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ObjectiveTo investigate the clinical value of serum creatinine-to-cystatin C ratio （CCR） in evaluating the prognosis of hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF）. MethodsA retrospective analysis was performed for the clinical data of 130 patients with HBV-ACLF （treatment group） who were hospitalized in Department of Infectious Diseases， The First Affiliated Hospital of Soochow University， from January 2021 to November 2022. According to the treatment outcome， they were divided into survival group with 87 patients and death group with 43 patients； according to the presence or absence of infection， they were divided into infection group with 37 patients and non-infection group with 93 patients. A total of 30 individuals who underwent physical examination during the same period of time were enrolled as control group. Routine blood test results were collected on the day of admission， including white blood cell count， platelet count， neutrophil count， and lymphocyte count； serum creatinine， cystatin C， serum albumin （Alb）， and prothrombin time （PT） were observed on the day of admission and on days 5， 10， and 15 of hospitalization， and related indicators were calculated， including CCR， neutrophil-to-lymphocyte ratio （NLR）， platelet-to-lymphocyte ratio （PLR）， prognostic nutritional index （PNI）， CCR5 （CCR on day 5 after admission）， ΔCCR5 （CCR on day 5 after admission minus CCR on the day of admission）， CCR10 （CCR on day 10 after admission）， ΔCCR10 （CCR on day 10 after admission minus CCR on day 5 after admission）， CCR15 （CCR on day 15 after admission）， and ΔCCR15 （CCR on day 15 after admission minus CCR on day 10 after admission）. The above indicators were compared between the survival group and the death group and between the infection group and the non-infection group. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups. The univariate and multivariate logistic regression analyses were used to investigate the influencing factors for disease prognosis； the receiver operating characteristic （ROC） curve was used to assess the value of CCR in predicting HBV-ACLF death events， and the DeLong test was used for comparison of the area under the ROC curve （AUC）. ResultsThere were significant differences in CCR， NLR， PNI， PT， and Alb at baseline between the treatment group and the healthy control group （all P<0.001）， and there were significant differences in CCR， NLR， and PT between the survival group and the death group on the day of admission （all P<0.05）. Among the 130 patients with HBV-ACLF， there were 25 in the precancerous stage， 48 in the early stage， 32 in the intermediate stage， and 25 in the advanced stage， and there were significant differences in baseline CCR， PLR， and PT between the patients in different stages of HBV-ACLF （all P<0.05）. There were significant differences in ΔCCR5 and NLR between the infection group and the non-infection group （P<0.05）， and there were significant differences in ΔCCR5， CCR10， and CCR15 between the survival group and the death group （all P<0.05）. The multivariate logistic regression analysis showed that ΔCCR5 （odds ratio ［OR］=1.175， 95% confidence interval ［CI］： 1.098 — 1.256， P<0.001）， NLR （OR=0.921， 95%CI： 0.880 — 0.964， P<0.001）， and PT （OR=0.921， 95%CI： 0.873 — 0.973， P=0.003） were independent influencing factors for the prognosis of HBV-ACLF patients. ΔCCR5 had an AUC of 0.774， a sensitivity of 0.687， and a specificity of 0.757， and the AUC of ΔCCR5+PT+NLR was 0.824， which was significantly higher than the AUC of ΔCCR5， NLR， or PT alone （all P<0.05）. ConclusionΔCCR5， NLR， and PT can reflect the condition and prognosis of patients with HBV-ACLF and are independent predictive indicators for death events in patients with HBV-ACLF. The combination ofΔCCR5， PT， and NLR has the best predictive efficiency.
