Bülent Yılmaz

Pregnancy in women with primary biliary cirrhosis

BACKGROUND & AIMS Primary biliary cirrhosis (PBC) may present in all decades of life, also in childbearing age. Data on maternal and fetal outcome is limited. We aimed to investigate the impact of pregnancy and childbirth on the disease course and possible effects of PBC on fetal outcome. METHODS Retrospective study of local cases and a compact review of published reports between 1950 and 2014. RESULTS Our cases along with literature review provided 98 pregnancies in 72 PBC patients. PBC was diagnosed during pregnancy in 26 (36%) patients and 46 (64%) had the diagnosis before conception. Twenty-four (30%) of the pregnancies were associated with biochemical flares and 55 (70%) with clinical improvement or stabilization. De novo onset or worsening of pruritus was seen in 49% (45/92). No maternal deaths were reported. Post-partum disease activation was observed in 60% (53/88). One patient was referred for liver transplantation after delivery. A miscarriage rate of 24% and three stillbirths were reported. Most patients were treated with ursodeoxycholic acid (UDCA) during breastfeeding and 12 patients also received UDCA during the first trimester without any identified side effects. CONCLUSION Most women with PBC maintain a stable disease during pregnancy, but post-partum biochemical flares are common. Symptomatic pruritus may be challenging in pregnant PBC patients. UDCA appears to be safe during pregnancy and breastfeeding. A successful pregnancy outcome is a realistic expectation for women with PBC.

Endoscopic clips for the closure of acute iatrogenic perforations: Where do we stand?

Iatrogenic perforation of the gut during endoscopy remains an uncommon but critical complication with significant morbidity and probable mortality than usual surgical treatment. Some authors have adopted a non‐surgical closure method in chosen cases and, since 1993, endoclips have been used to close perforation in the stomach. The endoscopic practice of endoclips has been commonly used in the gut for hemostasis. Currently, the use of endoscopic techniques is increasing for the closure of endoscopic submucosal dissection or endoscopic mucosal resection. Endoscopic perforations that improved with endoscopic closure in the literature prior to 2008 have been previously described. In the present article, we present a descriptive review of cases with iatrogenic perforation in the gut treated with endoclips between 2008 and 2014.

Serum beta 2-microglobulin as a biomarker in inflammatory bowel disease.

AIM To investigate the diagnostic utility of beta 2 microglobulin (B2-M) levels and analyze this correlation with the activity of inflammatory bowel disease (IBD). METHODS Overall, 78 IBD patients and 30 healthy controls were enrolled in the study. We examined B2-M serum levels in 43 ulcerative colitis (UC) patients, 35 with Crohns disease (CD) and 30 control subjects, using an enzymatic method. Patients were divided into two groups according to two disease types: active and in remission. Subjects were also divided into two subgroups according to extent of the disease: left-side and pancolitis for UC and ileitis and ileocolitis for CD. All groups were compared for mean serum B2-M levels and also examined to see whether there was a correlation between serum B2-M levels and other inflammatory markers. RESULTS The mean serum B2-M levels in the control group, UC and CD were 1.71, 2.41 and 2.24 respectively. B2-M values ≥ 1.96 mg/L had a 62% sensitivity, 76% specificity, a 79% positive predictive value, and a 58% negative predictive value for UC patients. B2-M values ≥ 1.70 mg/L had 80% sensitivity, 53% specificity, 66% positive predictive value, and 69% negative predictive value for CD patients. Mean B2-M values were significantly higher in ulcerative colitis and Crohns disease patients than in healthy controls (UC 2.41 ± 0.87 vs 1.71 ± 0.44, P = 0.002; CD 2.24 ± 1.01 vs 1.71 ± 0.44, P = 0.033). Also, mean B2-M values were significantly higher in active disease when compared to patients in remission (UC 2.66 ± 0.92 vs 1.88 ± 0.41, P = 0.004; CD 2.50 ± 1.15 vs 1.73 ± 0.31, P = 0.033). The difference between groups (UC and CD) in terms of serum B2-M levels was statistically insignificant (2.41 ± 0.87 vs 2.24 ± 1.01, P > 0.05 respectively). CONCLUSION Serum B2-M levels may be used as an activity parameter in IBD.

