Through-the-Scope Suturing for Late-Onset Fistula Closure in the Setting of Bariatric Surgery.

Anastomotic leaks related to bariatric surgeries are uncommon but are related to increased morbidity and mortality. With the recent advances in intraluminal endoscopic interventions, there are some alternative options to close the leak via over-the-scope-clips/suturing or through-the-scope-clips/suturing or covered stent placement. Herein, we aimed to discuss the efficiency and the role of the through-the-scope suturing technique (X-Tack-160-H, Apollo Endosurgery, Austin, Texas, United States) in two different cases who presented with anastomotic leaks following bariatric surgery.

LOXL-2 and TNC-C are markers of liver fibrogenesis in HCV/HIV-, HIV- and HCV-infected patients.

Background: Lysil oxidase like enzyme-2 (LOXL-2) and TNC-C play important roles in organ fibrosis. We assessed circulating LOXL-2 and TNC-C levels and their relationship to fibrosis severity in HIV- and/or HCV-infected individuals. Methods: Healthy controls (n = 22), HIV mono- (n = 15), HCV mono- (n = 52) and HCV/HIV-co-infected (n = 92) subjects were included. Results: LOXL-2 and TNC-C levels were significantly higher in HCV mono- and HCV/HIV-co-infected individuals with F0 compared to healthy controls. In addition, in HCV/HIV-co-infected individuals, LOXL-2 levels were higher in intermediate fibrosis compared to no/mild fibrosis. Conclusion: In HCV/HIV-co-infected study participants, both LOXL-2 and TNC-C were significantly higher in intermediate fibrosis compared to no/mild fibrosis, but did not further increase with advanced fibrosis. Furthermore, both markers were elevated among HCV/HIV-positive individuals with mild/no fibrosis.

Hepatitis C Virus Infection in Pregnancy: An Update.

Parenteral transmission is the major route of hepatitis C virus transmission in adults; however, vertical transmission is most common in children. There are several factors that have been shown to be associated with vertical transmission of hepatitis C virus, including hepatitis C virus RNA, human immunodeficiency virus coinfection, and peripheral blood mononuclear cell infection. As there is no effective vaccine to prevent hepatitis C virus infection, and there are no human data describing the safety of the new direct acting antiviral agents in pregnancy, the only preventive strategy for vertical transmission is to treat the hepatitis C virus infection before becoming pregnant. Direct acting antiviral agents are interferon-free, and many are also ribavirin-free. Based on animal studies, sofosbuvir plus ledipasvir may be the best safety profile during pregnancy for now; however, it is too early to recommend treating hepatitis C virus-infected pregnant women with these direct acting antiviral agents currently.

Relationship between resolution of non-alcoholic steatohepatitis and changes in lipoprotein sub-fractions: a post-hoc analysis of the PIVENS trial.

BACKGROUND: Dyslipidaemia is frequent in non-alcoholic steatohepatitis (NASH); however, it is unclear if improvement in liver histology is associated with favourable changes in cardiovascular disease (CVD) risk. AIMS: To evaluate the relationship of NASH resolution and lipoprotein subfraction levels, markers of endothelial dysfunction, and macrophage activation. METHODS: One hundred and seventeen individuals with NASH who participated in the Pioglitazone vs Vitamin E vs Placebo for the Treatment of Nondiabetic Patients with NASH (PIVENS) trial with paired liver biopsies and serum samples available at baseline and after 96 weeks of treatment were included. Participants in the PIVENS trials received vitamin E, pioglitazone, or placebo for 96 weeks. Lipoprotein subfraction levels, intracellular adhesion molecule 1 (ICAM-1), vascular cellular adhesion molecule 1 (VCAM-1), E-selectin, and sCD163 levels were assessed at baseline and week 96 and their relationship with NASH resolution was examined. RESULTS: Fifty-seven individuals had NASH resolution and 60 individuals did not have resolution of NASH. NASH resolution was associated with favourable changes in lipoprotein subfraction levels compared to those without NASH resolution. Individuals with resolution of NASH had a significantly increased mean peak LDL diameter (ratio of geometric means [96 weeks vs baseline] 1.007 vs 0.996, P = 0.004), and higher frequency of LDL phenotype A (58% vs 33%, P = 0.003) at week 96, after adjustment for relevant co-variates including treatment group. No differences in VCAM, ICAM, E-selectin, or sCD163 levels by NASH resolution were found. CONCLUSIONS: NASH resolution is associated with favourable changes in a subset of serum lipoprotein levels. More studies are warranted to understand if these favourable changes are associated with decreased risk of CVD.

