Tea Polyphenols Exerts Anti-hepatitis B Virus Effects in a Stably HBV-transfected Cell Line

In this study, the anti-HBV effects of tea polyphenols （TP） were examined. After cells were exposed to TP for 3, 6, 9 days, amounts of HBsAg, HBeAg and HBV-DNA released into the supernatant of the cultured HepG2 2.2.15 cells were detected. TP, to some extent, inhibited the secretion of HBsAg and strongly suppressed the secretion of HBeAg in a dose-dependent （P〈0.01） and time-dependent manner, with 50% maximal inhibitory concentration （IC50） value being 7.34μg/mL on the 9th day, but the time-dependence was not significant （P=0.051）. Expression of HBV-DNA in the supernatant of the cell culture also was significantly decreased in a dose-dependent fashion （P〈0.01）. The ICS0 of TP in inhibiting HBV DNA was 2.54 pg/mL. It concluded that TP possessed potential anti-HBV effects and may be used as a treatment alternative for HBV infection.

Influence of nonalcoholic fatty liver disease on response to antiviral treatment in patients with chronic hepatitis B:A meta-analysis

BACKGROUND Although hepatitis B virus infection is the leading cause of chronic liver injury globally,nonalcoholic fatty liver disease(NAFLD)is gradually gaining attention as another major chronic liver disease.The number of patients having chronic hepatitis B(CHB)with concomitant hepatic steatosis has increased.AIM To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB.METHODS Relevant English studies were systematically searched across PubMed,EMBASE,Web of Science,and Cochrane Library until October 2023.Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included.RESULTS Of the 2502 retrieved studies,11 articles were finally included.Biochemical response until 48 wk(OR=0.87,95%CI:0.50–1.53,P=0.000)and 96 wk(OR=0.35,95%CI:0.24–0.53,P=0.24)and virological response until 96 wk(OR=0.80,95%CI:0.43–1.49,P=0.097)were lower in patients with hepatic steatosis than in patients with CHB alone.CONCLUSION Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.

Molecular diagnosis and treatment of drug-resistant hepatitis B virus

Oral antiviral agents have been developed in the last two decades for the treatment of chronic hepatitis B(CHB).However,antiviral resistance remains an important challenge for long-term CHB therapy.All of the clinically available oral antiviral agents are nucleoside or nucleotide analogues that target the activity of viral reverse transcriptase(RT),and all are reported to have resistant mutations.Since the hepatitis B virus(HBV)RT,like other viral polymerases,lacks proofreading activity,the emergence of drug-resistance occurs readily under selective pressure from the administration of antiviral agents.The molecular diagnosis of drug-resistant HBV is based on sequence variations,and current diagnostic methods include sequencing,restriction fragment polymorphism analysis,and hybridization.Here,we will discuss the currently available molecular diagnosis tools,in vitro phenotypic assays for validation of drug-resistant HBV,and treatment options for drug-resistant HBV.

Current therapeutic strategies for recurrent hepatitis B virus infection after liver transplantation

Hepatitis B virus (HBV)-related liver disease is the leading indication for liver transplantation (LT) in Asia,especially in China.With the introduction of hepatitis B immunoglobulin (HBIG) and oral antiviral drugs,the recurrent HBV infection rate after LT has been evidently reduced.However,complete eradication of recurrent HBV infection after LT is almost impossible.Recurrent graft infection may lead to rapid disease progression and is a frequent cause of death within the fi rst year after LT.At present,the availability of new oral medications,especially nucleoside or nucleotide analogues such as adefovir dipivoxil,entecavir and tenofovir disoproxil fumarate,further strengthens our ability to treat recurrent HBV infection after LT.Moreover,since combined treatment with HBIG and antiviral agents after liver re-transplantation may play an important role in improving the prognosis of recurrent HBV infection,irreversible graft dysfunction secondary to recurrent HBV infection in spite of oral medications should no longer be considered an absolute contraindication for liver re-transplantation.Published reviews focusing on the therapeutic strategies for recurrent HBV infection after LT are very limited.In this article,the current therapeutic strategies for recurrent HBV infection after LT and evolving new trends are reviewed to guide clinical doctors to choose an optimal treatment plan in different clinical settings.

