Suleyman Uraz

Serum levels of hepatoprotective peptide adiponectin in non-alcoholic fatty liver disease.

Objective Adiponectin is an adipose tissue-specific protein that has anti-inflammatory, antidiabetic and antiobesity effects. It has been suggested that adiponectin has a hepatoprotective role. Non-alcoholic fatty liver disease (NAFLD) is becoming more prevalent with increasingly adverse clinical outcomes. In this study, serum adiponectin levels were investigated in patients with NAFLD to determine its possible role on hepatic inflammation and injury. Methods Twenty-nine biopsy-proven NAFLD patients (14 women, 15 men) with elevated liver enzymes, 20 clinically diagnosed NAFLD patients (13 women, seven men) with normal liver enzymes, and 20 healthy adults (10 women, 10 men) were enrolled. From fasting blood samples, serum adiponectin levels were measured by enzyme-linked immunosorbent assay. The body mass index, serum glucose, insulin, cholesterol and triglyceride levels were determined. Results Serum adiponectin levels were 4.99±2.1, 9.49±3.91 and 7.74±4.41 μ/ml in the NAFLD with elevated liver enzymes, NAFLD with normal liver enzymes and healthy adult control groups, respectively. The mean serum adiponectin level in the NAFLD with elevated liver enzymes group was significantly lower than those of other groups tested (P<0.001). Insulin, cholesterol and triglyceride levels of NAFLD patients with elevated liver enzymes were significantly higher than control groups (P<0.05) but were not significantly different from the NAFLD group with normal liver enzymes (P>0.05). On histopathologic examination, the mean serum adiponectin levels of non-alcoholic steatohepatitis patients with grade 2 or more inflammatory activity was significantly lower than patients with grade 1 inflammatory activity (P=0.013). Conclusion Serum adiponectin levels are significantly lower in NAFLD patients with elevated liver enzymes. Non-alcoholic steatohepatitis patients show lower levels of adiponectin with higher grades of inflammation.

N-acetylcysteine expresses powerful anti-inflammatory and antioxidant activities resulting in complete improvement of acetic acid-induced colitis in rats

Abstract High free radical production, low antioxidant capacity and excessive inflammation are well known features in the pathogenesis of inflammatory bowel disease. N-acetylcysteine (NAC) is a powerful antioxidant and a scavenger of hydroxyl radicals. Recently, NAC has also been shown to have anti-inflammatory activities in tissues. Our study objective was to investigate the effects of NAC on tissue inflammatory activities using an ulcerative colitis model induced by acetic acid (AA) in rats. Wistar rats (n = 32) were divided into four groups. AA-induced colitis was performed in two of the groups while the other two groups were injected with saline intrarectally. One of the AA-induced colitis groups and one of the control groups were administered NAC (500 mg/kg/day) intrarectally, and the other control groups were given saline. After 4 days, colonic changes were evaluated biochemically by measuring proinflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6], myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) levels in tissue homogenates and by histopathological examination. AA caused colonic mucosal injury, whereas NAC administration suppressed these changes in the AA-induced colitis group (p < 0.001). AA-administration resulted in increased TNF-α, IL-1β, IL-6, MPO and MDA levels, and decreased GSH and SOD levels, whereas NAC reversed these effects (all p < 0.001). In conclusion, the present study proposes that intrarectal NAC therapy has a dual action as an effective anti-inflammatory and an antioxidant, and may be a promising therapeutic option for ulcerative colitis.

Celiac disease in an adult Turkish population with type 1 diabetes mellitus.

Celiac disease is a frequent cause of morbidity among patients with type 1 diabetes mellitus. In this study our objective was to determine the prevalance of celiac diasease in a Turkish adult population with type 1 diabetes mellitus. Patients included 122 type 1 diabetes cases from adult diabetes clinic. Total IgA and IgA-antiendomysial antibody (AEA) assays were performed. Patients positive for IgA-AEA were asked to undergo small intestinal biopsy. Of the 122 patients, none was IgA deficient and 3 had positive IgA-AEA results (2.45%). All three of these patients had biopsies diagnostic of celiac disease. The body mass index (BMI) values of patients with positive AEA were significantly lower than normal (P = 0.024). Among the gastrointestinal complaints there was an association between early satiety and AEA positivity (P = 0.02). None of the other gastrointestinal complaints or age, duration of diabetes, glycosylated hemoglobin values, or insulin doses used were found to be related to AEA positivity. Celiac disease has a high prevalence among Turkish paients with type 1 diabetes mellitus. Screening for IgA-AEA during routine investigations of type 1 diabetic patients is important to prevent celiac-associated symptoms.

