Real-world efficacy and safety of Ledipasvir plus Sofosbuvir and Ombitasvir/Paritaprevir/Ritonavir +/- Dasabuvir combination therapies for chronic hepatitis C: A Turkish experience

Background/Aims: This study aimed to evaluate the real-life efficacy and tolerability of direct-acting antiviral treatments for patients with chronic hepatitis C (CHC) with/without cirrhosis in the Turkish population.Material and Methods: A total of 4,352 patients with CHC from 36 different institutions in Turkey were enrolled. They received ledipasvir (LDV) and sofosbuvir (SOF)+/- ribavirin (RBV) ombitasvir/paritaprevir/ritonavir +/- dasabuvir (PrOD)+/- RBV for 12 or 24 weeks. Sustained virologic response (SVR) rates, factors affecting SVR, safety profile, and hepatocellular cancer (HCC) occurrence were analyzed.Results: SVR12 was achieved in 92.8% of the patients (4,040/4,352) according to intention-to-treat and in 98.3% of the patients (4,040/4,108) according to per-protocol analysis. The SVR12 rates were similar between the treatment regimens (97.2%-100%) and genotypes (95.6%-100%). Patients achieving SVR showed a significant decrease in the mean serum alanine transaminase (ALT) levels (50.90 +/- 54.60 U/L to 17.00 +/- 14.50 U/L) and model for end-stage liver disease (MELD) scores (7.51 +/- 4.54 to 7.32 +/- 3.40) (p<0.05). Of the patients, 2 were diagnosed with HCC during the treatment and 14 were diagnosed with HCC 37.0 +/- 16.0 weeks post-treatment. Higher initial MELD score (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.22-2.38; p=0.023]), higher hepatitis C virus (HCV) RNA levels (OR: 1.44, 95% CI: 1.31-2.28; p=0.038), and higher serum ALT levels (OR: 1.38, 95% CI: 1.21-1.83; p=0.042) were associated with poor SVR12. The most common adverse events were fatigue (12.6%), pruritis (7.3%), increased serum ALT (4.7%) and bilirubin (3.8%) levels, and anemia (3.1%).Conclusion: LDV/SOF or PrOD +/- RBV were effective and tolerable treatments for patients with CHC and with or without advanced liver disease before and after liver transplantation. Although HCV eradication improves the liver function, there is a risk of developing HCC.Turkish Association for the Study of The Liver (TASL

Impact of hepatic immunoreactivity of angiotensin-converting enzyme 2 on liver fibrosis due to non-alcoholic steatohepatitis

Background: We aimed to evaluate the hepatic immunoreactivity of angiotensin-convertingenzyme 2 (ACE2) in non-alcoholic steatohepatitis (NASH) patients, elucidate its associationwith the clinicopathological characteristics and also determine its role in fibrosis progression.Methods: The consecutive biopsy proven NASH patients were subdivided into two groups accordingto their fibrosis score. Fibrotic stages < 3 in mild fibrosis group and fibrotic stages?3 inadvanced fibrosis depending on the presence of bridging fibrosis. Liver biopsy specimens wereimmunohistochemically stained for ACE2 immunoreactivity. Demographics and clinical propertieswere compared between the groups. Univariate and multivariate analysis were alsoperformed to evaluate the independent predicting factors for the presence of advanced liverfibrosis caused by NASH.Results: One hundred and eight patients were enrolled in the study. Out of this, ninety-fourpatients representing 87% were classified as mild fibrosis group, whilst fourteen representing13% were in advanced fibrosis group. We compared high hepatic immunoreactivity of ACE2between mild and advanced fibrosis groups and found a statistically significant difference 65.9%vs 28.5%, respectively and P = 0.008. Hepatic ACE2 immunoreactivity was inversely correlatedwith the fibrosis score (r: —0.337; P < 0.001). The significant variables in the univariate analysiswere then evaluated in multivariate logistic regression analysis and hepatic ACE2 immunoreactivitywas an independent predicting factor of liver fibrosi

Presence and severity of estrogen receptor-alpha expression in patients with simple steatosis and nash

