Are There Differences in the Management of Acute Pancreatitis Cases Due to Severe Hypertriglyceridemia in Pregnant Women?

BACKGROUND The aim of this study was to determine the prognosis of severe disease and treatment approaches of both normal and pregnant, especially in patients with severe pancreatitis due to hypertriglyceridemia. MATERIAL AND METHODS We included 30 patients (20 females and 10 males) in this study whose follow-ups and treatments were performed after a diagnosis of hypertriglyceridemia-induced acute pancreatitis between January 2011 and May 2017. Patient personal information, such as age, sex, pre-treatment and post-treatment triglyceride levels, receipt of anti-hyperlipidemic treatments or plasmapheresis, and family history, were collected from hospital records and patient files. Patients with severe pancreatitis history, score, and prognosis were included to increase the value of our study. Mild and moderate cases were excluded. RESULTS The mean age of the patients was 35±6 years. Twenty-four patients (80%) received an anti-hyperlipidemic treatment before their pancreatitis attacks. Plasmapheresis was performed on 8 patients before their pancreatitis attacks. Eighteen patients (60%) had a family history suggesting familial hypertriglyceridemia. Twelve patients (40%) were pregnant. CONCLUSIONS The treatment of hypertriglyceridemia-induced acute pancreatitis was mostly confined to supportive, palliative treatments. However, plasmapheresis is a possible treatment option and should be used in the early stages of this disease. The response to medical treatment and support treatment was better in pregnant patients than in the other patient group, and pregnant patients did not require plasmapheresis.

Prophylactic Administration of Silybin Ameliorates L-Arginine-Induced Acute Pancreatitis.

BACKGROUND Oxidative stress have been shown to play a role in the pathogenesis of acute pancreatitis. The aim of this study was to investigate the potential effect of silybin, a potent antioxidant, on L-arginine-induced acute pancreatitis in an experimental rat model. MATERIAL AND METHODS Forty female Wistar Albino rats were divided into 5 groups as follows: Group 1 (C): control group (n=8), Group 2 (SL): silybin group (n=8), Group 3 (LA): acute pancreatitis group (n=8), Group 4 (SLLA): prophylaxis group (n=8), and Group 5 (LASL): treatment group (n=8). Group C (control) received 2 intraperitoneal (i.p.) injections of physiological saline at an interval of 1 h. Group SL received only a single i.p. injection of silybin. The SLLA group received a single i.p. injection of silybin before the induction of acute pancreatitis with L-arginine, whereas the LASL group received the same injection after the induction of acute pancreatitis with L-arginine. Pancreatic tissues were histopathologically examined. Levels of amylase and oxidative stress markers (total oxidant status and total anti-oxidant status) were determined in the blood samples. Oxidative stress index was calculated. RESULTS In comparison to the LA, the prophylaxis and treatment groups showed significant improvements in serum oxidative stress parameters (p=0.001 and p=0.005, respectively). Histopathological analysis showed that the treatment group had significant improvements in edema scores only (p=0.006), whereas the prophylaxis group had the same improvements in inflammation and necrosis scores as well as in total scores (p=0.004, 0.006, and 0.004, respectively). CONCLUSIONS When used for prophylactic rather than therapeutic purposes, silybin ameliorates serum oxidative stress parameters and improves histopathological results via its antioxidant and anti-inflammatory properties.