Macrophage Activation Marker Soluble CD163 Is a Dynamic Marker of Liver Fibrogenesis in Human Immunodeficiency Virus/Hepatitis C Virus Coinfection.

Background: Coinfection with human immunodeficiency virus (HIV) accelerates hepatitis C virus (HCV)-related liver fibrosis. Macrophages are triggered during both viral infections and are critical in liver inflammation/fibrogenesis. Liver fibrosis strongly associates with serum soluble CD163 (sCD163, a macrophage activation marker); comprehensive evaluation in HIV/HCV coinfection is lacking. Methods: We retrospectively analyzed sCD163 (enzyme-linked immunosorbent assay) and hepatic CD163 (immunofluorescent CD163/CD68 costaining) in patients infected with HIV/HCV, HCV, or HIV, pre- and post-antiviral therapy. Results: sCD163 was significantly higher in HIV/HCV compared to either monoinfection, and decreased following successful antiviral therapy, although did not fully normalize. In HIV/HCV, sCD163 was associated with necroinflammation, Ishak fibrosis scores, and noninvasive fibrosis scores. We observed a novel trend whereby sCD163 levels progressively increase with increasing Ishak fibrosis score, peaking at stage 4, above which levels plateaued. Periportal CD163+ macrophage frequency was also higher with increasing fibrosis score. When stratified by fibrosis stage, sCD163 levels were higher in HIV/HCV than HCV but only in individuals with mild to moderate fibrosis. Conclusions: In HIV/HCV, increasing sCD163 levels accompanied periportal CD163+ macrophage enrichment in mild to moderate fibrosis, but not in established cirrhosis, suggesting that sCD163 is a dynamic biomarker of fibrogenesis rather than accumulated fibrosis. Our findings implicate HIV-related macrophage activation in accelerated fibrosis progression in HIV/HCV coinfection.

Effects of Genetic Polymorphisms of Cytochrome P450 Enzymes and MDR1 Transporter on Pantoprazole Metabolism and Helicobacter pylori Eradication.

Pantoprazole is a proton pump inhibitor that is commonly used in the treatment of peptic ulcer disease (PUD) and metabolized by cytochrome P450 (CYP) enzymes CYP2C19 and CYP3A4. Pantoprazole is a substrate for multi-drug resistance protein 1 (MDR1). Single nucleotide polymorphisms (SNPs) in CYP2C19, CYP3A4 and MDR1 affect enzyme activity or gene expression of proteins and may alter plasma pantoprazole concentrations and treatment success in PUD. In this study, we aimed to investigate the association between genetic polymorphisms in CYP2C19, CYP3A4 and MDR1 and pharmacokinetics of pantoprazole and therapeutic outcome in patients with either Helicobacter pylori-associated [H.P.(+)]-PUD or [H.P.(+)]-gastritis. The plasma pantoprazole concentrations were determined by using an HPLC method at the third hour after a 40-mg tablet of pantoprazole administration in 194 newly diagnosed patients with either [H.P.(+)]-PUD or [H.P.(+)]-gastritis. Genotyping was performed by using PCR-RFLP and DNA sequencing. Among patients appearing for follow-up examination (n = 105), the eradication rate for H. pylori was 82.8% (n = 87). The median pantoprazole plasma concentrations in poor metabolizers (PM), rapid metabolizers (RM) and ultrarapid metabolizers (URM) were 2.07, 1.69 and 1.28 µg/ml, respectively (p = 0.04). CYP3A4*1G and *22 polymorphisms did not affect plasma pantoprazole concentrations and H. pylori eradication rate. The MDR1 genetic polymorphisms did not affect plasma pantoprazole concentrations. MDR1 3435CC-2677GG-1236CC haplotype carriers had lower H. pylori eradication rate (60%) than the remaining subjects (84.9%) while the difference was not statistically significant (p = 0.07). In conclusion, while CYP2C19 genetic polymorphisms significantly affected plasma pantoprazole concentrations, polymorphisms of CYP2C19, CYP3A4 and MDR1 did not affect H. pylori eradication rates.

The Role of M30 in Predicting the Severity of Liver Fibrosis and Inflammation in Chronic Hepatitis B Patients.

