Ali Özden

Treatment of chronic delta hepatitis with lamivudine vs lamivudine + interferon vs interferon

Summary.  Chronic delta hepatitis is the most severe form of chronic viral hepatitis for which interferon (IFN) is the only available treatment. In 39 patients (25 were treatment‐naïve, 14 had previously used IFN), efficacy of 1‐year treatment with IFN (9 MU, t.i.w.) or lamivudine (LAM; 100 mg, q.d.) alone was compared with IFN and LAM combination (2 months of LAM to be followed by combination treatment). IFN monotherapy was given only to treatment‐naïve patients. In both treatment‐naïve and previous IFN users, end of treatment virological and biochemical responses were similar with IFN–LAM combination and superior to LAM monotherapy (P < 0.05). Improvement in liver histology occurred more often with IFN ± LAM than with LAM alone (P < 0.05). In treatment‐naïve patients, combination treatment was not superior to IFN monotherapy. After treatment discontinuation, virological and biochemical response rates decreased in LAM and IFN combination and IFN monotherapy. On treatment virological response at month 6 of treatment predicted sustained virological response. The results of this study suggest that addition of LAM to IFN for the treatment of delta hepatitis is of no additional value and that both treatment modalities are superior to LAM monotherapy.

Lamivudine prophylaxis for prevention of chemotherapy-induced hepatitis B virus reactivation in hepatitis B virus carriers with malignancies.

Summary.  Although hepatitis B virus (HBV) reactivation in HBV carriers undergoing immunosuppressive therapy is clearly documented, the role of antiviral prophylaxis in such individuals is still controversial. The aim of this study was to determine the efficacy of lamivudine prophylaxis in HBV carriers with haemato/oncological malignancies, who receive chemotherapy. Eighteen HBV carriers with malignancy, who were candidates for chemotherapy, were enrolled. Eight subjects (three with leukaemia, four with lymphoma and one with multiple myeloma) were enrolled for prophylactic lamivudine therapy. The remaining 10 patients (six with leukaemia, three with lymphoma and one with breast cancer) were not treated with lamivudine and were used as a control. Lamivudine was administered beginning on the same day as the chemotherapy and was maintained for a year after chemotherapy was discontinued. No HBV‐related mortality was observed in either group. In the lamivudine‐treated group, none of the subjects had clinical, biochemical or serological evidence of HBV reactivation during the time they were receiving chemotherapy and after their chemotherapy was discontinued. In contrast, five of the 10 HBV carriers not receiving lamivudine therapy experienced a reactivation of HBV infection. This reactivation of HBV was observed during the chemotherapy in four with one individual experiencing a HBV activation 12 months after chemotherapy was discontinued. No lamivudine‐related major adverse effects were observed. Hence prophylactic lamivudine treatment in HBV carriers with haemato/oncological malignancy receiving chemotherapy prevents chemotherapy‐induced HBV reactivation.

Clinical trial: insulin‐sensitizing agents may reduce consequences of insulin resistance in individuals with non‐alcoholic steatohepatitis

Background  Currently, although only a few therapies normalize the liver test abnormalities with/without improving the liver histology, no pharmacologic therapy has proved to be effective for the treatment of non‐alcoholic steatohepatitis.

Thrombophilic gene mutations in cirrhotic patients with portal vein thrombosis.

Objective Thrombophilic gene mutations have been reported to be associated with the formation of portal vein thrombosis (PVT). This study aimed to investigate the role of thrombophilic gene mutations in cirrhotic patients with PVT. Patients and methods A total of 74 cirrhotic patients (17 with PVT, 57 without PVT), and 19 non-cirrhotic patients with PVT and 80 healthy controls were included. Factor V Leiden G1691A, prothrombin G20210A and methylenetetrahydrofolate reductase C677T mutations were analysed by restriction fragment length polymorphism. Results Aetiologies and Child–Pugh distribution of cirrhotic patients with and without PVT were similar. Five of 17 (29%) of cirrhotic patients with PVT but only two of 57 (3.5%) of cirrhotics without PVT, five of 80 (6%) of controls and none of the 19 non-cirrhotic patients with PVT had factor V Leiden G1691A mutation (P<0.05). Prothrombin G20210A mutation was found in five (29%) cirrhotic patients with PVT while only two (3.5%) cirrhotic patients without PVT, one (5%) non-cirrhotic patient with PVT and two (2.5%) controls had this mutation (P<0.05). The frequency of the homozygote methylenetetrahydrofolate reductase 677C-T mutation was similar in all four groups. Conclusions Inherited thrombophilic gene mutations appear to increase the risk of PVT formation in cirrhotic patients but not in patients without liver disease in a cohort of Turkish patients.