HLA DQB1 alleles are related with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD is a complex disease and inflammation is a crucial component in the disease pathogenesis. Recent genome wide association studies in hepatology area highlighted significant relations with human leukocyte antigen (HLA) DQ region and certain liver diseases. The previous animal models also emphasized the involvement of adaptive immune system in the liver damage pathways. To investigate possible polymorphisms in the HLA region that can contribute to the immune response affecting the NAFLD, we enrolled 93 consecutive biopsy proven NAFLD patients and a control group consisted of 101 healthy people and genotyped HLA DQB1 alleles at high resolution by sequence specific primers-polymerase chain reaction. The mean NAFLD activity score (NAS) was 5.2 ± 1.2, fibrosis score was 0.9 ± 0.9, ALT was 77 ± 47.4 U/L, AST was 49.4 ± 26.3 U/L. Among 13 HLA DQB1 alleles analyzed in this study, DQB1*06:04 was observed significantly at a more frequent rate among the NAFLD patients compared to that of healthy controls (12.9 vs. 2 % χ(2) = 8.6, P = 0.003, P c = 0.039, OR: 7.3 95 % CI 1.6-33.7). In addition, the frequency of DQB1*03:02 was significantly higher in the healthy control group than the NAFLD patients (24.8 vs. 7.5 %, χ(2) = 10.4, P = 0.001, P c = 0.013, OR: 0.2, 95 % CI 0.1-0.6). NAFLD patients were grouped according to their fibrosis score and NAS. The distribution of DQB1 alleles over stratified NAFLD patients did not reveal any statistically significant relation. Taken together, immune repertoire of individuals may have an effect on NAFLD pathogenesis and therefore, in NAFLD, adaptive immunity pathways should be investigated.

Efficacy of two levofloxacin-containing second-line therapies for Helicobacter pylori: a pilot study.

BACKGROUND: An ideal second-line therapeutic regimen for the treatment of patients who do not respond to standard triple therapy is currently being investigated. In this study, we aimed to investigate the efficacy of two levofloxacin-containing second-line therapies for Helicobacter pylori (H. pylori). MATERIALS AND METHODS: One hundred and forty eight consecutive H. pylori -positive patients who did not respond to the standard triple therapy (77 female, 71 male) were enrolled in the study. The patients were randomized consecutively to two-second-line therapy groups; 73 to the levofloxacin-containing sequential (LCS) and 75 to the levofloxacin-containing quadruple (LCQ) therapy group. The LCS therapy group received pantoprazole 40 mg and amoxicillin 1,000 mg twice daily for 5 days followed by pantoprazole 40 mg twice daily and metronidazole 500 mg three times daily and levofloxacin 500 mg one time daily for 7 days. The LCQ therapy group received pantoprazole 40 mg twice daily, tetracycline 500 mg four times daily, bismuth subcitrate 300 mg four times daily and levofloxacin 500 mg one time daily for 10 days. H. pylori eradication was confirmed by stool antigen testing at least 6 weeks after cessation of therapy. Side-effects and compliance were assessed by a questionnaire. RESULTS: Intention-to-treat cure rates were: 82.2% (95%CI; 73-91) and 90.6% (95%CI; 79-95) in the LCS and LCQ therapy, respectively. Per protocol cure rates were: 85.7% (95%CI; 75-92) and 93.1% (95%CI; 85-98) in the LCS and LCQ therapy, respectively. No statistically significant difference was found between two groups (p = .1). No differences in compliance or adverse effects were demonstrated between two groups. CONCLUSIONS: This prospective trial demonstrates that both levofloxacin-containing sequential therapy and levofloxacin-containing quadruple therapy regimens have higher H. pylori eradication rates and are well tolerated. The levofloxacin-containing quadruple therapy is likely the best treatment option for a second-line therapy, at least in the Turkish population.

Relationship between neutrophil gelatinase-associated lipocalin (NGAL) levels and inflammatory bowel disease type and activity.