Role of hepatitis B virus DNA integration in human hepatocarcinogenesis

Liver cancer ranks sixth in cancer incidence, and is the third leading cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, which arises from hepatocytes and accounts for approximately 70%-85% of cases. Hepatitis B virus (HBV) frequently causes liver inflammation, hepatic damage and subsequent cirrhosis. Integrated viral DNA is found in 85%-90% of HBV-related HCCs. Its presence in tumors from non-cirrhotic livers of children or young adults further supports the role of viral DNA integration in hepatocarcinogenesis. Integration of subgenomic HBV DNA fragments into different locations within the host DNA is a significant feature of chronic HBV infection. Integration has two potential consequences: (1) the host genome becomes altered (“cis” effect); and (2) the HBV genome becomes altered (“trans” effect). The cis effect includes insertional mutagenesis, which can potentially disrupt host gene function or alter host gene regulation. Tumor progression is frequently associated with rearrangement and partial gain or loss of both viral and host sequences. However, the role of integrated HBV DNA in hepatocarcinogenesis remains controversial. Modern technology has provided a new paradigm to further our understanding of disease mechanisms. This review summarizes the role of HBV DNA integration in human carcinogenesis.

Adverse effects of oral antiviral therapy in chronic hepatitis B

Oral nucleoside/nucleotide analogues(NAs) are currently the backbone of chronic hepatitis B(CHB) infection treatment. They are generally well-tolerated by patients and safe to use. To date, a significant number of patients have been treated with NAs. Safety data has accumulated over the years. The aim of this article is to review and update the adverse effects of oral NAs. NAs can cause class adverse effects(i.e., myopathy, neuropathy, lactic acidosis) and dissimilar adverse effects. All NAs carry a "Black Box" warning because of the potential risk for mitochondrial dysfunction. However, these adverse effects are rarely reported. The majority of cases are associated with lamivudine and telbivudine. Adefovir can lead to dose- and time-dependent nephrotoxicity, even at low doses. Tenofovir has significant renal and bone toxicity in patients with human immunodeficiency virus(HIV) infection. However, bone and renal toxicity in patients with CHB are not as prominent as in HIV infection. Entecavir and lamivudine are not generally associated with renal adverse events. Entecavir has been claimed to increase the risk of lactic acidosis in decompensated liver disease and high Model for End-Stage Liver Disease scores. However, current studies reported that entecavir could be safely used in decompensated cirrhosis. An increase in fetal adverse events has not been reported with lamivudine, telbivudine and tenofovir use in pregnant women, while there is no adequate data regarding entecavir and adefovir. Further long-term experience is required to highlight the adverse effects of NAs, especially in special patient populations, including pregnant women, elderly and patients with renal impairment.

Clinical implications of hepatitis B virus mutations:Recent advances

Hepatitis B virus(HBV)infection is a major cause of acute and chronic hepatitis,and of its long-term complications.It is the most variable among DNA viruses,mostly because of its unique life cycle which includes the activity of error-prone enzyme,reverse transcriptase,and the very high virion production per day.In last two decades,numerous research studies have shown that the speed of disease progression,reliability of diagnostic methods and the success of antiviral therapy and immunization are all influenced by genetic variability of this virus.It was shown that mutations in specific regions of HBV genome could be responsible for unwanted clinical outcomes or evasion of detection by diagnostic tools,thus making the monitoring for these mutations a necessity in proper evaluation of patients.The success of the vaccination programs has now been challenged by the discovery of mutant viruses showing amino acid substitutions in hepatitis B surface antigen(HBsAg),which may lead to evasion of vaccine-induced immunity.However,the emergence of these mutations has not yet raised concern since it was shown that they develop slowly.Investigations of HBV genetic variability and clinical implications of specific mutations have resulted in significant advances over the past decade,particularly in regard to management of resistance to antiviral drugs.In the era of drugs with high genetic barrier for resistance,on-going monitoring for possible resistance is still essential since prolonged therapy is often necessary.Understanding the frequencies and clinical implications of viral mutations may contribute to improvement of diagnostic procedures,more proper planning of immunization programs and creating the most efficient therapeutic protocols.

