Risk of hepatitis B virus reactivation (HBVr) in patients with resolved HBV infection receiving immunosuppressive therapy has been a growing concern, particularly in the era of biological and ...targeted therapies. HBV monitoring versus antiviral prophylaxis against HBVr in those patients remains controversial. The aim of the study was to determine the incidence of HBVr and HBV-related hepatitis in resolved HBV patients who received immunosuppressive therapy with or without antiviral prophylaxis. This retrospective study included 64 patients with resolved HBV infection who received different regimens of immunosuppressive medications, with moderate risk of HBVr, for variable underlying diseases. Patients who had chronic HBV infection or other viral infections were excluded. Patients who received B-cell depleting therapies were ruled out. They were divided into 2 groups: group 1 included 31 patients who received immunosuppressive therapy without antiviral prophylaxis, and group 2 included 33 patients who received antiviral prophylaxis (entecavir) within 2 weeks of commencing the immunosuppressive therapy. HBVr, HBV-related hepatitis, and HBV-unrelated hepatitis were assessed along a 1-year duration. The overall HBVr incidence was 1.56% (1/64). This patient who had HBVr was seen in group 1. There were no significant differences between the 2 groups regarding the incidence of HBVr, HBV-related hepatitis, HBV-unrelated hepatitis, and immunosuppressive therapy interruption along a 1-year duration. Based on this retrospective study, close monitoring was equal to antiviral prophylaxis regarding the outcome of resolved HBV patients who received moderate risk immunosuppressive therapy. HBV treatment should commence once HBVr is confirmed.
Patterns of hepatitis B virus reactivation (HBV‐R) in HBsAg (−)/HBcAb (+) patients with B‐cell non‐Hodgkin lymphoma (NHL) receiving rituximab based immunochemotherapy have not been well described. ...The retrospective study included 222 HBsAg (−)/HBcAb (+) NHL patients as training cohort and 127 cases as validation cohort. The incidence of HBV‐R in HBsAg (−)/HBcAb (+) B‐cell NHL patients was 6.3% (14/222), of which that in HBsAg (−)/HBsAb (−)/HBeAg (−)/HBeAb (+)/HBcAb (+) population was 23.7% (9/38). Multivariate analysis showed that HBsAg (‐)/HBsAb (−)/HBeAg (−)/HBeAb (+)/HBcAb (+) correlated with a high risk of HBV‐R in B‐cell lymphoma patients (training phase hazard ratio HR, 10.123; 95% confidence interval CI, 3.389–30.239; p < 0.001; validation phase HR, 18.619; 95% CI, 1.684–205.906; p = 0.017; combined HR, 12.264; 95% CI, 4.529–33.207; p < 0.001). In the training cohort, the mortality rate of HBsAg (−)/HBcAb (+) B‐cell NHL caused by HBV‐R was 14.3% (2/14) while that for HBV reactivated HBsAg (‐)/HBsAb (−)/HBeAg (−)/HBeAb (+)/HBcAb (+) population was up to 44.4% (4/9). As a high incidence of HBV‐R and high mortality after HBV‐R was found in HBsAg (−)/HBsAb (−)/HBcAb (+)/HBeAg (−)/HBeAb (+) patients with B‐cell NHL receiving rituximab based immunochemotherapy, prophylactic antiviral therapy is recommended for these patients.
Hepatitis B virus (HBV) infection remains an important cause of liver disease and continues to present several unique challenges in organ transplantation despite the availability of an effective ...vaccine to prevent HBV infection and the introduction of oral therapy to treat HBV infection over 20 years ago. HBV recurrence following liver transplantation can now be prevented with antiviral therapy, although controversy persists as to whether immunoprophylaxis with hepatitis B immunoglobulin is also necessary. HBV reactivation following organ transplantation can occur even in recipients with absent hepatitis B surface antigen at the time of transplantation and remains an important cause of morbidity and mortality. Expansion of the donor pool by using organs from hepatitis B core antibody-positive donors can result in HBV infection in the recipient. Another challenge is severe HBV reactivation leading to liver failure in HBV-infected patients receiving immunomodulatory agents, which are increasingly being used for a variety of nonneoplastic indications.
