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.

Efficacy and Safety of Sofosbuvir and Ledipasvir for Hepatitis C in Kidney Transplant Recipients: A Single-center Retrospective Observational Study

Background: Treatment using direct-acting antivirals provides high rates of sustained virologic response and a favorable safety profile for patients with chronic hepatitis C virus infection. However, data on the efficacy of direct-acting antivirals in kidney transplant recipients are still limited. Aims: To evaluate the safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination in kidney transplant recipients. Study Design: Retrospective, observational, single-center study. Methods: Data of 29 kidney transplant recipients who received a fixed-dose safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination for 12 or 24 weeks with or without ribavirin were analyzed. The primary outcome was SVR12, which was defined as undetectable HCV-RNA levels 12 weeks after the treatment. Secondary outcomes were graft function, proteinuria, and calcineurin inhibitor trough level variability. Results: The predominant hepatitis C virus genotype was 1b (n = 19, 65.6%). All patients achieved SVR12. No graft failures nor deaths were reported during the study period. Throughout and after the treatment, the levels of aspartate aminotransferase [21 (range: 18-29.5) to 16 (range: 14-20) U/l, p < 0.001] and alanine aminotransferase [22 (range: 15-34) to 14 (range: 12-17.5) U/l, p < 0.001] improved significantly, unlike bilirubin, hemoglobin, and platelet levels. Renal function remained stable. Dose adjustments for calcineurin inhibitors were required. Serious adverse events were not observed. Conclusion: Safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination was effective and safe in kidney transplant recipients with hepatitis C virus. However, cautious monitoring of trough levels of calcineurin inhibitorss is needed due to potential drug-drug interactions during the treatment episode.

Cell-free methylation of RASSF1 and CDKN2AIP genes in the diagnosis of hepatocellular carcinoma associated with hepatitis B virus cirrhosis.

Background and Aim: Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC). Circulating cell-free DNA (cfDNA) methylation of tumor suppressor genes are emerging potential biomarkers in HCC. We aimed to evaluate the cfDNA methylation status of RASSF1 and CDKN2AIP genes in patients with liver cirrhosis (LC) with or without HCC caused by HBV. Materials and Methods: A total of 47 patients with HBV cirrhosis were included in the study. Patients were divided into two groups: HCC and LC (HCC+LC, n=22) and HBV cirrhosis only (LC, n=25). cfDNA was isolated from the plasma samples of the patients. Methylation analysis was performed for RASSF1 and CDKN2AIP genes. Results: Mean methylation percentage of CDKN2AIP gene was 0.001±0.004% in the HCC+LC group and 0.008±0.004 % in the LC only group. The mean methylation percentage of RASSF1 gene was 5.1±16.1% in the HCC+LC group and 9.7±25.9% in the LC only group. The methylation rate of CDKN2AIP was significantly lower in the HCC+LC group (p=0.027). A positive correlation was found with the absence of cfDNA methylation of CDKN2AIP gene in the presence of HCC (R=0.667, p=0.018). Conclusion: cfDNA methylation of CDKN2AIP and RASSF1 genes may provide important diagnostic information regarding the development of HCC in the setting of HBV cirrhosis.

Mucocutaneous Manifestations and Associated Factors in Patients with Crohn's Disease.

BACKGROUND: One-third of all extraintestinal manifestations are mucocutaneous findings in patients with Crohn's disease and there is a relationship between some risk factors. Our aim is to evaluate factors associated with mucocutaneous manifestations in our cohort of patients with Crohn's disease with a follow-up duration of up to 25 years. METHODS: In the study, 336 patients with Crohn's disease who were followed up between March 1986 and October 2011 were included. The demographic characteristics, Crohn's disease-related data, and accompanying mucocutaneous manifestations were recorded. The cumulative probability of mucocutaneous extraintestinal manifestations and possible risk factors were analyzed. RESULTS: Oral and skin involvement were detected in 109 (32%) and 31 (9.2%) patients, respectively. The cumulative probability of developing oral and skin manifestations were 43.2% and 20.3%, respectively. Cox regression analysis showed that female gender (odds ratio: 3.28, 95% CI: 1.51-7.14, P = .003) and corticosteroid use (odds ratio: 7.88, 95% CI: 1.07-57.97, P = .043) are independently associated with the development of skin manifestations, while family history (odds ratio: 3.59, 95% CI: 2.18-5.93, P < .001) and inflammatory-type disease (odds ratio: 1.776, 95% CI: 1.21-2.61, P = .004) were independently associated with the development of oral ulcers. CONCLUSION: Mucocutaneous extraintestinal manifestations are associated with female gender, corticosteroid use, family history, and disease type in a large cohort of patients with Crohn's disease. Defining the specific relationships of immune-mediated diseases will help to better understand the pathogenesis of Crohn's disease and associated mucocutaneous manifestations and to use more effective treatments.

