Hepatitis B Virus Reactivation Research Articles

Reactivation rates of hepatitis B or C or HIV in patients with psoriasis using biological therapies: a systematic review and meta-analysis.

Some biological therapies for psoriasis can cause the reactivation of viral infections. Although recent studies suggest no increased rate of reactivation with biological therapies, some life-threatening cases have been reported. Therefore, this meta-analysis examined the rate of virus reactivation in patients with psoriasis with biological therapies and concurrent hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection. PubMed, Embase, and the Cochrane Library were searched for available papers from inception to December 2021. The outcome was the number of patients with virus reactivation after using biological therapies. The random-effect model was used in all analyses. Fourteen reports (1033 patients) were included. The pooled overall rate of virus reactivation was 0.04 (95%CI 0.01-0.09; I2 = 67.7%, P < 0.001). The pooled rates of HBV, HCV, and HIV reactivation were 0.04 (95%CI 0.00-0.10; I2 = 79.9%, P < 0.001), 0.07 (95%CI 0.02-0.14; I2 = 23.7%, P = 0.24), and 0.12 (95%CI 0.00-0.40), respectively. The pooled rates of HBV and HCV reactivation were 0.10 (95%CI 0.03-0.19) and 0.08 (95%CI 0.03-0.15) in Asia, but 0.00 (95%CI 0.00-0.01) and 0.04 (95%CI 0.00-0.21) in Europe. The publication type also influenced the results. The use of biological therapy in patients with psoriasis and HBV, HCV, or HIV infection might be associated with the rate of viral reactivation, but this meta-analysis had limitations, and the evidence might be weak. Nevertheless, it might suggest that at least a consultation with an infection specialist might be warranted in patients with psoriasis in whom biological therapies are considered.

Clinical usefulness of a novel high-sensitivity hepatitis B core-related antigen assay to determine the initiation of treatment for HBV reactivation.

A fully automated, novel, high-sensitivity hepatitis B core-related antigen assay (iTACT-HBcrAg) has been developing. The purpose of this study is to evaluate the efficacy of measuring HBcrAg, using that assay, to diagnose HBV reactivation in a multi-center setting, compared with ultra-high-sensitivity HBsAg (iTACT-HBsAg) and HBV DNA assays. Forty-four patients with HBV reactivation from 2008 to 2020 were enrolled in four hospitals. Serial serum specimens from the patients were assessed retrospectively for their HBcrAg levels by iTACT-HBcrAg (lower limit of detection; 2.0 log U/mL) and HBsAg levels by iTACT-HBsAg (lower limit of detection; 0.0005IU/mL); these were compared to the HBV DNA levels. HBV reactivation was defined as detection of serum HBV DNA, including unquantifiable detection. At HBV reactivation and/or thereafter, HBV DNA levels were quantified (≥ 1.3 log IU/mL) in the sera of 27 patients, and were below the level of quantification (< 1.3 log IU/mL) in the sera of 17 patients. Of the 27 patients with HBV reactivation and whose serum HBV DNA was quantified, the sera of 26 and 24 patients (96.3% and 88.9%) were positive by iTACT-HBcrAg and iTACT-HBsAg, respectively. HBcrAg was detectable by iTACT-HBcrAg before HBV DNA was quantifiable in 15 of the 27 patients. Of the 11 patients with HBV reactivation and undetectable HBcrAg by iTACT-HBcrAg at HBV reactivation and/or thereafter, 10 had unquantifiable HBV DNA and none developed HBV reactivation-related hepatitis. The iTACT-HBcrAg assay is useful for monitoring HBV reactivation to determine the initiation of treatment with nucleos(t)ide analogues.

Effect of an Electronic Alert System on Hepatitis B Virus Reactivation in Patients Receiving Immunosuppressive Drug Therapy.

Hepatitis B virus (HBV) reactivation (HBVr) can occur in patients receiving immunosuppressive drug therapies, causing significant morbidity and mortality. Although the guidelines for HBVr have been proposed by several academic societies, some providers do not follow them, resulting in HBVr and death. As HBV-DNA levels increase before liver enzyme levels do, we previously constructed an electronic alert system that recommends the measurement of HBV-DNA. Here, we investigated whether this alert system improves the HBV-DNA measurement rate and elicits responses according to guidelines. A total of 5329 patients were divided into two groups, before and after the introduction of the alert system, and the HBV-DNA measurement rates in both groups were compared. Because of the introduction of the alert system, the HBV-DNA measurement rate among HBsAg-negative patients with anti-HBs and/or anti-HBc before immunosuppressive drug therapy improved significantly. The HBV-DNA monitoring rate within 3 months also improved significantly (p = 0.0034) in HBV-remission phase patients. HBVr was detected immediately, and the affected patients were treated with nucleotide analogs before severe hepatitis onset. The introduction of the alert system for HBVr improved the HBV-DNA measurement rates in patients receiving immunosuppressive drug therapy, leading to the rapid treatment of patients with HBVr.