Chronic hepatitis B associated with hepatic steatosis, insulin resistance, necroinflammation and fibrosis

BACKGROUND The effect of hepatitis B virus (HBV) infection on fatty liver disease is unclear. OBJECTIVES The aim of this study was to investigate the viral and host causes of fatty liver in chronic hepatitis B (CHB) patients. This study included 88 CHB patients of which 17 were not treated. Liver biopsy was performed in each patient. Group 1 included those with hepatic steatosis (n=28) and group 2 those without hepatic steatosis. The groups were compared in terms of age, body mass index (BMI), Homeostasis Model Assessment- Insulin Resistance (HOMA-IR), viral load, biochemical parameters and histological findings. Patients in group 1 were subdivided according to the degree of steatosis as follows: grade 1 (15 patients, 53.6%), grade 2 (6 patients, 21.4%), and grade 3 (7 patients, 25%). RESULTS In group 1 (n=28), mean age, BMI, cholesterol, and HOMA-IR were found to be significantly higher than in group 2 (n=60). There were no significant differences in the positivity of viral load, HbeAg, treatment, fibrosis and other laboratory parameters between the two groups. HOMA-IR was the only independent predictive factor of liver steatosis in patients with CHB in logistic regression analysis. CONCLUSION Hepatic steatosis in CHB patients was associated with host metabolic factors.

Infliximab Leading to Autoimmune Hepatitis: An Increasingly Recognized Side Effect

To the Editor, We read the article by Colina et al. [1] titled ‘‘InfliximabRelated Hepatitis: A Case Study and Literature Review’’ with great interest. Autoimmune hepatitis secondary to infliximab use is an increasingly recognized entity. We also observed this instance in an ankylosing spondylitis (AS) patient: A 39-year-old woman with a 4-year ankylosing spondylitis (AS) was investigated for elevation in transaminase levels. She had been treated with methotrexate, salazopyrin and hydroxychloroquine until 4 months ago, when infliximab was initiated. After fourth infliximab dosage (5 mg/kg) at fourteenth week of initial infusion, transaminases including alanine and aspartate aminotransferases (ALT and AST) were found to be gradually increasing and finally became 500–600 iu/dL. We investigated and excluded viral, metabolic and toxic causes for hepatitis. Serum anti-nuclear antibody (ANA) was 1/320 positive, and serum IgG was higher than normal (17.5 g/L). The liver biopsy showed an acute autoimmune hepatitis with a predominantly lymphoplasmatic infiltration (Fig. 1). Infliximab was ceased and immunosuppressive therapy was started (prednisolone 30 mg and azathioprine 50 mg). Serum AST and ALT became normal range at the second week of immunosuppressive drug therapy. Ozorio et al. reported a similar AS case and suggested that infliximab might be leading to autoimmune hepatitis by: Triggering development of autoantibodies, TNF-a blockade interfering with cytotoxic T lymphocyte suppression of selfreactive B cell production, interference with CD8 T cell death induction which results in accentuated lymphocyte presence [2]. However, another reported case, in which switching to another anti TNF-a drug, adalimumab, resulted in remission of autoimmune hepatitis, makes identifying the mechanism of this side effect ever more puzzling [3]. To summarize, we congratulate Colina et al. for their comprehensive report and would like to highlight the lack of clarity in the mechanism for infliximab-associated autoimmune hepatitis. We believe that extensive surveillance in this class of drugs, and further studies that will lead to the identification of causal mechanisms is warranted.

Hepatic Mass Caused by Fasciola Hepatica: A Tricky Differential Diagnosis

Fascioliasis is a zoonotic infestation caused by the trematode fasciola hepatica. It presents a wide spectrum of clinical pictures ranging from fever and eosinophilia to ambiguous gastrointestinal symptoms in the acute phase. However, it may often be overlooked, especially in the acute phase, because of uncertain symptoms. Fasciola hepatica can have an initial presentation similar to the presentation of malignancy. Here, we report a case of a hepatic mass caused by fasciola hepatica.

A sociological study of public library use in Ankara, Turkey

Reports results of a sociological and demographic study of public library users in Ankara, Turkey, in order to determine the level of public use and to isolate the factors affecting this usage. A thorough survey of the history and statistics of Turkish public libraries is followed by the results of the user survey, employing the society survey method, involving 1800 users (aged six years and over) in three socioeconomic stratas. The study took usage of the library as the dependent variable and demographic and socioeconomic properties (age, sex, marital status, educational level, occupation, income level and geographic past) as the independent variables. Other socioeconomic factors (social status and social role) were also considered.

