Hepatitis B Virus Reactivation Research Articles

Tenofovir versus Entecavir on Outcomes of Hepatitis B Virus-Related Hepatocellular Carcinoma After FOLFOX-Hepatic Arterial Infusion Chemotherapy.

The efficacy of entecavir (ETV) versus tenofovir (TDF) on the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients who underwent FOLFOX-hepatic arterial infusion chemotherapy (HAIC) remains unclear. In this study, we compared the outcomes between ETV and TDF in HBV-related advanced HCC patients who underwent FOLFOX-HAIC. A total of 683 patients diagnosed with HBV-related HCC who underwent FOLFOX-HAIC and received TDF or ETV between January 2016 and December 2021 were included. Overall survival (OS), progression-free survival (PFS), HBV reactivation, and liver function of patients were compared between the ETV and TDF groups by propensity score matching (PSM). In the PSM cohort, for all patients and patients with ≥ 4 cycles of FOLFOX-HAIC, the median OS in the ETV group (15.2 months, 95% CI: 13.0-17.4 months; 16.6 months, 95% CI: 14.8-18.5 months; respectively) was shorter than that in the TDF group (23.0 months, 95% CI: 10.3-35.6 months; 27.3 months, 95% CI: 16.5-NA months; p=0.024, p=0.028; respectively). The median PFS in the ETV group (8.7 months, 95% CI: 7.9-9.5 months; 8.9 months, 95% CI: 8.0-9.8 months; respectively) was also shorter than that in the TDF group (11.8 months, 95% CI: 8.0-15.6 months; 12.7 months, 95% CI: 10.8-14.6 months; p=0.036, p=0.025; respectively). The rate of HBV reactivation in the ETV group was higher than that in the TDF group (12.3% vs 6.3%, p=0.040; 16.5% vs 6.2%, p=0.037, respectively). For liver function, the rate of ALBI grade that remained stable or improved in the ETV group was lower than that in the TDF group (44.6% vs 57.6%, p=0.006; 37.2% vs 53.8%, p=0.019, respectively). Compared with ETV, TDF was associated with a better prognosis, lower proportion of HBV reactivation, and better preservation of liver function in advanced HBV-HCC patients who underwent FOLFOX-HAIC, especially those who received ≥ 4 cycles.

Size Matters! Anti-HBs Titer and HBV Reactivation During Anti-TNF Therapy.

We and others have previously described that hepatitis B surface antibody (anti-HBs) seems to protect against clinically significant HBV reactivation in cohort studies of patients undergoing anti-tumor necrosis factor (TNF) therapy. However, there were too few cases of HBV reactivation within cohort studies to assess the role of anti-HBs titer on reactivation. The purpose of this study was to systematically review the correlation between anti-HBs titer and the degree of clinically relevant HBV reactivation in patients undergoing anti-TNF therapy. We systemically reviewed all studies discussing anti-TNF therapy in patients with resolved HBV infection, defined as hepatitis surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive. We identified a total of 48 cases of reactivation from 5 cohort studies and 10 case reports or case series; 21 were anti-HBs negative, 7 were only reported as anti-HBs positive, 16 were anti-HBs positive with titer below 100, and 4 were anti-HBs positive with titer above 100. HBsAg sero-reversion was dominantly seen in patients with negative, low and/or declining anti-HBs titers. There was a significant trend toward less clinically relevant form of reactivation with increase in baseline anti-HBs titer (p = 0.022). Anti-HBs titers greater than 100 iU/L protect against clinically relevant HBV reactivation, while patients with low anti-HBs titers or negative anti-HBs had more clinically relevant HBV reactivation and higher rates of HBsAg sero-reversion. This suggests the importance of baseline quantitative anti-HBs prior to starting anti-TNF therapy and consideration vaccination for boosting anti-HBs titers prior to and/or during therapy.

