Resolved Hepatitis B Virus Infection Research Articles

Serum IL-1β predicts de novo hepatitis B virus reactivation during direct-acting antiviral therapy for hepatitis C, not during anti-cancer/immunosuppressive therapy

De novo hepatitis B virus (HBV) reactivation occurs during direct-acting antiviral (DAA) treatment in hepatitis C virus (HCV)-infected patients with resolved HBV infection. We evaluated the predictive factors, mechanical insight, and differences of cytokine levels during anti-cancer/immunosuppressive and DAA. Eleven, 35, and 19 HCV-infected patients with previous HBV infection with HBV reactivation during DAA treatment, previous HBV infection without HBV reactivation during DAA treatment, and without HBV infection resolution receiving DAA treatment, respectively, were enrolled. Clinical data and baseline cytokine levels were analyzed. Low baseline serum interleukin (IL)-1β levels predicted de novo HBV reactivation during DAA treatment (odds ratio: 47.6, 95% confidence interval: 6.94–333.3). HCV-infected patients with the IL-1β gene single nucleotide polymorphism rs16944 AA allele had significantly higher IL-1β levels; no HCV-infected patient with the IL-1β AA allele experienced HBV reactivation during DAA treatment. Compared to HCV-infected patients with HBV infection resolution, non-HCV infected patients with or without HBV reactivation during anti-cancer/immunosuppressive therapy or bone marrow transplantation had remarkably lower baseline IL-1β levels. Low IL-1β levels were not associated with HBV reactivation. IL-1β levels before DAA for HCV-infected patients with resolved HBV infection could predict HBV reactivation during DAA treatment.

The impact of the covalently closed circular DNA level on recurrence of hepatocellular carcinoma after initial hepatectomy: an analysis of patients with resolved hepatitis B virus infection.

We assessed whether or not covalently closed circular DNA (cccDNA) levels in the background liver influence the recurrence of hepatocellular carcinoma (HCC) in patients with resolved hepatitis B virus (HBV) infection. Among 425 patients who underwent initial hepatectomy for HCC between 2010 and 2018, a retrospective review was performed in 44 with resolved HBV infection. The clinicopathologic characteristics were analyzed for correlation with tumor recurrence. The HBV cccDNA levels were tested via a droplet digital polymerase chain reaction assay. HBV cccDNA was detected in 27 of 44 patients (61%), and the median level was 1.0 copies/1000 ng (range, 0-931.3 copies/1000 ng). Anti-HBc ≥8.9 S/CO was associated with cccDNA detection (odds ratio, 11.08; 95% confidence interval [95% CI], 2.48-49.46; P = 0.002). Twenty-eight patients (64%) developed HCC recurrence after hepatectomy. The overall 3- and 5-year recurrence-free survival rates were 45.7% and 34.3%, respectively.19 HBV cccDNA levels was not significantly associated with HCC recurrence, while the presence of multiple tumors was an independent risk fact or (hazard ratio, 6.53; 95% CI, 2.48-17.19; P < 0.001. HBV cccDNA levels did not influence HCC recurrence after hepatectomy. Anti-HBc levels may be used as a surrogate marker for cccDNA.

S3234 A Cancer Encasing the Porta Hepatis: An Aggressive Intra-Abdominal B Cell Lymphoma Presenting as a Post-Obstructive Jaundice With Reactivation of Hepatitis C Virus

Introduction: Hepatitis C virus (HCV) is a lymphotropic virus that promotes HCV-mediated B-cell proliferation and transformation to Non-Hodgkin Lymphoma (NHL). Here we present a case of reactivation of HCV presenting as an aggressive intra-abdominal B cell lymphoma. Case Description/Methods: A 68-years-old-male with history of eradicated HCV with recombinant interferon-alfa and resolved HBV infection presented with painless jaundice and pruritus. CT abdomen revealed a 9.6 x 11.5 x 9.5 cm heterogeneous mass causing CBD and intrahepatic biliary duct dilation. Labs revealed reactivation of HCV infection with worsening of liver function tests with total bilirubin of >40mg/dl. FNA biopsy confirmed mature B-cell lymphoma. Given persistent worsening jaundice despite biliary stent, trial of high dose steroid was initiated to improve lymphoma burden in order to get a window to initiate chemotherapy. After tumor board discussion, he received radiation therapy for tumor shrinkage for this aggressive lymphoma. Prior to initiation of planned R-CHOP chemotherapy, he developed severe sepsis with hepatic abscess. Patient and family opted for hospice care and comfort care was initiated. Discussion: Chronic HCV is a fast-growing epidemic in the U.S.A which carries an enormous threat to general population and healthcare. HCV becomes chronic in >70% of infected patients with risk for cirrhosis, hepatocellular carcinoma and lymphoma. HCV can cause NHL via lymphocyte proliferation from viral antigenic stimulation, HCV replication inside B-cell and mutation via B-cell damage. Among patient who achieve sustained viral response (SVR), reactivation occurs in 1%, 11% and 15% among low-risk monoinfected HCV, high-risk monoinfected HCV and HIV/HCV coinfected group respectively. Treatment of HCV with resolution of NHL has been reported and there is some literature with sequential chemotherapy followed by antiviral therapy (AVT) showing promising results in HCV-NHL cases. Concurrent use of AVT and chemotherapy is primarily discouraged due to hematological toxicity. More evidence and studies need to be explored for such aggressive HCV-NHL management. Patient with SVR should have at least an annual testing and periodic follow-up to access for HCV reactivation or reinfection. Hepatitis C education regarding risk factors reduction and transmission prevention should be encouraged at every healthcare level and in general community and only then we can achieve WHO aim of eradication by 2030.

