Impact of HBV genotype and mutations on HBV DNA and qHBsAg levels in patients with HBeAg-negative chronic HBV infection.

BACKGROUND: HBV DNA and quantitative (q)HBsAg levels as prognostic markers for HBV-related disease are mostly validated in Asia and their significance in Western populations is uncertain. AIM: To analyse the impact of the HBV genotype and frequent mutations in precore (PC), basal core promoter (BCP) and preS on HBV DNA and qHBsAg levels. METHODS: HBV DNA and qHBsAg serum levels of 465 patients with HBeAg-negative chronic HBV infection were correlated with the HBV genotype and mutations in PC, BCP and preS. For a detailed analysis of the molecular virology, genotype A2 genomes harbouring these mutations were analysed for replication efficacy and HBsAg release in cell culture. RESULTS: While no impact of the HBV genotype on HBV DNA levels was observed, qHBsAg levels differed up to 1.4 log among the genotypes (P < 0.001), reflected by large differences regarding the 1000 IU/mL HBsAg cut-off. While PC mutations were associated with higher (P < 0.001), BCP mutations were associated with lower HBV DNA levels (P < 0.001). Higher qHBsAg levels were associated with preS and lower levels with PC mutations (P < 0.001 and P = 0.001, respectively). The cell culture experiments revealed a higher HBsAg release and shorter filaments in case of a HBV genome harbouring a preS deletion. In contrast, a perinuclear HBsAg accumulation was detected for the PC and BCP-variants, reflecting an impaired HBsAg release. CONCLUSIONS: qHBsAg serum levels depend on the HBV genotype and together with HBV DNA levels on frequent mutations in PC, BCP and preS in HBeAg-negative patients. qHBsAg cut-offs when used as prognostic markers require genotype-dependent validation.

No evidence of hepatitis B virus reactivation in patients with resolved infection treated with direct-acting antivirals for hepatitis C in a large real-world cohort.

BACKGROUND: Hepatitis B virus (HBV) reactivation has been observed following interferon (IFN)-based treatment in HBV/hepatitis C virus (HCV) co-infected patients. Recent reports suggest that reactivation may also occur in both hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative patients during HCV treatment with direct-acting antivirals (DAAs). AIM: To investigate the rate of patients with HBV reactivation during IFN-based and IFN-free HCV treatment in a large real-world cohort. METHODS: A total of 848 patients with chronic hepatitis C were treated with different combinations of DAAs. Among patients with available outcome and HBV data, there were 272 patients hepatitis B core antibody (HBcAb)-positive (HBsAg-positive, n=9; HBsAg-negative, n=263), and 536 were HBcAb-negative. All HBcAb-positive patients were tested for HBV DNA at the end of DAA therapy and alanine transaminase (ALT) levels were frequently measured during therapy and follow-up. RESULTS: Seventy-three percent (n=192/263) of HBsAg-negative/HBcAb-positive patients had elevated ALT levels at baseline, which declined to normal values in all but 18 patients, and no HBV reactivation was observed. Eight patients had detectable but not quantifiable HBV DNA (<20 IU/mL) at end of treatment, but none were associated with elevated ALT. Five of nine HBsAg-positive/HBcAb-positive patients experienced transient or permanent HBV reactivation, three of whom required nucleos(t)ide treatment during (n=1) or after (n=2) DAA therapy. CONCLUSIONS: HBV reactivation was not observed in HBsAg-negative/HBcAb-positive patients but common in HBsAg-positive/HBcAb-positive patients treated with different combinations of DAAs for HCV.

The efficacy and safety of direct acting antiviral treatment and clinical significance of drug-drug interactions in elderly patients with chronic hepatitis C virus infection.

BACKGROUND: Direct antiviral therapies for chronic hepatitis C virus (HCV) infection have expanded treatment options for neglected patient populations, including elderly patients who are ineligible/intolerant to receive interferon (IFN)-based therapy. AIM: To investigate the efficacy, tolerability and potential for drug-drug interactions (DDIs) of IFN-free treatment in patients aged ≥65 years in a large real-world cohort. METHODS: A total of 541 patients were treated with different combinations of direct antiviral agents (DAAs: ledipasvir/sofosbuvir ±ribavirin; daclatasvir/sofosbuvir ±ribavirin; paritaprevir/ombitasvir ±dasabuvir ±ribavirin or simeprevir/sofosbuvir ±ribavirin in genotype 1/4, and daclatasvir/sofosbuvir ±ribavirin or sofosbuvir/ribavirin in genotype 2/3). Efficacy, safety and potential DDIs were analysed and compared between patients aged <65 years (n = 404) and patients aged ≥65 years (n = 137) of whom 41 patients were ≥75 years. RESULTS: Sustained virological response rates were 98% and 91% in patients aged ≥65 years and <65 years, respectively. Elderly patients took significantly more concomitant medications (79% vs. 51%; P < 0.0001). The number of concomitant drugs per patient was highest in patients ≥65 years with cirrhosis (median, three per patient; range, 0-10). Based on the hep-druginteractions database, the proportion of predicted clinically significant DDIs was significantly higher in elderly patients (54% vs. 28%; P < 0.0001). The number of patients who experienced treatment-associated adverse events was similar between the two age groups (63% vs. 65%; P = n.s.). CONCLUSIONS: Elderly patients are at increased risk for significant DDIs when treated with DAAs for chronic HCV infection. However, with careful pre-treatment assessment of concomitant medications, on-treatment monitoring or dose-modifications, significant DDIs and associated adverse events can be avoided.

[New methods for endoscopic hemostasis: focus on non-variceal gastrointestinal bleeding]. / Neue Methoden zur endoskopischen Blutstillung: Fokus auf die nicht variköse Blutung.

Gastrointestinal bleeding is a frequent emergency in daily clinical practice of a gastroenterologist. While incidence and mortality of gastrointestinal bleeding are decreasing in many countries, numbers of endoscopic procedures are increasing. Endoscopic therapy of non-variceal gastrointestinal bleeding is still mainly based on "classical" procedures like injection of vasoactive drugs (i. e. epinephrine) or blood derivates, application of through-the-scope hemoclips (TTSC), Argon plasma coagulation and bipolar coagulation. However, in the last years new endoscopic techniques especially for non-variceal gastrointestinal bleedings have become available and enriched our endoscopic equipment. For example, over-the-scope clips (OTSCs) surpass the size of TTSCs and have been successfully established for treatment of gastrointestinal bleeding and leak closure of fistulas and perforations. In addition, hemostatic powders were shown to achieve primary hemostasis in several cases of gastrointestinal bleeding. Besides a brief overview of "classical" endoscopic procedures for hemostasis of non-variceal gastrointestinal bleeding, this review focuses on new epidemiological data and uprising methods for endoscopic hemostasis.