic hepatitis B and C who were referred to the Uludağ University Faculty of Medicine Gastroenterology outpatient clinic between January 2005-January 2011 and underwent liver biopsy were included in the study. Overall, 246 patients with hepatitis B and 151 patients with hepatitis C were enrolled. According to the evaluation based on the Ishak score, patients with a histological activity index (HAI) between 0-12 were defined as low activity, and those with an HAI between 13-18 were defined as high activity. In addition, patients with a fibrosis score of 0-2 were defined as low fibrosis, and those with a score between 3-6 were defined as high fibrosis; comparisons were made accordingly. RESULTS In patients with hepatitis B, the mean GGT level was 38.86±42.4 (IU/L) in the low activity group and 60.44±44.4 (IU/L) in the high activity group (p<0.05). In hepatitis B patients, the mean GGT level was 26.89±14.83 (IU/L) in the low fibrosis group, whereas it was 65.60±59.7 (IU/L) in the high fibrosis group (p<0.001). There was no significant difference between HAI and fibrosis group with regard to GGT levels in the hepatitis C patients. CONCLUSION In conclusion, it is proposed that in patients with chronic viral hepatitis, GGT levels can be taken into consideration to predict advanced histological liver damage, especially in patients with hepatitis B.

Serum pigment epithelium-derived factor levels are increased in patients with biopsy-proven nonalcoholic fatty liver disease and independently associated with liver steatosis.

BACKGROUND Increased serum concentrations of pigment epithelium-derived factor (PEDF) have been linked to the metabolic syndrome in the general population. However, the relationship between serum PEDF and nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, remains unknown. METHODS We assayed serum PEDF levels in 156 patients with biopsy-proven NAFLD and 103 nonsteatotic control subjects who were matched for age and sex. The association between levels of PEDF and clinical, biochemical, and histological phenotypes was examined. RESULTS NAFLD patients had significantly higher serum PEDF levels (1.97±0.50 μg/mL) than control subjects (1.51±0.49 μg/mL, Students t test, P<0.001). Multivariable-adjusted stepwise regression analysis showed that PEDF ([beta]=0.32, t=3.13, P=0.002) and triglycerides ([beta]=0.22, t=2.23, P=0.02) were, in the order they entered into the model, the main independent predictors of steatosis scores in our patients with NAFLD. CONCLUSIONS Serum PEDF levels are significantly increased in patients with biopsy-proven NAFLD and are associated with liver steatosis independently of traditional risk factors.

Gallstone Disease Does Not Predict Liver Histology in Nonalcoholic Fatty Liver Disease

Background/Aims We sought to examine whether the presence of gallstone disease (GD) in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) is associated with liver fibrosis and histological nonalcoholic steatohepatitis (NASH) score. Methods We included 441 Turkish patients with biopsy-proven NAFLD. GD was diagnosed in the presence of sonographic evidence of gallstones, echogenic material within the gallbladder with constant shadowing and little or no visualization of the gallbladder or absence of gallbladder at ultrasonography, coupled with a history of cholecystectomy. Results Fifty-four patients (12.2%) had GD (GD+ subjects). Compared with the GD- subjects, GD+ patients were older, had a higher body mass index and were more likely to be female and have metabolic syndrome. However, GD+ patients did not have a higher risk of advanced fibrosis or definite NASH on histology. After adjustment for potential confounding variables, the prevalence of GD in NAFLD patients was not associated with significant fibrosis (≥2) (odds ratio [OR], 1.06; 95% confidence interval [CI], 0.53 to 2.21; p=0.68) or definite NASH (OR, 1.03; 95% CI, 0.495 to 2.12; p=0.84). Conclusions The presence of GD is not independently associated with advanced fibrosis and definite NASH in adult Turkish patients with biopsy-proven NAFLD.

Association of adiponectin receptor (Adipo-R1/-R2) expression and colorectal cancer.

