Hepatitis B Virus Reactivation Research Articles

Risk of tocilizumab-related HBV reactivation

Risk of tocilizumab-related HBV reactivation

1074. Understanding Screening Practices for Hepatitis B Prior to Starting Biologics at an Academic Medical Center

BackgroundIt is estimated that 0.3% of the US population has chronic hepatitis B (HBV) infection, most of whom are asymptomatic. When a patient receives a biologic medication, chronic HBV can reactivate with mortality rates as high as 40%. We aim to understand HBV screening practices prior to starting biologics at a single tertiary academic medical center.MethodsWe retrospectively reviewed over 500 patient charts. These patients aged ≥ 18 years were prescribed a biologic medication at one of the three clinics (Dermatology, Rheumatology, or Gastroenterology) at Tufts Medical Center from January 2016 to April 2019. To determine the rate of HBV screening compliance, we reported the proportion of patients who had appropriate HBV serologies (HBV surface antigen and HBV core antibody) drawn prior to initiation of the biologic therapy. A survey was sent to providers from these departments to understand their current practices of HBV screening.Results133 of 541 patients (25%) had been appropriately screened for HBV within six months prior to starting biologic therapy. 207 of 541 (38%) had been screened with appropriate serologies within ten years prior to starting a biologic. 23 providers participated in the survey, 7 each from the department of Rheumatology and Gastroenterology, and 9 from Dermatology. One-third of the providers were currently in training, another third were practicing for < 5 years, and the remainder had > 5 years of experience. 57% of the providers said they would screen everyone for HBV before starting a biologic. 78% of them chose the appropriate serologies. The time interval for rescreening was evenly spread amongst different providers, ranging from 3 months to 5 years. If a patient was switched to a new biologic, 48% of physicians would repeat screening only if the patient was determined to be at risk of reactivation or new acquisition of HBV. The major barrier to screening was uncertainty regarding who to screen and which tests to order.ConclusionThis data reveals that there is inadequate screening for HBV prior to biologic therapy. The survey highlighted areas for quality improvement, including the need for wider dissemination of screening guidelines and development of a protocolized approach to ordering the correct tests.Disclosures All Authors: No reported disclosures

Risk factors for de novo hepatitis B during solid cancer treatment.

BACKGROUNDReactivation of hepatitis B virus (HBV) during anticancer treatment is a critical issue. When treating patients with solid tumors, it is unclear whether specific cancer types or treatments affect HBV reactivation in hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (HBcAb)-positive patients, so-called de novo hepatitis B patients. The risk of de novo hepatitis B may vary based on different background factors.AIMTo determine the frequency and risk factors for de novo hepatitis B during solid tumor treatment.METHODSThis retrospective cohort study comprised 1040 patients without HBsAgs and with HBcAbs and/or hepatitis B surface antibodies (HBsAbs). The patients were treated for solid cancer from 2008 to 2018 at the National Kyushu Cancer Center and underwent HBV DNA measurements. Patient characteristics and disease and treatment information were investigated. HBV DNA measurements were performed using TaqMan polymerase chain reaction (PCR). To identify the risk factors associated with HBV DNA expression, the age, sex, original disease, pathology, treatment method, presence or absence of hepatitis C virus (HCV), and HBsAb and/or HBcAb titers of all subjects were investigated. In patients with HBV DNA, the time of appearance, presence of HBsAgs and HBsAbs at the time of appearance, and course of the subsequent fluctuations in virus levels were also investigated.RESULTSAmong the 1040 patients, 938 were HBcAb positive, and 102 were HBcAb negative and HBsAb positive. HBV DNA expression was observed before the onset of treatment in nine patients (0.9%) and after treatment in 35 patients (3.7%), all of whom were HBcAb positive. The HBV reactivation group showed significantly higher median HBcAb values [9.00 (8.12-9.89) vs 7.22 (7.02-7.43), P = 0.0001] and significantly lower HBsAb values (14 vs 46, P = 0.0342) than the group without reactivation. Notably, the reactivated group showed a significantly higher proportion of cancers in organs related to digestion and absorption (79.0% vs 58.7%, P = 0.0051). A high HBcAb titer and cancers in organs involved in digestion and absorption were identified as independent factors for HBV reactivation (multivariate analysis, P = 0.0002 and P = 0.0095). The group without HBsAbs tended to have a shorter time to reactivation (day 43 vs day 193), and the frequency of reactivation within 6 mo was significantly higher in this group (P = 0.0459) than in the other group.CONCLUSIONA high HBcAb titer and cancers in organs involved in digestion and absorption are independent factors that contribute to HBV reactivation during solid tumor treatment.