Patients with COVID-19 and HBV Coinfection are at Risk of Poor Prognosis.

IntroductionThis study aimed to determine whether there is a difference in the risk of death/critical illness between different stages of hepatitis B virus (HBV) (resolved hepatitis B, HBeAg (−) chronic hepatitis B [CHB]/infection, HBeAg (+) CHB/infection, and HBV reactivation) coinfected with coronavirus disease 2019 (COVID-19); and if there is a difference, whether it is due to abnormal liver function and to what extent.MethodsThis cohort study included all COVID-19 inpatients of a single-center tertiary care academic hospital in Wuhan, Hubei, China, between February 4, 2020, and follow-up to April 14, 2020. A total of 2899 patients with COVID-19 were included as participants in this study, and they were divided into five groups based on hepatitis B infection status. Follow-up was conducted for mortality and ICU admission during hospitalization.ResultsThe median follow-up time was 39 days (IQR, 30–50), with 66 deaths and 126 ICU admissions. After adjustment, compared with patients without CHB, the hazard ratio (HR) for ICU admission was 1.86 (95% CI: 1.05–3.31) for patients with HBeAg (+) CHB/infection. The HR for death was 3.19 (95% CI: 1.62–6.25) for patients with HBeAg (+) CHB/infection. The results for the mediating effect indicated that the total effect of HBeAg (+) CHB/infection on death/ICU stay was partially mediated by abnormal liver function, which accounted for 79.60% and 73.53%, respectively.ConclusionPatients with COVID-19 coinfected with HBV at the HBeAg (+) CHB/infection stage have an increased risk of poor prognosis, and abnormal liver function partially mediates this increased risk of poor prognosis caused by the coinfection.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-022-00638-4.

Combining Telbivudine with Tenofovir in hepatitis B virus related acute on chronic liver failure reduce the risk of renal impairment.

Introduction: Chronic hepatitis B virus (HBV) infection is a major health problem because of its worldwide distribution and its potential adverse sequel, including acute-on-chronic liver failure (ACLF), liver cirrhosis and hepatocellular carcinoma. Short term prognosis of patients with spontaneous severe acute exacerbation of CHB leading to ACLF- like presentation is extremely poor, with mortality ranging from 30% to 70%. Therefore, early and rapid reduction of HBV DNA is the essence of therapy in ACLF-B. Methods: Patients with spontaneous reactivation of HBV [(ALT &gt;5 × upper limit of normal or &gt;2 × baseline) and HBV DNA &gt;20,000 IU/ml] were randomized to Tenofovir mono therapy (300 mg/day) or Tenofovir plus Telbivudine (600 mg/day) dual therapy along with standard medical treatment. Clinical and biochemical parameters were evaluated at baseline, 1 week, 4 weeks and at 3 months. Virological evaluation was done at baseline and at 3 months. Primary end point was reduction of HBV DNA. Secondary end point was reduction of liver related complication, therapy related adverse effects and survival at 3 months. Results: 27 patients were enrolled and 15 of them received mono therapy with Tenofovir and 12 patients received dual therapy (Tenofovir plus Telbivudine). Baseline parameters in two groups had no significant difference. Both groups significantly improve s. bilirubin, ALT, INR, CTP score and MELD score. Only MELD score showed significant improvement in patient with dual therapy at 3 months in comparison of mono therapy. 11 patient on Tenofovir mono therapy (n=15) showed undetected HBV DNA (91.7%) at 3 month and one patient had detectable HBV DNA (&lt;2,000 IU/ml). 10 patients on dual therapy (n=12) had undetectable HBV DNA (100%). Patients receiving dual therapy showed significant improvement in AKI on follow up compared to those on Tenofovir mono therapy. Among 5 deaths, 3 had received mono therapy with Tenofovir and 2 had received dual therapy. Predictors of mortality were high S. bilirubin (25.8±7.8), HBV DNA (5.18±1.17 log10 IU/ml), MELD score (33.0±4.2) and CTP score (12.2±0.8). Conclusion: In spontaneous reactivation of hepatitis B presenting as acute on chronic liver failure, combination of Telbivudine plus Tenofovir is potentially safer with less risk of Tenofovir related nephrotoxicity and hence improved outcomes. Bangladesh Crit Care J March 2022; 10 (1): 48-51