RISK OF HBV REACTIVATION DURING THERAPIES FOR HCC: A SYSTEMATIC REVIEW

Background: Hepatitis B virus (HBV) reactivation in the setting of immunosuppressive therapy, and in particular chemotherapy, has garnered increasing attention because reactivation can lead to hepatitis, liver failure, and death and also interrupt or delay treatment. The risk of reactivation depends on HBV serological status and the intensity of chemotherapy regimens. HBV reactivation can occur in hepatocellular carcinoma (HCC) treatment such as transarterial chemoemblization (TACE), resection, and radiofrequency ablation (RFA). The aim: This study aims to explain the risk of HBV reactivation during therapies for HCC Methods: By comparing itself to the standards set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study can show that it meets all requirements. So, experts can ensure that the research is up to date. For this search approach, publications that came out between 2013 and 2023 are taken into account. Several different online reference sources were used to conduct this study. It was decided not to take into account cut reviews, works that have already been published, or works that are only half finished. Result: On the PubMed database, our search results returned 49 articles, while our search results on Sage journal returned 105 articles. Search results conducted since 2013 yielded a total of 34 articles for PubMed and 80 articles for Sage journal. In the end, we compiled a total of 7 articles. We list five eligible studies. Conclusion: HBV reactivation occurs after the curative resection of HBV-related HCC in patients with low hepatitis B viral loads. Postoperative HBV reactivation was related to the recurrence of HBV-related HCC. Use of antiviral therapy and close monitoring of viral loads may be helpful to reduce the recurrence of HBV-related HCC after resection.

HBV reactivation in patients with rheumatoid arthritis treated with anti-interleukin-6: a systematic review and meta-analysis.

The objective of this study was to assess the possibility of HBV reactivation (HBVr) in patients with RA under anti-IL-6 treatment. Using PubMed, Scopus and EMBASE, we performed a systematic literature search for articles related to HBVr in RA patients under anti-IL-6 treatment. The search was performed with no date limits and was last updated 28 January 2023. The results from all the databases were combined and duplicates were excluded, as were non-English articles, case reports, position articles, comments, and paediatric studies. Our initial search led to 427 articles; 28 were duplicates, 46 non-English, 169 reviews, 31 books/letters, 25 case reports, and 88 irrelevant to the meta-analysis aim; 21 were excluded due to inadequate information, leaving 19 articles, with a sum of 372 RA patients with chronic HBV (CHB) or resolved HBV infection, for further analysis. The overall risk for HBVr in RA patients with CHB was 6.7%, increasing to 37% when only RA patients with CHB and no antiviral prophylaxis were included. On the contrary, HBVr was close to 0% in RA patients with resolved HBV infection, irrespective of antiviral prophylaxis. All RA patients experiencing HBVr in these studies were successfully managed with antiviral treatment and/or drug withdrawal. Overall, anti-IL-6 treatment comes with a significant risk of HBVr in RA patients with CHB; risk is diminished when antiviral prophylaxis is used. In contrast, in RA patients with resolved HBV infection, the risk of HBVr seems to be extremely low. Large, well-designed studies (either controlled trials or multicentre/international observational studies) are warranted to further validate these results.

Predictors for the effectiveness of 75 mg risankizumab in treating psoriasis-A real-word evidence from a 52-week retrospective study.

In the registration trial of risankizumab for patients with moderate-to-severe psoriasis in Japan, similar Psoriasis Area Severity Index (PASI) responses were observed for 75 mg or 150 mg risankizumab at most time points up to 52 weeks, except for PASI 100 at week 16. The use of 75 mg risankizumab offers an attractive option considering the high cost of risankizumab. However, it is unknown whether patients with mild-to-moderate psoriasis respond similarly, and the efficacy data of non-Japanese patients is also lacking. We retrospectively included 30 consecutive Chinese patients receiving half-dose (75 mg) risankizumab as scheduled up to 52 weeks. Compared with biologic-experienced group, biologic-naive group had a significantly higher PASI 50/75/90/100 achievement (p = 0.0098/0.0039/0.0016/0.0054) at week 52. PASI 50/75/90/100 curves in biologic-naive group (p = 0.0117/0.0239/0.0143/0.0269) were also significantly higher when analysed generalized estimating equations (GEE) model. Though there was no statistically significant difference in terms of PASI 50/75/90/100 responses at any time points between those with body weight ≦ 65 kg and those >65 kg, a tendency of secondary failure was noted in those >65 kg from week 40 onwards. Patients who were both biologic-naive and weighed ≦ 65 kg achieved sustained PASI 50/75/90 responses from week 16/28/40 onwards, respectively, indicating that they could be considered as potential candidates for 75 mg risankizumab. Though PASI 75 curve in patients without diabetes mellitus (DM) surpassed that in patient without DM, curves of other parameters did not reach significance when analysed by GEE model. There was no HBV, HCV or TB reactivation, nor other new safety signals during the 52-week observational period. Providing risankizumab with flexible dosing options is beneficial in clinical practice considering the high cost of this medication.

