Risk Of Hepatitis B Virus Reactivation Research Articles

Chronic hepatitis B in rheumatic diseases: issues of screening and reactivation of infection: A review

Patients with rheumatic diseases infected with hepatitis B virus (HBV) are difficult to manage not only due to the presence of risk factors for the development and rapid progression of liver cirrhosis, but also due to the likelihood of reactivation of this infection. Despite the successes achieved in the fight against HBV, the virus cannot be completely defeated due to the presence of hidden forms of the disease, escaping the field of vision of a rheumatologist and an infectionist. Based on the results of the analysis of current publications, the paper presents the rationale for a complete immunological screening of patients with rheumatic diseases when prescribing antirheumatic therapy. The issues of the role of COVID-19 in the exacerbation of chronic viral hepatitis B, antiviral prevention and monitoring are discussed, the classification of antirheumatic drugs according to the risk of HBV reactivation is presented.

Jaundice That Has Persisted for 5 Days

Hepatitis B virus (HBV) reactivation associated with various therapeutic interventions is a significant cause of morbidity and mortality among patients with current or resolved HBV infection. Since no curative treatment for HBV infection is currently available, a large number of individuals in the general population are at risk for HBV reactivation. Populations vulnerable to HBV reactivation include those currently infected with HBV or those who have had past exposure to the virus. The potential consequences of HBV reactivation are particularly concerning when these populations undergo anti-cancer chemotherapy, immunosuppressive or immunomodulatory therapies for managing various malignancies, rheumatologic diseases, inflammatory bowel disease, or undergo solid-organ or hematologic stem cell transplantation. This article aims to increase awareness of HBV reactivation and to elucidate the mechanisms and risks associated with HBV reactivation in various clinical settings.

Implementation of Guideline-Based HBV Reactivation Management in Patients with Chronic HBV Infections of HBsAg or Resolved HBV Infection Undergoing Immunosuppressive Therapy.

Although patients with HBVhave a risk of reactivation after immunosuppressive therapy (IST), the status of their risk management is unclear in Japan. This study aims to describe the proportion of patients who received preventive management of HBV reactivation during ISTs in patients with chronic HBV infection of HBsAg or resolved HBV infection. A retrospective cohort study was conducted using the JMDC Japanese claims database from April 2011 to June 2021. Patients with HBV infections of HbsAg who received ISTs or patients who had resolved HBV infections who received ISTs were identified from the database and evaluated for appropriate management to prevent HBV reactivation. In total, 6242 eligible patients were identified. The proportions of patients with appropriate HBV reactivation management, stratified by the HBV reactivation risk level of IST, was 43.1% (276/641) for high-risk, 40.2% (223/555) for intermediate-risk and 14.9% (741/4965) for low-risk patients. When the evaluation period for the outcome calculation was shortened from 360 to 180days, the proportion for high risk increased to 52.7%. The odds ratios of large hospitals for receiving appropriate management were 2.16 (95% CI 1.12-4.44) in the high-risk, 4.63 (95% CI 2.34-10.25) in the intermediate-risk and 3.60 (95% CI 3.07-4.24) in the low-risk patients. HBV reactivation management was tailored according to the reactivation risk associated with IST. However, adherence to HBV reactivation management guidelines was sub-optimal, even among high-risk patients. This is especially the case for ensuring smaller-sized medical institutions, highlighting the need for further educational activities.

Hepatitis B reactivation after solid organ transplantation: A single-center experience