P057 Is baseline screening enough for long term biologic treatment? Looking for hepatitis in biologic populations

Abstract Background/Aims With biological agents used for inflammatory arthritis (IA) for over 20 years and the more recent addition of targeted synthetic agents, it is no surprise that pre-screening has evolved as we continually learn about these drugs. The BSR biologic guidelines (2018) recommend that we screen hepatitis B (HBV) and hepatitis C (HCV) serology prior to commencing any biologic. However, in long-term treatment, infection risks are posed from both new exposure and from reactivation of latent disease in the context of immunosuppression. The latter has been well recognised for tuberculosis, but we report a case of hepatitis B in a patient treated for 11 years, initially with anti-TNF for 2.5 years and subsequently with rituximab (RTX). We present an 80-year-old female patient diagnosed with rheumatoid arthritis (RA) in 2001, who migrated from Hong Kong in 1972. After initial treatment with gold, sulfasalazine, methotrexate, hydroxychloroquine and leflunomide, eventually etanercept (ETN) was initiated in 2010. In accordance with earlier BSR guidance (2005) we tested for HBsAg and HCV in 2009, prior to ETN, both were undetected. In early 2018, hepatology advice recommended including antibodies to hepatitis B core antigen (anti-HBc) with our screening, later specified by the current 2018 BSR guidance. Initially, this was only undertaken in new patients, however, we decided to re-check all patients on biologics to include anti-HBc in 2019. Prior to this, re-screening was not undertaken routinely at any interval or when switching biologic, unless there were relevant risk factors. The relevant guidance and recommendations, at the time, only recognised prior screening and reactivation of HBV. On re-testing our case in July 2021, anti-HBc was detected. Subsequently the patient was referred to hepatology and commenced on anti-viral treatment (tenofovir). The aim was to review all patients on biologics not previously screened for anti-HBc, especially those in high-risk groups. Methods A retrospective review of the hepatitis screening profiles of 71 patients. These patients were actively receiving RTX or infliximab in the preceding three years, since including anti-HBc. Results HBV was not detected in 55/71 (77.5%). Twelve patients (16.9%) are yet to be re-screened. HBV was detected in four individuals (5.6%). Our index patient, receiving RTX since 2012, underwent additional screen in 2021, likely delayed by the pandemic. Of the other three, one had no viral load detected and the result deemed a false positive. One patient was new to RTX in 2019, and the final patient had HBsAg detected with anti-HBc not detected. Conclusion For patients with IA receiving long-term biologic therapy, there is a need to standardise screening protocols for viral hepatitis and to undertake repeat testing at a reasonable interval, such as every five years and possibly more frequently in high-risk groups. Disclosure A. Eden: None. S. Ellis: None. T. Marianayagam: None.

Risk of hepatitis B reactivation: From biologic therapies for psoriasis to immunosuppressive therapies for COVID-19 (Review).

The cytokine storm from the evolution of severe cases of COVID-19, requiring strong immunosuppressive therapies, has raised the issue of reactivation of hepatitis B virus (HBV) infections in these patients. An analysis of the first observational studies in patients with COVID-19 and immunosuppressive therapy and HBV infection along with special clinical cases was presented, as well as personal experience on a series of cases (a group of 958 patients with COVID-19), compared with the analysis of studies performed on patients with HBV infection that underwent biological therapies for psoriasis and personal experience (a group of 81 psoriasis patients treated with biological therapies). Clinical studies have revealed that HBV reactivation in patients undergoing biological therapies for psoriasis, can be prevented with monitoring and treatment protocols and thus, these therapies have been demonstrated to be safe and effective. In COVID-19, immunosuppressive therapies are short-lived but in high doses, and the conclusions of clinical trials are contradictory, but there are published cases of HBV reactivation, which requires a unitary attitude in the prevention of HBV reactivation in these patients. An algorithm was presented for monitoring and treatment of HBV infection for patients with psoriasis treated with biological therapy and the conditions when this protocol can be used for patients with COVID-19 and immunosuppressive therapy.

