AIMS:To evaluate patient profile for epidemiological and clinicopathological characteristics and potential risk/prognostic factors in newly diagnosed hepatocellular carcinoma (HCC) patients across Turkey. METHODS:A total of 547 patients (mean (SD) age 62.6 (10.3) years, 81.9% were males) were included in this registry study. Data on patient characteristics, etiologies of HCC, laboratory values, and tumor characteristics and stages were recorded at study enrollment. RESULTS:HBV infection (68.2%) was the leading etiology, followed by HCV infection (17.2%), HDV infection (5.5%), alcohol (6.4%), and NAFLD (3.5%), as the major etiologies. Considering that 51.6% of the patients had >5 cm HCC, 44% were Child-Pugh B/C and 57% were BCLC B-D, it appears that a significant group of HCC patients were diagnosed at advanced stages. Of 540 patients, 271 (50.2%) were referred or applied with the diagnosis of HCC. Patients with HCC at presentation had larger tumor size (median (min-max) 6.6 (0-30) vs. 4.8 (0-90) cm, P < .001) and more advanced BCLC stage (Stage C-D in 40.8% vs. 26.4%, respectively, P = .005), compared to patients who were diagnosed during follow-up. CONCLUSIONS:Our findings revealed that HBV infection was the leading etiology and a moderate-to-advanced disease was evident in more than half of patients at the time of diagnosis. HCC patients diagnosed at follow-up had smaller tumor size and earlier BCLC stage.

Cite this article as: Soytürk M, Bengi G, Oğuz D, et al. Turkish Gastroenterology Association Pancreas Study Group Chronic Pancreatitis Committee Consensus Report. Turk J Gastroenterol 2020; 31(Suppl 1) S1-41.

Infl uence of Uricacid Levels on PegylatedInterferon Plus Ribavirin Therapy in Patients with Chronic Hepatitis C Serhat Özer1, Zeynep Altın2, Sinem Namdaroglu3*, Betül Koyuncu4, Fatih Aslan5 and Belkıs Ünsal6 1Artvin State Hospital, Department of Gastroenterology, Artvin, Turkey 2İzmir Tepecik Training and Research Hospital, Department of Internal Medicine, İzmir, Turkey 3İzmir Bozyaka Training and Research Hospital, Department of Hematology, Stem Cell Transplantation Unit, İzmir, Turkey 4Uşak Training and Research Hospital, Department Of Internal Medicine ,Uşak,Turkey 5University of Koç Hospital, Department of Gastroenterology, İstanbul Turkey 6İzmir Ataturk Training and Research Hospital, Department of Gastroenterology, İzmir, Turkey

BACKGROUND/AIMS:The anastomotic strictures are one of the most common colorectal surgery complications, and various endoscopic techniques have been defined. Balloon dilation is the most well-known and the simplest procedure. In this article, we aimed to present our series of endoscopic interventions and electroincision management for anastomotic strictures. MATERIALS AND METHODS:The files of 59 patients, who underwent colorectal surgery between January 2010 and September 2017 in our hospital and were diagnosed during the follow-up with anastomotic stricture, were analyzed. The outcomes of endoscopic interventions such as balloon dilation and electroincision were compared and reported. RESULTS:The mean age of the 59 patients included in the study was 59.5±16.26 years. The primary operative indications were colorectal cancer in 46, inflammatory bowel disease in 7, diverticulum in 5, and penetrating trauma in one patient. Single- or multiple-balloon dilations were successful in 48 patients. Electroincision was performed in 11 patients because of the balloon dilation failure. None of the patients needed a secondary surgery. During the mean 33.75 months of the follow-up, the stricture recurred in seven patients who had undergone balloon dilation. Repeated balloon dilation was successful in these patients without any need for an additional surgical intervention. CONCLUSION:Balloon dilation can be performed safely as the primary treatment option, because of its easy access and noninvasive application. Electroincision is also a safe and effective endoscopic technique that can be preferred especially when the balloon dilation fails.

Cite this article as: Törüner M, Akpınar H, Akyüz F, et al. 2019 Expert opinion on biological treatment use in inflammatory bowel disease management. Turk J Gastroenterol 2019; 30(Suppl 4): S913-46.

