Hepatitis B Virus Reactivation Research Articles

Virological Factors Associated With the Occurrence of Hepatitis B Virus (HBV) Reactivation in Patients With Resolved HBV Infection Analyzed Through Ultradeep Sequencing.

Hepatitis B virus reactivation (HBVr) is an important complication of immunosuppressive drug therapy. It can occur via both virological and host factors; however, the underlying mechanisms remain largely unknown. We examined serum samples derived from patients with HBVr and those with acute hepatitis B (AHB). The targeted nucleic acid molecule in hepatitis B virus deoxyribonucleic acid was amplified and analyzed by next-generation sequencing. The percentage of patients infected with genotype Bj among the HBVr patients was significantly higher than that in the AHB patients. The frequency of mutation sites in the whole HBV genome, especially in the envelope region, in the HBVr was significantly higher than that in the AHB. The prevalence of the S3N amino acid substitution in the envelope protein and mutations at positions G1896A and G1899A in the precore region were significantly higher in the HBVr compared with AHB. The population of S3N amino acid substitution and nucleotide G1896A and G1899A mutations in each individual showed a similar percentage of occurrence. We identified specific virological factors in patients with HBVr through ultradeep sequencing. Our findings could be beneficial for the elucidation of mechanisms underlying HBVr development and for disease control.

Preventing complications: Hepatitis B screening in cancer patients undergoing systemic therapy.

237 Background: Chemotherapy is a risk factor for HBV reactivation in pts with cancer and chronic HBV. Anti-viral prophylaxis can prevent reactivation but requires identification of infected pts. Many guidelines recommend universal HBV screening prior to cytotoxic/immunosuppressive-therapy, but lack of screening is common globally. A serious safety event and high prevalence of pts from HBV endemic regions receiving treatment at our institution led to a quality improvement project to increase HBV screening prior to chemotherapy. We aimed to increase HBV screening in pts starting systemic therapy at Princess Margaret by 100% by February 28, 2019. Methods: Starting April 2017, an interrupted time series study was undertaken. Baseline HBV screening rate was 43%. Diagnostics including interviews, process mapping and root cause analysis were performed. Interventions to address identified root causes were implemented including specifying required HBV tests, tips for ordering HBV tests, provision of electronic Hepatology referral form, a safety alert email, grand rounds presentation of serious safety event, including HBV screening rate in departmental monthly quality emails and Divisional meetings and adding positive HBV results to the laboratory alerting system. The main outcome measure was the proportion of pts starting systemic therapy screened for HBV. Process measures included correct test ordering, number of Hepatology referrals was a balancing measure. Results were analysed with statistical process control charts. Results: From April 2017-Feb 2019, 5604 pts commenced systemic therapy. Interventions were modified iteratively as the project progressed. HBV screening rate improved from 43 to 79% (84% improvement). Incidence of chronic HBV was routinely above the Canadian average ( > 2%). The percent of correctly ordered screening tests fell from 48 to 33% (31% worsening), while the volume of Hepatology referrals remained manageable (1.5 pts/week). Conclusions: Our Quality Improvement project led to a significant improvement in HBV screening prior to systemic therapy. Further interventions are planned to achieve our target improvement of 100%.

Clinical and Virological Aspects of HBV Reactivation: A Focus on Acute Liver Failure

Hepatitis B virus (HBV) reactivation in immunosuppressed patients can cause considerable morbidity and mortality. The aim of our study was to evaluate factors associated with acute liver failure (ALF) in HBV reactivation. Clinical, laboratory, and virological data of 87 patients with HBV reactivation were analyzed retrospectively. Teno torque virus (TTV) plasma loads were measured as a measure of immune competence. HBV genomes isolated from 47 patients were analyzed by next-generation sequencing. A functional analysis of identified HBsAg mutants was performed. In patients with ALF the diagnosis was significantly later confirmed than in the non-ALF group. Patients diagnosed during immunosuppression had a milder clinical course compared to later diagnosed patients (p = 0.018, OR = 4.17). TTV viral loads did not differ significantly between the two groups. The HBV genomes isolated from ALF patients had higher viral complexity. A mutation in C-region of HBsAg (L216*), was associated with reduced HBsAg production and secretion. Patients diagnosed with HBV reactivation during immunosuppression had a milder clinical course compared to patients diagnosed during immune reconstitution. ALF was associated with higher viral complexity. An HBsAg mutation (L216*) was found to be more frequent in ALF patients and was associated with reduced HBsAg production and secretion.

