Acute pancreatitis in Turkey: Results of a nationwide multicenter study.

BACKGROUND: Acute pancreatitis (AP) is the most common gastrointestinal disease requiring hospitalization, with significant mortality and morbidity. We aimed to evaluate the clinical characteristics of AP and physicians' compliance with international guidelines during its management. METHODS: All patients with AP who were hospitalized at 17 tertiary centers in Turkey between April and October 2022 were evaluated in a prospective cohort study. Patients with insufficient data, COVID-19 and those aged below 18 years were excluded. The definitions were based on the 2012 revised Atlanta criteria. RESULTS: The study included 2144 patients (median age:58, 52 % female). The most common etiologies were biliary (n = 1438, 67.1 %), idiopathic (n = 259, 12 %), hypertriglyceridemia (n = 128, 6 %) and alcohol (n = 90, 4.2 %). Disease severity was mild in 1567 (73.1 %), moderate in 521 (24.3 %), and severe in 58 (2.6 %) patients. Morphology was necrotizing in 4.7 % of the patients. The overall mortality rate was 1.6 %. PASS and BISAP had the highest accuracy in predicting severe pancreatitis on admission (AUC:0.85 and 0.81, respectively). CT was performed in 61 % of the patients, with the majority (90 %) being within 72 h after admission. Prophylactic NSAIDs were not administered in 44 % of the patients with post-ERCP pancreatitis (n = 86). Antibiotics were administered to 53.7 % of the patients, and 38 % of those received them prophylactically. CONCLUSIONS: This prospective study provides an extensive report on clinical characteristics, management and outcomes of AP in real-world practice. Mortality remains high in severe cases and physicians' adherence to guidelines during management of the disease needs improvement in some aspects.

Possible relationship between IL28B rs12979860 and TLR2 -196 to -174 del/ins polymorphisms and the liver fibrosis stage in hepatitis C patients.

It has been shown that host factors play an important role in the progression of hepatitis C virus (HCV) infection. Toll-like receptor 2 (TLR2) del and interleukin 28B (IL28B) T alleles can mediate liver inflammation and pathogenesis of hepatocellular carcinoma. In the present study, the possible relationship between the IL28B rs12979860 C/T and TLR2 -196 to -174 del/ins gene variants and different fibrosis stages and host factors in hepatitis C patients was investigated. IL28B and TLR2 polymorphisms in the blood of 50 hepatitis C patients at different stages of fibrosis (24 mild/moderate, 26 advanced) and 24 healthy controls were examined by RT-qPCR. The highest frequency of the TLR2 del (26.9%) and IL28B T (46.2%) alleles was found in hepatitis C patients with the most advanced fibrosis, and the lowest frequency was found in healthy controls. There was a statistically significant difference between hepatitis C patients with advanced fibrosis and healthy controls in terms of the TLR2 del (p = 0.0062) and IL28B T (p = 0.0017) allele frequencies. However, no statistically significant difference was found between the mild/moderate fibrosis and severe fibrosis patient groups in terms of genotype or IL28B and TLR2 polymorphisms (p > 0.05). In addition, there was a significant difference between patients with mild/moderate or advanced fibrosis who carried the TLR2 del allele together with the IL28B CT genotype and healthy controls. The present study emphasizes that the TLR2 and IL28B gene variants cannot be single biomarkers for the determination of fibrosis stage in hepatitis C infection but together can play an important role in predicting severe disease.

Pancreatic Steatosis Is Associated with Both Metabolic Syndrome and Pancreatic Stiffness Detected by Ultrasound Elastography.

INTRODUCTION: There is increasing evidence that pancreatic steatosis (PS) is associated with metabolic syndrome (MS). However, it is not known whether it is associated with PS grade and pancreatic stiffness, or not. We aimed to evaluate the relationship between PS and its grade detected by transabdominal ultrasound, and pancreatic stiffness determined by two-dimensional shearwave elastography (2D-SWE), whether it has clinical significance and its relationship with MS. METHODS: Patients with and without PS were evaluated prospectively. RESULTS: Patients with PS had higher odds ratio for MS (OR 5.49). Also, ultrasonographic grade of PS was associated with MS parameters and hepatosteatosis. Pancreatic SWE value was significantly higher in PS group and positively correlated with PS grade, liver fat, MS, number of MS criteria. DISCUSSION/CONCLUSION: PS and its grade were associated with MS. In this first comprehensive PS-SWE study, we found that pancreas stiffness increased in the presence of PS, in correlation with PS grade and MS.

hsa-miR-17-5p: A Possible Predictor of Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir ± Ribavirin Therapy Efficacy in Hepatitis C Infection.