Safety and efficacy of tenofovir alafenamide in liver transplant recipients: A single center experience.

Tenofovir disoproxil fumarate (TDF) is frequently used for treatment of and prophylaxis against reactivation of hepatitis B virus (HBV) after liver transplant (LT). Because TDF can lead to renal impairment and a decrease in bone mineral density (BMD), the prodrug tenofovir alafenamide (TAF) may be considered a viable alternative with fewer adverse effects. Only limited information is available about the use of TAF for LT recipients. We report a European single-center experience with TAF as treatment for LT patients. This retrospective analysis involved 29 LT recipients receiving standard immunosuppressants (mainly calcineurin inhibitors). Demographic and clinical data were documented at baseline upon switch to TAF and at various time points thereafter. None of the patients experienced HBV reactivation after the switch to TAF. Liver and renal function remained stable. Drug levels of immunosuppressive agents did not change significantly after the switch. After 1year, 22 patients were still taking TAF; two patients had been lost to follow-up; one patient had died; and four patients had discontinued therapy because of TAF-related adverse effects. No serious adverse effects were reported. Tenofovir alafenamide exhibits high antiviral efficacy and a good safety profile for LT recipients. Still, the safety and tolerability of TAF for organ transplant patients should be evaluated in larger cohorts.

Hepatitis B Virus Screening and Real Life Data in Patients with Solid Tumor Receiving Chemotherapy.

Reactivation of the hepatitis B virus (HBV) either during or after chemotherapy may cause serious and sometimes fatal hepatitis. All patients undergoing chemotherapy should therefore be screened in terms of HBV before chemotherapy. The purpose of this research was to identify HBV screening rates in patients with solid cancer undergoing parenteral chemotherapy and to determine the outcomes of patients undergoing HBV screening. Data for patients undergoing parenteral chemotherapy for solid cancer from January 1, 2012 to December 30, 2018 were retrieved from our electronic health record patient files in this retrospective study. Screening was defined as hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) tests carried out within six months prior the first chemotherapy session. Four thousand fifty-eight (63%) of the 6440 patients who underwent parenteral chemotherapy were screened for HBsAg and/or HBcAb. The proportions of patients screened for HBsAg and HBcAb improved from 38.8% (2012) to 76.3% (2018), and from 0.2% (2012) to 43% (2018), respectively (P<0.001). The HBsAg and HBcAb positivity rates were 2.9% and 36.5%, respectively. Antiviral prophylaxis was started in 11.8% of HBsAg-negative/HBcAb-positive patients and 40.5% of HBsAg-positive patients. HBV reactivation did not occur in patients receiving antiviral prophylaxis, but was identified in 7.2% of HBsAg-positive patients and 0.6% of HBsAg-negative/HBcAb-positive patients without antiviral prophylaxis. Although HBV screening rates before chemotherapy are increasing among solid cancer patients, the rate of initiation of antiviral prophylaxis is still low. It is therefore important to raise awareness regarding HBV reactivation during/after chemotherapy.