BACKGROUND AND AIM: Neutrophil gelatinase associated lipocalin (NGAL) is a recently identified molecule, which is bacteriostatic, has tissue destructive effects and is pro-inflammatory with chemoattractant molecule binding properties. Our aim was to investigate the relationship between serum NGAL levels and the type and level of disease activity of IBD. METHODS: A total of 92 patients [43 with Crohn's disease (CD) and 49 with ulcerative colitis (UC)], and 30 age- and sex-matched healthy controls (HC) were included in this study. Serum NGAL levels were measured using ELISA. RESULTS: Serum NGAL levels were elevated in the IBD group [median 171, range (57-312) ng/mL] compared to the HC group [107 (45-234) ng/mL] (p<0.0001) and were elevated in UC patients [188 (74-312) ng/mL] compared to CD patients [168 (57-279) ng/mL] (p=0.006). When NGAL levels were further analysed based on localization of the CD and UC, the levels in ulcerative pancolitis [233 (144-312) ng/mL] were significantly higher (p=0.004) than the left-sided colitis [156 (103-309) ng/mL]. Similarly, NGAL levels were significantly higher in colonic CD [207 (125-249) ng/mL] than ileal CD [114 (78-210) ng/mL], and also in ileocolonic CD [198 (57-279) ng/mL] than ileal CD (p=0.033). When CD and UC groups were further categorized as active and inactive according to clinical and endoscopic activity indices, serum NGAL concentrations did not differ between inquiescent versus active stages. When a cut-off level of 129 ng/mL was used to distinguish IBD from HC, a sensitivity of 76.1% and a specificity of 60.9% was reached. CONCLUSIONS: The serum NGAL levels in the IBD group was significantly higher than the HC group. Serum NGAL levels were higher in more extensive colonic involvement.

Re-evaluation of cases with gastroenteropancreatic neuroendocrine tumors between 2004 and 2012 according to the 2010 criteria.

BACKGROUND/AIMS: We re-evaluated the clinical, histopathological and immunohistochemical features of neuroendocrine tumors (NETs) diagnosed in our pathology laboratory between 2004 and 2012 and re-classified them according to the WHO-2000 and WHO-2010 criteria. METHODOLOGY: The study included NET samples of 106 patients having gastroenteropancreatic and hepatobiliary tumors. The histopathological findings were re-assessed. The cases were re-appraised based on the WHO-2000 and WHO-2010 criteria. The association between survival and Ki-67 index was analysed. RESULTS: The most frequent localization was the stomach. The average tumor size was 3.0±4.1 cm. Differentiation was poor in 17 cases (16.0%). Lymphovascular invasion was detected in 16.1% (n = 17) and necrosis was identified in 15.1% (n = 16). The average number of Ki-67 was 9.1±19.9. Ki-67 measurements were significantly higher in patients who died compared to those who survived (p <0.01). In ROC analysis, the cut-off point for Ki-67 was 5. CONCLUSIONS: Our study is a single-center study comprising patients from Turkey for a period of 8 years. We found that the most frequent localization is the stomach. This ratio is associated with common use of endoscopy in our center. The specimens were re-evaluated according to the WHO-2000 and WHO-2010 classification systems the data and terminology have been updated.

Continued improvement in disease manifestations of acid sphingomyelinase deficiency for adults with up to 2 years of olipudase alfa treatment: open-label extension of the ASCEND trial.

BACKGROUND: Olipudase alfa is a recombinant human acid sphingomyelinase enzyme replacement therapy for non-central-nervous-system manifestations of acid sphingomyelinase deficiency (ASMD). The ASCEND randomized placebo-controlled trial in adults with ASMD demonstrated reductions in sphingomyelin storage, organomegaly, interstitial lung disease and impaired diffusion capacity of the lung (DLCO), during the first year of olipudase alfa treatment. In an ongoing open-label extension of the ASCEND trial, individuals in the placebo group crossed over to olipudase alfa, and those in the olipudase alfa group continued treatment. RESULTS: Thirty-five of 36 participants continued in the extension trial, and 33 completed year 2. Change-from-baseline results are presented as least-square mean percent change ± SEM. Improvements in the cross-over group after 1 year of treatment paralleled those of the olipudase alfa group from the primary analysis, while clinical improvement continued for those receiving olipudase alfa for 2 years. In the cross-over group, percent-predicted DLCO increased by 28.0 ± 6.2%, spleen volume decreased by 36.0 ± 3.0% and liver volume decreased by 30.7 ± 2.5%. For those with 2 years of olipudase alfa treatment, the percent predicted DLCO increased by 28.5 ± 6.2%, spleen volume decreased by 47.0 ± 2.7%, and liver volume decreased by 33.4 ± 2.2%. Lipid profiles and elevated liver transaminase levels improved or normalized by 1 year and remained stable through 2 years of treatment. Overall, 99% of treatment-emergent adverse events were mild or moderate, with one treatment-related serious adverse event (extrasystoles; previously documented cardiomyopathy). No individual discontinued due to an adverse event. CONCLUSION: Treatment with olipudase alfa is well tolerated and reduces manifestations of chronic ASMD with sustained efficacy. Trial registration NCT02004691 registered 9 December 2013, https://clinicaltrials.gov/ct2/show/NCT02004691.

