Gülseren Seven

Entecavir Treatment of Chronic Hepatitis D

BACKGROUND Hepatitis D virus (HDV) requires hepatitis B surface antigen (HBsAg) to propagate infection and cause disease. Entecavir is a nucleoside analog with potent antiviral efficacy, and in the woodchuck animal model it also decreased hepatitis B virus (HBV) cccDNA and woodchuck surface antigen. The aim of this study was to investigate the efficacy of entecavir in chronic hepatitis D (CHD). METHODS This single-center study was conducted in patients with compensated liver disease. All patients had to have detectable hepatitis HDV RNA and elevated levels of alanine aminotransferase (ALT). Entecavir was given at a dosage of 1 mg/d for 1 year. The primary end point was achievement of undetectable HDV RNA at the end of treatment. RESULTS Thirteen consecutive patients were assessed. All patients had detectable HDV RNA, and 8 had detectable HBV DNA at baseline. At the end of treatment, HBV DNA became undetectable in all patients (P = .001). No significant decline in HDV RNA, ALT, or quantitative HBsAg levels was observed. The primary end point of undetectable HDV RNA at the end of treatment was achieved in 3 patients who had significantly lower baseline HDV RNA levels than nonresponders (2.99 log(10) copies/mL ± .70 vs 4.68 ± .97; P = .0185). In all 3 patients, ALT levels were also normal at the end of treatment. CONCLUSIONS One year of entecavir treatment is ineffective in CHD. Any generalized beneficial effect of nucleoside/nucleotide analog treatment may necessitate prolonged treatment. Patients with CHD with HBV dominance, which is likely to occur in the later phases of CHD, may be a reasonable patient cohort in which to target nucleoside/nucleotide analog therapy.

Hepatitis B surface antigen seroconversion is associated with favourable long-term clinical outcomes during lamivudine treatment in HBeAg-negative chronic hepatitis B patients.

Summary.  The aims of this study were to assess hepatitis B surface antigen (HBsAg) seroconversion and to determine its impact on the natural course of the disease in patients with HBeAg‐negative chronic hepatitis B (CHB) during lamivudine (LMV) treatment. A total of 183 consecutive patients with HBeAg‐negative CHB who were treated with LMV were included in the study. Data were retrospectively collected from outpatient visit charts. The primary endpoint was HBsAg seroconversion to anti‐HBs. The secondary endpoint was to determine the development of cirrhosis. Loss of HBsAg was confirmed in 10 patients and seroconversion to anti‐HBs in nine patients during LMV treatment or after its discontinuation. HBsAg seroconversion was achieved on‐treatment in four patients after a median treatment duration of 30 months and off‐treatment in the remaining five patients in a median 61 months after LMV discontinuation. The cumulative probability of HBsAg seroconversion increased from 0.6% at 1 year and 1.9% at 5 years to 21.5% at 10 years of LMV during and after LMV treatment. HBsAg clearance was preceded by undetectable serum hepatitis B virus (HBV) DNA. The majority of the patients responding to treatment had undetectable HBV DNA levels at 24 weeks of treatment. The cumulative probability of LMV resistance increased from 2.2% at 1 year to 37.3% at 5 years. No baseline parameter predicting either HBsAg seroconversion or the emergence of LMV resistance was identified. None of the patients with HBsAg seroconversion experienced virological breakthrough or disease progression during the follow‐up period. These results indicate that HBsAg seroclearance can occur in patients with HBeAg‐negative CHB under LMV therapy and predicts better clinical outcome.

Clonal analysis of the quasispecies of antiviral-resistant HBV genomes in patients with entecavir resistance during rescue treatment and successful treatment of entecavir resistance with tenofovir.

BACKGROUND Clonal analysis of quasispecies of resistant HBV genomes in patients with entecavir (ETV) resistance receiving lamivudine (3TC) plus adefovir (ADV) rescue therapy has never been performed. METHODS A sample of 10 patients with ETV resistance who were switched to 3TC+ADV treatment were analysed for changes in viral quasispecies. Serum samples at baseline, and at months 3 and 6 of 3TC+ADV treatment could be clonally analysed in 7 of 10 patients; 3-82 clones per sample (total 1,068 clones, mean 63) were sequenced. RESULTS 3TC+ADV therapy led to a modest decline in HBV DNA. Almost all clones had L180M and M204V 3TC resistance mutations before and during combination therapy. All clones had ≥1 of the S202G, T184F, T184A, T184L, T184I and M250V ETV resistance mutations. The percentages of detected clones bearing 3TC (rtL180M and rtM204V) and ETV mutations did not change with rescue 3TC+ADV therapy. In 7 of 8 patients with detectable HBV DNA (median 5.17 log(10) copies/ml) after a median 24 months of ADV therapy, HBV DNA became undetectable with 3TC plus tenofovir after 6 months of treatment. CONCLUSIONS In patients with ETV resistance tenofovir is effective. Clonal analysis data indicate no selection of specific HBV mutants during rescue 3TC+ADV.