Epstein-Barr virus reactivation correlates with worse outcomes for patients exposed to hepatitis B virus after haploidentical hematopoietic stem cell transplantation.

Hepatitis B virus (HBV)has a high, chronic infection rate in Asian populations, but only few studies have analyzed the effect of Epstein-Barr virus (EBV) or Cytomegalovirus (CMV) reactivation in patients exposed to HBV after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). This study aimed to assess the clinical outcomes of these patients. We conducted a retrospective research including 61 patients exposed to HBV after undergoing haplo-HSCT. The patients were classified into two groups: the CMV reactivation group and no CMV reactivation group. The results were compared between the two groups using the K-W test for continuous variables, Pearson's chi-square test for categorical variables, Kaplan-Meier curves to estimate overall survival (OS) and leukemia-free survival (LFS), and a Cox proportional hazards model to analyze multivariable influences. The 3-year cumulative HBV reactivation rate was 8.2%. The median duration of HBV reactivation was 16months (16-22months) after haplo-HSCT. The CMV reactivation group had a higher cumulative incidence of HBV reactivation than the group without CMV reactivation. The EBV reactivation was substantially higher in the CMV reactivation group compared to that in the no CMV reactivation group (37.0% vs.5.9% respectively; P = 0.002). Furthermore, EBV reactivation was a risk factor for 1-year LFS and 1-year OS. Based on our data, EBV reactivation was related to worse outcomes in patients exposed to HBV after haplo-HSCT, whereas CMV reactivation was not.

Stratified management based on surface antibody for the prevention of hepatitis B virus reactivation in lymphoma patients.

This study aimed to investigate a stratified approach based on hepatitis B virus (HBV) surface antibody (anti-HBs) for managing HBV reactivation (HBVr) in lymphoma patients with serological protection against HBV. A retrospective analysis was conducted on 209 lymphoma patients with a baseline anti-HBs titre of ≥10 iu/L, who were either positive or negative for HBV core antibody (anti-HBc). The results revealed that 15.7% of patients lost serological protection following 6-month anti-lymphoma therapy. With a median follow-up of 28.1 months, the cumulative rates of HBVr at 6 months, 2 years and 4 years were 2.9%, 4.7% and 6.3% respectively. Without intervention, the overall rate of reactivation was 2.0% for patients with isolated anti-HBs and 10.5% for those with positive anti-HBs and anti-HBc. To identify patients at high risk of losing seroprotection and susceptible to HBVr, a predictive model was developed. The high-risk group had significantly higher rates of serological protection loss (27.8% vs. 2.2%) and cumulative incidence of HBVr (22.0% vs. 0%) compared to the low-risk group. Overall, this study highlights the risk of HBVr in lymphoma patients with positive anti-HBs, with or without positive anti-HBc, and recommends periodic monitoring for low-risk patients and early intervention for high-risk patients.

Frequency, Clinical Presentation, and Outcome of Acute-on-Chronic Liver Failure among Decompensated Cirrhosis of Liver Patients in a Tertiary Care Hospital

