Functional Bowel Disorder Management in Routine Practice with Tips for Hot Topics: Expert Opinion Review.

Functional gastrointestinal system disorders are common problems in practice. The most common symptoms are abdominal pain, gas, bloating, diarrhea, constipation, and a mixture of these, and similar symptoms can be seen in conditions such as inflammatory bowel disease, colorectal cancer, and celiac disease depending on the age of the patient, indicating the importance of differential diagnosis. The importance of patient management is shown by making a symptom-based diagnosis and making cost-effective, that is, limited advanced examinations. The pathophysiology of irritable bowel syndrome (IBS) is multifactorial, and stress is one of the leading triggers of IBS symptoms. Therefore, terminology will change to gut-brain interaction disorders in the future, and the patient-physician relationship has a special place in the treatment of functional bowel disorder. Dietary recommendation and medical treatment in IBS should be determined according to the predominant symptom and symptom severity. In addition to diet, some lifestyle changes can also be helpful in reducing IBS symptoms. Antispasmodics and antidepressants are not fast-acting. These drugs should be used for at least 2-4 weeks to see the efficacy of treatment. Drugs should be used according to the standard recommended duration and dose in intermittent treatments.

Is the Y90-radioembolization treatment effective on the intermediate-advanced stage of hepatocellular carcinoma and what is the albumin-bilirubin score's prediction factor for survival?

Background and Aim: Radioembolization (RE) is a one of the palliative treatments that have been used to down stage and/or increase the survival time in intermediate-advanced stages of HCC. We aimed to evaluate the clinical impact of RE and the clinical use of the albumin-bilirubin (ALBI) score as a predictor for survival in HCC patients. Materials and Methods: Fifty-nine unresectable hepatocellular carcinoma (HCC) patients were enrolled. RE was performed in 28 of them (group 1) and 31 patients were followed up in the natural course (NC) (group 2). Patients were classified according to the Child-Pugh score (only cirrhotic patients), Barcelona clinic liver cancer (BCLC) staging, and ALBI scores were also calculated. Results: All patients in Group 1 were cirrhotic and their BCLC stages were as follows: 60.7% stage B and 39.3% stage C. In Group 2, 83.9% of patients were cirrhotic and their BCLC stages were as follows: 9.7% stage B, 51.6% stage C, and 38.7% stage D. Mortality rates were 82% and 100% in Groups 1 and 2, respectively. The median overall survival (OS) was 13.5 months (95% CI: 10.4-16.6 months) and 4.5 months (95% CI: 3.5-5.5 months) in Groups 1 and 2, respectively (p=0.000). When RE was applied to patients with ALBI Grade 1 and 2, the median OS was statistically higher than in the NC group, respectively (p<0.001, p<0.001). Conclusion: RE is an effective treatment method at the advanced stages of HCC. The ALBI score is a more useful and practical than the other prognostic tools.

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.

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.

A Case of Budd-Chiari Syndrome Associated With Antiphospholipid Syndrome Treated Successfully by Transjugular Intrahepatic Portosystemic Shunt.

