Kadir Ozturk

Nonalcoholic fatty liver disease is an independent risk factor for atherosclerosis in young adult men

INTRODUCTION The possible cause of accelerated atherosclerosis in NAFLD may be the relationship with the MetS and its components. Our primary goal was to evaluate the relationship between NAFLD and subclinical atherosclerosis in adult male patients between 20 and 40 years of age. Moreover, we aimed to investigate the changes in this association according to the presence or absence of MetS. METHOD Sixty-one male patients with biopsy-proven NAFLD and 41 healthy male volunteers were enrolled. In order to exclude any interference of confounding factors, we studied a specifically selected group with no additional cardiovascular risk. PWV, CIMT and FMD levels were measured in all patients and controls. RESULTS The levels of cf-PWV were significantly higher in SS and NASH patients compared to the control group (P < 0.001); no significant difference was found between SS and NASH patients (P > 0.05). We found significantly decreased FMD levels in patients with SS and NASH compared with control subjects (P < 0.001). Subjects with NASH had significantly greater CIMT measurements than the SS and controls (P = 0.026, P < 0.001, respectively). Although, NAFLD patients with MetS had increased cf-PWV and CIMT and reduced FMD compared to healthy subjects (P < 0.05), no significant difference existed between NAFLD with Mets and NAFLD without MetS in terms of cf-PWV, CIMT and FMD (P > 0.05) CONCLUSION: The present study showed that the presence of NAFLD leads to increased risk of endothelial dysfunction and atherosclerosis in adult male patients, independent of MetS.

The effect of fatty pancreas on serum glucose parameters in patients with nonalcoholic steatohepatitis

OBJECTIVE Fatty pancreas (FP) is related to obesity, and may have some clinical implications on glucose metabolism. The frequency and importance of FP in patients with nonalcoholic steatohepatitis (NASH) are not clear. This study aimed to investigate: the frequency of FP in patients with NASH, and its effects on serum glucose parameters. METHODS FP was detected and graded by transabdominal ultrasonography (USG) in patients with biopsy-proven NASH and healthy controls. Body Mass Index and waist circumference were recorded, and serum lipids, fasting serum glucose, HbA1c, OGTT 2-h, insulin level, insulin resistance, type 2 diabetes mellitus (DM) and prediabetes rates were detected. RESULTS Eighty-four subjects with NASH and 35 healthy controls were enrolled in the study. There was no FP in 41 (48.8%) of the NASH patients according to the study criteria. Forty-three of the NASH patients and 5 of the controls had different grades of fat in their pancreas (51.2% vs. 14%, p=0.001). The HbA1c and OGTT 2-h results were significantly higher in NASH patients with FP compared to those without FP (p=0.003 and p=0.018). The rates of both prediabetes and DM were also found to be significantly increased in NASH patients with FP (p=0.004). The mean waist circumference was higher in patients with FP (p=0.027). Grade of FP by USG showed no effect on study parameters in subgroup analysis. CONCLUSION FP is common in patients with NASH and increases the rate of prediabetes and DM. The coexistence of both NASH and FP has a further impact on glucose metabolism and DM frequency.

Pulse Wave Velocity, Intima Media Thickness, and Flow-mediated Dilatation in Patients with Normotensive Normoglycemic Inflammatory Bowel Disease.

Background:Patients with inflammatory bowel disease (IBD) have increased risk for atherosclerosis. The cause of increased cardiovascular risk is not fully understood. Chronic inflammatory process may predispose to atherosclerosis. We aimed primarily to investigate subclinical atherosclerosis in patients with IBD, by measuring carotid femoral pulse wave velocity (PWV), carotid intima media thickness, and flow-mediated dilatation compared with matched normal controls. Methods:Patients with IBD were recruited among individuals proven to have Crohns disease (CD) and ulcerative colitis (UC). To exclude any interference of confounding factors for endothelial dysfunction or atherosclerosis, we studied a specifically selected group with no additional cardiovascular risk. PWV, carotid intima media thickness, and flow-mediated dilatation levels were measured in all patients and controls. Results:The carotid femoral PWV levels were 8.13 ± 1.61 m/sec in the patients with UC, 8.16 ± 1.74 m/sec in the patients with CD, and 6.85 ± 0.95 m/sec in the healthy subjects. The levels of carotid femoral PWV were significantly higher in patients with CD and UC than control group (P < 0.001). Flow-mediated dilatation levels were significantly decreased in patients with UC and CD (9.6% ± 5.1% versus 108% ± 4.4%) when compared with control subjects (15.1% ± 9.7%) (P = 0.004). No significant difference in carotid intima media thickness was detected between UC, CD, and control groups (P = 0.152). Conclusions:This study suggests that patients with IBD without traditional cardiovascular risk factors have increased risk of endothelial dysfunction and atherosclerosis.

