Effect of pantoprazole and Helicobacter pylori therapy on uninvestigated dyspeptic patients.

BACKGROUND/AIMS: This study aimed to test the efficacy of empirical proton pump inhibitor use and Helicobacter pylori therapy for uninvestigated dyspepsia in a population with a high prevalence of H. pylori. MATERIAL AND METHODS: The study had a two-stage design. In the first stage, the efficacy of 4-week pantoprazole treatment was compared with placebo in patients with uninvestigated dyspepsia. In the second stage, the efficacies of 2-week treatment with pantoprazole in H. pylori-negative patients and H. pylori eradication therapy (pantoprazole + amoxicillin + clarithromycin) in H. pylori-positive patients were compared. The primary endpoint was sufficient overall symptom relief (Global Overall Symptom score ≤2; no or minimal symptoms) at the end of treatment. RESULTS: In the first stage, sufficient overall symptom relief was achieved by 25.2% of patients in the pantoprazole group and 15.5% of patients in the placebo group, a difference that was not statistically significant (p=0.06). In the second stage, the rate of sufficient overall symptom relief was higher in the H. pylori therapy group than in the pantoprazole group (37.1% vs. 23.4%; p=0.02). After untreated follow-up, sufficient overall symptom relief remained significantly higher in the H. pylori therapy group than in the pantoprazole group (39.7% vs. 18%; p<0.001). Almost all patients receiving pantoprazole experienced symptom relapse after treatment. CONCLUSIONS: This study validated the use of a test-and-treat strategy against H. pylori in uninvestigated dyspepsia, which may be an advisable treatment approach for uninvestigated dyspeptic patients in countries with a high prevalence of H. pylori.

Routinely evaluated clinical assays and laboratory tests [real test] and fibrosis stages of chronic hepatitis B and C.

BACKGROUND/AIMS: To provide a new mathematical formula to predict liver fibrosis in patients with chronic viral hepatitis. MATERIALS AND METHODS: Patients with chronic hepatitis B and C who underwent liver biopsy at different centers were included in this study. Chronic hepatitis B was defined as immunopositivity for the hepatitis B surface antigen for at least 6 months, and chronic hepatitis C was defined as positivity for HCV RNA for at least 3 months. The histological features were evaluated by the histological activity index and fibrosis. RESULTS: In total, 1299 patients were included in the study. The distribution and the mean of the parameters of the patients were as follows: 1009 patients with chronic hepatitis B with a mean age of 45±13/years [emale/male (F/M)=47.5/52.5%] and 290 patients with hepatitis C with a mean age of 52±10.3/years [F/M=61/39%]. When the cut-off value of the REAL TEST formula"[(age x pT x AST)/(PLT/1000)]/100" in patients with hepatitis B was determined to be ≥1.37, it was found that it could predict fibrosis with 79% specificity, 78% sensitivity, 85% negative predictive value (NPV), and 70% positive predictive value (PPV) (area under the curve (AUC)=0.852, 95% CI:0.82-0.87). When the cut-off value of the REAL TEST formula in patients with hepatitis C was determined to be ≥1.99, it was found that it could predict significant fibrosis with 87% specificity, 90% sensitivity, 94.4% NPV, and 79.4% PPV (AUC:0.95, 95% CI:0.93-0.98). CONCLUSION: The REAL TEST formula results correlated with the pathological findings and may be a useful method for the evaluation of patients with chronic hepatitis B and C.

Evaluation of concentrations of pro/anti-inflammatory cytokines after complication-free ECRP in cholangiocarcinoma.