Incidence of post-transplant hepatitis B virus reactivation with the use of kidneys from donors with resolved hepatitis B virus infection.

Donors with resolved hepatitis B virus (HBV) infection may be a solution for the organ shortage for kidney transplantation (KT). The purpose of this study was to clarify the current state of HBV markers after KT from donors with resolved HBV infection to HBV naïve recipients and the rate of HBV reactivation in recipients with resolved HBV infection. Furthermore, we investigated HBV covalently closed circular DNA (cccDNA) in transplanted organs from donors with resolved HBV infection and the capability of HBV replication in kidney cell lines. We retrospectively analysed the HBV status of 340 consecutive donors and recipients who underwent KT in a single centre. We prospectively measured cccDNA by real-time polymerase chain reaction in kidney biopsy specimens of 32 donors with resolved HBV infection. HBV reactivation was found in three recipients with resolved HBV infection (4.8%, 3/63) after KT. We analysed 45 cases of transplantation from donors with resolved HBV infection to HBV-naive recipients. One case (2.2%, 1/45) became seropositive for hepatitis B core antibody (anti-HBc) and in another case (2.2%, 1/45), HBV-DNA was detected qualitatively in an HBV naive recipient with a donor with resolved HBV infection. In the latter case, cccDNA was measured in the donor kidney during KT. HBV replication was observed in kidney cell lines with HBV plasmid transfection. In conclusion, the risk of reactivation in anti-HBc-positive donors is relatively low. However, post-transplant HBV monitoring should be conducted in all at-risk cases.

Risk of HBV reactivation in relapsed or refractory diffuse large B-cell lymphoma patients receiving Bruton tyrosine kinase inhibitors therapy.

BackgroundBruton tyrosine kinase inhibitors (BTKis) interrupt B-cell receptor signaling and thereby could potentially reactivate hepatitis B virus (HBV). However, data about the risk for HBV reactivation (HBVr) of BTKis in relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) patients are sparse.MethodsA total of 55 R/R DLBCL patients receiving BTKis therapy in the Tongji Hospital of Tongji University were enrolled. Patient clinical characteristics, treatment outcomes and details of HBVr were collected and analyzed, aiming to demonstrate the risk of HBVr in R/R DLBCL patients post BTKis therapy and the efficacy of BTKis in HBV-associated R/R DLBCL patients.ResultsOf 55 R/R DLBCL patients treated with ibrutinib (N=38) and zanubrutinib (N=17), 4 were with chronic HBV infection (HBsAg positive), 26 with resolved HBV infection (HBsAg negative and HBcAb positive) and 25 without HBV infection (HBsAg negative and HBcAb negative). In resolved HBV infection group, 2 patients developed HBVr after the use of ibrutinib and zanubrutinib respectively. Neither of them developed HBV-related hepatitis. Our finding showed that the incidence of HBVr in resolved HBV infection group was 7.69% (95% CI, 0.9-25.1%). In this study, Overall response rate (ORR) was 70.9%. 1-year overall survival (OS) rate was 80.0%. Median progression-free survival (PFS) was 4 months (95% CI, 3-5 months). In addition, HBV infection was not associated with response rates or survival among R/R DLBCL patients post BTKis treatments.ConclusionOur study suggested that HBV infection do not affect the efficacy of BTKis’ treatment. However, R/R DLBCL patients with resolved HBV infection are at a moderate risk of developing HBVr throughout BTKis treatment. Patients should be screened for HBVr during BTKis therapy.

