Hepatitis B Virus Reactivation upon Immunosuppression: Is There a Role for Hepatitis B Core-Related Antigen in Patients with Immune-Escape Mutants? A Case Report

The reactivation of hepatitis B virus (HBVr) in patients undergoing pharmacological immunosuppression is a potentially fatal clinical event that may occur in patients with overt or occult HBV infection. The risk of HBVr is mainly determined by the type of immunosuppressive therapy and the HBV serologic profile, with a higher risk in patients positive for the hepatitis B surface antigen (HBsAg), and a lower risk in HBsAg-negative/antibodies to core antigen-positive subjects. Notably, a considerable proportion of patients experiencing HBVr showed a high degree of variability of the HBV S gene, possibly leading to immune escape mutants. These mutations, usually in the “a-determinant” of the HBsAg, can cause diagnostic problems and consequently hamper the appropriate management strategy of patients at risk of HBVr. Here, we describe a case of HBVr in a patient with a diagnosis of chronic myeloid leukemia and a previous history of kidney transplant, providing evidence of the potential usefulness of hepatitis B core-related antigen measurement in patients with HBV immune-escape mutants at risk of viral reactivation.

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The association between hepatitis B virus mutations and the risk of liver disease and hepatocellular carcinoma

Current Molecular Medicine ◽

10.2174/1566524021666210816094412 ◽

2021 ◽

Vol 21 ◽

Author(s):

Hassan Akrami ◽

Mohammad Rafiee Monjezi ◽

Shahrzad Ilbeigi ◽

Farshid Amiri ◽

Mohammad Reza Fattahi

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Disease ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Immune Escape ◽

Vaccine Failure ◽

Occult Hbv Infection ◽

Occult Hbv ◽

B Virus ◽

The World

: Hepatitis B virus [HBV], the best-described hepadnavirus, distributed all around the world and may lead to chronic and acute liver disease, cirrhosis, and hepatocellular carcinoma. Despite the advancement in treatment against HBV, an error-prone reverse transcriptase which is require for HBV replication as well as host immune pressure lead to constant evolution and emergence of genotypes, sub-genotypes and mutant viruses; so, HBV will be remained as a major healthcare problem around the world. This review article mainly focuses on the HBV mutations which correlated to occult HBV infection, Immune scape, vaccine failure and eventually liver cirrhosis and HCC. Current study indicated that preS/S region mutations are related to vaccine failure, immune escape, occult HBV infection and the occurrence of HCC. Whereas, P region Mutations may lead to drug resistance to NA antivirals. PreC/C region mutations are associated to HBeAg negativity, immune escape, and persistent hepatitis. Moreover, X region Mutations play an important role in HCC development.

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Detection of hepatitis B virus isolates with mutations associated with immune escape mutants among pregnant women in Ibadan, southwestern Nigeria

SpringerPlus ◽

10.1186/s40064-015-0813-1 ◽

2015 ◽

Vol 4 (1) ◽

Cited By ~ 9

Author(s):

Temitope Oluwasegun Cephas Faleye ◽

Moses Olubusuyi Adewumi ◽

Ijeoma Maryjoy Ifeorah ◽

Ewean Chukwuma Omoruyi ◽

Solomon Adeleye Bakarey ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Pregnant Women ◽

Immune Escape ◽

Southwestern Nigeria ◽

B Virus ◽

Escape Mutants ◽

Virus Isolates

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Impaired Virion Secretion by Hepatitis B Virus Immune Escape Mutants and Its Rescue by Wild-Type Envelope Proteins or a Second-Site Mutation

Journal of Virology ◽

10.1128/jvi.02701-12 ◽

2012 ◽

Vol 87 (4) ◽

pp. 2352-2357 ◽

Cited By ~ 36

Author(s):

K. Kwei ◽

X. Tang ◽

A. S. Lok ◽

C. Sureau ◽

T. Garcia ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Immune Escape ◽

Envelope Proteins ◽

Wild Type ◽

Site Mutation ◽

B Virus ◽

Escape Mutants

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Detection and circulation of hepatitis B virus immune escape mutants among asymptomatic community dwellers in Ibadan, southwestern Nigeria

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2015.08.008 ◽

2015 ◽

Vol 39 ◽

pp. 102-109 ◽

Cited By ~ 4

Author(s):

Temitope Oluwasegun Cephas Faleye ◽

Olubusuyi Moses Adewumi ◽

Ijeoma Maryjoy Ifeorah ◽

Adegboyega Akere ◽

Adeleye Solomon Bakarey ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Immune Escape ◽

Southwestern Nigeria ◽

B Virus ◽

Escape Mutants ◽

Community Dwellers

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Molecular Analysis of Immune-Escape Mutants of Hepatitis B Virus from Local Clinical Samples

Microbiology Indonesia ◽

10.5454/mi.6.1.2 ◽

2012 ◽

Vol 6 (1) ◽

pp. 9-14 ◽

Cited By ~ 2

Author(s):

CHANDRA JINATA ◽

ERNAWATI ARIFIN GIRI-RACHMAN ◽

DEBBIE SOEFIE RETNONINGRUM

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Molecular Analysis ◽

Immune Escape ◽

Clinical Samples ◽

B Virus ◽

Escape Mutants

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Hepatitis B Virus (HBV) Reactivation Following Pharmacological Eradication of Hepatitis C Virus (HCV)