BACKGROUND/AIMS: Variations in pro and anti-inflammatory cytokine levels occur commonly after ERCP procedure complications, such as in post-ERCP pancreatitis. Besides, the relationship between increased cytokine levels and multidrug resistance has been shown in cholangiocarcinoma patients. Our aim was to investigate the impact of cytokine level changes on treatment strategy after uncomplicated ERCP procedures in cholangiocarcinoma patients. MATERIALS AND METHODS: Of 75 patients enrolled in this study, 25 were cholangiocarcinoma, and 50 were choledocholithiasis patients. Levels of serum IL-1ß, IL-6, IL-8, IL-10, and TNF-α were evaluated 2 hours before and 12 hours after complication-free ERCP, and statistical analysis of the results was obtained; if p value<0.05, it was accepted as statistically significant. RESULTS: There was no statistically significant difference in the distribution of age (23-87 years; range: 59.8±16.6), gender (37 males vs 38 females), and levels of pre- and post-ERCP serum IL-1ß, IL-6, IL-8, IL-10, and TNF-α in both patient groups, despite the presence of some change in test means (p:0.179, 0.445, 0.522, 0.937, and 0.065, respectively). However, significantly decreased levels of TNF-α were observed in the benign group, when comparing pre- and post-ERCP period (p<0.05). CONCLUSION: Serum concentrations of IL-1ß, IL-6, IL-8, IL-10, and TNF-α evaluated after complication-free ERCP performed in patients with cholangiocarcinoma do not cause any change in treatment planning that would affect multidrug resistance.

QT interval changes and reversibility of QT dispersion in patients with acute pancreatitis.

BACKGROUND/AIMS: QT dispersion is a sign of heterogeneity of ventricular myocardial wall and is associated with cardiac mortality and morbidity. Data regarding with the persistence of QT interval changes in cases with acute pancreatitis (AP) that required clinical follow-up, are insufficient. Therefore, in this study, we aimed to evaluate the QT interval changes during attack and after remission of the disease, in cases with AP. MATERIALS AND METHODS: The cases admitted to the Gastroenterohepatology Clinic with the diagnosis of AP were included into the study. Ranson's score parameters, electrocardiography and echocardiography of all patients included into the study were evaluated. Electrocardiographic changes were evaluated two times, during attack and after remission of the disease. RESULTS: A total of 134 subjects (F/M:54/80, 41/59%) diagnosed as AP were included into the study. Seventy two (54%) of the AP cases included into the study were biliary, 32 (24%) were alcohol dependant, 19 (14%) were idiopathic, 9 (7%) were hyperlipidemic and 2 (1%) were ERCP related cases. Mean age of the patents was 57.7±15 years old (range: 19-82 years old) and mean Ranson's score was 3.8±1.9 (range: 1-7), according to the numerical scoring system. We compared QT interval changes during the attack and after the remission of AP and found significant increase in QT dispersion levels during acute attack of AP (p<0,001). CONCLUSION: The most common electrocardiographic changes in AP patients are QT interval changes including QT dispersion. QT dispersion which was emerged during the attack recovered after the remission of the disease.

[HBV vaccine escape mutations in a chronic hepatitis B patient treated with nucleos(t)ide analogues]. / Nükleoz(t)id analoglari tedavisi altinda HBV asi kaçagi mutasyonlari gelisen bir kronik hepatit B olgusu.

The hepatitis B virus (HBV) polymerase (pol) gene completely overlaps with the envelope (S) gene. Nucleos(t)ide analogue (NA) resistance mutations in the pol gene of HBV, either from selection of primary or secondary resistance mutations, typically result in changes in the overlapping hepatitis B surface antigen (HBsAg). Recent studies have conferred a new acronym to these HBV pol/S gene overlap mutants; ADAPVEMs, for antiviral drug-associated potential vaccine-escape mutants. The present report aimed to assess the determined multiple HBV vaccine-escape mutants in a Turkish patient with chronic hepatitis B (CHB), undergoing NAs treatment. The liver biopsy of HBsAg positive, HBeAg negative 53-year old female patient with CHB, revealed a score as histological activity index; 9 and fibrosis; 2 according to Ishak classification. NA treatment backgrounds consisted of 24 months lamivudine, followed by 18 months entacavir and lastly 3 months tenofovir monotherapies. Since HBV DNA load was determined as 7.030.000 IU/ml at the 4th month of tenofovir therapy, entecavir was added as current treatment regimen, and tenofovir + entecavir therapy decreased the HBV DNA load (400 IU/ml). Sequence analysis was performed for HBV pol/S gene and overlapping pol/S gene amino acid substitutions, primary/compensatory NA resistance mutations and antiviral drug-associated potential vaccine-escape mutations (ADAPVEM) were analysed. The patient isolate was identified as genotype D/subgenotype D1 of HBV. Primary drug resistance mutations (rtV173L + rtL180M + rtM204V) to lamivudine and telbivudine and a compensatory mutation (rtQ215H) to lamivudine and adefovir were described in the HBV pol gene sequence. However, multiple HBV vaccine-escape mutations (sS143T + sD144E + sG145R + sE164D + sI195M) have been determined on the HBV overlapping pol/S gene region. Lamivudine and telbivudine which are the frequently preferred drugs for the treatment of CHB in Turkey, have the potential to lead to ADAPVEMs. Thus ADAPVEMs should be monitored in infected and NA treated CHB patients and their public health risks should be assessed.

Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome concomitant with immune hemolytic anemia and immune thrombocytopenic purpura (Evans syndrome).

Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) associated with Evans syndrome; combination of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP) has rarely been reported. We report the case of a 53-year-old patient who presented with weakness, myalgia, arthralgia, shortness of breath and purpura. Initial laboratory investigations revealed liver dysfunction, anemia and thrombocytopenia. Anti-nuclear (ANA) and antimitochondrial M2 (AMA M2) antibodies were positive. Diagnose of PBC-AIH overlap was made by clinical, serological and histological investigations. AIHA and ITP was identified with clinical-laboratory findings and bone marrow puncture. She was treated with IVIG followed by prednisolone and ursodeoxycholic acid. Hemoglobin-thrombocytes increased rapidly and transaminases improved at day 8. We have reported the first case in the literature with AIH-PBC overlap syndrome concurrent by ITP and AIHA which suggest the presence of shared genetic susceptibility factors in multiple autoimmune conditions including AIH, PBC, ITP and AIHA.

Prognostic value of increased B type natriuretic peptide in cases with acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a systemic disease with a rising incidence. Cardiac dysfunction may occur as an early complication of AP. B type natriuretic factor (BNP) is a diagnostic and prognostic indicator of cardiac disorders. Therefore, in this study we aimed to assess the relationship between serum BNP concentrations and severity of AP. METHODS: Patients with AP who were admitted to gastroenterology clinic of our center, were included in this study. BNP measurements were performed twice, once on admission to the hospital and another after clinical and laboratory remission of the disease. All patients underwent echocardiography, abdominal ultrasonography and/or computed tomography chest X-ray and routine biochemical assays. Disease severity was determined by Ranson, Balthazar and Glasgow scoring systems. RESULTS: A total of 55 patients with AP (33 male, 60%) were enrolled in the study. Causes of AP were biliary in 32 patients (58%), alcoholic in 10 (18%), idiopathic in 8 (15%), hyperlipidemic in 4 (7%) and ERCP related in one patient (2%), respectively. Serum BNP levels in first 2 days of admission and after the clinical and laboratory remission of disease were 444 ± 295.9 and 124 ± 109.5 pg/ml, respectively (p<0.001). Increased serum BNP levels were positively correlated with severity of the disease (p<0.001). We could not find a difference between serum BNPe levels of edematous and necrotizing patients (P = 0.683). CONCLUSION: Increased serum BNP levels might be a plausible indicator of severity of AP during the course of the disease.

Serum complement C4 in chronic hepatitis C: correlation with histopathologic findings and disease activity.

BACKGROUND/AIMS: Hepatitis C virus leads to chronic liver disease, cirrhosis and hepatocellular cancer. Viral markers and other laboratory tests used in the diagnosis and follow-up of chronic hepatitis C do not correlate well with disease activity and liver histopathology. Therefore, alternative tests that indicate disease activity and relate with liver biopsy findings are needed. We aimed to investigate the relationship between serum complement levels and biopsy findings in patients with chronic hepatitis C. METHODS: One hundred cases (70 patients, 30 healthy controls) were included in the study. Patients were divided into two groups: chronic hepatitis C patients with high transaminase levels were evaluated as the first group and patients with normal transaminase levels as the second group. Patients with a high transaminase level were biopsied and activity scores were evaluated against complement C3c and C4 levels. In addition, demographic data and laboratory tests were evaluated. Patients with chronic hepatitis C without proteinuria, acute phase response, cirrhosis, or coinfection with another hepatitis virus were included in the prospective study. RESULTS: Serum complement C3c (p<0.01) and C4 (p<0.01) levels were significantly lower in the first group than the second group. Serum complement C3c levels did not correlate with laboratory tests, hepatitis C virus-RNA levels, histological activity index, or fibrosis scores in patients with high transaminase levels, whereas complement C4 levels showed significant correlation with alanine aminotransferase (r: -0.368, p: 0.001) and histological activity index (r: -0.639, p: 0.001). We could not find any relation between serum complement C4 level and fibrosis. CONCLUSIONS: Serum complement C4 levels correlate with the histological activity index of the Knodell scoring system.