Inhibition of hepatitis B virus by oxymatrine in vivo

AIM To investigate the anti-HBV effect ofoxymatrine (oxy) in vivo.METHODS HBV transgenic mice were producedby micro-injection of a 4.2kb fragmentcontaining the complete HBV genomes.Expression level of HBsAg and HBcAg in thetransgenic mice liver was determined byimmunohistochemical assay.RESULTS Four groups (6 mice in each group)were injected intraperitoneally with oxy at thedosage of 100,200, and 300 mg/kg or with salineonce a day for 30 days. Both HBsAg and HBcAgwere positive in livers of all the six mice in thecontrol group (injected with saline), and werepositive in livers of two mice in 100 mg/kg groupand 300mg/kg group. In 200mg/kg group,HBsAg and HBcAg were negative in livers of allthe six mice. Based on the results, 200 mg/kg isthe ideal dosage to explore the effect of oxy atdifferent time points. According to the oxytreatment time, mice were divided into fourgroups: 10 d, 20 d, 30 d and 60 d (4 mice in eachgroup). Each mouse underwent liver biopsy twoweeks before the treatment of oxy. Down-regulation of HBsAg and HBcAg appeared aftertreatment of oxymatrine for 10 d and 20 d, Dane-like particles disappeared after the treatment ofoxy for 20d under electron microscopy,however, the expression level of HBsAg andHBcAg returned to normal 60 d later after oxytreatment.CONCLUSION oxymatrine can reduce thecontents of HBsAg and HBcAg in transgenic miceliver, longer treatment time and larger dosagedo not yield better effects.

Novel approaches towards conquering hepatitis B virus infection

Currently approved treatments for hepatitis B virus （HBV） infection include the immunomodulatory agent, IFN-α, and nucleos（t）ide analogues. Their efficacy is limited by their side effects, as well as the induction of viral mutations that render them less potent. It is thus necessary to develop drugs that target additional viral antigens. Chemicals and biomaterials by unique methods of preventing HBV replication are currently being developed, including novel nucleosides and newly synthesized compounds such as capsid assembling and mRNA transcription inhibitors. Molecular therapies that target different stages of the HBV life cycle will aid current methods to manage chronic hepatitis B （CriB） infection. The use of immunomodulators and gene therapy are also under consideration. This report summarizes the most recent treatment possibilities for CHB infection. Emerging therapies and their potential mechanisms, efficacy, and pitfalls are discussed.

Clinical relevance of hepatitis B virus variants

The hepatitis B virus(HBV) is a global public health problem with more than 240 million people chronically infected worldwide, who are at risk for end-stage liver disease and hepatocellular carcinoma. There are an estimated 600000 deaths annually from complications of HBV-related liver disease. Antiviral therapy with nucleos/tide analogs(NA) targeting the HBV polymerase(P) can inhibit disease progression by long-term suppression of HBV replication. However, treatment may fail with first generation NA therapy due to the emergence of drugresistant mutants, as well as incomplete medication adherence. The HBV replicates via an error-prone reverse transcriptase leading to quasispecies. Due to overlapping open reading frames mutations within the HBV P can cause concomitant changes in the HBV surface gene(S) and vice versa. HBV quasispecies diversity is associated with response to antiviral therapy, disease severity and long-term clinical outcomes. Specific mutants have been associated with antiviral drug resistance, immune escape, liver fibrosis development and tumorgenesis. An understanding of HBV variants and their clinical relevance may be important for monitoring chronic hepatitis B disease progression and treatment response. In this review, we will discuss HBV molecular virology, mechanism of variant development, and their potential clinical impact.

Naturally derived anti-hepatitis B virus agents and their mechanism of action

Despite that some approved drugs and genetically engineered vaccines against hepatitis B virus(HBV)are available for HBV patients,HBV infection is still a severe public health problem in the world.All the approved therapeutic drugs(including interferonalpha and nucleoside analogues)have their limitations.No drugs or therapeutic methods can cure hepatitis B so far.Therefore,it is urgently needed to discover and develop new anti-HBV drugs,especially nonnucleoside agents.Naturally originated compounds with enormous molecular complexity and diversity offer a great opportunity to find novel anti-HBV lead compounds with specific antiviral mechanisms.In this review,the natural products against HBV are discussed according to their chemical classes such as terpenes,lignans,phenolic acids,polyphenols,lactones,alkaloids and flavonoids.Furthermore,novel mode of action or new targets of some representative anti-HBV natural products are also discussed.The aim of this review is to report new discoveries and updates pertaining to anti-HBV natural products in the last 20years,especially novel skeletons and mode of action.Although many natural products with various skeletons have been reported to exhibit potent anti-HBV effects to date,scarcely any of them are found in the list of conventional anti-HBV drugs worldwide.Additionly,in anti-HBV mechanism of action,only a few references reported new targets or novel mode of action of antiHBV natural products.