The efficacy, safety and tolerability of pantoprazole-based one-week triple therapy in H. pylori eradication and duodenal ulcer healing

SUMMARY Objective: Recently, proton pump inhibitor (PPi)-based triple therapy has been recommended as a first line treatment in the eradication of Helicobacter pylori. The aim of this open, multicentre trial was to investigate the efficacy, safety, tolerability and the ulcer healing rate of a triple regimen consisting of pantoprazole∗ 40 mg, clarithromycin 500 mg and amoxicillin 1000 mg twice daily for 7 days, in the eradication of H. pylori in patients with duodenal ulcer in Turkey. Research design and methods: H. pylori infection was assessed by histological examination and rapid urease test at baseline and 4 weeks after the completion of the therapy. Seventy-seven patients were enrolled, 5 were excluded due to various reasons and 72 completed the entire course of the trial. Results: H. pylori eradication was confirmed in 49 of these patients; the eradication rate was 68% by per-protocol analysis and 63.6% by intention-to-treat analysis. The ulcers were completely healed in 61 patients (85%) at the second endoscopic examination. Drug compliance was excellent (97.3%) and there were no serious adverse events. Conclusion: Pantoprazole-based 1-week triple therapy was well tolerated and the ulcer healing rate was high (85%). Relatively low H. pylori eradication rates may be attributed to rising antibiotic resistance over recent years. A large scale, comparative study with other PPi-based regimens is warranted based on the results of this open study with the pantoprazole-based regimen.

Serum iron levels and hepatic iron overload in nonalcoholic steatohepatitis and chronic viral hepatitis.

Our objective was to determine the effect of serum iron levels and hepatic iron overload on hepatocellular damage in nonalcoholic steatohepatitis (NASH) and to compare this with chronic viral hepatitis. Twenty-five patients who had elevated transaminase levels on at least two occasions, without any evidence of viral and autoimmune hepatitis and diabetes, without a history of significant alcohol use, and with a liver biopsy consistent with NASH were enrolled in the study. Twenty-five patients with chronic viral hepatitis (13 patients with chronic hepatitis C and 12 with chronic hepatitis B) who were not under any antiviral treatment were taken as controls. Metabolic factors were studied in the NASH and chronic hepatitis groups. Biopsy specimens were stained with hematoxylin–eosin, and the grade of steatosis and the stage of fibrosis were evaluated as I, II, or III, I being mild and III being severe. Iron overload in the hepatic tissue was studied by Prussian blue staining. Serum ALT, AST, ALP, GGT, globulin, and ferritin levels were comparable in both steatohepatitis and chronic viral hepatitis groups. However, patients with chronic hepatitis had a lower albumin level and a higher serum iron level, with higher transferrin saturation. Among patients with NASH, mild, moderate, and severe steatosis was found in 7, 10, and 8 patients, respectively. Inflammatory infiltration was grade I in 24 patients and grade III in 1 patient. Fibrosis was mild in 12 patients and 13 patients had no fibrosis. Among patients with chronic viral hepatitis, inflammatory infiltration of grade I was seen in 11 patients, grade II in 11 patients, and grade III in 3 patients. Fibrosis was mild in 9 patients, moderate in 13 patients, and severe in 2 patients; 1 patient had no fibrosis. Compared to patients with NASH, those with chronic viral hepatitis cases had more severe inflammatory infiltration and fibrosis (P < 0.01). While five patients with chronic viral hepatitis had mild iron overload, patients with NASH had no hepatic paranchymal iron overload. Neither NASH nor chronic viral hepatitis revealed a relationship between hepatic iron overload and disease activity. This suggests that the iron overload actually may be a result of hemachromatosis gene mutation. The absence of hepatic parenchymal iron overload in the NASH group and only mild iron accumulation in the chronic hepatitis group may be explained by a lower frequency of the gene mutation in our country.

Ciprofloxacin and Achilles' tendon rupture: a causal relationship.