Outcome after kidney transplantation in hepatitis B surface antigen-positive patients

Few reports detail the actual outcome of Hepatitis B Surface Antigen-positive patients after kidney transplant. HBsAg-positive patients who underwent kidney transplant between January, 1999, and December, 2018, were reviewed retrospectively. Outcomes including hepatitis B reactivation rate, risk factors for reactivation, and patient and graft survival rates were analyzed. Seventy-seven patients were enrolled (47.1 ± 11.5 years old). Patients received ABO-incompatible (n = 5), crossmatch positive transplant (n = 2), and re-transplant (n = 4). Forty-six patients received prophylactic; 19, medication at least 3 months before the transplant; and 12, did not receive medication. Seventeen out of 76 patients developed reactivation post-transplant. 52.9% of HBV reactivation was accompanied by hepatitis. Inappropriate, other than lifelong prophylactic, antiviral agents (HR = 7.34, 95% CI 1.51-35.69, P = 0.01) and high hepatitis DNA (≥ 1000 IU/ml) pre-transplant (HR = 4.39, 95% CI 1.08-17.81, P = 0.04) increased reactivation risk. There was no significant difference in patient and graft survival between antigen positive patients who received antiviral agent and propensity score matched negative patients. HBsAg positivity in kidney transplant recipients is associated with substantial HBV reactivation rate. Lifelong antiviral therapy is mandatory, and patients with high preop HBV titer should be monitored closely for HBV reactivation.

Effect of SARS-CoV-2 coinfection was not apparent on the dynamics of chronic hepatitis B infection

In patients coinfected with SARS-CoV-2 and HBV, liver injury was common. However, the interactions between SARS-CoV-2 and HBV coinfection remained unknown. Sixty-seven COVID-19 patients from the previous cohort were enrolled and classified into 2 groups (7 with HBsAg+ and 60 with HBsAg-). The association of HBV- and SARS-CoV-2-related markers were analyzed. During the acute course of SARS-CoV-2 infection, markers of HBV replication did not extensively fluctuate during SARS-CoV-2 infection. Coinfection with HBV did not extend the viral shedding cycle or incubation periods of SARS-CoV-2. Effects of SARS-CoV-2 on the dynamics of chronic HBV infection seemed not apparent. SARS-CoV-2 infection would not be the source of HBV reactivation in these individuals.

Risk of hepatitis B reactivation in patients receiving anti-tumor necrosis factor-α therapy.

The purpose of this study was to determine hepatitis B virus (HBV) screening rates in patients receiving anti-tumor necrosis factor (TNF)-α therapy and the frequency of HBV reactivation in patients with resolved hepatitis B virus infection (hepatitis B surface antigen [HBsAg] negative, hepatitis B core antibody [Anti-HBc] positive). Data from 1834 patients who underwent anti-TNF-α therapy in the Rheumatology, Gastroenterology and Dermatology Departments of our hospital between 2010 and 2020 were retrospectively analyzed. Within 6months before the initial anti-TNF-α therapy, performing a HBsAg and/or anti-HBc test is defined as HBV screening. HBV reactivation is defined as the presence of detectable serum HBV DNA or HBsAg seroconversion from negative to positive. The overall HBV screening rate was 82.3% before starting anti-TNF-α therapy. There was an increasing trend in HBV screening rates during the years analyzed (64% in 2010, 87.4% in 2019) (P<.001). Before anti-TNF-α therapy was initiated, 272 patients were HBsAg negative and anti-HBc positive. Among these patients, HBV reactivation did not occur in 31 patients who received antiviral prophylaxis, whereas HBV reactivation occurred in only 1 (0.4%) of the 241 patients who did not receive antiviral prophylaxis. Hepatitis B virus screening rates prior to starting anti-TNF-α therapy were relatively high, and its trend was increased by year. HBV reactivation because of anti-TNF-α use rarely occurred in patients with resolved HBV infection. Further studies are needed on whether routine anti-HBc screening and/or HBV DNA follow-up are necessary in these patients aside from HBsAg.

Prevalence and genetic variability of occult hepatitis B virus in a human immunodeficiency virus positive patient cohort in Gondar, Ethiopia.