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ObjectiveTo investigate the clinical features and outcomes of critically ill pregnant and parturient women with chronic hepatitis B virus （HBV） infection， and to provide clinical experience for the rescue of critically ill pregnant and parturient women and the prevention and treatment of the severe exacerbation of liver disease. MethodsA total of 41 pregnant and parturient women with chronic HBV infection who were admitted to Department of Critical Care Medicine， Nanjing Second Hospital， from March 2013 to March 2023 were enrolled in this study， and their clinical data were collected through the electronic medical record system of hospital to summarize the main causes of transfer to the intensive care unit （ICU）， the causes of death， and treatment. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The chi-square test was used for comparison of categorical data between two groups. ResultsAmong the 41 patients， 13 （31.71%） did not receive regular antenatal examination and 8 （19.51%） with a high viral load （HBV DNA ≥2×105 IU/mL） did not receive antiviral therapy. Cesarean section was the main mode of delivery in 32 patients （78.05%）； 23 patients （56.10%） had premature delivery， and 5 patients died （12.20%）. The top three causes of transfer to the ICU were liver failure， postpartum hemorrhage， and hypertensive disorders of pregnancy. Liver failure mainly occurred in late pregnancy， with hepatic encephalopathy as the most common complication （28.57%） and intrahepatic cholestasis of pregnancy as the most common comorbidity （21.43%）； among the 14 patients with liver failure， 6 （42.86%） received regular antenatal examination， and 13 （92.86%） did not receive antiviral therapy before admission. The mean length of ICU stay was 3.31±1.65 days for the patients with postpartum hemorrhage， among whom the patients with severe liver disease had coagulation disorders before delivery， which were difficult to correct after 48 hours of treatment. ConclusionPregnant and parturient women with chronic HBV infection tend to have complex conditions and a relatively high mortality rate. For pregnant and parturient women with chronic HBV infection， assessment of liver status， regular antenatal examination， and timely antiviral therapy are of vital importance to reduce severe exacerbation and mortality rate.
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Intrahepatic cholangiocarcinoma （ICC） is a type of primary liver cancer that accounts for about 10% — 15% of the total cases， and its incidence and mortality rates tend to increase significantly around the world， especially in Asian countries. At present， radical liver resection is the only possible cure for ICC， but with a fairly high postoperative recurrence rate and a poorer prognosis than hepatocellular carcinoma. Therefore， it is urgently needed to further investigate the mechanisms of the development and progression of ICC and search for more effective treatment methods. Some epidemiological data suggest that chronic hepatitis B virus infection is one of the most important predisposing factors for ICC， yet little is known about its oncogenic effects. This article summarizes the epidemiological evidence that links the two diseases and briefly elaborates on the mechanisms of the development and progression of HBV-associated ICC， so as to help to gain a better understanding of the role of HBV in the development and progression of ICC.
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Tenofovir disoproxil fumarate （TDF） is a first-line treatment for chronic hepatitis B. With increasing use worldwide， the adverse events of renal injury caused by this drug have also attracted industry attention. This article reports a 61- year-old patient with liver cancer complicated with hepatitis B virus （HBV） infection. The patient started using TDF in mid-March 2022 and developed kidney injury after 2 months of treatment， during which he received 2 courses of donafenib combined with sintilimab chemotherapy and irregular administration of diclofenac for pain relief. In this paper， Naranjo’s assessment scale was used to evaluate the drugs that may be associated with renal injury， including TDF and sintilimab， and the drugs that are suspected to be associated with renal injury are donafenib and diclofenac. The renal injury caused by TDF can be judged according to the changes in the patient’s condition， the incidence of drug-induced renal injury， clinical manifestations， occurrence time， occurrence mechanism， drug combination， and high-risk factors. The changes of serum creatinine in patients with liver cancer complicated with HBV infection after TDF should be dynamically monitored in the clinic， and the dose of antiviral drugs should be adjusted if necessary and other antiviral drugs with less impact on renal function can be selected， to provide individualized medication recommendations for tumor patients， reduce the incidence of TDF-related renal injury.