Endoscopic treatment of biliary complications following liver transplantation

BACKGROUND/AIMS The aims of the present study were to review biliary complications following liver transplantation in a single-center experience, to identify the factors associated with biliary complications, and to evaluate the success of endoscopic and percutaneous treatment in such patients. MATERIALS AND METHODS Between January 1994 and June 2010, a total of 176 patients with liver disease underwent liver transplantation; 119 recipients were included in this retrospective analysis. Median posttransplant follow-up period was 49 months. RESULTS Mean age was 43.0±12.7 years. Living donor liver transplantation (LDLT) and deceased-donor liver transplantation (DDLT) were performed in 71 and 48 patients, respectively. Duct-to-duct anastomosis and Roux-en-Y hepaticojejunostomy were performed in 68 and 51 patients, respectively. The overall incidence of posttransplant biliary complications was 36%; anastomotic biliary strictures were the most common biliary complications (42%), followed by biliary leakage (28%). On logistic regression analysis, duct-duct anastomosis was the only risk factor associated with the development of biliary complications (Odds ratio (OR), 3.346; p=0.005). Endoscopic and percutaneous treatment was successful in the majority of patients (81%), and the remaining 19% recipients underwent surgery for biliary repair. Endoscopic retrograde cholangiopancreatography (ERCP) guided drainage and balloon dilatation with stent placement were the most common treatment modalities. CONCLUSION Biliary complications were most frequent after liver transplantation; biliary strictures were the most commonly seen. The use of duct-to-duct anastomosis for biliary reconstruction is a risk factor for the development of biliary complications. Endoscopic and percutaneous treatment was successful in the majority of these patients.

Manometric assessment of esophageal motor function in patients with primary biliary cirrhosis

INTRODUCTION/AIM Primary biliary cirrhosis is associated with other autoimmune diseases including Sjögrens syndrome, and scleroderma. Esophageal dysmotility is well known in scleroderma, and Sjögrens syndrome. The aim of this study is to investigate whether any esophageal motor dysfunction exists in patients with primary biliary cirrhosis. METHOD The study was performed in 37 patients (36 women, mean age: 56.29 ± 10.01 years) who met diagnostic criteria for primary biliary cirrhosis. Thirty-seven functional dyspepsia patients, were also included as a control group. Patients entering the study were asked to complete a symptom questionnaire. Distal esophageal contraction amplitude, and lower esophageal sphincter resting pressure were assessed. RESULTS Manometric findings in primary biliary cirrhosis patients vs. controls were as follows: Median lower esophageal sphincter resting pressure (mmHg): (24 vs 20, p=0.033); median esophageal contraction amplitude (mmHg): (71 vs 56, p=0.050); mean lower esophageal sphincter relaxation duration (sc, x ± SD): (6.10 ± 1.18 vs 8.29 ± 1.92, p<0.001); and median lower esophageal sphincter relaxation (%) (96 vs 98, p=0.019); respectively. No significant differences were evident in median peak velocity (sc) (3.20 vs 3.02, p=0.778) between patients with primary biliary cirrhosis and the functional dyspepsia patients. Esophageal dysmotility was found in 17 (45.9%) primary biliary cirrhosis patients (non-specific esophageal motor disorder in ten patients, hypomotility of esophagus in five patients, nutcracker esophagus in one patient and hypertensive lower esophageal sphincter in one patient). CONCLUSION Esophageal dysmotility was detected in 45.9% of patients. The study suggests that subclinic esophageal dysmotility is frequent in patients with primary biliary cirrhosis.

