ABSTRACT
New immunosuppressive and antineoplastic drugs are becoming both more numerous and more widely used, even during several years. Most of them present a low-moderate risk of hepatitis B virus (HBV) reactivation in HBsAg-negative and anti-HBc-positive patients. However, their reactivation capacity has not been clearly studied. We present the clinical case of a patient with these serological characteristics who, after 5 years of treatment with ibrutinib for chronic lymphocytic leukaemia, developed VHB reactivation, which was controlled with tenofovir. The occurrence of this event with drugs such as ibrutinib may lead to changes in HBV reactivation prophylaxis.
Subject(s)
Adenine/analogs & derivatives , Hepatitis B virus , Hepatitis B , Humans , Hepatitis B/chemically induced , Hepatitis B Surface Antigens , Piperidines/pharmacology , Piperidines/therapeutic use , Virus Activation , Antiviral Agents/adverse effectsABSTRACT
The vibration controlled transient elastography (VCTE) technique was used to assess the effectiveness of a Biejia Decoction pill in combination with Entecavir in the treatment of hepatitis B liver fibrosis/cirrhosis. We randomly selected 120 patients to receive entecavir and 119 patients to receive both entecavir and Biejia Decoction Pill, which both with hepatitis B liver fibrosis/cirrhosis visited the Second Affiliated Hospital of Nanchang University between January 2019 and February 2022. The observation group got ETV (entecavir) and Biejia Decoction pills, whereas the control group received only standard ETV antiviral medication. Based on the grading of the VCTE detection value (LSM) initially diagnosed for patients with hepatitis B liver fibrosis/cirrhosis, we divided the patients into two subgroups of liver fibrosis and cirrhosis. In addition, patients with liver fibrosis were divided into mild and moderate subgroups according to their VCTE values. Patients were measured for liver hardness after three, six, nine, and twelve months of treatment with VCTE. Biejia Decoction Pill combined with ETV on HBV liver fibrosis/cirrhosis was evaluated by comparing patients' changes in liver hardness and HBV-DNA negative conversion rates before and after treatment in each group at the same baseline. The LSM (liver elasticity value) of the observation group and the control group after treatment was lower than that before treatment, and the difference was statistically significant (P < 0.0001); The LSM of the observation group after treatment was significantly lower than that of the control group, and the difference was also statistically significant (P = 0.0005 < 0.05). In the subgroup of liver fibrosis, the number of patients with moderate and severe liver fibrosis who completely reversed liver fibrosis after treatment in the treatment group was far more than that in the control group, and the difference between the two groups was statistically significant (χ2 = 4.82 P = 0.028 < 0.05) ã When the treatment course was more than 9 months, the negative conversion rate of patients in the observation group reached 87.4%, which was higher than that in the control group (70.8%), and the difference was statistically significant (P = 0.002 < 0.05); After 12 months of treatment, the negative conversion rate of patients in the observation group was as high as 95%, which was significantly higher than 76.67% in the control group (P < 0.001). The degree of liver fibrosis was significantly improved when Biejia Decoction Pill was combined with ETV in patients with liver fibrosis/cirrhosis due to hepatitis B. The virological response rate to HBV-DNA increased with the prolongation of treatment, and the Biejia Decoction Pill assists with entecavir in antiviral therapy.