BackgroundThe risk of HBV reactivation after solid organ transplantation and the strategies to prevent it are not well defined. MethodsWe reviewed patients who received liver, kidney, pancreas, or heart transplants at our center between September 2015 and November 2020. We collected recipient and donor data on HBV serologies, prophylactic strategies, and known risk factors that associate with HBV reactivation in post-transplant patients. ResultsIn the study period, 2126 solid organs were transplanted into 1951 patients. The recipient (R), donor (D), or both were HBcAb(+)/HBsAg(-) in 360 transplants. Post-transplant HBV DNA developed in 0/10 heart, 0/3 pancreas-kidney, 2/1517 (0.1 %) kidney, and 10/430 (2.3 %) liver recipients. Both kidney recipients with HBV DNA tested negative on re-testing without treatment. HBV DNA developed in 17.5 % of liver recipients who were D+/R- for HBcAb (10/57). All 10 liver recipients developing HBV DNA received prophylaxis. 5 patients developed detectable HBV DNA while on prophylaxis at a median 886 days (range 139 to 2287) after transplant. 5 patients developed HBV DNA after prophylaxis was discontinued at a median 955 days (range 756 to 2003) after transplant and 596 days (395 to 1638) after discontinuation. ConclusionHBcAb is found in a significant portion of our solid organ transplant donors and recipients, and HBcAb(+)/HBsAg(-) liver allografts represent the primary risk factor for HBV post-transplant. HBV infection in non-liver solid organ transplant is minimal risk using current monitoring strategies. Infection can occur long after the transplant event. Monitoring and prophylaxis strategies in this group should be reassessed.

Management of Hepatitis B Virus and Hepatitis C Virus Infections in Patients with Cancer Receiving Immune Checkpoint Inhibitors.

Patients with cancer with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are excluded from many cancer clinical trials of immune checkpoint inhibitors (ICIs). Therefore, data are limited regarding the management of HBV and HCV infections in patients with cancer treated with ICIs. To address this gap, we reviewed the literature on management of HBV and HCV infections in patients with cancer receiving ICIs. We searched MEDLINE and PubMed for all original research articles, case reports, and systematic reviews published in English between Jul 2013 and Jul 2023 on patients with cancer with HBV or HCV infection receiving ICIs. We found 28 studies (three prospective clinical trials, seven retrospective cohort studies, nine retrospective case series, and nine case reports) that evaluated the safety of ICI therapy in patients with HBV infection and cancer. The overall rate of HBV reactivation was 1.4% (38/2799), and no HBV-related deaths were reported. The frequency of HBV reactivation in patients with chronic and past HBV infections was 2% (35/1667) and 0.3% (3/1132), respectively. The risk of HBV reactivation was significantly higher among patients with chronic HBV infection not receiving antiviral prophylaxis than among those receiving antivirals (17% vs 1%, p < 0.05). Based on high-quality evidence, for patients with chronic HBV infection, antiviral prophylaxis is recommended before ICI therapy initiation. For patients with past HBV infection, monitoring and on-demand antiviral treatment are sufficient. We found 11 studies (five clinical trials, five retrospective studies, and one prospective observational study) that evaluated the safety of ICI therapy in patients with HCV infection and cancer. The overall rate of HCV reactivation was 0.5% (2/387), and no HCV-related deaths were reported. HCV reactivation occurs primarily in patients receiving immunosuppressants for ICI-related toxic effects. ICIs are safe for HCV-infected patients with solid tumors. Chronic HBV or HCV infection should not be considered a contraindication for ICI therapy. Specific risk assessment, monitoring, and management strategies are necessary to reduce the risk of ICI-related liver injury in patients with cancer and chronic HBV or HCV infection.

A cross-sectional survey of hepatitis B virus screening in patients who received immunosuppressive therapy for rheumatoid arthritis in Japan.

Patients with a history of hepatitis B virus (HBV) infection who are receiving immunosuppressive therapy are at risk of HBV reactivation and disease. Therefore, HBV screening is required prior to administering antirheumatic drugs with immunosuppressive effects. This study aimed to determine the status of hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and hepatitis B surface antibody (HBsAb) screening prior to the initiation of drug therapy, including new antirheumatic drugs, in patients with rheumatoid arthritis. This retrospective cross-sectional study used data from April 2014 to August 2022 from the Japanese hospital-based administrative claims database. The inclusion criteria were rheumatoid arthritis and first prescription date of antirheumatic drugs. A total of 82,282 patients with rheumatoid arthritis who were first prescribed antirheumatic drugs between April 2016 and August 2022 were included. Of the eligible patients, 9.7% (n=7,959) were screened for all HBV (HBsAg, HBsAb, and HbcAb) within 12 months prior to the date of initial prescription. The HBsAg test was performed in 30.0% (n=24,700), HBsAb test in 11.8% (n=9,717), and HBcAb test in 13.1% (n=10,824) of patients. The proportion of patients screened for HBV infection has been increasing since 2018; however, the proportion of patients screened for rheumatoid arthritis remains low. Our findings suggest that HBV screening may be insufficient in patients who received antirheumatic drugs. With the increasing use of new immunosuppressive antirheumatic drugs, including biological agents, healthcare providers should understand the risk of HBV reactivation and conduct appropriate screening.