INTRODUCTIONSevere acute respiratory syndrome-coronavirus 2 (SARSCoV2) pandemic has been an unceasing plight with a wide range of clinical presentations. The direct effects of the virus, increased ...use of medications, and lifestyle changes have contributed to the vulnerability to co-infections. Fungal and bacterial co-infections led to increased morbidity and mortality during the pandemic. Similarly, the surge of skin signs in conjunction with herpes zoster (HZ) manifestations has been reported. In this study, we pooled the data on the clinical characteristics of SARS-CoV-2 patients co-infected with HZ. METHODOLOGYElectronic databases including PubMed, Scopus, and Google Scholar were extensively searched to identify the relevant studies on HZ infection among the SARS-CoV-2 patients. RESULTSA total of 79 patients (from case reports, series, and retrospective studies) were included in the analysis. Fever was the most common constitutional symptom recorded, followed by cough and dyspnea. A systemic rash was reported in 78.5% of cases with mild symptoms of HZ and SARS-CoV-2 in 87% and 76%, respectively. Only 19% of the cases presented during the prodrome period of SARS-CoV-2. HZV polymerase chain reaction (PCR) was positive in 8.9% of the cases, and the remaining were diagnosed clinically. SARS-CoV-2 PCR was reported positive in 65 cases (82.3%). Leukopenia was observed in 7 cases (8.9%) and lymphopenia in 25 (31.6%). All patients recovered through conservative treatment. CONCLUSIONSARS-CoV-2 escalated the incidence of HZ reactivation. Most of the patients were seen with older individuals either simultaneously or a few days after the SARS-CoV-2 infection, but a few cases were reported during the asymptomatic prodrome period of SARS-CoV-2.
Background
The safety of immune‐checkpoint inhibitors (ICIs) has not been thoroughly investigated in non–small cell lung cancer (NSCLC) patients with chronic hepatitis B (CHB) or occult hepatitis B ...infection (OBI). The authors analyzed the incidence of hepatitis B virus (HBV) reactivation, immune‐related hepatitis and jaundice in NSCLC patients in a real‐world setting.
Methods
A total of 1277 NSCLC patients treated with ICIs were analyzed. Among them, 52 patients were hepatitis B surface antigen (HBsAg) (+) (group A, CHB), 759 patients were HBsAg (–)/hepatitis B core antibody immunoglobulin G (anti‐HBc IgG) (+) (group B, OBI), and 466 patients were HBsAg (–)/anti‐HBc IgG (–) (group C). Among the 52 patients with CHB, 38 (73.1%) were receiving antiviral therapy. The primary end point was HBV reactivation, immune‐related hepatitis, and jaundice. The secondary end points included other immune‐related adverse events and efficacy.
Results
HBV reactivation was observed in two patients (0.2%) who were both in group A (CHB). Among CHB patients who were not receiving antiviral therapy, HBV reactivation was observed in 14.3% (2 of 14 patients). The incidences of immune‐related hepatitis and jaundice were comparable among the three groups. The incidence of ≥grade 3 other immune‐related adverse events and efficacy were all comparable among the three groups (p > .05 for all comparisons).
Conclusions
In this large, real‐world cohort study, the safety and efficacy of ICIs were comparable in patients with CHB and OBI. HBV reactivation was observed in patients with CHB without antiviral therapy indicating antiviral prophylaxis should be required for them. For patients with OBI, the risk of HBV reactivation was minimal.
Hepatitis B virus (HBV) reactivation was observed in patients with chronic hepatitis B without antiviral therapy indicating antiviral prophylaxis should be required for them. For patients with occult hepatitis B infection, the risk of HBV reactivation was minimal.
