Evaluation of the histologic and immunohistochemical (CD34, glutamine synthetase) findings in idiopathic non-cirrhotic portal hypertension (INCPH).

AIM: Idiopathic non-cirrhotic portal hypertension (INCPH) is a vascular disorder of uncertain origin. Diagnosis can be challenging on liver biopsy. Despite diverse histomorphologic findings documented in literature, studies on the frequency of these findings are lacking. This study aims to assess both the histomorphologic features and the immunoexpression patterns of CD34 and glutamine synthetase (GS) in liver biopsies and searched for their contribution to the pathologic diagnosis of INCPH. MATERIALS AND METHODS: Hematoxylin-eosin, CD34, and GS-stained liver needle biopsy sections of 16 patients clinically diagnosed with INCPH were retrospectively analyzed. Histologic findings such as portal vein narrowing, obliteration, or loss were grouped as major findings, while portal vein herniation, hypervascularized portal tracts, and periportal abnormal vessels were grouped as minor findings, and their frequency were evaluated. Periportal endothelial CD34 stained areas were measured via ocular micrometer. The distribution of GS immunoexpression was evaluated. Eighteen healthy liver donor biopsies were evaluated as controls. RESULTS: In INCPH cases, 58% of portal tracts showed major findings, compared to 15% in the control group (p < 0.001). Minor findings were observed in 16% of INCPH cases and 7% of controls (p = 0.014). The number of portal tracts with histologic findings is significantly higher in INCPH than in control liver biopsies. Abnormal portal tract distribution, like being close to each other, was seen in 75% of INCPH cases but not in controls (p < 0.001). Nodular regenerative hyperplasia (NRH) was present in 31% of cases. Periportal CD34 expression was higher in INCPH, and affected areas were larger than in controls (p < 0.001). Irregular GS staining, i.e. GS staining with patchy distribution in zone 3, and/or periportal and zone 2 hepatocytes, was found in 62% of INCPH cases, while controls showed the usual pattern (p < 0.001). CONCLUSION: In the biopsy diagnosis of INCPH, in addition to the presence of major histologic findings and the amount of portal tracts displaying these features, the expression of endothelial CD34 in periportal areas, and irregular hepatocellular GS expression can also be considered as supporting feature.

Diagnosis and Treatment of Autoimmune Hepatitis: Questions, Answers, and Illustrative Cases: Endorsed by Autoimmune Liver Diseases Special Interest Group, Turkish Association for the Study of Liver.

Autoimmune hepatitis (AIH) is a rare, immune-mediated liver disease. It has a heterogeneous nature with varied clinical presentations. The management of patients with AIH is challenging in many ways. The main difficulties are inexperience due to the rarity of the disease, diagnostic confusion in controversial areas such as variant/overlap cases, acute presentations, the presence of non-alcoholic fatty liver disease or drug-induced liver injury features, and the long and complex course of treatment. Here, we provide a clear, concise, and visualized review regarding the diagnosis and treatment of AIH, including illustrative cases.

Neoadjuvant intermediate-course versus long-course chemoradiotherapy in T3-4/N0+ rectal cancer: Istanbul R-02 phase II randomized study.

Radiation therapy (RT) is typically applied using one of two standard approaches for preoperative treatment of resectable locally advanced rectal cancer (LARC): short-course RT (SC-RT) alone or long-course RT (LC-RT) with concurrent fluorouracil (5-FU) chemotherapy. The Phase II single-arm KROG 11-02 study using intermediate-course (IC) (33 Gy (Gray)/10 fr (fraction) with concurrent capecitabine) preoperative chemoradiotherapy (CRT) demonstrated a pathologically complete response rate and a sphincter-sparing rate that were close to those of LC-CRT. The current trial aim to compare the pathological/oncological outcomes, toxicity, and quality of life results of LC-CRT and IC-CRT in cases of LARC. The prescribed dose was 33 Gy/10 fr for the IC-CRT group and 50.4 Gy/28 fr for the LC-CRT group. Concurrent chronomodulated capecitabine (Brunch regimen) 1650 mg/m2/daily chemotherapy treatment was applied in both groups. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer Module (EORTC QLQ-CR29) was administered at baseline and at three and six months after CRT. A total of 60 patients with LARC randomized to receive IC-CRT (n = 30) or LC-CRT (n = 30) were included in this phase II randomized trial. No significant difference was noted between groups in terms of pathological outcomes, including pathological response rates (ypT0N0-complete response: 23.3% vs. 16.7%, respectively, and ypT0-2N0-downstaging: 50% for each; p = 0.809) and Dworak score-based pathological tumor regression grade (Grade 4-complete response: 23.3 vs. 16.7%, p = 0.839). The 5-year overall survival (73.3 vs. 86.7%, p = 0.173) rate was also similar. The acute radiation dermatitis (p < 0.001) and any hematological toxicity (p = 0.004) rates were significantly higher in the LC-CRT group, while no significant difference was noted between treatment groups in terms of baseline, third month, and sixth month EORTC QLQ-CR29 scores.

