Real-world effectiveness and safety of sofosbuvir/velpatasvir and ledipasvir/sofosbuvir hepatitis C treatment in a single centre in Germany.

Background: Newer direct-acting antiviral therapies are increasingly becoming the therapy of choice in patients with hepatitis C virus (HCV) infection. Here, we report the safety and effectiveness of sofosbuvir/velpatasvir (SOF/VEL) and ledipasvir/sofosbuvir (LDV/SOF) in real-world cohorts in Germany.

Methods: Patients initiated on SOF/VEL 12 weeks or LDV/SOF 8, 12 or 24 weeks regimens in a single German centre were included in this study.

Discontinuation of oral antivirals in chronic hepatitis B: A systematic review.

Unlabelled: The possibility of safe discontinuation of therapy with nucleos(t)ide analogues (NAs) remains one of the most controversial topics in the management of chronic hepatitis B. Therefore, we systematically reviewed the existing data on NA discontinuation in this setting and tried to identify factors affecting the probability of posttherapy remission. A literature search was performed in order to identify all published studies including patients who discontinued NAs in virological remission (VR) and were followed for ≥12 months thereafter.

Variability in long-term hepatitis B virus dynamics under antiviral therapy.

Hepatitis B virus (HBV) dynamics in treated patients can be complex and differ considerably from other viral infections. We analyse dynamics of liver and serum levels of HBV DNA in 24 chronically HBV-infected individuals undergoing 1 year of combination therapy with pegylated interferon alpha and adefovir dipivoxil (ADV), followed by 2 years of ADV monotherapy. Serum viral dynamics differentiated the patients into four response groups dependent on how quickly viremia became undetectable: quickly suppressed (HBV DNA <100 copies/ml within 8 weeks and staying suppressed, GRP1); quickly suppressed but some rebound (<10,000 copies/ml, GRP2); slow decay (GRP3); virological failures (>10,000 copies/ml, GRP4).

Telbivudine plus pegylated interferon alfa-2a in a randomized study in chronic hepatitis B is associated with an unexpected high rate of peripheral neuropathy.

Background & Aims: This study investigated the antiviral efficacy and safety of telbivudine in combination with pegylated interferon (PegIFN) alpha-2a in chronic hepatitis B (CHB) patients.

Methods: This was a randomized, open-label, multicentre study, in treatment-naïve patients with HBeAg-positive CHB, comparing the efficacy and safety of telbivudine in combination with PegIFN alpha-2a with telbivudine monotherapy and PegIFN alpha-2a monotherapy. The study was terminated early due to increased rates of peripheral neuropathy in the combination-therapy group.

Hepatitis B virus DNA quantification with the three-in-one (3io) method allows accurate single-step differentiation of total HBV DNA and cccDNA in biopsy-size liver samples.

Background: Hepatitis B virus (HBV) replicates via reverse transcription converting its partially double stranded genome into the covalently closed circular DNA (cccDNA). The long-lasting cccDNA serves as a replication intermediate in the nuclei of hepatocytes. It is an excellent, though evasive, parameter for monitoring the course of liver disease and treatment efficiency.

Increased HEV seroprevalence in patients with autoimmune hepatitis.

Background: Hepatitis E virus (HEV) infection takes a clinically silent, self-limited course in the far majority of cases. Chronic hepatitis E has been reported in some cohorts of immunocompromised individuals. The role of HEV infections in patients with autoimmune hepatitis (AIH) is unknown.

Improved immune status corresponds with long-term decline of quantitative serum hepatitis B surface antigen in HBV/HIV co-infected patients.

In HBV/HIV-co-infected individuals, the course of hepatitis B is aggravated, leading to higher morbidity and mortality rates. Increasing evidence suggests an important role for hepatitis B surface antigen (HBsAg) quantification in monitoring treatment efficacy in HBV monoinfection. However, data concerning any HBsAg decline during treatment of HBV/HIV coinfection are limited.

In vivo selection of transplanted hepatocytes by pharmacological inhibition of fumarylacetoacetate hydrolase in wild-type mice.