Angiotensin-converting enzyme for noninvasive assessment of liver fibrosis in autoimmune hepatitis.

Background and aim There are no validated noninvasive markers of liver fibrosis in autoimmune hepatitis (AIH). An activated renin–angiotensin system (RAS) and its key element angiotensin-converting enzyme (ACE) have been implicated in the pathogenesis of hepatic fibrogenesis. We aimed to study the assumed role of activated RAS in the fibrogenic process and whether the serum concentration of ACE can predict different fibrosis stages in AIH. Patients and methods Serum samples of 73 consecutive patients who were diagnosed with AIH were analysed for ACE concentration. All patients underwent a liver biopsy. Results Serum ACE levels increased significantly for each fibrosis score. The median ACE was 45 U/l in patients with fibrosis score I, 54 U/l in patients with fibrosis score II, 68 U/l in patients with fibrosis score III and 87 U/l in patients with fibrosis score IV. For significant fibrosis (⩽F2), a 56 U/l cut-off value of ACE had 95.5% sensitivity and 74.5% specificity, and receiver-operating characteristic curves showed an area under the curve (AUC) of 0.89. For advanced fibrosis (⩽F3), a 64 U/l cut-off level of ACE had 85.2% sensitivity and 94.8% specificity, and AUC was 0.91. For cirrhosis, a 68 U/l cut-off level of ACE had 100% sensitivity and 84.4% specificity, and AUC was 0.95. Conclusion Our results suggest that activated RAS may sustain hepatic fibrogenesis in AIH. Measurement of serum ACE offers an easy, accurate and inexpensive noninvasive method that differentiates significant from nonsignificant liver fibrosis in AIH. Blockade of RAS may exert beneficial effects on fibrosis progression in AIH.

The Syk Inhibitor Fostamatinib Decreases the Severity of Colonic Mucosal Damage in a Rodent Model of Colitis

BACKGROUND AND AIMS Inflammatory bowel disease is a chronic inflammatory disease of the gastrointestinal system. In some cases, current medications used for inflammatory bowel disease may not be enough for remission, creating a need for more potent and reliable medications. There is no study showing the efficacy of fostamatinib, with proven effects on some inflammatory diseases, on ulcerative colitis. In our study we planned to research the efficacy of fostamatinib, a spleen tyrosine kinase inhibitor, on acetic acid-induced colitis. METHODS The study included 28 male Sprague-Dawley rats, randomly divided into control group, fostamatinib group, colitis group and fostamatinib + colitis group, each containing seven rats. Colitis induction was performed with 4% acetic acid. Colonic inflammation was assessed with disease activity index, macroscopic and histological damage scores, colonic myeloperoxidase, malondialdehyde and superoxide dismutase activity, and tumour necrosis factor alpha [TNFα], CD3, Syk, and phospho-Syk expression. RESULTS There was a significant difference between the colitis and control groups in terms of all parameters. The disease activity index, macroscopic and microscopic damage scores, immunohistochemical TNFα, CD3, Syk, and phospho-Syk expression, and tissue myeloperoxidase activity were found to be significantly lower in the colitis + fostamatinib group compared with the colitis group. There was no significant difference between the two groups in terms of myeloperoxidase and malondialdehyde activity. CONCLUSIONS Fostamatinib reduced the inflammatory damage in the experimental colitis. This effect may be due to suppression of TNFα, T-lymphocytes, and neutrophils in colonic mucosa via suppression of Syk. Fostamatinib may be an appropriate treatment alternative for ulcerative colitis. Further clinical studies are required to support this.

Air leak syndrome after endoscopic retrograde cholangiopancreatography: A rare and fatal complication

Endoscopic retrograde cholangiopancreatography (ERCP) is a state of the art diagnostic and therapeutic procedure for various pancreatic and biliary problems. In spite of the well-established safety of the procedure, there is still a risk of complications such as pancreatitis, cholangitis, bleeding and perforation. Air leak syndrome has rarely been reported in association with ERCP and the optimal management of this serious condition can be difficult to establish. Our group successfully managed a case of air leak syndrome following ERCP which was caused by a 3cm Stapfer type I perforation in the posterolateral aspect of the second part of the duodenum and was repaired surgically. Hereby, we describe the presentation and subsequent therapeutic approach.