Malignant Colorectal Polyps: Are Pathology Reports Sufficient for Decision Making?

AIM: This study aims to assess the completeness of pathology reports of T1 colorectal cancers from different healthcare centers and the change of treatment decision after reevaluation of the polyps. MATERIALS AND METHODS: In this single-center retrospective cohort study, several pathology reports of endoscopically excised malignant colorectal polyps at diverse healthcare centers in Turkey were reassessed at a comprehensive cancer center in Istanbul. Reassessment was mainly focused on core elements such as the size of invasive carcinoma, histologic type and grade, tumor extension, surgical margin (deep and mucosal), and lymphovascular invasion. RESULTS: Sixty-seven endoscopically resected malignant polyps were analyzed. The mean age of patients was 62.2 years and 38 (58%) patients were males. Tumor size, histologic type and grade, surgical margin (deep and mucosal), and lymphovascular invasion were reported in 11%, 100%, 31%, 9%, and 19%, respectively. All 5 prognostic factors were reported only in 1 (1.5%) pathology report. Because of the missing (incomplete) data, the pathologic examination of 59 (88%) patients was determined to be inadequate to make an accurate treatment decision. CONCLUSION: Several variables are not considered and frequently missing for decision-making, suggesting the reassessment of the specimen by a second pathologist at a high-volume comprehensive cancer center.

BRAF, NRAS, KIT, TERT, GNAQ/GNA11 Mutation Profile and Histomorphological Analysis of Anorectal Melanomas: A Clinicopathologic Study.

OBJECTIVE: Primary anorectal melanomas (AMs) are uncommon neoplasms with aggressive behavior. Molecular profile and clinicopathologic features of AMs are still not well established. In this study, we aimed to investigate BRAF, NRAS, KIT, TERT, and GNAQ/GNA11 mutation status and clinicopathologic features of AMs. MATERIAL AND METHOD: All diagnostic slides of 15 AMs were reviewed. Histopathological and follow-up information were documented. Mutations in exon 15 of the BRAF gene; exons 2 and 3 of the NRAS gene; exons 9, 11, 13, 17, and 18 of the KIT gene; and exons 4 and 5 of the GNAQ/GNA11 genes and mutations in the promoter region of the TERT gene (chr.5, 1,295,228C > T and 1,295,250C > T) were analyzed. RESULTS: BRAF(V600E) and KIT(V555I and K642E) mutations were observed in one (7%) and two cases (14%), respectively. NRAS, TERT and GNAQ/GNA11 mutations were not detected. The mean age was 65. Patients presented with rectal mass, rectal bleeding, pain, and weight loss. 73% of the lesions were macroscopically polypoid. The most common tumor cell type was epithelioid. Mean tumor thickness was 10.4 mm. One third of the cases lacked pigmentation. In situ melanoma was present in one third of the cases. Among 14 patients with follow-up data, 12 succumbed to disease. The mean overall survival was 36 months. CONCLUSION: AMs are uncommon tumors with dismal survival, usually occurring in the elderly in various gross and microscopic appearances. In terms of molecular profile, BRAF and KIT mutations are rarely detected. Profiling of larger cohorts is required to elucidate the pathogenesis and to identify potential molecular indicators that may contribute to the development of individualized targeted therapies.

The effects of IL28B rs12979860 and rs8099917 polymorphism on hepatitis B infection.