Loss of estrogen receptor-alpha (ER-?) in the liver is associated with hepatic steatosis and inflammation.We conducted a study in order to investigate the presence and extent of ER-? expression in NASH, andits relationship with histological findings. Fifty-four patients with histologically confirmed NASH, 12patients with simple steatosis (SS), and 6 patients with normal liver tissue (NLT) were included. NASHactivity score and fibrosis score were calculated according to biopsy findings. Liver biopsy specimenswere immunohistochemically stained for ER-? expression. Nuclear ER-? expression percentage (stainingindex) was calculated. Mean staining index was significantly different across the NASH, SS, and NLT groups(6.3±9.9 vs. 22.1±26.4 vs. 44.2±24.8, respectively, p < 0.001 for all comparisons). Staining index wassignificantly higher in women than in men (19.4±22.2 vs. 7.9±15.3, respectively, p = 0.003). Stainingindex negatively correlated with serum ALT (r =-0.240; p = 0.04), fasting plasma glucose (r =-0.261;p = 0.027), and fibrosis score (r =-0.312; p = 0.011). As a conclusion, hepatic nuclear ER-? expressionpercentage (staining index) is lower in patients with NASH when compared to SS and NLT groups. Stainingindex is negatively correlated with serum ALT levels, plasma glucose, and fibrosis score. Further studiesare required to clarify the significance of ER-? expression in NASH

The importance of serum biglycan levels as a fibrosis marker in patients with chronic hepatitis B

WOS: 000411716300040PubMed ID: 27925300BackgroundLiver biopsy is recommended in the majority of patients with chronic viral hepatitis for fibrosis evaluation. Because of the potential risks of liver biopsy, many studies related to non-invasive biomarkers of hepatic fibrosis have been performed. We aimed to assess the diagnostic value of serum biglycan as a non-invasive fibrosis marker in chronic hepatitis B patients. MethodsThis study included 120 patients with biopsy-proven hepatitis B patients and 60 healthy controls. Fibrosis stage and necroinflammatory activity were assessed in liver biopsy specimens. Biglycan level was measured using an ELISA assay. ResultsSerum biglycan levels of chronic hepatitis B patients were found to be significantly higher than those of healthy controls (337.3363.0pg/mL vs 189.1 +/- 61.9pg/mL, respectively, P<.001). There was a statistically significant positive correlation between serum biglycan level and fibrosis stage (P=.004; r=.213). Besides, a statistically significant positive correlation was found between serum biglycan level and necroinflammatory activity (P<.001; r=.271). The AUROC of BGN levels was 0.702 for fibrosis stage, differentiating patients from healthy controls with statistical significance (P<.001). The AUROC of BGN levels was 0.632 for necroinflammatory activity score, differentiating patients from healthy controls with statistical significance (P=.004). ConclusionsSerum biglycan might be used as a non-invasive marker of liver fibrosis. Further studies are needed to evaluate the usefulness of this marker

Lack of association of hepatic estrogen receptor-alpha expression with histopathological and biochemical findings in chronic hepatitis C

Estrogens exert a protective effect against hepatic steatosis and fibrosis. Loss of estrogen receptor-alpha(ER- ) in the liver is associated with hepatic steatosis and inflammation in animal models. We conducteda study in order to investigate the presence and extent of ER- expression in HCV infection,and its relationship with histological and biochemical findings. Ninety biopsy-proven chronic hepatitis C(CHC) patients were enrolled in the study. Liver biopsy specimens were immunohistochemically stainedfor ER- expression. Nuclear ER- expression percentage was calculated. ER- was positive in 69 of thepatients (76%). ER- positive and negative groups were not significantly different in terms of age, gender,necroinflammatory activity, fibrosis, steatosis, serum levels of AST, ALT, ALP, GGT, and bilirubin. ER- expression percentage was not correlated with fibrosis, steatosis, necroinflammatory activity and biochemicalfindings. Although estrogens are known to be protective against fibrosis and steatosis in animalmodels, we did not find any significant correlation between ER- expression and histopathological andbiochemical findings in CHC patients. These findings should be verified in further large scale studies

Association between Plasma Endothelin-1, Transforming Growth Factor-β, Fibroblast Growth Factor, and Nitric Oxide Levels and Liver Injury in Hematopoietic Stem Cell Transplantation Recipients with Persistent Iron Overload after Transplantation.