Characterization of nonalcoholic fatty liver disease unrelated to the metabolic syndrome.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MS). However, not all patients with the MS will develop NAFLD and not all patients with NAFLD have the MS. We sought to investigate the differences between patients with biopsy-proven NAFLD with and without the MS. METHODS: A total of 357 consecutive patients with biopsy-proven NAFLD were analysed. Of them, 216 patients had nonalcoholic steatohepatitis (NASH) and 96 a fibrosis score ≥ 2. The MS was defined as ≥ 3 of the ATP III criteria. RESULTS: A total of 214 patients with NAFLD met the criteria for the MS, while the remaining 143 did not. In NAFLD patients with the MS, homeostasis model of insulin resistance (P = 0·03; OR, 1·06; 95% CI, 1·023-1·25 per unit increase) and diabetes (P = 0·01; OR, 1·2; 95% CI, 1·1-2·4) were independent predictors of NASH. In NAFLD patients without the MS, the only variable independently associated with NASH was haemoglobin (P = 0·007; OR, 1·9; 95% CI, 1·4-3·6 per 50 g/L increase). Alanine aminotransferase (P = 0·03; OR, 1·04; 95% CI, 1·006-1·11 per 10 U/L increase) was an independent predictor of fibrosis ≥ 2 in NAFLD patients with the MS, while haemoglobin (P = 0·02; OR, 1·4; 95% CI, 1·2-1·9 per 50 g/L increase) was the only variable significantly associated with fibrosis ≥ 2 in NAFLD patients without the MS. CONCLUSIONS: Increased haemoglobin in NAFLD subjects without MS should be considered in the selection of cases for histological assessment.

Hepatic expression and serum levels of syndecan 1 (CD138) in patients with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Syndecan-1 (CD138) is a transmembrane heparan sulfate proteoglycan expressed in the liver which may exert metabolic effects by mediating the hepatic clearance of triglyceride-rich lipoproteins. In the present study, we assayed serum levels and the hepatic expression of syndecan-1 and examined their association with clinical, biochemical, and histologic phenotypes in patients with histology-proven nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 59 patients with biopsy-proven NAFLD and 54 matched controls were enrolled. The analysis of syndecan-1 expression in liver biopsies was performed by immunohistochemistry on formalin-fixed, paraffin-embedded samples. Serum syndecan-1 levels were measured by ELISA. RESULTS: NAFLD patients had significantly higher serum syndecan-1 levels [median: 61 ng/mL (interquartile range: 36-97 ng/mL)] than controls [median: 37 ng/mL (interquartile range: 25-59 ng/mL, Mann-Whitney U test, p < 0.001]. However, we did not find any significant association between serum syndecan-1 and the mean syndecan-1 immunohistochemical score (n = 59, r = 0.064, p = 0.63). Interestingly, the syndecan-1 immunohistochemical score was an independent predictor of HDL cholesterol in NAFLD patients (ß = 0.27; t = 1.99, p < 0.05). CONCLUSIONS: Our data suggest that serum syndecan-1 levels are raised in patients with NAFLD. Moreover, the syndecan-1 immunohistochemical score in the liver is independently associated with HDL cholesterol in this group of patients. These pilot results support further investigation of this molecule in metabolic liver diseases.