Although persistent sustained viral response rates are increased in hepatitis C infection following administration of direct-acting antiviral (DAA) agents, the pre-use predictive parameters of these antivirals and the clinical progression in patients post-treatment remain unknown. To obtain data pertaining to the predictive parameters prior to the use of ombitavir/paritaprevir/ritonavir + dasabuvir and the clinical progression in patients following antiviral treatment. The expression profiles of miR-223-3p, miR-17-5p, miR-24-3p, and TLR2 - 196 to - 174 del/ins polymorphisms from the blood/serum of 34 hepatitis C virus (HCV)-infected patients pre- and post-ombitavir/paritaprevir/ritonavir + dasabuvir treatment were determined by RT-qPCR. The expression levels of miR-17-5p (P < 0.001) and miR-24-3p (P = 0.011) were significantly downregulated post-treatment as compared with those pre-treatment; however, there was no significant difference between these two groups in terms of miR-223-3p expression. In addition, there was no significant difference in TLR2 genotype or allele distribution between pre-and post-treatment (P > 0.05); nevertheless, the TLR2 del allele was decreased post-treatment (16.2%) as compared with that pre-treatment (19.1%), although the difference was not statistically significant. Moreover, a significant difference was found between the mRNA levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and HCV RNA pre-and post-treatment (P < 0.05). Further, miR-17-5p expression correlated with both ALT and AST mRNA levels post-treatment (P.

Controlling Nutritional Status (CONUT) Score and Prognostic Nutritional Index (PNI) Are Good Candidates for Prognostic Markers for Acute Pancreatitis.

Background and Objectives: It has been demonstrated that parameters such as the Controlled Nutrition Status (CONUT) score and Prognostic Nutrition Index (PNI) are beneficial for the assessment of patients' nutrition. In this study, our objective was to investigate the potential benefits of CONUT and, as a prognostic marker of acute pancreatitis, the PNI. Materials and Methods: The data of 361 patients were analysed retrospectively. The PNI and CONUT scores of these patients were retrospectively calculated. They were categorised as CONUT-high (≥3) and CONUT-low (≤2). A PNI ≥ 45 was considered high and a PNI < 45 low. The AP severity and organ failure due to disease were evaluated based on Atlanta 2012. Results: According to the CONUT score, it was found that 209 patients had normal to mild, whereas 152 patients had severe malnutrition. A total of 293 patients had mild AP and 68 thereof had severe AP. The patients with a high CONUT score used more antibiotics, were hospitalised more in intensive care units and experienced organ failure more frequently. There were no intensive care hospitalisations, mortalities, surgical needs and local complications among the patients with a higher PNI score. Conclusions: CONUT and the PNI have proven to be useful prognostic markers not only for predicting nutritional status but also for estimating the severity and results of AP.

The course and prognostic value of increased pancreas stiffness detected by ultrasound elastography during acute pancreatitis.

BACKGROUND: In this study, we determined the pancreatic stiffness (PS) changes in the course of acute pancreatitis (AP) by ultrasound elastography and evaluated its relation with prognosis. MATERIAL/METHODS: Pancreatic shear wave velocity measurements (SWM) were evaluated at the time of admission to the hospital, following clinical improvement, and one-month after for AP patients and compared to healthy volunteers. Its relationship with clinical severity indexes was evaluated. RESULTS: The pancreatic SWM value in the healthy group was 7.72 ± 2.50 kPa, and in AP group was 10.97 ± 2.26 kPa (p = 0.000). There was no difference between mild and severe pancreatitis. The mean SWM was 8.96 ± 1.53 kPa after disease remission, and 8.83 ± 1.24 kPa after 1-month. CONCLUSIONS: PS increases significantly during AP and decreases with clinical improvement, but this was still higher than controls, and it kept its elevation after 1-month. We think that larger, long-term studies are needed to determine the clinicopathological significance of this.

Trimebutine Maleate Monotherapy for Functional Dyspepsia: A Multicenter, Randomized, Double-Blind Placebo Controlled Prospective Trial.