Subject(s)
Elasticity Imaging Techniques , Hepatitis B, Chronic , Hepatitis B , Humans , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/diagnosis , DNA, Viral , Vibration , Treatment Outcome , Hepatitis B/complications , Hepatitis B/drug therapy , Hepatitis B/chemically induced , Liver Cirrhosis/diagnosis , Antiviral Agents/therapeutic use , Hepatitis B virus/geneticsABSTRACT
BACKGROUND: In patients with kidney or hepatic diseases, an increment of circulating pasireotide is also expected. Therefore, this open-label, phase I study aimed to evaluate the pharmacokinetic profiles and safety of subcutaneous (SC) and long-acting release (LAR) intramuscular injections of pasireotide in male Taiwanese volunteers who are hyperendemic hepatitis B/C and chronic kidney disease (CKD). METHODS: A total of 45 male volunteers were randomized to receive one of nine treatment sequences, involving a single subcutaneous injection of 300, 600, or 900 µg pasireotide, a multiple SC injection of the same dosage of pasireotide [300, 600, or 900 µg, twice daily (b.i.d.) for 4 days and a single dose for 1 day], and a single dose of 20, 40, or 60 mg LAR pasireotide intramuscular injection. The pasireotide SC and LAR formulations were prepared and supplied to the study center by Novartis. Pharmacokinetic parameters were assessed from both formulations. All adverse events that occurred in participants throughout the study period, including abnormalities in fasting levels of glucose, insulin, and glucagon, as well as laboratory measurements and electrocardiograms, were recorded. RESULTS: Analysis of plasma concentration over time revealed a rapid absorption of pasireotide, with a maximal concentration at 0.5 h after SC injection(s) of pasireotide (300-900 µg). Following a single dose of pasireotide LAR (20-60 mg), a sustained release was observed following an initial increase on day 1, a plateau around day 20, and a decline over the next 7 weeks. CONCLUSIONS: Both pasireotide formulations showed dose-proportional pharmacokinetics and 300-900 µg of SC pasireotide and 20-60 mg LAR pasireotide treatment showed favorable safety profiles and was well-tolerated when administered in male Taiwanese volunteers who are hyperendemic hepatitis B/C and CKD.
Subject(s)
Hepatitis B , Renal Insufficiency, Chronic , Humans , Male , Somatostatin/adverse effects , Insulin , Renal Insufficiency, Chronic/drug therapy , Hepatitis B/chemically induced , Hepatitis B/drug therapyABSTRACT
BACKGROUND: Daratumumab and isatuximab are anti-CD38 monoclonal antibodies indicated for the treatment of multiple myeloma. These agents can increase the risk of infectious complications, including viral infections. Cases of hepatitis B virus (HBV) reactivation have been reported in the literature in patients receiving anti-CD38 monoclonal antibody-based therapies. AIM: The objective of this analysis was to determine if the association between anti-CD38 monoclonal antibody exposure and the development of hepatitis B reactivation had a detectable reporting signal in the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). METHOD: We conducted a post marketing pharmacovigilance analysis by querying the FAERS for reports of HBV reactivation with daratumumab or isatuximab exposure reported between 2015 and 2022. Disproportionality signal analysis was conducted by calculating reporting odds ratios (RORs). RESULTS: Sixteen cases of hepatitis B virus reactivation were reported in the FAERS database among patients receiving daratumumab or isatuximab reported between 2015 and 2022. The ROR for HBV reactivation was statistically significant for both daratumumab (ROR 4.76, 95% CI 2.76-8.22) and isatuximab (ROR 9.31, 95% CI 3.00-28.92). CONCLUSION: Overall, our analysis demonstrates a significant reporting signal for HBV reactivation with daratumumab and isatuximab.
Subject(s)
Antineoplastic Agents , Hepatitis B , Multiple Myeloma , United States , Humans , Multiple Myeloma/drug therapy , Multiple Myeloma/epidemiology , Pharmacovigilance , Antibodies, Monoclonal/adverse effects , Antineoplastic Agents/adverse effects , Hepatitis B/chemically induced , Hepatitis B/epidemiology , Hepatitis B/complicationsABSTRACT
The chronic infection of the hepatitis B virus (CHB) represents a major public health problem worldwide. Despite the availability of an effective prophylactic vaccine, millions of hepatitis B patients are at increased risk of developing chronic liver disease. The currently available treatments for HBV infection include interferon and nucleos(t)ide analogues that are effective at suppressing viral load and preventing or delaying the progression of liver disease. However, these treatments offer somewhat unsatisfactory clinical cures due to the persistence of the intrahepatic pool of covalently closed circular DNA (cccDNA) that serves as a reservoir for viral progenies and a potential source of recurring infections. Elimination of viral cccDNA remains a challenge for scientists and pharmaceutical industries in order to achieve the eradication and control of HBV infection. This would involve a detailed understanding of the molecular mechanisms of cccDNA formation, its intracellular stability, and regulation during replication and transcription. Recent advances in drug therapy have heralded a new horizon of novel therapeutic approaches for CHB infection, with several promising antiviral and immunomodulatory agents currently in preclinical or clinical testing. However, approval of any new curative therapy would involve rigorous evaluation of the efficacy and safety of each treatment and defining correct endpoints associated with improved clinical outcomes. This article summarizes the current landscape of HBV treatments, and drugs in clinical trials and highlights the most recent anti-HBV small molecules designed to directly target HBV or to improve immune response during chronic infection.