Post-transplant hepatitis B virus reactivation impacts the prognosis of patients with hepatitis B-related hepatocellular carcinoma: a dual-centre retrospective cohort study in China.

Highly active hepatitis B virus (HBV) is known to be associated with poor outcomes in patients with hepatocellular carcinoma (HCC). This study aims to investigate the relationship between HBV status and HCC recurrence after liver transplantation. The study retrospectively analyzed HCC patients undergoing liver transplantation in two centres between January 2015 and December 2020. The authors reviewed post-transplant HBV status and its association with outcomes. The prognosis of recipients with hepatitis B surface antigen (HBsAg) reappearance ( n =58) was poorer than those with HBsAg persistent negative ( n =351) and positive ( n =53). In HBsAg persistent positive group, recipients with HBV DNA reappearance or greater than 10-fold increase above baseline had worse outcomes than those without ( P <0.01). HBV reactivation was defined as (a) HBsAg reappearance or (b) HBV DNA reappearance or greater than 10-fold increase above baseline. After propensity score matching, the 5-year overall survival rate and recurrence-free survival rate after liver transplantation in recipients with HBV reactivation were significantly lower than those without (32.0% vs. 62.3%; P <0.01, and 16.4% vs. 63.1%; P <0.01, respectively). Moreover, HBV reactivation was significantly related to post-transplant HCC recurrence, especially lung metastasis. Cox regression analysis revealed that beyond Milan criteria, microvascular invasion and HBsAg-positive graft were independent risk factors for post-transplant HBV reactivation, and a novel nomogram was established accordingly with a good predictive efficacy (area under the time-dependent receiver operating characteristic curve=0.78, C-index =0.73). Recipients with HBV reactivation had worse outcomes and higher tumour recurrence rates than those without. The nomogram could be used to evaluate the risk of post-transplant HBV reactivation effectively.

Risk of HBV reactivation in HCC patients undergoing combination therapy of PD-1 inhibitors and angiogenesis inhibitors in the antiviral era

BackgroundAlthough routine antiviral therapy has been implemented in HCC patients, the risk of HBV reactivation (HBVr) remains with the use of programmed cell death-1(PD-1) blockade‐based combination immunotherapy and the relevant risk factors are also unclear. Therefore, we aimed to identify the incidence and risk factors of HBVr in HCC patients undergoing combination therapy of PD-1 inhibitors and angiogenesis inhibitors and concurrent first-line antivirals.MethodsWe included a total of 218 HBV-related HCC patients with first-line antivirals who received PD-1 inhibitors alone or together with angiogenesis inhibitors. According to the anti-tumor therapy modalities, patients were divided into PD-1 inhibitors monotherapy group (anti-PD-1 group) and combination therapy group (anti-PD-1 plus angiogenesis inhibitors group). The primary study endpoint was the incidence of HBVr.ResultsHBVr occurred in 16 (7.3%) of the 218 patients, 2 cases were found in the anti-PD-1 group and the remaining 14 cases were in the combination group. The Cox proportional hazard model identified 2 independent risk factors for HBVr: combination therapy (hazard ratio [HR], 4.608, 95%CI 1.010–21.016, P = 0.048) and hepatitis B e antigen (HBeAg) positive (HR, 3.695, 95%CI 1.246–10.957, P = 0.018). Based on the above results, we developed a simple risk-scoring system and found that the high-risk group (score = 2) developed HBVr more frequently than the low-risk group (score = 0) (Odds ratio [OR], 17.000, 95%CI 1.946–148.526, P = 0.01). The area under the ROC curve (AUC-ROC) was 7.06 (95%CI 0.581–0.831, P = 0.006).ConclusionHBeAg-positive patients receiving combination therapy have a 17-fold higher risk of HBVr than HBeAg-negative patients with PD-1 inhibitors monotherapy.