Background and Objectives: Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders; it has a great impact on patient quality of life and is difficult to treat satisfactorily. This study evaluates the efficacy and safety of trimebutine maleate (TM) in patients with FD. Materials and Methods: Α multicenter, randomized, double-blind, placebo controlled, prospective study was conducted, including 211 patients with FD. Participants were randomized to receive TM 300 mg twice per day (BID, 108 patients) or placebo BID (103 patients) for 4 weeks. The Glasgow Dyspepsia Severity Score (GDSS) was used to evaluate the relief of dyspepsia symptoms. Moreover, as a pilot secondary endpoint, a substudy (eight participants on TM and eight on placebo) was conducted in to evaluate gastric emptying (GE), estimated using a 99mTc-Tin Colloid Semi Solid Meal Scintigraphy test. Results: Of the 211 patients enrolled, 185 (87.7%) (97 (52.4%) in the TM group and 88 (47.6%) in the placebo group) completed the study and were analyzed. The groups did not differ in their demographic and medical history data. Regarding symptom relief, being the primary endpoint, a statistically significant reduction in GDSS for the TM group was revealed between the first (2-week) and final (4-week) visit (p-value = 0.02). The 99 mTc-Tin Colloid Semi Solid Meal Scintigraphy testing showed that TM significantly accelerated GE obtained at 50 min (median emptying 75.5% in the TM group vs. 66.6% in the placebo group, p = 0.036). Adverse effects of low to moderate severity were reported in 12.3% of the patients on TM. Conclusion: TM monotherapy appears to be an effective and safe approach to treating FD, although the findings presented here warrant further confirmation.

[Determination of reverse transcriptase inhibitor nucleoside analogue resistance profile in pretreatment phase of patients with viral hepatitis B]. / Viral hepatit B hastalarinda ilk tedavi öncesi revers transkriptaz inhibitörü nükleozid analogu ilaç direnç profilinin belirlenmesi.

HBV is a DNA virus and the causative agent of hepatitis B infection. Hepatitis B is a contagious disease and is still a major health problem all over the world. When the infection become chronic, it may cause serious diseases such as fibrosis, cirrhosis and/or hepatocellular carcinoma. Interferon/pegylated interferon by intravenous route and nucleoside/nucleotide (NA) analogues such as lamivudine, adefovir, entecavir, telbivudine and tenofovir given by oral route are used in the treatment. Antivirals given by oral route are mostly preferred in the treatment. However, because of the replication strategy and biological properties of HBV, mutations that cause antiviral resistance against these drugs can occur at different rates, although they can vary from drug to drug over time. It is possible that drug resistant virus may transmit from patient to healthy individuals. Therefore, there is a possibility of infection with drug-resistant HBV before treatment. Antiviral resistance mutations are divided into four categories; i) Nucleos(t)ide analog resistance (NAr)-related mutations, ii) primary drug resistance mutations, iii) secondary/compensatory mutations, iv) putative antiviral resistance mutations and pre-treatment variations. Recent studies have focused particularly on putative mutations and pre-treatment variations. The aim of this study was to better understanding of the antiviral resistance profiles of chronic hepatitis B (CHB) patients treated and untreated with NA, and help to prevent unnecessary drug use, minimize the side effects and economic damages. A total of 124 patients who have received nucleoside analog (NA) drug treatments (n= 72) and patients without NA treatment (n= 52) were included in the study. Viral DNA was isolated from the plasma samples of the patients. A DNA fragment, which is 551 bp, was amplified and sequenced including the binding side of all nucleoside analogs containing the B, C and D domains located in the reverse transcriptase region in the HBV genome. Different types of mutations were detected in 13 (18.05%) of 72 treated patients and in 18 (34.61%) of 52 untreated patients (p< 0.05). Primary drug resistance mutations such as rtI169T, rtA181T/V, rtT184A/C/F/G/I/L/M/S, rtA194T, rtS202C/G/I, rtM204I/V/S, rtN236T, rt M250I/L/V and rtV173L were not detected in any of the patient samples. However, potential drug resistance mutations such as rtR164R, rtG165D/A, rtG172Q, rtS176N, rtF178V, rtA181G, rtS185N/G/C, rtV207M, rtQ215H/S, rtL231V, rtI233K, rtN238S, rtV253T, rtC256G/S and rtI266R/V were detected in untreated patient samples in B, C, D and D domains of reverse transcriptase region. Our results have suggested that the detection of pretreatment variations could be helpful for choosing the correct antiviral drug for the better treatment management.

Mutations in RIPK4 cause the autosomal-recessive form of popliteal pterygium syndrome.

The autosomal-recessive form of popliteal pterygium syndrome, also known as Bartsocas-Papas syndrome, is a rare, but frequently lethal disorder characterized by marked popliteal pterygium associated with multiple congenital malformations. Using Affymetrix 250K SNP array genotyping and homozygosity mapping, we mapped this malformation syndrome to chromosomal region 21q22.3. Direct sequencing of RIPK4 (receptor-interacting serine/threonine kinase protein 4) showed a homozygous transversion (c.362T>A) that causes substitution of a conserved isoleucine with asparagine at amino acid position 121 (p.Ile121Asn) in the serine/threonine kinase domain of the protein. Additional pathogenic mutations-a homozygous transition (c.551C>T) that leads to a missense substitution (p.Thr184Ile) at a conserved position and a homozygous one base-pair insertion mutation (c.777_778insA) predicted to lead to a premature stop codon (p.Arg260ThrfsX14) within the kinase domain-were observed in two families. Molecular modeling of the kinase domain showed that both the Ile121 and Thr184 positions are critical for the protein's stability and kinase activity. Luciferase reporter assays also demonstrated that these mutations are critical for the catalytic activity of RIPK4. RIPK4 mediates activation of the nuclear factor-κB (NF-κB) signaling pathway and is required for keratinocyte differentiation and craniofacial and limb development. The phenotype of Ripk4(-/-) mice is consistent with the human phenotype presented herein. Additionally, the spectrum of malformations observed in the presented families is similar, but less severe than the conserved helix-loop-helix ubiquitous kinase (CHUK)-deficient human fetus phenotype; known as Cocoon syndrome; this similarity indicates that RIPK4 and CHUK might function via closely related pathways to promote keratinocyte differentiation and epithelial growth.