Patients with inflammatory bowel disease have a lower response rate to HBV vaccination compared to controls.

BACKGROUND: Hepatitis B (HBV) is a vaccine-preventable infection that may cause severe infections, particularly in patients who are being treated with immunosuppressive therapy [(i.e., inflammatory bowel disease (IBD)]. Limited data are available about IBD patients' response rate to HBV vaccine. AIM: To assess the efficacy of HBV vaccine in IBD patients and healthy controls. METHODS: Serological markers of HBV were assessed in IBD patients, and HBV vaccine was administered to seronegative patients. The subsequent determination of anti-HBs antibody was recorded. An adequate immune response (AIR) and an effective immune response (EIR) to HBV were defined as more than 10 and 100 mIU/ml, respectively. The single dose vaccine was administered at 0, 1 and 6 months. RESULTS: A total of 102 patients with IBD (39 Crohn's disease, 63 ulcerative colitis; 54 female, 48 male) and 52 (25 female, 27 male) healthy controls were included. Mean age for patients and controls were 38 ± 12 and 31 ± 8, respectively (P < 0.001). Both AIR and EIR were significantly lower in patients than in controls (P < 0.001), but they were similar between patients with CD and UC (P = 0.302). Forty-four (43%) patients were on immunosuppressive therapy before vaccination. After vaccination, 76 and 53% of the patients had AIRs and EIRs, respectively, whereas 100 and 87% of the controls had AIRs and EIRs, respectively (P < 0.001 and P < 0.001, respectively). CONCLUSIONS: The response rate of IBD patients receiving HBV vaccinations were significantly lower compared to controls. The response rate of those receiving immunosuppressive therapy and with active disease was much too low. Vaccination should be given during remission and at immunosuppression-free times.

Comparison of the efficacy of entecavir and tenofovir in chronic hepatitis B.

BACKGROUND/AIMS: This study aimed to compare the efficacy of entecavir and tenofovir in nucleos(t)ide-naive chronic hepatitis B patients after 48 weeks of therapy. METHODOLOGY: We retrospectively reviewed our data of chronic hepatitis B patients. Nucleos(t)ide-naive patients who had received entecavir or tenofovir for at least 48 weeks were included. We compared entecavir and tenofovir after 48 weeks of therapy with respect to virological, biochemical, serological and histological responses. RESULTS: Of the 44 patients, 24 received entecavir and 20 received tenofovir. Pretreatment characteristics of the patients were similar. After 48 weeks, serum HBV DNA levels decreased by 6.93±1.54log copy/ mL in the entecavir group and 6.89±1.22log copy/mL in the tenofovir group (p=0.65). A similar proportion of patients in entecavir and tenofovir groups achieved undetectable serum HBV DNA (87.5% vs. 95%, p=0.39) and serum ALT normalization (79.2% vs. 85%, p=0.62). The mean histological activity index score improved by 3.83±3.51 points in the entecavir group and 2.20±1.91 points in the tenofovir group (p=0.07), and the mean fibrosis scores improved by 0.38±1.61 points in the entecavir group and 0.70±1.17 points in the tenofovir group after 48 weeks (p=0.44). CONCLUSIONS: Entecavir and tenofovir are similarly effective in nucleos(t)ide-naive chronic hepatitis B patients with high viral load and/or high fibrosis scores after 48 weeks of therapy.

In a Real-Life Setting, Direct-Acting Antivirals to People Who Inject Drugs with Chronic Hepatitis C in Turkey.