Amaç: Otoimmun hastalıklar genel olarak birliktelik gösterme eğilimindedirler. Primer biliyer siroza (PBS) da diğer otoimmun hastalıkların yanı sıra çölyak hastalığı (ÇH) eşlik edebilmektedir. Bu çalışmada PBS’li hastalarda ÇH’nin prevalansı değerlendirildi.Gereç ve Yöntem: Çalışmada Nisan 2006-Aralık 2017 tarihleri arasında tanı alan ve takipli olan 238 PBS’li hasta, kontrol grubu olarak alınan 205 sağlıklı gönüllü ile prospektif olarak karşılaştırıldı. Hastalarda Anti Gliadin IgA ve IgG (AGA), Anti Endomisyum IgA ve IgG (EMA) antikorları immunofloresans yöntemi ile bakıldı. Antikorları pozitif saptanan hastalardan duodenum ikinci kısmından biyopsi alındı.Bulgular: Çalışmaya alınan 238 hastanın yaş ortalaması 54,2±12 olup 16’sı erkekti. Kontrol grubundaki 205 kişinin 115’i kadın (%56,1), 90’ı erkek ve yaş ortalaması 43,8±14,4’tü. PBS’li 4 hastada AGA ve EMA pozitifliği (%1,7) saptandı. PBS’li hastaların hiçbirinde ÇH semptomları yoktu. On üç (%5,46) hastada ise düşük titrede AGA pozitifliği saptandı. Kontrol grubundaki bir (%0,4) hastada EMA, AGA IgA ve IgG yüksek titrede pozitif saptandı ve PBS’li grup ile istatistiksel fark saptanmadı (p=0,379). PBS tanısı olan ve EMA, AGA pozitif saptanan dört hastanın biyopsisinde, bir hastada Marsh 1, bir hastada Marsh 2 ve iki hastada Marsh 3 ile uyumlu duodenum biyopsi bulguları saptandı. EMA ve AGA’sı pozitif olan kontrol grubundaki bir hastanın ince barsak biyopsisi ise Marsh 3 ile uyumluydu. Sonuç: PBS ve ÇH, birbiri ile ilişkili olabilen hastalıklardır. PBS tanılı hastalarda, ÇH açısından seropozitif olan hastaların takibinin ÇH ve komplikasyonlarına de yönelik olması ve tanı konulan hastalara glutensiz diyetin başlanması gerekmektedir.

Amaç: Primer biliyer kolanjit (PBK) sıklıkla diğer otoimmün hastalıklarla, özellikle de otoimmün tiroit hastalığı ile ilişkilendirilmektedir. Çalışmalar, otoimmün tiroid hastalığı ve anti-tiroid antikorlarının prevalansının PBK’de %14-24 olduğunu göstermiştir. Bu çalışmanın amacı, PBK’li hastalarda eşlik eden tiroid otoimmünitesini ve diğer tiroid hastalıklarını araştırmaktır. Yöntemler: Bu retrospektif kohort, Haziran 1999 ile Aralık 2017 tarihleri arasında üçüncü basamak merkezimizin gastroenteroloji bölümünde tedavi edilen 263 PBK hastasının tıbbi dosyalarından alınan verilere dayanmaktadır. Tiroid otoimmünitesi, normal aralığın üzerinde anti TPO ve/veya anti TG şeklinde tanımlanmaktadır. Otoimmün tiroid hastalığı olan ve olmayan PBK hastalarının klinik özellikleri ve laboratuvar bulgularındaki farklılıklar kaydedilmiştir. Bulgular: Tiroid otoimmünitesi, serimizdeki 80 hastada (%30,4) saptanmıştır. Hashimato tiroiditi 47 hastada tespit edilmiştir. Otoimmun tiroid hastalığı olan grupta hipertiroidi olan iki hastanın birinde Graves hastalığı, diğerinde ise Hashimato hastalığı olduğu belirlenmiştir. Otoimmün dışı tiroid hastalıkları grubunda 19 hasta olup, bunlar arasında 15 hastada multinodüler guatr, 3 hastada toksik tiroid nodül ve bir hastada tiroid kanseri olduğu belirlenmiştir. Otoimmün dışı tiroid hastalığı grubunda 9 hipertiroidi hastası saptanmıştır. Bu hastalar, toksik tiroid nodülü olan 3 hasta, akut tiroiditi olan 1 hasta ve diğer tiroid hastalıkları olan 5 hasta şeklindedir. Toksik tiroid nodülü olan bir hastada tiroid papiller mikrokarsinom olduğu belirlenmiştir.Sonuç: Tiroid otoimmünitesi, PBK hastalarında sıklıkla görülmektedir. PBK’li hastaların tiroid otoimmünitesi açısından taranması gerekir.