Graft-versus-host disease, iron overload, and infections are the major causes of liver dysfunction in allogeneic hematopoietic stem cell transplantation (AHSCT) recipients. We investigated the relationship between serum iron parameters and the levels of transforming growth factor-β (TGF-β), fibroblast growth factor (FGF), endothelin-1 (ET-1), and nitric oxide (NO) as predictors of chronic liver injury in 54 AHSCT recipients who survived at least a year after transplantation. Serum samples from patients were obtained for the evaluation of ET-1, TGF-β, FGF, NO, and nontransferrin bound iron at the first year follow-up visit using commercially available ELISA kits. Patients were categorized depending on serum ferritin and transferrin saturation levels. The parameters were compared between the groups, and survival analysis was also performed. Most of the AHSCT recipients (81.5%) were in complete remission during the study. After a median follow-up time of 73 months (range, 13 to 109 months), 72.2% of the patients were alive. Mean serum levels of ET-1, NO, TGF-β, and FGF were 81.54 ± 21.62 μmol/mL, 31.82 ± 26.42 μmol/mL, 2.56 ± 0.77 ng/mL, and 50.31 ± 32.69 pg/mL, respectively. Nineteen patients (35.2% of the cohort) had serum ferritin levels higher than 1000 ng/mL. Mean serum levels of ET-1, NO, TGF-β, and FGF were similar in patients with serum ferritin levels below or above 1000 ng/mL (P > .05). Serum ferritin levels were positively correlated with serum alanine aminotransferase (r = .284, P = .042) and γ-glutamyl transferase (r = .271, P = .05) levels and were negatively correlated with serum albumin levels (r = .295, P = .034). There was a significant positive correlation between serum transferrin saturation and alanine aminotransferase levels (r = .305, P = .03). Serum ET-1 level was positively correlated with alkaline phosphatase levels (r = .304, P = .026). In univariate Cox regression analysis serum levels of iron parameters, ET-1, NO, TGF-β, and FGF did not have an impact on overall survival (P > .05). The probability of progression-free survival was also similar in patients with ferritin levels above or below 1000 ng/mL (P = .275). The probability of survival was similar in patients with transferrin saturation ≥70% and .05). Serum iron parameters showed a positive correlation with liver injury. However, there was no correlation between fibrogenic cytokines and liver transaminases. Our results suggest that iron overload at least with the current levels of ferritin might have a relatively benign course. Prospective randomized trials will guide the actual role of iron chelation in the post-transplantation setting

Evaluation of Plasma Urokinase-Type Plasminogen Activator Receptor (UPAR) in Patients With Chronic Hepatitis B, C and Non-Alcoholic Fatty Liver Disease (NAFLD) as Serological Fibrosis Marker.

Progressive hepatic fibrosis is the main predictor of outcome and prognosis in chronic liver diseases. The importance of the coagulation cascade has been defined in liver fibrosis; however, the role of the fibrinolytic pathway has not been clear yet. We aimed to evaluate the association between the plasma levels of soluble urokinase Plasminogen Activator Receptor (uPAR) and the severity of liver fibrosis in chronic hepatitis B, C and Non-Alcoholic Fatty Liver Disease (NAFLD)

Hepatitis B-related events in autologous hematopoietic stem cell transplantation recipients

AIM: To investigate the frequency of occult hepatitis B, the clinical course of hepatitis B virus (HBV) reactivation and reverse seroconversion and associated risk factors in autologous hematopoietic stem cell transplantation (HSCT) recipients

Characteristics of Newly Diagnosed Hepatocellular Carcinoma Patients Across Turkey: Prospective Multicenter Observational 3K Registry Study

Aims: To evaluate patient profile for epidemiological and clinicopathological characteristics and potential risk/prognostic factors in newly diagnosed hepatocellular carcinoma (HCC) patients across Turkey