Hepatitis B Virus Vaccination after Allogeneic Hematopoietic Cell Transplantation Prevents Post-Transplantation Hepatitis B Virus Reactivation

Hepatitis B virus (HBV) reactivation in allogeneic hematopoietic cell transplantation (HCT) recipients with evidence of pretransplantation resolved HBV infection is an important cause of morbidity, usually occurring 1 year or later after HCT. We retrospectively studied a cohort of allogeneic HCT recipients with resolved HBV infection, some of whom were vaccinated for HBV following transplantation, to understand whether post-HCT HBV vaccination influenced the risk of HBV reactivation. The study included all patients with resolved HBV who underwent allogeneic HCT at our institution between January 1, 2000, and December 31, 2015, where HBV vaccination starting at 1 year after HCT became standard in 2012 and antiviral prophylaxis is not used. Resolved HBV infection was defined as positive HBV-core IgG (HBcAb), negative HBV-surface antigen (HBsAg), and undetectable HBV DNA before HCT. HBV reactivation was defined as the development of detectable HBsAg and HBV DNA after HCT. Follow-up for outcomes concluded on January 1, 2018. Among 136 patients with resolved HBV infection before HCT, 19 developed reactivation during follow-up (cumulative incidence, 14%). The median time to HBV reactivation was 21 months (range, 2 to 47 months). When accounting for competing risks, the cumulative incidence of HBV reactivation among HCT recipients who survived for 1 year or longer after transplantation without early HBV reactivation and were HBV vaccinated versus those who were unvaccinated was 2.9% versus 10.0% at 2 years post-HCT and 6.6% versus 26.5% at 4 years post-HCT (P=0.03, Gray's test). In a time-dependent Cox model, the adjusted hazard ratio (aHR) of HBV reactivation in patients with a pretransplantation HBsAb level >10 IU/L was 0.34 (95% confidence interval [CI], 0.13 -0.90). The aHR of HBV reactivation in patients who were vaccinated with 2 or more doses of recombinant HBV vaccine after HCT was 0.18 (95% CI, 0.04-0.80) compared with those who received 1 or no post-HCT vaccine doses. HBV reactivation is a late complication of allogeneic HCT in at-risk recipients, particularly in those with low pre-HCT HBsAb. HBV vaccination starting at 1 year after HCT may be protective.

Hepatitis B and C screening in hospitalized patients with SARS-CoV-2 infection

AimsTo evaluate the results of a hepatitis B and C screening program in hospitalized COVID-19 patients.MethodTransversal prospective study conducted in two Spanish hospitals. Patients admitted from March 1st to December 31st 2020 with a diagnosis of COVID-19 were tested for markers of hepatitis B (HBsAg, anti-HBc) and C (anti-HCV, HCV RNA) infection.ResultsIn this period, 4662 patients with COVID-19 were admitted to our centers: 56.3% were male, median age was 76 (0–104) years. Data regarding HBV infection was available in 2915 (62.5%) patients; 253 (8.75%) were anti-HBc + and 11 (0.38%) HBsAg+. From these, 4 patients did not have a previous diagnosis of hepatitis B, 7 received corticosteroids and one received prophylaxis. There was one HBV reactivation. Anti-HCV were available in 2895 (62%) patients; 24 (0.83%) were positive. From these, 13 patients had a previous hepatitis C diagnosis: 10 patients had been treated with SVR, one achieved spontaneous cure and 2 did not receive treatment. From the 11 previously unknown anti-VHC + patients, 10 had a negative HCV RNA. Overall, only 3 (0.10%) patients tested RNA HCV + . However, none received HCV treatment (2 older than 90 years with comorbidities, 1 died from COVID-19).ConclusionScreening of hepatitis C infection in hospitalized COVID-19 patients seems less useful than expected. The low prevalence of active infection after antiviral treatments and the high age of our population limit the detection of potential candidates for treatment. HBV screening should be aimed to prevent reactivation under immunosuppressive treatments.

Occult hepatitis B virus infection in hepatitis C virus negative chronic liver diseases.

Data concerning the prevalence of hepatitis B virus (HBV) occult infection (OBI) varies greatly in the different studies according to the sensitivity and specificity of the diagnostic approaches and the HBV prevalence in the different populations examined. The clinical implications of OBI are still debated. While the impact of OBI in HBV transmission as well as in HBV reactivation under immunosuppression are well established, the role of OBI in liver disease and hepatocellular carcinoma (HCC) development are still not definitively elucidated. It has been hypothesized that OBI might contribute to worsening the liver disease course when other causes of liver damage co‐exist. Furthermore, much evidence suggests a role of OBI in the hepato‐carcinogenesis processes through both indirect and direct oncogenic mechanisms that might favour HCC development. Data on the OBI clinical implications mainly come from studies performed in patients with hepatitis C virus (HCV) infection. However, HCV prevalence has dramatically fallen in the past years also because of the advent of specific and highly effective direct acting antivirals, with a consequent abrupt change of the worldwide scenario of chronic liver disease. Information about OBI prevalence and possible clinical impact in non‐HCV‐related liver disease are fragmentary, and the objective of this review is to critically summarize the available data in this field.