Is the measurement of inferior thyroid artery blood flow velocity by color-flow Doppler ultrasonography useful for differential diagnosis between gestational transient thyrotoxicosis and Graves' disease? A prospective study.

OBJECTIVE: To determine the role of peak systolic velocity, end-diastolic velocity and resistance indices of both the right and left inferior thyroid arteries measured by color-flow Doppler ultrasonography for a differential diagnosis between gestational transient thyrotoxicosis and Graves' disease during pregnancy. METHODS: The right and left inferior thyroid artery-peak systolic velocity, end-diastolic velocity and resistance indices of 96 patients with thyrotoxicosis (41 with gestational transient thyrotoxicosis, 31 age-matched pregnant patients with Graves' disease and 24 age- and sex-matched non-pregnant patients with Graves' disease) and 25 age and sex-matched healthy euthyroid subjects were assessed with color-flow Doppler ultrasonography. RESULTS: The right and left inferior thyroid artery-peak systolic and end-diastolic velocities in patients with gestational transient thyrotoxicosis were found to be significantly lower than those of pregnant patients with Graves' disease and higher than those of healthy euthyroid subjects. However, the right and left inferior thyroid artery peak systolic and end-diastolic velocities in pregnant patients with Graves' disease were significantly lower than those of non-pregnant patients with Graves' disease. The right and left inferior thyroid artery peak systolic and end-diastolic velocities were positively correlated with TSH-receptor antibody levels. We found an overlap between the inferior thyroid artery-blood flow velocities in a considerable number of patients with gestational transient thyrotoxicosis and pregnant patients with Graves' disease. CONCLUSIONS: This study suggests that the measurement of inferior thyroid artery-blood flow velocities with color-flow Doppler ultrasonography does not have sufficient sensitivity and specificity to be recommended as an initial diagnostic test for a differential diagnosis between gestational transient thyrotoxicosis and Graves' disease during pregnancy.

Selective transitional zone sampling approach versus random biopsy in cases with malignant liver masses: is there any superiority?

BACKGROUND/AIMS: Currently, the diagnostic sensitivity of malignant liver mass biopsies is an important problem in the definitive diagnosis. In this study, we aimed to investigate the role of selective peripheral approach to lesion biopsies for diagnostic sensitivity of liver masses. MATERIALS AND METHODS: Between June 2007 and March 2011, totally 88 patients (50 male, 38 female), referred to our Interventional Radiology Department for sonographically guided Tru-cut biopsies for liver lesions, were examined.All biopsies were performed by an experienced radiologist with an 18-gauge Tru-cut biopsy needle with a spring-loaded biopsy gun under sonographic guidance. We describe two locations (peripheral and central) for liver lesions, with the inner 2/3 part of the mass as central and the outer 1/3 part as peripheral. We obtained biopsy from both of these locations, and samples were transferred to the Pathology Department separately. RESULTS: According to pathological and immunohistochemistry studies, there were 42 hepatocellular carcinomas and 46 metastases. All of the metastatic tumors were stained by cytokeratin (10 lung adenocarcinoma, 15 breast adenocarcinoma, 16 gastrointestinal tract, 4 prostate, and 1 malignant melanoma of these 46 metastases were reported as primary). According to histopathological results, diagnostic sensitivity was 97.7% in peripherally located biopsies and 86.3% in biopsies taken from the center of the masses (p=0.0063). CONCLUSIONS: Selective peripheral biopsy approach in Tru-cut biopsies of liver lesions has better sensitivity rates for histopathologic diagnosis compared to the centrally located and random biopsies.