NOD2/CARD15, NOD1/CARD4, and ICAM-1 gene polymorphisms in Turkish patients with inflammatory bowel disease

PurposeThe genetic susceptibility of people with certain NOD2/CARD15, NOD1/CARD4, and ICAM-1 gene variants to inflammatory bowel disease is still under investigation. The aim of this study was to investigate polymorphisms in the NOD2/CARD15 (R702W, G908R, and 3020insC), NOD1/CARD4 (E266K, D372N), and ICAM-1 (G241R, K469E) genes, which are known to be associated with inflammation, in Turkish patients with inflammatory bowel disease and healthy control groups.MethodsThe genotypes of 70 patients with endoscopically and histopathologically diagnosed Crohns disease (38 men, 32 women; mean age, 38.8 ± 1.3), 120 patients with ulcerative colitis (67 men, 53 women; mean age, 41.7 ± 1.3) and 106 healthy control subjects (37 men, 69 women; mean age, 35.7 ± 1.4), who stated that they had never had any prior bowel disease history, were compared. A polymerase chain reaction-restriction fragment length polymorphism analysis was performed for two variants of the ICAM-1 gene, the three main variants of the NOD2/CARD15 gene, and the E266K variant of the NOD1/CARD4 gene, and DNA sequencing was used for the D372N polymorphism of the NOD1/CARD4 gene.ResultsIn this study, the three previously described Crohns disease-predisposing variants of the NOD2/CARD15 gene and the polymorphisms examined in the NOD1/CARD4 and ICAM-1 genes were not found to be associated with ulcerative colitis or Crohns disease.ConclusionsThese findings suggest that the polymorphisms observed in the NOD2/CARD15, NOD1/CARD4, and ICAM-1 genes are not genetic susceptibility factors for Crohns disease or ulcerative colitis in Turkey.

Barrett's esophagus: Prevalence and its relationship with dyspeptic symptoms

Background and Aim:  Barretts metaplasia is a premalign condition which plays a pivotal role in the development of esophageal adenocarcinoma. It is considered a complication of chronic gastroesophageal reflux disease. Although esophageal adenocarcinoma is an uncommon cancer, its incidence is rapidly increasing. The aims of the present study were to determine the prevalence of Barretts metaplasia in outpatients referred for gastroscopy for upper gastrointestinal symptoms, and to clarify the relationship between Barretts metaplasia and upper gastrointestinal symptoms.

Cytokine gene polymorphisms in Turkish patients with inflammatory bowel disease

Objective. Crohns disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the bowel, the causes of which are not fully known. Ethnic differences in disease prevalence, familial aggregation of the disease and studies of twins provide the most important evidence to suggest that genetic factors play a role in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to examine the allelic polymorphisms that can determine the immune response levels in tumor necrosis factor alpha (TNFα), interleukin-1β (IL-1B), interleukin-1 receptor antagonist ( IL-1RN) and interleukin-10 (IL-10) genes and to investigate their roles in the inflammatory pathway in IBD. Material and methods. The study included 120 patients with UC and 70 patients with CD who were diagnosed either endoscopically or histopathologically. The control group comprised 105 healthy individuals who stated that they had never had any bowel disease during their life span. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method for polymorphisms in the TNFα gene at positions −308 and −238, the IL-10 gene at positions −1082 and −627, the IL-1B gene at −511 regions and the variable number of tandem repeat (VNTR) method for polymorphism in the intron 2 of the IL-1RN gene were performed. The results were analyzed on agarose gel electrophoresis. Results. No significant differences were found in the allele and genotype frequencies of the polymorphisms in the IL-1B, IL10, TNFα and IL-1RN genes between the patients with UC and CD and controls. Conclusions. The results suggest that these polymorphisms were not important risk factors in the susceptibility to IBD in Turkish patients.