Viruses ◽

10.3390/v11090850 ◽

2019 ◽

Vol 11 (9) ◽

pp. 850 ◽

Cited By ~ 1

Author(s):

Mariantonietta Pisaturo ◽

Margherita Macera ◽

Loredana Alessio ◽

Federica Calò ◽

Nicola Coppola

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Hbv Infection ◽

Clinical Event ◽

Hbv Reactivation ◽

Occult Hbv Infection ◽

Occult Hbv ◽

B Virus

The US Food and Drug Administration issued a black box warning related to the risk of reactivation of overt/occult hepatitis B virus (HBV) infection during direct acting-antivirals (DAA) treatment. This review evaluated the prevalence of HBV reactivation after hepatitis C virus (HCV) pharmacological suppression and hypothesized the management and prevention of this reactivation. During and after DAA-based treatment, reactivation of HBV infection is common in patients with detectable serum HBsAg (from 2% to 57%) and very low (less than 3%) in individuals with isolated anti-HBc antibodies. The severity of hepatic damage may range from HBV reactivation without hepatitis to fulminant hepatic failure requiring liver transplantation. Thus, HBsAg-positive patients should receive nucleo(s)tide analog (NA) treatment or prophylaxis at the same time as DAA therapy. For those patients with occult B infection, there are no sufficient recommendations to start prophylactic treatment. Reactivation of overt or occult HBV infection during or after eradication of HCV infection is an issue to consider, and additional studies would help to determine the best management of this virological and clinical event.

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Hepatitis B Virus Reactivation in Malignant Lymphoma with Occult HBV Carrier.

Blood ◽

10.1182/blood.v114.22.4794.4794 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4794-4794

Author(s):

Noriyasu Fukushima ◽

Toshihiko Mizuta ◽

Chisako Urata ◽

Mariko Tanaka ◽

Masako Yokoo ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Liver Function ◽

Malignant Lymphoma ◽

Prospective Studies ◽

Hbv Dna ◽

Core Antigen ◽

Hbv Reactivation ◽

Occult Hbv ◽

B Virus

Abstract Abstract 4794 Background In surface antigen of hepatitis B virus (HBsAg)-positive carrier for anticancer treatment of malignant lymphoma, it is well recognized that reactivation of hepatitis B virus (HBV) occasionally occurs. However, there have been only a few studies of HBV reactivation in serum HBsAg-negative and hepatitis B core antigen (HBcAb)-positive occult HBV carriers. We looked at both retrospective and prospective studies to determine the prevalence, clinical course and risk factor of HBV reactivation during chemotherapy in lymphoma patients. Patients and methods Forty-nine of 128 (38.3%) lymphoma patients were HBsAg negative and HBcAb positive, and 25 of these patients were then given liver function tests and HBsAg tests monthly and serum HBV DNA every 3 months. Results HBV reactivation was observed in two patients (4.0%) who had received intensive chemotherapy including steroid and rituximab. Immediate administration of entecavir therapy after elevation of HBV DNA level was conducted, and this resulted in reduction of it and improvement of liver function test. Conclusions Rituximab plus steroid-containing regimens may increase the risk of HBV reactivation in HBsAgnegative and HBcAb-positive lymphoma patients. More ambitious prospective studies are required to establish clinically useful or cost-effective follow-up methods for control of HBV reactivation in lymphoma patients with occult HBV infection. Disclosures: No relevant conflicts of interest to declare.

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Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan

PeerJ ◽

10.7717/peerj.6583 ◽

2019 ◽

Vol 7 ◽

pp. e6583 ◽

Cited By ~ 4

Author(s):

Nidaa A. Ababneh ◽

Malik Sallam ◽

Doaa Kaddomi ◽

Abdelrahman M. Attili ◽

Isam Bsisu ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Reverse Transcriptase ◽

Mutation Analysis ◽

Phylogenetic Analyses ◽

Public Health Problem ◽

University Hospital ◽

Considerable Proportion ◽

B Virus ◽

Escape Mutants

Background Hepatitis B virus (HBV) is an important infectious cause of morbidity and mortality in Jordan. HBV genotype D is the most prevalent in the country. Virus escape mutants in the HBV S region is an important public health problem halting preventive efforts. The aim of the current study was to investigate patterns of HBV escape and resistance mutations and to assess domestic transmission of the virus. Methods Patients infected with HBV were recruited at Jordan University Hospital (n = 56) and were diagnosed during (1984–2012). A total of 37 partial HBV S sequences were generated using Sanger’s method. Mutation analysis was done using the HIV grade HBV drug resistance interpretation online tool and Geno2pheno (HBV) online tools. Domestic transmission of HBV was assessed using maximum likelihood phylogenetic inference with similar GenBank sequences. Results Genotyping revealed an exclusive presence of sub-genotype D1. Typical HBV escape mutants were identified in seven patients. These mutations included: L109R, Q129R, M133L, S143L and D144E with overall prevalence of 18.9% (95% CI [9.5–34.2]). Reverse transcriptase (RT) sequence analysis showed mutations in three patients with overall prevalence of 8.1% (95% CI [2.8–21.3]). RT mutations included: V173L, S202I, L180M, M204V and T184A. Transmission cluster analysis revealed a relatively high proportion of infections taking place as a result of domestic spread (29.7%). Conclusions Based on our findings, RT mutation analysis appears to be of high value before the initiation of therapy in patients with chronic HBV infection in Jordan. Phylogenetic analyses revealed a considerable proportion of local spread in the country which should be considered in the preventive infection control efforts.

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