Management of psoriasis patients with hepatitis B or hepatitis C virus infection

The systemic therapies available for the management of Psoriasis (PsO) patients who cannot be treated with more conservative options, such as topical agents and/or phototherapy, with the exception of acitretin, can worsen or reactivate a chronic infection. Therefore, before administering immunosuppressive therapies with either conventional disease-modifying drugs (cDMARDs) or biological ones (bDMARDs) it is mandatory to screen patients for some infections, including hepatitis B virus (HBV) and hepatitis C virus (HCV). In particular, the patients eligible to receive an immunosuppressive drug must be screened for the following markers: antibody to hepatitis B core, antibody to hepatitis B surface antigen (anti-HBsAg), HBsAg, and antibody to HCV (anti-HCV). In case HBV or HCV infection is diagnosed, a close collaboration with a consultant hepatologist is needed before and during an immunosuppressive therapy. Concerning therapy with immunosuppressive drugs in PsO patients with HBV or HCV infection, data exist mainly for cyclosporine a (CyA) or bDMARDs (etanercept, adalimumab, infliximab, ustekinumab). The natural history of HBV and HCV infection differs significantly as well as the effect of immunosuppression on the aforementioned infectious diseases. As a rule, in the case of active HBV infection, systemic immunosuppressive antipsoriatic therapies must be deferred until the infection is controlled with an adequate antiviral treatment. Inactive carriers need to receive antiviral prophylaxis 2-4 wk before starting immunosuppressive therapy, to be continued after 6-12 mo from its suspension. Due to the risk of HBV reactivation, these patients should be monitored monthly for the first 3 mo and then every 3 mo for HBV DNA load together with transaminases levels. Concerning the patients who are occult HBV carriers, the risk of HBV reactivation is very low. Therefore, these patients generally do not need antiviral prophylaxis and the sera HBsAg and transaminases dosing can be monitored every 3 mo. Concerning PsO patients with chronic HCV infection their management with immunosuppressive drugs is less problematic as compared to those infected by HBV. In fact, HCV reactivation is an extremely rare event after administration of drugs such as CyA or tumor necrosis factor-α inhibitors. As a rule, these patients can be monitored measuring HCV RNA load, and ALT, aspartate transaminase, gamma-glutamyl-transferase, bilirubin, alkaline phosphatase, albumin and platelet every 3-6 mo. The present article provides an updated overview based on more recently reported data on monitoring and managing PsO patients who need systemic antipsoriatic treatment and have HBV or HCV infection as comorbidity.

Differing profiles of people diagnosed with acute and chronic hepatitis B virus infection in British Columbia,Canada

AIM To describe the characteristics of people diagnosed with acute and chronic hepatitis B virus(HBV) infection in British Columbia(BC).METHODS We used data from the BC Hepatitis Testers Cohort(BCHTC),which includes all individuals tested for hepatitis C virus(HCV) or human immunodeficiency virus(HIV) or those diagnosed with HBV or active tuberculosis in BC since 1990.These data were integrated with prescription drug,medical visit,hospitalization and mortality data.HBV cases were classified as acute or chronic according to provincial guidelines.We compared characteristics of individuals by HBV infection group(acute,chronic and negative).Factors associated with acute or chronic HBV infection were assessed with multinomial logistic regression models in comparison to the HBV negative group.RESULTS46498 of the 1058056 eligible BC-HTC participants were diagnosed with HBV infection.4.3% of HBV positive individuals were diagnosed with acute HBV infections while 95.7% had chronic infections.Problematic alcohol use,injection drug use,and HIV or HCV co-infection were more common among individuals diagnosed with acute HBV compared to those with chronic infections and HBV negative individuals.In multivariable multinomial logistic regression models,we observed significant associations between acute or chronic HBV diagnosis and being male,age at HBV diagnosis or birth cohort,South and East Asian ethnicity,HCV or HIV infection,and injection drug use.The odds of acute HBV decreased with increasing age among people who inject drugs,while the opposite was true for chronic HBV.Persons with acute HBV were predominantly White(78%) while those with chronic HBV were mostly East Asian(60%).Relative to Whites,East Asians had 12 times greater odds of being diagnosed with chronic HBV infection.These odds increased with increasing socioeconomic deprivation.CONCLUSION Differences in the profiles of people diagnosed with acute and chronic HBV infection necessitate differentiated screening,prevention,care and treatment programs.

