Hepatitis B Virus Reactivation Research Articles

1406. Hepatitis B and C Prevalence in Patients with Active and Latent Tuberculosis in an Ethnically Diverse Area of London, UK

BackgroundNorth West London has one of the highest tuberculosis (TB) rates in the UK, at 24.8 per 10,000. The UK prevalence of hepatitis B virus (HBV) is 0.1-0.5% and for hepatitis C virus (HCV) is 0.5-1%. Chronic infection with HBV or HCV can lead to an increased risk of adverse treatment outcomes, such as drug-induced liver injury (DILI) in patients with active or latent TB. National guidelines recommend routinely screening for HBV/HCV prior to initiating TB treatment. Our objectives were to 1) evaluate the HBV/HCV screening practice in local TB clinics, 2) establish the prevalence of HBV/HCV in patients receiving TB treatment.MethodsRetrospective analysis of laboratory and medical records of patients treated for active or latent TB identified from the London TB register and clinic records from 01/01/2018 to 31/12/2020 from London North West NHS Trust.Results1409 patients received treatment for TB during the time period of interest; 574 (40.7%) had active disease and 835 (59.3%) had latent infection. 966/1409 patients (68.56%) were screened for HBV and HCV. 55.9% of the active TB group and 77.2% of the latent infection group were tested. 66 (6.8%) patients had isolated anti-HBc positivity, 22 (2.3%) were HBV surface antigen positive and 8 (0.8%) were HCV-antibody positive. HBV surface antigens were more prevalent in active TB patients: 9/321 (2.80%) with active TB versus 13/645 (2.02%) with latent TB. 36/321 (11.21%) active TB patients had HBV core antibodies compared to 30/645 (4.65%) latent TB patients (p < 0.001). Three patients started antiviral treatment following their viral hepatitis diagnosis (one with HBV, two with HCV).ConclusionThe prevalence of chronic HBV in the study population was higher than the estimated UK prevalence. Fifteen diagnoses of hepatitis were new, allowing specialist referral for monitoring of fibrosis and development of hepatocellular carcinoma. Three patients required hepatitis treatment. 6.8% of patients were positive for anti-HBc and therefore identified as being at future risk of HBV reactivation if requiring immunosuppressive therapies.TB disproportionately affects marginalised communities; screening for viral hepatitis in TB clinic represents an opportunity to target these hard-to-reach groups to maximise the impact of public health interventions.Disclosures All Authors: No reported disclosures

919. Rates of False-Positive Hepatitis B Surface Antigen Is Low in Cancer Patients

BackgroundAccurate interpretation of hepatitis B virus (HBV) laboratory testing is paramount in avoiding inaccurate diagnosis and incorrect management that could lead to unnecessary and overtreatment. This is particularly relevant in patients with cancer where universal testing is recommended in order to avoid HBV reactivation. Hepatitis B surface antigen testing (HBsAg) positivity indicates chronic or acute HBV infection. The rates and outcomes of a false-positive HBsAg have not been established for patients with cancer.MethodsThree hundred and ninety-seven patients with any type of cancer and positive HBsAg seen at MD Anderson Cancer Center from January 2016 – January 2021 were retrospectively reviewed in this study approved by the institutional review board. Cases of false-positive HBsAg were defined as those patients with a positive HBsAg but negative HBsAg quantitative, negative HBV core antibody (total Ig), and undetectable HBV DNA within 30 days of positive HBsAg testing. Serum samples from patients were tested for HBsAg using Vitros Enhanced Chemiluminescent Immunoassay (Ortho-Clinical Diagnostics, Raritan, NJ, USA). Data collection includes demographics, past medical history, underlying cancer and its stage, prior cancer treatment, risk factors for HBV, co-infections (hepatitis C, HIV), symptoms, liver function tests, anti-HBV treatment, and interruptions on cancer treatment.ResultsOut of 397 patients with a positive HBsAg, 33 were excluded as they did not meet the diagnostic criteria or have insufficient HBV data. Of them, 3 cases (0.8%) were identified as false positive HBsAg. All 3 patients were female, white, and had progressive malignancy (Table 1). No prior history of liver disease or liver function abnormalities were noted with these 3 patients. Initially, antiviral treatment was started on 1 patient which was discontinued shortly after confirmation of false-positive HBsAg. All 3 patients had additional workup and evaluation by an HBV specialist. In 2 patients, cancer treatment was canceled or delayed. ConclusionAlthough uncommon, cancer patients with false-positive HBsAg need further workup to avoid overtreatment and unnecessary interruptions in cancer careDisclosures Jessica P. Hwang, MD, MPH , Merck (Grant/Research Support)

Ledipasvir/Sofosbuvir for Patients Coinfected With Chronic Hepatitis C and Hepatitis B in Taiwan: Follow-up at 108 Weeks Posttreatment.

