Cryptogenic liver cirrhosis and hepatitis E virus (HEV): Are they related?

INTRODUCTION AND OBJECTIVES: Hepatitis E virus (HEV) is one of the most common causes of acute hepatitis. In recent years, its role in the development of chronic hepatitis and cirrhosis especially in immunosuppressed patients and its wide range of extrahepatic involvement have increased the amount of research on HEV. In this study we aimed to investigate the presence of HEV infection in individuals with cryptogenic cirrhosis. MATERIALS AND METHODS: HEV antibodies were analysed using the Anti HEV enzyme-linked immunosorbent assay (ELISA) kit (anti-HEV ELISA; Diapro Prodiagnostic Bioprobes, Milan, Italy). HEV RNA was isolated with using QIAMP Viral RNA mini kit (QIAGEN, Hilden, Germany). The HEV RNA titre was detected with the Rotor Gene 3000 real time polymerase chain reaction (PCR) system using GenoSen's HEV (Rotor Gene) Quantitative Real Time PCR Kit (Genome Diagnostics Private Limited, the Netherlands). RESULTS: Our study included 21 healthy volunteers (12 males) and 35 cryptogenic cirrhosis patients (19 males). The ages of the patients and the controls were similar (46±12.1 vs. 37.5±9.7years). The mean Child-Pugh score was 8±2.5. The anti HEV immunoglobulin G(IgG) positivity rate was 9.5% and 25.7% in the control and patient groups respectively (p>0.05). HEV RNA positivity was not detected in the control group, but 3 cases (8.6%) in the patient group were positive (p>0.05). The HEV RNA, aspartate aminotransferase (AST) and alanine aminotransferase(ALT) levels for these 3 cases were 326.461copies/mL, 91IU/L and 67IU/L; 480copies/mL, 68IU/L and 36IU/L and 72copies/mL, 42IU/L and 24IU/L respectively. There were positive correlations between HEV RNA levels and AST and ALT levels (p<0.05). CONCLUSIONS: Anti HEVIgG and HEV RNA positivity rates are high in cryptogenic cirrhosis although it is not statistically significant and there is a positive correlation between HEV RNA and aminotransferases.

Mutations in RAD21 disrupt regulation of APOB in patients with chronic intestinal pseudo-obstruction.

BACKGROUND & AIMS: Chronic intestinal pseudo-obstruction (CIPO) is characterized by severe intestinal dysmotility that mimics a mechanical subocclusion with no evidence of gut obstruction. We searched for genetic variants associated with CIPO to increase our understanding of its pathogenesis and to identify potential biomarkers. METHODS: We performed whole-exome sequencing of genomic DNA from patients with familial CIPO syndrome. Blood and lymphoblastoid cells were collected from patients and controls (individuals without CIPO); levels of messenger RNA (mRNA) and proteins were analyzed by quantitative reverse-transcription polymerase chain reaction, immunoblot, and mobility shift assays. Complementary DNAs were transfected into HEK293 cells. Expression of rad21 was suppressed in zebrafish embryos using a splice-blocking morpholino (rad21a). Gut tissues were collected and analyzed. RESULTS: We identified a homozygous mutation (p.622, encodes Ala>Thr) in RAD21 in patients from a consanguineous family with CIPO. Expression of RUNX1, a target of RAD21, was reduced in cells from patients with CIPO compared with controls. In zebrafish, suppression of rad21a reduced expression of runx1; this phenotype was corrected by injection of human RAD21 mRNA, but not with the mRNA from the mutated p.622 allele. rad21a Morpholino zebrafish had delayed intestinal transit and greatly reduced numbers of enteric neurons, similar to patients with CIPO. This defect was greater in zebrafish with suppressed expression of ret and rad21, indicating their interaction in the regulation of gut neurogenesis. The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector. The gut-specific isoform of APOB (APOB48) is overexpressed in sera from patients with CIPO who carry the RAD21 mutation. APOB48 also is overexpressed in sporadic CIPO in sera and gut biopsy specimens. CONCLUSIONS: Some patients with CIPO carry mutations in RAD21 that disrupt the ability of its product to regulate genes such as RUNX1 and APOB. Reduced expression of rad21 in zebrafish, and dysregulation of these target genes, disrupts intestinal transit and the development of enteric neurons.