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With the rapid growth of metabolic dysfunction （MD） worldwide， there is also a gradual increase in the number of patients with chronic hepatitis B virus （HBV） infection and MD. Comorbidity with metabolic disorders such as hyperglycemia， hypertension， and dyslipidemia may increase the risk of adverse liver outcomes and cardiovascular events in patients with chronic HBV infection and affect the response to anti-HBV therapy. The standardized management of patients with chronic HBV infection and MD has become a challenge at present， and further in-depth research on the interaction between MD and HBV and targeted management strategies will help to optimize the clinical management of patients with chronic HBV infection.
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Chronic hepatitis B virus （HBV） infection is a worldwide public health issue and a leading cause of liver fibrosis， liver cirrhosis， liver failure， and primary liver cancer in China. The incidence rate of nonalcoholic fatty liver disease （NAFLD） is gradually increasing with the improvement in the living standards of people and the changes in dietary structure. Population-based studies have found that HBV infection can influence the development of NAFLD， but the mechanism remains unknown. Hepatic steatosis can also influence the expression of HBV serum pathogenic indicators， and its combination with NAFLD and other metabolic dysfunction diseases can increase the risk of liver fibrosis， liver cirrhosis， and liver cancer. Chronic HBV infection is closely associated with metabolic dysfunction， and more studies are needed in the future to better understand related mechanisms， so as to provide a theoretical foundation for clinical diagnosis and treatment.
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Hepatitis B virus （HBV） is considered a “metabolic virus” that can influence a variety of metabolic processes. There is still a lack of definite conclusion on the association between chronic HBV infection and the various types of metabolic dysfunction， and little is known about the mechanism of the association of chronic HBV infection with the diseases characterized by metabolic disorder， such as metabolic syndrome， diabetes， and metabolic associated fatty liver disease. Currently it is believed that hepatitis B x gene （HBx）， derived from HBV genome， might play an important role in mediating systemic metabolic alterations after HBV infection， and HBx influences the metabolism of carbohydrates and lipids and causes metabolic dysfunction by retgulating the expression profiles of the key proteins such as PPARγ， C/EBPα， SREBP， and FATP2. Nonalcoholic fatty liver disease （NAFLD） is the most severe manifestation of metabolic dysfunction in the liver， and since both NAFLD and HBV infection can cause liver injury， the research on the interaction between them has attracted more and more attention， with controversies requiring further exploration. Therefore， this article elaborates on the research advances in chronic HBV infection and metabolic dysfunction， so as to provide ideas for subsequent studies.
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Chronic hepatitis B virus （HBV） infection is the main cause of the disease burden of viral hepatitis worldwide， and meanwhile， due to changes in lifestyle and dietary habits， the incidence rate of metabolic associated fatty liver disease （MAFLD） is constantly increasing， making MAFLD the leading chronic liver disease around the world. Chronic HBV infection comorbid with MAFLD is becoming more and more common in clinical practice. Metabolic factors， rather than viral factors， are the main cause of chronic HBV infection comorbid with MAFLD. During disease progression， steatohepatitis and fibrosis， rather than steatosis， are the main influencing factors for the progression to liver cirrhosis and hepatocellular carcinoma. For patients with chronic HBV infection and MAFLD， integrated management of virus and metabolic factors is of great importance. This article reviews the tissues regarding the interaction， prognosis， and clinical management of chronic HBV infection and MAFLD.