Mutations of the gene encoding otogelin are a cause of autosomal-recessive nonsyndromic moderate hearing impairment.

Already 40 genes have been identified for autosomal-recessive nonsyndromic hearing impairment (arNSHI); however, many more genes are still to be identified. In a Dutch family segregating arNSHI, homozygosity mapping revealed a 2.4 Mb homozygous region on chromosome 11 in p15.1-15.2, which partially overlapped with the previously described DFNB18 locus. However, no putative pathogenic variants were found in USH1C, the gene mutated in DFNB18 hearing impairment. The homozygous region contained 12 additional annotated genes including OTOG, the gene encoding otogelin, a component of the tectorial membrane. It is thought that otogelin contributes to the stability and strength of this membrane through interaction or stabilization of its constituent fibers. The murine orthologous gene was already known to cause hearing loss when defective. Analysis of OTOG in the Dutch family revealed a homozygous 1 bp deletion, c.5508delC, which leads to a shift in the reading frame and a premature stop codon, p.Ala1838ProfsX31. Further screening of 60 unrelated probands from Spanish arNSHI families detected compound heterozygous OTOG mutations in one family, c.6347C>T (p.Pro2116Leu) and c. 6559C>T (p.Arg2187X). The missense mutation p.Pro2116Leu affects a highly conserved residue in the fourth von Willebrand factor type D domain of otogelin. The subjects with OTOG mutations have a moderate hearing impairment, which can be associated with vestibular dysfunction. The flat to shallow "U" or slightly downsloping shaped audiograms closely resembled audiograms of individuals with recessive mutations in the gene encoding α-tectorin, another component of the tectorial membrane. This distinctive phenotype may represent a clue to orientate the molecular diagnosis.

Serum microRNAs; miR-30c-5p, miR-223-3p, miR-302c-3p and miR-17-5p could be used as novel non-invasive biomarkers for HCV-positive cirrhosis and hepatocellular carcinoma.

Recently, serum miRNAs have been evolved as possible biomarkers for different diseases including hepatocellular carcinoma and other types of cancers. Investigating certain serum miRNAs as novel non-invasive markers for early detection of HCV-positive cirrhosis and hepatocellular carcinoma (HCC). The expression profiles of 58 miRNA were analyzed in patient's plasma of chronic hepatitis C (CHC), HCV-positive cirrhosis and HCV-positive HCC and compared with control group samples. Totally 94 plasma samples; 64 patient plasma (26 CHC, 30 HCV-positive cirrhosis, 8 HCV-positive HCC) and 28 control group plasma, were included. The expression profiles of 58 miRNAs were detected for all patient and control group plasma samples by qRT-PCR using BioMarkTM 96.96 Dynamic Array (Fluidigm Corporation) system. In CHC group, expression profiles of miR-30a-5p, miR-30c-5p, miR-206 and miR-302c-3p were found significantly deregulated (p < 0.05) when compared versus control group. In HCV-positive cirrhosis group, expression profiles of miR-30c-5p, miR-223-3p, miR-302c-3p, miR-17-5p, miR-130a-3p, miR-93-5p, miR-302c-5p and miR-223-3p were found significantly deregulated (p < 0.05). In HCV-positive HCC group, expression profiles of miR-17-5p, miR-223-3p and miR-24-3p were found significant (p < 0.05). When all groups were compared versus control, miR-30c-5p, miR-223-3p, miR-302c-3p and miR-17-5p were found significantly deregulated for cirrhosis and HCC. These results imply that miR-30c-5p, miR-223-3p, miR-302c-3p and miR-17-5p could be used as novel non-invasive biomarkers of HCV-positive HCC in very early, even at cirrhosis stage of liver disease.

[Characterization of basal core promoter/precore gene mutations in chronically infected patients with hepatitis B virus genotype D in Mersin Province, Turkey]. / Mersin ilinde hepatit B virus genotip D ile kronik enfekte hastalarda bazal kor promotor/prekor gen bölgesi mutasyonlarinin karakterizasyonu.