Association of the MEFV gene variations with inflammatory bowel disease in Turkey.

BACKGROUND: Association of NOD2 (CARD15) gene mutations with inflammatory bowel diseases (IBD) is well known. We herein aimed to investigate the role of familial Mediterranean fever-associated MEFV variations in IBD patients as additional regional-specific risk factor. STUDY: One hundred thirty-seven (78 female, 56.9%) IBD patients [62 Crohn's disease (CD), 75 ulcerative colitis (UC)] were enrolled into the study. The diagnosis of all patients was confirmed by colonoscopy, histopathology, and the clinical findings. One hundred one healthy donors' samples were used as healthy controls. All patients were genotyped for the most common E148Q, M608I, M694V, and V726A variations of the MEFV and R702W, G908R, and 1007fs of the NOD2. RESULTS: The overall MEFV variation frequency was found to be higher in the IBD (25.5%) patients (28% in UC, 22.6% in CD) compared with controls (9.9%, P=0.006). This association was stronger with the penetrant exon 10 variations (M694V, M680I, V726A; odds ratio =4.5, P=0.001). Contribution of M694V was higher compared with the other variations (14.5% in CD, 17.3% in UC and 3% in controls, odds ratio =6.039, 95% confidence intervals, 1.7-20.7, P=0.002). The overall frequency of 3 NOD2 variants in the IBD group was not different from that of controls. CONCLUSIONS: The results of this study suggest that the MEFV variations may be an additional susceptibility factor for IBD in certain parts of the world where the carrier rate is high, and the genetic background of the IBD patients may show regional changes.

Anticoagulant therapy and Budd-Chiari syndrome: is it successful?

BACKGROUND/AIMS: Anticoagulant therapy is an accepted treatment for Budd-Chiari syndrome (BCS). However, the natural course of untreated patients is unclear. We aimed to evaluate the efficacy of anticoagulant therapy on survival in BCS. METHODOLOGY: Between 1995 and 2007, 45 patients diagnosed with BCS based on the clinical, biochemical, radiological and histological findings were retrospectively evaluated with respect to underlying disease, therapeutic interventions, complications and overall outcome. Complications and survival during the follow-up period were compared in between anticoagulant treated and untreated cases. RESULTS: Mean patient age was 34.4 +/- 11.8 years and 46.7% (21) of them were male. Median followup time was 24 months (6-132); 8.9% of patients were diagnosed as acute, 31.1% as subacute and 60% as chronic BCS according to disease duration. Centrilobular necrosis was found in 16 of 36 biopsy performed patients. Etiological factors were detected in 60% of patients and 40% of them were cryptogenic. Twenty four of them received anticoagulant therapy, the remaining 21 were followed-up with supportive medical therapy. Five patients who had shunt operation were excluded for survival analyses. Complications were similar between treated and untreated cases (p>0.05). There was a positive correlation between survival and centrilobular necrosis (r=0.376, p=0.037). The mean survival periods were 95.5 months (%95 CI 73-117 months) and 72.5 months (%95 CI 42-103 months) in anticoagulant treated and untreated patients, respectively (p>0.246). CONCLUSION: Most patients with BCS are admitted to hospital at the chronic stage and more than half of them have underlying thrombotic risk factor. In our study, no beneficial effects of anticoagulant therapy were observed on the survival and complications of liver disease.

Effect of proton pump inhibitor (PPI) treatment in obstructive sleep apnea syndrome: an esophageal impedance-pHmetry study.