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ABSTRACT Introduction: In Brazil, the blood donor screening for hepatitis B virus (HBV) includes laboratory testing for serological (HBsAg and Anti-HBc) and molecular (HBV DNA) markers. This study aims to correlate serology reactive results with HBV DNA detection among blood donors with at least one HBV infection marker detected in a blood bank in northern Brazil. Method: A retrospective search for HBV reactive blood donor data from January 2017 to December 2019 was performed. Serological screening was performed by chemiluminescent microparticle immunoassays Architect HBsAg and Architect Anti-HBc, whereas molecular screening was performed by the HBV nucleic acid test (HBV NAT). Main results: A total of 556 HBsAg reactive results were detected, between positive (47.66%) and inconclusive (52.34%). A total of 3,658 Anti-HBc reactive results were detected, between positive (83.71%) and inconclusive (16.29%). None of the inconclusive results were associated with HBV DNA detection. The HBV DNA detection rates were 47.55% among HBsAg positive samples and 4.08% among Anti-HBc positive samples. The signal-to-cutoff (S/CO) ratio median of HBV NAT positive samples was superior in comparison to HBV NAT negative samples (p < 0.0001). The thresholds found to optimize sensitivity and specificity were 404.15 for Architect HBsAg and 7.77 for Architect Anti-HBc. Three blood donors were in the window period and 1 occult HBV infection case was detected. Conclusion: High S/CO ratios were more predictive of HBV DNA detection. However, a number of HBV NAT positive samples gave low values, while some HBV NAT negative samples showed high values, reaffirming the significance of molecular testing to enhance transfusion safety.
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Background: Hepatitis B infection is common in Dialysis population. Hemodialysis patients have high risk of hepatitis B virus transmission not only due to frequent blood or blood product transmission, decreased response to Hepatitis B vaccine and length on hemodialysis but also due to their immunosuppressed state. Hepatitis B vaccination has the potential to reduce the risk of HBsAg infection in dialysis units. Effective vaccination, blood donor screening, the use of erythropoietin and the isolation of HBV carriers have successfully regulated HBV infection in hemodialysis units (1). This study aims to assess the immunity to HBV & the seroconversion of HBsAg infection in hemodialysis unit. This retrospective observational study evaluated serological markers, hepatitis B vaccination status and co morbidities which can affect the immunity levels of patients undergoing hemodialysis. The patient’s data were collected from laboratory investigations and patient record for analysis. Out of 153 CKD-5D patients on maintenance hemodialysis, 39 patients had anti HBs titer <10U/ml, 30 patients had anti HBs titer between 10-100U/ml, 38 patients had anti HBs titer between100-1000 U/ml, 21 patients had anti HBs titer >1000U/ml and 24 patients didn’t check their titer value. Hypertension was the common co morbidity followed by anaemia and diabetes mellitus.
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Background: Chronic viral hepatitis is a major global public health problem, an important cause of morbidity and mortality. We conducted this study to evaluate the behavioral risk factors of HBV infection and its association with HBsAg positivity among residents of Kaza sub-division of district Lahaul & Spiti in Himachal Pradesh. Material & Methods: The study was carried out by the Gastroenterology, Community Medicine, and Microbiology Department at Indira Gandhi Medical College Shimla at Kaza, a subdivision of Lahaul & Spiti. The cluster sampling technique was used to get the desired sample size of 4000. Forty clusters were chosen using a probability proportionate to size sampling method, and 100 research participants were added to each cluster using a simple random sampling method. The data was gathered using a pre-tested interview plan. A blood sample of 5ml from each study participant was obtained, and its HBsAg content was examined. Results: In our study, 2.7% of the interviewed respondents’ parents were positive for hepatitis B and 3.7% reported one positive family member. Injectable drug use was reported by 1.6 (68/4231). Among these users 8.8% (6/68) shared needles with other IDUs in last 12 months and 35.3% (24/68) used a common container to draw up drug solution. Sexual intercourse was reported to be experienced by 15.5 (655/4231) and 12.2% either did not disclose or were children. Out of those who ever experienced sexual/penetrative intercourse 38.3% (251/655) had reported it with someone else other than a spouse. Majority of these had two partners other than a spouse (30.3%; 76/251). Around 30% (195/655) reported of using a condom in their last intercourse. Body piercings or a tattoo from someone who doesn’t sterilize his or her equipment, including local treatment from lamas, was prevalent among 16.3% of the population (689/4231). Acupuncture was taken as a remedy for any medical condition by 9% of participants. Regression analysis also revealed that one infected family member emerged as an independent factor associated with HBsAg positive test after adjusting for confounders. Conclusion: Our study provided much important information concerning hepatitis B risk factors in this tribal group. Health education about behavioral risk factors among this tribal population should be the main intervention that might help limit the spread of these blood-borne infections.