Treatment of hepatitis B virus-associated glomerulonephritis:A meta-analysis

AIM:To evaluate the efficacy of antiviral or corticosteroid treatment on hepatitis B virus-associated glomerulonephritis(HBV-GN) . METHODS:Six and five trials were used respectively to evaluate the efficacy of either antiviral or corticosteroid treatment on HBV-GN.Pediatric patients were pooled separately to assess their response to the above treatment modalities.The primary and secondary outcomes were remission of proteinuria and clearance of Hepatitis B e-antigen(HBeAg) ,respectively.A fixed or random effect model was established to collect the data. RESULTS:The remission rate of proteinuria(RR=1.69,95%CI:1.08-2.65) and the clearance rate of HBeAg(RR =6.44,95%CI:3.11-13.35) were significantly higher in antiviral treatment group than in control group.The proteinuria remission was significantly associated with HBeAg clearance(P=0.002) .However,the difference in proteinuria remission rate was not statistically significant between corticosteroid treatment group and controlgroup(RR=1.45,95%CI:0.68-3.11) .Antiviral therapy could significantly promote the HBeAg clearance in pediatric patients,but neither antiviral nor corticosteroid therapy could significantly decrease proteinuria in pediatric patients compared to controls. CONCLUSION:Antiviral but not corticosteroid treatment can decrease proteinuria and promote HBeAg clearance in HBV-GN patients.

Application of hepatitis B virus replication mouse model

AIM:To evaluate the value of the hepatitis B virus(HBV) replication mouse model with regard to several aspects of the study of HBV biology.METHODS:To evaluate the HBV replication mouse model in detecting the efficacy of anti-HBV agents,the interferon inducer polyinosinic-polytidylin acid(polyIC) and nucleotide analogues adefovir and entecavir were administered to mice injected with wild type pHBV4.1,and the inhibiting effect of these agents on HBV DNA replication was evaluated.To identify the model's value in a replication ability study of HBV drug-resistant mutants and a HBx-minus mutant,telbivudine resistance mutants(rtM204I,ayw subtype),adefovir resistance mutants(rtA181V + rtN236T,ayw subtype) and HBxminus mutants were injected respectively,and their corresponding HBV DNA replication intermediates in mouse liver were assessed.RESULTS:Compared with the wild type HBV replication mouse model without antiviral agent treatment,the HBV DNA replication intermediates of the polyICtreated group were decreased 1-fold;while in the entecavir-and adefovir-treated groups,the levels of HBV DNA replication intermediates were inhibited 13.6-fold and 1.4-fold,respectively.For the mouse models injected with telbivudine resistance mutant,adefovir resistance mutant and HBx-minus mutant,HBV DNA replication intermediates could still be detected,but the levels of HBV DNA replication intermediates of these mutants decreased 4.5-fold,5.6-fold and 2.9-fold respectively,compared with the mouse model with wild type HBV plasmid.CONCLUSION:The HBV replication mouse model we established was a useful and convenient tool to detect the efficacy of antiviral agents and to study the replication ability of HBV mutants in vivo.

Resistant mutants induced by adefovir dipivoxil in hepatitis B virus isolates

AIM: To investigate the loci of adefovir dipivoxil (ADV)-induced resistance in hepatitis B virus (HBV) isolates and optimize the management of ADV-treated patients.

Long-term effects of lamivudine treatment in Japanese chronic hepatitis B patients