The basal core promoter (BCP) and precore (PC) gene regions of hepatitis B virus (HBV) genome are important for the viral replication and synthesis of "e" antigen. Genetic variability has been described in PCP and PC gene regions, commonly in HBeAg negative patients. The aim of this study was to determine the frequency of the predominant mutation patterns of BCP/PC gene regions and their correlations with HBeAg status, HBV-DNA levels, and liver biochemical profiles in chronic hepatitis B (CHB) patients infected with genotype D, in Mersin province which is located at Mediteranean part of Turkey. A total of 54 CHB patients (33 male, 21 female; mean age: 40.05±12.91 years) infected with HBV genotype D were enrolled in the study. Serum HBV-DNA levels, serological markers (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc) and biochemical profiles (ALT and AST) were analyzed in all patients. BCP and PC gene regions were determined by polymerase chain reaction (PCR) and mutations of these regions were determined by direct sequencing of PCR products then aligned with known wild-type HBV sequences. BCP [nucleotide (nt.) 1753-1762/1764] and/or PC (nt. 1896) mutations were detected in 87.75% (43/49) of the patients. Mutation rates were detected as 97.1% (33/34) and 66.7% (10/15) in the HBeAg negative and in HBeAg positive patient groups, respectively (p=0.008). PC nt. G1896A mutation was more common in HBeAg negative samples than in HBeAg positive samples (73.5% vs. 20%, p=0.001), however there was no significant differences in the occurrence of BCP mutations between the two groups (p=0.331). No correlation was found between the presence of BCP and/or PC mutations and serum HBV-DNA or ALT-AST levels. Our study reveals that significant number of chronically infected patients with genotype D HBV have BCP and PC variants. G1896A stop codon mutation in precore region seems to have a significant role in the loss of HBeAg in our patients. The results of our study provided important data about the frequency and the genetic heterogeneity of different kinds of mutations occurring at BCP and PC gene regions.

Profiles of serum microRNAs; miR-125b-5p and miR223-3p serve as novel biomarkers for HBV-positive hepatocellular carcinoma.

Recently, circulating miRNAs have been reported as promising biomarkers for various pathologic conditions including cancer. Certain microRNAs (miRNAs) have been shown early diagnostic potential for many types of cancer. The objective of this study was to investigate the potential of certain serum/plasma miRNAs as novel non-invasive biomarkers for early diagnosis of hepatitis B virus (HBV) related hepatocellular carcinoma (HCC). For this reason, the expression levels of 24 miRNA (let-7c, miR-92a-3p, 423-5p, 150-5p, 223-3p, 125b-5p, 342-3p, miR-206, 122-5p, 375, 223-5p, 10a-5p, 23b-5p, 99a-5p, 23a-5p, 10a-3p, 122-3p, 125b-1-3p, 23b-3p, 125b-2-3p, 23a-3p, 92a-1-5p, 92a-2-5p, 99a-3p) were analyzed in plasma of patients with chronic hepatitis B, HBV-positive cirrhosis and HBV-positive HCC and compared with control group samples. Totally 94 plasma samples; 28 control and 66 patient plasma (24 CHB, 22 HBV-positive cirrhosis, 20 HBV-positive HCC) and were included in this study. The expression levels of 24 miRNAs were detected for all control and patient group plasma samples by qRT-PCR using BioMark™ 96.96 Dynamic Array (Fluidigm Corporation) system. The expression levels of miR-125b-5p were detected 2.85 fold, 2.46 fold and 1.89 fold (p = 0.01513, p = 0.0009440, p = 0.0001446) up regulated in CHB, HBV-positive cirrhosis and HBV-positive HCC, respectively when compared versus control group individually by Mann-Whitney U test. The expression levels of miR-223-3p were detected 5.55 fold, 13.88 fold and 12.65 fold (p = 0.01513, p = 0.0009440, p = 0.0001446) down regulated in same comparisons. When all groups were compared versus control group by one-way ANOVA test, the expression levels of miR-223-3p were also found statistically significant (p < 0.05). Although not statistically significant, miR-125b-5p tended to be upregulated. (p = 0.07192). These results significantly imply that miR-125b-5p and miR223-3p could be used as novel non-invasive biomarkers of HBV-positive HCC in very early, even at CHB stage of liver disease.

[Determination of hepatitis C virus genotype distribution in Mersin province, Turkey]. / Mersin ilinde hepatit C virusu genotip dagiliminin belirlenmesi.