OBJECTIVE: The purpose of this study was to evaluate the relationship of IL28B rs12979860 and rs8099917 polymorphisms with the clinical, histological, and virological outcomes of patients with chronic hepatitis B (CHB) also the treatment responses of patients who received Nucleos(t)ide analogs (NAs) therapy. METHODS: This study included 152 CHB patients who were underwent liver parenchymal biopsy. The IL28B rs12979860 and rs8099917 polymorphism were genotyped using the TaqMan assay. RESULTS: The IL28B rs12979860 CC and IL28B rs8099917 TT were identified as the genotypes with the highest frequency in all patients. On the other hand, IL28B rs12979860 TT and IL28B rs8099917 GG were the genotypes with the lowest frequency. The frequency of IL28B rs8099917 TG genotype was significantly different between patients with hepatitis B, who has histologically defined liver cirrhosis and no-fibrosis (p=0.02). In addition, a statistically significant correlation was found between the presence of IL28B rs8099917 G allele and virological unresponsiveness to NAs treatments in CHB patients (p=0.028). CONCLUSION: The presence of the IL28B rs8099917 G allele in CHB patients might be associated with the risk of developing cirrhosis and virological unresponsiveness to NAs treatments.

Comparison of S gene mutations in patients with occult and chronic hepatitis B virus infection.

BACKGROUND AND AIM: This study aimed to detect mutations in the HBV S gene and evaluate their relationship to occult hepatitis B virus (HBV) infection (OBI). METHODS: The study included 32 patients with negative serum HBsAg and HBV DNA who underwent liver biopsy due to different clinical indications defined as the OBI group and 32 patients who underwent liver biopsy due to chronic hepatitis B (CHB) as the comparison group. The HBV S gene region was amplified by Nested PCR, and Sanger sequencing was performed. RESULTS: At least one amino acid (aa) mutation was detected in the major hydrophilic region (MHR) of the HBV S gene in 14/32 (43.75%) of the patients with OBI and 8/32 (25.0%) with CHB. The genotype of all patients with OBI and CHB was HBV/D. Although 9 (28.1%) of the cases with OBI had sub-genotype HBV/D3, none of the patients with CHB had sub-genotype HBV/D3. Unlike patients with CHB, L15*, D33N, Q51P, V63F, L91I, P108S, T115I, P120L, T125M, Q129H, T189I, L216F, P217L mutations were detected in the HBV S gene in OBI cases. Also, P127T aa polymorphism was frequently detected. Mutation frequency in the HBV S gene in the major hydrophilic region (MHR) was higher in patients with OBI with sub-genotypes HBV/D3 and D2 than those with HBV/D1 and those with serotype HBV/ayw3 compared to those with HBV/ayw2 (p < 0.05). CONCLUSIONS: Sub-genotypic-specific mutation patterns were seen in the "a" determinant region and T helper cell epitopes of HBsAg, especially in the C-terminus domain; this may be associated with OBI.

What is the clinical impact of occult HBV infections and anti-HBc positivity in patients with chronic hepatitis C?

Occult hepatitis B infection (OBI) is defined by the persistence of the hepatitis B virus (HBV) genome in the liver of individuals testing negative for hepatitis B surface antigen (HBsAg). Hepatitis B core antibody (anti-HBc) is the serological marker that indicates HBV exposure. The impact of anti-HBc and OBI on patients with chronic hepatitis C remains unclear. The aim of the present study was to determine the prevalence of anti-HBc and OBI and to evaluate their impact on the clinical and pathological outcomes of patients with chronic hepatitis C. The study included 59 HBsAg-negative chronic hepatitis C patients who underwent a liver parenchymal biopsy. The presence of HBV DNA was investigated using an in-house nested PCR method. OBI was detected in 16 (27.1%) of the 59 cases and also in 10 (62.5%) of 22 (37.3%) anti-HBc-positive patients. None of the patients had positive serum HBV DNA. OBI was associated with the presence of anti-HBV antibodies (P < 0.05). There was also an association between anti-HBc positivity and the activity grades and fibrosis stages of the liver and also a prevalence of liver steatosis (P < 0.05). Positive anti-HBc results may predict OBI and may also be associated with the progression of liver injury in HBsAg-negative patients with chronic hepatitis C. Therefore, it is suggested that patients with chronic hepatitis C should be screened for anti-HBc positivity, and anti-HBc-positive patients should be carefully evaluated for disease progression.

Acinar Cystic Transformation of the Pancreas: Report of Three Cases.

