Extremely high titer of hepatitis B surface antigen antibodies in a primary hepatocellular carcinoma patient:A case report

BACKGROUND Hepatocellular carcinoma(HCC)may be caused by hepatitis B virus(HBV)infection.Post-infection recovery-associated changes of HBV indicators include decreased hepatitis B surface antigen(HBsAg)level and increased anti-HBsAg antibody titer.Testing to detect HBV DNA is conducted rarely but could detect latent HBV infection persisting after acute infection and prompt administration of treatments to clear HBV and prevent subsequent HBV-induced HCC deve-lopment.Here,we present an HCC case with an extremely high anti-HBsAg antibody titer and latent HBV infection.CASE SUMMARY A 57-year-old male patient with abdominal pain who was diagnosed with primary HCC presented with an extremely high level(over 2000 ng/mL)of serum alpha-fetoprotein.Abdominal B-ultrasonography and computed tomography scan results indicated focal liver lesion and mild splenomegaly.Assessments of serological markers revealed a high titer of antibodies against hepatitis B core antigen(anti-HBcAg antibodies),an extremely high titer(1000 mIU/mL)of hepatitis B surface antibodies(anti-HBsAg antibodies,anti-HBs)and absence of detectible HBsAg.Medical records indicated that the patient had reported no history of HBV vaccination,infection or hepatitis.Therefore,to rule out latent HBV infection in this patient,a serum sample was collected then tested to detect HBV DNA,yielding a positive result.Based on the aforementioned information,the final diagnosis was HCC associated with hepatitis B in a compensated stage of liver dysfunction and the patient was hospitalized for surgical treatment.CONCLUSION A rare HCC case with high serum anti-HBsAg antibody titer and detectable HBV DNA resulted from untreated latent HBV infection.

Mutations in surface and polymerase gene of chronic hepatitis B patients with coexisting HBsAg and anti-HBs

AIM： To investigate the clinical significance and presence of mutations in the surface （S） and overlapping polymerase gene of hepatitis B patients with coexisting HBsAg and anti-HBs. METHODS： Twenty-three patients with chronic hepatitis B were studied. Of the 23 patients, i i were both positive for hepatitis B virus （HBV） surface antigen （HBsAg） and antibody to HBV surface antigen （anti-HBs）, 12 were negative for anti-HBs while positive for HBsAg. DNA was extracted from 200 μL serum of the patients. Nucleotide of the surface and overlapping polymerase gene from HBV-infected patients was amplified by PCR, and the PCR products were sequenced. RESULTS： Forty-one mutations were found within the surface gene protein of HBV in 15 patients （10 with coexisting HBsAg and anti-HBs）. Six （14.6%） out of 41 mutations were located at ＂α＂ determinant region in 5 patients （4 positive for HBsAg and anti-HBs）. Eleven mutations （26.8%） occurred in the downstream or upstream of ＂α＂ determinant region. Lamivudine （LMV）- selected mutations were found in three patients who developed anti-HBs, which occurred in amino acid positions （196, 198, 199） of the surface protein and in YMDD motif （M204I/V） of the polymerase protein simultaneously. Presence of these mutations did not relate to changes in ALT and HBV DNA levels.CONCLUSION： Besides mutations in the ＂α＂ determinant region, mutations at downstream or upstream of the ＂α＂ determinant region may contribute to the development of anti-HBs. These mutations do not block the replicating competency of HBV in the presence of high titer of anti-HBs.

Antibody prevalence and immunotherapy response in Chinese patients with epilepsy and encephalopathy scores for patients with different neuronal surface antibodies