Hepatitis C virus (HCV) is a member of the Flaviviridae family and the RNA genome e x hibit high genetic heterogeneity. Six major genotypes were phylogenetically determined and each genotype contains different subtypes. The distribution of HCV genotypes varies geographically throughout the world. Determination of viral genotype has great importance in the selection of antiviral therapy, treatment duration and monitoring the response to treatment. The aim of this study was to determine the distribution of HCV genotypes in Mersin province located at the Southern part of Turkey. A total of 236 patients (137 females, 99 males; mean age: 53.28 ± 14.99 years) with chronic HCV infection who were admitted to Mersin University Hospital Microbiology Laboratory during March 2010-May 2012 period were included in the study. The patients were anti-HCV (ELISA; Abbott Laboratories, USA) and HCV-RNA (Cobas TaqMan 48, Roche Diagnostic, USA) positive. HCV genotype analysis was determined by using a commercial LiPA kit (Line Probe Assay; AMPLIQUALITY HCV-TS; AB Analitica, Italy) based on the reverse hybridization of amplification products of viral 5'-UTR region. Out of the 236 patients, genotype 1b was observed in 84.7% (n= 200), genotype 3a in 4.2% (n= 10), genotype 1 in 3.8% (n= 9), genotype 1a/1b in 2.1% (n= 5), genotype 4a in 2% (n= 2), genotype 1a in 1.7% (n= 4), genotype 2b in 1.3% (n= 3), genotype 2 in 0.4% (n= 1), genotype 2a/2c in 0.4% (n= 1) and genotype 6 in 0.4% (n= 1). In the cases infected with genotype 1b, statistically significant differences were detected between gender distribution with the mean serum ALT (46.14 IU/L in females, 63.9 IU/L in males; p= 0.029) and HCV-RNA (634 x 103 IU/L in females, 20 x 105 IU/L in males; p= 0.005) levels. This was the first study that reflected the distribution of HCV genotypes in southern Turkey region. Genotype 1b, associated with poor prognosis and which had the highest prevalence in Turkey, was also determined as the most common genotype with a rate of 84.7% in our region. In addition, low rates of genotype 1a, 2b, 3a and 4a which were identified with low frequency in our country and newly introduced genotype 6 were also demonstrated.

Detection of hepatitis B virus X gene and PreC promoter mutations from chronic hepatitis B patients in the south of Turkey.

Hepatitis B virus (HBV) infection is a global health problem with more than 2 billion infected individuals. HBV infection leads to diverse outcomes ranging from acute to chronic hepatitis, which may result in severe complications as liver cirrhosis and hepatocellular carcinoma (HCC). HBV is one of the most important human DNA viruses having strong oncogenic potential. Recently, many studies have reported on HBV X gene and PreC promoter mutations associated with HCC. In order to detect the prevalence of HBx gene and PreC promoter mutations possibly related to HCC, we have analyzed sera samples collected from 61 patients with chronic hepatitis B. We have detected TI653 mutation in 1 of 61 (1,63%), A1896 mutation in 10 of 61 (16,39%), and T1762 - A1764 dual mutation in 4 of 61 (6,55%). T1653 and T1762- A1764 dual mutations were suggested significantly related to HCC in earlier reported studies. Our findings demonstrate that HBx gene and PreC promoter mutations related to HCC are present in our region and prospective clinical chord studies would be useful for better patient management and of early diagnosis of possible HCC cases.

The Abdominal Ultrasonography Results of Cappadocia Cohort Study of Turkey Reveals High Prevalence of Fatty Liver.

BACKGROUND: There is limited data about the prevalence of frequent gastrointestinal diseases in developing parts of the world based on community-based screening studies. Therefore, we aimed to present the detailed transabdominal ultrasonography results of the previously completed Turkey Cappadocia cohort study, which included a population-based evaluation of gastrointestinal symptoms and diseases in adults. METHODS: This cross-sectional study was conducted in Cappadocia cohort. The transabdominal ultrasonography, anthropometric measurements, and disease questionnaires were applied to cohort persons. RESULTS: Transabdominal ultrasonography was performed in 2797 subjects (62.3% were female and the mean age was 51 ± 15 years). Among them, 36% were overweight, 42% were obese, and 14% had diabetes mellitus. The most common pathological finding in transabdominal ultrasonography was hepatic steatosis (60.1%). The severity of hepatic steatosis was mild in 53.3%, moderate in 38.8%, and severe in 7.9%. Age, body mass index, liver size, portal vein, splenic vein diameter, hypertension, diabetes mellitus, and hyperlipidemia were significantly higher while physical activities were significantly lower in hepatic steatosis group. Ultrasonographic grade of hepatic steatosis was positively correlated with liver size, portal vein and splenic vein diameter, frequency of diabetes mellitus, hypertension, and coronary artery disease. Hepatic steatosis was observed in none of the underweight, 11.4% of the normal weights, 53.3% of the overweight, and 86.7% of the obese subjects. The percentage of hepatic steatosis cases with normal weight (lean nonalcoholic fatty liver disease) was 3.5%. The rate of lean nonalcoholic fatty liver disease in the entire cohort was 2.1%. Regression analysis revealed male gender (hazard ratio [HR]: 3.2), hypertension (HR: 1.5), and body mass index (body mass index: 25-30 HR: 9.3, body mass index >30 HR: 75.2) as independent risk factors for hepatic steatosis. The second most common ultrasonographic finding was gallbladder stone (7.6%). In the regression analysis, female gender (HR: 1.4), body mass index (body mass index: 25-30 HR: 2.1, body mass index >30 HR: 2.9), aging (30-39 age range HR: 1.5, >70 years HR: 5.8), and hypertension (HR: 1.4) were the most important risk factors for gallbladder stone. CONCLUSIONS: Cappadocia cohort study in Turkey revealed a high prevalence of hepatic steatosis (60.1%) while the prevalence of gallbladder stones was 7.6% among the participants. The results of the Cappadocia cohort located in central Anatolia, where overweight and lack of physical activity are characteristic, showed that Turkey is one of the leading countries in the world for nonalcoholic fatty liver disease.