The Risk Factors and Clinical Outcomes in Hepatitis B Seropositive and Seronegative Renal Transplant Patients

Introduction: Hepatitis B virus (HBV) infection is prevalent in Asia including Taiwan. We retrospectively evaluated the risk of HBV reactivation and clinical outcomes in HBV+ and HBV– kidney transplant recipients. Methods: Patients who underwent kidney transplantation between January 2004 and December 2021 were reviewed. The outcomes of interest included risks of HBV reactivation and patient/graft survival. Results: We identified 337 patients (47.5 ± 12 years) in our final cohort. Fifty-two (15.4%) had hepatitis B surface antigen (HBsAg) positive at the time of transplantation. Seventeen developed viral reactivations, with 41.2% of them accompanied by active hepatitis. The graft survival, acute rejection rate, and cancer development after kidney transplantation did not differ in terms of HBsAg status. The Cox multivariate analysis indicated the HBV reactivation risk was increased by a lack of pretransplant anti-HBV medication (hazard ratio [HR], 5.95; 95% confidence interval [CI], 1.31–27.02; p = 0.021) or an absence of lifelong antiviral therapy (HR: 3.14; 95% CI: 1.01–9.74; p = 0.047). Conclusion: Individuals, independent of HBsAg status, had similar prognosis in terms of patient and graft survival, acute rejection rate, and cancer development. The absence of either pretransplant anti-HBV medication or lifelong antiviral therapy was significantly associated with an increased risk of HBV reactivation.

Occult HBV Infection in Patients Infected by HIV or HCV: Comparison between HBV-DNA and Two Assays for HBsAg.

We investigated the frequency and serological correlates of occult hepatitis B virus infection (OBI) and the potential impact of a highly sensitive assay for HBsAg in subjects infected by human immunodeficiency virus (HIV) or hepatitis C virus (HCV), who are also at risk for hepatitis B virus (HBV) infection, often in an occult form. Samples from 499 patients with HIV, all HBsAg negative and anti-HBc positive, and 137 patients with HCV were tested for HBV-DNA, anti-HBc, anti-HBs, and HBsAg by a conventional and highly sensitive assay. HBV biomarkers were detected in 71.5% of HCV-RNA-positive, with a higher prevalence of cases positive only for anti-HBc in patients with HCV than in those with HIV. HBV-DNA was detectable in 0.6% of HIV-positive and 7.3% of HCV-RNA-positive patients. Among patients with HCV, four were positive for HBsAg and negative for HBV-DNA, bringing the rate of HBV-active infection in this group to 10.2%. Active HBV infection was not related to gender or specific patterns of HBV biomarkers but was higher in HCV patients coinfected by HIV compared to those infected only by HCV. Monitoring patients at high risk for HBV infection and reactivation may require testing for both HBV-DNA and HBsAg.

Consensus Guidelines: Best Practices for the Prevention, Detection and Management of Hepatitis B Virus Reactivation in Clinical Trials with Immunosuppressive/Immunomodulatory Therapy.

Hepatitis B virus reactivation (HBVr) during and after immunosuppressive/immunomodulatory (IS/IM) therapy is associated with significant morbidity and mortality, including hepatic decompensation and acute liver failure. The risk of HBVr with IS/IM has been heterogeneous and often unpredictable. As a result, patients with active or previous HBV infection are often excluded from clinical drug trials of such agents. Thorough screening for HBV infection, antiviral prophylaxis, and careful monitoring for HBVr have proven to be effective in reducing the rate of HBVr and improving its outcome in the context of IS/IM. Therefore, safe enrollment and management of certain HBV-marker-positive patients in clinical trials is possible. There is a great, unmet need for consistent, evidence-based recommendations for best practices pertaining to enrollment, monitoring, and management of HBVr in clinical trial participants receiving IS/IM. The aim of these consensus guidelines is to provide a step-by-step blueprint to safely enroll, monitor and manage the patient with inactive chronic or resolved HBV in IS/IM clinical trials from the time of screening through to the end of post-treatment follow up.