Subject(s)
Hepatitis B, Chronic , Hepatitis B , Humans , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/genetics , Persistent Infection , Hepatitis B/chemically induced , Hepatitis B/drug therapy , Hepatitis B virus/genetics , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , DNA, Viral/pharmacology , DNA, Viral/therapeutic use , DNA, Circular/pharmacology , DNA, Circular/therapeutic use , Virus ReplicationABSTRACT
BACKGROUND: The risk of hepatitis B virus (HBV) reactivation after biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) therapy in patients with rheumatoid arthritis (RA) combined with HBsAg-/HBcAb+ is still inconsistent. METHODS: We conducted a systematic review of existing databases from 1977 to August 22, 2021. Studies of RA patients combined with HBsAg-/HBcAb +, treated with b/tsDMARDs and the reported number of HBV reactivation were included. RESULTS: We included 26 studies of 2252 HBsAg-/HBcAb+ RA patients treated with b/tsDMARDs. The pooled HBV reactivation rate was 2.0% (95% confidence interval [CI]: 0.01-0.04; I2 = 66%, p < .01). In the subgroup analysis, the HBV reactivation rate of rituximab (RTX), abatacept, and inhibitors of Janus kinase (JAK), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were 9.0% (95% CI: 0.04-0.15; I2 = 61%, p = .03), 6.0% (95% CI: 0.01-0.13; I2 = 40%, p = .19), 1.0% (95% CI: 0.00-0.03; I2 = 41%, p = .19), 0.0% (95% CI: 0.00-0.02; I2 = 0%, p = .43), 0.0% (95% CI: 0.00-0.01; I2 = 0%, p = .87), respectively. While HBsAb- patients have a significant risk of reactivation (odds ratio [OR] = 4.56, 95% CI = 2.45-8.48; I2 = 7%, p = .37), low HBsAb+ group also display a significant risk of reactivation (OR = 5.45, 95% CI: 1.35-21.94; I2 = 0%, p = .46). CONCLUSIONS: This meta-analysis demonstrates the highest potential risk of HBV reactivation in HBsAg-/HBcAb+ RA patients receiving RTX treatment, especially HBsAb- patients. Our study furthers the understanding of the prophylactic use of anti-HBV drugs in such patients. However, it is relative safety to use the inhibitors of IL-6, TNF-α, and JAK in these patients.
Subject(s)
Arthritis, Rheumatoid , Biological Products , Hepatitis B , Janus Kinase Inhibitors , Humans , Arthritis, Rheumatoid/drug therapy , Biological Products/adverse effects , Biological Products/therapeutic use , Hepatitis B/chemically induced , Hepatitis B/drug therapy , Hepatitis B Antibodies , Hepatitis B Surface Antigens , Hepatitis B virus/physiology , Interleukin-6 , Janus Kinase Inhibitors/adverse effects , Janus Kinase Inhibitors/therapeutic use , Rituximab/adverse effects , Rituximab/therapeutic use , Tumor Necrosis Factor-alphaABSTRACT
PURPOSE: Heplisav-B is a novel recombinant adjuvanted vaccine for hepatitis B virus (HBV) that has been approved as a 2-dose regimen and shown to have similar seroconversion rates in healthy adults as single-antigen HBV vaccines. More data are needed to determine whether similarly high rates of seroconversion and immunity are observed in immunocompromised patient populations such as in patients with end-stage renal disease (ESRD) on hemodialysis. METHODS: Patients with ESRD who presented for emergency-only hemodialysis and either were HBV vaccine naive or had a hepatitis B surface antibody (anti-HBs) titer of less than 10 IU/mL received 3 standard 20-µg doses of Heplisav-B at week 0, week 4 (±2 weeks), and week 24 (±2 weeks), with anti-HBs titer measured at week 28 (±2 weeks). RESULTS: Thirty-two patients received at least one dose in the study timeframe, with 24 patients completing the vaccine series and measurement of anti-HBs titer. The mean age of the patients was 46 years, and 58% of patients were male. Of the 24 patients who completed the vaccine series, 20 (83%) seroconverted after the third dose. Three of the 4 patients who did not seroconvert after 3 doses were revaccinated with an additional 20-µg dose, and 2 of the 3 patients had an anti-HBs titer of greater than 10 IU/mL 4 weeks after this dose. CONCLUSION: Patients with ESRD who received three 20-µg doses of recombinant HBV vaccine had a seroconversion rate of 83%, representing a similar seroconversion rate and fewer doses of vaccine as compared to the standard HBV vaccine regimen for patients with ESRD.