Occult hepatitis B (OHB) is a major concern in HIV infected patients as it associates with a high risk of HBV reactivation and disease progression. However, data on the prevalence of OHB among HIV positive patients in Ethiopia is lacking. This study aims to determine the prevalence of OHB in HBV/HIV co-infected patients from Gondar, Ethiopia. A total of 308 consented HIV positive patients were recruited from the University of Gondar Teaching Hospital, Ethiopia. Clinical and demographic data of the participants were recorded. Plasma was tested for HBsAg and anti-HBc using commercial assays (Abbott Architect). In HBsAg negative anti-HBc positive patient samples, total DNA was isolated and amplified using nested PCR with primers specific to HBV polymerase, surface and pre-core/core regions, followed by Sanger sequencing and HBV mutational analysis using MEGA 7.0. Of the total study subjects, 62.7% were female, median age 38.4 years, interquartile range (IQR): 18-68, and 208 (67.5%) had lifestyle risk factors for HBV acquisition. Two hundred and ninety-one study subjects were HIV+/HBsAg-, out of which 115 (39.5%) were positive for anti-HBc. Occult hepatitis B was detected in 19.1% (22/115) of anti-HBc positive HIV patients. HBV genotype D was the predominant genotype (81%) among OHB positive patients. Mutations associated with HBV drug resistance, HBV reactivation, and HCC risk were detected in 23% (5/22), 14% (3/22) and 45.5% (10/22) of patients, respectively. This study found a high rate of occult hepatitis B in HIV patients. Further, high rates of mutations associated with HBV reactivation, drug resistance, and HCC risk were detected in these patients. These data highlighted the need for integrating OHB screening for proper management of liver diseases in HIV patients.

Prevalence of Hepatitis B Virus Markers in Patients with Autoimmune Inflammatory Rheumatic Diseases in Italy.

Chronic hepatitis B virus (HBV) infection may be reactivated by immunosuppressive drugs in patients with autoimmune inflammatory rheumatic diseases. This study evaluates HBV serum markers’ prevalence in rheumatic outpatients belonging to Spondyloarthritis, Chronic Arthritis and Connective Tissue Disease diagnostic groups in Italy. The study enrolled 302 subjects, sex ratio (M/F) 0.6, mean age ± standard deviation 57 ± 15 years, 167 (55%) of whom were candidates for immunosuppressive therapy. The Spondyloarthritis group included 146 subjects, Chronic Arthritis 75 and Connective Tissue Disease 83 (two patients had two rheumatic diseases; thus, the sum is 304 instead of 302). Ten subjects (3%) reported previous anti-HBV vaccination and tested positive for anti-HBs alone with a titer still protective (>10 IU/mL). Among the remaining 292 subjects, the prevalence of positivity for HBsAg, isolated anti-HBc, anti-HBc/anti-HBs, and any HBV marker was 2%, 4%, 18%, and 24%, respectively. A total of 26/302 (9%) patients with γ-globulin levels ≤0.7 g/dL were more frequently (p = 0.03455) prescribed immunosuppressive therapy, suggesting a more severe rheumatic disease. A not negligible percentage of rheumatic patients in Italy are at potential risk of HBV reactivation related to immunosuppressive therapy. Before starting treatment, subjects should be tested for HBV markers. Those resulting positive should receive treatment or prophylaxis with Nucleos (t) ides analogue (NUCs) at high barrier of resistance, or pre-emptive therapy, according to the pattern of positive markers. HB vaccination is recommended for those who were never exposed to the virus.

Hepatitis B surface antibody titres and hepatitis B reactivation with direct-acting antiviral therapy for hepatitis C.

