Evaluation of Predisposing Metabolic Risk Factors for Portopulmonary Hypertension in Patients with NASH Cirrhosis.

PURPOSE: Metabolic parameters are important for the development of portopulmonary hypertension (PoPH) during nonalcoholic steatohepatitis (NASH)-associated cirrhosis. This study evaluated patients with NASH-associated cirrhosis to determine metabolic risk factors for portopulmonary hypertension. PATIENTS AND METHODS: Data on 171 patients (120 men and 51 women) with NASH-associated cirrhosis who were seen in Florence Nightingale Hospital's gastroenterology Clinic from 2009 to 2018 was obtained from the Hospital database. A pulmonary artery systolic pressure >35 mmHg was defined as PH (pulmonary hypertension) according to standard transthoracic echocardiography. Portal hypertension was diagnosed from clinical symptoms and dilated portal veins shown by abdominal ultrasound or computed tomography (CT). Pulmonary patients with portal hypertension were diagnosed with portopulmonary hypertension (PoPH). RESULTS: A total of 171 patients with NASH-associated cirrhosis were included in this study. Of these, 43 patients had PoPH. These patients had increased TSH (p=0.004), bilirubin (p=0.023) and triglyceride (p=0.048) levels, higher MELD scores (p=0.018) and decreased hemoglobin (p=0.05). MELD score and hemoglobin, total bilirubin, TSH, and triglyceride levels were all included in a multivariate logistic regression model and TSH levels were independently associated with increased risk of PoPH. CONCLUSION: Increased TSH is an independent risk factor for PoPH.

Clinical Value of CXCL5 for Determining of Colorectal Cancer

Background: Several studies indicate that chemokines play important roles in colorectal mucosal immunity. The chemokine CXCL5 which is expressed by epithelial cells within colorectal mucosa is a promoter of cell proliferation, migration and invasion, is a novel serum prognostic marker in patients with colorectal cancer. The purpose of this study was to investigate whether serum and tissue CXCL5 levels is altered in colorectal carcinomas (CRC) compared to colonic adenoma and normal mucosa.It also aimed to compare colon adenoma and colorectal cancer for blood CXCL5 and CEA levels, their sensitivity, and specificity. Methods: CXCL5 expression was assessed with immunohistochemistry staining in biopsy samples taken during colonoscopy in 22 colonic adenomas, 23 colorectal carcinomas and 23 normal colonic tissue samples. Also all patients' serum CXCL5 and CEA levels were measured. This stduy was prospective observational study. Results: The number of cases who were stained positive with immunohistochemistry was found to be higher in the group with CRC. When compared with the other groups, both levels of serum CXCL5 and CEA were significantly high in the group CRC. Sensitivity and specificity of serum CXCL5 were found to be low as a result of the ROC analysis. Conclusion: Although the level of CXCL5 is high in CRC, its level in serum is not significant enough to support the early diagnosis of the disease.

The association of variations in TLR genes and spontaneous immune control of hepatitis B virus.

BACKGROUND: Toll-like receptors (TLRs) are suspected to play a critical role in liver diseases and the progression of chronic hepatitis B (CHB) infection. In this study, we investigated the possible association between TLRs and hepatitis B virus (HBV) infection chronicity in Turkish population. METHODS: TLR4 (+896 A→G) (rs4986790), TLR5 (+1846 T→C) (rs5744174) and TLR9 (-1237T→C) (rs5743836) polymorphisms were screened in 131 CHB patient and 168 individuals by polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) technique. RESULTS: Of the screened polymorphisms, TT genotype of the missense variant TLR5 (rs5744174) (NM_003268.5:c.1846T>C (p.Phe616Leu) is significantly more frequent in the control group than CHB patients (P<0.001), presence of TT genotype of the upstream variant TLR9 (rs5743836) (NM_017442.3:c.-1237T>C) is more frequent in CHB group (P=0.043). However, no significant association was found for the missense variant TLR4 (rs4986790) NM_138554.4:c.896A>G (p.Asp299Gly) polymorphism and CHB in Turkish population. CONCLUSIONS: From all three analyzed SNPs association of TLR5 (rs5744174) with CHB is the most significant. Since TLR5 is associated with interferon-γ production, a high frequency of TT at rs5744174 in controls subjects suggests that it represents a protective genotype against CHB plausibly associated with an increased interferon-γ production.

An association study of functional polymorphic genes IRF-1, IFNGR-1, and IFN-γ with disease progression, aspartate aminotransferase, alanine aminotransferase, and viral load in chronic hepatitis B and C.

BACKGROUND: Investigational approaches based on genome-wide association studies have proven useful in identifying genetic predictors for many diseases, including susceptibility to chronic hepatitis B and C. In these studies, the majority of genetic variants that have shown a positive association have been identified in genes involved in the immune response. In this study IFN-γ, IFNGR-1, and IRF-1 genes were analyzed for their role in susceptibility to the development of chronic hepatitis B and chronic hepatitis C in a Turkish population. METHODS: Polymorphic genes IRF-1 (-410, -388), IFNGR-1 (-56, -611), and IFN-γ (+874) were analyzed in a total of 400 individuals: 100 chronic hepatitis B patients, 100 hepatitis B carriers, 100 chronic hepatitis C patients, and 100 healthy controls. A single base primer extension assay was used. Correlations between genes and gender, viral load, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were also investigated. RESULTS: The IRF-1 gene at positions -388 and -410 were observed to be candidate gene markers for susceptibility to the development of chronic hepatitis B and C (p<0.05). IFN-γ +874 and IFNGR-1 (-56 and -611) correlated with chronic hepatitis B but not chronic hepatitis C. Correlation of functional genotype with viral load and AST and ALT levels revealed an association of IFN-γ +874 and IFNGR-1 -611 with chronic hepatitis C and IFN-γ +874 with viral load and chronic hepatitis B (p<0.05). CONCLUSIONS: Findings suggest that IFN-γ (+874), IRF-1 (-410, -388), and IFNGR-1 (-56, -611) are candidate gene markers for determining patient susceptibility to the development of chronic hepatitis B and C.