Risk of hepatitis B virus reactivation and its effect on survival in advanced hepatocellular carcinoma patients treated with hepatic arterial infusion chemotherapy and lenvatinib plus programmed death receptor-1 inhibitors.

Hepatitis B virus (HBV) reactivation is a common complication in hepatocellular carcinoma (HCC) patients treated with chemotherapy or immunotherapy. This study aimed to evaluate the risk of HBV reactivation and its effect on survival in HCC patients treated with HAIC and lenvatinib plus PD1s. We retrospectively collected the data of 213 HBV-related HCC patients who underwent HAIC and lenvatinib plus PD1s treatment between June 2019 to June 2022 at Sun Yat-sen University, China. The primary outcome was the risk of HBV reactivation. The secondary outcomes were overall survival (OS), progression-free survival (PFS), and treatment-related adverse events. Sixteen patients (7.5%) occurred HBV reactivation in our study. The incidence of HBV reactivation was 5% in patients with antiviral prophylaxis and 21.9% in patients without antiviral prophylaxis, respectively. The logistic regression model indicated that for HBV reactivation, lack of antiviral prophylaxis (P=0.003) and tumor diameter (P=0.036) were independent risk factors. The OS and PFS were significantly shorter in the HBV reactivation group than the non-reactivation group (P=0.0023 and P=0.00073, respectively). The number of AEs was more in HBV reactivation group than the non-reactivation group, especially hepatic AEs. HBV reactivation may occur in HCC patients treated with HAIC and lenvatinib plus PD1s. Patients with HBV reactivation had shorter survival time compared with non-reactivation. Therefore, HBV-related HCC patients should undergo antiviral therapy and HBV-DNA monitoring before and during the combination treatment.

Prevention of hepatitis B reactivation in patients with hematologic malignancies treated with novel systemic therapies: Who and Why?

The risk of reactivation in patients with chronic or past/resolved hepatitis B virus (HBV) infection receiving chemotherapy or immunosuppressive drugs is a well-known possibility. The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy. Though the advent of new drugs is occurring in all the field of medicine, in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment. As novel therapies, there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging. Moreover, patients are often treated with a combination of different drugs, so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult. First results are now available, but further studies are still needed. Patients with chronic HBV infection [hepatitis B surface antigen (HBsAg) positive] are reasonably all treated. Past/resolved HBV patients (HBsAg negative) are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.

Hepatitis B Virus Reactivation with Immunosuppression: A Hidden Threat?

Hepatitis B virus (HBV) reactivation in the setting of immunosuppressive therapy is an increasingly recognized and preventable cause of elevated liver enzymes and clinical hepatitis in treated patients. However, not all immunosuppressive therapies confer the same risk. The purpose of this article was to review the literature on risks of HBV reactivation associated with immunosuppressive agents and propose a management algorithm. We searched Google Scholar, PubMed, and MEDLINE for studies related to hepatitis B reactivation and various immunosuppressive agents. The risk of HBV reactivation was found to differ by agent and depending on whether a patient had chronic HBV (HBsAg+) or past HBV (HBsAg-, anti-HBc+). The highest risk of reactivation (>10%) was associated with anti-CD20 agents and hematopoietic stem cell transplants. Multiple societies recommend HBV-specific anti-viral prophylaxis for patients with positive HBsAg prior to the initiation of immunosuppressive therapy, while the guidance for HBsAg- patients is more variable. Clinicians should check HBV status prior to beginning an immune-suppressive therapy. Patients with positive HBsAg should be initiated on antiviral prophylaxis in the majority of cases, whereas HBsAg- individuals should be evaluated on a case-by-case basis. Further research is required to determine the optimum duration of therapy.