The efficacy and tolerability of glecaprevir/pibrentasvir treatment in a real-world chronic hepatitis C patients cohort.

Background and Aim: The aims of the present study were to evaluate the real-life efficacy and tolerability of glecaprevir (GLE)/pibrentasvir (PIB) in the treatment of patients with chronic hepatitis C (CHC). Materials and Methods: Between May 2019 and May 2022, 686 patients with CHC, treated with GLE/PIB combination from 21 participating centers in Turkiye, were enrolled in the study. Results: All patients were Caucasian, and their median age was 56 years. At the start of GLE/PIB treatment, the median serum Hepatitis C virus RNA and serum alanine amino transaminase (ALT) levels were 6.74 log10 IU/mL and 47 U/L, respectively. Fifty-three percent of the patients were infected with genotype 1b, followed by genotype 3 (17%). Diabetes was the more common concomitant disease. The sustained virological response (SVR12) was 91.4% with intent-to-treat analysis and 98.5% with per protocol analysis. The SVR12 rates were statistically significant differences between the patients who were i.v. drug users and non-user (88.0% vs. 98.8%, p=0.025). From the baseline to SVR12, the serum ALT levels and Model for End-Stage Liver Disease score were significantly improved (p<0.001 and p=0.014, respectively). No severe adverse effect was observed. Conclusion: GLE/PIB is an effective and tolerable treatment in patients with CHC.

TASL Practice Guidance on the Clinical Assessment and Management of Patients with Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease and is significantly associated with obesity, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. NAFLD has become the most prevalent chronic liver disease in Western countries, and the proportion of NAFLD-related cirrhosis among patients on liver transplantation waiting lists has increased. In light of the accumulated data about NAFLD, and to provide a common approach with multi-disciplines dealing with the subject, it has become necessary to create new guidance for diagnosing and treating NAFLD. This guidance was prepared following an interdisciplinary study under the leadership of the Turkish Association for the Study of the Liver (TASL), Fatty Liver Special Interest Group. This new TASL Guidance is a practical application guide on NAFLD and was prepared to standardize the clinical approach to diagnosing and treating NAFLD patients. This guidance reflects many advances in the field of NAFLD. The proposals in this guidance are meant to aid decision-making in clinical practice. The guidance is primarily intended for gastroenterology, endocrinology, metabolism diseases, cardiology, internal medicine, pediatric specialists, and family medicine specialists.

[Detection of Helicobacter pylori and antimicrobial resistance in gastric biopsy specimens]. / Mide Biyopsi Örneklerinden Helicobacter pylori'nin Tanimlanmasi ve Antimikrobiyal Direncinin Arastirilmasi