Fluoroquinolones are commonly used antimicrobials with favorable pharmacokinetic properties and a broad spectrum of activity. These drugs are very well tolerated. Tendinous involvement is a rare complication of fluoroquinolone use [1]. We describe a case of spontaneous rupture of the Achilles tendon associated with ciprofloxacin use on one side, and the development of the same complication on the other side 1 year later following another use of the same drug. A 32-year-old male surgeon presented with a severe pain in his right Achilles tendon region while walking. He recalled no specific injury. He had used ciprofloxacin (500 mg tablets twice daily, 10 days) for typhoid fever 1 month ago. The right Achilles tendon was tender to mild palpation. The clinical suspicion of Achilles tendon rupture was confirmed by MRI. He was treated surgically with an uneventful outcome. One year later he suddenly fell down with severe pain in his left foot while walking. He had again used ciprofloxacin (500 mg tablets twice daily, 10 days) for urinary tract infection 1 month ago. An orthopedic surgeon diagnosed left Achilles tendon rupture, confirmed by MRI (Fig. 1). Surgical repair was again carried out uneventfully. After the first report of fluoroquinolone-induced tendinitis in 1983 [2], many others have reported it subsequently [3, 4, 5, 6, 7]. The tendinopathy appears within a few weeks of the use of the drug, although extremes (1 day to 5–6 months) have also been reported [5, 6]. The patients are usually elderly. The risk factors are renal failure, steroid use, and collagen vascular diseases [6, 7]. However, the mechanism of this complication and the reason why tendinopathy and rupture occur more frequently in the Achilles tendon are not precisely known. Fluoroquinolone use and repeated tendon ruptures in our patient, who did not have any risk factors, both suggested a clear causal relationship and emphasized the roles of individual factors. Because these antimicrobials are in common use, physicians should consider this side effect even in the absence of the risk factors.

Cell Transplantation: A Possible Alternative to Orthotopic Liver Transplant (OLT)

The progress made in the field of liver organ transplantation has revolutionized the treatment of a wide spectrum of liver diseases. Orthotopic liver transplantation (OLT), which requires removal of the entire native liver and transplantation of a high quality graft, has become an almost routine procedure with 1-year survival rates higher than 80%. However, with the ensuing interminable increase in the waiting list, the current major limitation is the considerable shortage in organ donors and the need of timely availability of suitable livers. As a result, although death rate after surgery is slowly decreasing, the number of total deaths in waiting list patients is steadily rising. Several solutions have been proposed to overcome this problem, such as legislative measures, mass media campaigns, optimization of available organ allocation, or innovative surgical techniques such as split-liver, living donor, non-heart beating donor, and domino transplantation. However, these measures have been met with only limited success in providing enough liver grafts (Neuberger, 2000; Thalheimer & Capra, 2002). Hence, the research community endeavoured to establish clinical alternatives to liver transplantation. Cell-based therapies are emerging as an alternative to whole-organ transplantation, which has shown initial promise in both animal models and clinical cases. This novel technique may provide functional liver support while the native liver regenerates in patients of acute liver failure, may provide a short-term “bridge” to sustain critical patients until OLT, or may aid in replacing a missing enzyme function in metabolic conditions with the aim of avoiding OLT. Some of the most promising cells types that could be used in this emerging field are hepatocytes, embryonic stem cells (ESC), mesenchymal stromal cells (MSC), amnion epithelial (AE) cells, and induced pluripotent stem cells (iPSC).

A rare gastric outlet anomaly: pyloric ostium on incissura angularis.

Congenital gastric outlet anomalies are rarely seen defects resulting from early embryologic development of foregut. We report a case of congenital pyloric outlet anomaly in a 60-year-old man with mild postprandial epigastric discomfort of approximately 3 months’ duration. Endoscopic examination of the stomach showed a pyloric ostium on incissura angularis connecting the stomach to the duodenum. Usual site of pylorus at the end of antrum was closed like a sac. No signs of acute or chronic peptic ulcer were noted. A biopsy was taken from the region showed normal mucosal layers with a mild gastritis. There was no history of surgery, ulcer disease, or use of any medication. The case was considered to be congenital in origin and was successfully treated conservatively with proton-pump inhibitors and gastrokinetics.