Conventional DMARD therapy (methotrexate-sulphasalazine) may decrease the requirement of biologics in routine practice of ankylosing spondylitis patients: a real-life experience.

AIM: The effect of disease-modifying antirheumatic drugs (DMARDs) in ankylosing spondylitis (AS) is still controversial. We aimed to evaluate the efficacy of sulphasalazine (SSZ) mono- or combination therapy with methotrexate (MTX) in AS patients naive to anti-tumor necrosis factor alpha (TNFα) agents. METHODS: Patients with AS (n = 87, male : female, 46 : 41) treated with SSZ (n = 61) or SSZ + MTX (n = 26) combination and a documented 6-month follow-up were evaluated retrospectively. Disease activity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), C-reactive protein and erythrocyte sedimentation rate. Requirement for anti-TNFα therapy was assessed after 6 months. RESULTS: Mean (SD) age was 43.0 (11.0) versus 40.2 (11.1) and disease duration was 11.0 (8.6) versus 8.2 (5.2) years, in the SSZ and SSZ + MTX groups, respectively. Initially, 59% (34/61) of the patients in SSZ monotherapy and 68% (17/26) in the combination arm had BASDAI > 4. At the end of the study, BASDAI scores decreased similarly in both groups (mono: 1.4 [-7-6] versus combination: 0.7 [-3-6] P = 0.2). BASDAI was > 4 in 32.8% (20/61) of patients in the SSZ monotherapy and in 44% (11/26) in the combination arm. Only 4 (6.6%) patients in the SSZ group and 2 (7.7%) in the ombination arm were switched to anti-TNFα therapies. DISCUSSION: A significant subset of our AS patients responded to SSZ mono or SSZ + MTX combination therapies at 6 months follow-up. Using BASDAI, the requirement for biological therapies decreased by 21-24%. In AS patients, including those with axial involvement only, DMARD therapy may be a reasonable first alternative to anti-TNFα therapy and may delay the switch to biologic agents.

The frequency of microscopic and focal active colitis in patients with irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic functional bowel disorder. The frequency of microscopic colitis and focal active colitis in the colonic mucosa has been investigated in IBS patients. METHODS: Between June 2007 and September 2010, 378 patients (between 16 and 84 years) were recruited prospectively. Of these 378 patients, 226 patients were diagnosed with IBS using the Rome III criteria. 152 control patients were also enrolled who were undergoing colonoscopy for colorectal cancer screening or investigation of anemia. Histopathological abnormalities identified during colonoscopy were compared between the IBS and control groups. RESULTS: The average age of the IBS group was 46.13 ± 14.16 years and and the average age of the control group was 57.01 ± 13.07 years. The prevalence of microscopic colitis (MC) in the diarrhea predominant and the mixed subgroup of IBS patients was 4.32% (7/162) whereas in all IBS patients, the prevalence was 3.09% (7/226). MC was not found in the 152 control cases, (p = 0.045). Lymphocytic colitis was seen in 7 IBS patients, with 1 case in the mixed group and 6 cases in the diarrhea group and there was a significant difference in the frequency of lymphocytic colitis between the IBS subgroups (p < 0.01). Focal active colitis was found in 6.6% (15/226) of the IBS patients and in none of the controls (p < 0.01), and there was no differences between IBS subtypes. CONCLUSION: Microscopic colitis was more often found in the diarrhea predominant/mixed subgroups of IBS patients and in patients who were older women. In patients who are older woman with non-constipated IBS, it may be reasonable to perform a biopsy to screen for microscopic colitis. Focal active colitis was significantly increased in patients with IBS compared to controls.

Situs inversus totalis and secondary biliary cirrhosis: a case report.

Situs inversus totalis is is a congenital anomaly associated with various visceral abnormalities, but there is no data about the relationship between secondary biliary cirrhosis and that condition. We here present a case of a 58 year-old female with situs inversus totalis who was admitted to our clinic with extrahepatic cholestasis. After excluding all potential causes of biliary cirrhosis, secondary biliary cirrhosis was diagnosed based on the patient's history, imaging techniques, clinical and laboratory findings, besides histolopathological findings. After treatment with tauroursodeoxycholic acid, all biochemical parameters, including total/direct bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gama glutamyl transferase, returned to normal ranges at the second month of the treatment. We think that this is the first case in literature that may indicate the development of secondary biliary cirrhosis in a patient with situs inversus totalis. In conclusion, situs inversus should be considered as a rare cause of biliary cirrhosis in patients with situs inversus totalis which is presented with extrahepatic cholestasis.