Hakan Akin

Melatonin ameliorates methionine- and choline-deficient diet-induced nonalcoholic steatohepatitis in rats.

Abstract:  Nonalcoholic steatohepatitis (NASH) may progress to advanced fibrosis and cirrhosis. Mainly, oxidative stress and excessive hepatocyte apoptosis are implicated in the pathogenesis of progressive NASH. Melatonin is not only a powerful antioxidant but also an anti‐inflammatory and anti‐apoptotic agent. We aimed to evaluate the effects of melatonin on methionine‐ and choline‐deficient diet (MCDD)‐induced NASH in rats. Thirty‐two male Wistar rats were divided into four groups. Two groups were fed with MCDD while the other two groups were fed a control diet, pair‐fed. One of the MCDD groups and one of the control diet groups were administered melatonin 50 mg/kg/day intraperitoneally, and the controls were given a vehicle. After 1 month the liver tissue oxidative stress markers, proinflammatory cytokines and hepatocyte apoptosis were studied by commercially available kits. For grading and staging histological lesions, Brunt et al.’s system was used. Melatonin decreased oxidative stress, proinflammatory cytokines and hepatocyte apoptosis. The drug ameliorated the grade of NASH. The present study suggests that melatonin functions as a potent antioxidant, anti‐inflammatory and antiapoptotic agent in NASH and may be a therapeutic option.

Arterial stiffness in patients with non-alcoholic fatty liver disease is related to fibrosis stage and epicardial adipose tissue thickness

OBJECTIVE Non-alcoholic fatty liver disease (NAFLD) is associated with atherosclerosis and reduced vascular compliance. The purpose of this study was to examine the relationships between arterial stiffness measures, the histological severity of NAFLD, and epicardial fat thickness (EFT). METHODS A total of 100 patients with biopsy-proven NAFLD and 50 age- and sex-matched controls were enrolled. The histological severity was assessed in all NAFLD patients. Measurements of arterial stiffness [pulse-wave velocity (PWV) and augmentation index (AIx)] were carried out using a Mobil-O-Graph arteriograph system. EFT was assessed by means of echocardiography. RESULTS Compared with controls, NAFLD patients had significantly higher PWV and AIx values. Stepwise linear regression analysis demonstrated that the liver fibrosis score and EFT were independent predictors of both PWV and AIx values in NAFLD patients. CONCLUSIONS Patients with NAFLD have an increased arterial stiffness, which reflects both the severity of liver fibrosis and increased EFT values.

Diet, microbiota, and colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer in the world causing nearly 500,000 deaths every year. In addition to genetic background, environmental factors including diet and lifestyle are accepted as major contributors to adenoma and CRC development. Lifestyle factors include high BMI, obesity, and reduced physical activity. Growing interest and accumulating data on human microbiota implicate that host-microbe interplay has an important role in the development of metabolic, neoplastic, and inflammatory diseases. Findings from recent studies suggest that colon cancer risk is determined by the interaction between diet and gut microbiota. Dietary changes affect gut microbiota and conversely microbiota mediates the generation of dietary factors triggering colon cancer. Identification of the microbial communities associated with carcinogenesis is of crucial importance. Nowadays, with the evolvement of culture-independent molecular techniques, it has become possible to identify main bacterial species in healthy individuals, inflammatory conditions, and CRC. Some recent studies have shown the differences in intestinal microbiota between colon cancer patients and healthy individuals. Animal studies have provided a better understanding of interaction between pathobionts and symbionts in the development of colon cancer. There is no single causative organism identified in CRC; however, there is strong evidence that reduction of protective bacteria, increase in some bacteria (ie, fusobacterium members; Bacteroides/Prevotella), and age-related changes in microbiota have an impact on adenoma or cancer development. Future studies will enable us to understand procarcinogenic and anticarcinogenic mechanisms and give insights to rational manipulation of the microbiota with prebiotics, probiotics, or dietary modifications.

Noninvasive detection of hepatic steatosis in patients without ultrasonographic evidence of fatty liver using the controlled attenuation parameter evaluated with transient elastography.