Electrocardiographic changes and importance of repolarization changes in cases with acute pancreatitis.

BACKGROUND/AIMS: Acute pancreatitis is a systemic disease with high mortality. The most common electrocardiography finding in acute pancreatitis cases is reported to be nonspecific repolarization changes in the literature. Recently, it is reported that repolarization changes carry high mortality risk. In this study, we aimed to investigate the association between repolarization changes and prognosis in acute pancreatitis cases. METHODS: Patients with acute pancreatitis referred to gastroenterohepatology clinic between 2009 and 2010 were included into the study. Echocardiography, electrocardiography, chest graph, abdominal sonography and/or computerized tomography, Ranson's and Glasgow's parameters and routine biochemistry tests of all patients were evaluated. RESULTS: A total of 55 cases [F/M: 22 (40%) / 33 (60%)] were included into the study. Thirty-nine of acute pancreatitis cases (70%) had electrocardiography changes. Electrocardiography changes were seen most frequently in cases with biliary (73%) and alcohol dependant pancreatitis cases (21%). The most frequently seen electrocardiographic finding was lateral early repolarization. There was a significant correlation between lateral early repolarization and Ranson score (p = 0.005). CONCLUSION: Early repolarization is the most common electrocardiographic findings and consistent with severity of acute pancreatitis cases.

Lipid profile changes and importance of low serum α-lipoprotein fraction (high-density lipoprotein) in cases with acute pancreatitis.

OBJECTIVES: Acute pancreatitis (AP) is a common systemic inflammatory disorder of the pancreas. The data related to the lipid changes in patients with AP were insufficient. In this study, we aimed to investigate the relation between high-density lipoprotein (HDL) and the other lipid parameters and the severity of the disease in AP cases. METHODS: Seventy-five cases admitted to the Gastroenterohepatology Clinic with diagnosis of AP were included in the study. Ranson scores and Glasgow scores were used for prognosis. Lipid parameters were evaluated for the first 24 hours and after clinic and laboratory remission. RESULTS: The causes of the disease among patients included in the study were as follows: 44 biliary origin (58.7%), 14 alcohol dependent (18.7%), 10 idiopathic (13.3%), 6 hyperlipidemic (8%), and 1 endoscopic retrograde cholangiopancreatography dependent (1.3%). Triglyceride (TG) levels of the patients included in the study measured in the first 2 days were significantly higher than TG levels measured after clinic and laboratory remission (P = 0.013). High-density lipoprotein was significantly lower in alcoholic and hypertriglyceridemic AP cases. There was a statistical correlation between HDL and Ranson (P = 0.023). CONCLUSION: The low levels of HDL in AP cases during acute attack are associated with severity of the disease.

The role of Helicobacter pylori in patients with hypothyroidism in whom could not be achieved normal thyrotropin levels despite treatment with high doses of thyroxine.

BACKGROUND: Helicobacter pylori infection is a most frequent cause of chronic gastritis. H. pylori may decrease absorption of oral thyroxine by decreasing gastric acid secretion in the stomach. In this study, we aimed to investigate the change in thyroid function tests of the cases after H. pylori eradication who were not responding to high doses of thyroxine treatment before H. pylori eradication. METHODS: Hypothyroid cases who were not responding to high doses of thyroxine among the ones presented to Endocrinology and Gastroenterohepatology Clinics of Sisli Etfal Training and Research Hospital between 2009 and 2010 were included in the study. Thyroid function tests were performed two times in all cases before and after H. pylori eradication. Duodenal, antral and corporal biopsies, and jejunal aspirates and biopsies were taken during upper gastrointestinal system endoscopies performed in all patients. Cases without intestinal pathology were included in the study. RESULTS: Serum thyrotropin (TSH), free T3, and free T4 values before H. pylori eradication were 30.5 ± 28.8 IU/mL, 2.64 ± 0.56 pg/mL, and 0.92 ± 0.32 ng/mL, respectively, and after eradication were found to be 4.2 ± 10.6 IU/mL, 3.02 ± 0.61 pg/mL, and 1.3 ± 0.34 ng/mL, respectively (p values <.001, .002, and <.001, respectively). After H. pylori eradication treatment, TSH decreased in all of the cases, factitious thyrotoxicosis developed in % 21 of these cases. CONCLUSION: In hypothyroid cases, H. pylori gastritis may be responsible for an inadequate response to the treatment. H. pylori eradication in the cases receiving high doses of thyroxine has a risk for thyrotoxicosis.