Reactivation of Occult Hepatitis B Virus Infection During Long-Term Entecavir Antiviral Therapy.

Up to now, it has not been clear whether occult hepatitis B virus (HBV) infection (OBI) can be treated with antiviral therapy whether OBI can develop drug resistance gene mutation or not. We report a middle-aged female patient with OBI who showed HBV reactivation (HBVr) during more than 3 years of intermittent entecavir (ETV) antiviral therapy: seropositive HBV surface antigen (HBsAg), increased e antigen (HBeAg), and repeatedly elevated serum HBV DNA. Genotype analysis showed that the patient was infected with HBV type B. Genetic sequencing of HBV showed the mutants of S143T, D144G, and G145R in the S gene region, and the mutant of site 1896 in the pre-Core region coexisted with the wild type (G1896A/G). No mutation was found in other HBV gene segments. Drug resistance gene analysis found RtL229W mutant, resistant to lamivudine but sensitive to ETV and other nucleoside analogs. This case of OBI provides us with the following clinical experiences: Firstly, it is necessary to detect HBV genotype, mutation, and drug-resistant genes at the initial diagnosis, which can be helpful for reasonable treatment. Secondly, identifying the risk factors and mechanisms associated with HBVr could help quantify the risk of HBVr and manage the clinical consequences. Thirdly, the OBI patients with hepatitis B e antigen-positive, HBV DNA > 1 × 103 IU/ml should be recommended regular and continuous antiviral therapy as soon as possible to prevent the occurrence of hepatocirrhosis and hepatocellular carcinoma (HCC).

Management of hepatitis B virus (HBV) reactivation in patients with resolved HBV infection based on a highly sensitive HB core-related antigen assay.

To prevent hepatitis B virus (HBV) reactivation-related hepatitis, we examined the clinical usefulness of a highly sensitive HB core-related antigen (iTACT-HBcrAg) assay in patients with resolved HBV infection after nucleos(t)ide analog (NA) treatment for HBV reactivation. We retrospectively analyzed 27 patients with resolved HBV infection who experienced HBV reactivation (defined as HBV DNA levels of 1.3 log IU/ml or more), and who received systemic chemotherapies for hematological malignancies between 2008 and 2020. iTACT-HBcrAg, HBsAg-HQ, and antibodies against hepatitis B surface antigen (anti-HBs) were measured using samples stored after HBV reactivation. The lower limit of quantification for iTACT-HBcrAg was 2.0 log U/ml. HBV reactivation was diagnosed at a median HBV DNA level of 1.8 log IU/ml, and then all patients received NA treatment. No patient had HBV-related hepatitis with a median maximum HBV DNA level of 2.0 log IU/ml. The positivities of iTACT-HBcrAg and HBsAg-HQ were 96% and 52% after HBV reactivation, respectively. Of 25 patients with detectable iTACT-HBcrAg at the initiation of NA treatment, 17 (68%) achieved iTACT-HBcrAg loss. Median durations from NA treatment to HBV DNA loss and iTACT-HBcrAg loss or the last follow-up were 35 and 175days, respectively. Recurrence of HBV reactivation after NA cessation was not observed in seven of eight patients who achieved iTACT-HBcrAg loss or seropositive for anti-HBs during follow-up, except for one without anti-HBs after allogeneic transplantation. iTACT-HBcrAg could be a potential surrogate marker for diagnosing early-stage HBV reactivation as well as safe cessation of NA treatment in patients with resolved HBV infection after HBV reactivation.

Different Kinetics of HBV-DNA and HBsAg in HCV Coinfected Patients during DAAs Therapy.

Direct-acting antivirals (DAAs) for hepatitis C virus (HCV) may induce hepatitis B virus (HBV) reactivations in co-infected patients, whose dynamics and outcomes could depend on the phase of HBV infection. We investigated HBsAg and HBV-DNA kinetics in fifteen untreated HBeAg Negative Infection (ENI) (4F-11M, 62.1y) and eight Nucleos(t)ide Analogs (NAs) treated Chronic Hepatitis B (CHB) (3F-6M, 54.8y) with HCV co-infection, receiving DAAs-regimens including Sofosbuvir (13) or not (10). All achieved a sustained virologic response (SVR) and normalized alanine-aminotransferase (ALT). At the direct acting antivirals’ (DAAs) baseline (BL), the HBV-DNA was undetectable (<6 IU/mL) in eight ENI and all CHB, the mean Log-HBsAg was lower in ENI than CHB (0.88 vs. 2.42, p = 0.035). During DAAs, HBV-DNA increased in untreated ENI by >1 Log in five and became detectable in two. Accordingly, mean BL Log-HBV-DNA (0.89) increased at week-4 (1.78; p = 0.100) and at the end of therapy (1.57; p = 0.104). Mean Log-HBsAg decreased at week-4 in ENI (from 0.88 to 0.55; p = 0.020) and CHB (from 2.42 to 2.15; p = 0.015). After DAAs, the HBsAg returned to pre-treatment levels in CHB, but not in ENI (six cleared HBsAg). Female gender and SOF were associated with a greater HBsAg decline. In conclusion, HBV reactivations during DAAs in HCV co-infected ENI caused moderate increases of HBV-DNA without ALT elevations. The concomitant HBsAg decline, although significant, did not modify individual pre-treatment profiles.