Subject(s)
Hepatitis B , Kidney Failure, Chronic , Adult , Humans , Male , Middle Aged , Female , Hepatitis B Vaccines/adverse effects , Seroconversion , Safety-net Providers , Hepatitis B/prevention & control , Hepatitis B/chemically induced , Kidney Failure, Chronic/therapy , Hepatitis B AntibodiesABSTRACT
Hepatitis B (HBV) reactivation (HBVr) is a potentially fatal complication in patients with past HBV exposure receiving immunosuppressive therapy. HBVr can occur in patients with chronic HBV infection as well as in patients with resolved HBV infection. In this article, we present the cases of four patients with resolved hepatitis B who presented with HBVr during or after immunosuppressive treatment, of whom two died as a consequence of HBVr. We then reflect on and summarize the recommendations of four major societies for the screening and management of previously HBV-exposed patients planned to receive immunosuppressive treatment. Current guidelines recommend screening for HBV in all patients planned to receive immunosuppressive therapy. Risk of HBVr is assessed based on the serological status of the patient and the planned immunosuppressive drug regimen. For patients considered to be at low risk of HBVr, management consists of serological monitoring for HBVr and immediate preemptive antiviral therapy in the case of HBVr. For patients considered to be at intermediate or high risk for HBVr, antiviral prophylaxis should be initiated concordantly with the immunosuppressive therapy and continued for up to 18 months after cessation of the immunosuppressive regimen. Areas of uncertainty include the risk of novel and emerging immunosuppressive and immune modulatory drugs and the exact duration of antiviral prophylaxis. Greater awareness is needed among clinicians regarding the risk of HBVr in patients receiving immunosuppressive therapy, especially in low-endemicity settings. Implementation of screening and management programs and decision support tools based on the presented guidelines may improve the management of these patients.
Subject(s)
Hepatitis B virus , Hepatitis B , Humans , Antiviral Agents/therapeutic use , Hepatitis B/chemically induced , Hepatitis B/drug therapy , Hepatitis B/prevention & control , Hepatitis B virus/physiology , Immunosuppression Therapy , Immunosuppressive Agents/adverse effects , Virus ActivationABSTRACT
BACKGROUND AND OBJECTIVE: Biologics for psoriasis, especially anti-tumor necrosis factor-α therapies, may reactivate hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, as well in inactive carriers or patients with occult infection. However, some biologics, including anti-interleukin-17 therapies such as secukinumab, seem to be less likely to cause hepatitis reactivation. This study assessed the safety of secukinumab treatment in patients with psoriasis with HBV or HBC infection. METHODS: This was a retrospective cohort study of patients with moderate-to-severe psoriasis treated with secukinumab at seven Italian centers. Patients serologically positive for one or more of the following viral hepatitis markers were included: HCV antibody (± HCV-RNA positivity) and/or hepatitis B surface antigen, and/or HBV core antibody and/or HBV surface antibody (± HBV-DNA positivity). Patients received secukinumab 300 mg subcutaneously at week 0/1/2/3/4 then every 4 weeks; prophylactic therapy before starting secukinumab was prescribed where indicated. The primary study endpoint was the reactivation of hepatitis viral infection, defined as conversion to HBV-DNA or HCV-RNA positivity, with or without elevation of transaminases. RESULTS: Sixty patients (17 with concomitant psoriatic arthritis) were included. Thirteen subjects were hepatitis B surface antigen positive, 19 were HBV core antibody positive, and 30 were positive for the HCV antibody; however, all were HCV-RNA negative. After 53.5 ± 37.5 weeks of secukinumab therapy, hepatitis reactivation occurred in only one patient, who had a reactivation of both hepatitis B and hepatitis C. This patient had not undergone hepatitis B prophylaxis or hepatitis C treatment before secukinumab. CONCLUSIONS: These real-world data support the safety of secukinumab in patients with positive markers of HBV or HCV infection, when administered together with dedicated prophylaxis.