Cyclosporine Therapy as a Rescue Treatment in Steroid Refractory Acute Severe Ulcerative Colitis: A Real Life Data From a Tertiary Center.

BACKGROUND: Cyclosporine is a rescue treatment alternative to avoid colectomy in corticosteroid refractory acute severe ulcerative colitis. In this study, we aimed to evaluate the long-term efficacy and safety of cyclosporine therapy in acute severe ulcerative colitis patients. METHODS: Acute severe ulcerative colitis (basal Lichtiger score > 10) patients who did not respond to 40 mg intravenous methylpredniso- lone therapy after 3-5 days were included in the study. The presence of clinical response and remission was assessed at 1st week, 1st, 6th, and 12th month according to the Lichtiger index. RESULTS: In this study, 40 patients, whose steroid refractory acute severe ulcerative colitis and basal Lichtiger score > 10 points were enrolled. The median disease duration was 49.3 months (2-204). All patients received cyclosporine for 132 ± 78 days (7-270). Clinical response was obtained on seventh day in 82.5%. The clinical response rates of the first and sixth months were 72.5% and 62.5%, respectively. A total of 17/40 (42.5%) patients underwent colectomy within 1 year. In the patients who underwent colectomy, the basal LS (14.2 ± 1.9 vs 12.3 ± 1.7) (P = .002) was higher and the basal hemoglobin value (11.8 ± 2.3 vs 10.1 ± 1.5) (P = .037) was lower than those who did not undergo colectomy. CONCLUSION: Our findings suggest that cyclosporine treatment may be successfully and safely used in steroid refractory acute severe ulcerative colitis patients. Cyclosporine is a drug that has recently started to come up again with the introduction of new maintenance treatments. Especially in patients who develop a loss of response to infliximab therapy, or where infliximab therapy is contraindicated, or who have azathioprine intolerance, or are unresponsive.

Evaluation of safety and efficacy of tenofovir disoproxil in hemodialysis and renal transplant patients monoinfected with hepatitis B virus based on real life data.

Introduction: There are limited data about the safety of tenofovir disoproxil fumarate (TDF) in chronic renal failure (CRF). In this study, we aimed to evaluate the safety and efficacy of TDF in renal transplant recipients and hemodialysis patients with chronic hepatitis B (CHB) during long-term follow-up. Material and methods: CHB patients undergoing hemodialysis (group 1), renal transplant recipients (group 2) and patients with normal renal function were included in the study. All patients were treated with TDF for at least 6 months. The groups were compared with regards to safety and efficacy. HBV-DNA levels were studied using a Cobas-TaqMan 96 system. Results: A total of 217 patients with CHB (group 1: 8 patients, group 2: 9 patients, group 3: 200 patients) were enrolled in this study. The frequency of clinical adverse effects was significantly higher in groups 1 and 2compared with group 3 (37.5% vs. 11.1% vs. 0.5%, respectively, p < 0.001). However, no patients discontinued the drug due to the adverse effects. Serum creatinine levels were similar at baseline and at the end of follow-up in groups 1 and 2 (6.5 ±1.8 mg/dl and 6.9 ±1.5 mg/dl; 1.3 ±0.2 and 1.4 ±0.4 mg/dl, respectively, p < 0.05). HBV-DNA negativity rates were comparable at the 12th month and at the end of follow-up (50-83% for group 1, 60-67% for group 2 and 70-75% for group 3, respectively, p > 0.05). Conclusions: Clinical adverse effects of TDF were more common in patients with CRF in comparison with patients without CRF. However, the occurrence of adverse effects did not necessitate discontinuation of the drug. TDF was safe and effective for this group of patients.

Is Having Inflammatory Bowel Disease a Risk Factor for Severe Acute Respiratory Syndrome Coronavirus 2?