BACKGROUND/AIMS: There is an increasing interest for a link between gastroesophageal reflux (GER) and obstructive sleep apnea syndrome (OSAS). There is no study in the literature which examines the relationship between OSAS and esophageal functions in adults with impedance. We first evaluated the role of reflux in OSAS with simultaneous polysomnography and impedance-pHmetry and then investigated whether the effect of proton pump inhibitor (PPI) treatment changes in these parameters. METHODOLOGY: Twenty two OSAS patients who had applied to sleep laboratory between September 2007 and May 2008 were consecutively enrolled to the study. Twenty four hours esophageal impedance study was performed during polysomnographic recording. At least 50% of all apneas in patients must proceed with a reflux event in 2 minute intervals in order to be considered reflux related apnea patient. RESULTS: Pathologic reflux episodes were determined in 20 patients (8 were weakly acidic, 12 were acidic). Reflux dependent apnea was found in 6 patients. There was endoscopically esophagitis in all reflux related apnea patients. There was a negative correlation between initial mean SaO2 and gas reflux events at night (p=0.004, r =-0.588) and mixed reflux events at night (p=0.02, r=0.493). There was a statistically significant regression of AHI (apnea hypopnea index) after 3-months PPI treatment (p=0.012). CONCLUSIONS: Reflux may trigger apnea in some of the OSAS patients. Therefore, each OSAS patient must be inquired about esophageal and extraesophageal symptoms of reflux.

Second-line levofloxacin-based triple therapy's efficiency for Helicobacter pylori eradication in patients with peptic ulcer.

OBJECTIVES: First-line standard eradication efficacy with lansoprazole, amoxicillin and clarithromycin regressed over 10 years. The aim of this study was to evaluate the efficacy and tolerability of a levofloxacin-based regimen in patients with peptic ulcer after failure of the standard first-line H.pylori eradication therapy in a country with a high rate of infection. METHODS: A total of 91 peptic ulcer patients who were diagnosed H.pylori positive proven by rapid urease test and histology between November 2005 to March 2008 were given lansoprazole 30 mg bid, amoxicillin 1 g bid and clarithromycin 500 mg bid (LAC) for 14 days. After three months from the first line eradication treatment omeprazole 20 mg bid, levofloxacin 500 mg bid, amoxicillin 1 g bid (OLA) 7 day treatment regimen was recommended as a second-line therapy for 37 patients who failed at first-line standard triple therapy. RESULTS: Eradication rates for LAC regimen were found to be 57.14% (52/91) for intention to treat and 58.42% (52/89) for per protocol analysis. Eradication rates for OLA regimen were found to be 37.83% (14/37) for ITT and 41.17% (14/34) for PP analysis. CONCLUSION: OLA regimen eradication rate was successful only in 40% of patients who failed in the first-line eradication. New eradication treatment strategies must be performed, at least in Turkey.

Is portal hypertensive enteropathy an important additional cause of blood loss in portal hypertensive patients?

OBJECTIVE: Recently, mucosal changes of small bowel were defined by developing new imaging techniques including capsule endoscopy (CE) in portal hypertensive patients. However, the clinical impact of these changes is unknown. In this study, we aimed to determine the additional cause of blood loss in portal hypertensive patients. MATERIAL AND METHODS: A total of 444 portal hypertensive patients, hospitalized in our clinic between 2005 and 2007, were evaluated. Patients with obscure bleeding were enrolled to this prospective case-control study. CE was performed in 21 patients who met inclusion criteria. Gastroscopy, colonoscopy and computerized tomography/small bowel enema were performed in all patients. RESULTS: Fourteen cirrhotic and seven noncirrhotic portal hypertensive patients were enrolled to this study. Mean age of patients was 47.9±15.6 years, and 13 of 21 were male. Small bowel varices were found in 7 patients (1 active bleeding) and other mucosal abnormalities in 10 patients (vascular ectasia, erosion and edema, 1 active bleeding). Although two of them were normal, jejunal malignant mass was found in two patients (1 active bleeding). Of 21 patients, 19 (90.5%) patients had portal hypertensive abnormalities (including varices). However, ileal varices rate was 57.1% (4 patients) in noncirrhotic portal hypertensive patients and 21.4% (3 patients) in cirrhotics. CONCLUSION: Ninety percent of patients had portal hypertensive abnormalities in small bowel and one-third of them had small bowel varices. Small bowel varices and vascular ectasia were the main causes of obscure bleeding in portal hypertensive patients.