Objectives: Gallstones are the most common cause of acute biliary pancreatitis. Laboratory and imaging findings as well as age are important predictors for mortality. Hospitalization rate is also higher in elderly patients. In this study, we investigated clinical parameters and total mortality in patients with acute pancreatitis aged >65 years. Methods: In this study, 852 patients who entered the Gastroenterology Clinic for acute biliary pancreatitis between April 2006 and October 2013 were included. Data were retrospectively collected from the electronic record system. The patients with elevated aspartate aminotransferase levels (i.e. three times higher than normal value), cholelithiasis, cholecystectomy history, or choledocholithiasis were accepted as the patients with acute biliary pancreatitis. Patients were divided into two groups based on their age, i.e., >65 and <65 years. Results: In the group with patients aged <65 years, serum alanine aminotransferase, albumin, hematocrit, and amylase, and in the group with patients aged >65 years, urea, leukocyte, and C-reactive protein levels were significantly different. Median hospital stay was similar in both the groups. The rate of detection of choledocholithiasis was significantly higher in elderly patients (p<0.001). Mortality rate was significantly higher in elderly patients for 28 day (0.21% and 2.95%, p<0.001)and 90 day (1.25% and 5.63%, p<0.001). In logistic regression multivariate analysis, age (OR 2.0, 95% CI 1.54-1.36; p=0.006), elevated urea levels (OR 1.12, 95% CI 1.05-1.19; p=0.001), elevated hematocrit levels (OR 1.42, 95% CI 1.13-1.77; p=0.002), and decreased albumin levels (OR 0.05, 95% CI 0.004-0.652; p=0.022) were found predictors for 90-day mortality. Conclusion: Laboratory findings in elderly patients with acute pancreatitis may differ from those in younger patients. Although radiological findings are similar in both the groups, mortality is higher in the group with patients aged >65 years.

Background and Aims: Cytokeratin-18 is the known substrate for caspases, which are encountered during hepatic and pancreatic acinar apoptosis. Studies performed in recent years have indicated that the cleavage level of serum cytokeratin-18 (M30 antigen) is correlated with hepatic fibrosis and disease severity in both chronic hepatitis C and non-alcoholic steatohepatitis. It was shown that antiviral therapy in chronic viral hepatitis C patients significantly reduced hepatocellular apoptosis and cytokeratin-18 is accepted as a reliable marker of hepatocyte apoptosis. Our aim was to determine the correlation between the cytokeratin-18 level and treatment response in patients with chronic viral hepatitis C. Materials and Methods: Sixty patients with chronic viral hepatitis C were included in the study. A 48-week course of peginterferon- ribavirin therapy was given to appropriate patients. Hepatitis C virus RNA was measured at 0, 12, and 24 weeks at the end of therapy and 72 weeks. In addition, cytokeratin-18 levels were measured at 0, 24, and 72 weeks. Results: The mean age of 60 patients was 52±10.9 years. While 31 (51.6%) of patients were in the sustained viral response group, 29 (8.4%) of patients were in the non-sustained viral response group. It was determined that while the cytokeratin-18 level at week 0 in the sustained viral response group was 243±21, the cytokeratin-18 level at week 24 was 115±12 U/L and the difference between the level of cytokeratin-18 at weeks 0 and 24 were 127±209 U/L (p: .014). While the cytokeratin-18 level at week 0 in the non- sustained viral response group was 270±14; at week 24, the cytokeratin-18 level was 136±19 U/L and the difference between cytokeratin-18 levels at weeks 0 and 24 was 136±156 U/L (p > .5). At week 72, the cytokeratin-18 level in the sustained viral response group was 109±38 and the difference between weeks 0 and 72 was 134±215 (p < .002). Conclusion: In chronic viral hepatitis C patients, there was a correlation between sustained viral response and cytokeratin-18, which is a marker of apoptosis. During treatment, it was found that there was a relationship between sustained viral response and the decrease in cytokeratin-18 levels. Thisfinding indicates that cytokeratin-18 level monitoring may be used as a predictive marker of sustained viral response.