Hematological Malignancies and HBV Reactivation Risk: Suggestions for Clinical Management.

It is well known that hepatitis B virus reactivation (HBVr) can occur among patients undergoing treatment for hematological malignancies (HM). The evaluation of HBVr risk in patients undergoing immunosuppressive treatments is a multidimensional process, which includes conducting an accurate clinical history and physical examination, consideration of the virological categories, of the medication chosen to treat these hematological malignancies and the degree of immunosuppression induced. Once the risk of reactivation has been defined, it is crucial to adopt adequate management strategies (should reactivation occur). The purpose of treatment is to prevent dire clinical consequences of HBVr such as acute/fulminant hepatitis, and liver failure. Treatment will be instituted according to the indications and evidence provided by current international recommendations and to prevent interruption of lifesaving anti-neoplastic treatments. In this paper, we will present the available data regarding the risk of HBVr in this special population of immunosuppressed patients and explore the relevance of effective prevention and management of this potentially life-threatening event. A computerized literature search was performed using appropriate terms to discover relevant articles. Current evidence supports the policy of universal HBV testing of patients scheduled to undergo treatment for hematological malignancies, and clinicians should be aware of the inherent risk of viral reactivation among the different virological categories and classes of immunosuppressive drugs.

Rheumatologists' awareness of hepatitis B reactivation before immunosuppressive therapy.

HBV reactivation (HBVr) is a well-known complication of immunosuppressive (IS) treatment. The aim of this study was to evaluate the awareness of rheumatologists about the risk of HBVr. A survey was sent via e-mail to 270 members of the Turkish Society for Rheumatology. It consisted of fourteen questions on their awareness of the major society guidelines, approach to hepatitis B virus (HBV) screening according to different IS regimens, decision process in screening patients for HBV, knowledge of antiviral treatments for HBV, follow-up strategies, experience and postgraduate training on HBVr. Forty-eight (17.8%) rheumatologists responded to the survey. Of the respondents, 93.8% reported that they screened all patients before IS treatment, while 6.2% screened patients with a high risk of HBV infection only. The screening rate was 95.8% (46/48) in patients undergoing high-risk IS treatment and 35.4% (17/48) in those undergoing low-risk treatment. All respondents screened for HBsAg, and 83.3% (40/48) screened for anti-HBc IgG and anti-HBs. Forty-four (91.7%) rheumatologists had previously initiated antiviral prophylaxis, and 14 (29.2%) had detected HBVr in at least one patient. Rheumatologists had a high awareness of the necessity for HBV screening before IS treatment. However, the screening rates were still lower than desired, especially in patients receiving IS treatments with moderate or low risk of reactivation.

Hepatitis B Virus (HBV) Reactivation Following Pharmacological Eradication of Hepatitis C Virus (HCV)

The US Food and Drug Administration issued a black box warning related to the risk of reactivation of overt/occult hepatitis B virus (HBV) infection during direct acting-antivirals (DAA) treatment. This review evaluated the prevalence of HBV reactivation after hepatitis C virus (HCV) pharmacological suppression and hypothesized the management and prevention of this reactivation. During and after DAA-based treatment, reactivation of HBV infection is common in patients with detectable serum HBsAg (from 2% to 57%) and very low (less than 3%) in individuals with isolated anti-HBc antibodies. The severity of hepatic damage may range from HBV reactivation without hepatitis to fulminant hepatic failure requiring liver transplantation. Thus, HBsAg-positive patients should receive nucleo(s)tide analog (NA) treatment or prophylaxis at the same time as DAA therapy. For those patients with occult B infection, there are no sufficient recommendations to start prophylactic treatment. Reactivation of overt or occult HBV infection during or after eradication of HCV infection is an issue to consider, and additional studies would help to determine the best management of this virological and clinical event.