On hepatitis B virus and vasculitis

We have read the paper of Lee et al. with great interest [1]. They examined whether resolved hepatitis B virus (HBV) infection was associated with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and affected AAV activity at diagnosis and prognosis. Fifty patients had antiHBc, and 61 had anti-HBs. In eosinophilic granulomatosis with polyangiitis (EGPA) patients, those with HBsAg negative/anti-HBc positive showed the higher initial mean Birmingham vasculitis activity score (BVAS) and five factor scores (FFS) than those without, significantly increased risk of relapse of EGPA than those having not and meaningfully lower cumulative relapse-free survival rates than those without during the follow-up duration. They included HBsAg-negative and anti-HBc-positive patients to represent resolved HBV infection and compared with HBsAg-negative and anti-HBc-negative patients. The data presented in the study are enough to pick and organize groups considering anti-HBs status with corresponding patient numbers (Fig. 1). Among anti-HBc (+) group, those with anti-HBs (+) (A in the Fig. 1) represent resolved HBV, while anti-HBs (−) ones (B) are named anti-HBc-only. Anti-HBc-only, as discussed in the paper, is a heterogeneous group potentially including acute, resolved, chronic HBV, and occult HBV infections [2]. Among anti-HBc (−) individuals, anti-HBs (+) ones (C) represent vaccinated ones, while anti-HBs (−) ones (D) are neither vaccinated nor infected individuals. A and B denote exposure to the virus, while C represents exposure to a recombinant HBsAg. Only D is free of exposure to neither viral nor recombinant antigens and provides an opportunity to test the HBsAg–vasculitis association as a control group. HBV and vasculitis association has been attributed to the development through immune-complex reactions; immune complexes of HBsAg with anti-HBs precipitate and become entangled in the walls of small-to-medium-sized vessels, resulting in both injuries in adjacent tissues and aneurysmal dilatation or occlusion of affected vessels [3]. Beside numerous papers reporting vasculitides associated with HBV infection, there have been some reports with recombinant HBV vaccination [4–10]. In the presented study, among anti-HBc negative individuals, further differential analysis of C and D may probably contribute to understanding of any effect of HBsAg on development and clinical course of vasculitides. Rheumatology INTERNATIONAL

Does resolved HBV or anti-HBc-only carry the same risk of HBV reactivation?

We have read the study of Yeo et al. with great interest. They reviewed 75 lymphoma patients with resolved hepatitis B virus (HBV) infection over a two-year period for HBV reactivation. They defined resolved HBV as documented positive anti-HBc, negative HBsAg, and negative HBV DNA prior to initiation of rituximab or within six months of rituximab initiation. The resolved HBV infection is defined by clearance of HBsAg with development of antibody to HBsAg. The definition in the study (positive anti-HBc, negative HBsAg, and negative HBV DNA) can be either ‘‘resolved’’ hepatitis (if the HBs antibodies are positive) or anti-HBc-only (if the HBs antibodies are negative). The HBs antibodies were tested in 65 patients and reported positive in 54. The patients in the study include 10 undetermined (resolved or anti-HBc-only), 54 resolved, and 11 anti-HBc-only. They reported three reactivations: one in undetermined group and two in anti-HBc-only. Anti-HBc-only represents a heterogeneous group of acute, resolved, chronic HBV, and occult HBV infections. Measurement of serum anti-HBs responses after the administration of a booster HBV vaccination can be useful to further distinguish this serological profile. Anti-HBc-only represents a much higher risk of reactivation after chemotherapy or immunosuppressive therapy. In a recent meta-analysis, in 20 studies involving 1672 patients not receiving antiviral prophylaxis, the reactivation risk was 14% (95% confidence interval (CI) 9.4%–19%) in 388 patients who had antiHBc-only versus 5.0% (95% CI: 3.0%–7.0%) in 1284 patients who also had anti-HBs. It was also shown that anti-HBs reduced reactivation risk with a pooled OR of 0.21 (95% CI: 0.14–0.32) versus patients with antiHBc-only. Similar results were found when limiting the analysis to rituximab chemotherapy (OR1⁄4 0.19, 95% CI: 0.11–0.32) and lymphoma (OR1⁄4 0.18, 95% CI: 0.11–0.28). The protective effect of anti-HBs against HBV reactivation was also reported in solid organ transplanted patients. Anti-HBc-only represents a much higher risk of reactivation after chemotherapy or immunosuppressive therapy compared to resolved HBV infection. The risk of reactivation should be studied separately.