Filiz Akyuz

Occult HBV infection and YMDD variants in hemodialysis patients with chronic HCV infection.

BACKGROUND/AIMS End-stage renal disease patients on chronic hemodialysis are at risk for both hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Although the prevalence is unknown in hemodialysis patients, occult HBV infection is frequent in subjects with chronic HCV infection. We aimed to investigate (1) the prevalence and clinical impact of occult HBV infection in hemodialysis patients with chronic HCV infection, and (2) the frequency of YMDD variants (tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase) in this setting. METHODS Thirty-three anti-HCV and HCV-RNA-positive, HBsAg-negative hemodialysis patients (mean age 36.9+/-10.4 years, 22 male) were admitted to this study. HBV-DNA (Innogenetics kit) and HCV-RNA (Cobas Amplicor HCV kit) were investigated by polymerase chain reaction technique (PCR). YMDD mutation was studied in all HBV-DNA-positive patients by the BOOM method. RESULTS HBV-DNA was detected in 12 of 33 patients (36.4%) by PCR. Their mean age was 33.0+/-9.0 years. Age, dialysis period (years) and biochemical parameters were not significantly different in patients with and without occult HBV infection. YMDD variants were identified in six of 12 (50%) patients with occult HBV infection. CONCLUSIONS Occult HBV infection is frequent in hemodialysis patients with chronic HCV infection. YMDD variants are common in this setting.

Efficacy of Tenofovir in Patients with Lamivudine Failure Is Not Different from That in Nucleoside/Nucleotide Analogue-Naïve Patients with Chronic Hepatitis B

ABSTRACT We evaluated the efficacy of tenofovir disoproxil fumarate (TDF) in patients with lamivudine failure (LAM-F) in comparison with that in nucleoside/nucleotide analogue (NA)-naïve patients with chronic hepatitis B (CHB). The criteria for inclusion were being NA naïve or having previous LAM-F and receiving TDF therapy for at least 6 months. Biochemical and virological tests were performed at the baseline, at 3-month intervals in the first year, and every 6 months thereafter. The primary outcome measure for efficacy was a complete virological response (CVR), defined as an HBV DNA level of <20 IU/ml. CVR rates were calculated by Kaplan-Meier analysis, and a multivariate Cox proportional-hazard model was generated in order to find predictive factors independently associated with the time to a CVR. We included 197 patients in the study (136 males; mean age, 43 ± 12 years; 105 patients were NA naïve). Sixty-five patients had hepatitis B e antigen (HBeAg)-positive CHB. The median duration of TDF treatment was 29 (range, 6 to 52) months. Seventy-one patients (77%) in the LAM-F group were treated with TDF add-on therapy. The CVR rates of the NA-naïve and LAM-F groups were comparable in HBeAg-negative (94% versus 96% at month 36, P = 0.10) and HBeAg-positive patients (67% versus 83% at month 36, P = 0.48). According to the multivariate Cox regression model, only HBeAg positivity (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.26 to 0.59; P < 0.001) and a high baseline HBV DNA level (HR, 0.44; 95% CI, 0.29 to 0.67; P < 0.001) had a significant influence on the time to a CVR. The similar cumulative CVR rates during the follow-up show that TDF has comparable efficacy in lamivudine-experienced and NA-naïve patients, and the presence of resistance mutations did not alter the response rates.

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 Childs B and 11 Childs 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.

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).

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.

Non-alcoholic fatty liver disease: What has changed in the treatment since the beginning?

Non-alcoholic fatty liver disease (NAFLD) is an umbrella term to describe the entire spectrum of this common liver disease. In patients with NAFLD, especially those with non-alcoholic steatohepatitis (NASH), most often have one or more components of the metabolic syndrome, but this is not universal. Although most patients with NAFLD share many clinical features, only a subset of patients develops significant liver inflammation and progressive fibrosis. On the other hand, not all patients with NASH exhibit insulin resistance. NASH can be seen in patients who are lean and have no identifiable risk factors. Many clinical studies have tried numerous drugs and alternative medicine, however, investigators have failed to identify a safe and effective therapy for patients with NASH. As summarized, the heterogeneity of pathogenic pathways in individual patients with NASH may warrant the development of an individualized treatment according to the underlying pathogenic pathway. The differentiation of pathogenetic targets may require the development of diagnostic and prognostic biomarkers, and the identification of genetic susceptibilities. At present, evidence-based medicine provides only a few options including life-style modifications targeting weight loss, pioglitazone and vitamin E in non-diabetic patients with biopsy-proven NASH.

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

Abstract 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.

Prevalence and virological features of occult hepatitis B virus infection in female sex workers who work uncontrolled in Turkey.

Background: There is little information about the prevalence of occult hepatitis B virus infection (OHBVI). We have investigated the prevalence and virological features of OHBVI among female sex workers (FSWs) in Istanbul.

Efficacy of pegylated interferon-α treatment for 24 months in chronic delta hepatitis and predictors of response.

BACKGROUND To determine the efficacy of pegylated interferon-α (PEG-IFN-α) therapy for 24 months in chronic delta hepatitis (CDH). METHODS Patients with CDH who were treated by PEG-IFN-α2a or -2b for 24 months were included in the study. Demographic, biochemical and virological parameters were recorded at baseline and during follow-up. All included patients completed a treatment period of 24 months and at least a 6 month (range 6-60) follow-up period. Biochemical and virological response rates at end of treatment and end of follow-up were calculated, and predictors of sustained virological response (SVR) were analysed. RESULTS In total, 32 patients (22 males; mean age ± SD 42.7 ± 12 years) with CDH who were treated with PEG-IFN-α2a (180 µg) or -2b (1.5 µg/kg) once a week subcutaneously for 24 months were included in the study. All patients had compensated liver disease (25 [78%] were non-cirrhotic), increased transaminase levels and HDV RNA positivity at baseline. Genotypic analyses of HDV showed genotype I in all. Mean duration of follow-up was 19.5 months. At the end of treatment, virological response was achieved in 16 (50%) patients. SVR at the end of follow-up was achieved in 15 (47%) patients. A negative HDV RNA at 6 months of treatment was the only predictor of SVR (OR = 20; 95% CI 2, 195; P = 0.01). CONCLUSIONS PEG-IFN-α treatment achieved SVR in approximately half of the patients with CDH, and relapse rate was very low during the follow-up. Negativity of HDV RNA at 6 months may predict SVR in CDH.

Familial visceral myopathy with pseudo-obstruction, megaduodenum, Barrett's esophagus, and cardiac abnormalities

This report describes a new subgroup of familial visceral myopathy. Three patients from within this family were admitted to the hospital with pseudo-obstruction. Barium x-ray, abdominal plain film, esophageal manometry, colonoscopy, gastroscopy, and echocardiography were performed in all siblings for diagnostic evaluation. Two of our patients had surgery because of suspicion of acute abdomen. In one of them, full-thickness biopsy, which was performed during laparotomy, revealed findings that were compatible with familial visceral myopathy. Three siblings from this family with visceral myopathy, in which the parents were consanguineous, had megaduodenum, long-segment Barretts esophagus, and different cardiac abnormalities.