Rituximab increases the risk of hepatitis B virus reactivation in non-Hodgkin lymphoma patients who are hepatitis B surface antigen-positive or have resolved hepatitis B virus infection in a real-world setting: a retrospective study.

BackgroundHepatitis B virus (HBV) reactivation with a hepatitis flare is a common complication in lymphoma patients treated with immunotherapy and/or chemotherapy. Anti-HBV prophylaxis is suggested for non-Hodgkin lymphoma (NHL) patients undergoing rituximab therapy, even those with resolved HBV infection. Since anti-HBV prophylaxis for patients with resolved HBV infection is not covered by national health insurance in Taiwan, a proportion of these patients receive no prophylaxis. In addition, late HBV reactivation has emerged as a new issue in recent reports, and no consensus has been reached for the optimal duration of antiviral prophylaxis. Thus, the aim of our study was to investigate the incidence and outcomes of HBV reactivation in NHL patients in a real-world setting and to study the frequency of late HBV reactivation.MaterialsNon-Hodgkin lymphoma patients who received rituximab and/or chemotherapy at our institute between January 2011 and December 2015 and who were hepatitis B surface antigen (HBsAg)- or hepatitis B core antibody (HBcAb)-positive were reviewed retrospectively.ResultsA total of 388 patients were screened between January 2011 and December 2015. In total, 196 patients were excluded because HBsAg was not assessed, HBcAb was negative or not assessed, or they were not treated with immunosuppressive therapy. Finally, the retrospective study included 62 HBsAg-positive NHL patients and 130 NHL patients with resolved HBV infection (HBsAg-negative and HBcAb-positive). During a median 30.5-month follow-up period, seven patients experienced HBV reactivation, five of whom had a hepatitis flare. The incidence of HBV reactivation did not significantly differ between the HBsAg-positive patients and the resolved HBV infection population without anti-HBV prophylaxis (4.8% vs. 3.1%, P = 0.683). All patients with HBV reactivation were exposed to rituximab. Notably, late HBV reactivation was not uncommon (two of seven patients with HBV reactivation events, 28.6%). Hepatitis B virus reactivation did not influence the patients’ overall survival. An age ≥65 years and an advanced disease stage were independent risk factors for poorer overall survival.ConclusionThe incidence of HBV reactivation was similar between the HBsAg-positive patients with antiviral prophylaxis and the resolved HBV infection population without anti-HBV prophylaxis. All HBV reactivation events occurred in NHL patients exposed to rituximab. Late reactivation was not uncommon. The duration of regular liver function monitoring for more than 1 year after immunosuppressive therapy or after withdrawal of prophylactic antiviral therapy should be prolonged. Determining the exact optimal duration of anti-HBV prophylaxis is warranted in a future prospective study for NHL patients treated with rituximab-containing therapy.

Risk of hepatitis B surface antigen seroreversion after corticosteroid treatment in patients with previous hepatitis B virus exposure