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 virus was found to have effects not only in the lungs but also in many different organs. We aimed to evaluate the management of our patients with inflammatory bowel disease in this pandemic, the incidence of coronavirus disease 2019 in terms of clinical, medical treatment, and features of inflammatory bowel disease, and to investigate the effects of the severe acute respiratory syndrome coronavirus 2 on this particular group of patients. METHODS: During the coronavirus disease 2019 pandemic, 207 patients who had inflammatory bowel disease for at least 6 months were questioned for coronavirus disease 2019 at their outpatient clinic admissions, and their medical records were evaluated prospectively. RESULTS: Of the 207 patients, 146 had Crohn's disease. The mean disease duration was determined as 118.15 ± 72.85 months. Of the patients, 127 (61.4%) were using mesalazine, 110 (53.1%) azathioprine, and 148 (71.5%) biological agents. It was found that 66 (31.9%) patients changed their medications during the coronavirus disease 2019 pandemic. As a medication change, anti-Tumor Necrosis Factor (TNF) dose was observed to be omitted most frequently at a rate of 80%. Diarrhea was present in 20.8%, abdominal pain in 20.3%, nausea in 10.6%, anorexia in 13.5%, and weight loss in 15.9% of the patients. Twelve (5.79%) patients were diagnosed with coronavirus disease 2019. Lung involvement was present in 11 (91.7%) of the patients diagnosed with coronavirus disease 2019. Of the patients diagnosed and not diagnosed with coronavirus disease 2019, 75% vs. 71.6% were using biological agents (P = .80), respectively. Half of the patients diagnosed with coronavirus disease 2019 were active in terms of inflammatory bowel disease at the time of diagnosis, and 2 of these patients were severely active. CONCLUSION: The incidence of coronavirus disease 2019 infection in patients with inflammatory bowel disease was not different from the general population during the severe acute respiratory syndrome coronavirus 2 pandemic. Coronavirus disease 2019 infection does not progress with poor prognosis in patients with inflammatory bowel disease who receive immunosuppressive therapy including biological agents.

Is there any predictor for relapse after treatment withdrawal in autoimmune hepatitis patients in the real life?

BACKGROUNDS AND AIMS: In autoimmune hepatitis, there are uncertainties about whether to discontinue the treatment, when the treatment should be discontinued, and the risks of relapse in the cases where remission is achieved with immunosuppressive therapy. In this study, patients with AIH, whose immunosuppressive treatments were discontinued, were evaluated for the rates of remission and the risk of relapse. MATERIALS AND METHODS: A total of 119 patients, who were diagnosed with AIH based on the AIHG scoring systems between 1990 and 2015, were evaluated. Patients were receiving standard azathioprine and steroid therapy. The treatment was discontinued in patients, who had been receiving treatment for at least 2 years, who had no clinical complaints, and whose aminotransferases were normal and when an increase occurred in AST values more than two times the normal after the treatment was interrupted, the case was considered as a relapse. RESULTS: Among the patients, 83%(n = 99) were women. When the patients were diagnosed with AIH, their mean age was 36 ± 16(8-79) years; 70.6%(n = 84) were type 1, 3.4%(n = 4) type 2, and 26%(n = 31) were autoantibody-negative AIH. At the time of discontinuation, liver biopsy was performed in 8 of the patients and minimal-mild abnormalities were detected. Patients whose treatment was discontinued received treatment for an average of 101 ± 75(range: 24-280, median: 68.5) months; and, they were followed up for an average of 19 (1-110) months during the period without medication. Relapse occurred in 67%(n = 12) of the patients with drug withdrawal. Relapse occurred within the first 12 months in 67% of these patients (n = 8) and developed with an acute hepatitis attack in 42%. None of the clinical, laboratory, and histological data were found to be effective on relapse. CONCLUSION: In patients with AIH, relapse occurs in two-thirds of patients within an average of 19 month after the discontinuation of the medication. Most relapses occur at the early period and they are accompanied by an acute hepatitis attack.

The development of extraintestinal manifestation and related risk factors in Crohn's patients.