Long-Term Safety of Rituximab in DLBCL Patients With Hepatitis B-Related Cirrhosis: A Retrospective Case Series

ObjectiveChemotherapy regimens containing rituximab (RTX) have been extensively used to treat diffuse large B cell lymphoma (DLBCL). However, data looking at long-term safety of DLBCL patients with hepatitis B-related cirrhosis are still lacking. This study aims to report the safety and outcomes of RTX administration in DLBCL patients with hepatitis B-related cirrhosis.MethodsA retrospective case series was designed and implemented, using data from January 1, 2011 to December 31, 2020. Consecutive patients who were diagnosed with DLBCL and hepatitis B-related cirrhosis receiving RTX treatment were included. The primary outcomes included HBV reactivation, hepatitis flares or abnormal liver function. Survival status, the secondary outcome measure, was observed until death, loss to follow-up, or the end of follow-up, whichever occurred first.ResultsA total of 8 DLBCL patients combined with hepatitis B-related cirrhosis were included in this study [4 men; median age 62.5 years (range, 44–77 years); median RTX-containing regimen course 5 (range, 2–11)]. Of them, 6 patients had current HBV infection with HBsAg-positive and anti-HBc-positive, whereas 2 patients had previously resolved HBV infection with HBsAg-negative and anti-HBc-positive. The HBV reactivation was observed in only one patient, who received 11 courses of RTX-containing immunochemotherapies within 15 months. No hepatitis flares or abnormal liver function occurred in any patients included. All patients received standardized antiviral therapy for a lifelong time. Of 8 patients included, 3 patients died, and 1 patient was lost to follow-up, and the median overall survival among patients was 39 months (range, 7–82 months).ConclusionThe findings provide support for the concept that, on the premise of standardized and valid management strategy, RTX containing regimens may be a safe option for use as the treatment of DLBCL patients combined with hepatitis B-related cirrhosis.

Cost-effectiveness of managing HBV reactivation in patients with resolved HBV infection treated with anti-CD20 antibody for B-cell non-Hodgkin lymphoma.

There is no universal recommendation for managing the reactivation of HBV in patients with resolved HBV infection treated with anti-CD20 monoclonal antibodies for B-cell non-Hodgkin lymphoma. This study compared the cost-effectiveness of two commonly used strategies: prophylactic anti-HBV nucleos(t)ide analog therapy (Pro NAT), and HBV DNA monitoring followed by on-demand antiviral therapy (HBV DNA monitoring). Using a decision tree model, the incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained was calculated. The threshold for cost-effectiveness was set at 5,000,000 JPY, equivalent to 45,662 USD. In a base–case analysis, HBV DNA monitoring was found to be more cost-effective based on the calculation of ICER as 132,048 USD per QALY, a value that far exceeds 45,662 USD. The same results were consistently obtained by a one-way deterministic sensitivity analysis, even after changing each parameter value within the predetermined range. A probabilistic sensitivity analysis with 10,000 simulations also revealed that HBV DNA monitoring is more cost-effective than Pro NAT in 96.8% of cases. Therefore, this study suggests that HBV DNA monitoring is an appropriate managing measure in Japan from a cost-effectiveness perspective.

Safety and efficacy of secukinumab in psoriasis patients infected with hepatitis B virus: a retrospective study

The burden of hepatitis B virus (HBV) infection in China is high. The safety and efficacy of secukinumab in psoriasis patients with HBV infection have not been fully elucidated. To investigate the safety and efficacy of secukinumab in psoriasis patients with HBV infection in China. In this retrospective study, 20 psoriasis patients with HBV infection were identified, all of whom had been treated with secukinumab for ≥24 weeks Four patients had chronic inactive HBV infection, two patients had occult HBV infection, and the other 14 patients had resolved HBV infection. The HBV-DNA load and HBV markers measured at baseline and Week 24 showed no viral reactivation. Nineteen patients showed normal levels of liver enzymes after 24 weeks of therapy. However, one patient with resolved HBV infection and fatty liver with elevated baseline liver enzymes experienced hepatitis, with negative HBV load at baseline and Week 24. All patients showed a significant improvement in the Psoriasis Area and Severity Index (−13.35 ± 7.41: p < 0.0001), per cent of body surface area (−17.11 ± 17: p = 0.0002), Investigator Global Assessment (−2.55 ± 0.94: p < 0.0001), and Dermatology Life Quality Index (−12.3 ± 7.39; p < 0.0001) Secukinumab showed good efficacy in psoriasis patients with HBV infection. Chronic, inactive, occult and resolved HBV infection may not increase the risk of hepatitis during secukinumab treatment. Patients with poor baseline liver function, without any intervention during secukinumab treatment, may experience hepatitis. Periodic monitoring with HBV markers, HBV-DNA load, and serological liver function tests is necessary during secukinumab treatment.