Background:The scale assessment was helpful in predicting the presence of antibodies to autoimmune encephalitis.This study aimed to evaluate the application of antibody prevalence in Chinese patients with epilepsy and encephalopathy(APE2-CHN)and response to immunotherapy in Chinese patients with epilepsy and encephalopathy(RITE2-CHN)for patients with different neuronal surface antibodies.Methods:A total of 1365 patients with epileptic seizures as the prominent feature in Xuanwu Hospital,Capital Medical University,from June 2016 to June 2020 were enrolled in our study.Of these,915 patients with epilepsy of unknown etiology whose serum and/or cerebrospinal fluid samples were examined for autoimmune antibodies were selected.All patients were scored with antibody prevalence in patients with epilepsy and encephalopathy(APE2),response to immunotherapy with epilepsy and encephalopathy(RITE2),APE2-CHN,and RITE2-CHN scores.Results:Of the 915 patients,191 patients were positive for neural-surface specific antibodies(115 N-methyl-D-aspartate receptor(NMDAR)Ab,47 leucine-rich glioma-inactivated protein 1(LGI1)Ab,8 contactin-associated protein 2(CASPR2)Ab,4 AMPA2RAb,and 11 GABAR-B-Ab;3 CASPR2-Ab and LGI1-Ab,2 NMDAR-Ab and CASPR2-Ab,and 1 NMDAR-Ab and myelinoligodendrocyte glycoprotein[MOG]Ab).The sensitivity and specificity of APE2≥4 in predicting the presence of neural-surface specific antibodies in our study were 74.35%and 81.77%,respectively,and the sensitivity and specificity of APE2-CHN≥4 were 75.92%and 84.53%,respectively.Eight cases had an APE2 score<4 and APE2-CHN score≥5;all these patients had memory decline as the prominent manifestation.We divided the patients into six groups according to the different antibodies.APE2-CHN scores showed higher sensitivity for the prediction of NMDAR-Ab,but lower sensitivity for LGI1-Ab.A total of 187/191(97.91%)patients received immunotherapy and 142/191(74.35%)patients benefited from the treatments.The patients who were positive for LGI1-Ab with RITE2-CHN≥8 responded well to immunotherapy.Conclusions:APE2-CHN had the highest value for predicting the positivity of NMDAR-Ab and RITE2-CHN evaluated the response of immunotherapy for anti-LGI1 encephalitis appropriately.However,RITE2 and RITE2-CHN do not appear to be good predictors of immunotherapy outcomes for patients with specific neuronal-surface antibodies and high APE2-CHN scores are often indicative of a poor response to immunotherapy.

Risk factors for de novo hepatitis B during solid cancer treatment

BACKGROUND Reactivation of hepatitis B virus(HBV)during anticancer treatment is a critical issue.When treating patients with solid tumors,it is unclear whether specific cancer types or treatments affect HBV reactivation in hepatitis B surface antigen(HBsAg)-negative and hepatitis B core antibody(HBcAb)-positive patients,socalled de novo hepatitis B patients.The risk of de novo hepatitis B may vary based on different background factors.AIM To determine the frequency and risk factors for de novo hepatitis B during solid tumor treatment.METHODS This retrospective cohort study comprised 1040 patients without HBsAgs and with HBcAbs and/or hepatitis B surface antibodies(HBsAbs).The patients were treated for solid cancer from 2008 to 2018 at the National Kyushu Cancer Center and underwent HBV DNA measurements.Patient characteristics and disease and treatment information were investigated.HBV DNA measurements were performed using TaqMan polymerase chain reaction(PCR).To identify the risk factors associated with HBV DNA expression,the age,sex,original disease,pathology,treatment method,presence or absence of hepatitis C virus(HCV),and HBsAb and/or HBcAb titers of all subjects were investigated.In patients with HBV DNA,the time of appearance,presence of HBsAgs and HBsAbs at the time of appearance,and course of the subsequent fluctuations in virus levels were also investigated.RESULTS Among the 1040 patients,938 were HBcAb positive,and 102 were HBcAb negative and HBsAb positive.HBV DNA expression was observed before the onset of treatment in nine patients(0.9%)and after treatment in 35 patients(3.7%),all of whom were HBcAb positive.The HBV reactivation group showed significantly higher median HBcAb values[9.00(8.12-9.89)vs 7.22(7.02-7.43),P=0.0001]and significantly lower HBsAb values(14 vs 46,P=0.0342)than the group without reactivation.Notably,the reactivated group showed a significantly higher proportion of cancers in organs related to digestion and absorption(79.0%vs 58.7%,P=0.0051).A high HBcAb titer and cancers in organs involved in digestion and absorption were identified as independent factors for HBV reactivation(multivariate analysis,P=0.0002 and P=0.0095).The group without HBsAbs tended to have a shorter time to reactivation(day 43 vs day 193),and the frequency of reactivation within 6 mo was significantly higher in this group(P=0.0459)than in the other group.CONCLUSION A high HBcAb titer and cancers in organs involved in digestion and absorption are independent factors that contribute to HBV reactivation during solid tumor treatment.