HBV reactivation can occur while undergoing direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV). The role of hepatitis B surface antibody (HBsAb) has not been systematically explored. Therefore, the purpose of this systematic review was to explore the role of the presence of HBsAb on the risk of HBV reactivation related to DAA therapy. We reviewed MEDLINE, CINAHL, EMBASE and Cochrane Central for studies on DAA therapy and data on HBsAb in patients with resolved hepatitis B (hepatitis B surface antigen-negative and hepatitis B core antibody-positive). We identified twenty-nine reports: thirteen case reports with HBV reactivation (10 HBsAb-negative and 3 HBsAb-positive patients) and sixteen cohort studies totalling 2528 patients with resolved HBV infection (1429 HBsAb negative, 1099 HBsAb positive). Reactivation was found in 12 (0.8%) HBsAb-negative and 7 (0.6%) HBsAb-positive individuals of cohort studies. All but two HBV reactivation occurred in patients with HBsAb titre <30 iU/L. The presence of HBsAb showed a trend towards delayed reactivation (median 12weeks vs 9.5weeks; P=.07). Importantly, with the exception of a patient with escape variant and an HIV-infected individual, no HBsAb-positive individual demonstrated clinical reactivation. HBsAb presence seems to protect from clinical HBV reactivation related to DAA therapy. The most pronounced prevention for reactivation may require titres greater than 30iU/L.

Updates on management strategies of hepatitis B virus reactivation in patients with resolved hepatitis virus B infection undergoing immunosuppressive therapy in rheumatology and the current situation in Niigata Rheumatic Center

With the introduction of methotrexate, biological disease-modifying antirheumatic drugs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs), the disease activity of patients with rheumatoid arthritis has been dramatically ameliorated. However, these drugs have strong immunosuppressive effects and can cause reactivation of hepatitis B virus (HBV) in patients with resolved HBV infection. Corticosteroids or immunosuppressants used for other connective tissue diseases or vasculitis also carry a risk of inducing reactivation of HBV. Therefore, every rheumatologist should know how to detect the resolved infection of HBV in patients with rheumatic diseases receiving immunosuppressive therapy and how to monitor it when resolved infection is revealed. Of note, the cut-off index was changed from 2.1 log copies/ml to 20 IU/ml (1.3 Log IU/ml) in 2017. Rheumatologists should start nucleic acid analog administration at reactivation of HBV while performing ongoing immunosuppressive therapy in order to prevent severe or fulminant hepatitis. A low titer of HBs antibody (Ab) or lack of HBs Ab is a risk factor of reactivation of HBV. However, the reactivation of HBV cannot be prevented by HBs Ab titers at baseline or changes overtime. Rheumatologists should recognize that every immunosuppressive therapy, regardless of the mode of action, has a potential risk of reactivation. To facilitate proper management of patients with HBV infection, collaboration between rheumatologists and hepatologists is strongly encouraged. Patients’ education, systems for checking electronic medical charts, and multidisciplinary efforts are considered important for detecting HBV reactivation.

Hepatitis B virus reactivation during temozolomide administration for malignant glioma.

The purpose of this study is to clarify the clinical features of temozolomide (TMZ)-related hepatitis B virus (HBV) reactivation and to identify HBV reactivation predictive factors. We retrospectively reviewed the clinical course of 145 patients newly diagnosed or with recurrent malignant glioma treated with TMZ. Before treatment, we screened patients for HB surface antigen (HBsAg) positivity (HBV carrier) and HBsAg negativity. Patients were also screened for antibody for HB core antigen (anti-HBc) positivity and/or for HB surface antigen positivity (resolved HBV infection). The patients were monitored by HBV DNA, alanine, and aspartate aminotransaminase during and after the completion of TMZ. HBV carriers and those with resolved HBV infections with HBV reactivation received preemptive entecavir treatment. In those with resolved HBV infections, we analyzed clinical characters for the predictive factors for HBV reactivation. In one of two HBV carriers, HBV DNA turned positive 8months after the completion of TMZ and entecavir. In four (16.7%) of 24 resolved HBV infections, HBV DNA turned detectable at completion of concomitant radiation and TMZ or during monthly TMZ. HBV DNA turned negative with entecavir in all patients without liver dysfunction. In resolved HBV infections, those with a high anti-HBc titer had significantly higher incidence of HBV reactivation than those with low anti-HBc titers (60% vs. 5.3%: p = 0.018). Screenings, monitoring, and preemptive entecavir were important for preventing TMZ-related HBV reactivations. Anti-HBc titers could be the predictive markers for HBV reactivation in the those with resolved HBV infections.

