Search

Abstract: Despite the availability of a preventive vaccine and active antiviral treatments that stop disease progression and reduce the risk of hepatocellular carcinoma, hepatitis B is still a major public health problem. Only an estimated 10% of the 257 million people living with HBV have been diagnosed and as few as 1% are being adequately treated. Barriers to diagnosis and treatment include: (i) limited awareness and lack of knowledge about HBV infection and HBV‐related diseases; (ii) under‐diagnosis with insufficient screening and referral to care; (iii) limited treatment due to drug availability, costs, reimbursement policies and the need for long‐term or life‐long therapy. These barriers and the actions needed to improve access to treatment are strongly influenced by the prevalence of infection and affect middle‐high vs low‐middle income countries differently, where most HBV carriers are found. In high‐prevalence regions and low‐to middle‐income countries, the main challenges are availability and cost while in low‐prevalence regions and middle‐to high‐income countries low screening rates, public awareness, social stigma and discrimination play an important role. Overcoming these challenges on a global scale is a complex clinical and public health challenge and multilateral commitment from pharmaceutical companies, governments, funders and the research community is lacking. The new WHO 2016 Global Health Sector Strategy on viral hepatitis targets testing and treatment, suggesting that important but strong actions are needed from advocacy groups, scientific societies and funding agencies to foster awareness and access to cure. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infections remain a major public health problem worldwide. According to World Health Organization estimates, more than 300 million people are chronically infected and exposed to the risk of developing severe complications including cirrhosis and hepatocellular carcinoma (HCC). Major progress in the treatment of chronic hepatitis B (CHB) has been made during the last decade with the development of antivirals that inhibit viral polymerase activity. Antiviral drug resistance is an important factor in determining the success of long-term therapy for CHB. The development of resistance to nucleoside analogues (NUCs) has been associated with exacerbations of liver disease. Sequential therapy increases the risk of the emergence of multidrug resistance. The selection of a potent antiviral with a high barrier to resistance as a first-line therapy provides the best chance of achieving long-term treatment goals and should be used whenever possible. This has led to a significant decrease in drug resistance in countries where this strategy is affordable. However, the barrier to resistance of a given antiviral agent is influenced by the genetic barrier, drug potency, patient adherence, pharmacological barrier, viral fitness, the drug mechanisms of action and cross resistance. Furthermore, because of specific viral kinetics, prolonged treatment with NUCs does not result in the clearance of the viral genome from the infected liver. It is therefore important to continue research to identify new viral and immune targets and develop novel antiviral strategies for controlling viral replication as well as preventing drug resistance and its complications in the long term. [ABSTRACT FROM AUTHOR]

Treatment with either pegylated interferon-alpha (peg IFN-α) or last generation nucleos(t)ide analogues ( NAs) successfully leads to serum viral load suppression in most chronically infected hepatitis B ( CHB) patients, but HBsAg loss is only achieved in 10% of the cases after a 5-year follow-up. Thus, therapy must be administered long-term and it will not completely eliminate infection because of the persistent hepatitis B virus ( HBV) minichromosome in infected cells, and cannot completely abolish the risk of developing severe sequelae such as cirrhosis and hepatocellular carcinoma. Recent progress in the development of in vitro and in vivo models of HBV infection have helped renew interest in the investigation of the viral life cycle, as well as specific virus-host cell interactions to identify new targets for the development of new antiviral drugs. This includes either direct inhibition of viral replication by targeting fundamental steps such as entry, ccc DNA formation/stability, viral transcripts, capsid assembly and secretion or the manipulation of the host immune system for better defence against infection. Multiple strategies are currently under investigation, including boosting endogenous innate responses and/or restoring adaptive immunity via engineering of HBV-specific T cells or via the use of inhibitors of negative regulators, as well as therapeutic vaccines. It is increasingly clear that multiple therapeutic strategies must be combined to reach a cure of HBV and that the definition of clinical, virological and immunological correlates for the management of treatment are urgently needed. [ABSTRACT FROM AUTHOR]

Hepatitis B virus ( HBV) remains a public health concern with 240 million people affected worldwide. HBV is an hepadnavirus that replicates its genome in hepatocytes. One of the key steps of the viral life cycle is the formation of ccc DNA - covalently closed circular DNA - in the nucleus, the equivalent of a viral mini-chromosome that acts as a template for subsequent virus replication. Current antiviral medications are not effective in eradicating ccc DNA, which can persist in the infected liver even in the absence of detectable HBV DNA or HBsAg in the blood. ccc DNA cannot be measured in serum, and few surrogate markers have been proposed. Persistent ccc DNA has been associated with various clinical events, including viral reactivation induced by immunosuppressive therapies, HBV recurrence after liver transplantation and hepatocellular carcinoma ( HCC). ccc DNA remains the main target to achieve a cure of HBV infection, thus extensive efforts are being made to develop new antiviral concepts to degrade or silence ccc DNA. [ABSTRACT FROM AUTHOR]

Background & Aims Few data are available on the prevalence of renal abnormalities in chronic hepatitis B virus ( HBV)-infected patients. The multicentric cross-sectional HARPE study evaluated the prevalence of kidney disease indicators, in chronic HBV surface antigen carriers patients ( HBsAg+) with active or inactive infection. Patients and methods Two hundred and sixty-eight HBsAg+ adult patients, naïve of any oral antihepatitis B virus treatment were prospectively included over 2 years. Data for renal assessment were collected once from patient files. Univariate tests and multiple linear regressions were performed with the SAS software, version 8.02 ( SAS, Inc., Cary, NC, USA). Results Among the 260 patients analysed, 58% were men, the mean age was 42 ± 14 years, 59.6% were inactive carriers whereas 47 patients, mostly active, were about to start an antiviral therapy. Prevalence of proteinuria, haematuria, glycosuria, uninfectious leukocyturia was 38.1%, 20.6%, 3.9% and 9% respectively. According to the international definition, a total of 64.6% of patients were found to have kidney disease. Diabetes, hypertension and dyslipidaemia were observed, respectively, in 4.6%, 9.2% and 38.8% patients. There were no significant differences in these results within the three subgroups. Conclusion Renal abnormalities are highly prevalent in our population and pre-exist before the initiation of any antihepatitis B virus treatment. This emphasizes the need for: (i) a baseline renal evaluation in all HBs antigen-positive patients; (ii) a regular renal monitoring before and during antihepatitis B virus treatment to diagnose and manage renal impairment and adjust antihepatitis B virus treatment doses to renal function when necessary. [ABSTRACT FROM AUTHOR]