Background and aims: We aimed to determine the utility of M30 and M65 antigen concentration levels for predicting hepatic injury in chronic hepatitis B disease.Materials and Methods: This study compared concentration levels of M30 and M65 antigens between patients with hepatitis B e-antigen negative chronic hepatitis B and healthy subjects. Furthermore, the correlations between either M30 or M65 antigen levels and aspartate aminotransferase, alanine aminotransferase, HBV-DNA, histological activity index and fibrosis were evaluated in the patient group.Results: A total of 81 subjects were included in the study; 50 patients with HBeAg negative chronic hepatitis B and 31 healthy subjects. The concentration of the M30 antigen was significantly higher in the chronic hepatitis B patient group than in the healthy subject group (p <0.05). However, there was no difference in M65 antigen concentration values between the two groups (p >0.05). Correlation analysis performed in the patient group revealed a significant correlation between M30 antigen concentration levels and aspartate aminotransferase levels (r: 0.207, p <0.05), and between M65 antigen concentration levels and HBV-DNA levels (r: 0.204, p <0.05). There was no significant correlation observed between M30 or M65 antigen concentration levels and both the histological activity index and fibrosis. Discussion: The presence of high M30 antigen levels in HBeAg negative chronic hepatitis B patients may suggest that M30 antigen concentration might be beneficial in disease monitoring and evaluation of treatment efficacy. This observation must be tested further in more comprehensive studies. However, the absence of a significant correlation between the concentration levels of either antigen or both the histological activity index and fibrosis suggests that pathological examination is unique in detecting hepatic injury.

Background and Study Aims:We aimed to demonstrate the association between fecal elastase levels and Rosemont categories in patients with chronic changes in pancreas detected with endoscopic ultrasound.Patients and Methods:Patients were selected consecutively from endosonography examinations performed for upper gastrointestinal subepithelial lesions and for pancreas evaluation. Pancreas imaging findings were categorized according to the Rosemont criteria using echoendoscope. Patients who were indeterminate of, suggestive of, and consistent with chronic pancreatitis were included in the study. Fecal elastase measurements were performed after the patients were qualified to participate in the study according to endosonography findings.Results:Seventy patients were included in the study. 54 of them were male. Mean age of the patients was 51.7 ± 10.2 year. There were 36 patients in the indetermine group for chronic pancreatitis. Mean fecal elastase level was 507.1 ± 14.6 μg/g in the indeterminate group. There were 24 patients in the suggestive group of chronic pancreatitis. Mean fecal elastase level was 400.4 ± 121.4 μg/g in the suggestive group of chronic pancreatitis. There were 10 patients, in the consistent group with chronic pancreatitis. Mean fecal elastase level was 134.8 ± 86.1. The difference between the three groups of fecal elastase values was statistically significant compared with Kruskal Wallis test. Ordinal logistic regression analysis showed that there was a significant relation between endosonografic categories and fecal elastase values with Nagelkerke value of 0.704.Conclusions:Fecal elastase levels of each of the endosonographic categories were significantly different from each other. Also, fecal elastase values can predict chronic changes in pancreas detected with endoscopic ultrasound.

OBJECTIVE: The objective of this study was to evaluate the serology of hepatitis A, B, and C in patients with cirrhosis and intensive alcohol consumption. METHODS: We retrospectively reviewed the viral serology results of 817 patients with cirrhosis and intensive alcohol consumption who presented to the Gastroenterology Clinic of Atatürk Training and Research Hospital of Izmir Katip Çelebi University between April 2008 and December 2017. The diagnosis of cirrhosis was based on clinical and biochemical evaluations and imaging results. Patients consuming absolute alcohol 40 g/day for >10 years were included and those who quit drinking ≥15 years ago were excluded. RESULTS: Of all the patients, 806 (98.7%) were positive for anti-HAV IgG, 159 (19.5%) for HBsAg, and 32 (3.9%) for anti-HCV. Genotyping was performed in 13 patients. Genotype 1 was detected in 10 patients (1a, one patient; 1b, nine patients) and genotype 3 in three patients. Of the patients with HBV, 10.0% had HBeAg and 7.6% had anti-delta. One-hundred and two (12.5%) patients had HCC, and of these, six (5.9%) were HCV-positive and 53 (52.0%) were HBsAg-positive. CONCLUSION: Patients with cirrhosis and intensive alcohol consumption have an increased hepatitis B and C prevalence. Patients with chronic viral hepatitis with alcohol habit are at a higher risk for HCC. Therefore, patients with cirrhosis and intensive alcohol consumption should be screened for hepatitis B and C.