Chronic hepatitis B:New potential therapeutic drugs target

liverrelated morbidity and mortality worldwide.It impacts nearly 300 million people.The current treatment for chronic infection with the hepatitis B virus(HBV)is complex and lacks a durable treatment response,especially hepatitis B surface antigen(HBsAg)loss,necessitating indefinite treatment in most CHB patients due to the persistence of HBV covalently closed circular DNA(cccDNA).New drugs that target distinct steps of the HBV life cycle have been investigated,which comprise inhibiting the entry of HBV into hepatocytes,disrupting or silencing HBV cccDNA,modulating nucleocapsid assembly,interfering HBV transcription,and inhibiting HBsAg release.The achievement of a functional cure or sustained HBsAg loss in CHB patients represents the following approach towards HBV eradication.This review will explore the up-to-date advances in the development of new direct-acting anti-HBV drugs.Hopefully,with the combination of the current antiviral drugs and the newly developed direct-acting antiviral drugs targeting the different steps of the HBV life cycle,the ultimate eradication of CHB infection will soon be achieved.

Vaccination Coverage and the Risk of Hepatitis B Virus Infection amongst Medical and Paramedical Students Practicing at the Bamenda Regional Hospital in Cameroon Sub-Saharan Africa

Introduction: The endemic nature of hepatitis B virus (HBV) in Sub-Saharan Africa is a significant public health problem that places health care providers (medical students inclusive) at increased risk of occupational exposure. However, vaccination against HBV is not systematic among medical students in Cameroon. Thus, we sought to evaluate awareness and HBV vaccine coverage amongst medical students in Cameroon. Aim: The present study was aimed at determining the proportion of Medical and Paramedical students on internship at the Bamenda Regional Hospital (BRH) who are vaccinated and immune to hepatitis B virus (HBV). Methods: This was a hospital-based cross sectional study carried out at the BRH in Cameroon. Questionnaires were administered to 120 participants who signed an informed consent form and venous blood samples collected in dry tubes for the HBV-5 PANEL test. Data were collected within a period of two weeks. HBV vaccine status was defined as complete (3 doses), partial (1 or 2 doses), and unvaccinated. Results: Of 120 participants (87 females and 33 males), 56 (46.7%) were vaccinated at least once against HBV;15 (12.5%) were partially vaccinated and 41 (34.2%) completely vaccinated. Out of the 56 vaccinated individuals, only 13 (23.2%) were confirmed immunized against HBV by testing positive for hepatitis B surface antibodies. Only 3 (5.4%) students had done post-vaccination serologic test to confirm their immunized status. There was high exposure to potentially infected body fluids like blood (97.5%) and urine (87.5%). There was equally poor practice of adequate preventive measures like regular hand washing and the proper use of personal protective equipment. A prevalence of 3.1% of HBV amongst the unvaccinated group was recorded. Conclusion: Only 1 in 3 medical students had completed the HBV vaccination series and only 26.8% of this cohort was confirmed immunized against HBV. This highlights the need for improved health policies aimed at increasing access and coverage of HBV immunization in high risk groups such as health workers.

B cell dysfunction in chronic hepatitis B virus infection

Chronic hepatitis B(CHB)remains a global health problem.The persistence of hepatitis B surface antigen(HBsAg)in the blood for longer than 6 months after the initial infection is a sign of CHB.The therapeutic goal for the functional cure of CHB is the generation of antibodies against HBsAg.However,the adaptive immune response of patients with CHB cannot generate an efficient antiviral response.Many previous studies have evaluated T cell function and T cell therapy specifically designed to counter hepatitis B virus(HBV)infection.As one of the major components of adaptive immunity,B cells also display dysfunctions in anti-HBsAg antibody(HBsAb)production and antigen presentation.Patients with CHB have amplification of CD19^(+)CD10^(-)CD27^(-)CD21^(-)atypical memory B cell subsets and CD19^(+)CD24^(hi)CD38^(hi) regulatory B cells.Currently,no reviews have summarized specific B cell responses during CHB infection.Thus,in this study,we summarized B cell dysfunction during CHB progression and the potential mechanisms behind these dysfunctions to further our understanding of the mechanisms of adaptive immune response of B cells in the process of CHB development and help provide new methods and ideas for the treatment of CHB.