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Clinical events and the host immune response during hepatitis B virus (HBV) infection are intricately linked. Despite decades of research, important questions concerning the immunopathogenesis of chronic HBV infection remain unanswered. For example, it is unclear which immune parameters facilitate persistence, and if HBV can be completely cleared from the human liver. Recent technological breakthroughs now allow researchers to address these seemingly basic, but essential questions surrounding HBV immunity. It will be important to better define the molecular underpinnings of immune cell function and dysfunction during chronic disease and in controlled infection, with particular focus on the liver, as little information is available on the intrahepatic compartment. In the near future, it may be possible to solve some of the controversy surrounding the immune responses to HBV, and establish the features of both the innate and adaptive arms of the immune system required to achieve sustained control of HBV infection., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Currently, much effort is directed at further improving treatment for chronic hepatitis B patients by assessing the effect of immunomodulatory agents during therapy with nucleotide analogues (NUC). Although there are some reports on the effect of NUC therapy on peripheral natural killer (NK) cells, no studies investigated the long-term effects of NUC treatment on intrahepatic NK cells of chronic HBV patients. We aimed to prospectively investigate cell frequencies, phenotype, and activation status of intrahepatic NK cells of CHB patients on prolonged treatment with TDF., Methods: Fine needle aspiration biopsies were collected from 11 chronic HBV patients at baseline, and at 12, 24, and 48 weeks of treatment with a daily 245 mg dose of TDF. Four patients underwent an additional aspiration biopsy after appoximately 6 years of treatment., Results: Longitudinal evaluation of these patients during tenofovir therapy showed that all patients achieved a viral load reduction with undetectable DNA load after 48 weeks of therapy. Repeated sampling of the liver during therapy showed that the frequency of distinct lymphocyte populations in the liver remained unchanged despite viral load reduction. During the course of therapy, no modulation of the expression levels and frequencies of CD69, HLA-DR, NKG2A and NKG2D on liver NK cells were detected. However, evaluation of intrahepatic NK cell activation after continuous TDF therapy for 6 years demonstrated a mild increase in 3 out of 4 patients., Conclusions: Our findings provide a unique insight in the intrahepatic NK cell compartment in chronic HBV patients during prolonged treatment. We observed that long-term NUC-induced viral suppression, accompanied by gradual decrease of HBsAg levels, had no or only a limited effect on the frequencies, phenotype, and activation status of intrahepatic NK cells., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Evidence over the past decades have shown that HIV/HCV coinfected patients did not respond as well to HCV therapy as HCV mono-infected patients. However, these paradigms are being recently reassessed with the improvements of care for HIV and HCV patients. This article reviews these original paradigms and how the new data is impacting upon them. Treatment efficacy now appears comparable for HIV/HCV coinfected and HCV mono-infected patients, while liver fibrosis progression is increasingly similar in optimally managed patients. Additional importance of therapy is directed to drug-drug interactions and the impact of HCV reinfection, as well as the possibility of transmitted drug resistance., (Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)