BACKGROUND: Liver biopsy is an invasive procedure that is currently still necessary for predicting underlying hepatic injury related to chronic viral hepatitis B (CVHB). To date, none of the studied non-invasive methods have been able to replace liver biopsy. An apoptotic serum marker, M30, which has been reported to indicate ongoing liver fibrosis, has been popular in recent years. OBJECTIVES: We aimed to investigate the possible role of M30 in predicting CVHB-associated hepatic injury and its severity. METHODS: Forty-eight patients undergoing liver biopsy for evaluation of the severity of CVHB-related liver injury and 40 healthy controls were included in this cross-sectional study. M30 levels were determined for all CVHB patients and controls, and other laboratory parameters and demographic features were obtained from our hospital's database. RESULTS: The mean ages of patients and controls were 39.7 and 45.7 years, respectively, and 35% of the controls and 52% of the patients were male. In contrast to lower platelet counts, transaminase and M30 levels were both higher in the patient group than in the controls. Among the investigated parameters, only transaminase increased as the fibrosis stage changed from mild to moderate; however, none of the laboratory parameters, including M30, differed as the histological activity index (HAI) score increased. CONCLUSIONS: M30 levels were higher in CVHB patients compared to healthy controls. However, M30 levels were similar in the mild and moderate stages of fibrosis, so they did not indicate the severity of underlying fibrotic or inflammatory processes in CVHB patients.

Will a second biopsy sample affect treatment decisions in patients with chronic hepatitis B?

BACKGROUND AND AIM: Liver biopsy is the gold standard for assessment of fibrosis in patients with hepatitis B. However, it has some disadvantages, including inter-observer and intra-observer variability in biopsy interpretation and specimen variation. A standard biopsy specimen represents only about 0.0002 % of the whole liver. It has been shown that two biopsy samples collected during a procedure have significant influence on the diagnostic performance of interpretation in patients with hepatitis C or non-alcoholic steatohepatitis. Therefore, we aimed to assess the influence of collecting two liver biopsy samples during a single procedure for staging and grading chronic hepatitis B. PATIENTS AND METHODS: 27 patients were included in the study. The median age of the patients was 43.51 ± 11.69. Fifteen patients were female, 12 patients were male. In the biopsy procedure, two samples of liver lobes were obtained. Grade and stage scores were compared between the two samples. Fibrosis staging and grading were assessed according to the Ishak scoring system. RESULTS: Numbers of portal tract and biopsy size were equal in the two samples. There was a significant difference between the samples in terms of histological activity index (p value = 0.04). However, the difference was not enough to distinguish the mild and moderate stages. On the other hand, no significant difference in fibrosis staging between the two samples was found. CONCLUSIONS: With this relatively small size of patients, in this study, we showed that a proper liver biopsy size is sufficient to predict treatment decisions in chronic hepatitis B patients. However, further studies are needed to show the association of sampling variability in patients with hepatitis B.

Eosinophilic colitis under etanercept.

Eosinophilic colitis (EC) is a rare manifestation of eosinophilic gastrointestinal disorder. Even though the cut-off value of eosinophils per HPF for the diagnosis of EC is not clear, histopathological examination is still a cornerstone. Corticosteroids are the main drugs for EC treatment today. Here, we aim to report a woman with EC who showed clinical remission with budesonide and was maintained with adalimumab alone.

Maintenance therapy for Crohn's disease: should it be indefinite?

Crohn's disease (CD) is a chronic, persistent, and destructive disorder with different forms of clinical behavior and the disease appears to be progressive over the long term. Providing greater levels of mucosal healing and resolution of clinical symptoms may modify the course of CD. This will often necessitate long-term therapy with immunosuppressant or biological therapies. Both these classes of drugs have side-effects and the latter are also very expensive. Identification of a subgroup of patients with a low risk of relapse and validation of the relevant predictors in various cohort studies are the key points to be able to cease immunosuppressant and/or biological therapy in patients with CD in stable remission. The individual parameters 'mucosal healing', 'deep remission', 'fecal calprotectin', and 'C-reactive protein' or various combinations of these parameters seem to be promising tools for predicting successful withdrawal of maintenance therapy.

What is the main target: a clearer colon with a sennoside-based regime, or adequate bowel cleansing before colonoscopy with a PEG-EL-based regime?