Fecal microbiota transplantation is a rescue treatment modality for refractory ulcerative colitis

Background: Fecal microbial transplantation (FMT) provides to replace beneficial bacteria with more favorable microbiomes in recipient with dysbiosis. The aim of the present study was to prospectively investigate the efficacy of FMT by assessing the clinical and endoscopic response in patients with ulcerative colitis (UC) who had failed anti-inflammatory and immunosuppressive therapy. Methods: In this prospective and uncontrolled study, 30 patients with UC were included. All medications except mesalazine were stopped 4 weeks before FMT. Colonoscopy was performed both before and after FMT. To assess the efficacy of FMT, Mayo scores were calculated at week 0 and week 12. A total of 500 mL extracted fresh fecal suspension was administered into the 30 to 40 cm proximal of terminal ileum of recipients. Results: After FMT, 21 of the (70%) 30 patients showed clinical response, and 13 of the 30 (43.3%) patients achieved clinical and endoscopic remission at the week 12. Nine patients (30%) were accepted as a nonresponder at the end of the week 12. There was no significant difference among donors concerning both the rate of clinical remission and clinical response. No adverse events were observed in the majority of patients during FMT and 12 weeks follow-up. Seven patients (23.3%) experienced mild adverse events such as nausea, vomiting, abdominal pain, diarrhea, and fewer after FMT. Conclusion: FMT could be considered as a promising rescue treatment modality before surgery in patients with refractory UC. Besides, FMT also appears to be definitely safer and more tolerable than the immunosuppressive therapy in patients with UC (NCT02575040).

The association of nonalcoholic fatty liver disease with genetic polymorphisms: a multicenter study

Introduction Growing evidence suggests that multiple factors, such as insulin resistance, nutritional factors, gut microbiota, and hormones released from the adipose tissue, act together on genetically predisposed individuals. We aimed to investigate whether various single-nucleotide polymorphisms (SNPs) play a role in the development of nonalcoholic fatty liver disease (NAFLD) and severity of liver damage in the Anatolian population. Methods Two hundred and sixteen patients with biopsy-proven NAFLD and 150 control participants, aged 18–70 years, were consecutively enrolled in this multicenter study. Blood samples were genotyped for the PNPLA3 (rs738409), IL28B (rs12979860, rs12980275, rs8099917), PPAR-&agr; 227 ALA, PPAR-&ggr; pro 12 ALA, SOD2 C47T, and LOX-1 IVS4–14 polymorphisms using the custom-made LightSNiP assays on a LightCycler 480 II instrument. Results Genotypic distributions of PNPLA3 rs738409 SNPs were different between NAFLD and control participants, but not for other SNPs. The PNPLA3 rs738409 GG polymorphism was associated with a 27-fold increased risk of development of NAFLD (odds ratio=27.8, 95% confidence interval: 3.5–218.4; P=0.002). Patients with the PNPLA3 GG genotype had higher nonalcoholic fatty liver disease activity score levels compared with patients with the PNPLA3 CC genotype (P<0.005). NAFLD patients without fibrosis had a higher frequency of IL28B rs12979860 TT and rs12980275 GG genotypes compared with NAFLD patients with fibrosis (P<0.005). Conclusion The present study proposes that polymorphisms in the PNPLA3 gene have highly predictive value in the development of NAFLD and are independently associated with the severity of liver histology in patients with NAFLD. The results of this study suggest that IL28B rs12979860 TT or rs12980275 GG may play an important protective role against the development of advanced fibrosis and even cirrhosis.

Pentraxin 3 Is a Predictor for Fibrosis and Arterial Stiffness in Patients with Nonalcoholic Fatty Liver Disease

Objective. The aim of the present study was to investigate whether pentraxin 3 (PTX3) can be a new noninvasive marker for prediction of liver fibrosis in patients with NAFLD. We also aimed to evaluate the relationship between PTX3 and atherosclerosis in patients with NAFLD. Method. Fifty-four male patients with biopsy-proven NAFLD and 20 apparently healthy male volunteers were included. PTX3 levels were determined, using an ELISA method (R&D Sysytems, Quantikine ELISA, USA). To detect the presence of subclinical atherosclerosis in NAFLD, measurements of CIMT, FMD, and cf-PWV levels were performed. Results. PTX3 levels in NAFLD patients with fibrosis were higher than both NAFLD patients without fibrosis and controls (P = 0.032 and P = 0.028, respectively), but there was no difference between controls and NAFLD patients without fibrosis in terms of PTX3 levels (P = 0.903). PTX3 levels were strongly correlated with cf-PWV (r = 0.359, P = 0.003), whereas no significant correlation was found with other atherosclerosis markers, CIMT and FMD. Conclusion. Elevated plasma PTX3 levels are associated with the presence of fibrosis in patients with NAFLD, independently of metabolic syndrome components. This study demonstrated that for the first time there is a close association between elevated PTX3 levels and increased arterial stiffness in patients with NAFLD.