Background: Acute-on-chronic liver failure (ACLF) is characterised by the presence of organ failure in patients with decompensated cirrhosis and is associated with high short-term mortality. Different international entities have taken initiatives to define the condition in different times but recommendations and definitions from The European Association for the Study of the Liver- Chronic Liver Failure (EASL-CLIF) Consortium Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC) study are most comprehensive and widely accepted till date. Only limited data are available on the prevalence, clinical characteristics, and short-term outcomes of ACLF in Bangladesh. It would be very useful for clinicians to identify patients with ACLF early and initiate focused therapy including referral to transplant centers if these data are available. Objective: To evaluate frequency, clinical presentation, and outcome of acute-on-chronic liver failure among decompensated cirrhosis of liver patients. Materials and Methods: This prospective observational study was carried out at the Department of Gastrointestinal, Hepatobiliary and Pancreatic Disorders (GHPD), BIRDEM General Hospital, Shahbagh, Dhaka, Bangladesh from July, 2019 to September, 2021. Total 175 patients with decompensated cirrhosis of liver were screened, out of which 22 patients were dropped out due to various reasons. Purposive type of non-probability sampling technique was used. Formal ethical clearance was taken from the Institutional Review Board and ethical measures were ensured in concordance with the Declaration of Helsinki. An informed written consent was taken from all participants. Diagnosis of decompensated cirrhosis was based on clinical, biochemical, radiological and endoscopic findings. Laboratory data sent within 24 hours were collected. Oxygen saturation was measured using fingertip pulse oximeter. Investigations for ACLF triggers were done as necessary which included but not limited to urine routine and microscopic examination, urine culture, blood culture, and Anti HEV IgM. Patients’ prognosis and survivability were observed by follow up phone call at 30 days. All data were recorded in a separate case record form and finally, it was analyzed by SPSS 23. Results: Out of 153 patients, 49 patients (32%) had ACLF: grade 1 ACLF in 26 (17%), grade 2 in 18 (11.8%), and grade 3 in 5 (3.3%) patients. Patients had an average age of 59.54±11.55 years with no significant difference between ACLF and no ACLF groups. Most patients in both groups had others (NAFLD, autoimmune hepatitis, secondary biliary cirrhosis, idiopathic) as the main underlying cause of cirrhosis. Bacterial infection, GI bleeding, HEV infection, reactivation of HBV were the precipitating events in 81.6% of patients with ACLF, with bacterial infection being the most common trigger (63.3%). Overall, 44.9% ACLF patients died within 30 days of admission. Older age, male sex, hepatic encephalopathy, GI bleeding, presence of any trigger and higher Child-Turcotte-Pugh (CTP) score were associated with increased risk of death in ACLF. Conclusion: Follow up of 153 patients with decompensated cirrhosis of liver revealed that 1 in 3 patients had ACLF and 44% of them would die in 30 days. Bacterial infection and GI bleeding were the most common triggers of ACLF. Early identification and intervention with multidisciplinary approach and referral to transplant centers are likely to improve survival outcomes in this population. Bangladesh Crit Care J September 2023; 11 (2): 113-120

Hepatitis B infection or reactivation after switch to two-drug antiretroviral therapy: A case series, literature review, and management discussion.

Two-drug antiretroviral therapy (ART) without hepatitis B virus (HBV) activity is prescribed for persons with HIV as simplified or salvage therapy. While two-drug regimens are not recommended for persons with chronic HBV infection, guidelines do not address use in those with HBV susceptibility and/or core antibody reactivity. We present a case series of individuals with HBV infection or reactivation following switch to two-drug, non-HBV-active ART. HIV primary care clinics of an academic medical center in New York, NY. Case surveillance was conducted to identify persons with HBV surface antigenemia and viremia following two-drug ART switch. Clinical characteristics and outcomes were ascertained through chart review. Four individuals with HBV infection or reactivation after ART switch were identified. Two had HBV susceptibility, one had core antibody reactivity, and one had surface antigen reactivity pre-switch. All eligible persons had received HBV vaccination, two with low-level antibody response and one with persistent nonresponse. Two presented with fulminant hepatitis, one requiring liver transplantation. Two-drug ART switch may pose risk of HBV infection or reactivation. We propose careful patient selection and monitoring through the following: 1) Assessment of HBV serologies before switch and periodically thereafter, 2) Vaccination and confirmation of immunity before switch, 3) Risk stratification and counseling about HBV reactivation for those with core antibody, 4) Preemptive HBV DNA monitoring for those at risk of reactivation, 5) Continuation of HBV-active prophylaxis when above measures are not feasible, 6) Continuation of HBV-active therapy and surveillance for chronic HBV infection.