In this retrospective cohort study, 60 patients with moderate-to-severe psoriasis were treated with secukinumab at seven Italian centers. Secukinumab is a fully human monoclonal antibody targeting interleukin-17A, a key cytokine associated with the development of psoriatic disease. All patients had markers of hepatitis B and/or C. Where appropriate, patients received prophylactic antiviral therapy before starting secukinumab at the standard dose for treating psoriasis in Italy. Secukinumab was administered at the labeled dose. After a mean duration treatment of 53.5 weeks, hepatitis reactivation (both B and C) occurred in one patient. This patient had not undergone hepatitis B prophylaxis or hepatitis C treatment before receiving secukinumab. The study is important, as some biologics for psoriasis, especially anti-tumor necrosis factor-α therapies, have been shown to reactivate both hepatitis B virus or hepatitis C virus infections in inactive carriers, patients with occult hepatitis B virus infection, or patients with hepatitis C virus infections. However, there is evidence that second-generation biologic therapies, including those with anti-interleukin-17 activity, are less likely to cause hepatitis reactivation. This study supports the safety of secukinumab treatment in patients with psoriasis with hepatitis B and/or C.
Subject(s)
Biological Products , Hepatitis B, Chronic , Hepatitis B , Hepatitis C , Psoriasis , Antibodies, Monoclonal, Humanized , Antiviral Agents/therapeutic use , Biological Products/adverse effects , DNA, Viral , Hepacivirus/physiology , Hepatitis B/chemically induced , Hepatitis B/diagnosis , Hepatitis B/drug therapy , Hepatitis B Surface Antigens/pharmacology , Hepatitis B Surface Antigens/therapeutic use , Hepatitis B virus/physiology , Hepatitis B, Chronic/drug therapy , Hepatitis C/drug therapy , Humans , Psoriasis/drug therapy , RNA/pharmacology , RNA/therapeutic use , Retrospective Studies , Virus ActivationABSTRACT
Real-world data are limited on tenofovir alafenamide (TAF). We aimed to study TAF real-world outcomes with other first-line regimens for chronic hepatitis B (CHB). We enrolled patients with CHB from 10 centers retrospectively and followed them for 36 months prospectively. We analyzed switching patterns of antiviral therapy and treatment outcomes of TAF, tenofovir disoproxil fumarate (TDF), and entecavir therapy. For efficacy and safety, we analyzed a subset of patients with complete data at 24 months after switching to TAF or remaining on TDF or entecavir. Among 1037 enrollees, 889 patients were analyzed. The mean age was 52%, and 72% were hepatitis B e antigen-negative. After enrollment, shifts in therapies were mostly in reduced use of TDF from 63% to 30% due to switching to TAF. Clinical parameters were compared at enrollment or initiation to measures at 24 months for patients remaining on TAF (187), TDF (229), or entecavir (181). At 24 months, a significantly higher portion of patients on TAF achieved hepatitis B virus (HBV) DNA ≤ 20 IU/ml (93% vs. 86%; p = 0.012) and normalized alanine aminotransferase (ALT) (66% vs. 56%; p = 0.031) with stable estimated glomerular filtration rates (eGFRs). However, a higher percentage of the patient with eGFR < 60 ml/mi/1.7 m2 was observed in the TDF-treated group (9% vs. 4%; p = 0.010). In patients who remained on entecavir or TDF for 24 months, ALT and HBV-DNA results did not differ significantly from baseline. Treatment of CHB in the United States has significantly shifted from TDF to TAF. Our data suggest that switching from TDF or entecavir to TAF may result in increased frequency of ALT normalization and potential clearance of viremia at the 24-month time point.