A Rare Case of Upper Gastrointestinal Bleeding: Duodenal Metastasis of Transitional Cell Carcinoma Originating from Renal Pelvis

To the Editor Transitional cell carcinoma (TCC) is the predominant histologic type of bladder cancer. Much less commonly, TCC can arise in the renal pelvis, which is known as upper tract urothelial cancers. Local invasion through direct extension of the tumor is the most common mechanism of spread. However, vascular or lymphatic metastases may occur [1]. At diagnosis, 75 % of patients have superficial disease, 20 % have locally invasive disease, and only 5 % have distant metastasis, frequently to the lymph nodes, liver, lungs, and bone [2]. Although oral and intestinal metastases of TCC from bladder have been reported previously [2, 5], we present here a rare case of upper gastrointestinal (GI) bleeding secondary to duodenal metastasis of TCC of renal pelvis. A 45-year-old man referred to our clinic from Medical Oncology department for endoscopic evaluation of black stool and decrease in hematocrit level (from 33 to 25 %). In his medical history, radical right nephrectomy was performed to treat patient with invasive high-grade urothelial cell (T3 N1 Mx) cancer at the renal pelvis 2 years ago, and 2 months after, he began treated with radiotherapy and chemotherapy because of metastasis to the cerebellum, peritoneum, and lung. He denied using any medication other than chemotherapeutic agents. On examination, he appeared pale and dark sticky stool was observed at digital rectal examination. At endoscopy, we found a large ulcerated mass at the junction of second and third stage of duodenum (Fig. 1). The bleeding was not observed during the procedure, and any other lesion that explains the bleeding was not observed. For diagnosis, biopsies were performed and the biopsies showed malignant cells in the duodenum. After supportive and acid suppression therapy and erythrocyte replacement, the hematocrit levels remained stable and recurrent hemorrhage was not observed. The patient accepted as inoperable due to disseminated metastasis. After 2 weeks, the patient died due to extensive metastatic disease and sepsis. Urinary bladder TCC is the ninth most common malignancy worldwide [3]. Intestinal metastases of TCC are rarely of clinical significance. Most of them are found in postmortem examinations. In autopsy case series, nearly 13 % of TCC has been found with gastrointestinal metastasis [4]. Upper GI bleeding from duodenal metastasis of TCC was reported in a few studies [2, 5]. But these metastases are originating from the bladder. In our patient, primary origin of TCC is the renal pelvis. To our knowledge, this is the first case with upper GI bleeding originating from the renal pelvis. Although most cases of upper GI bleeding are from peptic ulcer diseases, with these rare cases, duodenal metastasis of TCC must be taken into account as in * Yusuf Serdar Sakin ysakin@gata.edu.tr

Neutrophil-to-lymphocyte ratio for predicting fibrosis in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is not only associated with liver-related mortality and morbidity, but also is linked to an increased cardiovascular disease risk, on the basis of rapidly expanding evidence [1]. Several clinical studies have reported that the neutrophil-tolymphocyte ratio (NLR) is an independent marker of cardiovascular disease-related mortality in the general population and in patients who have cardiovascular risk factors [2]. Recently, we read with great interest the article by Kara et al. [3], evaluating the role of NLR in predicting the liver histology in patients with NAFLD. They reported that NLR is not associated with the severity of liver histology in this large-scale study and suggested that NLR cannot be used as an indicator of liver injury in patients with NAFLD. The results seem important with regard to the relationship between NLR and liver histology. However, we believe that some points should be addressed. The authors did not include patients without cardiovascular risk factors such as diabetes mellitus and hypertension in this study. However, the presence of hyperglycemia was excluded only on the basis of fasting plasma glucose levels, and standard oral glucose tolerance tests (OGTTs) were not performed. OGTT has been accepted as the gold-standard method for the diagnosis of diabetes mellitus and impaired glucose tolerance. Therefore, OGTT would be more appropriate to clarify glucose tolerance in the patients. In addition, there were no data on blood pressure levels. It is well known that NLR is associated independently with different levels of glucose tolerance and blood pressure [4]. In the present study, the authors aimed to investigate the relationship between NLR and liver histology as a predictor of the presence of chronic subclinical inflammation in biopsy-proven NAFLD. C-reactive protein (CRP) has been identified as an independent marker of liver fibrosis in NAFLD and has been shown to be associated with NLR in recent studies [5]. However, levels of CRP and other inflammatory markers were not measured in this study. The use of other inflammatory markers such as CRP and erythrocyte sedimentation rate may accurately support the relationship between histologic findings and NLR in NAFLD. Moreover, healthy individuals were not included for comparison with the patient group in this study. We think that the presence of a control group would increase the reliability of the results of this study. NLR is a cheap and easy-to-reach parameter to show inflammation. However, there can be small but important differences in each measurement in the parameters of complete blood count. The parameter levels can vary even if we measure the same sample again. We believe that taking an average of two to three complete blood count measurements could be better for the study. Consequently, excluding these confounding factors before making certain interpretations would reveal any independent association between NLR and liver injury more accurately and provide the readers of the journal clearer information.