İntestinal graft versus host hastalığının endoskopik bulgularının retrospektif değerlendirilmesi

Background and Aims: Acute graft-versus-host disease occurs after allogeneic hematopoietic stem cell transplantation and is a reaction of donor immune cells against host tissues. Activated donor T cells damage host epithelial cells. About 35%-50% of hematopoietic stem cell transplant recipients will develop acute graft-versus-host disease. The endoscopic findings varied markedly and included mild mucosal edema with focal erythema, diffuse erythema, and diffuse polypoid indurations with multiple bleeding ulcerations. We investigated endoscopic findings in a graft-versus-host disease patient population. Materials and Methods: A retrospective review of endoscopic data was performed in 18 adult allogeneic bone marrow transplant recipients at our institution. Results: In this study, 18 allogeneic bone marrow transplant patients (mean age 33.9 years; 62% male) were evaluated. In 6 graftversus- host disease patients, the endoscopic appearances of the esophagus, stomach and duodenum varied from subtle mucosal erythema and edema to frank ulceration. Colonoscopy was performed with biopsies in 12 graft-versus- host disease patients. The colonoscopic findings varied markedly and ranged from mild mucosal edema with focal erythema to multiple bleeding ulcerations. Conclusions: The diagnostic accuracy of endoscopy was high in gastrointestinal graft-versus-host disease. Accurate diagnosis of gastrointestinal graft-versus-host disease might be obtained with mucosal biopsies from either the upper or lower gastrointestinal tract. Endoscopy may play a significant role in establishing early diagnosis and treatment for gastrointestinal graft-versus-host disease patients.

Helikobakter pilori'nin klaritromisine karşı kazandığı dirençteki artış stabilitemi kazanmakta?

Background and Aims: We aimed to evaluate the efficiency of the standard triple therapy (clarithromycin, amoxicillin, proton pump inhibitors) in Helicobacter pylori eradication over the period 2004 2008. Materials and Methods: 390 patients who were treated for Helicobacter pylori between 1999 and 2009 and assessed after treatment were examined retrospectively. 169 patients who were treated with standard triple therapy between 2004 and 2008 were also analyzed. Results: The mean age was 45.9±15 years, and 46.1% of patients were female. Eradication rates were 66.2%, 75.4%, 71.5%, 72%, and 73.4%, respectively, from 2004 to 2008. Eradication rates were not statistically different over time. The recent data were compared with the clinical studies made with triple therapy in our clinic before 2000, and it was determined that after 2000, eradication rates declined significantly and remained stable thereafter. Conclusions: Eradication rates significantly declined with the standard triple therapy after 2000. Clarithromycin resistance appears to be the main factor. Alternative therapy regimens are needed.

Son iki dekatta endoskopi merkezinde kolorektal kanser görülme sıklığı

Background and Aims: Colorectal cancer is seen more frequently in people and societies with higher socioeconomic status. In recent years, more evidence has emerged about the increasing involvement of the proximal colon. The purpose of this study was to evaluate the occurrence rate, localization and annual change in the rate of colorectal cancer. Materials and Methods: 18,484 lower gastrointestinal endoscopy procedures performed between 1993-2008 in the Endoscopy Units of Ankara University, Department of Gastroenterology were evaluated retrospectively. Among these, 8,249 (44.6%) were total colonoscopy and 10,235 (55.4%) rectosigmoidoscopy. Age, sex, occurrence of cancer, localization and annual changes in these parameters were determined. Results: Mean age of the patients was 47.8, and 52.2% were male. Colorectal cancer was detected in 659 (3.5%) of the cases. Cancer detection rate in males (4.5%) was significantly higher than in females (2.5%) (p

Özofageal melanositozis - Üç olgu ve literatürün gözden geçirilmesi

Endoscopic or macroscopic esophageal melanocytosis is a benign, rare clinic and pathologic condition characterized by melanocytic proliferation in the basal layer of esophageal squamous epithelium and an increased amount of melanin in the esophageal mucosa. Esophageal melanocytosis is also called melanosis. Little is known about the etiology and natural course of this condition, although it has been suggested that esophageal melanocytosis may be a result of gastroesophageal reflux disease or other chronic stimuli that cause mucosal damage and keratinocytic hyperplasia. Differential diagnosis of esophageal melanocytosis includes benign melanocytic nevi and malignant melanoma. Although it has been suggested to be a precursor of primary esophageal melanocytosis, this awaits further investigations. Because esophageal melanocytosis is rare, there has been no report of esophageal melanocytosis that resulted in specific symptoms or special treatments. We present three patients with esophageal melanocytosis and review the literature.