BACKGROUND: People who inject drugs (PWID) should be treated in order to eliminate hepatitis C virus in the world. The aim of this study was to compare direct-acting antivirals treatment of hepatitis C virus for PWID and non-PWID in a real-life setting. METHODS: We performed a prospective, non-randomized, observational multicenter cohort study in 37 centers. All patients treated with direct-acting antivirals between April 1, 2017, and February 28, 2019, were included. In total, 2713 patients were included in the study among which 250 were PWID and 2463 were non-PWID. Besides patient characteristics, treatment response, follow-up, and side effects of treatment were also analyzed. RESULTS: Genotype 1a and 3 were more prevalent in PWID-infected patients (20.4% vs 9.9% and 46.8% vs 5.3%). The number of naïve patients was higher in PWID (90.7% vs 60.0%), while the number of patients with cirrhosis was higher in non-PWID (14.1% vs 3.7%). The loss of follow-up was higher in PWID (29.6% vs 13.6%). There was no difference in the sustained virologic response at 12 weeks after treatment (98.3% vs 98.4%), but the end of treatment response was lower in PWID (96.2% vs 99.0%). In addition, the rate of treatment completion was lower in PWID (74% vs 94.4%). CONCLUSION: Direct-acting antivirals were safe and effective in PWID. Primary measures should be taken to prevent the loss of follow-up and poor adherence in PWID patients in order to achieve World Health Organization's objective of eliminating viral hepatitis.

Efficacy and Safety of Direct-Acting Antivirals in Elderly Patients with Chronic Hepatitis C: A Nationwide Real-Life, Observational, Multicenter Study from Turkey.

BACKGROUND: The number and proportion of elderly patients living with chronic hepatitis C are expected to increase in the coming years. We aimed to compare the real-world efficacy and safety of direct-acting antiviral treatment in elderly and younger Turkish adults infected with chronic hepatitis C. METHODS: In this multicenter prospective study, 2629 eligible chronic hepatitis C patients treated with direct-acting antivirals between April 2017 and December 2019 from 37 Turkish referral centers were divided into 2 age groups: elderly (≥65 years) and younger adults (<65 years) and their safety was compared between 2 groups in evaluable population. Then, by matching the 2 age groups for demographics and pretreatment risk factors for a non-sustained virological response, a total of 1516 patients (758 in each group) and 1244 patients (622 in each group) from the modified evaluable population and per-protocol population were included in the efficacy analysis and the efficacy was compared between age groups. RESULTS: The sustained virological response in the chronic hepatitis C patients was not affected by the age and the presence of cirrhosis both in the modified evaluable population and per-protocol population (P = .879, P = .508 for modified evaluable population and P = .058, P = .788 for per-protocol population, respectively). The results of the per-protocol analysis revealed that male gender, patients who had a prior history of hepatocellular carcinoma, patients infected with non-genotype 1 hepatitis C virus, and patients treated with sofosbuvir+ribavirin had a significantly lower sustained virological response 12 rates (P < .001, P = .047, P = .013, and P = .025, respectively). CONCLUSION: Direct-acting antivirals can be safely used to treat Turkish elderly chronic hepatitis C patients with similar favorable efficacy and safety as that in younger adults.

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.

Can an immunohistochemistry method differentiate intestinal tuberculosis from Crohn's disease in biopsy specimens?

BACKGROUND: It is sometimes difficult to diagnose whether a patient has intestinal tuberculosis or Crohn's disease because both have similar clinical, pathologic, and endoscopic features. However, their therapies are completely different and a mistake in diagnosis can result with deterioration. Many laboratory methods for the diagnosis of tuberculosis require considerable time to receive a diagnostic result. We wanted to evaluate whether an immunohistochemical tuberculosis staining method can be helpful for faster differentiation of biopsy materials. METHODS: We used formalin-fixed paraffin-embedded histologically diagnosed small intestine (n=1), colon (n=7), skin (n=8), lung (n=5), lymph node (n=24) tuberculosis and Crohn's disease (n = 28) biopsy materials only with granulomas. Demographic characteristics like age and gender were also obtained. Pathology specimens were stained immunohistochemically with an antibody to VP-M660, targeting the 38-kDa antigen of Mycobacterium tuberculosis. RESULTS: In the M. tuberculosis group, 33/45 of patients have positive immunohistochemistry (IHC) staining (73% sensitivity, 93% specificity), whereas only two of 28 patients have positive staining in the Crohn's group (p<0.001). The positive staining with IHC was detected as 85.7, 75, 75, and 60% in colon, lymph node, skin, and lung granulomas, respectively, in M. tuberculosis patients. CONCLUSIONS: Immunohistochemical staining of biopsy specimens with anti-VP-M660 seems to be a simple and fast technique with 73% sensitivity and 93% specificity for establishing an earlier differentiation of M. tuberculosis from Crohn's disease.