Helicobacter pylori is reported as the etiological agent of gastritis, gastric and duodenal ulcer, gastric adenoid carcinoma and mucosa-associated lymphoid tissue lymphoma. In the diagnosis of H.pylori infections invasive (culture, histopathological examination, rapid urease test and molecular tests) and non-invasive (urea breath test, serological tests, stool culture and stool antigen/nucleic acid tests) methods may be used. Clarithromycin, amoxicillin and combination of metronidazole and protonpump inhibitor or ranitidine bismuth citrate triple treatment protocol is applied in order to treat and eradicate the infection. However, increasing rates of antibiotic resistance among H.pylori strains reduces the success of eradication therapy. The aim of this study was to investigate the presence of H.pylori in the gastric antral biopsy specimens and to determine the antimicrobial resistance of the isolates. A total of 149 gastric antral biopsy specimens obtained from patients (age range: 17-83 years; 73 were male) who admitted to Mersin University Faculty of Medicine Department of Internal Medicine Gastroenterology clinic with dyspeptic complaints were included in the study. H.pylori presence was investigated by culture, polymerase chain reaction (PCR) and urease test from gastric biopsy specimens, and H.pylori-specific antigen (HpSA) was investigated by ELISA in the stool samples of patients. Resistance to tetracycline, amoxicillin, metronidazole and levofloxacin was determined with E-test method. Clarithromycin resistance was determined both by E-test and PCR-RFLP (restriction fragment length polymorphism) methods. H.pylori was detected in 29.6% (43/145) of patients with culture, 55.2% (80/145) of patients with urease test, 57% (65/114) of patients with HpSA test and 71.3% (102/143) of patients with PCR. The sensitivity and specificity of culture, PCR, HpSA and urease tests were determined as 52.4% and 100%, 96.3% and 62.3%, 80.3% and 81.4%, 86.6% and 85.7%, respectively. According to the E-test results, resistance to clarithromycin was 18.2%, to tetracycline 9.1%, to metronidazole 45.5%, to levofloxacin 18.2% and no resistance was determined to amoxicillin. Clarithromycin resistance was searched in 94 of PCR positive 102 samples, and 17 (18.1%) of them yielded clarithromycin resistance. Of them 11 (64.7%) harbored A2144G (at 2144. nucleotide), and 6 (%35.3) harbored A2143G (at 2143. nucleotide) point mutations. In our study, PCR was determined as the most sensitive method, however due to its low specificity, the results should be confirmed with at least one of the other methods. The specificity of culture method was high, but sensitivity was found to be quite low compared with other methods. The sensitivity and specificity of urease and HpSA tests were found to be similar. In conclusion, in cases which endoscopy could not be done, non-invasive, rapid and practical HpSA method can be used in diagnosis and monitorization of the treatment. In the case of treatment failure, culture should be performed for antibiotic susceptibility testing of the isolate.

[Determination of hepatitis B virus genotypes in chronic hepatitis B patients in Mersin province, Turkey]. / Mersin Ilinde Kronik Hepatit B Hastalarinda Hepatit B Virusu Genotiplerinin Belirlenmesi.

Currently, ten genotypes (A-J) of hepatitis B virus (HBV) are identified based on the nucleic acid sequence heterogeneity, and these genotypes have been shown to have distinct geographic distribution. Reports of previous studies indicated that the genotype D is the predominant type among hepatitis B patients in different regions of Turkey, however there is no data for HBV genotypes to date from Mersin region. The aim of this study was to investigate the HBV genotypes by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in chronic hepatitis B patients in Mersin province (located in the Mediterranean region of Turkey). A total of 54 serum samples were obtained from the chronic hepatitis B patients (33 male, 21 female; mean age: 40.05 years) followed-up at Gastroenterology Clinic of Mersin University Hospital. Patients had detectable HBV-DNA levels in their serum samples, and they were under antiviral therapy for at least one year. Genotyping of HBV was performed by RFLP analysis with the use of AvaII and MboI restriction enzymes after amplification of pre-S gene region by PCR. Confirmation of selected 18 cases was carried out with direct DNA sequencing. The genotypes were determined by phylogenetic comparison with 43 reference NCBI (National Center for Biotechnology Information) HBV sequences. Genotype determination was not successful in seven cases; since three of them were negative in preS-PCR, three of them yielded non-specific bands, and one of them exhibited a deleted PCR product, at the 300 bp level that was shorter than expected. Four different restriction patterns were determined in PCR-RFLP analysis of the remaining 47 samples. One of these patterns which was AvaII [-]/MboI [306/89/51], was clearly discriminated in 72.3% (34/47) of the samples as genotype D. Genotype discrimination of three patterns could not be done properly and these patterns were AvaII [- ]/MboI [357/306/89/51] (7/47, 14.9%), AvaII [300/146]/MboI [306/89/51] (5/47, 10.7%), and AvaII [- ]/MboI [357/89/---] (1/47, 2.1%). Phylogenetic comparison of HBV sequences demonstrated that all patterns in our cases were clustered in NCBI genotype D sequences. Patterns of AvaII [300/146]/MboI [306/89/51] and AvaII [-]/ MboI [357/89/---] and deleted sample were recognized as pre-S gene variants of HBV isolates. Our data indicated that the predominant HBV type was genotype D as commonly seen in Turkey and other Mediterranean countries. The results of this study also showed that the genotype uniformity and pre-S gene variants within the HBV isolates could be crucial in terms of understanding the molecular epidemiology of HBV circulating in the Mediterranean region of Turkey.