S3591 A Rare Case of HBV Reactivation With Delayed Cholestatic Effect Secondary to Acalabrutinib

S3591 A Rare Case of HBV Reactivation With Delayed Cholestatic Effect Secondary to Acalabrutinib

İmmunsupresif Tedavi Alan Hastalarda HBV Reaktivasyonu ve Antiviral Profilaksinin Değerlendirilmesi

Aim: Patients with chronic hepatitis B and people with a history of hepatitis B (HBV) infection are at risk of HBV reactivation (HBVr) when they receive immunosuppressive therapy. In this study, we aimed to evaluate the hepatitis B serology, risk groups and antiviral prophylaxis of patients receiving various immunosuppressive therapies due to rheumatological diseases.
 Material and Method: The study included 375 patients over 18 years of age who received tumor necrosis factor-α (TNF-α) inhibitor, tyrosine kinase inhibitor, steroids, methotrexate or anti-CD20 antibodies due to rheumatic diseases in a training and research hospital between May 2022 and May 2023. Hepatitis B surface antigen (HbsAg), hepatitis B surface antibody (anti-Hbs), hepatitis B core protein antibody (anti-Hbc IgG) serologies, immunosuppressive therapies and oral antivirals were retrospectively analyzed.
 Results: The average age of the 375 patients included in the study was 43.77±13.07 years. 193 (51.5%) of the patients were male. 11 patients were HbsAg positive, 150 patients were anti-Hbs positive, 19 patients were isolated anti-Hbc IgG positive, and 79 patients were both anti-Hbs and anti-Hbc IgG positive. According to serological findings, 109 (29%) patients had HBV exposure. All three test results of 194 (51.7%) patients were negative. A total of 85 (22.7%) patients received oral antiviral prophylaxis due to the use of immunosuppressive agents. In terms of HBVr, 16.5% were evaluated as high risk, 75.3% as moderate risk, and 8.2% as low risk. Out of 85 patients 79 received entecavir, 5 reveived tenofovir disoproxil fumarate (TDF) and 1 received tenofovir alafenamide fumarate (TAF). The mean duration for the immunosuppressive therapy was 6.41±4.20 years. The mean duration of oral antiviral prophylaxis among patients was 1.02±1.72 years. HBVr was not observed in any of our patients.
 Conclusion: Before patients receive immunosuppressive therapy, hepatitis B serologies and prophylaxis indication should be evaluated firstly. In addition, as a preventive medicine activity, hepatitis B vaccinations of unvaccinated patients should be completed as quickly as possible.

Hepatitis B reactivation is a rare event among patients with resolved infection undergoing anti-CD20 antibodies in monotherapy without antiviral prophylaxis: results from the HEBEM study

IntroductionProspective data on the risk of hepatitis B reactivation (HBVr) among patients with resolved HBV infection undergoing anti-CD20 antibodies monotherapy is scarce. We aimed to assess the risk of HBVr in patients with resolved HBV infection treated with rituximab or ocrelizumab in monotherapy for multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) without antiviral prophylaxis.MethodsHEBEM is a prospective study that included all consecutive adults HBsAg-negative/anti-HBc-positive who initiated anti-CD20 antibodies for MS or NMOSD at Cemcat. Inclusion criteria encompassed undetectable HBV-DNA, absence of other immunosuppressants or antiviral therapy. Every 6 months HBsAg, ALT and HBV-DNA were performed to rule out HBVr (defined by 2-log increase in HBV-DNA or seroconversion to HBsAg+).ResultsFrom August/2019 to August/2022, 540 subjects initiated anti-CD20 antibodies, 28 (5.2%) were anti-HBc-positive and were included. Twenty-two received rituximab and 6 ocrelizumab. The majority (89.3%) had previously received ≥ 1 immunomodulatory drug, with corticosteroids (82.1%) and interferon (42.9%) as the most common. At inclusion, all presented normal transaminases and undetectable HBV-DNA. Median anti-HBs levels were 105.5 mIU/mL (IQR 0–609). Median follow-up was 3.1 years (2.1–4.0). Median number of cycles of anti-CD20 antibodies was 6 (3–7), with a cumulative dose of 8.5 g (5.8–11.2) of rituximab and 3 g (1.8–3.8) of ocrelizumab. Neither cases of HBVr nor changes in anti-HBs titers were observed per 83.6 patient-years treated with monotherapy with anti-CD20 antibodies.ConclusionsIn this cohort of patients with MS or NMOSD and resolved HBV infection, anti-CD20 monotherapy was not associated with detectable risk of HBV reactivation despite the lack of antiviral prophylaxis.