Hepatitis B Virus Reactivation in Patients Receiving Chemotherapy and Immunosuppressive Therapy

Hepatitis B virus (HBV) infection is a serious and common infectious disease of the liver, affecting millionsof people throughout the world. The incubation period for HBV is 45-180 days, most commonly 60-90 days.Hepatitis B reactivation is the reappearance or rise of hepatitis B virus (HBV) DNA in the serum of patientswith past or chronic HBV infection. Reactivation can occur in a variety of clinical settings, usually in thecontext of an immunosuppressed state or immunosuppressive therapy. The aim of study is to find out thereasons that lead to reactivation of hepatitis B virus. The study conducted during the period from September2019 to February 2020 the sample size were 135 individuals include 85 patients and 50 control with 56.47%female and 43.53% male) blood samples. A 42 (49.41%) from patients have reactivated HBV positive resultsas detected by ELISA assay . A five samples at a rate of 5.88% from these are HBV reactivation by PCRtechnique.

Low risk of hepatitis B reactivation in patients with severe COVID-19 who receive immunosuppressive therapy.

A significant proportion of patients infected with SARS‐CoV‐2 develop severe respiratory symptoms due to an excessive immune response. Treatment of this condition may include immunosuppressive therapies, such as IL‐6 receptor antagonists and corticosteroids, which pose a risk for patients with active or past hepatitis B virus (HBV) infection. In this prospective cohort study, we analysed the risk of HBV reactivation in patients with severe COVID‐19 and resolved HBV infection undergoing immunosuppressive therapy. From 15th March to 30th April 2020, 600 patients with severe COVID‐19 were admitted to our hospital and treated with immune modulators. Data regarding HBV infection were available in 484, of whom 69 (14%) were HBsAg negative/anti‐HBc positive. For these patients, HBV reactivation prophylaxis with entecavir was strongly recommended. Complete follow‐up was available in 61 patients: 72% were male, median age was 67 years, and anti‐HBs was >10 IU/mL in 72%. The immunosuppressive drug most used was tocilizumab (72%). Despite HBV prophylaxis recommendation, 38 (62%) patients received entecavir and 23 (38%) did not. Baseline features of both groups were similar. At follow‐up, we found no cases of HBsAg seroreversion and only 2 (3%) patients (no prophylaxis group) had detectable serum HBV‐DNA (<15 IU/mL). Both were anti‐HBs negative and had normal aminotransferase levels. Our data show that the risk of HBV reactivation in patients with severe COVID‐19 and resolved HBV infection undergoing immunosuppressive treatment is low. However, if a systematic follow‐up after hospital discharge is unfeasible in patients without anti‐HBs, a short course of antiviral prophylaxis may be a safe option.

Serum ammonia is a strong prognostic factor for patients with acute-on-chronic liver failure