BACKGROUND: Crohn's disease (CD) primarily involves gastrointestinal tract; however, it can present with extraintestinal manifestations (EIMs), which leads to significant morbidity. Frequency of EIMs and associated risk factors vary due to genetic and environmental differences in studies. AIM: To examine the frequency and risk factors associated with EIMs in CD. METHOD: Patients with CD under follow-up from March 1986 to October 2011 were included in this study. Demographics, type of EIMs, autoimmune diseases, and clinical features of CD were recorded. Frequency of EIMs and associated risk factors were analyzed. RESULTS: Three hundred thirty-six patients with CD were included in the study (mean follow-up duration 7.54 years). 55.4% (n: 186) were male and the mean age at diagnosis of CD was 30.6 years (range, 10.3-68.2 years). At least one EIM was detected in 47.3% and multiple EIMs in 22.9% of the cohort. Oral, joint, and skin involvements (32.4%, 24.7%, 9.2%, respectively) were the most common EIMs. Female gender (OR: 2.19, 95% CI: 1.34-3.58, p = 0.001), corticosteroid usage (OR: 2.32, 95% CI: 1.28-4.22, p = 0.007), and positive family history (OR: 5.61, 95% CI: 1.95-3.58, p = 0.001) were independent risk factors for EIM development. Colonic involvement (OR: 3.93, 95% CI: 1.59-9.68, p = 0.003), no surgical operation (OR: 2.31, 95% CI: 1.14-4.68, p = 0.020), and corticosteroid usage (OR: 2.85, 95% CI: 1.07-7.61, p = 0.037) were independent risk factors for multiple EIM development. CONCLUSION: Although the immunological and clinical associations between EIMs and CD cannot be fully elucidated, identifying specific relationships of immune-mediated diseases will help to better understand CD pathogenesis.

Gastroesophageal Reflux in Asymptomatic Patients with Diabetes: An Impedance Study Diabetes, Obesity and Gastroesophageal Reflux.

INTRODUCTION: Gastroesophageal reflux disease (GERD) is more frequent in patients with diabetes mellitus (DM).The aim of the present study was to evaluate gastroesophageal reflux (GER) in asymptomatic patients with DM using 24-h pH impedance. MATERIALS AND METHODS: 19 healthy controls and 35 patients with DM without typical GERD symptoms were enrolled in the study. A 24-h pH-impedance study, esophageal manometry and gastroscopy were performed on all patients with DM. In the control group, an impedance study was performed on all subjects, and gastroscopy and esophageal manometry were performed on those who consented to the procedures. Patients with diabetes were categorized as obese [body mass index (BMI)>30 kg/m2] or non-obese (BMI<30 kg/m2) and both groups were compared with healthy controls. RESULTS: The mean BMI was similar in the control group (27.3±2.6 kg/m2) and the diabetic group (28.7±5 kg/m2) (p>0.05).Erosive esophagitis was found in 7.5% of the DM group. Esophageal dysmotility was higher in diabetics compared to the control group (45.5 vs. 11%, p=0.04). Neuropathy was found to be an independent risk factor for dysmotility. The mean DeMeester score (DMS) (25.6±32.5 vs. 11.2±17, p=0.01) and bolus exposure time (2.1±1.3 vs.1.3±1.3 min, p=0.009) were higher in the DM group compared with the control group.The difference was mainly observed between obese diabetics and the control group (p<0.05). The mean DMS, pathologic acid reflux, and esophageal dysmotility rate were higher in patients without complications of DM (p<0.05). BMI was higher in these patients than in patients with complications. CONCLUSION: Acid reflux is common in patients with diabetes.GER is associated with the existence of obesity rather than hyperglycemia.

Risk factors associated with progression to intestinal complications of Crohn disease.

BACKGROUND: Crohn disease is a chronic bowel disease that causes serious complications. Prevalence of Crohn disease is increasing. Studies have shown that the behavior of the disease is not stable and severe complications secondary to behavior change over time have been shown. In this study, we aimed to evaluate the prognostic risk factors associated with phenotypic change in Crohn disease in a Turkish patient cohort. METHODS: Patients followed up from March 1986 to August 2011 were evaluated for demographic and clinical characteristics to determine possible risk factors and initial clinical phenotype of the disease based on the Montreal classification. The cumulative probabilities of developing stricturing or penetrating intestinal complications were estimated using the Kaplan-Meier analysis. Univariate and multivariate Cox-proportional hazard models were used to assess associations between baseline clinical characteristics and intestinal complications. RESULTS: Three hundred and thirty patients (mean age, 30.6 ±â€Š11.1 years; 148 female) were included in the study. Mean follow-up duration was 7.4 ±â€Š5.3 years (range: 1.0-25.0 years). At baseline 273 patients had inflammatory-type disease, 57 patients experienced stricturing/penetrating intestinal complications before or at the time of diagnosis. The cumulative probability of developing complicated disease was 37.4% at 5 years, 54.3% at 10 years, 78.8% at 25 years. Independent predictors associated with progression to intestinal complications were current smoking, perianal disease, extra-intestinal manifestations, and location of disease. CONCLUSIONS: Location of disease is the most powerful indicator for the development of stenosis and penetrating complications in inflammatory-type disease. Patients with ileal involvement should be considered for more aggressive immunosuppressive therapy.