BackgroundFor patients coinfected with hepatitis C virus (HCV) and hepatitis B virus (HBV), HCV treatment with direct-acting antivirals can lead to HBV reactivation. We evaluated HBV reactivation during ledipasvir/sofosbuvir treatment and 108-week follow-up.MethodsIn Taiwan, 111 patients with HCV genotype 1 or 2 and HBV received ledipasvir/sofosbuvir (90mg/400mg) once daily for 12 weeks. HBV virologic reactivation was defined as postbaseline increase in HBV DNA from either less than the lower limit of quantification (LLOQ, 20 IU/mL) to equal to or more than LLOQ or equal to or more than LLOQ to >1 log10 IU/mL. HBV clinical reactivation was HBV virologic reactivation with alanine aminotransferase (ALT) >2× upper limit of normal. Factors associated with development of HBV virologic or clinical reactivation were evaluated with logistic regression analysis.ResultsAll patients (100%, 111/111) maintained HCV suppression through 108 weeks after treatment. HBV virologic reactivation occurred in 73% of patients (81/111). Clinical reactivation occurred in 9% (10/111). The majority of HBV virologic reactivations (86%, 70/81) occurred by follow-up week 12, whereas clinical reactivation was generally more delayed. Eight (7%, 8/111) initiated HBV therapy. In regression analyses, baseline HBV DNA and hepatitis B surface antigen (HBsAg) levels were associated with HBV virologic reactivation and baseline ALT and HBV DNA, and HBsAg levels were associated with HBV clinical reactivation.ConclusionAmong HCV/HBV coinfected patients treated with direct-acting antivirals for HCV, HBV virologic reactivation occurred in a majority of patients during treatment and follow-up. In most patients, HBV virologic reactivation was asymptomatic; only a small proportion initiated HBV treatment. Notably, clinical reactivation may still occur >3 months after end of therapy.Clinical Trials RegistrationNCT02613871.

Entecavir Prevents HBV Reactivation During Direct Acting Antivirals for HCV/HBV Dual Infection: A Randomized Trial

A strategy to prevent hepatitis B virus (HBV) virologic reactivation (HBVr) and clinical reactivation (CR) during direct acting antiviral (DAA) treatment of hepatitis C virus (HCV)/HBV dual infection remains an unresolved issue. Noncirrhotic patients with dual HCV/HBV infection were enrolled and allocated randomly to 1 of 3 groups as follows: 12 weeks of DAA alone (group 1), 12 weeks of DAA plus 12 weeks of entecavir (group 2), or 12 weeks of DAA plus 24 weeks of entecavir (group 3). The entire study duration was 72 weeks. The primary end point was the occurrence of HBVr (defined by an increase of HBV DNA level >10-fold with quantifiable HBV DNA at baseline or the presence of HBV DNA with prior unquantifiable HBV DNA) and CR (defined by serum alanine aminotransferase level >2-fold the upper limit of normal in addition to HBVr). Fifty-six patients were allocated randomly as follows: 20 patients in group 1, 16 patients in group 2, and 20 patients in group 3. In group 1, HBV DNA levels increased significantly as early as 4 weeks after initiation of DAA and persisted until the end of the study. During DAA treatment, HBVr occurred in 50% in group 1 vs 0% in group 2 and 0% in group 3 (P < .001), whereas the majority of HBVr in groups 2 and 3 occurred 12 weeks after cessation of entecavir (cumulative incidence, 93.8% in group 2 and 94.7% in group 3). Three patients (5.4%; 1 in each group) showed CR at week 48 and did not receive entecavir treatment. Twelve weeks of entecavir is suggested to be co-administered with DAA for HCV/HBV dually infected patients. gov no: NCT04405011.