Could complement C4 be an alternative to biopsy for chronic hepatitis B histopathologic findings?

BACKGROUND: Hepatitis B leads to chronic liver disease, cirrhosis, and hepatocellular cancer. Viral markers and other laboratory tests used in diagnosis and follow-up of chronic hepatitis B (CHB) do not correlate well with disease activity and liver histopathology. For this reason, alternative tests that indicate disease activity are needed. We aimed to investigate the utility of serum complement levels for follow-up in patients with CHB with normal and high transaminase levels. METHODS: One hundred forty-three patients that were evaluated between 2009 and 2010 were included in the study. Hepatitis B early antigen negative CHB cases with high transaminase levels were evaluated as the first group, and cases with normal transaminase level (inactive hepatitis B surface antigen carrier) as the second group, patients with cirrhosis were included as a third group. Age, sex, hepatitis B surface antigen, anti-HBcAg IgM, hepatitis B early antigen, anti-δ, anti-HCV, anti-HIV, serum hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT), complement C3, and C4 levels of both groups were compared. The relationship between Knodell histologic activity index (HAI) score and fibrosis in liver biopsy specimens and serum complement levels of cases with high transaminase levels were investigated. FINDINGS: There were 49 patients with CHB with high transaminase levels; (Female/Male: 22/27). Mean age was 42.3±15.7 y, ALT=104.41±101.74, AST=69.7±65.2, GGT=35.37±20.4, C3 level=104.2±28.8, C4=16.11±4.17, and HBV DNA >2000 IU/mL (>105 copies/mL) in all cases. Remaining 27 patients had cirrhosis. There were 67 patients with CHB with normal transaminase levels (Female/Male: 32/35). Mean age was 39.56±12.9 y, ALT=22.7±5.5, AST=22±5.18, GGT=48.8±60.4, C3=117.85±22.15, and C4=21.44±5.46. Serum complement C4 level in 4 of the CHB cases with normal transaminase levels was low. Serum C3 (P=0.024) and C4 (P=0.001) levels in patients with CHB with high transaminase level were significantly lower. Low serum complement levels were negatively correlated with Knodell-HAI scores in patients with high transaminase levels (r=-0.84; P<0.001). There was no correlation between HAI and HBV DNA, AST, ALT, and GGT. There was no significant correlation between complement C3 and C4 levels and ALT, AST, HBV DNA, and GGT in any of the groups. Child score in patients with cirrhosis negatively correlated with both C3 (P=0.001) and C4 levels (P=0.001). Complement levels in patients with cirrhosis and CHB with high transaminase levels did not significantly differ. RESULTS: Serum complement C4 levels (in contrast to virologic markers and transaminases) significantly correlate with liver biopsy findings and may be a useful indicator of disease activity and/or damage in patients with CHB with high transaminase levels.

Infliximab- and azathioprine-related severe neutropenia and thrombocytopenia in a case with Crohn's disease.

A 25-year-old female patient with Crohn's disease had been using azathioprine and metronidazole for an extended period because of recurrent perianal and rectovaginal fistulae. Infliximab was added to the treatment regimen following postoperative recurrence of a rectovaginal fistula. Upon the development of severe neutropenia and thrombocytopenia after the third dose of infliximab, azathioprine and infliximab were stopped. Neutropenia work-up did not reveal any other cause. Neutropenia was ameliorated with use of granulocyte colony-stimulating factor. Treatment was restarted with infliximab alone upon leakage from the rectovaginal fistula with no hematologic toxicity. This case was considered as a serious adverse effect of infliximab and azathioprine combination therapy.