Systemic corticosteroids may cause HBV reactivation, but the impact on patients with previous HBV exposure is poorly defined. We aimed to study the risk of HBsAg seroreversion and hepatitis flare in patients with previous HBV exposure. Patients who were negative for HBsAg and received corticosteroids between 2001-2010 were included. Patients who were positive for antibody to HBsAg (anti-HBs) and/or to HBcAg (anti-HBc) were defined as having previous HBV exposure. The primary endpoint was HBsAg seroreversion; the secondary endpoint was hepatitis flare (alanine aminotransferase >80 U/L) at 1 year. A total of 12,997 patients fulfilled the inclusion criteria: anti-HBs positive only (n = 10,561); anti-HBc positive only (n = 970); anti-HBs & anti-HBc positive (n = 830) and anti-HBs & anti-HBc negative (n = 636). HBsAg seroreversion occurred in 165 patients. Patients who were anti-HBc positive only had a higher risk of HBsAg seroreversion (1-year incidence 1.8%) than those negative for both anti-HBs & anti-HBc (0%; p = 0.014). Patients with previous HBV exposure had a similarly low risk of liver failure as unexposed individuals (1.1% vs. 0.9%). The risk of a hepatitis flare started to increase in those receiving corticosteroids at peak daily doses of 20-40 mg (adjusted hazard ratio [HR] 2.19, p = 0.048) or >40 mg (aHR 2.11, p = 0.015) prednisolone equivalents for <7 days, and was increased at treatment durations of 7-28 days and >28 days (aHR 2.02-3.85; p <0.001-0.012). In HBsAg-negative patients who were only anti-HBc positive, high peak daily doses of corticosteroids increased the risk of hepatitis flare, but not seroreversion. The rate of liver failure was low and similar in HBV exposed and unexposed individuals; there were no deaths, nor any requirement for liver transplantation. It is important to know the hepatitis B virus (HBV) status before starting corticosteroid therapy. Patients with resolved HBV infection without detectable immunity are at an increased risk of HBV surface antigen seroreversion after corticosteroid therapy. High peak daily doses of corticosteroids (>40 mg prednisolone equivalents) increase the risk of hepatitis flare, but not seroreversion, in patients with previous exposure to HBV, irrespective of the duration of treatment. Interval monitoring of liver biochemistries is essential for the early detection of hepatitis flares in these patients.

Management Of Patients With Hepatitis B Virus Reactivation Post-DAA Treatment Of Chronic Hepatitis C Virus Infection In HCV-HBV Coinfected Patients With Pretreatment HBeAg Seroconversion And Early Degree Of Hepatic Fibrosis.

Background and aimHepatitis C virus (HCV)–HBV coinfection is a significant health problem with rapid progression of liver disease without precise diagnosis and treatment. We aimed in this study to identify if there were any role of HBV antiviral therapy in patients with HBV reactivation after direct-acting antiviral therapy in HCV–HBV coinfected patients.MethodsA prospective random study was carried out on 140 patients presenting with chronic HCV and chronic HBV coinfection. All patients had pretreatment HBeAg seroconversion, HBV DNA <2,000 IU/mL, normal liver enzymes, and F0/F1 hepatic fibrosis. They treated with sofosbuvir 400 mg and daklatasvir 60 mg once daily for 3 months. All patients underwent pretreatment hepatic fibrosis assessment using Fibro Scan and laboratory investigations: platelet count, liver-function tests, quantitative HCV PCR, HBsAg, HBc IgG, HBeAg, and HBeAb. All patients were followed up at 1, 3, 6, and 12 months from the start of HCV therapy.ResultsThe study enrolled 140 HCV–HBV coinfected patients: 55% were F0 and the rest F1. All our patients had negative HCV PCR at 1 month posttreatment and had achieved sustained virologic response with negative HCV PCR 3 months after treatment end. Four patients showed HBV reactivation with raised HBV DNA PCR and liver enzymes. Their mean age was 23.7±2.7 years, and three were male. Regarding patients with HBV reactivation, at 12 months posttreatment they showed significant decreases in liver enzymes, bilirubin, and INR, with increased platelet count (P=0.001), each with undetectable HBV PCR (P=0.001).ConclusionHBV–HCV coinfected patients with no/mild hepatic fibrosis, HBeAg seroconversion, and HBV DNA <2,000 IU/mL can complete direct-acting antiviral therapy without HBV antiviral treatment with close monitoring.

Association of Prophylactic Anti-Hepatitis B Virus Therapy With Improved Long-term Survival in Patients With Hepatocellular Carcinoma Undergoing Transarterial Therapy.