A 72-year-old woman presented to our hospital with elevation of serum transaminases. Her blood tests showed the hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) negative. ...Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were given for the diffuse large B-cell lymphoma. She didn't receive anti- hepatitis B virus (HBV) drug for the isolated HBcAb positive. HBV reactivation confirmed based on the serum HBV DNA detectable until 19 months after stopping R-CHOP regimen. HBV DNA became undetectable after 4 weeks therapy with Tenofovir alafenamide fumarate (TAF). Serum transaminases went down to normal 3 months later after receiving TAF. HBV reactivation is a substantial risk for patients with isolated HBcAb positive receiving rituximab-containing chemotherapy without anti- HBV drug. Regular monitoring with a frequency of 1-3 months is the basis for timely diagnosis and treatment of HBV reactivation. Serum transaminases abnormalities may be the initial manifestation of HBV reactivation.
Patients with resolved hepatitis B virus (HBV) infection, i.e., hepatitis B surface antigen (HBsAg)-negative/antihepatitis B core antigen (anti-HBc)-positive, undergoing rituximab (RTX)-based ...chemotherapy for hematological malignancies without anti-HBV prophylaxis are at risk of HBV reactivation, but the risk in such patients receiving RTX for rheumatological disorders is not clear. We evaluated this risk in HBsAg-negative/anti-HBc-positive patients with rheumatoid arthritis (RA) undergoing RTX without prophylaxis.
Thirty-three HBsAg-negative/anti-HBc-positive outpatients with RA with undetectable HBV DNA by sensitive PCR assay 73% women, median age 60 years, 85% with HBsAg antibodies (anti-HBs), 37% with antihepatitis B envelope antigen received a median of 3 cycles of RTX (range 1-8) over 34 months (range 0-80) combined with disease-modifying antirheumatic drugs (DMARD) without prophylaxis. All underwent clinical and laboratory monitoring during and after RTX administration, including serum HBsAg and HBV DNA measurements every 6 months or whenever clinically indicated.
None of the patients seroreverted to HBsAg during RTX treatment, but 6/28 (21%) showed a > 50% decrease in protective anti-HBs levels, including 2 who became anti-HBs-negative. One patient (3%) who became HBV DNA-positive (44 IU/ml) after 6 months of RTX treatment was effectively rescued with lamivudine before any hepatitis flare occurred. Among the 14 patients monitored for 18 months (range 0-70) after RTX discontinuation, no HBV reactivation was observed.
The administration of RTX + DMARD in patients with RA with resolved HBV infection leads to a negligible risk of HBV reactivation, thus suggesting that serum HBsAg and/or HBV DNA monitoring but not universal anti-HBV prophylaxis is justified.
Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, ...especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. 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(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBs Ag-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.
Hepatitis B virus reactivation (HBV-R) is a serious complication that can occur in patients with resolved HBV infection during cancer chemotherapy. We examined the levels of HBV surface antibody ...(HBsAb) and HBV core antibody (HBcAb) to assess the incidence of HBV-R in cancer patients including hematopoietic stem cell transplantation (HSCT) and rituximab administration. This retrospective cohort study included 590 patients with resolved HBV infection. The incidence of HBV-R was evaluated 761.5 (range, 90–3898) days after the inititiation of chemotherapy. Of the patients, 13 (2.2%) developed HBV-R after the start of chemotherapy. All 13 patients exhibited lower HBsAb (<100 mIU/mL) levels at baseline. A higher level of HBcAb (≥100 cut off index (C.O.I.)) was a possible risk factor for HBV-R as well as HSCT and rituximab administration. The simultaneous presence of HBsAb <100 mIU/mL and HBcAb ≥100 C.O.I. increased the risk of HBV-R by 18.5%. Patients treated with rituximab were at a higher risk of HBV-R (18.4%) despite having HBcAb <100 C.O.I. Our results suggest that assessment of HBsAb and HBcAb levels prior to the chemotherapy is important for identifying patients at high risk of HBV-R, especially in solid cancers without HSCT and rituximab administration.
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