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 prophy-lactic 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 antivi-ral 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.

Transfusion-transmitted hepatitis E:What we know so far?

Hepatitis E virus(HEV)is a major cause of viral hepatitis globally.There is growing concern about transfusion-transmitted HEV(TT-HEV)as an emerging global health problem.HEV can potentially result in chronic infection in immunocompromised patients,leading to a higher risk of liver cirrhosis and even death.Between 0.0013%and 0.281%of asymptomatic blood donors around the world have HEV viremia,and 0.27%to 60.5%have anti-HEV immunoglobulin G.HEV is infectious even at very low blood concentrations of the virus.Immunosuppressed patients who develop persistent hepatitis E infection should have their immunosuppressant regimen reduced;ribavirin may be considered as treatment.Pegylated interferon can be considered in those who are refractory or intolerant to ribavirin.Sofosbuvir,a nucleotide analog,showed modest antiviral activity in some clinical studies but sustained viral response was not achieved.Therefore,rescue treatment remains an unmet need.The need for HEV screening of all blood donations remains controversial.Universal screening has been adopted in some countries after consideration of risk and resource availability.Various pathogen reduction methods have also been proposed to reduce the risk of TT-HEV.Future studies are needed to define the incidence of transmission through transfusion,their clinical features,outcomes and prognosis.

Gastrointestinal and hepatic side effects of potential treatment for COVID-19 and vaccination in patients with chronic liver diseases

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.

Efficacy of Vaccine Protection Against COVID-19 Virus Infection in Patients with Chronic Liver Diseases

The outbreak of coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Vaccination against coronavirus disease 2019 is a use-ful weapon to combat the virus. Patients with chronic liver diseases (CLDs), including compensated or decompensated liver cirrhosis and noncirrhotic diseases, have a decreased immunologic response to coronavirus disease 2019 vaccines. At the same time, they have increased mortality if infected. Current data show a reduction in mortality when patients with chronic liver diseases are vaccinated. A suboptimal vac-cine response has been observed in liver transplant recipi-ents, especially those receiving immunosuppressive therapy, so an early booster dose is recommended to achieve a better protective effect. Currently, there are no clinical data com-paring the protective efficacy of different vaccines in patients with chronic liver diseases. Patient preference, availability of the vaccine in the country or area, and adverse effect profiles are factors to consider when choosing a vaccine. There have been reports of immune-mediated hepatitis after coronavi-rus disease 2019 vaccination, and clinicians should be aware of that potential side effect. Most patients who developed hepatitis after vaccination responded well to treatment with prednisolone, but an alternative type of vaccine should be considered for subsequent booster doses. Further prospec-tive studies are required to investigate the duration of immu-nity and protection against different viral variants in patients with chronic liver diseases or liver transplant recipients, as well as the effect of heterologous vaccination.