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era.

Hepatitis due to hepatitis B virus (HBV) reactivation can be serious and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver. The expression of these silent genomes is controlled by the immune system. Suppression or ablation of immune cells, most importantly B cells, may lead to reactivation of seemingly resolved HBV infection. Thus, all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen. Patients found to be positive for HBsAg should be given prophylactic antiviral therapy. For patients with resolved HBV infection, there are two approaches. The first is pre-emptive therapy guided by serial HBV DNA monitoring, and treatment with antiviral therapy as soon as HBV DNA becomes detectable. The second approach is prophylactic antiviral therapy, particularly for patients receiving high-risk therapy, especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation. Entecavir and tenofovir are the preferred antiviral choices. Many new effective therapies for hematological malignancies have been introduced in the past decade, for example, chimeric antigen receptor (CAR)-T cell therapy, novel monoclonal antibodies, bispecific antibody drug conjugates, and small molecule inhibitors, which may be associated with HBV reactivation. Although there is limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, including Bruton's tyrosine kinase inhibitors, B-cell lymphoma 2 inhibitors, and CAR-T cell therapy. Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy.

Role of Laboratory in the Management of HBV Reactivation in Rheumatic Diseases

Role of Laboratory in the Management of HBV Reactivation in Rheumatic Diseases

Hepatitis B virus-related cryoglobulinemia: Clinical characteristics, virological features, and treatment

BackgroundHepatitis B virus (HBV) infection is a rare etiology of cryoglobulinemia, and its clinical characteristics, virological features and treatment are poorly understood. MethodsThis retrospective study enrolled 23 patients with HBV-related cryoglobulinemia from 497 cryoglobulinemia patients at Peking Union Medical College Hospital between January 2015 and February 2023. We analyzed the clinical characteristics, virological features and management of patients with HBV-related cryoglobulinemia. ResultsThe 23 patients (13 males; median age 48 years) were all mixed cryoglobulinemia and serological HBsAg positive, while 15 patients exhibited HBV-DNA replication. The presence of HBsAg in cryoglobulins was evaluated in 7 patients, all of whom were positive. The most commonly involved organs were kidneys (69.6%), skin (65.2%), peripheral nerves (21.7%), joints (8.7%), gastrointestinal tract (4.3%), and cardiac (4.3%). Eight patients received antiviral therapy with nucleot (s)ide analogues (NAs) alone, 12 patients received NA- and corticosteroid-based regimens, and 3 patients received NA- and rituximab-based regimens based on the severity of clinical symptoms. After a median follow-up of 44 months, four patients died, and one patient was lost to follow-up. All remaining patients (n = 18) achieved clinical remission, and HBV-DNA replication was not detected in 16 out of 18 patients. There was no HBV reactivation in patients treated with rituximab. The three-year overall survival and progression-free survival were 87.0% and 80.3%, respectively. ConclusionsHBV-related cryoglobulinemia patients should be treated with antiviral therapy. Corticosteroids and rituximab are effective for severe cases, but patients need to be closely monitored for therapy-related infection.

Incidence of Reactivation of Hepatitis B in Co-Infected HB V/HCV Patients Treated with Regiments of Sofosbuvir and Daclatasvir with or without Ribavirin