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Objetivo: A pesquisa visa determinar o perfil bioquímico e sorológico das hepatites B e C em internos de um centro de recuperação, Ananindeua, Pará, Brasil. Métodos: Estudo transversal, descritivo e quantitativo, desenvolvido entre 2015 e 2018. Os dados foram coletados com o uso de Ficha de Inquérito e entrevista. Os participantes foram submetidos à coleta de sangue para realização de testes sorológicos para as hepatites virais B e C e bioquímicos. Resultados: Participaram 125 internos, com frequência de 97,6% para o sexo masculino, prevalecendo a faixa etária de 31 a 40 anos (38,4%). Os marcadores bioquímicos que mais sofreram alterações: ácido úrico, alanina aminotransferase e lipoproteína de alta densidade. O HBsAg não foi detectado, porém houve detecção de anti-HBc total reagente isolado em 1,6% dos indivíduos. Em 20,8% pode-se observar resposta vacinal contra o vírus da hepatite B. A pesquisa detectou prevalência de 3,2% de anti-VHC reagente. Conclusão: É baixa prevalência da infecção pelos vírus das hepatites B e C, apesar dessa população ser considerada de elevado risco para a transmissão desses vírus, os examinados na sua maioria referiu utilizar apenas drogas inaláveis. A baixa cobertura vacinal encontrada entre os examinados demonstrou a vulnerabilidade em adquirir a hepatite B e a importância de estudos entre usuários de drogas no Pará. (AU)
Objective: The research aims to determine the biochemical and serological profile of hepatitis B and C in inmates of a recovery center, Ananindeua, Pará, Brazil. Methods: Cross-sectional, descriptive and quantitative study, developed between 2015 and 2018. Data were collected using an Inquiry Form and an interview. Participants underwent blood collection to perform serological tests for viral hepatitis B and C and biochemicals. Results: 125 inmates participated, with a frequency of 97.6% for males, with the age group of 31 to 40 years old prevailing (38.4%). The biochemical markers that suffered the most changes: uric acid, Alanine aminotransferase and High density lipoprotein. HBsAg was not detected, but total anti-HBc reagent isolated was detected in 1.6% of individuals. In 20.8%, a vaccine response against the hepatitis B virus can be observed. The survey found a 3.2% prevalence of anti-HCV reagent. Conclusion: The prevalence of infection by the hepatitis B and C viruses is low, although this population is considered to be at high risk for the transmission of these viruses, the majority of those examined reported using only inhalable drugs. The low vaccination coverage found among those examined demonstrated the vulnerability to acquire hepatitis B and the importance of studies among drug users in Pará. (AU)
Objetivo: La investigación tiene como objetivo determinar el perfil bioquímico y serológico de la hepatitis B y C en los reclusos de un centro de recuperación, Ananindeua, Pará, Brasil. Métodos: Estudio transversal, descriptivo y cuantitativo, desarrollado entre 2015 y 2018. Los datos se recopilaron mediante el Formulario de encuesta y la entrevista. Los participantes se sometieron a extracción de sangre para pruebas serológicas de hepatitis viral B y C y bioquímicos. Resultados: Participaron 125 reclusos, con una frecuencia del 97,6% para los hombres, prevaleciendo el grupo de edad de 31 a 40 años (38,4%). Los marcadores bioquímicos que sufrieron más cambios: ácido úrico, Alanina aminotransferasa y Lipoproteínas de alta densidad. No se detectó HBsAg, pero se detectó el reactivo anti-HBc total aislado en el 1,6% de los individuos. En 20.8%, se puede observar una respuesta de vacuna contra el virus de la hepatitis B. La encuesta encontró una prevalencia del 3.2% Del reactivo anti-VHC. Conclusiones: La prevalencia de infección por los virus de la hepatitis B y C es baja, aunque se considera que esta población tiene un alto riesgo de transmisión de estos virus, la mayoría de los examinados informaron que usaban solo medicamentos inhalables. La baja cobertura de vacunación encontrada entre los examinados demostró la vulnerabilidad a contraer hepatitis B y la importancia de los estudios entre usuarios de drogas en Pará. (AU)
Subject(s)
Drug Users , Hepatitis B virus , Hepacivirus , Vaccination CoverageABSTRACT