Cryptogenic liver cirrhosis and hepatitis E virus (HEV): Are they related?

INTRODUCTION AND OBJECTIVES: Hepatitis E virus (HEV) is one of the most common causes of acute hepatitis. In recent years, its role in the development of chronic hepatitis and cirrhosis especially in immunosuppressed patients and its wide range of extrahepatic involvement have increased the amount of research on HEV. In this study we aimed to investigate the presence of HEV infection in individuals with cryptogenic cirrhosis. MATERIALS AND METHODS: HEV antibodies were analysed using the Anti HEV enzyme-linked immunosorbent assay (ELISA) kit (anti-HEV ELISA; Diapro Prodiagnostic Bioprobes, Milan, Italy). HEV RNA was isolated with using QIAMP Viral RNA mini kit (QIAGEN, Hilden, Germany). The HEV RNA titre was detected with the Rotor Gene 3000 real time polymerase chain reaction (PCR) system using GenoSen's HEV (Rotor Gene) Quantitative Real Time PCR Kit (Genome Diagnostics Private Limited, the Netherlands). RESULTS: Our study included 21 healthy volunteers (12 males) and 35 cryptogenic cirrhosis patients (19 males). The ages of the patients and the controls were similar (46±12.1 vs. 37.5±9.7years). The mean Child-Pugh score was 8±2.5. The anti HEV immunoglobulin G(IgG) positivity rate was 9.5% and 25.7% in the control and patient groups respectively (p>0.05). HEV RNA positivity was not detected in the control group, but 3 cases (8.6%) in the patient group were positive (p>0.05). The HEV RNA, aspartate aminotransferase (AST) and alanine aminotransferase(ALT) levels for these 3 cases were 326.461copies/mL, 91IU/L and 67IU/L; 480copies/mL, 68IU/L and 36IU/L and 72copies/mL, 42IU/L and 24IU/L respectively. There were positive correlations between HEV RNA levels and AST and ALT levels (p<0.05). CONCLUSIONS: Anti HEVIgG and HEV RNA positivity rates are high in cryptogenic cirrhosis although it is not statistically significant and there is a positive correlation between HEV RNA and aminotransferases.

Inflammatory bowel disease and mycobacteria: how much can we trust isoniazid prophylaxis during antitumor necrosis factor therapy?

OBJECTIVES: Isoniazid (INH) prophylaxis is recommended for the prevention of tuberculosis (TB) reactivation before or/and during initiation of treatment with tumour necrosis factor antagonists (anti-TNF agents). Nonetheless, the long-term effectiveness of chemoprophylaxis is not clear. In this study, we aimed to evaluate the characteristics of patients who developed TB reactivation in spite of INH prophylaxis associated with anti-TNF treatment. PATIENTS AND METHODS: In this retrospective study, medical records of 1263 patients with inflammatory bowel disease were reviewed. Baseline TB screening tests (purified protein derivative test and/or QuantiFERON-TB Gold test) were performed on all patients before initiation of anti-TNF therapy. Patients with purified protein derivative of more than 5 mm and/or a positive result of the QuantiFERON-TB Gold test received INH prophylaxis for 9 months. We analysed the data of patients diagnosed with TB reactivation during the anti-TNF treatment despite INH chemoprophylaxis. RESULTS: Overall, 175 patients underwent anti-TNF treatment. Sixty of these 175 patients had pretreatment testing showing latent TB infection and therefore were treated concomitantly with INH for 9 months in addition to their anti-TNF treatment. TB reactivation occurred in four of these 60 co-INH/anti-TNF treated patients. Active TB was diagnosed after 37.5±27 (range: 18-84) months of anti-TNF treatment. In two of the four patients that active TB was diagnosed, was also detected other Mycobacterium spp.: M. bovis in one patient and M. genavense in the other one. CONCLUSION: INH chemoprophylaxis may not prevent the reactivation of TB during anti-TNF therapy in the long-term. Patients should be carefully and periodically screened for TB reactivation during anti-TNF therapy.