AIM： To analyze the association between the emergence of tyrosine-methionine-asparatate-asparatate （YMDD） mutants （reverse transcription; rtM204I/V） and deterioration of liver function during long-term lamivudine treatment of Japanese patients with chronic hepatitis B virus （HBV） infection. METHODS： The data of 61 consecutive Japanese pa- tients with chronic hepatitis B who underwent continu- ous lamivudine treatment for more than 24 mo and had a virological response were analyzed. Analysis of YMDD mutants was done by real-time polymerase chain reaction with LightCycler probe hybridization assay for up to 90 mo （mean, 50.8 too; range, 24-90 too）.RESULTS： A mixed mutant-type （YMDD ＋ tyrosine-iso- leucine-asparatate-asparatate： YIDD or tyrosine-valineasparatate-asparatate： YVDD） or a mutant-type （YIDD or YVDD） were found in 57.4% of 61 patients at i year, 78.7% of 61 patients at 2 years, 79.6% of 49 patients at 3 years, 70.5% of 34 patients at 4 years, 68.4% of 19 patients at 5 years, 57.1% of 14 patients at 6 years, and 33.3% of 6 patients at 7 years. Of the 61 patients, 56 （92%） had mixed mutant- or a mutant-type. Only 5 （8%） had no mutants at each observation point. Vi- rological breakthrough was found in 26 （46.4%） of 56 patients with YMDD mutants, 20 of whom had a hepa- titis flare-up： the remaining 30 （53.6%） had neither a virological breakthrough nor a flare-up. All 20 patients who developed a hepatitis flare-up had a biochemical and virological response after adefovir was added to the lamivudine treatment. CONCLUSION： Our results suggest that it is possible to continue lamivudine treatment, even after the emergence of YMDD mutants, up to the time that the patients develop a hepatitis flare-up.

Hepatitis B virus recurrence after liver transplantation: An old tale or a clear and present danger?

Hepatitis B virus(HBV) recurrence after liver transplantation(LT) has been described more than 50 years ago. Similarly, to other clinical conditions, in which impairment of host immune defense favors viral replication, early reports described in details recurrence and reactivation of HBV in liver transplant recipients. The evidence of a possible, severe, clinical evolution of HBV reappearance in a significant percentage of these patients, allowed to consider,for some years, HBV positivity a contraindication for LT. Moving from the old to the new millennium this picture has changed dramatically. Several studies contributed to establish efficient prophylactic protocols for HBV recurrence and with the advent of more potent anti-viral drugs an increased control of infection was achieved in transplanted patients as well as in the general immunecompetent HBV population. Success obtained in the last decade led some authors to the conclusion that HBV is now to consider just as a "mere nuisance".However, with regard to HBV and LT, outstanding issues are still on the table:(1)A standard HBV prophylaxis protocol after transplant has not yet been clearly defined;(2) The evidence of HBV resistant strains to the most potent antiviral agents is claiming for a new generation of drugs;and(3) The possibility of prophylaxis withdrawal in some patients has been demonstrated, but reliable methods for their selection are still lacking. The evolution of LT for HBV is examined in detail in this review together with the description of the strategies adopted to prevent HBV recurrence and their pros and cons.

Dried blood spots,valid screening for viral hepatitis and human immunodeficiency virus in real-life

AIM To detect chronic hepatitis B(CHB),chronic hepatitis C(CHC) and human immunodeficiency virus(HIV) infections in dried blood spot(DBS) and compare these samples to venous blood sampling in real-life.METHODS We included prospective patients with known viral infections from drug treatment centers,a prison and outpatient clinics and included blood donors as negative controls. Five drops of finger capillary blood were spotted on filter paper,and a venous blood sample was obtained. The samples were analyzed for HBs Ag,antiHBc,anti-HBs,anti-HCV,and anti-HIV levels as well as subjected to a combined nucleic acid test(NAT) for HBV DNA,HCV RNA and HIV RNA.RESULTS Samples from 404 subjects were screened(85 CHB,116 CHC,114 HIV and 99 blood donors). DBS had a sensitivity of > 96% and a specificity of > 98% for the detection of all three infections. NAT testing did not improve sensitivity,but correctly classified 95% of the anti-HCV-positive patients with chronic and past infections. Anti-HBc and anti-HBS showed low sensitivity in DBS(68% and 42%).CONCLUSION DBS sampling,combined with an automated analysis system,is a feasible screening method to diagnose chronic viral hepatitis and HIV infections outside of the health care system.

Current trends in management of hepatitis B virus reactivation in the biologic therapy era

Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonalantibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and longlasting immunosuppression. Emerging data indicatethat HBV reactivation could also develop following theuse of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is di-agnosed, it is mandatory to suspend biologic treatmentand start antiviral agents immediately. However, preemptive antiviral therapy prior to monoclonal antibodyadministration is crucial in preventing HBV reactivationand its clinical consequences. Several lines of evidencehave shown that risk of HBV reactivation is greatlyreduced by the identifi cation of high-risk patients andthe use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.