The effect of prophylactic antiviral therapy (AVT) on survival of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unknown. This study aimed to determine whether prophylactic AVT could improve long-term survival in patients undergoing transarterial chemotherapy (TAC). Between 2002 and 2016, 2860 newly diagnosed HBV-related patients with HCC treated with TAC were screened to analyze 2 groups based on prophylactic use of antivirals. Treatment effects were analyzed using propensity score (PS) matching (1:1) separately for the entire cohort and each subgroup. The primary endpoint was overall survival. A total of 1547 patients met the inclusion criteria and 1084 were PS matched for the 2 groups. Median follow-up duration was 16.55 months. In the entire unmatched cohort, patients receiving prophylactic AVT survived significantly longer than those who did not. Among AVT-untreated patients, baseline high viremia and HBV reactivation during treatment were significantly associated with shorter survival. Regarding types of antivirals, survival was significantly longer for patients receiving high-potency antivirals than those receiving low-potency antivirals. Survival differed with antiviral response. In the PS-matched cohort, the prophylactic AVT group survived significantly longer than the nonprophylactic group, irrespective of viral status or tumor stage. Prophylactic AVT remained an independent factor for survival. The association of prophylactic AVT with decreased risk of mortality persisted in patient subgroups after adjusting for baseline risk factors. Sensitivity analyses also confirmed estimated treatment effects. Prophylactic AVT is associated with significantly improved long-term survival among patients undergoing TAC. High-potency antivirals are indicated for this approach.Hepatitis B virus-associated morbidity is a well-known complication during transarterial chemotherapy (TAC). Our large-scale study demonstrated that prophylactic therapy with high-potency antivirals provides a significantly better survival in TAC-treated patients, irrespective of baseline viremia status or tumor stage.

Low Risk of HBV Breakthrough Infection in Immunosuppressive Children with HBcAb-Positive Blood Transfusion: Retrospective and Prospective Studies

Background & Aims: Immunosuppressive adults with occult hepatitis B can experience HBV reactivation. Blood transfusion was common in acute lymphoblastic leukemia (ALL) children with immunosuppressive therapy, in which may inevitable with hepatitis B core antibody (HBcAb)-positive blood components. This study aims to evaluate the risk of HBV breakthrough infection in immunosuppressive children with HBcAb-positive blood components transfusion. Method: Cohort study was conducted in ALL children receiving blood components infusion during immunosuppressive therapy from Sep, 2012 to June, 2019. Eligible children were hepatitis B surface antigen (HBsAg) and HBcAb-negative pre-transfusion. The main outcome was HBV breakthrough infection with detectable HBsAg or HBV DNA in children during chemotherapy. Findings: HBV infection was identified in 0.98% (4/410) of children during chemotherapy. Significant difference existed in the percentage of HBcAb-positive at pre-transfusion, 2 and 10 month post-transfusion (6.3% vs. 37.7% vs. 0.67% , p <0.05), at which time same changes were also found in the HBsAb levels, and especially prominent in group II children with detectable HBcAb (p <0.05). Eleven patients have been prospective follow-up, 66.7% of patients had detectable HBV DNA at HBcAb seroreversion post-transfusion, but no HBV infection was detected during the recent follow-up. Interpretation: Low risk of HBV breakthrough infection in immunosuppressive children with HBcAb-positive blood conponents infusion. Occult hepatitis B in children with a family history of HBV infection should be taken more attention. Passive transfer of HBV antibody in children after blood components infusion was transient, and notably, low level of HBsAb in cancer children after immunosuppressive therapy is needed to take seriously. Further trials with larger cohorts are needed to verify our findings. Trial Registration: (ClinicalTrials.gov identifier NCT-03529760) Funding Statement: National Natural Science Foundation of China (No.81371876), Health and Family Planning Commission of Chongqing [2013] 39-2013-1-025, Chongqing Municipal Colleges and Universities Outstanding Talent Support Program. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the Ethics Review Committee of Children’s Hospital of Chongqing Medical University.

New Markers in Monitoring the Reactivation of Hepatitis B Virus Infection in Immunocompromised Hosts.