Abstract Background HCV management was dramatically changed by the recent advent of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection, where DAA regimens are associated with a sustained virological response (SVR) rate of > 90–95% and are considered safe; nevertheless, a few complications have been reported including reactivation of hepatitis B virus (HBV). Aim of the Work To evaluate the incidence of re activation of HBV among patients treated by sof/dac with or without RBV Patients and Methods This study was held in out in centers for treatment of HCV in –Ain- Shams University Hospital and Aswan Fever Hospital from May 2019 to October 2020., All patients were subjected to history taking, clinical examination, abdominal ultrasound, laboratory investigations (CBC, liver function, HCV Ab, HBsAg, HBV eAg PCR for HCV RNAand PCR for HBV DNA. All patients were positive for HCVAb, HCV PCR, HBVsAg with HBV DNA less than 2000IU/ML and negative for HBVeAg. This study was conducted on 90 patients who were selected according to National Committee for Control of Viral Hepatitis (NCCVH) protocol were divided according to treatment protocol into two groups. Results In our study, 57% of cases aged < 50 years, 33% aged > 50 years, and 61% were males and 39% were females; In the present study, there were 23 patients were smokers,16 patients were diabetics and 21 patients were hypertensives. All treated patients were negative PCR for HCV RNA at week 12 with 100% (SVR12)response in all treated patients which is still negative till end of treatment and 12 week after end of treatment (SVR 24), AS regard HBV DNA, no statistically significant difference was found at the beginning, at the end of 12 weeks, and at the end of 24 week of treatment by DAAs (p-value > 0.05), except for one patient who was treated with SOF/DAC/RBV. This patient, with compensated cirrhosis at baseline, developed fatigue and anorexia at week 12, with HBV reactivation (HBV DNA levels increased from245 IU/mL at baseline to 532000IU/mL), after which entecavir was added to the SOF/RBV regimen. This patient did not show significant increase in ALT level. Conclusion Our study confirmed the importance of screening for HBV in patients undergoing DAA therapy and importance of follow. For those for positive HBsAg, to avoid HBV reactivation and particularly HBV-related hepatitis. Our study limits the benefit of systematic nucleoside analogue prophylaxis for all HBsAg-positive patients. In our Egyptian cohort, for example, if we had followed the EASL recommendation (ie, starting nucleos(t)ide analogue prophylaxis for all 90 HBsAg-positive patients irrespective of their HBV DNA levels at baseline), this could have prevented 1 case of HBV-related reactivation during the course of DAAs, but resulted in overtreatment in the rest of patients

Systemic Lupus Erythematosus in a Patient with Liver Cirrhosis: Case Report and Literature Review

Background: There are no treatment guidelines for systemic lupus erythematosus (SLE) for the patients with decompensated cirrhosis, especially for those who have a history of hepatitis B virus (HBV) infection, gastrointestinal bleeding and gastric fundus ulceration. Case Presentation: A 50-year-old woman who had a six-year history of lupus was admitted to our hospital. One month prior, at the Department of Gastroenterology, she was diagnosed with decompensated liver cirrhosis with gastric fundal varicose bleeding, and HBV-related infection. During her visit to the hospital, gastroscopy showed esophageal varices and a large gastric fundus ulcer. Laboratory data indicated the rapid decrease of red blood cells, granulocytes and platelets and the persistent increase of serum globulin levels. According to the patient's medical history and existing laboratory examination, the patient experienced an exacerbation of SLE, which could be life-threatening.-While it remained uncertain whether the liver cirrhosis was caused by SLE or the HBV infection, immediate treatment was necessary. Consequently, she was treated with a low dose of methylprednisolone and mycophenolate mofetil (MMF). The treatment resulted in significant clinical improvement. Moreover, there was no indication of HBV reactivation, gastrointestinal bleeding, liver dysfunction or other drug-induced side effects. Conclusion: This case indicated that irrespective of the underlying causes of liver cirrhosis, the combination of a low dose of methylprednisolone and MMF is an effective treatment method to inhibit the disease process for patients with SLE and decompensated liver cirrhosis, a large gastric fundus ulcer and HBV infection.

Hepatitis B Virus Reactivation in Patients Receiving Bruton Tyrosine Kinase Inhibitors.