Budd Chiari syndrome (BCS) is defined as obstruction of hepatic venous outflow that can be located anywhere from small hepatic venules up to the entrance of inferior vena cava (IVC) into right atrium. Etiologies of BCS include myeloproliferative disorders, congenital, and acquired hypercoagulable states. Anticoagulation is the mainstay of treatment for all cases of BCS with a demonstrable hypercoagulable state. Interventional radiology procedures such as transjugular intrahepatic portosystemic shunting (TIPS) can be utilized to reduce portal hypertension and to improve complications related to portal hypertension. We present a patient with systemic lupus erythematosus who first presented with fever, weight loss, malar rash, alopecia, livedo reticularis, symmetric polyarthritis, pancytopenia, and class IV lupus nephritis when she was 23 years old. After receiving an induction treatment of cyclophosphamide and glucocorticoids, she received a maintenance treatment of azathioprine. She presented with ascites and abdominal pain when she was 36 and the abdominal imaging revealed reduced calibration of hepatic venules and intrahepatic segment of inferior vena cava. Lupus anticoagulant was positive and anti cardiolipin IgM and IgG were positive. Work up for hereditary hypercoagulable states was negative. Thus, the diagnosis was secondary antiphospholipid syndrome where BCS was the first clinical manifestation of the antiphospholipid syndrome. Patient was anticoagulated with warfarin and received diuretics for ascites. After the ascites became refractory to diuretics and the patient had multiple vertebral compression fractures due to volume overload secondary to ascites, she was successfully treated with TIPS. When control imaging was performed, 50% of stenosis was observed in the stent. Balloon dilation of the stent was performed. Interventional radiology techniques like TIPS can be used in BCS patients secondary to APS, in cases when medical treatment is insufficient to control complications of portal hypertension. In BCS patients secondary to APS, TIPS enables clinical improvement but due to the presence of endothelial dysfunction in APS patients, there is a risk of shunt dysfunction secondary to thrombosis or stenosis secondary to intimal hyperplasia. Therefore, strict anticoagulation and regular follow up of patients after TIPS is recommended. In cases with stent stenosis, reintervention may be necessary.

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.

Complementary Roles of Cadaveric and Living Donor Liver Transplantation in Acute Liver Failure.

BACKGROUND: Living donor liver transplantation may complement cadaveric transplantation in acute liver failure (ALF) patients. METHODS: Between 2008 and 2017, 89 patients were treated for ALF; 15 patients (17%) recovered with intensive care treatment; 31 (35%) died without transplant. The records of the remaining 43 patients (median (range) age: 14 (1-62)) who underwent transplantation were evaluated. RESULTS: The etiologic factors were toxic agents (10; mushrooms: 8; herbs: 2), hepatitis viruses (7; A: 1; B: 6), Wilson's disease (7), autoimmune hepatitis (4), and Budd-Chiari syndrome (2); 13 cases were idiopathic. Cadaveric organs (whole, split, reduced) were transplanted to 32 patients; 11 patients underwent living donor transplantation. One patient (2%) died of septic shock on the second postoperative day. Bacterial infection was the most common early (< 3 months) complication in the remaining patients (31/42; 74%), followed by delirium (5/42; 12%) and acute rejection requiring steroid pulse (5/42; 12%). Seven other patients died during median (range) follow-up of 94 (14-142) months: various infections (5), leukemia (1), and acute myocardial infarction (1). The 1-, 5-, and 10-year survival rates were 100%, 96%, and 92% in children and 94%, 82%, and 65% in adults respectively. CONCLUSIONS: Cadaveric organ sharing and transplantation from living donors when appropriate yield a high survival rate, despite high early morbidity, in ALF patients whose conditions deteriorate despite intensive care treatment. Efforts to eliminate preventable causes of acute liver failure will lead to more efficient use of health care resources.

ATA Index: A novel score for predicting fibrosis stage in chronic viral hepatitis.

Background and Aim: This study was designed to predict the fibrosis stage with a clinical scoring system that may reduce the need for liver biopsy. Materials and Methods: The study cohort included the treatment of 430 chronic hepatitis B (CHB) and 170 chronic hepatitis C (CHC) of naive patients. The patients were divided into two groups as mild to moderate and severe fibrosis. After an index obtained in the study cohort, the index was tested in a validation cohort and compared with the FIB-4 Index. Results: The AUC of CHC index was found of 0.89 the sensitivity of 0.91 the specificity of 0.74, the positive predictive value (PPV) of 0.54 and the negative predictive value (NPV) of 0.96. The FIB-4 Index was applied to the CHC study cohort and the ATA Index Hepatitis C was found to be superior in terms of AUC (0.89-0.82), sensitivity (0.91-0.76) and NPV (0.96-0.86). The AUC of CHB Index was determined of 0.92, the sensitivity of 0.90, the specificity of 0.84, the PPV of 0.53 and the NPV of 0.98. Compared to the FIB-4 Index in CHB study cohort, the ATA Index Hepatitis B was predominant in terms of AUC (0.92-0.88), sensitivity (0.90-0.75), NPV (0.98-0.94) and PPV (0.53-0.49). Conclusion: ATA Indexes can predict the non-existence of severe fibrosis with an accuracy similar to FIB-4 Index and may reduce the need for liver biopsy.