Changing epidemiology of chronic hepatitis C: patients are older and at a more advanced stage at the time of diagnosis.

INTRODUCTION AND AIM: Over the years, there has been a change in the profile of patients with chronic hepatitis C (CHC). In recent years, more patients with CHC have presented to the clinics at the cirrhotic stage, with decompensated liver disease, and with hepatocellular carcinoma. The aim of this study was to investigate the changing epidemiological, clinical, and virological characteristics of CHC patients. PATIENTS AND METHODS: A total of 313 CHC patients were included in this study. The patients were classified into group 1 (1996-2001) and group 2 (2011-2016). Epidemiological, clinical, and virological differences were investigated between two periods. RESULTS: Overall, 44.7% (n = 140) of the patients were in group 1. The sex distribution between the two groups was similar. The patients in group 2 was older than those in group 1 (54 ± 15 vs. 45 ± 12 years, retrospectively, P < 0.001). Whereas 19.8% of the patients in group 1 were treatment-experienced, this rate was found to be 35.5% in group 2 (P = 0.01). Patients who presented in the first period had fewer comorbidities compared with group 2 (P < 0.001). More patients in group 2 had liver cirrhosis than group 1 (45.1 vs. 18.6%, respectively, P < 0.001). Among the patients with cirrhosis, the rate of decompensation was higher in group 2 (46.7 vs. 23.3%, P = 0.03). The presence of hepatocellular carcinoma was significantly higher in group 2 than group 1 (12.8 vs. 3.6%, respectively, P = 0.004). CONCLUSION: In recent years, CHC patients have presented to hospitals with advanced stage of liver disease; these patients are older and have more comorbidities.

Does the number of mucosal immune cells differ in irritable bowel syndrome and its subtypes?

BACKGROUND/AIMS: Recently, mucosal inflammation has been proposed to be one of the mechanisms underlying the pathophysiology of irritable bowel syndrome (IBS); however, there are controversial results regarding this hypotheses. Our aim was to evaluate immune cell infiltration in rectal and ileal biopsy specimens of patients with IBS and to compare it with those of healthy controls. MATERIALS AND METHODS: In total, 36 patients with IBS (15 with diarrhea and 21 with constipation) and 16 healthy volunteers were enrolled. Ileocolonoscopy and ileal/rectal biopsies were performed. Rectal and terminal ileal biopsy specimens were evaluated for mucosal immune cell infiltration using immunohistochemical analysis. Serotonin positivity as well as counts of intraepithelial lymphocytes (IEL) and CD4+, CD8+, CD20+, and CD3+ cells were determined by a single pathologist who is an expert in the gastrointestinal system. RESULTS: CD3+ and CD4+ cell counts in rectal and terminal ileal biopsy specimens were lower in the IBS group than in the controls. Conversely, there was no statistically significant difference between the IBS and control groups in terms of serotonin positivity as well as counts of IEL and CD20+ and CD8+ cells. Comparison between the IBS subgroups revealed a higher number of IEL in rectal biopsy specimens of the diarrhea dominant group. In the IBS subgroups, immune cell counts in terminal ileal and rectal biopsy specimens showed a positive correlation. CONCLUSION: IBS and its subgroups showed lower immune cell counts than the controls in our study. These results indicate that there is no significant mucosal inflammation in homogeneous groups of patients with IBS. Rectal biopsies may be sufficient for the evaluation of inflammation in IBS.

Predicting mortality in patients with spontaneous bacterial peritonitis using routine inflammatory and biochemical markers.