Hepatitis B virus infection is a serious threat to human life and health. The approved anti-HBV drugs including interferons and nucleos(t)ide analogues have serious adverse effect, rebound phenomena after drug withdrawal, and drug resistance. And the cccDNA cannot be completely eliminated by both of them, which is the reason why a complete cure for hepatitis B cannot be achieved. Therefore, developing anti-HBV drugs directly targeting protein or nucleic acid of HBV remains a current public health priority. Based on the analysis of representative literature from the last decade, this article reviews recent developments in small molecule inhibitors directly targeting HBV from a medicinal chemistry perspective.
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Hepatitis B virus (HBV) represents a significant global public health challenge. Despite the availability of several approved drugs for hepatitis B treatment, the persistence of covalently closed circular DNA (cccDNA) renders HBV eradication elusive, thereby leading to disease relapse after drug withdrawal. This paper reviews the regulatory mechanisms of cccDNA formation, transcription and replication, and summarizes the research progress of related small molecule regulators from the perspective of medicinal chemistry.
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Liver failure is an acute and critical disease in the field of liver diseases， and liver failure in China is mainly caused by hepatitis B virus （HBV） infection. Professor Mao Dewen has made remarkable achievements in the prevention and treatment of HBV-related liver failure in basic and clinical research by using the detoxicating， stasis-resolving， and Yang-warming method， and in particular， with this method as the technical core， the new clinical prevention and treatment regimen for reconstructing immune balance in HBV-related liver failure lays a foundation for synergistic integrated traditional Chinese and Western medicine therapy for HBV-related liver failure， highlights the therapeutic advantages of traditional Chinese medicine， and makes breakthroughs in the technical and therapeutic bottlenecks of current clinical treatment of HBV-related liver failure， thereby attempting to reduce the incidence and mortality rates of liver failure.
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ObjectiveTo investigate the diagnostic efficacy and optimal cut-off values of alpha-fetoprotein （AFP） and alpha-fetoprotein variant L3 （AFP-L3） in hepatitis B virus （HBV）-related early-stage hepatocellular carcinoma （HCC）. MethodsA total of 1 080 patients with HBV-related HCC （HBV-HCC） who were diagnosed for the first time and not yet treated in The Third Affiliated Hospital of Sun Yat-Sen University from January 2019 to July 2022 were enrolled as HCC group in the study， among whom there were 620 patients with CNLC Ⅰa-Ⅱa HCC， and in addition， 346 patients with HBV-related chronic hepatitis B （CHB group） and 293 patients with HBV-related liver cirrhosis （LC group） were enrolled as controls. The diagnostic efficacy of AFP and AFP-L3% in screening for HBV-related early-stage HCC was analyzed， including sensitivity， specificity， and the area under the ROC curve （AUC）. The Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups； the Kruskal-Wallis H test was used for comparison between multiple groups， and the Bonferroni method was used for further comparison between two groups. ResultsThe HCC group had significantly higher levels of AFP and AFP-L3% than the CHB group and the LC group （H=542.479 and 418.974， both P<0.001）. In early-stage HCC， AFP and AFP-L3% had an optimal cut-off value of 8.7 ng/mL and 5%， respectively， and AFP alone had the largest AUC of 0.816， with a sensitivity of 66.9% and a specificity of 85.1%. There was no significant difference in AUC between AFP-L3%+AFP and AFP alone （Z=0.609， P=0.543）， but both AFP-L3%+AFP and AFP alone had a significantly larger AUC than AFP-L3% alone （AFP vs AFP-L3%： Z=8.173， P<0.001； AFP+AFP-L3% vs AFP-L3%： Z=8.802， P<0.001）. ConclusionAFP has a good value and is superior to AFP-L3% in the diagnosis of HBV-related early-stage HCC， and the screening cut-off value of AFP should be lowered in order to improve the detection rate of early-stage HCC.