Risk of Hepatitis B Reactivation in Patients Receiving Ibrutinib: The National Veterans Affairs Cohort.

Ibrutinib has been a first-line treatment for chronic lymphocytic leukemia since 2014. Case reports of hepatitis B virus (HBV) reactivation after ibrutinib initiation have been presented. The association between the risk of HBV reactivation and ibrutinib initiation remains unclear. This nationwide study aimed to estimate the incidence of HBV reactivation after ibrutinib initiation. This study included patients who received ibrutinib between 1 February 2014 and 31 October 2019. Possible reactivations were searched by (1) changes in HBV surface antigen or HBV DNA from no data or negative status to positive after ibrutinib initiation, (2) alanine aminotransferase levels that were at least 3 times the baseline value after ibrutinib initiation, and (3) new antiviral prescriptions against HBV after ibrutinib initiation. Individual chart reviews were conducted to identify HBV reactivation attributed to ibrutinib. The cumulative incidence of HBV reactivation was calculated. A total 4130 patients were eligible during the study period. Of these, patients with negative HBV core antibody (anti-HBcAb; n = 1670) and patients who were taking antivirals against HBV (n = 60) were excluded. There were 2219 patients without anti-HBcAb testing results. Among the remaining 181 patients with positive anti-HBcAb, 7 HBV reactivations were directly attributable to ibrutinib treatment after chart review, for a 3.9% cumulative incidence. Our study revealed a low cumulative incidence of HBV reactivation after ibrutinib initiation among patients with previous anti-HBcAb positivity, indicating a moderate risk of HBV reactivation.

5-FU promotes HBV replication through oxidative stress-induced autophagy dysfunction

Background & aimsHepatitis B virus (HBV) reactivation is a major problem that must be overcome during chemotherapy for HBV-related hepatocellular carcinoma (HCC). However, the mechanism underlying chemotherapy-associated HBV reactivation is still not fully understood, hindering the development of improved HBV-related HCC treatments. MethodsA meta-analysis was performed to assess the HBV reactivation risk during transcatheter arterial chemoembolization (TACE). To investigate the regulatory effects and mechanisms of 5-FU on HBV replication, an HBV mouse model was established by pAAV-HBV1.2 hydrodynamic injection followed by intraperitoneal 5-FU injection, and different in vitro models (HepG2.2.15 or Huh7 cells) were established. Realtime RT‒qPCR, western blotting, luciferase assays, and immunofluorescence were used to determine viral parameters. We also explored the underlying mechanisms by RNA-seq, oxidative stress evaluation and autophagy assessment. ResultsThe pooled estimated rate of HBV reactivation in patients receiving TACE was 30.3 % (95 % CI, 23.1%–37.4 %). 5-FU, which is a chemotherapeutic agent commonly used in TACE, promoted HBV replication in vitro and in vivo. Mechanistically, 5-FU treatment obviously increased autophagosome formation, as shown by increased LC3-II levels. Additionally, 5-FU impaired autophagic degradation, as shown by marked p62 and mCherry-GFP-LC3 upregulation, ultimately promoting HBV replication and secretion. Autophagy inhibition by 3-methyladenine or chloroquine significantly altered 5-FU-induced HBV replication. Furthermore, 5-FU-induced autophagy and HBV replication were markedly attenuated with a reactive oxygen species (ROS) scavenger. ConclusionsTogether, our results indicate that ROS-induced autophagosome formation and autophagic degradation play a critical role in 5-FU-induced HBV reactivation.