Ammonia is thought to be central to the pathogenesis of hepatic encephalopathy (HE), but its prognostic role in acute-on-chronic liver failure (ACLF) is still unknown. We aimed to determine the association between serum ammonia level and short-term prognosis in ACLF. Furthermore, we performed an in-depth evaluation of the independent effect of serum ammonia level on the short-term prognosis of hepatitis B virus (HBV) reactivation-induced ACLF patients. We identified 174 patients as part of prospective observational studies in patients with ACLF. Plasma ammonia levels were measured on admission, and several prognostic scores were used to determine the prognostic effect of ammonia. The 28-day patient survival was determined. Receiver operating characteristic analysis was used to identify the cut-off points for ammonia values, and multivariable analysis was performed using the Cox proportional hazard regression model. Plasma ammonia was significantly higher in nonsurvivors (83.53 ± 43.78 versus 67.13 ± 41.77 µmol/L, P = 0.013), and ACLF patients with hyperammonemia had significantly higher 28-day mortality than those without hyperammonemia. Ammonia was also closely related to ACLF grade (P < 0.001) and organ failure, including liver (P = 0.048), coagulation (P < 0.001) and brain (P < 0.001). HBV reactivation serves as the main precipitating factor in the ACLF population. Subgroup analysis showed that ammonia is also a strong prognostic factor in the HBV reactivation-induced ACLF population. Ammonia level is closely correlated with failure of other organs and is an independent risk factor for mortality in ACLF and the special population defined as HBV reactivation-related ACLF. Based on the results from our study, we measured serum ammonia in the population with ACLF, which strongly indicates their prognosis. It serves as an important biomarker and a therapeutic target.

Outcome of nucleos(t)ide analog intervention in patients with preventive or on-demand therapy for hepatitis B virus reactivation.

Preventive or on-demand nucleos(t)ide analog (NA) therapy can prevent severe hepatitis related to hepatitis B virus reactivation (HBV-R). However, it is unclear if NA can be safely stopped in such patients after cytotoxic therapies or during immunosuppressive therapies.We retrospectively evaluated 133 patients who initiated NA therapy between 2007 and 2018. A total of 103 patients were positive for HBV surface antigen (HBsAg) at baseline, and NA therapy was started before cytotoxic or immunosuppressive therapy (preventive group). Thirty patients with resolved HBV infection were treated with NA therapy after HBV reactivation (on-demand group). Virological relapse was defined as a serum HBV DNA level >20 IU/ml.NA therapy was stopped in 12 (12%) patients (preventive group), and in 16 (53%) patients (on-demand group). After the cessation of NA therapy, the cumulative rates of relapse were 36% and 39% at 12 and 24 months, respectively. High levels of HBsAg both at baseline and at the cessation of NA therapy were related to the occurrence of relapse. Relapse did not occur in patients with HBsAg levels <20 IU/ml (preventive group). HBV relapse occurred in five (33%) patients in the on-demand group. Relapse occurred only in anti-HBs-negative patients at the cessation of NA therapy. There were no cases of hepatitis flare after the cessation of NA therapy.HBsAg predicted HBV relapse after the cessation of NA therapy in HBsAg-positive patients. Anti-HBs could be a predictive marker for NA therapy cessation in patients with resolved HBV.

S3497 A Case of Hepatitis B Virus Reactivation Triggered by an Acute Epstein-Barr Virus Infection

INTRODUCTION: Reactivation of Hepatitis B virus (HBV) is not an uncommon condition. It is known to occur with immunosuppressive therapy, especially with rituximab. There are several viral infections that can trigger HBV reactivation such as human immunodeficiency virus (HIV) infection. However, there is no reported case of HBV reactivation triggered by Epstein-Barr virus (EBV) infection in the literature. To date, we report the first case of reactivation of HBV secondary to acute EBV infection. CASE DESCRIPTION/METHODS: A 47-year-old Caucasian male with a remote history of resolved acute Hepatitis B virus infection, who presented to our hospital with severe acute hepatitis which manifested as epigastric pain, jaundice, dark urine, light-colored stools, hyperbilirubinemia, and transaminitis in the 1000s. Ultimately, the patient was diagnosed with reactivation of HBV triggered by acute EBV infection. After several days of supportive treatment, his hepatic function normalized. He was discharged with a scheduled follow-up at a hepatology clinic. DISCUSSION: To date, this is the first case of HBV reactivation triggered by acute EBV infection described in the literature. In conclusion, EBV infection should be suspected as a trigger in cases with HBV reactivation, particularly when common etiologies are excluded.

