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The long-lasting persistence of hepatitis B virus (HBV) genomes in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing negative for the HBV surface antigen (HBsAg) is termed occult HBV infection (OBI). Although in a minority of cases the lack of HBsAg detection is due to infection with variant viruses unrecognized by available assays (S-escape mutants), the typical OBI is related to replication-competent HBVs strongly suppressed in their replication activity. The causes of HBV suppression are not yet well clarified, although the host’s immune surveillance and epigenetic mechanisms are likely involved. OBI is a worldwide diffused entity, but the available data of prevalence in various categories of individuals are often contrasting because of the different sensitivity and specificity of the methods used for its detection in many studies. OBI may have an impact in several different clinical contexts. In fact, it can be transmitted (i.e., through blood transfusion and liver transplantation) causing classic forms of hepatitis B in newly infected individuals. The development of an immunosuppressive status (mainly by immunotherapy or chemotherapy) may induce OBI reactivation and development of acute and often severe hepatitis. Finally, evidence suggests that OBI can favor the progression of liver fibrosis, in particular in HCV-infected patients. The possible contribution of OBI to the establishment of cirrhosis also implies its possible indirect role in the development of hepatocellular carcinoma. On the other hand, OBI may maintain most of the direct transforming properties of the overt HBV infection, such as the capacity to integrate in the host’s genome and to synthesize pro-oncogenic proteins.

Hepatitis B Virus (HBV) is a significant public health challenge. Around 250 million people live with chronic HBV infection. With a global approach to this issue, we focus on new perspective in diagnosis, management and prevention of HBV chronic infection. Precise diagnosis of HBV status is crucial to guide patient management. Although available drugs reduce the risk of liver disease progression, they are not able to definitely eradicate HBV, and new therapeutic options are urgently needed. Thus, prevention of HBV infection is still the most effective strategy to achieve the control of the disease. Key aspects of prevention programs include surveillance of viral hepatitis, screening programs and immunization strategies. In spite of the high success rate of licensed HBV vaccines, a need for improved vaccine persists, especially in order to provide coverage of current non-responders.

Hepatitis B virus infection affects over 250 million chronic carriers, causing more than 800,000 deaths annually, although a safe and effective vaccine is available. Currently used antiviral agents, pegylated interferon and nucleos(t)ide analogues, have major drawbacks and fail to completely eradicate the virus from infected cells. Thus, achieving a “functional cure” of the infection remains a real challenge. Recent findings concerning the viral replication cycle have led to development of novel therapeutic approaches including viral entry inhibitors, epigenetic control of cccDNA, immune modulators, RNA interference techniques, ribonuclease H inhibitors, and capsid assembly modulators. Promising preclinical results have been obtained, and the leading molecules under development have entered clinical evaluation. This review summarizes the key steps of the HBV life cycle, examines the currently approved anti-HBV drugs, and analyzes novel HBV treatment regimens.

Hepatocellular carcinoma (HCC) represents the second leading cause of cancer mortality worldwide and is mostly caused by hepatitis B virus (HBV) infection. HBV can induce HCC by an indirect mechanism of continuous necro-inflammation, contributing to hepatocyte damage and promoting cancer, as well as by viral intrinsic factors. Among them, the major contributors to the development of HBV-related HCC are represented by (i) HBV DNA integration in genes modulating cell proliferation, (ii) HBV pro-oncogenic proteins, such as HBx and HBs, and (iii) the accumulation of viral mutations, enhancing the tumorigenic features of HBV proteins. The currently available antiviral treatments, based on the usage of Nucleos(t)ide analogs (NUCs), substantially control HBV replication. However, even a successful NUC treatment does not completely abrogate HCC risk, since it rarely allows achievement of an HBV functional cure, the therapeutic end-point associated with HBsAg loss and more favorable liver outcomes. To date, novel therapeutic strategies based on innovative direct antivirals (nucleic acid polymers, small interfering RNAs, antisense oligonucleotides, covalently closed circular DNA (cccDNA) inhibitors, and capsid assembly modulators) and immune-therapeutics (therapeutic vaccines, checkpoint inhibitors, and Toll-like receptor agonists) are under evaluation in clinical trials. These approaches are showing promising data in terms of an HBV functional cure, thus representing novel strategies that could be beneficial for reducing the burden of HBV-related HCC. Lastly, further efforts in drug development are necessary to identify new compounds that could achieve a sterilizing HBV cure, implying the complete elimination of cccDNA and integrated HBV DNA, the only end-point that completely eradicates HBV and its related oncogenic risk.

Cabotegravir plus rilpivirine long-acting (CAB + RPV-LA) injectable therapy marks a major milestone in HIV care, offering an efficacious, well-tolerated alternative to daily oral antiretroviral treatment. This article reviews data from pivotal trials and observational studies of CAB + RPV-LA, addressing emerging questions and highlighting key research priorities. We examine factors influencing virological outcomes, including issues related to HIV subtype, archived drug resistance, body mass index, and pharmacokinetics, and discuss challenges related to hepatitis B virus immunity and infection, pregnancy, and adherence. We outline strategies to address barriers to implementation, advocating for a tailored approach to maximize the potential of CAB + RPV-LA in improving outcomes across diverse populations with HIV.