Establishment and validation of a prognostic model for hepatitis B virus‑related acute-on-chronic liver failure patients with bacterial infection.

Bacterial infection is one of the most frequent complications in acute-on-chronic liver failure (ACLF), which leads to high mortality. However, a specific prognostic model for ACLF patients with bacterial infection has not been well established. To establish and validate a nomogram for predicting 30-day mortality of hepatitis B virus-related ACLF (HBV-ACLF) patients with bacterial infection. A total of 513 ACLF patients for HBV reactivation were enrolled in the prospective cohort, and 224 patients with bacterial infection were for derivation. Independent predictors were identified using multivariate logistic model and then assembled into a nomogram to predict 30-day mortality. The performance of the nomogram was assessed based on its calibration, discrimination and clinical utility in a retrospective cohort of 192 HBV-ACLF patients with bacterial infection. Age, total bilirubin, lactate dehydrogenase, international normalized ratio and soluble interleukin-2 receptor were shown to be independent risk factors for 30-day mortality of HBV-ACLF patients with bacterial infection and the nomogram was constructed. The nomogram showed a good calibration and discrimination in the derivation cohort, with an area under the receiver operating characteristic curve (AUC) of 0.883. Application of the nomogram in the validation cohort also showed a good calibration and discrimination, with the AUC of 0.852. Decision curve analysis confirmed the clinical utility of the nomogram. The nomogram was established and validated for predicting 30-day mortality of HBV-ACLF patients with bacterial infection, which may facilitate optimal therapeutic strategies to improve the prognosis of these patients.

Hepatitis B-related acute-on-chronic liver failure induced by hepatotropic viral insult is associated with worse prognosis than that induced by non-virus insult

BackgroundThe manifestations and prognoses of acute-on-chronic liver failure (ACLF) with different precipitating events remain heterogeneous. We aimed to investigate the characteristics and prognosis of patients with hepatotropic viral insult (HVI)-induced hepatitis B-related ACLF (HBV-ACLF).Methods452 patients with confirmed diagnosis of ACLF were screened in three medical centers in China, and 203 HBV-ACLF patients with definite acute precipitating events were retrospectively analyzed. According to the precipitating events, HBV-ACLF patients induced by HBV reactivation and super-infection with HAV were classified as the hepatotropic viral insult group and those induced by other factors, as the non-virus insult (NVI) group. The clinical characteristics, predictive scoring model, and prognosis of the two groups were compared.ResultsHepatitis B virus reactivation accounted for the largest proportion (39.9%) among all precipitating events. Exacerbation time frame of the HVI group was significantly longer than that of the NVI group (20 days vs. 10 days, P < 0.001). Comparison of intergroup prognosis showed that there was no significant difference in the 28 day mortality (20.9 vs. 13.7%, P = 0.125), while the 90 day and 1 year mortality in the HVI group were higher than those in the NVI group (36.3 vs. 24.4%, P = 0.014; 39.5% vs. 27.5%, P = 0.020, respectively). In the HVI group, the lactic acid-free APASL-ACLF Research Consortium (AARC) had better predictive value for 90 day mortality (0.741).ConclusionsThe 90 day and 1 year survival rate was lower in HBV-ACLF patients induced by HVI than by NVI. The lactate-free AARC score was a better predictor of short- and long-term prognosis in patients with HVI-induced HBV-ACLF.

Significance of anti-HBc serological status in primary immune thrombocytopenia.

The association of previous hepatitis B virus (HBV) exposure [hepatitis B surface antigen (HBsAg) negative, hepatitis B core antibody (anti-HBc/HBcAb) positive] with disease severity and decision on treatment option in primary immune thrombocytopenia (ITP) patients remains unclear. Data from 725 patients diagnosed with ITP were analyzed to elucidate the association between anti-HBc serological status and disease severity. Data from a published prospective study [high-dose dexamethasone (HD-DXM), HD-DXM plus recombinant human thrombopoietin, NCT01734044] and two retrospective studies (standard-dose and low-dose rituximab) were rearranged to evaluate the impact of anti-HBc serological status on the response and outcome to ITP-specific treatments and the risk of HBV reactivation related to these treatments. The prevalence of HBsAg- HBcAb+ and HBsAg- HBcAb- in ITP patients was 51·03% and 48·97% respectively. Compared to the HBsAg- HBcAb- group, patients in the HBsAg- HBcAb+ group had lower platelet count, higher bleeding score, and longer hospitalization (P = 0·002, 0·033, and 0·008 respectively). Moreover, the initial complete response rate of HBsAg- HBcAb+ patients was lower than that of HBsAg- HBcAb- patients (45·2% vs 59·8%, P = 0·027). In conclusion, previous HBV exposure was correlated with disease severity and hospitalization in ITP patients. Anti-HBc positivity may be considered as a predictor for poor response to ITP-specific treatments.