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.

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.

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.

Hepatitis B Virus Reactivation Associated With Therapeutic Interventions

Hepatitis B virus (HBV) reactivation associated with various therapeutic interventions is an important cause of morbidity and mortality in patients with current or resolved HBV infection. Because no curative treatment for HBV infection is yet available, there are many individuals at risk for HBV reactivation in the general population. Populations at risk for HBV reactivation include patients who are currently infected with HBV or who have been exposed to HBV in the past. HBV reactivation and its potential consequences is a concern when these populations are exposed to anti-cancer chemotherapy, immunosuppressive or immunomodulatory therapies for the management of various malignancies, rheumatologic diseases, inflammatory bowel disease, or solid-organ or hematologic stem cell transplantation. Accordingly, it has become important to understand the basics of HBV reactivation and the mechanisms by which certain therapies are more susceptible to HBV reactivation. This review aims to raise the awareness of HBV reactivation and to understand the mechanisms and the risks of HBV reactivation in various clinical settings.

Safety of therapies using ustekinumab in patients with psoriasis who have had hepatitis B virus infection

Biological therapies used in psoriasis treatment pose a risk of reactivation of hepatitis B virus (HBV) infection. This risk occurs not only in patients with HB surface antigen (HBsAg) (+) but also in patients with past or occult HBV infection (with negative HBsAg, positive HB core antibodies (HBcAb), and positive HBV deoxyribonucleic acid [DNA]). Ustekinumab (UST) is a biologic agent acts by blocking the IL-12/23 pathway. Thus, hindering this response may lead to HBV reactivation. UST therapy is associated with mild HBV-r risk; however, there is insufficient data to confirm that hypothesis. Herein, we present observations on the safety of UST therapy in patients with psoriasis and serologically proved past HBV infection. One-hundred and six consecutive patients with moderate to severe psoriasis treated with biological therapy between May 2013 and January 2020 were retrospectively analyzed. Out of 106 patients, there were five who reported having past HBV. Those five patients were tested for the presence of HBsAg, HBcAb, HBsAb as well as HBV DNA at baseline and at the end of the follow-up period. HBV reactivation was defined as changing of "undetectable" to "detectable" viremia. All five patients were treated with UST. Five patients in our cohort group were found to have resolved HBV infection: HBsAg (-), HBcAb (+), and HBV DNA (-); 4/5 were HBsAb (+) and 1/5 HBsAb (-). None of the patients experienced an increase in their liver function tests values and no signs of hepatitis or HBV reactivation were observed at any point during the study. All the patients were HBsAg and HBV DNA negative at the end of the follow-up period. The average treatment time was 82.4 (28, 96) weeks. The average follow-up time was 75.2 (31, 176) weeks. Based on the available literature and the results from our observations, UST therapy seems to be a safe option for patients with resolved HBV infection.

Average corticosteroid dose and risk for HBV reactivation and hepatitis flare in patients with resolved hepatitis B infection

ObjectivesCorticosteroids remain the mainstay of treatment for rheumatic diseases but can cause hepatitis B virus (HBV) reactivation in patients with resolved HBV infection. Risk assessment and stratification are needed to...

The Use of Electronic Medical Records-Based Big-Data Informatics to Describe ALT Elevations Higher than 1000 IU/L in Patients with or without Hepatitis B Virus Infection.

Hepatitis B virus (HBV) infection is one of the serious health problems in the world as HBV causes severe liver diseases. Moreover, HBV reactivation has occasionally been observed in patients with resolved HBV infection and patients using immunosuppression and anticancer drugs. Large-scale hospital data focused on HBV infection and severe liver function were analyzed at our hospital, located in an urban area adjacent to Tokyo, the capital city of Japan. A total of 99,932 individuals whose blood samples were taken at 7,170,240 opportunities were analyzed. The HBV surface antigen (HBsAg)-positive group had a more frequent prevalence of patients with higher transaminase elevations than the HBsAg-negative group. However, among the HBsAg-negative group, patients who were positive for anti-HBV surface antibody and/or anti-HBV core antibody, had more severe liver conditions and fatal outcomes. More careful attention should be paid to alanine transaminase (ALT) elevations higher than 1000 IU/L in patients who had current and previous HBV infection.