Hepatitis B virus coinfection in patients treated for chronic hepatitis C: clinical characteristics, risk of reactivation with long-term follow-up, and effectiveness of antiviral therapy.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) share a similar transmission route, which increases coinfection odds and worsens clinical outcomes. Our aim was to investigate coinfected patients undergoing HCV treatment with direct-acting antivirals (DAAs) to understand their characteristics, risk of HBV reactivation, and effectiveness of the therapy. Our study comprehensively analyzed 1118 patients with chronic HCV infection, divided into 3 subgroups based on their HBV status. We documented that 0.7% of the analyzed population was positive for hepatitis B virus surface antigen (HBsAg), while 14.3% had evidence of a past HBV infection. The patients without HBV coinfection were less burdened with comorbidities, and were mostly treatment-naive, while the individuals suffering from coinfection were younger and more likely to have a history of a previous therapy. Infection with HCV genotype 3 was more common among the HBsAg-positive patients than in the other studied groups. Response to DAA therapy was comparable between the groups, and most patients completed the course of treatment as planned. Only 3 cases of HBV reactivation were observed, all of which achieved sustained virologic response after DAA therapy. Two were women on immunosuppressants with antihepatitis B core positive antibodies, and the third patient was an HBsAgpositive man. These patients remained in long-term follow-up. Neither the presence of HBV markers nor HBV reactivation during DAA treatment reduced effectiveness of the therapy. Our findings are important for future recommendations and guidelines on managing HBV/HCV coinfection.

Immune checkpoint inhibitor use and the incidence of hepatitis B virus reactivation or immune-related hepatitis in non-small cell lung cancer patients with chronic hepatitis B.

The safety of immune-checkpoint inhibitors (ICIs) has not been thoroughly investigated in non-small cell lung cancer (NSCLC) patients with chronic hepatitis B (CHB) or occult hepatitis B infection (OBI). The authors analyzed the incidence of hepatitis B virus (HBV) reactivation, immune-related hepatitis and jaundice in NSCLC patients in a real-world setting. A total of 1277 NSCLC patients treated with ICIs were analyzed. Among them, 52 patients were hepatitis B surface antigen (HBsAg) (+) (group A, CHB), 759 patients were HBsAg (-)/hepatitis B core antibody immunoglobulin G (anti-HBc IgG) (+) (group B, OBI), and 466 patients were HBsAg (-)/anti-HBc IgG (-) (group C). Among the 52 patients with CHB, 38 (73.1%) were receiving antiviral therapy. The primary end point was HBV reactivation, immune-related hepatitis, and jaundice. The secondary end points included other immune-related adverse events and efficacy. HBV reactivation was observed in two patients (0.2%) who were both in group A (CHB). Among CHB patients who were not receiving antiviral therapy, HBV reactivation was observed in 14.3% (2 of 14 patients). The incidences of immune-related hepatitis and jaundice were comparable among the three groups. The incidence of ≥grade 3 other immune-related adverse events and efficacy were all comparable among the three groups (p>.05 for all comparisons). In this large, real-world cohort study, the safety and efficacy of ICIs were comparable in patients with CHB and OBI. HBV reactivation was observed in patients with CHB without antiviral therapy indicating antiviral prophylaxis should be required for them. For patients with OBI, the risk of HBV reactivation was minimal.

The Role of Interleukins in HBV Infection: A Narrative Review.

Hepatitis B virus (HBV) infection is a worldwide medical issue with significant morbidity and mortality, as it is the main cause of chronic liver disease and hepatocellular carcinoma (HCC). Both innate and adaptive immune responses play a key role in HBV replication and suppression. Recently, the pathophysiological function of interleukins (IL) in the natural course of HBV has gained much attention as a result of the broad use of anti-interleukin agents for a variety of autoimmune diseases and the accompanying risk of HBV reactivation. We present a narrative review regarding the role of IL in HBV infection. Collectively, the pro-inflammatory ILs, namely IL-1, IL-5, IL-6, IL-12 and IL-21, seem to play a critical role in the suppression of HBV replication. In contrast, the anti-inflammatory cytokines IL-10, IL-23 and IL-35 probably act as HBV replication enhancers, while IL-17 has been correlated with HBV-related liver injury. Interestingly enough, IL-2, IL-4 and IL-12 have been tried as therapeutic options against HBV infection with contradictory results. Lastly, the role of IL-22 remains largely ill defined, although preliminary data suggest that it may play a significant role in HBV replication, proliferation and subsequent liver damage.