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ObjectiveTo investigate and compare the value of albumin-related ratios ［total bilirubin-to-albumin ratio （TAR）， creatinine-to-albumin ratio （CAR）， prothrombin time-international normalized ratio-to-albumin ratio （IAR）， neutrophil count-to-albumin ratio （NAR）， and red blood cell distribution width-to-albumin ratio （RAR）］ in predicting the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF）. MethodsA retrospective analysis was performed for 354 patients with HBV-ACLF who were admitted to Department of Infectious Diseases， The Affiliated Hospital of Southwest Medical University， from June 2017 to February 2022， and according to their prognosis at 3 months of follow-up， they were divided into survival group （n=272） and death group （n=82）. Related indices were recorded for all patients， including age， sex， complications， and the results of routine blood test， liver function， and coagulation for the first time after admission， and albumin-related ratios and Model for End-Stage Liver Disease （MELD） score were calculated. The t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distribution continuous data between groups； the chi-square test was used for comparison of categorical data between groups. The Spearman correlation test was used to investigate the correlation between albumin-related ratios and MELD score. The Logistic regression analysis was used to explore the association of MELD score， TAR， CAR， IAR， NAR， and RAR with poor prognosis. The area under the ROC curve （AUC） was used to as sess the accuracy of albumin-related ratios and MELD score in predicting the short-term prognosis of HBV-ACLF patients， and the De-Long test was used for the comparison of AUC. ResultsCompared with the death group， the survival group had significantly lower MELD score （Z=-8.071， P<0.001）， TAR （Z=-6.695， P<0.001）， CAR （Z=-4.463， P<0.001）， IAR （Z=-7.912， P<0.001）， NAR （Z=-4.061， P<0.001）， and RAR （Z=-4.788， P<0.001）. MELD score was positively correlated with CAR （r=0.616， P<0.001）， IAR （r=0.733， P<0.001）， TAR （r=0.657， P<0.001）， NAR （r=0.392， P<0.001）， and RAR （r=0.380， P<0.001）. The multivariate regression analysis of MELD score and albumin-related ratios showed that high TAR （odds ratio ［OR］=1.014， 95% confidence interval ［CI］： 1.008 — 1.020， P<0.001） and high IAR （OR=22.052， 95%CI： 6.937 — 70.103， P<0.001） were independent risk factors for death. The ROC curves were plotted for albumin-related ratios and MELD score to evaluate their discriminatory ability for mortality， and the results showed that MELD score， TAR， CAR， IAR， NAR， and RAR had an AUC of 0.794， 0.744， 0.663， 0.788， 0.648， and 0.674， respectively， among which MELD score had the highest sensitivity of 86.59% and CAR had the highest specificity of 77.57%. TAR combined with IAR had an AUC of 0.809， with a sensitivity of 76.8% and a specificity of 71.3%. Subgroup analysis of HBV-ACLF showed that TAR combined with IAR had the highest AUC values of 0.884 and 0.733， respectively， in patients with type A or type C HBV-ACLF. ConclusionTAR and IAR can be used as simple and effective prognostic tools to predict the 90-day mortality of HBV-ACLF patients.