DOI: 10.21276/sjams.2018.6.9.59 Abstract: Term and quantity of alcohol consumption is one of the most significant factors in terms of occurrence of alcoholic liver disease. In some studies, it has been found out that due to prevalence of smoking-related morbidity, reason of death of alcoholics is more probably smoking related diseases more than alcohol-related disorders. In this study, we aimed to determine characteristics of smoking in cirrhosis with heavy alcohol consumption, its effect on mortality and risk factors. 401 cirrhotic patients with heavy alcohol consumption applying to gastroenterology clinic between the years of 2008-2018 successively were assessed retrospectively. Patients used to consume alcohol minimum 40 g/day a day and for more than 10 years. Term of alcohol abuse, type of alcohol and smoking condition were questioned for the patients. Patients with GIS malignity and diseases other than liver were not included in the study. Patients were divided into 3 groups as smoker, ex-smokers and non-smokers. Rate of smoking was found as 90.3%. Age of starting alcohol and body mass index was found as significantly lower in patients who have still smoked. Quantity of daily alcohol use in smokers was significantly higher. In multi-variate analysis, age and quantity of smoking was significantly related to the mortality. Mortality was found less in persons abusing alcohol with strength of 15% above. In our study, smoking has been found as related to the mortality in cirrhosis patients with heavy alcohol consumption. For this reason, we suppose that quitting smoking will be beneficial for increasing rate of survival in in cirrhosis patients with heavy alcohol consumption.

Purpose: Hepatitis C is an important medical problem which causes chronic liver disease. 170 million people are believed to be infected throughout the world. While spontaneous hepatitis C virus (HCV) clearance occurs in almost 30 % of patients with hepatitis C, it becomes chronic in 70 % which may progress to cirrhosis or hepatocellular carcinoma (HCC). In recent years, IL28B polymorphism on chromosome 19q13 has been suggested as the most important predictor among the host factors for sustained virologic response (SVR). In the present study, we aimed to evaluate the effect of IL28B gene polymorphism on conventional treatment response. Materials and methods: Totally 95 patients treated with a combination of peginterferon and ribavirin during 48 weeks were included the study. Age, gender, AST and ALT levels, insulin and fasting glucose levels, BMI, fibrosis levels on liver biopsy and 0-4-12-24-48-72-week HCV RNA values were recorded. Results: In the study group of 95 HCV-infected patients, the mean age was 52.4±11 years. SVR was observed in 54 (%56.8) of patients at the follow up. Demographical and laboratory variables were similar in SVR and non-SVR groups. IL28B SNP rs12979860 was positive in CC 26 (47.2 %), CT 25 (45.4%) and TT 4 (7.2 %) patients with SVR group and in CC 4 (10 %), CT 23 (57.5 %), TT 13 (32.5 %) patients with non-SVR group. Conclusion: SVR was achieved more likely in HCV genotype 1 rs12979860, and treatment decision may be changed based on the degree of liver disorder. In this regard, new studies involving larger patient population from our country are needed.

Abstract Background In this study it was aimed to evaluate the effect of pegylated interferon alfa-2a/2b and ribavirin, which are used for treatment of chronic hepatitis C (CHC), on insulin resistance and metabolic factors. Materials and methods A total of 104 CHC patients aged 20–75 years with available serum insulin data at 0 and 48 weeks, and hepatitis C virus (HCV)-RNA data at 0, 12, 24, 48 and 72 weeks were included in the study. All clinical para-meters were assessed according to the therapy response. Results Among 104 patients, sustained virologic response (SVR) was achieved in 55 cases. A statistically significant difference was noted between SVR and non-SVR groups regarding γ-glutamyltranspeptidase (GGT), insulin level plus homeostasis model assessment (HOMA) score and insulin resistance at week 48, log HCV-RNA and stage of fibrosis. Conclusion Insulin resistance is accepted to have a negative effect on SVR. Insulin resistance may improve once SVR is achieved. Presence of IR at week 48 has been found associated with SVR. In this context, it can be advocated that insulin resistance at week 48 may be a predictive factor for prediction of SVR at week 72.