Objective Although ultrasound is a useful technique for detecting hepatic steatosis, it cannot provide a precise determination of hepatic fat content. A novel attenuation parameter named controlled attenuation parameter (CAP) has been developed to process the raw ultrasonic signals acquired by Fibroscan. The aim of this study was to determine the percentage of hepatic steatosis in apparently healthy Turkish individuals using the proposed diagnostic cut-off points for CAP. In addition, we sought to investigate the association of CAP with the traditional risk factors for nonalcoholic fatty liver disease in a screening setting. Materials and methods In the present study, 102 Turkish individuals without evidence of fatty liver on ultrasound and normal aminotransferase levels underwent CAP measurements by means of Fibroscan. Results The mean (SD), median (minimum−maximum), and 5th and 95th percentile values of CAP values in this cohort of 102 individuals were 206.99 (48.12), 210.5 (100.0−314.0), 113.4 and 280.2 dB/m, respectively. Using the cut-offs of 222, 238, and 283 dB/m for CAP, there were 39 (38.2%), 23 (22.5%), and five (4.9%) individuals out of 102 who had at least 10% steatosis despite normal liver findings on ultrasound. After allowance for potential confounders, CAP was independently associated with BMI (&bgr;=0.39, t=3.5, P<0.001) and the number of metabolic syndrome criteria (&bgr;=0.24, t=2.1, P<0.05). Conclusion These results hold promise for early noninvasive detection of hepatic steatosis on the basis of CAP assessment.

The effects of psychiatric treatment on depression, anxiety, quality of life, and sexual dysfunction in patients with inflammatory bowel disease

Objective Depression and anxiety are common disorders in inflammatory bowel disease (IBD). Our aim is to prospectively determine the effect of psychiatric treatment on scores for depression, anxiety, quality of life (QoL), and sexual dysfunction in an outpatient population diagnosed with IBD and also anxiety and/or depression disorder. Patients and methods Patients who scored higher than the cutoff point on the Hospital Anxiety Depression Scale were referred for further structured psychiatric evaluation and determination of the need for psychiatric drug treatment. Patients who underwent drug therapy completed Short Form-36 (SF-36) and the Arizona Sexual Experience Scale at baseline and after 6 months of follow-up. Results Major depressive disorder and generalized anxiety disorder were the most common diagnoses. After 6 months, 47 patients had completely adhered to drug treatment (group A), whereas 20 were nonadherent (group B). In group A, all domains of SF-36, Arizona Sexual Experience Scale, depression/anxiety scores, and Crohn’s disease activity index were statistically improved after treatment when compared with the baseline. In group B, the three domains of SF-36, platelet count, and mean corpuscular volume were worse between baseline and at 6 months. Conclusion In IBD patients having any psychiatric disorder, 6 months of antidepressant drug treatment is associated with an improvement in depression, anxiety, QoL, and sexual functioning scores, as well as an improvement in Crohn’s disease activity index. On the other hand, insufficient psychiatric treatment seems to be related to a poor QoL.

Association between bactericidal/permeability increasing protein (BPI) gene polymorphism (Lys216Glu) and inflammatory bowel disease

BACKGROUND Increasing evidence suggests that innate immune system may have a key role in the pathogenesis of the inflammatory bowel disease (IBD). Bactericidal/permeability increasing protein (BPI) has an important role in the recognition and neutralization of gram-negative bacteria by host innate immune system. The polymorphism on BPI gene called Lys216Glu is on the suspected list of IBD pathogenesis. METHODS We studied the Lys216Glu polymorphism on BPI gene, in a Turkish IBD patient population. A total of 238 IBD patients; 116 Crohns disease (CD) and 122 ulcerative colitis (UC), besides 197 healthy controls were included in this study. RESULTS The Glu/Glu genotype and allele frequencies were found to be statistically higher compared to healthy control group not only in CD patients [P: 0.03, OR: 1.87 (CI 95% 1.02-3.42) and P: 0.00001 (OR: 2.07 CI 95% 1.47-2.91) respectively] but also in UC patients [P: 0.0002, OR: 2.71 (CI 95% 1.53-4.80) and P: 0.00002 (OR: 2.71 CI 95% 1.53-4.80) respectively]. CONCLUSIONS BPI polymorphism (Lys216Glu) is associated both to CD and UC. Our findings differ from the two Western European studies; one without any association and the other indicating an association only with CD. Our study is the first one reporting a novel association between BPI gene mutation (Lys216Glu) and UC.