Hepatitis B and C virus reactivations under biologic treatments in patients with rheumatic diseases: long-term results from a single-center

Objectives: To find out the effects and prevalence of disease-modifying antirheumatic drugs (DMARDs) and anti-TNF agents on hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-positive patients with rheumatic diseases (RD). Methods: This retrospective study was conducted on 1,548 RD patients. Patients’ medical records regarding immunological profiles, clinical courses, and outcomes, were obtained. In this research, the patient used conventional DMARDs (cDMARDs) and biological DMARDs (bDMARDs). A drug exposure was considered when a patient was administered GC, cDMARDs, or bDMARDs for &amp;gt; 4 weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin were measured. HBsAg, HBV DNA assay, anti-HCV and HIV were identified. Results: HBsAg was positive in 19 (37.3%) patients. Anti-HBs in 5 (9.8%) patients and anti-HBc IgG in 35 (68.6%) patients were positive. All patients with HBsAg positivity were receiving antiviral prophylaxis. Anti-HCV was positive in 25.5% (n = 13) of individuals . There was not any reactivation among the patients. No HBV reactivation was observed. Conclusions: Screening before treatment and give prophylaxis to patients who have occult hepatitis or hepatitis B, may be an important factor in the absence of reactivation. Hepatitis screening should be performed in all patients prior to biological treatment is initiated.

Role of Hepatitis B Surface Antibodies in Risk for Hepatitis B Virus Reactivation During Anti–Tumor Necrosis Factor Therapy

An estimated 250 million people are chronically infected with hepatitis B virus (HBV), with more than 800,000 deaths related to HBV.1 Although the prevalence of HBV has been decreasing, reactivation remains a cause for concern.2 Reactivation is defined by the resurgence of HBV DNA and/or HBV surface antigen (HBsAg) seroreversion in patients with resolved HBV or an increase in HBV viral load in chronic hepatitis.3 Anti-tumor necrosis factor (TNF) therapies have been shown to place patients at a risk for HBV reactivation.4.

HBV Reactivation in Patients with Past Infection Affected by Non-Hodgkin Lymphoma and Treated with Anti-CD20 Antibody Based Immuno-Chemotherapy: A Multicenter Experience.

Hepatitis B virus reactivation (HBVr) can develop in HBV surface antigen (HBsAg) positive or HBsAg-negative and anti-hepatitis B core antigen antibodies (anti-HBc) positive (past HBV infection) patients receiving immuno-chemotherapy for hematological malignancies. A higher rate of HBVr is associated with the use of rituximab (R) in patients with past HBV infection, thus justifying an antiviral prophylaxis. In this study we evaluated the incidence of HBVr in a real-life cohort of 362 anti-HBc-positive subjects affected by non-Hodgkin lymphoma (NHL), mainly receiving lamivudine (LAM) prophylaxis (93%) and all undergoing a R-containing regimen. A retrospective, multicenter, observational study was conducted in 4 Italian Hematology Departments. The primary endpoint was the incidence of virologic (HBV DNA-positive), serologic (HBsAg-positive) and clinical (ALT increase > 3 × upper limit of normal) HBVr, which occurred in five, four and one patients, respectively, with a total HBVr rate of 1.4%. None of them had to discontinue the chemotherapy program, while two patients required a delay. Treatment-related adverse events (AEs) were reported during LAM prophylaxis in three patients (0.9%). In conclusion, this study confirms the efficacy and safety of LAM prophylaxis in anti-HBc-positive patients undergoing R-containing regimens.

