Management of antiviral drug resistance in chronic hepatitis B

Rescue antiviral treatment for patients with resistance to preexisting nucleos(t)ide analogues remains a clinical challenge. The correct choice of a first-line treatment of high potency and with a high genetic barrier to achieve sustained long-term suppression of viral replication provides the best chance of preventing treatment failure and the emergence of drug resistance. The management of treatment failure and drug resistance requires a precise and accurate clinical and virologic monitoring. Combination treatment with antiviral drugs that belong to different groups is associated with a lower chance of developing resistance to rescue drugs. To guarantee better control of viral replication in patients with drug resistance, the addition of another drug without a cross resistance profile should be given as early as possible, preferably at the time when genotypic resistance emerges. Long-term surveillance for treatment efficacy and possible emergence of drug resistance should be continued to prevent the emergence of multidrug-resistant strains.

Management of chronic hepatitis B infection: Current treatment guidelines, challenges, and new developments

Chronic hepatitis B(CHB)virus infection is a global public health problem,affecting more than 400 million people worldwide.The clinical spectrum is wide,ranging from a subclinical inactive carrier state,to progressive chronic hepatitis,cirrhosis,decompensation,and hepatocellular carcinoma.However,complications of hepatitis B virus(HBV)-related chronic liver disease may be reduced by viral suppression.Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon,entecavir,or tenofovir,but the optimal treatment for an individualpatient is controversial.The indications for treatment are contentious,and increasing evidence suggests that HBV genotyping,as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response.The likelihood of achieving a sustained virological response is also increased by extending treatment duration,and using combination therapy.Hence the paradigm for treatment of CHB is constantly evolving.This article summarizes the different indications for treatment,and systematically reviews the evidence for the efficacy of various antiviral agents.It further discusses the shortcomings of current guidelines,use of rescue therapy in drug-resistant strains of HBV,and highlights the promising clinical trials for emerging therapies in the pipeline.This concise overview presents an updated practical approach to guide the clinical management of CHB.

Direct-acting Antiviral Agents Resistance-associated Polymorphisms in Chinese Treatment-na（i）ve Patients Infected with Genotype 1b Hepatitis C Virus

Background：It has been reported that several baseline polymorphisms of direct-acting antivirals （DAAs） agents resistance-associated variants （RAVs） would affect the treatment outcomes of patients chronically infected with hepatitis C virus （CHC）.The aim of this study is to investigate the prevalence of DAAs RAVs in treatment-na（i）ve GT1b CHC patients.Methods：Direct sequencing and ultra-deep sequencing of the HCV NS3,NS5A,and NS5B gene were performed in baseline serum samples of treatment-ha（i）ve patients infected with genotype lb hepatitis C virus （HCVs）.Results：One hundred and sixty CHC patients were studied.Complete sequence information was obtained for 145 patients （NS3）,148 patients （NS5A）,and 137 patients （NS5B）.Treatment-failure associated variants of DAAs were detected：56.6％ （82/145） of the patients presented S122G for simeprevir （NS3 protease inhibitor）;10.1％ （14/148） of the patients presented Y93H for daclatasvir and ledipasvir （NS5A protein inhibitors）;94.2％ （129/137） of the patients presented C316N for sofosbuvir （NS5B polymerase inhibitor）.Nearly,all of the DAAs RAVs detected by ultra-deep sequencing could be detected by direct sequencing.Conclusions：The majority of genotype lb CHC patients in China present a virus population carrying HCV DAAs RAVs.Pretreatment sequencing of HCV genome might need to be performed when patients infected with GTlb HCV receiving DAAs-containing regimens in China.Population sequencing would be quite quantified for the work.

DNA-guided hepatitis B treatment,viral load is essential,but not sufficient

Hepatitis B virus （HBV） infection is a global public health problem that concerns 350 million people worldwide. Individuals with chronic hepatitis B （CriB） are at increased risk of developing liver cirrhosis, hepatic de-compensation and hepatocellular carcinoma. To maintain undetectable viral load reduces chronic infection complications. There is no treatment that eradicates HBV infection. Current drugs are expensive, are associated with adverse events, and are of limited efficacy. Current guidelines try to standardize the clinical practice. Nevertheless, controversy remains about management of asymptomatic patients with CriB who are hepatitis B e antigen （HBeAg）-positive with normal alanine aminotransferase, and what is the cut-off value of viral load to distinguish HBeAg- negative CriB patients and inactive carriers. We discuss in detail why DNA level alone is not sufficient to begin treatment of CriB.