Subject(s)
Hepatitis B, Chronic , Hepatitis B , Alanine/therapeutic use , Antiviral Agents/adverse effects , Hepatitis B/chemically induced , Hepatitis B, Chronic/drug therapy , Humans , Prospective Studies , Retrospective Studies , Tenofovir/adverse effects , United States/epidemiologyABSTRACT
Genome editing techniques such as CRISPR/Cas9 have both become common gene engineering technologies and have been applied to gene therapy. However, the problems of increasing the efficiency of genome editing and reducing off-target effects that induce double-stranded breaks at unexpected sites in the genome remain. In this study, we developed a novel Cas9 transduction system, Exci-Cas9, using an adenovirus vector (AdV). Cas9 was expressed on a circular molecule excised by the site-specific recombinase Cre and succeeded in shortening the expression period compared to AdV, which expresses the gene of interest for at least 6 months. As an example, we chose hepatitis B, which currently has more than 200 million carriers in the world and frequently progresses to liver cirrhosis or hepatocellular carcinoma. The efficiencies of hepatitis B virus genome disruption by Exci-Cas9 and Cas9 expression by AdV directly (Avec) were the same, about 80-90%. Furthermore, Exci-Cas9 enabled cell- or tissue-specific genome editing by expressing Cre from a cell- or tissue-specific promoter. We believe that Exci-Cas9 developed in this study is useful not only for resolving the persistent expression of Cas9, which has been a problem in genome editing, but also for eliminating long-term DNA viruses such as human papilloma virus.
Subject(s)
Adenoviridae/genetics , CRISPR-Associated Protein 9/metabolism , CRISPR-Cas Systems , Gene Editing , Hepatitis B virus/genetics , Hepatocytes/metabolism , Integrases/metabolism , CRISPR-Associated Protein 9/genetics , Genetic Vectors , HEK293 Cells , HeLa Cells , Hep G2 Cells , Hepatitis B/chemically induced , Hepatitis B/genetics , Hepatocytes/virology , Humans , Integrases/geneticsABSTRACT
The reactivation of the hepatitis B virus(HBV)induced by chemotherapy can cause fulminant hepatitis, followed by death. In Japan, the Ministry of Health, Labor and Welfare released the guideline on the prevention of chemotherapy- induced reactivation of HBV in 2009. The NCGM's pharmacy department conducted a study on the HBV screening rate and the guideline compliance rate in patients undergoing chemotherapy who met the criteria for monthly HBV DNA monitoring during chemotherapy and 12 months after. We also conducted a study on the influence on the guideline compliance rate with inquiries by pharmacists. The HBV screening rate was 100%(68/68 cases), and there were inquiries in 10.3% (7/68 cases). This suggests that inquiries contributed to the improvement in the HBV screening rate. However, the guideline compliance rate in high-risk cases was 75.0%(12/16 cases). It is necessary to raise awareness in physicians and patients on the management of HBV reactivation and to establish a follow-up system for HBV DNA monitoring.
Subject(s)
Hepatitis B , Neoplasms , Hepatitis B/chemically induced , Hepatitis B Antibodies , Hepatitis B Surface Antigens , Hepatitis B virus , Humans , Virus ActivationABSTRACT
This case series is to create awareness among clinicians on the importance of Hepatitis B screening prior to administration of chemotherapeutic agents and immunosuppressant in preventing Hepatitis B reactivation (HBVr). We also highlight the importance of identifying patients who are at risk of HBVr and when to initiate antiviral prophylaxis based on the current evidence-based guidelines. The case series consists of four patients seen in Hospital Selayang, Malaysia who developed fulminant liver failure secondary to chemotherapeutic agents or immunosuppressant induced HBVr. HBVr is likely to be of increasing clinical significance as potent immunosuppressive regimens are used more widely across all medical specialties. Clinicians should be made aware of the potential risk of patients developing fulminant liver failure following HBVr and its association with high morbidity and mortality. In the era of inexpensive Hepatitis B blood screening tests and safe potent antivirals, there is now a paradigm shift to make the test compulsory to screen all patient prior to initiation of chemotherapeutic agents or immunosuppressive therapy. Antiviral prophylaxis may be offered to more patients who are at risk of HBVr and the duration of both prophylaxis and subsequent monitoring may be extended until 6 to 18 months following completion of treatment.