SIRT1 as a potential therapeutic target for treatment of nonalcoholic fatty liver disease.

Sirtuins are members of the silent information regulator 2 (Sir2) family, a group of Class III histone/protein deacetylases. There are 7 different sirtuins in mammals (SIRT1-7), of which SIRT1 is the best known and most studied. SIRT1 is responsible for the regulation of protein activation by means of deacetylating a variety of proteins that play important roles in the pathophysiology of metabolic diseases. Recently, it has been shown that SIRT1 plays key roles in the regulation of lipid and glucose homeostasis, control of insulin secretion and sensitivity, antiinflammatory effects, control of oxidative stress and the improvements in endothelial function that result due to increased mitochondrial biogenesis and ß-oxidation capacity. Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver disease, and it has been accepted as the hepatic component of metabolic syndrome. Recent studies have shown that SIRT expression in the liver is significantly decreased in an NAFLD model of rats fed a high-fat diet, and moderate SIRT1 overexpression protects mice from developing NAFLD. In addition to resveratrol, a natural SIRT1 activator, small-molecule pharmacologic SIRT1 activators have positive effects on metabolic diseases. These effects are particularly promising in the case of diabetes mellitus, for which phase studies are currently being performed. With this information, we hypothesized that the pharmacologic activation of SIRT1, which has been implicated in the pathogenesis of NAFLD, will be a potential therapeutic target for treating NAFLD. In this paper, we review the metabolic effects of SIRT1 and its association with the pathophysiology of NAFLD.

Collagenous colitis: a retrospective survey of patients with chronic diarrhea.

BACKGROUND/AIMS: The aim of this retrospective survey is to determine the frequency of collagenous colitis among patients who presented with chronic diarrhea to our gastroenterology outpatient clinic and to evaluate the demographic, clinical and laboratory findings of these patients and the treatment modalities. METHODOLOGY: We reviewed the charts of the patients who had presented with chronic diarrhea to our outpatient clinic during four years. We identified the patients who were diagnosed to have collagenous colitis on histopathological examination. RESULTS: Among the 93 patients who presented with chronic diarrhea, 7 (7.5%) were diagnosed as collagenous colitis. Six of these patients were female, the mean age was 64 ± 11.5 years. Celiac disease was diagnosed in 2 of these patients. Laboratory examination showed anemia in 2 patients, hypoalbuminemia in 4 patients and high C-reactive protein levels in 3 patients. Five patients were treated with mesalazine, 1 patient with salazopyrine and 1 with methylprednisolone. Remission was obtained in all of these patients except for one; in this case budesonide was started instead of mesalazine. CONCLUSIONS: Collagenous colitis was detected in 7.5% of the patients who presented with chronic diarrhea to our gastroenterology outpatient clinic. They were usually middle aged female patients. Mesalazine was effective in most of these patients.

Levofloxacin based sequential and triple therapy compared with standard plus probiotic combination for Helicobacter pylori eradication.