INTRODUCTION Human adiponectin (ApN) is a 30 kDa glycoprotein of 244-amino acids which is extensively produced by adipocytes. ApN acts via two receptors, namely adiponectin receptor-1 (Adipo-R1) and adiponectin receptor-2 (Adipo-R2). Studies have shown the presence of Adipo-R1 and Adipo-R2 expression immunohistochemically in human colorectal cancers (CRCs). However, only a few studies exist which investigated effects of adiponectin receptor expression on CRC characteristics. OBJECTIVES In the present study, we aimed to explore Adipo-R1/-R2 expression in human colorectal cancers and any association with clinicopathological characteristics and survival. MATERIALS AND METHODS The study enrolled 58 colorectal cancer patients with tumor resection and a control group of 30 subjects with normal colon mucosa. RESULTS Positivity for Adipo-R1/-R2 expression was significantly more common in the control group in comparison to the patient group (both p<0.001). There was no significant association between Adipo-R1/-R2 expression and clinicopathological characteristics including age, sex tumor location, pTNM stage, Dukes stage, metastasis, histological differentiation, perineural invasion, venous invasion sex, lymphatic invasion, cancer-related mortality, tumor size and recurrence. Adipo- R1/-R2 positivity was also not significantly linked to progression-free or overall survival [p values (0.871, 0.758 ) and (0.274, 0.232), respectively]. CONCLUSIONS Although significantly reduced Adipo-R1/-R2 expression was found in colorectal cancer patients, it had no influence on survival.

Lack of prognostic significance of SOCS-1 expression in colorectal adenocarcinomas.

INTRODUCTION Recent studies have indicated that down-regulation of the suppressor of cytokine signaling-1 (SOCS-1) gene results in tumor formation and that SOCS-1 acts as a tumor suppressor gene. SOCS-1 has been also suggested to function as a tumor suppressor with colorectal cancer. OBJECTIVES In the present study, we aimed to determine the association of SOCS-1 expression in colorectal cancer tissues with clinicopathologic characteristics immunohistochemically and also to identify its prognostic significance. MATERIALS AND METHODS SOCS-1 expression was studied immunohistochemically in 67 patients diagnosed with resected colorectal carcinomas and 30 control subjects. RESULTS SOCS-1 expression was found in 46.3% of tumor tissues and 46.7% of the control group. Statistical analyses did not establish any significant association between SOCS-1 expression and clinicopathologic characteristics. Also, no significant association with SOCS-1 expression was found using progression-free survival and overall survival analyses (p=0.326 and p=0.360, respectively). CONCLUSIONS Our results show that SOCS-1 has no prognostic significance in colorectal cancer.

Lack of any Prognostic Relationship between Adiponectin Receptor (Adipo R1/R2) Expression for Early/Advanced Stage Gastric Cancer

INTRODUCTION Adiponectin (ApN) is a complement C1q-related protein, mainly secreted from adipose tissue, that signals through ApN receptor 1 (Adipo-R1) and ApN receptor 2 (Adipo-R2). Low serum ApN concentrations are associated with obesity-related malignancies. However, there are very few studies on any prognostic role of ApN receptors in gastric cancer. OBJECTIVES The aim of this study is to investigate the relationship between AdipoR1/R2 expression and early/advanced stage gastric cancer in terms of clinicopathologic characteristics and survival. MATERIALS AND METHODS Eighteen patients with early and 39 with advanced stage gastric cancer who underwent surgical gastric resection were included in this study. RESULTS Adipo-R1 expression was low in 2 of the 18 patients with early stage gastric cancer (11.1%), while 4 had low Adipo-R2 expression (22.2%). In those with advanced stage gastric cancer, 7 of 39 had low Adipo-R1 expression (17.9%) and 16 had low Adipo-R2 expression (41%). Adipo-R2 expression was significantly higher (p=0.011) in moderately differentiated tumors when compared to well-differentiated tumors. While there was nearly a statistically significant relationship between TNM stage (T, tumor size; N, regional lymph node; M, whether distant metastases exist) and Adipo-R2 expression (p=0.054), there was no relationship between Adipo-R1/-R2 expression with tumor stage and survival. CONCLUSION Adipo-R1/-R2 expression has no prognostic significance of in early/advanced stage gastric cancer.