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.

Steroid-induced reconstitution of the biliary tree ravaged by IgG4-related disease.

The steroid-induced, rapid healing of the biliary tree ravaged by IgG4-related disease shows that the point of irreversibility remains to be defined.

The effect of liver test abnormalities on the prognosis of COVID-19.

INTRODUCTION: COVID-19 caused by the SARS-CoV-2 continues to spread rapidly across the world. In our study, we aim to investigate the relationship between the liver enzymes on admission (AST, ALT, ALP, GGT) and severity of COVID-19. We evaluated course of disease, hospital stay, liver damage and mortality. MATERIALS AND METHODS: Our study included 614 patients who were hospitalized with the diagnosis of COVID-19 between 03.16.20 and 05.12.20. Patients with liver disease, hematological and solid organ malignancy with liver metastases were excluded, resulting in 554 patients who met our inclusion criteria. We retrospectively evaluated liver transaminase levels, AST/ALT ratio, cholestatic enzyme levels and R ratio during hospital admission and these were compared in terms of morbidity, mortality and clinical course. RESULTS: Mean age of 554 subjects were 66.21±15.45 years, 328 (59.2%) were men. The mean values of liver enzymes on admission were AST (36.2±33.6U/L), ALT (34.01±49.34U/L), ALP (78.8±46.86U/L), GGT (46.25±60.05U/L). Mortality rate and need for intensive care unit were statistically significant in subjects that had high ALT-AST levels during their admission to the hospital (p=0.001). According to the ROC analysis AST/ALT ratio was a good marker of mortality risk (AUC=0.713: p=0.001) and expected probability of intensive care unit admission (AUC=0.636: p=0.001). R ratio, which was used to evaluate prognosis, showed a poor prognosis rate of 26.5% in the cholestatic injury group, 36.1% in the mixed pattern group and 30% in the hepato-cellular injury group (p 0.001). CONCLUSIONS: ALT-AST elevation and AST/ALT ratio >1 was associated with more severe course and increased mortality in COVID-19.

A micro-elimination approach to addressing hepatitis C in Turkey.

BACKGROUND: In 2016, WHO passed the Global Health Sector Strategy on Viral Hepatitis (GHSS), calling for its elimination by 2030. Two years later, Turkey approved a strategy to reach the WHO targets. This study reports new national prevalence data, breaks it down by subpopulation, and models scenarios to reach HCV elimination. METHODS: Literature was reviewed for estimates of HCV disease burden in Turkey. They were discussed with stakeholders and used as inputs to develop a disease burden model. The infected population was estimated by sequelae for the years 2015-2030. Three scenarios were developed to evaluate the disease burden in Turkey: a Base 2017 scenario, representing the current standard of care in Turkey; an increased treatment scenario, representing the impact of improved access to DAAs; and a WHO targets scenario, which meet the WHO GHSS viral hepatitis targets of a 65% reduction in mortality and 90% diagnosis rate of the infected population by 2030. RESULTS: At the beginning of 2017, 271,000 viremic infections were estimated. Of these, 58,400 were diagnosed and 10,200 treated. Modelling results showed that, with the current treatment paradigm in Turkey, by 2030 the total number of viremic HCV infections would decline by 35%, while liver-related deaths, hepatocellular carcinoma (HCC), and decompensated cirrhosis would decrease by 10-25%. In the increased treatment scenario, by 2030 viremic HCV infections would decrease by 50%; liver-related deaths, HCC and decompensated cirrhosis would decrease by 45-70%. In the WHO targets scenario, HCV infections would decrease by 80%; sequelae would decrease by 80-85%. Data on disease burden in micro-elimination target subpopulations are largely unavailable. CONCLUSIONS: To meet the WHO Global Health Sector Strategy targets for the elimination of HCV, Turkey needs to increase treatment. Better data are needed as well as countrywide access to DAAs.