Electron microscopic findings in non-alcoholic fatty liver disease: is there a difference between hepatosteatosis and steatohepatitis?

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease has long been accepted as benign; however, recent evidence suggests that the disease may progress to cirrhosis and hepatocellular carcinoma, although the natural course of the disease is still unclear. This study was designed to comparatively evaluate electron microscopic features of non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). METHODS: Quantitative and semi-quantitative ultrastructural evaluations were performed on liver biopsies from 23 patients, 10 with NAFL and 13 with NASH. RESULTS: No statistically significant difference was noted between NAFL and NASH patients in ultrastructural features of hepatocytes including megamitochondria, intramitochondrial crystalline inclusions, mitochondrial matrix granules, foamy cytoplasmic appearance, electron-lucent and glycogen-containing nuclear regions, lipofuscin granules, or an increased frequency of vesicles containing electron-dense material in peribiliary Golgi zone; however, the mitochondrial diameter was significantly higher in the NASH patients. Intercellular distance and microvilli between hepatocytes, collagen and electron-dense material accumulation in the space of Disse, electron-dense material accumulation and microvillus density in bile canaliculi did not differ significantly between the groups. CONCLUSIONS: Our data show that, although NAFL and NASH can be distinguished by their distinct light microscopic features, ultrastructural characteristics are similar, which suggests that NAFL may also have the potential to progress to fibrosis and cirrhosis like NASH.

Decreased prohepcidin levels in patients with HBV-related liver disease: relation with ferritin levels.

BACKGROUND: Levels of prohepcidin, a homeostatic regulator of iron absorption, are altered in chronic hepatitis C and liver cirrhosis. However, data on the potential alterations of prohepcidin in patients with HBV-related liver disease are scarce. We investigated whether serum prohepcidin is related to iron overload and perenchymal dysfuction in HBV-related liver disease. METHODS: Three groups of subjects were studied: 66 patients with chronic hepatitis B, 32 patients with HBV-related cirrhosis, and 42 healthy controls without evidence of liver disease. Serum levels of prohepcidin were determined by enzyme-linked immunosorbent assay. RESULTS: Serum prohepcidin levels were significantly lower in patients with HBV-related cirrhosis (175.85 ± 71.5 ng/ml) than in patients with chronic hepatitis B (209.02 ± 62.7 ng/ml P < 0.05) and controls (222.4 ± 128.4 ng/ml, P < 0.05). After adjustment for potential confounders, prohepcidin was found to be an independent predictor of ferritin levels in multiple linear regression analysis (ß = -1.10, t = -3.11, P < 0.01). CONCLUSION: These results demonstrate that prohepcidin levels are reduced in patients with HBV-related cirrhosis and are an independent correlate of serum ferritin.

Upper socioeconomic status is associated with lower Helicobacter pylori infection rate among patients undergoing gastroscopy.

INTRODUCTION: Socioeconomic factors play an important role in the prevalence of Helicobacter pylori (HP) infection. The aim of this study is to investigate HP prevalence among symptomatic patients in the upper socioeconomic segment of the population undergoing gastroscopy in an endemic urban region. METHODOLOGY: Over a 12-month period, data were collected from the first consecutive 1000 patients (500 from university hospital, 500 from community hospital) who had gastroscopy and HP evaluation. RESULTS: Overall, 211/1000 patients (21.1 %) were found to have HP in gastric biopsies. The specificity, sensitivity, positive predictive value, negative predictive value and diagnostic accuracy of rapid urease test were 87.5%, 99.7%, 99%, 96.5%, and 96.9% respectively. Atrophic gastritis, gastric and duodenal ulcers were significantly more common in HP positive patients. Age based distribution of HP prevalence: > 6 decades (15.5%), 3rd-5th decades (26.1%), < 3rd decades (10.4%). CONCLUSION: In an HP endemic country, the prevalence of HP infection among symptomatic patients belonging to the upper socioeconomic segment of the population appears to be markedly lower. The lowest prevalence in young patients is expected to result in future decrease in HP prevalence.