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Hepatitis B virus （HBV） has the characteristics of wide transmission， a high chronic infection rate， and a low cure rate， and improving the cure rate of HBV may help to improve the long－term prognosis of patients. Heat shock protein 90 （Hsp90） is a chaperone protein widely present in organisms. In recent years， more and more studies have shown that Hsp90 is associated with HBV infection and plays an important role in HBV replication. It can not only interact with specific proteins of the virus to promote its replication， but also interact with the host’s own proteins to perform its function. This article reviews the role of Hsp90 in HBV replication in recent studies， so as to provide new theoretical guidance and directions for the development of new anti－HBV drugs targeting Hsp90 and the prevention and treatment of HBV infection in the future.
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ObjectiveTo investigate whether cytotoxic T lymphocyte （CTL）－derived exosomes can downregulate HBx expression and inhibit hepatic stellate cell （HSC） activation. MethodsThe supernatants of HepG2， HepGA14， and CTL cells were collected to extract exosomes， which were referred to as NC－exo， HBV－exo， and CTL－exo， respectively）. Transmission electron microscopy was used to observe their morphology， and Western Blot was used to measure the expression of the markers of exosomes CD63 and TSG101. NC－exo， HBV－exo， and CTL－exo labeled by BODIPY dye were mixed with HBV－exo at different ratios and were then co－cultured with HSC LX－2 （HSC－LX2）. A fluorescence microscope was used to observe whether exosomes could enter LX－2 cells， and an fluorescence microscope was used to observe cell morphological changes； quantitative real－time PCR （qPCR） was used to measure the expression of the activated biomarkers such as transforming growth factor－β1 （TGF－β1）， ɑ－smooth muscle actin （ɑ－SMA）， and collagen type I （Collagen I） in LX－2 cells. CTL－exo was added to the HepGA14 culture system； then qPCR was used to measure the mRNA expression level of HBV DNA， cccDNA， and HBx in exosomes in HepGA14 cells， and Western Blot was used to measure the protein expression level of HBx in exosomes. The t-test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe exosomes were all microcysts with a double－layer membrane structure and were circular or elliptical in shape， with the expression of the signature proteins CD63 and TSG101， and the vesicles had a diameter of 50－100 nm. The fluorescence microscope showed that exosomes could enter LX－2 cells， and HSC were enlarged with extended cell processes. The results of qPCR showed that there were significant differences in the expression levels of TGF－β1， ɑ－SMA， and Collagen I genes between the NC－exo， HBV－exo， NC－exo+HBV－exo， and Con groups （F=444.678， 417.144， and 571.508， all P<0.05）. After the intervention of HepGA14 cells with CTL－exo， qPCR results showed that compared with the control group， there were significant reductions in the expression levels of HBV DNA and cccDNA in HepGA14 cells （all P<0.05）， the relative mRNA expression level of HBx in exosomes （P<0.05）， and the protein expression level of HBx （P<0.05）. CTL－exo and HBV－exo were mixed at different ratios （2∶1， 5∶1， 10∶1） and were then used for the intervention of LX－2 cells， and qPCR results showed that the expression levels of TGF－β1， ɑ－SMA， and Collagen I genes in LX－2 cells gradually decreased with the increase in the ratio of CTL－exo between groups （P<0.05）. ConclusionCTL－exo can downregulate the protein expression of HBx in HBV－exo to inhibit HSC activation， suggesting that CTL－exo has an anti－hepatitis B liver fibrosis effect.
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This paper discusses further on the antiviral treatment of chronic hepatitis B patients with indeterminate phase. These patients have a high proportion of significant necroinflammation and fibrosis in the liver， and a higher risk of disease progression compared with those with true HBeAg－positive chronic hepatitis B virus （HBV） infection （formerly called the immune tolerance phase） or HBeAg－negative chronic HBV infection （formerly called the immune control phase）. Antiviral therapy may reduce the risk of HBV－related hepatocellular carcinoma in chronic hepatitis B patients with indeterminate phase.