Bruton tyrosine kinase (BTK) inhibitors are used to treat B-cell hematologic malignancies. Ibrutinib has been associated with hepatitis B virus (HBV) reactivation. We sought to identify patients with hematologic malignancies who developed HBV reactivation after receiving first-generation (ibrutinib) or second-generation (acalabrutinib and zanubrutinib) BTK inhibitors. We retrospectively studied all consecutive patients with hematologic malignancies with past HBV infection (HBV surface antigen [HBsAg] negative and hepatitis B core antibody [anti-HBc] positive) or chronic HBV infection (HBsAg positive and anti-HBc positive) treated with BTK inhibitors at our institution from November 1, 2015, through November 1, 2022. Of 82 patients initially identified, 53 were excluded (11 because of false-positive anti-HBc results, and 42 because they were receiving anti-HBV prophylaxis owing to recent receipt of anti-CD20 monoclonal antibodies). The 29 remaining patients were further analyzed and 3 (10%; 2/28 with past and 1/1 with chronic HBV infection) were found to have HBV reactivation. One patient received ibrutinib, and 2 received acalabrutinib. All developed HBV-associated hepatitis requiring anti-HBV therapy and survived. One patient continued receiving acalarutinib. Among the patients with past HBV infection, 13 received ibrutinib and 1 (8%) had HBV reactivation; 14 received acalabrutinib and 1 (7%) had HBV reactivation (P=1.0). HBV reactivation risk is intermediate in patients with past HBV infection who receive BTK inhibitors. For patients with past HBV infection who received BTK inhibitors, data are insufficient to recommend universal anti-HBV prophylaxis, but monitoring for HBV reactivation is warranted.

Low incidence of hepatitis B virus reactivation in patients with hematological malignancies receiving novel anticancer drugs: A report from a high epidemic area and literature review.

More and more novel anticancer drugs have been approved for patients with hematological malignancies in recent years, but HBV reactivation (HBV-R) data in this population is very scarce. This study aimed to evaluated HBV-R risk in patients with hematological malignancies receiving novel anticancer drugs. HBV markers and serum HBV DNA levels of patients with hematological malignancies receiving novel anticancer drugs in a tertiary cancer hospital were retrospectively collected. HBV-R risk in the whole cohort and subgroups was described. The relevant literature was reviewed to make a pooled analysis. Of 845 patients receiving novel anticancer drugs, 258 (30.5%) were considered at risk for HBV-R. The median duration of exposure to novel drugs was 5.6 (0.1-67.6) months. The incidence of HBV-R was 2.1% in patients with past HBV infection without prophylactic antiviral treatment (PAT) and 1.2% in all patients at risk of HBV-R. In a pooled analysis of 11 studies with 464 patients, the incidence of HBV-R was 2.4% (95% CI: 1.3-4.2) in all at-risk patients receiving novel anticancer drugs and 0.6% (95% CI: 0.03-3.5) in patients with anticancer drugs plus PAT. The incidence of death due to HBV-R was 0.4% (95% CI: 0.1-1.6) in all at-risk patients and 18.2% (95% CI: 3.2-47.7) in patients with HBV-R. Most episodes of HBV-R are preventable, and most cases with HBV-R are manageable. We recommend that novel anticancer drugs should not be intentionally avoided when treating cancer patients with HBV infection.

Hepatitis B virus reactivation in seronegative occult hepatitis B patient receiving ibrutinib therapy

BackgroundIbrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor approved for the treatment for several mature B-cell malignancies. Reactivation of hepatitis B virus (HBV) is a well-described complication in patients with chronic HBV infection or prior HBV exposure undergoing cytotoxic or immunosuppressive chemotherapy for hematologic malignancies. This phenomenon has been frequently reported with rituximab. However, published data on the risk of HBV reactivation induced by ibrutinib are scarce. Cases of HBV reactivation in hematologic patients receiving ibrutinib therapy have recently been described, but limited only to overt hepatitis B patients or seropositive occult hepatitis B patients.Case presentationWe report the first case of HBV reactivation during ibrutinib treatment in an asymptomatic 82-year-old woman with seronegative occult hepatitis B patient (i.e., negative for HBsAg, anti-HBc and anti-HBs). Four months after ibrutinib treatment, her liver function test (LFT) was deranged, with seroconversion to HBsAg positivity. Serum hepatitis B virus DNA was quantified to be 1.92 × 108 IU/ml. Antiviral treatment was initiated, and viral load was gradually suppressed with improvement in LFT.ConclusionsOur case illustrated that in populations with a high incidence of HBV exposure, systematic screening for HBV exposure is essential prior to ibrutinib treatment, followed by serial monitoring of serologic and molecular markers of hepatitis B. There is a need for an international consensus to support the recommendation of antiviral prophylaxis against HBV reactivation in patients using ibrutinib.