Background. There is no standard management of reactivation of hepatitis B virus (HBV) infection in HBV-resolved patients without hepatitis B surface antigen (HBsAg), but with antibodies against hepatitis B core antigen and/or antibodies against HBsAg (anti-HBs). Methods. We conducted a prospective observational study to evaluate the occurrence of HBV reactivation by serial monthly monitoring of HBV DNA and to establish preemptive therapy guided by this monitoring in B-cell non-Hodgkin lymphoma (B-NHL) treated with rituximab plus corticosteroid-containing chemotherapy (R-steroid-chemo). The primary endpoint was the incidence of HBV reactivation defined as quantifiable HBV DNA levels of ≥11 1U/mL. Results. With a median HBV DNA follow-up of 562 days. HBV reactivation was observed in 21 of the 269 analyzed patients. The incidence of HBV reactivation at 1.5 years was 8.3% (95% confidence interval, 5.5–12.4). No hepatitis due to HBV reactivation was observed in patients who received antiviral treatment when HBV DNA levels were between 11 and 432 IU/mL. An anti-HBs titer of <10 mIU/mL and detectable HBV DNA remaining below the level of quantification at baseline were independent risk factors for HBV reactivation (hazard ratio, 20.6 and 56.2, respectively; P<.001). Even in 6 patients with a rapid increase of HBV due to mutations, the monthly HBV DNA monitoring was effective at preventing HBV-related hepatitis. Conclusions. Monthly monitoring of HBV DNA is useful for preventing HBV reactivation–related hepatitis among B-NHL patients with resolved HBV infection following R-steroid-chemo (UMIN000001299).

HBV reactivation (HBVr) can occur due to the ability of HBV to remain latent in the liver as covalently closed circular DNA and by the capacity of HBV to alter the immune system of the infected individuals. HBVr can occur in patients undergoing hematopoietic stem cell transplantation (HSCT) with a clinical spectrum that ranges from asymptomatic infection to fulminant hepatic failure. The risk of HBVr is determined by a complex interplay between host immunity, virus factors, and immunosuppression related to HSCT. All individuals who undergo HSCT should be screened for HBV. HSCT patients positive for HBsAg and also those HBcAb-positive/HBsAg-negative are at high risk of HBV reactivation (HBVr) due to profound and prolonged immunosuppression. Antiviral prophylaxis prevents HBVr, decreases HBVr-related morbidity and mortality in patients with chronic or previous HBV. The optimal duration of antiviral prophylaxis remains to be elucidated. The vaccination of HBV-naïve recipients and their donors against HBV prior to HSCT has an important role in the prevention of acquired HBV infection. This narrative review provides a comprehensive update on the current concepts, risk factors, molecular mechanisms, prevention, and management of HBVr in HSCT.

The hepatitis B virus (HBV) infection leads to chronic hepatitis, cirrhosis, and hepatocarcinoma. However, about 20% of patients experience extrahepatic manifestations such as polyarteritis nodosa, non-rheumatoid arthritis, non-Hodgkin lymphoma, cryoglobulinemic vasculitis, and glomerulonephritis. These influence the patient’s morbidity, quality of life and mortality. The treatment of an HBV infection is based on nucleotide analogues (NAs) which are safe and effective for the suppression of HBV-DNA in almost 100% of cases. A few studies have shown that NAs induce a viral response and an improvement of extrahepatic diseases. There is a lack of a thorough analysis of the available treatments for extrahepatic HBV manifestations. In 90% to 100% of cases, the NAs stop the HBV replication, and they produce a clinical response in the majority of patients with mild to moderate extrahepatic signs/symptoms. Arthritis can definitely disappear after the HBV elimination and, in some cases, the HBV eradication following NAs therapy appears to improve the renal function in HBV-related nephropathies. Plasma exchange can be used in subjects who are suffering from the most aggressive forms of cryoglobulinemic vasculitis and glomerulonephritis, progressive peripheral neuropathy, and life-threatening cases, and this can be combined with glucocorticosteroids and antiviral agents. In selected refractory patients, the use of rituximab in conjunction with NAs therapy can be considered. The review provides an update on extrahepatic conditions that are linked to HBV and the impact of treating HBV with NAs.

BackgroundA greater understanding of the determinants of health behavior among those with and at-risk of chronic hepatitis B virus (HBV) infection is needed for effective design and implementation of public health initiatives.AimsTo determine factors associated with (1) willingness to accept HBV antiviral treatment and (2) satisfaction with provider communication regarding HBV care in a diverse cohort of HBV-infected patients.MethodsUsing a multifaceted model of health behavior, the Health Behavior Framework, we conducted a comprehensive assessment of knowledge, attitudes, beliefs, and barriers to HBV care.ResultsWe enrolled 510 patients, with mean age 46 years; 53.1% men; and 71.6% Asian or Hawaiian/Pacific Islander. Patients were knowledgeable about HBV infection, but one-fifth did not think that HBV was a treatable disease; over a quarter felt it was so common among family and friends that it did not concern them, and less than half of patients believed they were likely to have liver problems or transmit HBV to others during their lifetime. Perceived susceptibility to disease risk was the only independent predictor of willingness to accept HBV treatment (β = 0.23, p = 0.0005), and contrary to expectations, having a doctor that speaks the same language was predictive of lower patient satisfaction with provider communication about their HBV care (β = − 0.65, p < 0.0001).ConclusionsPatients with greater perceived susceptibility to the health consequences of HBV infection are more likely to accept treatment, and patient–provider language concordance impacts patient satisfaction with communication regarding HBV care in an unexpected direction.