Risk of Hepatitis B Virus (HBV) Reactivation in Patients with Immune-Mediated Inflammatory Diseases Receiving Biologics: Focus on the Timing of Biologics after Anti-HBV Treatment.

Background/AimsAnti-hepatitis B virus (HBV) therapy is required for patients with HBV infection receiving biologics because of the high risk of HBV reactivation. However, it is unclear when to start biologics after anti-HBV treatment. We investigated the risk of HBV reactivation according to the timing of biologics initiation after anti-HBV treatment in immune-mediated inflammatory disease (IMID) patients with HBV infection.MethodsWe retrospectively evaluated the incidence of HBV reactivation in IMID patients who received biologics between July 2005 and April 2020. The patients were divided into two groups (within 1-week and after 1-week) according to the timing of biologics initiation after anti-HBV treatment. The cumulative probabilities and factors associated with HBV reactivation were evaluated.ResultsA total of 60 hepatitis B surface antigen-positive patients with IMID received biologics (within 1-week group, n=23 [38%]; after 1-week group, n=37 [62%]). During a median follow-up of 34 months (interquartile range, 20 to 74 months), three patients (5%) developed HBV reactivation. In univariate analysis, the timing of biologics after anti-HBV treatment was not significantly associated with the risk of HBV reactivation (hazard ratio, 0.657; 95% confidence interval, 0.059 to 7.327; p=0.733). The cumulative probabilities of HBV reactivation did not significantly differ according to the timing of biologics (p=0.731).ConclusionsThe risk of HBV reactivation was not significantly associated with the timing of biologics administration after anti-HBV treatment. Thus, biologics may be initiated early in patients with IMID undergoing treatment for HBV.

Impact of compensated cirrhosis on survival in patients with acute-on-chronic liver failure

Background and aimsAcute-on-chronic liver failure (ACLF) is considered a main prognostic event in patients with chronic liver disease (CLD). We analyzed the 28-day and 90-day mortality in ACLF patients with or without underlying cirrhosis enrolled in the ACLF Research Consortium (AARC) database.MethodsA total of 1,621 patients were prospectively enrolled and 637 (39.3%) of these patients had cirrhosis. Baseline characteristics, complications and mortality were compared between patients with and without cirrhosis.ResultsAlcohol consumption was more common in cirrhosis than non-cirrhosis (66.4% vs. 44.2%, p < 0.0001), while non-alcoholic fatty liver disease/cryptogenic CLD (10.9% vs 5.8%, p < 0.0001) and chronic HBV reactivation (18.8% vs 11.8%, p < 0.0001) were more common in non-cirrhosis. Only 0.8% of patients underwent liver transplantation. Overall, 28-day and 90-day mortality rates were 39.3% and 49.9%, respectively. Patients with cirrhosis had a greater chance of survival compared to those without cirrhosis both at 28-day (HR = 0.48; 95% CI 0.36–0.63, p < 0.0001) and 90-day (HR = 0.56; 95% CI 0.43–0.72, p < 0.0001), respectively. In alcohol CLD, non-cirrhosis patients had a higher 28-day (49.9% vs. 23.6%, p < 0.001) and 90-day (58.4% vs. 35.2%, p < 0.001) mortality rate than cirrhosis patients. ACLF patients with cirrhosis had longer mean survival than non-cirrhosis patients (25.5 vs. 18.8 days at 28-day and 65.2 vs. 41.2 days at 90-day). Exaggerated systemic inflammation might be the reason why non-cirrhosis patients had a poorer prognosis than those with cirrhosis after ACLF had occurred.ConclusionsThe 28-day and 90-day mortality rates of ACLF patients without cirrhosis were significantly higher than those with cirrhosis in alcoholic CLD. The presence of cirrhosis and its stage should be evaluated at baseline to guide for management. Thai Clinical Trials Registry, TCTR20191226002.