Subject(s)
Hepatitis B , Immunosuppressive Agents , Antiviral Agents/adverse effects , Hepatitis B/chemically induced , Hepatitis B virus , Humans , Immunosuppressive Agents/adverse effects , Virus ActivationABSTRACT
AIMS: Hepatitis B virus (HBV) infection is a worldwide distributing viral disease. Hepatitis caused by HBV reactivation may progress to chronic illness and associated with increased risk of hepatic failure and hepatocellular cancer. Rituximab (RTX) is an immunosuppressive agent, is particularly used in the treatment of non-Hodgkin's Lymphoma. Patients have significant risk for HBV reactivation following chemotherapy with a RTX-containing regimen. This study aimed to determine the HBV screening manner and reactivation rates in patients with haematological neoplasm following chemotherapy including Rituximab. METHODS: This is a single-centered retrospective cohort study. A total of 331 adults with haematological disorders who received chemotherapy regimen including RTX between years of 2006 and 2016 were enrolled. Patients who experienced reactivation were evaluated. RESULTS: Only 130 of 331 patients were screened appropriately for HBV infection for 10-year period. We found 18 patients were Hepatitis B surface antigen (HBsAg) (+) and 16 (88.8%) of them received antiviral prophylaxis. Among screened patients, 27 were HBsAg (-)/AntiHBc (+) and only 10 (37%) of them received HBV prophylaxis. In total, nine patients experienced reactivation, six were from screened and three were from unscreened group. CONCLUSION: Incomplete screening and inappropriate prophylaxis may result in HBV reactivation in patients under RTX-based chemotherapy and related complications such as death.
Subject(s)
Hepatitis B , Virus Activation , Adult , Hepatitis B/chemically induced , Hepatitis B/diagnosis , Hepatitis B Surface Antigens , Humans , Retrospective Studies , Rituximab/adverse effectsABSTRACT
The US is in the midst of a major drug epidemic fueled in large part by the widespread recreational use of synthetic opioids such as fentanyl. Persons with opioid use disorder are at significant risk for transmission of injection-associated infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV). Commonly abused substances may antagonize immune responses and promote viral replication. However, the impact of synthetic opioids on virus replication has not been well explored. Thus, we evaluated the impact of fentanyl and carfentanil using in vitro systems that replicate infectious viruses. Fentanyl was used in cell lines replicating HBV or HCV at concentrations of 1 ng, 100 ng, and 10 ug. Viral protein synthesis was quantified by ELISA, while apoptosis and cell death were measured by M30 or MTT assays, respectively. HCV replicative fitness was evaluated in a luciferase-based system. RNAseq was performed to evaluate cellular gene regulation in the presence of fentanyl. Low dose fentanyl had no impact on HCV replication in Huh7.5JFH1 hepatocytes; however, higher doses significantly enhanced HCV replication. Similarly, a dose-dependent increase in HCV replicative fitness was observed in the presence of fentanyl. In the HepG2.2.15 hepatocyte cell line, fentanyl caused a dose-dependent increase in HBV replication, although only a higher doses than for HCV. Addition of fentanyl resulted in significant apoptosis in both hepatocyte cell lines. Cell death was minimal at low drug concentrations. RNAseq identified a number of hepatocyte genes that were differentially regulated by fentanyl, including those related to apoptosis, the antiviral / interferon response, chemokine signaling, and NFκB signaling. Collectively, these data suggest that synthetic opioids promote viral replication but may have distinct effects depending on the drug dose and the viral target. As higher viral loads are associated with pathogenesis and virus transmission, additional research is essential to an enhanced understanding of opioid-virus pathogenesis and for the development of new and optimized treatment strategies.