Characterization of a library of 20 HBV-specific MHC class II-restricted T cell receptors

CD4+ T cells play an important role in the immune response against cancer and infectious diseases. However, mechanistic details of their helper function in hepatitis B virus (HBV) infection in particular, or their advantage for adoptive T cell therapy remain poorly understood as experimental and therapeutic tools are missing. Therefore, we identified, cloned, and characterized a comprehensive library of 20 MHC class II-restricted HBV-specific T cell receptors (TCRs) from donors with acute or resolved HBV infection. The TCRs were restricted by nine different MHC II molecules and specific for eight different epitopes derived from intracellularly processed HBV envelope, core, and polymerase proteins. Retroviral transduction resulted in a robust expression of all TCRs on primary T cells. A high functional avidity was measured for all TCRs specific for epitopes S17, S21, S36, and P774 (half-maximal effective concentration [EC50] <10 nM), or C61 and preS9 (EC50 <100 nM). Eight TCRs recognized peptide variants of HBV genotypes A to D. Both CD4+ and CD8+ T cells transduced with the MHC II-restricted TCRs were polyfunctional, producing interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, and granzyme B (GrzB), and killed peptide-loaded target cells. Our set of MHC class II-restricted TCRs represents an important tool for elucidating CD4+ T cell help in viral infection with potential benefit for T cell therapy.

Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) infections among undocumented migrants and uninsured legal residents in the Netherlands: A cross-sectional study, 2018-2019.

BackgroundMigrants are not routinely screened for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) in the Netherlands. We estimated the prevalence and determined factors associated with HBV, HCV and/or HIV infections among undocumented migrants and uninsured legal residents.MethodsIn this cross-sectional study, undocumented migrants and uninsured legal residents were recruited at a non governmental organization (NGO), healthcare facility in the Netherlands and were invited to be tested for hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibodies (anti-HBcAb), HCV-RNA, and anti-HIV antibodies or HIV antigen at a local laboratory.ResultsOf the 1376 patients invited, 784 (57%) participated. Participants originated from Africa (35%), Asia (30%) and North/South America (30%). 451/784 (58%) participants went to the laboratory for testing. Of participants 30% were HBV exposed (anti-HBcAb-positive), with 27% (n = 119/438, 95% CI 23.1% to 31.6%) having resolved HBV infection (HBsAg-negative) and 2.5% (n = 11/438, 95%CI 1.3% to 4.5%, 64% new infection) having chronic HBV infection (HBsAg-positive). Compared to HBV non-exposed, HBV exposed individuals were older (p = 0.034) and more often originated from Africa (p<0.001). Prevalence of chronic HCV infection (HCV-RNA-positive) was 0.7% (n = 3/435, 95%CI 0.1% to 2.0%, all new infections) and HIV infection 1.1% (n = 5/439, 95%CI 0.04% to 2.6%, 40% new infection).ConclusionPrevalence of chronic HBV, chronic HCV and HIV infections in our study population is higher compared to the Dutch population, thus emphasizing the importance of case finding for these infections through primary care and public health in this specific group of migrants. Screening uptake could be improved by on-site testing.

Worse outcome and distinct mutational pattern in follicular lymphoma with anti-HBc positivity

AbstractEpidemiological studies have demonstrated the association between hepatitis B virus (HBV) infection and B-cell non–Hodgkin lymphoma (NHL), mainly for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). We studied a cohort of 121 patients with FL for HBV infection status, clinical features, and gene mutational profile. Anti-HBc was detectable in 16 patients (13.2%), although all had undetectable HBV DNA. Anti-HBcore+ (anti-HBc+) cases presented with older age at diagnosis than anti-HBc− cases (68.1 vs 57.2 years; P = .007) and higher β2-microglobulin (56.3% vs 28.9%; P = .04). All patients included in the study fulfilled criteria for treatment and received therapy with rituximab or rituximab-containing chemotherapy. There were no episodes of HBV reactivation or HBV hepatitis during treatment and/or maintenance. Remarkably, anti-HBc+ patients had significantly lower 10-year progression-free survival (PFS; 12.9% vs 58.3%; P < .0001) and overall survival (OS; 22.0% vs 86.2%; P < .0001), that remained at multivariate analysis. Gene mutational profiling of all cases showed that anti-HBc+ cases had higher incidence of ARID1A mutations and absence of EP300 mutations, 2 key epigenetic regulators in FL. Overall, our study shows that FL patients with resolved HBV infection have a worse outcome independently of other well-known clinical risk factors and a distinct gene mutational profile.