Clinical Outcomes of Hepatitis B Virus-Related Hepatocellular Carcinoma Patients with Undetectable Serum HBV DNA Levels.

Some hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients show undetectable serum HBV DNA levels at HCC diagnosis. The risk of HBV reactivation and its impact on clinical outcomes are not well-unknown. This retrospective cohort study included a total of 985 HBV-related HCC patients with undetectable serum HBV DNA levels (< 12IU/mL) at HCC diagnosis (112 were antiviral treatment (AVT)-naïve; 873 were receiving AVT). Incidence and risk factors for HBV reactivation (re-detection of HBV DNA in serum) during follow-up, as well as its association to overall survival, were assessed. During a median of 33.4months of follow-up (range: 0.2-124.2months), HBV reactivation was observed in 279 patients. HBV reactivation rate was significantly lower for patients receiving AVT than AVT-naïve patients (three-year cumulative incidence rate: 27.3% versus 56.0%; P < 0.001). In multivariable-adjusted analysis, the risk of HBV reactivation was lower for those receiving AVT compared to AVT-naïve patients (adjusted hazard ratio: 0.39, 95% confidence interval: 0.29-0.54). Overall survival was significantly lower for those experiencing HBV reactivation than those who did not (71.5% and 85.7% at five-year) and was associated with higher risk of overall mortality (adjusted hazard ratio: 5.15, 95% confidence interval: 3.60-7.38). More than half of AVT-naïve patients experienced HBV reactivation within three years, which was associated with increased risk of overall mortality. The risk of HBV reactivation was lower for those receiving AVT, suggesting that prompt AVT needs to be considered for AVT naïve HBV-related HCC patients with undetectable HBV DNA levels.

Prevalence and Severity of HBV-Associated Acute-on-Chronic Liver Failure Due to Irregular Medication of Nucleos(t)ide Analogs

Abstract Hepatitis B virus (HBV) represents the commonest etiologic agent of acute-on-chronic liver failure (ACLF) in most Asian countries. Nucleos(t)ide analogs (NAs) are effective in the treatment of chronic HBV infections, but may also exacerbate the disease and stimulate its development into HBV-associated ACLF if not used appropriately. The current study aimed to assess the prevalence and severity of HBV-associated ACLF as a result from irregular medication of NAs (IMNA). A total of 1134 individuals with HBV-associated ACLF in nine hospitals in Heilongjiang Province were enrolled in this study between 2005 and 2015. Among these, 777 chronic hepatitis B (CHB) and 357 HBV-associated liver cirrhosis cases were classified based on various predisposing factors, including IMNA, HBV reactivation (HBVR), infections, treatment drugs, alcohol use and others (hepatitis C virus, hepatitis E virus, gastrointestinal bleeding and unknown reasons). The percentage and improvement rate were examined. Among individuals with HBV-associated ACLF and CHB, IMNA was found in 9.01%, HBVR in 46.20%, infections in 9.52%, treatment drugs in 14.67%, alcohol in 11.71%, and others in 24.58% as predisposing factors. Improvement rates in cases with IMNA, HBVR, infections, treatment drugs, alcohol and others were 41.43%, 58.50%, 58.11%, 56.14%, 53.85%, and 65.97%, respectively. Multivariable analysis showed that IMNA, others, infections, hepatic encephalopathy and hepatorenal syndrome were associated with prognosis. Only IMNA independently predicted HBV-associated ACLF prognosis. Overall, our study demonstrated that the percentage of IMNA-induced HBV-associated ACLF was 12.61%, and worse disease conditions resulted from IMNA compared with other factors. Thus, the suitability of treatment with NAs should be thoroughly evaluated.

Risk and Prevention of Hepatitis B Virus Reactivation during Immunosuppression for Non-Oncological Diseases.