Acinar cystic transformation (ACT) of the pancreas is a rare non-neoplastic cystic lesion. It is most frequently observed in the head of the pancreas. Despite advances in radiologic imaging methods, preoperative diagnosis of acinar cystic transformation is difficult, it is often confused with other cystic lesions. Here, we report three cases of acinar cystic transformation, one of which showed diffuse involvement of the pancreas, and the remaining two were multilocular localized cystic lesions. We analyzed their histomorphologic and immunohistochemical features. The patients' ages ranged between 15 and 43 years and the ratio of females to males was 2:1. On microscopic examination, the cysts were lined by a single layer of flattened-cuboidal or columnar epithelial cells. The epithelial cells were diffusely positive with trypsin and keratin 7, but patchy with keratin 19. Due to its rarity and lack of radiologic and clinical awareness compared with other pancreatic cystic lesions, preoperative diagnosis of acinar cystic transformation is difficult and not definitive. All cases reported to date have been clinically benign and there is no evidence of recurrence or malignant transformation. The optimal treatment and whether to perform surgery remain controversial.

Can Interferon Therapy Change the Natural Course of Hepatitis Delta Infection?: a Clinical and Pathological Study.

Chronic delta hepatitis (CDH) has a worse outcome than other types of viral hepatitis. High-dose, long-term alpha interferon (IFN-α) is the approved treatment and may ameliorate the course of infection. We evaluated long-term histological outcomes of CDH patients treated with IFN-α. Patients with histologically proved noncirrhotic CDH who were treated with high-dose IFN-α for at least 1 year were classified as cirrhotic or noncirrhotic at the end of treatment. Noncirrhotic patients also had posttreatment liver biopsies. Patients were designated histologically responsive or nonresponsive on the basis of fibrosis status. Histological, virological, and biochemical courses were analyzed. Forty-eight patients were treated with IFN-α (conventional and/or pegylated) for a median of 24 months with a posttreatment follow-up of 5 years. During the follow-up, cirrhosis developed in 24 patients, 5 of whom were decompensated. There was no difference between pre- and posttreatment fibrosis scores for 24 noncirrhotic patients at the end of follow-up. Among patients, 13% (n = 6) had decreased, 21% (n = 10) had steady, and 16% (n = 8) had increased fibrosis scores. Persistent viral response (PVR) was achieved in 16 patients (33%). Twenty percent of the entire group was histologically responsive (decreasing or steady fibrosis scores with improved necroinflammatory scores), while nearly 80% had histological progression/cirrhosis. PVR was significantly associated with histological response. The long-term natural course of patients who were treated with high dose IFN-α for at least 1 year was evaluated clinically and histologically. Despite the association of PVR with histological response, IFN-α treatment did not change the natural course of CDH; clinical and histological progression continued in two-thirds of the cases despite treatment.

Metastases to the Stomach: Clinicopathologic Features of Metastases Mimicking Gastric Primaries.

OBJECTIVE: Metastatic involvement of the stomach is a rare event. Our aim in this study was to document the clinicopathological findings in patients with gastric metastases and find out if there are any potentially significant features to be used in the differential diagnosis. MATERIAL AND METHOD: Our cohort consisted of 17 histologically verified gastric metastasis cases. Clinical, endoscopic and microscopic features were retrospectively analyzed. RESULTS: The primary sites were the breast, skin, lungs, ovaries, colon, and gluteal soft tissue. Three patients were symptomatic because of the metastatic involvement of the stomach and 9 patients had concomitant metastasis in other sites. Invasive lobular breast carcinoma and malignant melanoma were the most common metastatic malignancies. The most common macroscopic appearance was the diffuse infiltrative type (Borrmann Type 4). Most of the metastatic lesions endoscopically mimicked primary gastric cancer. Furthermore, some of the metastatic lesions, particularly invasive lobular carcinoma of the breast and malignant melanoma, displayed histopathologic features similar to the primary gastric malignancies to a certain extent. CONCLUSION: The possibility of metastatic involvement of stomach must be kept in mind while dealing with a gastric mass lesion in a cancer patient, even though the clinical and endoscopic features suggest primary gastric cancer. Our study points out the importance of conveying the information about medical history and clinical findings of the patients for correct pathologic differential diagnosis.

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.

Hepatocellular adenomas in the Turkish population: reclassification according to updated World Health Organization criteria.