Are acquired hepatocerebral degeneration and hepatic myelopathy reversible?

BACKGROUND: Acquired hepatocerebral degeneration (AHD) and hepatic myelopathy (HM) are rare complications of chronic liver disease and are usually resistant to medical therapy. MATERIALS AND METHODS: The clinical and laboratory findings of 14 male and 2 female patients with AHD or HM were evaluated. RESULTS: The prevalence of AHD and HM was 2% inpatient case series in the last 10 years. The median age of the patients (5 Child's B and 11 Child's C) was 48.7 years (28 to 66 y), and the mean known duration of the liver disease was 75 months (24 to 194 mo). The median time of onset of neurologic findings after diagnosis of the liver disease was 14.5 months. Eight patients who had marked spastic paraparesis or tetraparesis were included in the HM group and all others had AHD group. Sixty-nine percent of the patients had a spontaneous or surgical portosystemic shunts, and the remaining dense retroperitoneal collaterals. During the follow-up period of median 29 months (4 to 72 mo), 12 patients died while waiting for liver transplantation, and these patients suffered from the several complications of chronic liver disease more than the living patients. A marked improvement was observed in 2 of the patients (1 with AHD and the other with HM) at 6 and 8 months after the liver transplantation, respectively. CONCLUSIONS: Our data suggest that liver transplantation had an important effect on the improvement in these patients.

A new agent for tumour necrosis factor-alpha inhibition: In vitro effects of dipyridamole in Crohn's disease.

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) plays a central role in inflammatory cascade in Crohn's disease (CD). Our study aims to investigate the in vitro effects of dipyridamole (DP) on the TNF-alpha and interleukin-10 (IL-10) production in the intestinal mononuclear cells of CD patients. MATERIAL AND METHODS: Thirteen patients with CD and in 17 healthy individuals underwent colonoscopy and biopsy samples were taken. Cultured mononuclear cells were preincubated with DP1 (0.7 microg/ml), DP2 (1.25 microg/ml), methotrexate (MTX)1 (0.5 nmol/L) and MTX2 (1.5 nmol/L). These cells were then stimulated with lipopolysaccaride (LPS) and phytohemagglutinin (PHA). The levels of TNF-alpha and IL-10 in supernatants were measured with standard immunoassay monoclonal antibody method. RESULTS: An appropriate cell culture could be obtained in 10 patients with CD and 12 healthy individuals. In LPS stimulated cells, MTX1 and MTX2 were superior to DP1 and DP2 in suppressing TNF-alpha in both groups. In PHA stimulated cells, while MTX1 was superior to DP1, MTX2 and DP2 had an equivalent effect in CD patients (p<0.05, p>0.05, respectively). In LPS-stimulated cells DP2 was significantly superior to MTX2 in increasing IL-10 levels in both groups (p<0.05). In PHA stimulated cells, DP1 and DP2 caused a higher increase in IL-10 levels compared with MTX1 and MTX2 in CD group (p<0.05). CONCLUSIONS: Dipyridamole suppresses TNF-alpha similar with MTX. It seems to be superior to MTX in increasing IL-10 levels. Addition of DP to anti-TNF medications may create a synergy in cytokine modulation.

Intestinal metaplasia in portal hypertensive gastropathy: a frequent pathology.