S1012 Outcomes of Liver Transplantation in Patients With Pre-Existing Extra-Hepatic Malignancies: A Systematic Review

INTRODUCTION: Liver transplantation (LT) is rarely carried out in patients with pre-existing extra-hepatic cancers, and little is known about patient survival and cancer recurrence in patients with a history of extra-hepatic cancer who undergo LT. METHODS: A systematic review of Medline and Embase was conducted from inception-March 2020 to identify studies reporting outcomes in patients with pre-existing extra-hepatic malignancies who underwent LT. Case reports and series were included in the systemic review due to the expected scarcity of data. Descriptive statistics were employed to report findings; results were reported as proportions. RESULTS: Overall, 112 cases were identified, 61 of which were extracted from 4 case series. Females constituted 50% of the cohort. The prevalence of solid tumors and hematological malignancies was 52.6% and 47.3%, respectively. The most commonly reported solid tumor and hematological malignancy was colorectal cancer (18.6%) and Hodgkin’s Lymphoma (24.5%), respectively. The most common indication for LT was HBV/HCV associated liver disease (22.3%), followed by sclerosing cholangitis (16.1%), and Budd-Chiari syndrome (15.2%). When stratified according to cancer type, HBV/HCV associated liver disease and Budd-Chiari syndrome were the most common indications for LT among patients with solid tumors and hematological malignancies, respectively. Additionally, 6 (5.4%) patients with hematological malignancies underwent LT due to acute liver failure (ALF) from HBV reactivation. The mean time from malignancy diagnosis to LT was 12.61 months (SD 14.74). T-cell antibody induction regimens were used in only two cases. The most used immunosuppressants were corticosteroids (36.6%), followed by cyclosporine (32.1%). Acute graft rejection was reported in 50 (44.6%) of patients. Nine (8%) patients experienced recurrent or progressive malignancy (4 solid tumors, 5 hematological malignancies/MPD). 86.6% of patients were alive over a mean follow-up period of 39 months. CONCLUSION: Liver transplantation can be offered in select patients with a history of extrahepatic malignancies and has an acceptable survival at three years. This literature review suggests a higher rate of rejection in these patients, which is likely reflective of a lower degree of immunosuppression.Table 1

Prediction of survival according to kinetic changes of cytokines and hepatitis status following radioembolization with yttrium-90 microspheres

Yttrium-90 radioembolization (Y90-RE) may exert an immunomodulatory effect on the tumor microenvironment of hepatocellular carcinoma (HCC). Whether the host immune alterations after Y90-RE correlated with outcomes and whether Y90-RE affects viral hepatitis reactivation remains unclear. Between July 2014 and July 2015, 18 patients undergoing Y90-RE for HCC were prospectively enrolled. Serum levels of virological markers, cytokines and chemokines were measured at baseline, 2, 4, and 12 weeks after Y90-RE. Factors associated with the clinical outcomes were evaluated. The disease control rate of Y90-RE was 44.4% (8 of 18) at 12 weeks, including 1 case with complete response, 4 cases with partial response, and 3 cases with stable disease. Significant elevation from baseline to week 2 and week 4 were noted in IL-10 level (8.4±33.8, 15.7±31.6, and 16.0±41.7pg/mL, P=0.041 and 0.013, respectively) and IP-10 level (113.5±97.8, 189.1±164.4, and 168.6±150.5pg/mL, P=0.027 and 0.026, respectively). After Y90-RE, transient HBV reactivation occurred in 2 patients, and 1 out of 3 HCV-infected patients exhibited HCV reactivation. Univariate analysis revealed that lower baseline IP-10 (≤200pg/mL) and alanine aminotransferase (ALT) (≤50 U/L) levels were associated with better overall survival. Multivariate analysis identified an IP-10 level of 200pg/mL (HR=4.374, P=0.045) as a predictor of overall survival. Baseline serum IP-10 level is a predictor of survival for HCC patients undergoing Y90-RE. HBV and HCV reactivation may develop after Y90-RE treatment.