BACKGROUND/AIM: Even though polyethylene glycol-electrolyte lavage (PEG-EL)-based regimes have become the gold standard in recent years, to finish drinking 4 L of PEG-EL solution can be difficult. The quality of sennoside-based bowel-cleansing regimes used in Turkey has been known for some time. Therefore, we aimed to investigate the efficacy of both bowel-cleansing regimes. MATERIALS AND METHODS: Patients over 18 years old undergoing elective colonoscopic procedures between January and March 2011 were included in the study. The patients were divided into 2 groups; in Group 1, 91 patients were given sennoside a + b calcium 500 mg/250 mL (X-M solution, Yenisehir Laboratuari, Ankara, Turkey), and in Group 2, 94 patients were given 4 L of PEG-EL (Golytely, Boston, MA, USA). RESULTS: The mean age of the patients and the male distribution were similar in the 2 groups. Both inadequate bowel cleansing and the best cleansed bowels were seen in Group 1. The number of inadequate colonoscopies declined when using a whole bowel-cleansing regime from 24.5% to 19.3% in Group 2, but it did not decline in Group 1. CONCLUSION: The best bowel cleansing can be achieved with sennoside-based regimes, whereas a greater proportion of adequate results via colonoscopy were reached with the PEG-EL-based regimes.

Utility of M30, an apoptotic serum marker, in liver diseases.

The aim of this paper is to evaluate the role of apoptosis in some common liver diseases, and the utility of M30, an apoptotic serum marker, in the diagnosis of the severity of underlying hepatic injury. As is widely known, apoptosis is programmed cell death, and its deregulation results in an uncontrolled inflammatory process leading to upregulation of liver fibrogenesis. Both extrinsic and intrinsic pathways are crucial in apoptosis, and caspase cleavage of cytokeratin proteins occurs in both. Therefore, the measurement of caspase- cleaved cytokeratin fragments could be a novel method to assess the intensity of apoptotic cell numbers in epithelial tissue damage. M30 levels were found to increase not only in acute liver disorders, but also in some chronic liver injuries. We tried to summarize the recent studies focused on the role of apoptotic processes in liver diseases, mainly those that investigated the use of M30 in determining the severity of, or in predicting, ongoing liver injury.

Economic Impact and Complications of Treated and Untreated Hepatitis C Virus Patients in Turkey.

BACKGROUND: According to the Turkish Ministry of Health's guidelines, standard double therapy, a combination of pegylated interferon-alpha and ribavirin, was the only treatment option for patients with hepatitis C virus (HCV) infection until the end of 2011. OBJECTIVE: The primary objective was to compare risk-adjusted clinical and economic outcomes between treated and untreated patients with HCV infection. METHODS: Patients with HCV infection were identified from the Turkish National Health Insurance Database (2009-2011) using International Classification of Diseases, 10th Revision, Clinical Modification codes. The first prescription date was designated as the index date. Mortality and hepatocellular carcinoma (HCC) rates and health care costs of treated and untreated patients were compared using propensity score matching. Baseline demographic and clinical factors were controlled in the models. Subgroup analysis was conducted for patient groups with and without a cirrhosis diagnosis. RESULTS: Out of 12,990 patients included in the study, 1,583 were treated for HCV infection. Out of 2,467 patients who had a cirrhosis diagnosis, 231 were treated, whereas out of 10,523 patients without cirrhosis, 1,352 patients were treated. Treated patients were younger, less likely to be diagnosed with comorbid conditions, and less likely to reside in Central or Eastern Anatolia. After adjusting for baseline demographic and clinical factors, mortality (2.27% vs. 5.31%; P < 0.001) and HCC rates (0.69% vs. 1.96%; P < 0.001) were found to be lower for treated patients. Differences were more significant among patients diagnosed with cirrhosis. Treated patients incurred higher risk-adjusted annual costs (€6172 vs. €1680; P < 0.001), mainly because of pharmaceutical costs (€4918 vs. €583; P < 0.001). CONCLUSIONS: HCV infection treatment, although costly, significantly reduces mortality and HCC rates in Turkey.

The relation between Helicobacter pylori and ulcerative colitis.

BACKGROUND/AIM: Besides some genetic explanations of the native course of ulcerative colitis (UC), the most attributable factors are pathogenic bacterial agents. There are some conflicting data about the relationship between Helicobacter pylori and the rate of UC in the literature. Therefore, we aimed to investigate the rate of H. pylori in UC patients. MATERIALS AND METHODS: Forty-nine individuals diagnosed with UC who had undergone upper gastrointestinal tract endoscopy for different reasons were included in the study. The presence of H. pylori in the stomach was checked by histopathological examination. RESULTS: H. pylori positivity was present in 57.1% of patients with UC. Interestingly, H. pylori positivity was lower (11.1%) in pancolitis patients compared to those presenting with more limited illnesses. There were no relationships among the severity of the underlying disease, medication already used, and H. pylori positivity rate. CONCLUSION: The extension of UC is important for the positivity rate of H. pylori. It could not be determined whether the low positivity of H. pylori in extended UC cases was due to immunosuppressive drugs or to the UC itself.