OBJECTIVE: To compare the frequency of intestinal metaplasia (IM) in patients with portal hypertensive gastropathy (PHG) to the control group with functional dyspepsia. METHODS: Two-hundred and eighty-nine cases were prospectively evaluated in three groups (controls:group I--123 patients; cirrhotics: group II--135 patients; noncirrhotic portal hypertensives: group III--31 patients). Mucosal biopsies (three antrum, one angulus, two corpus) were taken and examined for atrophy, IM, dysplasia, Helicobacter pylori (Hp) and histologic PHG. RESULTS: Frequencies of IM in groups I, II and III were 17.1% (type I, 3.3%; type II, 10.6%; type III, 3.3%), 34.3% (type I, 9.6%; type II, 17%; type III, 6.7%) and 33.3% (type I, 9.7%; type II, 12.9%; type III, 9.7%), respectively. In patients with PHG, frequency of IM was significantly higher than in control group (P<0.05) and correlated with the severity of PHG (P<0.05). The frequency of type III IM was not statistically different among the three groups. Frequency of atrophy in cirrhotic patients was higher than in control group (17.9% in group I, 32.6% in group II, 25.8% in group III; P<0.05). In the control group, Hp prevalence was significantly higher than in patients with PHG (P<0.05) and there was a positive correlation between Hp and atrophy (P<0.05). In multivariate analysis, PHG and age were found as independent predictors for IM; PHG, age and Hp for atrophy. CONCLUSION: Frequencies of atrophy and IM are higher in patients with PHG. PHG is a reliable marker for IM and atrophy in gastric mucosa.

A novel locus for syndromic chronic idiopathic intestinal pseudo-obstruction maps to chromosome 8q23-q24.

Chronic idiopathic intestinal pseudo-obstruction (CIIP) is a rare and severe clinical syndrome characterized by symptoms and signs of intestinal occlusion, in the absence of any mechanical obstruction of the gut lumen. In the attempt to identify the genetic basis of CIIP, we analyzed a Turkish pedigree with a high degree of consanguinity in which three siblings presented with a syndromic form of CIIP. All affected family members were characterized by recurrent, self-limiting subocclusive episodes, long-segment Barrett esophagus, and a variety of minor cardiac valve or septal defects. In some patients full-thickness intestinal biopsy samples were obtained and tissues were processed for immunohistochemistry using antibodies to different markers of the intestinal neuromuscular tract. Full-thickness biopsies of the gut wall showed abnormalities of both the neural and muscular components suggesting an underlying intestinal neuro-myopathy. Blood samples were collected for DNA extraction from each available family member and DNAs were genotyped using 382 microsatellites spanning the entire genome with the aim to take advantage of the homozygosity mapping approach. Linkage analysis identified a new syndromic locus on chromosome 8q23-q24 (multipoint LOD score=5.01). Our data strongly support the presence of a new genetic locus associated with CIIP, long-segment Barrett esophagus, and cardiac involvement on chromosome 8.

What is the reason of elevated alanine aminotransferase level in HBeAg negative patients with low viremia: NAFLD or chronic hepatitis?

BACKGROUND AND STUDY AIMS: Increased alanine aminotransferase (ALT) levels with negative hepatitis B virus (HBV) DNA by hybridization is a common problem in Turkey where is a mild endemic region. We aimed to evaluate the causes of elevated ALT levels in patients who are negative for hepatitis B e antigen (HBeAg) and HBV DNA (by hybridization) for at least 6 months. PATIENTS-METHODS: Forty-nine patients were enrolled in this study. Histological changes [histological activity index (HAI), and the extent of fibrosis] were assessed according to the Knodell scoring system and steatosis were graded by Brunt's classification for NAFLD in all patients. RESULTS: A mean age of the patients was 34.9 +/- 12.1 years (16-70). 43 (87.8%) of them were male. Mean ALT level was 95 +/- 39.7 IU/L (50- 258). Hyperglycemia (>100 mg/dL) and hyperlipidemia were found in 12 and 24 patients, respectively. Hepatic steatosis (7 patients grade 1; 5 patients grade 2; and 7 patients grade 3), ground-glass hepatocyte, chronic hepatitis, and Wilson disease were found in liver biopsy in 38.8%, 32.6%, 26.6%, 2%, respectively. Mean HAI was 6.5 +/- 3.6 (4-12) in chronic hepatitis. Seven patients (53.9%) were in stage 1 and 2 while 6 patients (46.1%) were in stage 3 and 4. CONCLUSIONS: Nonalcoholic fatty liver disease is the most common cause of elevated ALT levels in HBeAg negative/HBV DNA negative patients. Chronic hepatitis B was found in 26.6% of these patients.