Detection of hepatic steatosis using the controlled attenuation parameter: a comparative study with liver biopsy

Abstract Objective. Measurements of controlled attenuation parameter (CAP) with transient elastography (FibroScan®; EcoSens SA, Paris, France) may provide an accurate noninvasive assessment of hepatic steatosis. Herein, we prospectively determined the accuracy of liver fat quantification with CAP values in patients with chronic liver diseases and compare the results with those of histological assessment of steatosis as reference standard. Materials and methods. We enrolled 50 Turkish patients with various forms of chronic liver diseases. All patients underwent both CAP assessment and ultrasonography-guided liver biopsy. Results. On liver biopsy, 16 (32%) patients had S0, 12 (24%) had S1, 9 (18%) had S2, and 13 (26%) had S3. The CAP values increased significantly (p < 0.001) for each steatosis stage on liver biopsy: S0, 222 dB/m; S1, 250 dB/m; S2, 270 dB/m; and S3, 318 dB/m. A cutoff value of 257 dB/m could distinguish significant steatosis (S2–S3) from S0 (Sn 89%, Sp 83%, positive likelihood ratio 5.33, negative likelihood ratio 0.13, AUROC = 0.93). Multivariable analysis indicated that neither liver fibrosis (p = 0.58) nor disease etiology (p = 0.96) had a significant impact on the association between CAP and the stage of steatosis. Conclusion. The determination of CAP using transient elastography can represent an important step forward toward the goal of an “imaging liver biopsy”.

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.

Bactericidal permeability increasing protein gene polymorphism is associated with inflammatory bowel diseases in the Turkish population

Background/Aims: Inflammatory bowel disease, a chronic inflammatory disease with unknown etiology, affects the small and large bowel at different levels. It is increasingly considered that innate immune system may have a central position in the pathogenesis of the disease. As a part of the innate immune system, bactericidal permeability increasing protein has an important role in the recognition and neutralization of gram-negative bacteria. The aim of our study was to investigate the involvement of bactericidal permeability increasing protein gene polymorphism (bactericidal permeability increasing protein Lys216Glu) in inflammatory bowel disease in a large group of Turkish patients. Patients and Methods: The present study included 528 inflammatory bowel disease patients, 224 with Crohns disease and 304 with ulcerative colitis, and 339 healthy controls. Results: Bactericidal permeability increasing protein Lys216Glu polymorphism was found to be associated with both Crohns disease and ulcerative colitis (P = 0.0001). The frequency of the Glu/Glu genotype was significantly lower in patients using steroids and in those with steroid dependence (P = 0.012, OR, 0.80; 95% confidence interval [CI]: 0.68-0.94; P = 0.0286, OR, 0.75; 95% CI: 0.66-0.86, respectively). There was no other association between bactericidal permeability increasing protein gene polymorphism and phenotypes of inflammatory bowel disease. Conclusions: Bactericidal permeability increasing protein Lys216Glu polymorphism is associated with both Crohns disease and ulcerative colitis. This is the first study reporting the association of bactericidal permeability increasing protein gene polymorphism with steroid use and dependence in Crohns disease.

Interstitial pneumonitis associated with pegylated interferon-alpha 2a and ribavirin for chronic hepatitis C infection: a case report

Interstitial pneumonitis is a rare but potentially fatal side effect occurring from 2 weeks to 16 weeks after the initiation of treatment with pegylated interferon alpha and ribavirin for chronic hepatitis C.Herein, we present a 68-year-old man with chronic hepatitis C virus infection who developed interstitial pneumonitis association with pegylated interferon after 36 weeks initiation of pegylated interferon-alpha and ribavirin therapy. He did not recover after discontinuation of pegylated interferon/ribavirin and improved by steroid therapy.