Hepatitis B virus (HBV) persistence is at the basis of HBV reactivation as a consequence of chemotherapy and immunosuppressive treatments. The identification of early viral replication indicators and markers of effective HBV immunological control would be useful in monitoring patients who are at risk of potential viral reactivation during the course of immunosuppressive treatment. Currently, international guidelines have shared some criteria to identify patients with a low, medium or high risk of HBV reactivation; however, permanently placing a patient in a definitive category is not always easy. More often, patients move from one category to another during the course of their immunosuppressive treatment; therefore, in many cases, there are no precise indicators or tools for monitoring possible reactivation and establishing the duration and suspension of antiviral prophylaxis. Historically, the sequence of HBV antigens and antibodies and HBV DNA levels has been used to evaluate the different stages of the acute and chronic phases of an HBV infection. In the last few years, new biomarkers, such as anti-HBs and anti-HBc titres, HBV core-related antigen (HBcrAg), ultra-sensitive HBsAg evaluation and HBV RNA, have been used in patients with an HBV infection to evaluate their diagnostic and prognostic potential. The aim of this review is to evaluate the published results on the use of new infection markers in the diagnosis and monitoring of HBV reactivation over the course of immunosuppressive treatments. Moreover, the importance of viral genotypic studies was emphasized, given the diagnostic and therapeutic implications of the mutational profiles of HBsAg during the HBV reactivation phase.

Immune-Escape Hepatitis B Virus Mutations Associated with Viral Reactivation upon Immunosuppression.

Hepatitis B virus (HBV) reactivation occurs as a major complication of immunosuppressive therapy among persons who have recovered from acute hepatitis and those who have controlled chronic infection. Recent literature data emphasize the presence of a high degree of S gene variability in HBV isolates from patients who developed reactivation. In reactivated HBV, the most frequently detected mutations belong to the second loop of “a” determinant in HBsAg. These mutations were identified to be immune escape and responsible for vaccine- and diagnostic-escape phenomena. Their emergence clearly provides survival in the presence of a developed humoral immune response and is often associated with impaired serological diagnosis of HBV reactivation. The knowledge of their existence and roles can elucidate the process of reactivation and strongly highlights the importance of HBV DNA detection in monitoring all patients with a history of HBV infection who are undergoing immunosuppression. This review discusses the possible influence of the most frequently found immune-escape mutations on HBV reactivation.

TNF-α polymorphisms affect persistence and progression of HBV infection.

BackgroundHepatitis B virus (HBV) infections are a major threat worldwide. Disease progression and outcome is diverse and depends on host genetic background. Recently, a high rate of HBV reactivation in individuals receiving tumor necrosis factor‐α (TNF‐α) antagonists showed the importance of this cytokine in HBV infection control. Here, we investigated the influence of TNF‐α promoter polymorphisms on susceptibility to chronic HBV infection (CHB), liver injury progression and outcomes.MethodsA total of 231 patients with CHB constituted the study group and 100 healthy volunteers—the local control group. TNF‐α −1031T/C, −863C/A, −857C/T, −308G/A, and −238G/A were genotyped using MALDI‐TOF mass spectrometry.Results TNF‐α −1031C and −863A alleles were observed more frequently in CHB group than in healthy controls. Carriers of TNF‐α −1031C and −863A variant alleles had lower baseline levels of serum HBV DNA and lower liver necroinflammatory activity than dominant homozygotes. A −857CT genotype predisposed to higher necroinflammatory activity. No associations between TNF‐α variants and liver fibrosis were found.ConclusionThis study indicates that TNF‐α −863A and −1031C alleles are associated with increased susceptibility to CHB in individuals from northern Poland. The same variants determine the course of CHB, lowering viremia and reducing necroinflammatory activity of the liver.

Hepatitis B Reactivation Rate and Fate Among Multiple Myeloma Patients Receiving Regimens Containing Lenalidomide and/or Bortezomib