Impact of Mogamulizumab-Containing Chemotherapy on HBV Reactivation in Patients with T-Cell Lymphoma: A Multicenter Retrospective Observational Study (PROACTIVE-MOGA)

INTRODUCTION Reactivation of hepatitis B virus (HBV) infection is a potentially lethal complication, but may be preventable in patients with chronic HBV infection or resolved HBV infection who receive systemic chemotherapy.The risk of HBV reactivation (HBVR) depends on not only HBV infectious status but also type of systemic chemotherapy. An anti-CCR4 antibody, mogamulizumab (Moga), has been developed for the treatment of peripheral T-cell lymphomas. Moga is known to suppress CCR4-positive regulatory T cells and helper T cells, which can lead to immunological dysfunction. However, there is little evidence regarding the risk of HBVR in patients with chronic HBV infection or resolved HBV infection who receive Moga-containing systemic chemotherapy. We conducted a retrospective observational study to evaluate the risk of HBVR and clinical outcome in those patients. METHODS &amp; MATERIALS: Patients treated with Moga-containing chemotherapy for T-cell lymphoma between May 2012 and March 2021, who were chronic HBV infection (defined as seropositive for HBsAg) or resolved HBV infection (defined as seronegative for HBsAg, but seropositive for anti-HBc or anti-HBs), were included. The primary endpoint was the rate of HBVR; HBVR in HBsAg-positive patients was defined as any of the following three criteria: 1) 2 log or more increase in HBV DNA from baseline, 2) 3.0 Log IU/ml or more of HBV DNA in patients with undetectable HBV DNA at baseline, 3) 4.0 Log IU/ml or more of HBV DNA in patients not available for HBV DNA at baseline. HBVR in HBsAg-negative patients was defined as any of following three criteria: 1) detectable for HBV DNA in patients with undetectable HBV DNA at baseline, 2) 1.3 Log IU/mL or more of HBV DNA in patients not available for HBV DNA at baseline, 3) seroconversion of HBsAg. RESULTS: A total of 23 HBsAg-positive patients and 246 resolved HBV-infected patients were retrospectively reviewed. Among the 23 HBsAg-positive patients, the median age was 65 years (interquartile range [IQR], 63-73) and 19 patients (82%) had adult T-cell leukemia-lymphoma (ATL). Baseline HBV DNA was undetectable level, detectable not quantifiable, and detectable in 9 (39%), 2 (9%), and 12 (52%) patients, respectively. All 23 HBsAg-positive patients received anti-HBV prophylaxis prior to Moga treatment. One of 23 (4.3%) patients experienced HBVR who led to HBV-related hepatitis. Among the 241 patients with resolved HBV infection, the median age was 65 years (IQR, 63-73) and 223 patients (91%) had ATL. Baseline serostatus of anti-HBc and anti-HBs were as follows: anti-HBc positive and anti-HBs positive in 177 patients (72%), anti-HBc-positive but anti-HBs negative in 50 (20%), the remaining 9 were anti-HBc negative but anti-HBs positive. Baseline HBV DNA was undetectable in 233 (95%), detectable not quantifiable in 5 (2%), and the remaining 3 were detectable for HBV DNA. Only 3 patients received anti-HBV prophylaxis. HBVR occurred in 11 patients, and the 2-year cumulative HBVR rate was 3.5% (95% CI, 1.6-16.5). Among the 11 patients with HBVR, the median peak HBV DNA level was 2.1 Log IU/mL (IQR, 1.7-5.0), the median time from first dose of Moga to HBVR was 140 days (IQR, 82-765) and 2 had HBV-related hepatitis. CONCLUSION: Our current study showed that the risk of HBVR was 4.3% (1 of 23) among HBsAg-positive patients with antiviral prophylaxis and 4.6% (11 of 238) among resolved HBV-infected patients without antiviral prophylaxis following Moga-containing chemotherapy. Anti-HBV prophylaxis and HBV DNA monitoring guided preemptive anti-HBV therapy are recommended to prevent HBV-related hepatitis for HBsAg-positive and resolve HBV-infected patients, respectively.