Reactivation of overt or occult HBV infection (HBVr) is a well-known, potentially life-threatening event which can occur during the course of immunosuppressive treatments. Although it has been described mainly in subjects receiving therapy for oncological or hematological diseases, the increasing use of immunosuppressant agents in non-oncological patients observed in recent years has raised concerns about the risk of reactivation in several other settings. However, few data can be found in the literature on the occurrence of HBVr in these populations, and few clear recommendations on its management have been defined. The present paper was written to provide an overview of the risk of HBV reactivation in non-neoplastic patients treated with immunosuppressive drugs, particularly for rheumatological, gastrointestinal, dermatological and neurological diseases, and for COVID-19 patients receiving immunomodulating agents; and to discuss the potential strategies for prevention and treatment of HBVr in these settings.

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.

Virological breakthrough after immune checkpoint inhibitor and nucleos(t)ide analog treatment in patients with hepatitis B surface antigen positive hepatocellular carcinoma: a real-world study

BackgroundImmune checkpoint inhibitors (ICIs) have been shown to be a promising and effective treatment for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, there is a lack of evidence-based data...

Critical Updates on Chronic Hepatitis B Virus Infection in 2021.

Chronic hepatitis B virus (HBV) infection is a global healthcare burden in the form of chronic liver disease, cirrhosis, liver failure and liver cancer. There is no definite cure for the virus and even though extensive vaccination programs have reduced the burden of liver disease in the future population, treatment options to eradicate the virus from the host are still lacking. In this review, we discuss in detail current updates on the structure and applied biology of the virus in the host, examine updates to current treatment and explore novel and state-of-the-art therapeutics in the pipeline for management of chronic HBV. Furthermore, we also specifically review clinical updates on HBV-related acute on chronic liver failure (ACLF). Current treatments for chronic HBV infection have seen important updates in the form of considerations for treating patients in the immune tolerant phase and some clarity on end points for treatment and decisions on finite therapy with nucleos(t)ide inhibitors. Ongoing cutting-edge research on HBV biology has helped us identify novel target areas in the life cycle of the virus for application of new therapeutics. Due to improvements in the area of genomics, the hope for therapeutic vaccines, vector-based treatments and focused management aimed at targeting host integration of the virus and thereby a total cure could become a reality in the near future. Newer clinical prognostic tools have improved our understanding of timing of specific treatment options for the catastrophic syndrome of ACLF secondary to reactivation of HBV. In this review, we discuss in detail pertinent updates regarding virus biology and novel therapeutic targets with special focus on the appraisal of prognostic scores and treatment options in HBV-related ACLF.

Hepatitis B Virus Reactivation: Overview and Management

Hepatitis B virus (HBV) can hide in the liver in the form of covalently closed circular DNA. When the body’s immunity changes, HBV reactivation (HBV-R) can occur. The risk of HBV-R is determined by the complex interaction among virological factors, medication factors and host factors. However, many patients do not know that they are infected with HBV, and doctors often do not invest enough time to systematically evaluate the patient’s HBV-R risk factors before immunosuppressive treatment. Therefore, HBV clinical screening should be vigorously promoted to achieve early detection and early prevention for patients with high risk of HBV-R. The mechanism, clinical features, risk factors, HBV-R under different disease etiologies, prevention and treatment of HBV-R were summarized to improve the in-depth understanding and awareness.

Hepatitis B Virus Infection in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation.

Considering a steady increase in the number of allogeneic hematopoietic stem cell transplantations (allo-HSCT) worldwide and the significant proportion of the world’s population that has been exposed to hepatitis B virus (HBV) infection, HBV reactivation following allo-HSCT remains an important issue for post-transplant morbidity and mortality. Antiviral prophylaxis can reduce HBV replication, severity of HBV-related hepatitis, and mortality; therefore, identification of patients at risk is crucial. It is recommended that all recipients and donors should be screened for active or prior HBV infection, including HBsAg, antiHBc, and antiHBs. Adoptive immunity transfer from the donor seems to have protective effects against HBV reactivation. Antiviral prophylaxis should be initiated in all HBsAg-positive patients. HBsAg-negative, antiHBc-positive patients remain at risk; therefore, antiviral prophylaxis should be considered if baseline serum HBV DNA is detectable. In HBsAg-negative, antiHBc-positive patients without detectable HBV DNA, close monitoring of viral load with an on-demand therapy is necessary. Entecavir or tenofovir rather than lamivudine are more appropriate for the emergence of lamivudine resistance. The treatment duration remains unclear, with 6- to 12-month therapy after cessation of immunosuppressive therapy commonly recommended. Here we review the updated evidence and recent recommendations regarding HBV reactivation in patients undergoing allo-HSCT for individualized therapy.