Objective:Reactivation of the hepatitis B virus (HBV) refers to an increase in HBV replication in a patient with inactive or resolved HBV. In this retrospective study, our aim is to present and compare HBV reactivation in multiple myeloma (MM) patients who received lenalidomide and/or bortezomib at any time during treatment, evaluate the factors associated with reactivation, and demonstrate the outcome of patients.Materials and Methods:We evaluated 178 MM patients who received lenalidomide (n=102) and/or bortezomib (n=174) during their treatment schedules. The HBsAg, anti-HBc, anti-HBs, HBeAg, and anti-HBe were detected by chemiluminescence by ARCHITECT lab analyzers using commercially available kits (Abbott, USA). HBV-DNA titers were determined by quantitative PCR. The results were evaluated by IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY, USA).Results:HBV reactivation was diagnosed in 6 patients (3%) after bortezomib and in 8 patients (8%) after bortezomib and lenalidomide. Three of the patients in each group had HBsAg+, HBeAg+, AntiHBeAg-, AntiHBc-, and AntiHBS+ status, whereas 5 patients in the bortezomib- and lenalidomide-treated group and 3 patients in the bortezomib-treated group had HBsAg-, HBeAg-, AntiHBeAg-, AntiHBc-, and AntiHBS+ status prior to treatment. There were no statistical differences observed between HBV reactivation in the bortezomib-treated or bortezomib- and lenalidomide-treated groups in terms of age at diagnosis, sex, International Staging System subtype, frequency of extramedullary disease, dialysis requirement, or receiving of autologous stem cell transplantation. In patients who received antiviral prophylaxis, a higher incidence of HBV reactivation was detected in HBsAg-positive patients compared to HBsAg-negative patients (4/4, 100% vs. 2/7, 29%; p=0.045). The 3-year and 5-year overall survival rates were similar in patients with or without HBV reactivation (83% vs. 84%, 73% vs. 74%, p=0.84).Conclusion:Close follow-up is recommended for not only HBsAg-positive but also HBsAg-negative patients.

Chronic Hepatitis B in US Veterans.

This review summarizes recent data on chronic Hepatitis B virus (HBV) epidemiology, issues in special populations undergoing immunosuppressive and hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy, and describes care delivery, adherence to guideline-recommended care, and barriers to access to care and high-quality care for chronic HBV. Chronic HBV is present in up to 1% of veterans and is more than in the general US population. HBV associated with more advanced liver disease in HCV, HIV, and delta hepatitis co-infection. Recent data on HBV reactivation show a substantial risk of reactivation with anti-CD20 antibodies, no documented cases of reactivation with anti-tumor necrosis factor (anti-TNF) therapy, and a low risk of reactivation with HCV DAA therapy. Adherence to guideline-recommended care for HBV is suboptimal for many quality indicators. Important studies in HBV epidemiology, long-term outcomes and care delivery practices have been conducted in the VA. Future studies should prospectively investigate how to improve guideline-recommended care for HBV.

Iranian guideline for rituximab therapy in pemphigus patients.

Pemphigus vulgaris (PV) is an autoimmune blistering disease affecting the skin and/or mucosa. Rituximab (RTX) has been approved recently by US FDA as an effective and safe treatment of PV. The high incidence of PV in Iran encouraged our team to prepare a consensus guideline for RTX administration based on literature review and a decade experience of an expert panel. RTX is recommended for the treatment of new cases of PV as well as patients not responding to conventional therapy. Contraindications include history of anaphylaxis or IgE-mediated hypersensitivity to murine proteins of RTX, severe active infections, pregnancy, breastfeeding, severe heart failure, and arrhythmia. Prophylactic antiviral therapy is recommended in patients at risk of reactivation of HBV and isoniazid for those at risk of reactivation of tuberculosis. Concomitant use of systemic corticosteroids is recommended as a rule. Except for methotrexate, the combination with other immunosuppressive drugs is discouraged. Intravenous immunoglobulin is recommended for those at risk of infections or with extensive disease. The recommended dosage of RTX for the first cycle is 2 g either 500 mg weekly or 1 g biweekly. There is no general consensus whether the next doses of RTX be administered upon relapse or as maintenance therapy. We strongly recommend RTX sooner in the course of pemphigus.

Validity of administrative database detection of previously resolved hepatitis B virus in Japan.

