Asli Ormeci

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.

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.

Effects of Polymorphisms in Interferon λ 3 (Interleukin 28B) on Sustained Virologic Response to Therapy in Patients With Chronic Hepatitis D Virus Infection

BACKGROUND & AIMS We investigated the association between interferon λ 3 (IFNL3) genotype (also known as interleukin 28B) and response to IFNα therapy in patients with chronic hepatitis D virus (HDV) infection. METHODS We studied IFNL3 genotypes of 32 patients (19 men; median age, 42.5 y) with chronic HDV infection. Nineteen patients (59%) were treated with pegylated IFNα and 13 patients (41%) were treated with standard IFNα, for at least 12 months. Levels of HDV RNA were measured before the initiation of treatment and every 6 months thereafter; patients were followed up for a median time of 16 months (range, 6-164 mo) after treatment ended. We used real-time polymerase chain reaction to classify the IFNL3 polymorphism rs12979860 as CC, CT, or TT, and rs8099917 as TT, GT, or GG. A virologic response was defined as undetectable HDV RNA in serum, and a sustained virologic response (SVR) was defined as undetectable HDV RNA after cessation of treatment until the end of the follow-up period. We evaluated the association between IFNL3 polymorphism and treatment response using univariate and multivariate analyses. RESULTS After treatment, a response was achieved in 16 patients (50%) and an SVR was achieved in 9 (28%). The percentages of patients with CC, CT, and TT at rs12979860 were 47%, 47%, and 6%, respectively; the percentages of patients with TT, GT, and GG at rs8099917 were 69%, 28%, and 3%, respectively. Rates of SVR were 27%, 27%, and 50% in patients with CC, CT, TT at rs12979860 (P = .78 for CC vs CT vs TT) and 36%, 11%, and 0% in patients with TT, GT, and GG at rs8099917 (P = .30 for TT vs GT vs GG). CONCLUSIONS The IFNL3 polymorphisms rs12979860 and rs8099917 do not significantly affect responses of patients with chronic HDV infection to treatment with IFNα.

Small bowel mucosal damage in familial Mediterranean fever: results of capsule endoscopy screening

Abstract Objective. Familial Mediterranean fever (FMF) is the most common form of autoinflammatory diseases. We aimed to evaluate the small bowel mucosa by capsule endoscopy (CE) in FMF patients for investigation of other possible causes of abdominal pain. Material and methods. The study group consisted of 41 patients with FMF. A standard questionnaire was used to record the gastrointestinal symptoms, other clinical findings, Mediterranean fever gene (MEFV) mutations, and history of medications including non-steroidal anti-inflammatory drugs (NSAIDs). Gastroscopy, colonoscopy and small bowel CE were performed in all patients, and biopsies were taken from terminal ileum and duodenum. Results. The mean age of the patients was 34 ± 11 years, 63% of them were female, and 76.5% of them were carrying MEFV exon 10 mutations. Only one patient used NSAIDs in addition to colchicine. In endoscopic investigations, gastric erosion was detected in only one patient, and no significant findings were detected in colonoscopy. CE showed small bowel mucosal defects in 44% (erosions in 26.8%, ulcer in 17.1%) and edema in 29.3% of the patients. Most (64%) of the ulcer and erosions were localized to jejunum, and only 24% were in ileum. Mitotic changes as an indirect finding of colchicine toxicity were not different from the changes observed in samples of independent group of patients with irritable bowel syndrome. Conclusion. Mucosal defect was observed in half of the FMF patients, which may be associated with underlying inflammation or chronic colchicine exposure. Detection of nonspecific chronic inflammation without mitotic changes supports that mucosal defects may be associated with the autoinflammatory process.

A novel two bases deletion in the albumin gene causes analbuminaemia in a young Turkish man.