In the palliative treatment of residual common bile duct stones, stenting is a treatment option. For this purpose standard plastic (Amsterdam type) or pig-tail plastic stents are commonly available. The aim of this study was to compare the effectivity of pig-tail plastic and standard plastic stents in the treatment of patients with dilated common bile duct and large stones which cannot be extracted with balloon and basket.

Objectives: Ductal and parenchymal changes detected with endoscopic ultrasound is correlated with fibrotic changes of pancreas.Rosemont criteria is often used to categorize patients with chronic changes in pancreas detected with endoscopic ultrasound.We aimed to demonstrate the association between fecal elastase levels and Rosemont categories in patients with chronic changes in pancreas detected with endoscopic ultrasound.Methods: Patients were selected consecutively from endosonography examinations performed for upper gastrointestinal subepithelial lesions and for pancreas evaluation.Pancreas imaging findings were categorized according to the Rosemont criteria using radial echoendoscope.Patients with normal pancreas imaging were excluded.We used pancreatic elastase Elisa kit, Bioserv Diagnostics Gmbh for pancreatic elastase measurements.Ordinal logistic regression was used to measure the association between endosonographic categories and fecal elastase values.Results: Seventy-two patients were included in the study.54 of them were male.Mean age of the patients was 51.7 ± 10.2 year.There were 36 patients in the indetermine for chronic pancreatitis group.Mean fecal elastase level was 507.1 ± 14.6 µg/g in the indetermine group.There were 24 patients in the suggestive of chronic pancreatitis group.Mean fecal elastase level was 400.4 ± 121.4 µg/g in the suggestive of chronic pancreatitis group.There were 10 patients in the consistent with chronic pancreatitis group.Mean fecal elastase level was 134.8 ± 86.1 The difference between the three groups fecal elastase values was statistically significant compared with Kruskal Wallis test.Ordinal logistic regression analysis showed that there was a significant relation between endosonografic categories and fecal elastase values with Nagelkerke value of 0.704.Conclusions: Fecal elastase levels of each of the endosonographic categories were significantly different from each other.Also, fecal elastase values can predict chronic changes in pancreas detected with endoscopic ultrasound.

Endoscopic submucosal dissection(ESD) has been widely accepted as an effective and minimally invasive treatment for patients with premalignant and malignant colorectal lesions. Due to the anatomic features of the colon and larger lesion sizes it may sometimes be difficult to perform colorectal ESD successfully. Here we present the results of traditional standard ESD and the new single tunneling technique in a comparative study for treatment of large laterally spreading tumors(LST) ≥5 cm which is the first to be presented.

Background and study aims: Standard sequential treatment for Helicobacter pylori (H. pylori) eradication has less success because of increasing clarithromycin resistance. Extended treatment and bismuth containing regimens were, therefore, investigated.Patients and methods: Consecutive H. pylori-positive patients with dyspepsia were randomly allocated to one of the three sequential regimens: The first group was given lansoprazole 30 mg b.i.d. plus amoxicillin 1 g b.i.d. for the first 5 days, followed by lansoprazole 30 mg b.i.d., clarithromycin 500 mg b.i.d., and metronidazole 500 mg t.i.d. for the second 5 days (standard sequential, SS). The second group was given the same regimen but for 7 + 7 days instead of 5 + 5 days (extended sequential, ES). In the third group, colloidal bismuth 600 mg b.i.d. was added to the second regimen for 14 days (extended sequential + bismuth subcitrate, ES + B). Urea breath test or histology was performed before enrolment and 6 weeks after the end of treatment to detect H. pylori.Results: A total of 280 patients were included in the study. Per-protocol eradication rates were 62% (56/90), 72%(56/78), and 75% (54/72) in patients who received SS, ES, and ES + B regimens, respectively. Moreover, intention-to-treat eradication rates were 53% (56/104), 62% (56/90) and 62% (54/86), respectively. The differences in eradication rates between the groups were not statistically significant.Conclusion: Although prolonging of the sequential treatment to 14 days may be considered, addition of bismuth to the regimen is of no avail. (C) 2017 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.

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-α 227 ALA, PPAR-γ 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.