The risk of hepatitis B virus (HBV) reactivation has increased owing to advances in the immunosuppressive therapy field. However, the HBV reactivation incidence among patients with previously resolved HBV (prHBV) infection during immunosuppressive therapy for rheumatoid arthritis (RA) remains unclear. The objective of this work is to describe the validity of detecting prHBV infection from administrative data through comparisons with chart abstraction and determine the incidence of HBV reactivation during immunosuppressive therapy for RA in Japan. In this retrospective cohort study, data on selected patients were extracted from administrative claims data. To identify patients with prHBV infection and de novo hepatitis, and HBsAg carriers, we conducted chart abstraction. The incidence rate of de novo hepatitis was 1.23 of 100 person‐years. The positive predictive value (PPV) and its 95% confidence interval (CI) of administrative data for the identification of suspected prHBV infections was 85.8% (95% CI: 81.7%‐89.3%). This study evaluated the PPV of the algorithm of HBV‐DNA testing with immunosuppressive therapy performed four times or more per year for the detection of prHBV infection from administrative data. Additionally, we determined the incidence rate of HBV reactivation among preHBV infections during immunosuppressive therapy for RA to be 1.23 of 100 person‐years.

Hepatitis B virus screening in patients with non-Hodgkin lymphoma in clinical practice in Poland - a report of the Polish Lymphoma Research Group.

IntroductionThe risk of HBV reactivation is important in lymphoma patients receiving immunosuppressive chemotherapy containing steroids or anti-CD20 antibodies. We aimed to establish the prevalence of HBV Ag and anti-HBc serologic positive results in patients with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) in Poland before anti-CD20 therapy initiation; to assess the frequency of insufficient HBV screening; and to assess the association between inadequate HBV screening and diagnosis according to the WHO classification and age or gender.Material and methodsWe retrospectively collected data from 805 patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia treated in 2016–2018.ResultsWe found a positive result of HBsAg in 13 (1.16%), and a negative result in 633 (78.64%) patients. The test was not done in 159 (19.75%) patients. In the HBsAg negative subgroup of 633 patients, we found that the anti-HBc was positive in 52 (8.22%), negative in 303 (47.87%) and not done in 278 patients. In 136 out of 805 (16.9%) patients diagnostics tests were not performed before therapy initiation. We found that age is significantly associated (p = 0.0002) with the lack of HBV infection screening, and in CLL this risk is significantly (p = 0.024) higher (by 49%) compared with other WHO diagnosis subgroups.ConclusionsIn Polish lymphoma patients the incidence of positive HBsAg and/or anti-HBc results is consistent with the prevalence in the United States or Australia. The adherence to appropriate HBV screening guidelines in Polish centers is not sufficient. We should intensify educational strategies in the global oncohematologic medical community.

Hepatitis B screening rates and reactivation in solid organ malignancy patients undergoing chemotherapy in Southern Thailand.

Background/AimsHepatitis B virus reactivation (HBVr) following chemotherapy (CMT) is well-known among hematologic malignancies, and screening recommendations are established. However, HBVr data in solid organ malignancy (SOM) patients are limited. This study aims to determine hepatitis B surface antigen (HBsAg) screening rates, HBV prevalence, and the rate of significant hepatitis caused by HBVr in SOM patients undergoing CMT.MethodsBased on the Oncology unit’s registration database from 2009–2013, we retrospectively reviewed records of all SOM patients ≥18 years undergoing CMT at Songklanagarind Hospital who were followed until death or ≥6 months after CMT sessions. Exclusion criteria included patients without baseline liver function tests (LFTs) and who underwent CMT before the study period. We obtained and analyzed baseline clinical characteristics, HBsAg screening, and LFT data during follow-up.ResultsOf 3,231 cases in the database, 810 were eligible. The overall HBsAg screening rate in the 5-year period was 27.7%. Screening rates were low from 2009–2012 (7.8–21%) and increased in 2013 to 82.9%. The prevalence of HBV among screened patients was 7.1%. Of those, 75% underwent prophylactic antiviral therapy. During the 6-month follow-up period, there were three cases of significant hepatitis caused by HBVr (4.2% of all significant hepatitis cases); all were in the unscreened group.ConclusionsThe prevalence of HBV in SOM patients undergoing CMT in our study was similar to the estimated prevalence in general Thai population, but the screening rate was quite low. Cases of HBVr causing significant hepatitis occurred in the unscreened group; therefore, HBV screening and treatment in SOM patients should be considered in HBV-endemic areas.