AIMS: Hepatocellular adenoma (HCA) is an uncommon liver neoplasm, and studies of HCA subtypes have been primarily limited to France, the USA, and Japan. The aim of this study was to describe the clinicopathological features of HCA subtypes in Turkey. METHODS AND RESULTS: The resection specimens of 59 cases diagnosed as 'hepatocellular adenoma' collected from 15 institutions were reviewed to confirm the diagnosis and to classify them according to the current World Health Organization 2019 classification. Immunostaining for glutamine synthetase, liver fatty acid-binding protein, C-reactive protein, ß-catenin and reticulin was performed. Of the 59 cases, 48 (81%) were diagnosed as HCA. We identified 24 (50%) hepatocyte nuclear factor 1α (HNF1α)-inactivated HCAs, five (10%) inflammatory HCAs, 15 (32%) ß-catenin-activated HCAs, three (6%) ß-catenin-activated inflammatory HCAs, and one (2%) unclassified HCA. HCA patients were predominantly female (female/male ratio of 5:1); they had a median age of 34 years and a median tumour diameter of 60 mm. In the ß-catenin-activated HCA group, nine cases (19%) showed cytoarchitectural atypia, and were also referred to as atypical hepatocellular neoplasms. In the ß-catenin-activated HCA group, three cases (6%) showed focal areas supportive of transition to HCA. The original diagnosis of HCA was changed to well-differentiated hepatocellular carcinoma in nine cases and to focal nodular hyperplasia in two cases. CONCLUSION: In our series, the major HCA subtype was HNF1α-inactivated HCA. We found a low incidence of inflammatory-type HCA. Our data also showed that ß-catenin-activated hepatocellular neoplasms, including cases with atypical histology, constituted a relatively high proportion of the cases. These findings are in contrast to those of most other studies of HCA subtypes.

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.

Diagnostic significance of cytomegalovirus DNA quantitation in gastrointestinal biopsies: comparison with histopathological data and blood cytomegalovirus DNA.

OBJECTIVES: This study aims to improve the diagnosis of gastrointestinal (GI) cytomegalovirus (CMV) disease. It presents the results of a novel study in which CMV blood viral load (BVL), tissue viral load (TVL) determined by PCR and hematoxylin-eosin (HE)/immunohistochemistry (IHC) results of GI biopsies are examined comparatively. METHODS: CMV DNA was investigated by quantitative real-time PCR in blood and GI biopsy specimens of 76 patients suspected of CMV disease. Biopsies were also performed HE/IHC stainings in the pathology laboratory. RESULTS: This study included 76 patients whose median age was 34.5 years and 58% (44) were male. Tissue CMV PCR positivity was detected in the highest colon (40/53;75.5%) samples. HE, IHC, blood and tissue CMV PCR positivity rates of all samples were 15.8, 25, 50 and 71.1%, respectively. When IHC was used as the gold standard test for ROC analysis, the optimal cutoff values for the maximum sensitivity and specificity for BVL and TVL were 1.91 log10 copies/ml and 3.82 log10 copies/mg, respectively. Sensitivity and specificity for the cutoff value of tissue CMV DNA were 78.9 and 74.3%, respectively (P < 0.001). CONCLUSION: In this study, CMV DNA was detected in 71.1% of the tissue samples of the cases by PCR. Since the sensitivity of the histopathological examinations accepted as the gold standard is low, simultaneous with the histopathological examinations, determination of BVL, TVL and the identification of optimal cutoff values have been shown to support the diagnosis of GI CMV disease.

Malignant Transformation of Parotid Gland Non-sebaceous Lymphadenoma: Case Report and Review of Literature.

Non-sebaceous lymphadenoma is a sporadic benign tumor of salivary glands. Histopathologic and immunohistochemical properties, diagnostic criteria, and theories for the histologic origin of the disease have been defined and well-discussed in the literature. However, none of the cases showed malignant transformation to date. We reported a case of 54 years old female patient with a right preauricular mass. Magnetic resonance imaging demonstrated a 2 cm, well-defined contrast-enhanced mass in the right parotid gland. Fine needle aspiration cytology was undiagnostic but suspicious for malignancy. Total parotidectomy with facial nerve preservation was done. In the histopathological examination, non-sebaceous lymphadenoma regions and malignant cells with abundant cytoplasm, large vesicular nuclei, and prominent nucleoli, which occupied approximately 70% of the mass, were seen. The diagnosis was undifferentiated carcinoma arisen from non-sebaceous lymphadenoma. Adjuvant radiotherapy was given. No recurrence was detected during ten months of follow-up. This case is the first case of a malignancy developed from non-sebaceous lymphadenoma.

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.