OBJECTIVES: Spontaneous bacterial peritonitis (SBP) is a common and high-mortality infectious complication of patients with cirrhosis. New inflammatory markers are associated with morbidity/mortality in various diseases. The aim of our study was to find the 30-day mortality rate of SBP and their predictors. PATIENTS AND METHODS: Seventy patients with cirrhosis complicated with SBP and 55 non-SBP controls were enrolled into the study, and patients were evaluated for mortality rate and its predictors. RESULTS: The 30-day and 3-month mortality rates in the SBP group were 26.1 and 50.7%, respectively. Mortality rates were higher in the SBP group than in the controls. Symptoms at hospital admission and cell counts in ascitic fluid made no difference in predicting 30-day mortality. Patients with SBP with high serum neutrophil counts, high neutrophil-lymphocyte ratio, high C reactive protein (CRP)/albumin ratio, and high model for end-stage liver disease (MELD) score had higher 30-day mortality rates. We determined optimal cutoff values of MELD scores and serum neutrophil counts for predicting 30-day mortality as 20.5 and 6850/mm, respectively. The sensitivity and specificity for the MELD cutoff value were 83.3 and 80.4%, respectively. We also followed up patients for 60 months after SBP; the patients with high inflammatory markers and MELD scores at the time of SBP diagnosis had worse survival compared with the group with lower levels. CONCLUSION: Our results suggest that SBP has high 30-day mortality. MELD scores and inflammatory markers (CRP, CRP albumin ratio, neutrophil-lymphocyte ratio) may be used to predict mortality in patients with SBP.

Current state and clinical outcome in Turkish patients with hepatocellular carcinoma.

AIM: To investigate clinical, etiological, and prognostic features in patients with hepatocellular carcinoma. METHODS: Patients with hepatocellular carcinoma who were followed-up from 2001 to 2011 were included in the study. The diagnosis was established by histopathological and/or radiological criteria. We retrospectively reviewed clinical and laboratory data, etiology of primary liver disease, imaging characteristics and treatments. Child-Pugh and Barcelona Clinic Liver Cancer stage was determined at initial diagnosis. Kaplan-Meier survival analysis was done to find out treatment effect on survival. Risk factors for vascular invasion and overall survival were investigated by multivariate Cox regression analyses. RESULTS: Five hundred and forty-five patients with hepatocellular carcinoma were included in the study. Viral hepatitis was prevalent and 68 patients either had normal liver or were non-cirrhotic. Overall median survival was 16 (13-19) mo. Presence of extrahepatic metastasis was associated with larger tumor size (OR = 3.19, 95%CI: 1.14-10.6). Independent predictor variables of vascular invasion were AFP (OR = 2.95, 95%CI: 1.38-6.31), total tumor diameter (OR = 3.14, 95%CI: 1.01-9.77), and hepatitis B infection (OR = 5.37, 95%CI: 1.23-23.39). Liver functional reserve, tumor size/extension, AFP level and primary treatment modality were independent predictors of overall survival. Transarterial chemoembolization (HR = 0.38, 95%CI: 0.28-0.51) and radioembolization (HR = 0.36, 95%CI: 0.18-0.74) provided a comparable survival benefit in the real life setting. Surgical treatments as resection and transplantation were found to be associated with the best survival compared with loco-regional treatments (log-rank, P < 0.001). CONCLUSION: Baseline liver function, oncologic features including AFP level and primary treatment modality determines overall survival in patients with hepatocellular carcinoma.

Analysis of Hepatitis C Virus NS5A Region in Patients with Cirrhosis Using an Ultra-Deep Pyrosequencing Method.

BACKGROUND: HCV (Hepatitis C Virus) is genetically more diverse than HBV and HIV (Human Immunodeficiency Virus) and exists as quasispecies within infected individuals. This is due to the lack of efficient proofreading of the viral RNA-dependent RNA polymerase. Consequently, quasispecies emerge depending on the mutation rate of the viral polymerase, which may display a high level of genetic variability in a population. In infected individuals, HCV replicates and circulates as quasispecies composed of a complex mixture of different but closely related genomes that undergoes continuous change due to competitive selection and cooperation between arising mutants. The aim of this study is to investigate mutations in the NS5A region as a whole, including ISDR, PKRBD, IRRDR, and V3 of HCV genotype 1b cirrhosis patients being naive and nonresponders, treated with IFN (interferon) + ribavirin (RBN) by using an ultra-deep pyrosequencing method (UDPS). METHODS: During the study, five patients (four females, and one male, mean age 59.8 ± 11 years) with HCV related cirrhosis were analyzed. Three patients received IFN + RBN for six months, but two patients did not receive any therapy. HCV-RNA concentrations in patients' sera were determined using a COBAS AMPLICOR HCV MONITOR Test, Version 2.0. Genotyping was performed by using a commercial reverse hybridization method, Line Probe Assay. The quasispecies for the NS5A region were investigated using UDPS. RESULTS: All five patients were HCV genotype 1b (Mean Child-Pugh score 7.2 ± 1.9, 2 pts Child A, 2 pts Child B, and one pt Child C) but only one patient had hepatocellular carcinoma (HCC). A total of 19 different mutations were detected in each of the five patients (ranging from 3 to 6 mutations per patient). In all five patients, several mutations in the ISDR and PKR-BD regions were detected. On the other hand, mutations in the V3 and IRRDR regions were only detected in one patient. CONCLUSIONS: UDPS is a new sequencing technology and a very sensitive method in detection of quasispecies with low frequency NS5A region mutations. These mutations may affect the antiviral response and development of HCC. However, further studies in larger number of patients should be conducted to clarify this hypothesis.