The degree of mucosal damage to the small intestine and serum immunoglobulin G4 levels correlate with celiac disease.

Background Celiac disease (CD) is an immune-mediated and chronic inflammatory enteropathy, triggered by the ingestion of gluten in genetically susceptible individuals. Immunoglobulin G4 (IgG4)-related diseases are a recently defined emerging clinical condition, characterized by increased serum IgG4 concentrations. The aim of this study was to investigate whether IgG4 levels correlate with the titers of intestinal antibodies and the degree of mucosal damage in CD patients. Materials and methods A total of 41 CD patients and 28 healthy controls were included in the study. All patients underwent a duodenal biopsy and were then diagnosed with the modified Marsh classification. Blood samples were obtained for IgG4 measurements. Serums were kept at −80°C until the analysis was carried out and plasma IgG4 levels were determined using an enzyme-linked immune sorbent assay method with a diagnostic cutoff value of 135 mg/dl. Results The mean age of the CD and the control group was 26.8±8.3 and 26.9±6.2 years, respectively. The mean IgG4 levels were significantly higher in CD patients (283.21±39.02 mg/dl) compared with the healthy control group (68.97±15.89 mg/dl, P<0.0001). In the CD group, 27/41 patients and in the control group, 4/28 patients had high IgG4 levels (>135 mg/dl, P<0.0001). A close correlation was found between the grade of mucosal damage, IgG4 levels, and antigliadin-IgA; the higher the grade Marsh score, the higher the measured IgG4 (P<0.05). Conclusion In our study, IgG4 levels of CD patients were higher than normal ranges whereas the results of the control group were within physiologic limits. We also showed for the first time that there was a correlation between IgG4 levels, autoantibody, and severity of mucosal damage. To the best of our knowledge, this is the first study to evaluate IgG4 levels and mucosal damage in CD patients.

Investigation of the arterial stiffness and associated factors in patients with familial Mediterranean fever.

Objective: Because of the ongoing and recurring inflammatory state in familial Mediterranean fever (FMF), patients may experience a high risk of cardiovascular events. Our aim was to investigate the arterial stiffness and associated factors in patients with FMF. Methods: Sixty-nine consecutive FMF patients (including 11 females) and 35 controls (including 5 females) were enrolled in the study. The demographical, clinical, and laboratory data and genetic mutations of the patients were recorded. In the study, FMF patients according to the Tel-Hashomer criteria were included, whereas patients with other known inflammatory rheumatologic disease, atherosclerotic cardiovascular disease, hypertension, diabetes, those under the age of 18 years, or those refusing to participate in the study were excluded. Arterial stiffness measurements were performed using the TensioMed device (TensoMed Ltd, Budapest, Hungary). Results: The patient and control groups were similar in terms of the mean ages, BMIs, gender, systolic blood pressures, and smoking. FMF patients had a higher pulse wave velocity (PWV) (7.73±1.3 and 7.18±1.1 m/s; p=0.03) and lower brachial and aortic augmentation indexes (–64.6±14.6% and –54.6±25.9%, p=0.041 and 4.9±7.4% and 14.0±11.5%, p=0.025, respectively) compared with the controls. Thirty-one (45%) patients were in the “during-attack” state and had higher PWV (8.17±1.6 and 7.38±0.9 m/s; p=0.027) compared with the asymptomatic patients. PWV was correlated to serum CRP, WBC, ESR, fibrinogen, and neutrophil/lymphocyte ratios (r=0.666, 0.429, 0.441, 0.388, and 0.460, respectively). The genetic mutation and predominant attack type had no effect on arterial stiffness. Conclusion: FMF patients have increased arterial stiffness during attacks compared with asymptomatic patients and controls. The impaired arterial stiffness is correlated to the severity of the inflammatory state rather than to the attack type or genetic mutations.