Bulent Baran

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.

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.

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.

Treatment failure may lead to accelerated fibrosis progression in patients with chronic hepatitis C

Chronic hepatitis C (CHC) patients with treatment failure (TF) remain at risk of continuing fibrosis progression. However, it has not been investigated whether there is an increased risk of accelerated fibrosis progression after failed interferon‐based therapy. We aimed to investigate long‐term influence of TF on fibrosis progression compared with untreated patients with CHC. We studied 125 patients with CHC who underwent paired liver biopsies from 1994 to 2012. Patients with advanced fibrosis were excluded from the analysis. Sixty‐three patients had TF, and 62 patients were treatment‐naïve (TN). Annual fibrosis progression rate (FPR) was calculated, and significant fibrosis progression (SFP) was defined as ≥2 stage increase in fibrosis during follow‐up. Multiple regression analyses were performed to find out independent predictors of FPR and SFP. Demographic characteristics and duration between paired liver biopsies were similar in TF and TN groups. Baseline alanine aminotransferase and gamma‐glutamyl transferase (GGT) levels (71 ± 31 vs 47 ± 22, P < 0.001 and 49 ± 39 vs 36 ± 28, P = 0.027, respectively), baseline mean fibrosis stage (2.2 ± 0.7 vs 1.9 ± 0.7, P = 0.018) and histologic activity index (6.3 ± 1.9 vs 4.3 ± 1.6, P < 0.001) were higher in the TF group compared with the TN group. In regression analyses, the strongest independent predictor of fibrosis progression was the GGT level (OR: 1.03, 95%CI 1.01–1.5, P < 0.001). Treatment experience (OR: 5.97, 95%CI 1.81–19.7, P = 0.003) also appeared as an independent predictor of both FPR and SFP. Failed interferon‐based CHC treatment may lead to accelerated FPR in the long‐term compared with the natural course.

Gastroesophageal reflux in asymptomatic obese subjects:An esophageal impedance-pH study

AIM To investigate the relationship between reflux and body mass index (BMI) in the asymptomatic obese population using the impedance-pH technique. METHODS Gastroesophageal reflux is frequent in the obese population. However, the relationship between acid reflux and BMI in asymptomatic obese people is unclear. Forty-six obese (BMI > 25 kg/m(2)) people were enrolled in this prospective study. We evaluated the demographic findings and 24-h impedance pH values of the whole group. Gas, acid (pH < 4), weak acid (pH = 4-7) and weak alkaline (pH ≥ 7) reflux parameters were analyzed. RESULTS The mean age of patients was 49.47 ± 12.24 years, and half of them were men. The mean BMI was 30.64 ± 3.95 kg/m(2) (25.14-45.58 kg/m(2)). BMI of 23 was over 30 kg/m(2). Seventeen patients had a comorbidity (hypertension, diabetes mellitus, or ischemic heart disease). Endoscopic examination revealed esophagitis in 13 of the 28 subjects (10 Grade A, 3 Grade B). The subjects were divided into two groups according to BMI (< 30 and > 30 kg/m(2)). Demographic and endoscopic findings, and impedance results were similar in these two groups. However, there was a positive correlation between BMI and total and supine pH < 4 episodes (P = 0.002, r = 0.414; P = 0.000, r = 0.542), pH < 4 reflux time (P = 0.015, r = 0.319; P = 0.003, r = 0.403), and DeMeester score (P = 0.012, r = 0.333). CONCLUSION Acid reflux is correlated with BMI in asymptomatic obese individuals.

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.

Co-infection with hepatitis B does not alter treatment response in chronic hepatitis C

BACKGROUND/AIM To investigate the clinical features and treatment response in patients with hepatitis B (HBV) and hepatitis C virus (HCV) co-infection receiving anti-HCV therapy. PATIENTS AND METHOD Patients with HBV/HCV co-infection, who were eligible for anti-HCV therapy, were included in the study. Patients had detectable HBsAg for at least 6 months and detectable HCV-RNA before the initiation of therapy. Primary end-point was the proportion of patients achieving sustained virological response (SVR). HBV serology and HBV-DNA results obtained during the follow-up were assessed to determine HBV clearance or reactivation after anti-HCV therapy. RESULTS There were 612 patients in the HCV cohort and 52 (8.5%) of them were HBV/HCV co-infected. Twenty-eight patients (20 male, mean age: 47 ± 12) received anti-HCV treatment and followed-up for a mean duration of 53 months (12-156). Fifteen patients received peginterferon/ribavirin combination while the remaining patients received standard interferon/ribavirin combination (n=6) or standard interferon monotherapy (n=7). Patients receiving interferon monotherapy were under chronic hemodialysis therapy. SVR was achieved in 14 (50%) patients at the end of follow-up. The proportion of patients with SVR in three treatment arms were not significantly different (P=0.78). Eight of 11 patients with detectable HBV-DNA cleared HBV-DNA during treatment. Seven (25%) patients experienced a rebound in HBV-DNA, and one patient experienced an acute hepatitis flare which was controlled by tenofovir therapy. Two (7%) patients cleared HBsAg and one of them was seroconverted to anti-HBs. CONCLUSION Co-infection with HBV does not have a negative impact on the efficacy of anti-HCV treatment, but HBV-DNA should be monitored to overcome the risk of HBV exacerbation.

Congenital Portal Vein Aneurysm Associated with Peliosis Hepatis and Intestinal Lymphangiectasia

Portal vein aneurisym (PVA), peliosis hepatis (PH) and intestinal lymphangiectasia (IL) all are very uncommon entities. Herein, we presented a unique patient with these three rare entities who was admitted to our hospital because of portal hypertensive ascites rich in protein and lymphocyte. PVA was extrahepatic and associated with coronary vein aneurysm. Peliosis hepatis was of microscopic form. Lymphangiectasia was present in peritoneum and small intestine. Diagnoses of these rare entities were made by imaging techniques and histopathological findings. Patient also had hydronephrosis caused by ureteropelvic junction narrowing. Best of our knowledge, there is no such a case reported previously with the association of PVA, PH and IL. Therefore, we propose PVAPHIL syndrome to define this novel association.

Practical Medical Management of Crohn’s Disease

Crohns disease is a chronic inflammatory disease of diagnostic and therapeutic challenges. After proper diagnosis, treatment decisions must be made on precise clinical judgment. During the course of the disease there are variable clinical features, so each case must be managed individually. Physicians who care for patients with Crohns disease should be prepared for treatment options in different states of the disease and possible complications of both the disease and medications. This paper will focus on the management of Crohns disease. We aim to discuss current treatment options in different presentations of the disease and to provide algorithmic management strategy.

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.