BACKGROUND/AIMS: Development of resistance to standard therapy for Helicobacter pylori (H. pylori) eradication is rapid. The aim of this study is to compare the efficacy of alternative treatment modalities for H. pylori. Compared treatments were standard triple treatment plus probiotic, sequential therapy with levofloxacin, and a 14-day regimen of PPI (proton pump inhibitor) and levofloxacin/amoxicillin combination. METHODOLOGY: Overall 285 patients were enrolled in the study and allocated into three groups. Group I (n=98) received lansoprazole, clarithromycin, amoxicillin and saccharomyces boulardii (probiotic) and group II (n=95) received esomeprazole, levofloxacin and amoxicillin for 14 days. Finally, group III (n=92) received esomeprazole and amoxicillin for five days, followed by esomeprazole, levofloxacin and metronidazole for seven days. Testing for H. pylori infection post-treatment was done using a stool antigen test five weeks after the completion of therapy. RESULTS: Patients in all three groups were treatment-naive. Response to treatment (Per Protocol/ITT analysis) was 77.1/72.4% in Group I, 89.1/86.3% in Group II, and 95.5% in Group III. Response to treatment was significantly higher in Groups II and III compared to Group I (p=0.03 and p<0.001, respectively). There was no difference between Groups II and III in terms of response to treatment (p=0.1). CONCLUSIONS: Levofloxacin-based sequential therapy and levofloxacin based triple therapy were significantly superior to standard triple therapy plus probiotic.

Conventional video-gastroscopes for the recognition of early gastric cancers.

BACKGROUND/AIMS: To determine the role of conventional video-gastroscopes for detection of early gastric cancers (EGC). METHODOLOGY: All conventional upper gastrointestinal endoscopy (UGE) reports (12000 UGE reports) and pathology reports of all UGEs, between January 2003-December 2008, were evaluated retrospectively. RESULTS: The endoscopist suspected for EGC in 163 patients. In pathological examination, EGC was confirmed only in 35 patients. In reports of another 8 patients, the endoscopist did not suspect for EGC, but in pathological examination EGC was detected. Totally EGC was defined in 43 patients [28 male, 15 female, median age; 64 years (range 29-96 years)]. Of these 43 patients, 11 were inoperable, and 32 were operated. Among those operated, finally 17 patients were diagnosed with real EGC (10% of suspected cases). The frequency of H. pylori and atrophy were 29% and 41%, respectively. Incomplete intestinal metaplasia was mostly with submucosal invasion (41%). The most common location was the corpus and the patients with mucosal EGC commonly underwent subtotal gastrectomy. The majority (82%) of the cancers were intestinal-type according to Lauren histological classification. No relation was detected between invasion-depth and lymph node metastasis and number. The sensitivity, specificity, positive and negative predictive values were found as 84%, 99%, 26% and 99% respectively. CONCLUSIONS: Conventional endoscopes have excellent specificity and negative predictive value and moderate sensitivity for early recognition of EGC. Most of early detected cancers were out of endoscopic treatment range. One-tenth of suspicious lesions were early gastric cancer, the corpus was frequent site and half of incomplete intestinal metaplasia cases were along with it.

Plasma fibrinogen-like protein 2 levels in patients with non-alcoholic fatty liver disease.

BACKGROUND/AIMS: Fibrinogen-like protein 2 (fgl2), has recently been identified as a new member of the fibrinogen-like family of proteins. In this study we assayed plasma levels of fgl2 in patients with biopsy proven non-alcoholic fatty liver disease (NAFLD) and examined their association with clinical, biochemical and histological phenotypes. METHODOLOGY: Levels of plasma fgl2 were measured by enzyme linked immunosorbent assay and compared between the study groups. Moreover, concentrations of fgl2 were assessed in relation to the general characteristics of the study participants and the results of the liver biopsy. RESULTS: Levels of fgl2 were significantly higher in patients with definite non-alcoholic steatohepatitis (NASH) (788±190pg/mL, p<0.001) and borderline NASH (710 ± 140pg/mL, p<0.001) compared with controls (515±174pg/mL). No significant differences were found in patients with simple steatosis (649 ± 162pg/mL) as compared with controls. There were no associations between the plasma fgl2 levels with the fibrosis stage and steatosis grade. CONCLUSIONS: Although subject to future confirmation, our data suggest that fgl2 levels are elevated in the more severe forms of NAFLD.