Fig. 1. Molecular effect of the novel c.229_230delTG. (A) Genomic DNA sequence electropherograms showing the mutation found in exon 3 of the proband. The arrow indicates the two bases that are deleted in the patient: TG at nucleotide positions c. 229–230. (B) DNA sequence and amino acid translation of a portion of exon 3 from the ALB gene for a wild-type allele [6] and the mutant Amasya allele. The underlined nucleotides indicate the two bases that are deleted in the Amasya allele. This deletion leads to a frameshift mutation that introduces a premature stop codon two amino acids downstream. Codon numbering is according to the HGVS rules, i.e. starting from the initiator codon. A novel two bases deletion in the albumin gene causes analbuminaemia in a young Turkish man

What is the impact of capsule endoscopy in the long term period

AIM To assess the clinical impact of capsule endoscopy (CE) in the long-term follow-up period in patients with obscure gastrointestinal bleeding (OGIB). METHODS One hundred and forty-one patients who applied CE for OGIB between 2009 and 2012 were retrospectively analyzed, and this cohort was then questioned prospectively. Demographic data of the patients were determined via the presence of comorbid diseases, use of non-steroidal anti-inflammatory drugs anticoagulant-antiaggregant agents, previous diagnostic tests for bleeding episodes, CE findings, laboratory tests and outcomes. RESULTS CE was performed on 141 patients because of OGIB. The capsule was retained in the upper gastrointestinal (GI) system in two of the patients, thus video monitoring was not achieved. There were 139 patients [62% male, median age: 72 years (range: 13-93 years) and a median follow-up duration: 32 mo (range: 6-82 mo)]. The overall diagnostic yield of CE was 84.9%. Rebleeding was determined in 40.3% (56/139) of the patients. The rebleeding rates of patients with positive and negative capsule results at the end of the follow-up were 46.6% (55/118) and 4.8% (1/21), respectively. In the multivariate analysis, usage of NSAIDs, anticoagulant-antiaggregant therapies (OR = 5.8; 95%CI: 1.86-18.27) and vascular ectasia (OR = 6.02; 95%CI: 2.568-14.146) in CE were detected as independent predictors of rebleeding. In the univariate analysis, advanced age, comorbidity, and overt bleeding were detected as predictors of rebleeding. CONCLUSION CE is a reliable method in the diagnosis of obscure GI bleeding. Negative CE correlated with a significantly lower rebleeding risk in the long-term follow-up period.

An Unusual Long-Term Survey of a Patient with Widespread Malignant Urachal Tumor, Not Given Chemotherapy or Radiotherapy

The urachus establishes a connection between the dome of the bladder and the umbilicus throughout fetal life. If the urachus does not close completely, malignancy is a potential complication. The primary treatment for malignant urachal tumor is surgical excision. A 61-year-old male patient diagnosed with urachal carcinoma had undergone partial cystectomy 25 years previously. Twenty years later, local recurrence was treated with another partial cystectomy without umbilical remnant excision. Recurrence at the umbilical site was excised 2 years later, but intraperitoneal invasion had occurred, and the patient underwent a total colectomy at that time. Local disease and disseminated metastases in the thorax and intra- and extraperitoneal areas were noted upon admission to our hospital. Urachal carcinomas are usually aggressive tumors, and surgical treatment should include partial or radical cystectomy and excision of the urachus and umbilicus, to prevent local recurrence and distant metastasis.

Predictors of treatment requirement in HBeAg-negative chronic hepatitis B patients with persistently normal alanine aminotransferase and high serum HBV DNA levels.

OBJECTIVES Serum alanine aminotransferase (ALT) is a controversial marker for disease monitoring in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. The aim of this study was to determine the fibrosis stage and histological activity index (HAI) in HBeAg-negative CHB patients with persistently normal ALT (PNALT) and high serum HBV DNA (≥2000 IU/ml) and to investigate clinical risk factors for the requirement of treatment through the examination of liver biopsy specimens. METHODS HBeAg-negative CHB patients with PNALT (≤40 IU/l) and high serum HBV DNA (≥2000 IU/ml) were included. HBV fibrosis stage and HAI were scored according to the Ishak system. Multivariate logistic regression analysis was used to estimate the independent risk factors for fibrosis stage ≥2 and/or HAI ≥6. Receiver operating characteristic curve analysis was used to determine an optimal age cut-off for liver biopsy. RESULTS A total 120 patients were enrolled. These patients had a mean HBV DNA level of 123680±494500 IU/ml; the HBV DNA load was 2000-20000 IU/ml in 68 patients (56.6%) and ≥20000 IU/ml in 52 (43.4%). Eighteen patients (15%) had moderate-to-severe histological activity (HAI ≥6). Forty-three patients (35.9%) had a fibrosis stage ≥2. Forty-eight patients (40%) had a fibrosis stage ≥2 and/or HAI ≥6. On multivariate logistic regression analysis, independent variables associated with fibrosis stage ≥2 and/or HAI ≥6 included age and HBV DNA viral load. Patients with HBV DNA 2000-20000 IU/ml were more likely to require treatment compared to those with a viral load ≥20000 IU/ml. The optimal age cut-off to predict fibrosis stage ≥2 and/or HAI ≥6 was 46 years. CONCLUSIONS Significant liver damage was detected in 40% of CHB patients with PNALT and high HBV DNA upon biopsy. Age and HBV DNA viral load were independent predictors of significant liver damage. A biopsy to determine the degree of liver damage is advisable for CHB patients older than 46 years.