Subject(s)
Fentanyl/adverse effects , Hepacivirus/drug effects , Hepatitis B virus/drug effects , Hepatitis B/virology , Hepatitis C/virology , Hepatocytes/virology , Virus Replication , Analgesics, Opioid/adverse effects , Apoptosis , Cytopathogenic Effect, Viral , Hep G2 Cells , Hepatitis B/chemically induced , Hepatitis B/pathology , Hepatitis C/chemically induced , Hepatitis C/pathology , Hepatocytes/drug effects , Hepatocytes/pathology , Humans , In Vitro Techniques , TranscriptomeABSTRACT
BACKGROUND/AIMS: Hepatitis B reactivation (HBVR) is an important risk of treatment with tumor necrosis factor inhibitors (anti-TNF). While antiviral prophylaxis is recommended before treatment in HBsAg-positive patients, there is no clear approach for the follow-up or prophylactic treatment of patients with past hepatitis B virus (HBV) infection. The aim of this study was to evaluate patients with past HBV infection treated with anti-TNF for HBVR and/or HBVR-associated biochemical breakthrough. MATERIAL AND METHODS: Patients who received anti-TNF therapy and had past HBV infection (HBsAg negative, anti-HBc IgG positive, anti-HBs negative or positive) were screened and evaluated at 3-month intervals for viral and biochemical breakthrough according to a liver function test (ALT) and HBV DNA level. RESULTS: A total of 653 patients who received anti-TNF therapy were screened. Ninety of these patients had past HBV infection and had not received antiviral prophylaxis. Anti-HBs positivity and isolated anti-HBc IgG positivity were seen in 87.7% (n: 79) and 12.2% (n: 11) of these patients, respectively. No HBVR was seen in 20% (n: 18) of patients who were followed up regularly, and no HBVR-associated biochemical breakthrough was found in patients who were not followed up regularly in terms of HBV DNA level (80%, n: 72) during the follow-up period (26±16 months). CONCLUSION: The use of anti-TNF in patients with past HBV infection has a low risk for HBVR. A follow-up for the ALT and HBV DNA levels at 3-month intervals may be more reasonable than administering antiviral prophylaxis to all patients.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B virus/genetics , Hepatitis B/drug therapy , Tumor Necrosis Factor Inhibitors/adverse effects , Virus Activation/drug effects , Adult , DNA, Viral/blood , Female , Hepatitis B/chemically induced , Hepatitis B/prevention & control , Hepatitis B Antibodies/blood , Hepatitis B Surface Antigens/blood , Humans , Immunosuppressive Agents/adverse effects , Liver Function Tests , Male , Middle Aged , Retrospective StudiesABSTRACT
Hepatitis B virus (HBV) reactivation, in the background of cleared and overt chronic HBV infection, can be seen in patients receiving immunosuppressive agents. Risk of reactivation is variably associated with HBV serologic status and types of immunosuppressive therapy. Prevention of HBV reactivation by antiviral prophylaxis is an effective strategy to reduce morbidity and mortality in those with immunocompromised states. This article defines HBV reactivation, discusses risk stratification and common medications that can induce HBV reactivation as well as guideline recommendations for prevention of HBV reactivation, and describes the prognosis and management of patients who experience HBV reactivation.
Subject(s)
Antineoplastic Agents/adverse effects , DNA, Viral/blood , Hepatitis B virus/physiology , Hepatitis B/chemically induced , Immunosuppressive Agents/adverse effects , Virus Activation , Antiviral Agents/therapeutic use , Hepatitis B/blood , Hepatitis B/drug therapy , Hepatitis B Antibodies/blood , Hepatitis B Core Antigens/immunology , Hepatitis B Surface Antigens/blood , Humans , Immunosuppression Therapy/adverse effects , Risk FactorsABSTRACT
Hepatitis B virus (HBV) reactivation can be a serious complication for patients with chronic or resolved HBV infection when treated with biologics. For HBsAg-positive patients receiving biologics, the risk of HBV reactivation is moderate to high. HBsAg-negative/anti-HBc positive patients are at lower risk of HBV reactivation than HBsAg-positive patients. However, patients taking anti-CD20 agents, such as rituximab, have high risk of HBV reactivation (>10%), so antiviral prophylactic therapies are required. This review provides the different classes of biologics associated with HBV reactivation, stratifies the various reactivation risk levels by HBV status and biologic agent, and discusses management strategies.