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 rituximab-containing 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 (HBsAg) and antibody to hepatitis B core antigen (anti-HBc). Patients found to be positive for HBsAg 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 high-risk 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 HBsAg-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.
Aminoleban EN is safe to administer and does not have significant adverse effects. It contributes to a shorter hospital stay and quicker improvement of liver function in the early postoperative period. These beneficial results require only a 12-week period of administration of BCAA after operation.
The distal end of mouse chromosome 7 (Chr 7) contains a large cluster of imprinted genes. In this region two cis-acting imprinting centers, IC1 (H19 DMR) and IC2 (KvDMR1), define proximal and distal subdomains, respectively. To assess the functional independence of IC1 in the context of Chr 7, we developed a recombinase-mediated chromosome truncation strategy in embryonic stem cells and generated a terminal deletion allele, DelTel7, with a breakpoint in between the two subdomains. We obtained germ line transmission of the truncated Chr 7 and viable paternal heterozygotes, confirming the absence of developmentally required paternally expressed genes distal of Ins2. Conversely, maternal transmission of DelTel7 causes a midgestational lethality, consistent with loss of maternally expressed genes in the IC2 subdomain. Expression and DNA methylation analyses on DelTel7 heterozygotes demonstrate the independent imprinting of IC1 in absence of the entire IC2 subdomain. The evolutionarily conserved linkage between the subdomains is therefore not required for IC1 imprinting on Chr 7. Importantly, the developmental phenotype of maternal heterozygotes is rescued fully by a paternally inherited deletion of IC2. Thus, all the imprinted genes located in the region and required for normal development are silenced by an IC2-dependent mechanism on the paternal allele.The 1-Mb imprinted domain on distal chromosome 7 (Chr 7) shares syntenic homology to the Beckwith-Wiedemann syndrome (BWS) region on human Chr 11p15.5 (69). Located less than 3 Mb from the telomere (Tel7q), this region contains two imprinting centers, IC1 and IC2. These conserved imprinting control elements are cis-acting sequences which carry opposite germ line DNA methylation marks and regulate the monoallelic expression of different flanking genes (9). In the proximal part of the Chr 7 domain, IC1 is located 2 kb upstream of the H19 promoter (Fig. 1A) (66). This sequence acquires a paternal DNA methylation imprint established during spermatogenesis and maintained throughout development (4,24,67). The methylated IC1 is required to initiate silencing of the paternal H19 allele (65), whereas the maternal IC1 controls the paternally expressed genes Igf2 and Ins2 via a methylation-sensitive insulator (6, 35). Distally, IC2 is located in intron 10 of Kcnq1 (Fig. 1A). This sequence is marked by a maternal DNA methylation imprint acquired during oogenesis (19). The unmethylated paternal IC2 is associated with the production of the Kcnq1ot1 noncoding RNA (ncRNA) and the silencing in cis of several genes in this subdomain (26). Consequently, these protein-coding genes are imprinted and expressed preferentially from the maternal Chr 7 homologue (62). These maternally expressed genes (MEGs) include transcripts expressed in the placenta and required for embryonic development, such as Ascl2 (31, 32), Cdkn1c (36), and Phlda2 (58). As in the case of IC1, IC2 appears to carry different allele-specific functions, such as promoter, enhancer, and CTCF binding insulator activities (2...
The outbreak of coronavirus disease 2019 (COVID-19) is a global pandemic. Many clinical trials have been performed to investigate potential treatments or vaccines for this disease to reduce the high morbidity and mortality. The drugs of higher interest include umifenovir, bromhexine, remdesivir, lopinavir/ritonavir, steroid, tocilizumab, interferon alpha or beta, ribavirin, fivapiravir, nitazoxanide, ivermectin, molnupiravir, hydroxychloroquine/chloroquine alone or in combination with azithromycin, and baricitinib. Gastrointestinal (GI) symptoms and liver dysfunction are frequently seen in patients with COVID-19, which can make it difficult to differentiate disease manifestations from treatment adverse effects. GI symptoms of COVID-19 include anorexia, dyspepsia, nausea, vomiting, diarrhea and abdominal pain. Liver injury can be a result of systemic inflammation or cytokine storm, or due to the adverse drug effects in patients who have been receiving different treatments. Regular monitoring of liver function should be performed. COVID-19 vaccines have been rapidly developed with different technologies including mRNA, viral vectors, inactivated viruses, recombinant DNA, protein subunits and live attenuated viruses. Patients with chronic liver disease or inflammatory bowel disease and liver transplant recipients are encouraged to receive vaccination as the benefits outweigh the risks. Vaccination against COVID-19 is also recommended to family members and healthcare professionals caring for these patients to reduce exposure to the severe acute respiratory syndrome coronavirus 2 virus.
Objective Patients with resolved hepatitis B virus (HBV) infection are at risk of HBV reactivation during treatment for hematological malignancies. We conducted a systematic review and meta‐analysis of the data on the efficacy of antiviral prophylaxis for the prevention of HBV reactivation in this group of patients. Methods We conducted a systemic literature search of PubMed including MEDLINE and EMBASE databases to 31 January 2019 to identify studies published in English comparing antiviral prophylaxis with no prophylaxis for HBV reactivation in patients treated for hematological malignancies. The search terms used were (“occult hepatitis B” OR “resolved hepatitis B”) AND (“reactivation”) AND (“haematological malignancy” OR “hematological malignancy” OR “chemotherapy” OR “immunotherapy” OR “chemoimmunotherapy” OR “lymphoma” OR “leukemia” OR “transplant”). The primary outcome was the reactivation of HBV infection. Pooled estimates of relative risk (RR) were calculated. Results We identified 13 relevant studies including two randomized controlled trials (RCT), one post hoc analysis from RCT and 10 cohort studies. There was a trend towards a lower rate of HBV reactivation using antiviral prophylaxis, but the difference was not significant (RR 0.57, 95% confidence interval [CI] 0.23–1.40, P = 0.22). When limiting the analysis to the three prospective studies of patients receiving anti‐CD20 monoclonal antibodies, we found antiviral prophylaxis was associated with a significantly lower risk of HBV reactivation (RR 0.17, 95% CI 0.06–0.49, P = 0.001). Conclusion Antiviral prophylaxis reduced the risk of HBV reactivation in patients receiving anti‐CD20 monoclonal antibodies for hematological malignancies but not in a broader group of patients receiving anticancer therapy.
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