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.

Hepatitis B Core-Related Antigen and New Therapies for Hepatitis B.

The hepatitis B core-related antigen (HBcrAg) is an unprecedented novel HBV biomarker that plays an essential role in reflecting covalently closed circular DNA (cccDNA) in chronic hepatitis B (CHB) because its levels correlate with intrahepatic cccDNA and serum HBV DNA. In this review, we describe the clinical application of serum HBcrAg in CHB patients, with a particular focus on new therapies targeting intrahepatic HBV replication. (1) HBcrAg can be detected in clinical cases where serum HBV DNA is undetectable during anti-HBV therapy. (2) A highly sensitive HBcrAg assay (iTACT-HBcrAg) may be useful for monitoring HBV reactivation, as an alternative to HBV DNA. (3) Decreased HBcrAg levels have been significantly associated with promising outcomes in CHB patients, reducing the risk of progression or recurrence of hepatocellular carcinoma. Additionally, we focus on and discuss several drugs in development that target HBV replication, and monitoring HBcrAg may be useful for determining the therapeutic efficacies of such novel drugs. In conclusion, HBcrAg, especially when measured by the recently developed iTACT-HBcrAg assay, may be the most appropriate surrogate marker, over other HBV biomarkers, to predict disease progression and treatment response in CHB patients.

S2911 A Case of Hepatitis B Reactivation Associated Hepatitis After Tocilizumab Therapy in a Patient With SARS-CoV-2 Infection

Introduction: Tocilizumab (TCZ) is an interleukin 6 (IL-6) receptor inhibitor well known as an immunomodulatory agent used in rheumatic disease that has currently gained greater relevance as an investigational agent in SARS-COV-2 patients. TCZ results in a profound immunosuppressive state, impairing the IL-6 physiologic effects in protective processes such as the HBV infection clearance, HBV replication suppression, and prevention of the accumulation of HBV covalently. We present a case of TCZ-associated HBV reactivation with acute hepatitis in a patient with SARS-COV-2 disease. Case Description/Methods: A 55-year-old Vietnamese man with a history of inactive chronic hepatitis B since childbirth presented in view of progressive shortness of breath. He was diagnosed with SARS-COV-2, placed on supplemental oxygen with no favorable clinical response. The patient was subsequently admitted to the intensive care unit and started in high-flow ventilation, dexamethasone, and apixaban in view of acute respiratory disease syndrome. He received convalescent plasma with no improvement. Therefore, a trial of TCZ was given. The patient gradually showed signs of respiratory and functional status improvement. Supplemental oxygen was de-escalated to a nasal cannula and the patient was discharged to acute rehabilitation. Laboratory workup after discharge revealed elevated liver tests with normal bilirubin and INR. HBV panel showed a rise in the DNA levels to 10 million IU/ml (table 1). Serologies for viral hepatitis were negative (Table 1). Imaging ruled out hepatocellular carcinoma but showed cirrhosis. The patient was started on Tenofovir with gradual improvement in liver enzymes and reduction in HBV viral load >1 log (figure 1). Discussion: TCZ interferes with IL-6 which plays a protective role in the HBV infection with inversely proportional disease severity correlation in HBV infection. Guidelines regarding HBV reactivation reports that TCZ has a moderate risk of reactivation in patients with HBsAg positive. Guidelines regarding therapeutic approaches of Hepatitis B virus recommend preventive therapy for those patients considered at high risk of re-activation such as undergoing immunosuppressive therapy, regardless of the duration, or previous HBV status. Hepatitis B reactivation is often seen within 2 weeks and up to 1 year after the onset of immunosuppressive therapy. No previous cases exist to our knowledge looking at short and long-term effects of TCZ in SARS-COV-2 patients with HBV infection.Figure 1.: Liver enzymes trend pre and post-Tocilizumab and Tenofovir therapies.Table 1.: Hepatitis viral serologies pre and post-Tocilizumab and Tenofovir therapies.