The prevalence of celiac disease in patients fulfilling Rome III criteria for irritable bowel syndrome

BACKGROUND AND AIMS Celiac disease shares several symptoms which constitute some of the ROME criteria used for the diagnosis of irritable bowel syndrome (IBS), and as such many patients with underlying Celiac disease may be mistakenly diagnosed as having IBS. The aim of the present study was to determine the prevalence of Celiac disease in patients with IBS fulfilling ROME III criteria. MATERIALS AND METHODS Patients who fulfilled ROME III criteria for irritable bowel syndrome were screened for Celiac disease using the Biocard(TM) Celiac Disease Stick test, and patients who tested positive had their serum samples analyzed for antigliadin IgA and IgG, and anti-tissue transglutaminase IgA antibodies. Patients with detectable antibody levels underwent endoscopic duodenal biopsy to confirm a diagnosis of Celiac disease. RESULTS Two of 100 patients who were diagnosed as having irritable bowel syndrome as per the Roma III criteria were found to have elevated levels of serum antigliadin IgA and IgG, and anti-tissue transglutaminase IgA antibodies, with histological evidence of Celiac disease on examination of duodenal biopsy. Both patients were started on a gluten-free diet, showing significant improvement in their symptoms on follow-up. CONCLUSIONS Celiac disease is a common finding among patients labeled as IBS. Celiac disease must be considered in differential diagnosis of IBS especially in the therapy refractory group.

Adjuvant therapeutic plasma exchange in liver failure: assessments of clinical and laboratory parameters.

Background Therapeutic plasma exchange (TPE) seems to be an effective approach for clearing toxins, immune-mediated antigens, and other particles from the circulation. The aim of this study was to analyze the positive effects of TPE on clinical and biochemical parameters of liver failure. Patients and Methods Between January 2001 and March 31, 2005 individuals (men/women, 17/14; median age, 42.7±15.8 y) with acute and chronic liver failure who underwent a total of 113 TPEs (median session 3.7) were retrospectively reviewed. TPE was performed using the Fresenius AS-TEC 204 cell separator (Fresenius AG, Germany). The indication for TPE was severe coagulopathy (prothrombin time >20 s), severe hepatic encephalopathy, hyperbilirubinemia, and candidacy for liver transplantation. All patients were examined before and immediately after the last TPE session. Results When compared with baseline, there was significant improvement in hepatic encephalopathy stage (from median score 3.0 to 1.0, P=0.001), serum prothrombin time (from median 26.0 to 20.0 s, P=0.003), aminotransferases (P<0.001), and total bilirubin levels (from median 35.0 to 23.3 mg/dL, P<0.001) after TPE. Thirteen of the thirty-one individuals (41.9%) died in the hospital. The mean follow-up period of 18 survival patients was 35.9±5.6 months and 10 of those survived (55.6%, 10/18). No serious adverse effect of TPE was observed in any of the patients during or after completion of TPE. Only 6 patients experienced minor transfusion reactions. Conclusions TPE seems to be effective in improving hepatic encephalopathy stage and liver tests in individuals with acute and chronic liver failure. The data suggest that TPE is safe and tolerable in such individuals, however, overall survival remains poor despite TPE.

Sexual dysfunctions in HCV patients and its correlations with psychological and biological variables.

The frequency of sexual dysfunction (SD) is not very well known in patients with chronic hepatitis C. In this study, the prevalence of SD and its correlations with psychological and biological variables was assessed in 46 HCV positive patients. The mean age of patients was 46.4±9.4 y; the mean duration of HCV infection was 43.4±34.0 months; 52% were male; 89% were living with a spouse. SD was assessed using the Arizona Sexual Experiences Scale (ASEX), the level of anxiety and depression measured with the Hospital Anxiety and Depression Scale (HADS). Biochemical parameters were also assessed. Overall, as indicated by ASEX criteria, SD was observed in 35% of our patients. Of 24 males, 21% described SD; problems with drive (25%), arousal (17%) and erection (17%) were the most frequent complaints. Of 22 female patients, 50% described SD; problems with drive (55%) arousal (50%), and reaching orgasm (59%) were the most frequent complaints. Total ASEX scores were correlated with age (P<0.07, significant at trend level), education (P<0.001), and was higher in female patients (P<0.02). After controlling for the effects of age, sex, education, duration of HCV and marital status, depression levels could still significantly predict the SD (P<0.05). Moreover, even after controlling the effects of all other variables, gamma glutamyl transpeptidase (GGT) levels could predict the SD status of the patients (P<0.05). Our results indicate that the prevalence of SD was 35% in HCV-infected patients and the level of depression and GGT levels were predictive of patients SD status.