Genetic fumarylacetoacetate hydrolase (Fah) deficiency is unique in that healthy gene-corrected hepatocytes have a strong growth advantage and can repopulate the diseased liver. Unfortunately, similar positive selection of gene-corrected cells is absent in most inborn errors of liver metabolism and it is difficult to reach the cell replacement index required for therapeutic benefit. Therefore, methods to transiently create a growth advantage for genetically modified hepatocytes in any genetic background would be advantageous.

Ectopic expression of murine CD47 minimizes macrophage rejection of human hepatocyte xenografts in immunodeficient mice.

Unlabelled: Macrophages play an important role in the rejection of xenogeneic cells and therefore represent a major obstacle to generating chimeric mice with human xenografts that are useful tools for basic and preclinical medical research. The signal inhibitory regulatory protein α (SIRPα) receptor is a negative regulator of macrophage phagocytic activity and interacts in a species-specific fashion with its ligand CD47. Furthermore, SIRPα polymorphism in laboratory mouse strains significantly affects the extent of human CD47-mediated toleration of human xenotransplants.

Hepatitis B surface antigen (HBsAg) decrease and serum interferon-inducible protein-10 levels as predictive markers for HBsAg loss during treatment with nucleoside/nucleotide analogues.

Background: Hepatitis B surface antigen (HBsAg) loss is the ultimate goal of antiviral therapy and its prediction may be important for treatment individualization. Quantitative HBsAg (qHBsAg) has been shown to predict response to interferon-α, but few studies have analysed qHBsAg during treatment with nucleoside/nucleotide analogues (NAs). Serum interferon-inducible protein-10 (IP-10) has been associated with treatment response in hepatitis C, but data in chronic hepatitis B are lacking.

Rapid early HDV RNA decline in the peripheral blood but prolonged intrahepatic hepatitis delta antigen persistence after liver transplantation.

Background & Aims: Chronic HDV infection is an inflammatory liver disease and liver transplantation (LTX) remains the only curative treatment option for most patients. The hepatitis D virus (HDV) uses HBsAg as its surface protein, however, it is controversial to what extend HDV may be detected independently of HBsAg in blood and liver after LTX. The aims of this study were to investigate kinetics of HDV RNA and HBsAg early after LTX, to apply the data to a mathematical model and to study long-term persistence of HDV after LTX.

Republished paper: Managing HBV in patients with impaired immunity.

Chronic hepatitis B is one of the most common infectious diseases worldwide. In patients with an impaired immune system the prevalence of HBsAg is even higher and the course of hepatitis B infection is often aggravated. In HIV/HBV co-infected patients, liver related morbidity and mortality can be reduced by implementing highly active antiretroviral treatment (HAART) that contains substances active against HBV.

Liver transplantation: A new risk factor for intestinal intussusceptions.

Background: Intestinal intussusception in adults is associated with chronic inflammatory bowel disease, celiac disease, abdominal tumors or previous abdominal surgery but most often of unknown origin.

Aim: The aim of our study was to evaluate circumstances and identify risk factors for intussusceptions.

Methods: All 65,928 abdominal ultrasound examinations performed at our tertiary medical center between January 2001 and June 2008 were analyzed retrospectively for the diagnosis "intussusception".

Different kinetics of HBV and HCV during haemodialysis and absence of seronegative viral hepatitis in patients with end-stage renal disease.

Background: Hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are common in haemodialysis units. Moreover, some studies reported seronegative cases of viral hepatitis. We and others have previously shown an HCV RNA decline during haemodialysis; however, limited data on HBV viraemia during haemodialysis are available.

Correlation between the Elecsys HBsAg II assay and the Architect assay for the quantification of hepatitis B surface antigen (HBsAg) in the serum.

Background: Hepatitis B surface antigen (HBsAg) clearance during chronic hepatitis B (CHB) infection is associated with improved long-term clinical outcome, so is considered an important therapeutic goal in CHB. Studies have shown that serum HBsAg quantification during, and at end of, treatment may predict long-term HBsAg loss.