A case of Aeromonas hydrophila enteritis in the course of ulcerative colitis.

A 24-year-old man with a previous diagnosis of ulcerative pancolitis presented with severe malabsorption with watery diarrhea, malaise, and weight loss. Physical examination revealed paleness, hypotension, tachycardia, edema, ascites, and left-sided pleural effusion. Laboratory analysis revealed hypoalbuminemia and hypocalcemia. Further examination revealed that malabsorption was related to Aeromanas hydrophila infection. Clinical improvement was observed upon oral ciprofloxacin treatment. No clinical or laboratory activation of ulcerative colitis was detected during this infection.

Which drugs are risk factors for the development of gastroesophageal reflux disease?

Gastroesophageal reflux disease (GERD), which is common in many communities, is associated with structural factors, eating habits, and the use of certain drugs. The use of such drugs can lead to the emergence of GERD and can also exacerbate existing reflux symptoms. These drugs can contribute to GERD by directly causing mucosal damage, by reducing lower esophageal sphincter pressure (LESP), or by affecting esophagogastric motility. In this article, we report our investigation of the relationships between GERD and medications within the scope of the "Turkish GERD Consensus Group." For the medication groups for which sufficient data were obtained (Figure 1), a systematic literature review in English was conducted using the keywords "gastroesophageal reflux" [MeSH Terms] and "anti-inflammatory agents, non-steroidal" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "acetylsalicylic acid" [MeSH Terms], "gastroesophageal reflux" [All Fields] and "estrogenic agents" [All Fields], "gastroesophageal reflux" [All Fields] and "progesterones" [All Fields], "gastroesophageal reflux" [All Fields] and "hormone replacement therapy" [All Fields], "gastroesophageal reflux" [MeSH Terms] and "diphosphonates" [MeSH Terms] OR "diphosphonates" [All Fields], "calcium channel blockers" [MeSH Terms] and "gastroesophageal reflux" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "nitrates" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "antidepressive agents" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "benzodiazepines" [MeSH Terms] and "hypnotic drugs" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "cholinergic antagonists" [MeSH Terms], "gastroesophageal reflux" [MeSH Terms] and "theophylline" [MeSH Terms], and "gastroesophageal reflux [MeSH Terms] AND "anti-asthmatic agents" [MeSH Terms]. The studies were analyzed and the results are presented here.

Gastroesophageal reflux disease and the relationship with Helicobacter pylori.

After Helicobacter pylori was identified, and its relationship with peptic ulcer disease was exactly shown, the relationship of this bacterium with gastroesophageal reflux disease (GERD) gained momentum and discussions continue to this day. We reviewed the literature for the relationship between H. pylori and GERD. According to the existing data, there is no relationship between GERD and H. pylori presence. Successful eradication therapy does not have an impact on the emergence or exacerbation of GERD. However Barrett's esophagus and esophageal adenocarcinoma are less frequent, especially in the presence of CagA positive H. pylori infections. Long-term use of proton pump inhibitor (PPI) may have an impact on the development of atrophy and/or intestinal metaplasia in H. pylori positive patients; therefore, H. pylori eradication is recommended in patients that should use long-term PPI. As a conclusion, H. pylori screening and the eradication decision should be independent of GERD, except for patients that will use long-term PPI.

Vildagliptin-induced acute pancreatitis without enzyme elevation.

We describe 2 patients with diabetes mellitus, presenting with upper abdominal pain. Although imaging findings were consistent with acute pancreatitis (AP), serum amylase and lipase levels were within normal limits. In both the cases, the only identifiable diagnostic culprit was vildagliptin. This is the first reported case of vildagliptin causing AP clinically and radiographically without elevated serum pancreatic enzymes. In conclusion, even when serum amylase and lipase levels are normal, AP should be kept in mind when making a differential diagnosis of patients with diabetes mellitus who present with abdominal pain and take dipeptidyl peptidase-4 (DPP-4) inhibitors.