Role of biochemistry and cytological analysis of cyst fluid for the differential diagnosis of pancreatic cysts: A retrospective cohort study.

BACKGROUND: Management of pancreatic cysts is based on neoplastic-nonneoplastic discrimination. Endoscopic ultrasound (EUS) enables to differentiate neoplastic-nonneoplastic lesions and also allows fine-needle aspiration (FNA). In this study, we aim to assess feasibility and clinical relevance of cytological and biochemical analysis in differential diagnosis of cystic pancreatic lesions in patients who had undergone endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) due to pancreatic cysts. METHODS: Participants were 96 patients who had undergone EUS-FNA for differential diagnosis of pancreatic cysts. Pancreatic cysts were classified as benign-mucinous, nonmucinous, and malignant according to patient history, physical examination, EUS appearance, and cystic fluid assessment. Tumor markers (CEA, CA(cancer antigens) 72.4, CA 19-9) , amylase, lipase and cytological assesment were compared between 3 different groups. Receiver-operating characteristics (ROC) curves were constructed to identify appropriate cut-off values. RESULTS: Fluid CEA and CA 72.4 levels for benign-mucinous and malignant cysts were significantly higher than for nonmucinous cysts (P ≤ 0.04). A cut-off CEA level of 207 ng/mL differentiated mucinous etiology with a sensitivity of 72.7%, specificity of 97.7%, and accuracy of 89.5%. The sensitivity, specificity, and accuracy of the CA 72.4 cut-off level of 3.32 ng/mL were 80%, 69.5%, and 73.6%, respectively. CONCLUSION: Cyst fluid CEA and CA 72.4 levels have a high accuracy in discriminating mucinous from nonmucinous cysts. When combined with cytology their accuracy rate increases.

Belching in Irritable Bowel Syndrome: An Impedance Study.

BACKGROUND/AIMS: There are limited data about the relation between belching and irritable bowel syndrome (IBS). We aim to evaluate belching in patients with IBS. METHODS: Twenty-five patients with IBS and 12 healthy volunteers were enrolled in the study. IBS was diagnosed in accordance with the Rome III criteria. All patients were questioned about the presence of symptoms for belching, gastroesophageal reflux disease, and dyspepsia. Esophageal manometry and 24-hour pH-impedance were performed in all patients and healthy volunteers. Each of the patients with IBS underwent gastroscopy and colonoscopy. RESULTS: Demographic features were similar in both groups (P > 0.05). The belching rate was 32% in patients with IBS. The mean DeMeester score was significantly higher in IBS patients (13.80 ± 14.40 vs 6.04 ± 5.60, P = 0.027) and 24% of patients had pathologic acid reflux (DeMeester score > 14). Gastroscopy was normal in all patients. Symptom association probability positivity was detected in 24% of patients in the impedance study. The rate of weak acid reflux was also significantly higher in patients with IBS (97.00 ± 56.20 vs 58.20 ± 29.30, P = 0.025). The number of supine gas reflux (7.50 ± 6.40 vs 2.42 ± 2.80, P = 0.001) and supragastric belches was significantly higher in patients with IBS (51.20 ± 41.20 vs 25.08 ± 15.20, P = 0.035). Although the number of gastric belching was higher in controls, the difference did not reach statistical significance (12.10 ± 17.60 vs 4.90 ± 3.80, P = 0.575). We did not find any correlation between belching and any symptoms of IBS. CONCLUSIONS: Belching is frequent in patients with IBS. Non-erosive reflux disease is frequent in IBS, which may be related to supragastric belching.