Abstract P1-15-02: Low incidence of hepatitis B reactivation after chemotherapy in Japanese breast cancer patients with resolved HBV

Abstract Background: Recently, chemotherapy-induced reactivation of hepatitis B virus (HBV) has been reported not only in patients with HBV surface antigen positive (HBsAg+) but also in patients with resolved HBV (HBsAg-, anti-HBV-core antibody positive (anti-HBc+). The incidnce of HBV reactivation after adjuvant/neo-adjuvant chemotherapy for breast cancer in patients with resolved HBV infection remains unclear. In this study, we surveyed the incidence of HBV reactivation in Japanese breast cancer patients who received adjuvant/neo-adjuvant chemotherapy. Methods: A total of 3042 breast cancer patients who received neoadjuvant and/or adjuvant chemotherapy from June 2008 to December 2016 were included in this study. HBsAg, anti-HBc and anti-HBV-surface antibody (anti-HBs) were tested before chemotherapy. Serum HBV-DNA levels were subsequently measured and monitored for one year after the completion of adjuvant/neo-adjuvant chemotherapy if the patient exhibited a resolved HBV infection. Results: Of the 3042 patients (pts), 32 (1.05%)cases were positive for HBsAg and 2992 pts were negative for HBsAg. 301 pts (9.9 %) were revealed resolved HBV infection; 221 pts were with anti-HBc+ and anti-HBs+, 40 pts were with anti-HBc+ and anti-HBs-, and 130 pts were with anti-HBc- and anti-HBs+. Of the 130 pts with anti-HBc- and anti-HBs+, 77 pts were previously vaccinated for hepatitis B. The antibody-positive rate by age group was 2.7% (1/37) for patients in their 20s, 4.1% (14/344) for those in their 30s, 6.5% (67/1037) for those in their 40s, 9.4% (77/817) for those in their 50s, 16.6% (109/655) for those in their 60s, 20% (30/150) for those in their 70s, and 0% (0/2) for those in their 80s. Among the 301 pts with resolved HBV infection, 71 pts were monitored for one year after the completion of their chemotherapy. The median monitoring period was 579 days (386-3458). In our monitoring period, only one patient (1.4%) was diagnosed with HBV reactivation based on a slightly elevated HBV-DNA level at 1-year-test. No death or hepatitis due to HBV reactivation occurred during the monitoring period. Conclusions: The prevalence of resolved HBV infection in Japan showed an increasing trend with age. Adjuvant/neoadjuvant chemotherapy for breast cancer patients with resolved HBV infection has a risk of HBV reactivation. Our study suggested the risk of reactivation was low and the risk of a flare of HBV disease could be controlled with screening and carefully monitoring. Citation Format: Takayo Fukuda, Masaya Hattori, Yukinori Ozaki, Lina Inagaki, Mari Hosonaga, Ippei Fukada, Kokoro Kobayashi, Fumikata Hara, Takayuki Kobayashi, Sachiyo Yoshio, Takayuki Ueno, Toshimi Takano, Shinji Ohno. Low incidence of hepatitis B reactivation after chemotherapy in Japanese breast cancer patients with resolved HBV [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-15-02.

Highly Sensitive HBsAg, Anti-HBc and Anti HBsAg Titres in Early Diagnosis of HBV Reactivation in Anti-HBc-Positive Onco-Haematological Patients.

The role of novel HBV markers in predicting Hepatitis B virus reactivation (HBV-R) in HBsAg-negative/anti-HBc-positive oncohaematological patients was examined. One hundred and seven HBsAg-negative/anti-HBc-positive oncohaematological patients, receiving anti-HBV prophylaxis for >18 months, were included. At baseline, all patients had undetectable HBV DNA, and 67.3% were anti-HBs positive. HBV-R occurred in 17 (15.9%) patients: 6 during and 11 after the prophylaxis period. At HBV-R, the median (IQR) HBV-DNA was 44 (27–40509) IU/mL, and the alanine aminotransferase upper limit of normal (ULN) was 44% (median (IQR): 81 (49–541) U/L). An anti-HBc > 3 cut-off index (COI) plus anti-HBs persistently/declining to <50 mIU/mL was predictive for HBV-R (OR (95% CI): 9.1 (2.7–30.2); 63% of patients with vs. 15% without this combination experienced HBV-R (p < 0.001)). The detection of highly sensitive (HS) HBsAg and/or HBV-DNA confirmed at >2 time points, also predicts HBV-R (OR (95% CI): 13.8 (3.6–52.6); 50% of positive vs. 7% of negative patients to these markers experienced HBV-R (p = 0.001)). HS-HBs and anti-HBc titration proved to be useful early markers of HBV-R. The use of these markers demonstrated that HBV-R frequently occurs in oncohaematological patients with signs of resolved HBV infection, raising issues of proper HBV-R monitoring.