Objectives: Performance comparison of the qualitative Elecsys HBsAg II assay using a quantitative research protocol and an established quantitative HBsAg assay.

Kinetics of hepatitis B surface antigen decline during 3 years of telbivudine treatment in hepatitis B e antigen-positive patients.

Unlabelled: The impact of prolonged direct antiviral therapy on hepatitis B surface antigen (HBsAg) levels in patients with chronic hepatitis B is poorly understood. We quantitatively assessed serum HBsAg levels during 3 years of telbivudine treatment, as well as their relationship with virologic and biochemical characteristics in 162 hepatitis B e antigen-positive patients who maintained undetectable serum hepatitis B virus (HBV) DNA long-term. Telbivudine treatment progressively reduced serum HBsAg levels (mean ± SD) from baseline (3.

Managing HBV in patients with impaired immunity.

Chronic hepatitis B is one of the most common infectious diseases worldwide. In patients with an impaired immune system the prevalence of HBsAg is even higher and the course of hepatitis B infection is often aggravated. In HIV/HBV co-infected patients, liver related morbidity and mortality can be reduced by implementing highly active antiretroviral treatment (HAART) that contains substances active against HBV.

Establishment of a novel quantitative hepatitis D virus (HDV) RNA assay using the Cobas TaqMan platform to study HDV RNA kinetics.

Determination of hepatitis D virus (HDV) viremia represents the "gold standard" for the diagnosis of HDV infection. Hepatitis B virus (HBV)-HDV coinfection frequently leads to end-stage liver disease and hepatocellular carcinoma. No commercial assay for HDV RNA quantification that includes automated nucleic acid extraction is available, and in-house PCR tests are not well standardized.

Hepatitis B surface antigen (HBsAg) levels in the natural history of hepatitis B virus (HBV)-infection: a European perspective.

Background & Aims: The quantifiable level of HBsAg has been suggested as a predictor of treatment response in chronic hepatitis B. However, there is limited information on HBsAg levels considering the dynamic natural course of HBV-infection. This study aimed to determine HBsAg levels in the different phases of HBV-infection in European HBsAg-positive patients.

Adeno-associated virus gene repair corrects a mouse model of hereditary tyrosinemia in vivo.

Unlabelled: Adeno-associated virus (AAV) vectors are ideal for performing gene repair due to their ability to target multiple different genomic loci, low immunogenicity, capability to achieve targeted and stable expression through integration, and low mutagenic and oncogenic potential. However, many handicaps to gene repair therapy remain. Most notable is the low frequency of correction in vivo.

Performance and clinical utility of a novel fully automated quantitative HCV-core antigen assay.

Background: Recently, a novel quantitative HCVcoreAg immunoassay developed for commercialisation by Abbott has become available in Europe and Asia.

Objectives: We evaluated the correlation of HCV-RNA and HCVcoreAg and investigated the stability of HCVcoreAg and HCV-RNA.

Study Design: HCVcoreAg was quantified by a novel fully automated immunoassay (Architect HCVAg, Abbott, Germany).

Food intake increases liver stiffness in patients with chronic or resolved hepatitis C virus infection.

Background And Aims: Transient elastography is increasingly being used in patients with chronic liver disease. It has proven particularly useful to identify patients with advanced fibrosis or cirrhosis, while classification of no or little fibrosis appears to be difficult. In general, stiffness values <6 kPa are considered normal, whereas patients with higher levels are candidates for a disease-specific treatment or further diagnostic evaluation.

Natural history: the importance of viral load, liver damage and HCC.

Chronic hepatitis B and hepatitis C virus infections are the major causes of liver disease, hepatocellular carcinoma (HCC) and liver-related mortality worldwide. Among factors known to influence the natural history of viral hepatitis are age at the time of infection, duration of infection, serum alanine aminotransferase (ALT) levels, male sex, alcohol consumption, and coinfections. In hepatitis B, serum HBV DNA concentration emerges as the key factor for predicting the development of liver disease.