Current state and clinical outcome in Turkish patients with hepatocellular carcinoma

AIM To investigate clinical, etiological, and prognostic features in patients with hepatocellular carcinoma. METHODS Patients with hepatocellular carcinoma who were followed-up from 2001 to 2011 were included in the study. The diagnosis was established by histopathological and/or radiological criteria. We retrospectively reviewed clinical and laboratory data, etiology of primary liver disease, imaging characteristics and treatments. Child-Pugh and Barcelona Clinic Liver Cancer stage was determined at initial diagnosis. Kaplan-Meier survival analysis was done to find out treatment effect on survival. Risk factors for vascular invasion and overall survival were investigated by multivariate Cox regression analyses. RESULTS Five hundred and forty-five patients with hepatocellular carcinoma were included in the study. Viral hepatitis was prevalent and 68 patients either had normal liver or were non-cirrhotic. Overall median survival was 16 (13-19) mo. Presence of extrahepatic metastasis was associated with larger tumor size (OR = 3.19, 95%CI: 1.14-10.6). Independent predictor variables of vascular invasion were AFP (OR = 2.95, 95%CI: 1.38-6.31), total tumor diameter (OR = 3.14, 95%CI: 1.01-9.77), and hepatitis B infection (OR = 5.37, 95%CI: 1.23-23.39). Liver functional reserve, tumor size/extension, AFP level and primary treatment modality were independent predictors of overall survival. Transarterial chemoembolization (HR = 0.38, 95%CI: 0.28-0.51) and radioembolization (HR = 0.36, 95%CI: 0.18-0.74) provided a comparable survival benefit in the real life setting. Surgical treatments as resection and transplantation were found to be associated with the best survival compared with loco-regional treatments (log-rank, P < 0.001). CONCLUSION Baseline liver function, oncologic features including AFP level and primary treatment modality determines overall survival in patients with hepatocellular carcinoma.

Does the number of mucosal immune cells differ in irritable bowel syndrome and its subtypes

BACKGROUND/AIMS Recently, mucosal inflammation has been proposed to be one of the mechanisms underlying the pathophysiology of irritable bowel syndrome (IBS); however, there are controversial results regarding this hypotheses. Our aim was to evaluate immune cell infiltration in rectal and ileal biopsy specimens of patients with IBS and to compare it with those of healthy controls. MATERIALS AND METHODS In total, 36 patients with IBS (15 with diarrhea and 21 with constipation) and 16 healthy volunteers were enrolled. Ileocolonoscopy and ileal/rectal biopsies were performed. Rectal and terminal ileal biopsy specimens were evaluated for mucosal immune cell infiltration using immunohistochemical analysis. Serotonin positivity as well as counts of intraepithelial lymphocytes (IEL) and CD4+, CD8+, CD20+, and CD3+ cells were determined by a single pathologist who is an expert in the gastrointestinal system. RESULTS CD3+ and CD4+ cell counts in rectal and terminal ileal biopsy specimens were lower in the IBS group than in the controls. Conversely, there was no statistically significant difference between the IBS and control groups in terms of serotonin positivity as well as counts of IEL and CD20+ and CD8+ cells. Comparison between the IBS subgroups revealed a higher number of IEL in rectal biopsy specimens of the diarrhea dominant group. In the IBS subgroups, immune cell counts in terminal ileal and rectal biopsy specimens showed a positive correlation. CONCLUSION IBS and its subgroups showed lower immune cell counts than the controls in our study. These results indicate that there is no significant mucosal inflammation in homogeneous groups of patients with IBS. Rectal biopsies may be sufficient for the evaluation of inflammation in IBS.