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.

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.

Low recurrence rate of hepatocellular carcinoma following ledipasvir and sofosbuvir treatment in a real-world chronic hepatitis C patients cohort.

The aims of the present study were to evaluate the efficacy and tolerability of ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin in the treatment of chronic hepatitis C (CHC) in patients with advanced liver disease and to analyse whether the use of LDV/SOF treatment is associated with a new occurrence of hepatocellular carcinoma (HCC) during and after LDV/SOF treatment. The Turkish Early Access Program provided LDV/SOF treatment to a total of 200 eligible CHC patients with advanced liver disease. The median follow-up period was 22 months. All patients were Caucasian, 84% were infected with genotype 1b, and 24% had a liver transplantation before treatment. The sustained virological response (SVR12) was 86.0% with ITT analysis. SVR12 was similar among patients with Child-Pugh classes A, B and C disease and transplant recipients. From baseline to SVR12, serum ALT level and MELD score were significantly improved (P < 0.001). LDV/SOF treatment was generally well tolerated. Only one patient developed a new diagnosed HCC. Seventeen of the 35 patients, who had a history of previous HCC, developed HCC recurrence during the LDV/SOF treatment or by a median follow-up of 6 months after treatment. HCC recurrence was less commonly observed in patients who received curative treatment for HCC compared with those patients who received noncurative treatment (P = 0.007). In conclusion, LDV/SOF with or without ribavirin is an effective and tolerable treatment in CHC patients with advanced liver disease. Eradication is associated with improvements in liver function and a reduced risk of developing a new occurrence of HCC.

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.

Mutations in Core Gene Region of Hepatitis B Virus in Patients with Chronic Hepatitis B.

BACKGROUND: The HBV core protein plays a major role in host immune response. Mutations occurring in the HBV core gene may cause alterations in the major epitopes being effective in the host immune response. Until now, the persistent effects of core gene mutations on HBV infections have not been fully understood. The aim of this study is to analyze the core gene mutations for epitopes in the T lymphocytes [T helper (Th) and cytotoxic (CTL)] and B cell and C terminal region in patients with chronic hepatitis using ultra-deep pyrosequencing (UDPS) method. METHODS: Eleven patients with chronic hepatitis B infection were included in the study. Amplification of the core gene was performed by a conventional PCR method. Mutations in the epitopes for T lymphocytes (Th and CTL) and B cell and in the C terminal region of HBV core gene were screened by UDPS. These mutations were analyzed in HBeAg positive and negative patients. RESULTS: The minimum percentages of amino acid substitutions were found with 0.9% in HBeAg positive patients and 1.2% in negative patients. The number of missense mutation was higher in patients with HBeAg positive than negative patients (p < 0.005). The number of amino acid substitutions in the region of aa49 - 69 in the Th epitopes was found to be the highest in both HBeAg positive and negative patients. The mutation frequency was higher in the C-terminal region of the core protein compared to the Th, CTL, and B cell regions and these were more common in subjects with high-grade fibrosis. Some types of mutations (V27I, R47H, Y132I, R174STOP, S181P, Q182K) were only detected in subjects with liver cirrhosis. CONCLUSIONS: Unlike literature, our results show that there is no significant increase in number of mutations in the core gene of the virus during the anti-HBe positive period. The role of low abundance variants and mutations in the immune system can be understood using methods such as UDPS in the near future.