Hepatitis B Reactivation in Patients Treated with Direct-Acting Antivirals for Hepatitis C

Introduction: There is limited research about HBV reactivation (HBVr) due to direct-acting antivirals (DAA) for HCV and most are limited by short duration of follow-up, small sample size, and absence of baseline HBV DNA. We aimed to determine the incidence and clinical course of HBVr in HBsAg and/or anti-HBcIgG positive patients treated with DAA for HCV. Methods: Seven centers retrospectively analyzed their database on HCV patients treated with DAA between 2015 and 2019. Patients with HBV coinfection or resolved HBV infection were enrolled. Serum transaminases, HBsAg, HBeAg, and HBV DNA were followed every 4 weeks during DAA treatment and every 12 weeks 1 year after treatment. Entecavir or tenofovir disoproxil fumarate was started in case of HBVr. The development of HBVr, HBV flare, liver failure, and mortality were determined. Results: 852 patients received DAA treatment for HCV. Among them, 35 (4.1%) had HBV coinfection and 246 (28.9%) had resolved HBV infection. 257 patients (53.3% male, mean age: 63 ± 9) constituted the study group (29 with coinfection and 228 with resolved infection). Three patients with coinfection were HBV DNA positive. HBVr developed in 10 (34.5%) HBsAg positive patients, either during (n = 3) or 12–48 weeks after finishing DAA treatment. HBV flare and acute liver failure developed in 1 patient (3.4%), each. Two patients with resolved infection developed HBVr (0.87%) and one (0.44%) had HBV flare. Overall, none of the patients died or underwent liver transplantation due to HBVr. Conclusion: Patients with HBV/HCV coinfection have a high risk of HBVr after DAA treatment and should receive antiviral prophylaxis. Patients with resolved infection have a low risk of HBVr and can be monitored by serial ALT measurements.

Clinical outcomes in patients (pts) with previously treated advanced hepatocellular carcinoma (HCC) experiencing hepatitis B virus (HBV) DNA increases during tislelizumab (TIS) treatment in RATIONALE-208.

411 Background: The effect of checkpoint inhibitor therapy on HBV infection is uncertain. TIS, an anti-PD-1 antibody, was clinically active and well tolerated in pts with previously treated advanced HCC in the phase 2 RATIONALE-208 study (NCT03419897). Objective response rate by independent committee review (IRC) in pts with a history of HBV infection was consistent with the overall population (12.5% vs. 13.3%, respectively). We explored whether TIS treatment was associated with increased HBV DNA and the clinical significance of HBV DNA elevations. Methods: Pts with ≥ 1 prior systemic therapy for advanced HCC received TIS 200 mg IV Q3W. Pts with inactive, chronic, or active HBV were eligible if HBV DNA levels were &lt; 500 IU/mL at screening (pts with detectable hepatitis B surface antigen [HBsAg] or detectable HBV DNA were required to be managed per treatment guidelines). HBV DNA testing was conducted every 4 cycles if HBV DNA was detectable at screening, or when clinically indicated. Results: Among 249 enrolled pts, 128 had a history of HBV infection. Of these pts, 114 were HBsAg positive at baseline (BL), 36 had detectable HBV DNA at BL, and 32 had detectable HBV DNA and HBsAg at BL. Clinically significant increases in HBV DNA levels from BL were reported in 7 pts, with no pattern relative to the time of TIS initiation (Table). All 7 pts were HBsAg positive at BL and had been receiving antiviral treatment for ≥ 3 months before the first dose of TIS. Six out of the 7 pts had increases in alanine transaminase (ALT) from BL during the study (Table), 4 of whom had ≥ 3-fold increases in ALT which were observed concurrently or soon after HBV DNA increases. IRC-assessed best overall response (BOR) was partial response (PR) for 1 pt with increased HBV DNA and progressive disease for the remaining 6. HBV-related treatment-emergent adverse events (TEAEs) were reported in 6 of the 7 pts (2 pts had a grade 3 TEAE of hepatitis B; 2 pts had a grade 2 TEAE of HBV reactivation; 2 pts had a TEAE of increased HBV DNA, with one grade 1 and one grade 3 event). All HBV-related TEAEs were non-serious and did not result in discontinuation of TIS. Conclusions: Clinically significant increases in HBV DNA from BL were reported in a small number of pts, which does not suggest that TIS is associated with increased HBV DNA. Tumor responses in these pts were consistent with the overall population and HBV-related TEAEs were manageable and did not require discontinuation of TIS, demonstrating that HBV DNA increases did not impact treatment. The effects of TIS in pts with HBV infection will be further investigated in an ongoing phase 3 trial (NCT03412773). Clinical trial information: NCT03419897. [Table: see text]