Adipo-R1 and Adipo-R2 Expression in Colorectal Adenomas and Carcinomas

BACKGROUND Human adiponectin (ApN), a 30 kDa glycoprotein of 244-amino acids which is predominantly produced by adipocytes, exerts its effects via two receptors, namely adiponectin receptor-1 (adipo-R1) and adiponectin receptor-2 (adipo-R2) with differential binding affinity to globular adiponectin. Adiponectin receptor expression has been studied in several cancer tissues. However, there are no studies of colorectal adenomas which are considered to be precursors for colorectal carcinoma (CRC). OBJECTIVES In the present study, the expression of adipo-R1 and adipo-R2 was investigated immunohistochemically in colorectal adenomas and colorectal carcinoma tissues in an attempt to determine associations with these tumors. MATERIALS AND METHODS The study enrolled 50 CRC patients with tumor resection and 82 patients who were diagnosed with adenomatous polyps, classified as negative for neoplasia, low-grade dysplasia (L-GD) or high- grade dysplasia (H-GD). RESULTS Expression of both adipo-R1 and adipo-R2 was found to be significantly lower in the CRCs than in colorectal adenomas (tubular and tubulovillous, p=0.009 and p<0.001, respectively). Adipo-R1 and adipo-R2 expression was also significantly lower in the CRC group when compared with the groups of patients with low grade dysplasia, high-grade dysplasia or no neoplasia (p=0.012 and p<0.001, respectively). In addition, it was observed that adipo-R2 expression was generally positive in the non-neoplastic group irrespective of the adipo-R2 expression. In the L-GD, H-GD and CRC groups, the adipo-R2 result was positive whenever adipo-R1 result was positive but some patients with negative adipo-R1 had positive adipo-R2 (p<0.001, p=0.004, p<0.001, respectively). CONCLUSIONS This study indicated that ApN may play a role in the progression of colorectal adenomatous polyps to carcinoma through actions on adipo-R1 and adipo-R2 receptors.

Sağ Kolon Yerleşimli Adenomlar: High-Grade Displazi veya İnvaziv Kanser için Risk Faktörü

Amac: Bu calismanin amaci high-grade displazi (HGD) ve invaziv kanser ( “ilerlemis patoloji (IP)” olarak tanimlanmistir) ile iliskili multipl hasta ve adenom karakterlerini degerlendirmektir. Materyal ve Metod: Toplam 6250 islem sonunda 894 hastada 1379 (% 22.06) polip mevcuttur. Biz patoloji sonuclarina ulasabildigimiz 914 polipi degerlendirmeye aldik. Bulgular: 914 polipte toplam 699 adenom tespit edildi. A total of 699 adenomas were detected from 914 polyps. Sag kolon yerlesimli poliplerde sola gore daha yuksek oranda IP ozellikleri bulundu (% 18.5 vs % 7.1 p: 0.002). Lojistik regresyon analizi sonucunda; erkek cinsiyet, 2 cm’e esit ya da buyuk boyut, villoz histoloji ve non-dimunitif gorunum adenomlardaki IP ozellikleri icin bagimsiz risk faktorleri olarak bulundu. Sonuc: Calismamizda, diger calismalara benzer olarak, erkek cinsiyet, 2 cm’e esit ya da buyuk boyut, villoz histoloji ve non-dimunitif gorunum adenomlardaki IP ozellikleri icin bagimsiz risk faktorleri olarak bulundu. Fakat diger bircok calismanin aksine biz sag kolon yerlesimli poliplerde sol taraf yerlesimli poliplere gore daha yuksek oranda IP ozellikleri bulduk.The long QT syndrome (LQTS) is characterized with arrhythmic attacks, repeating syncopes,seizures, and ventricular arrhythmias leading to sudden death. Arrhythmias with a potential ofmortal course develop due to elongation of ventricular repolarization, either acquired or inborn.Herein the present paper, a case of congenital LQTS, admitted after a sudden cardiac arrest andtotally recovered with implantable cardiac defibrillator (ICD), was focused on