Des-gamma-carboxy prothrombin is a promising biomarker of hepatocellular carcinoma and a predictor of complications in patients with chronic liver diseases

To the Editor: Although des-gamma-carboxy prothrombin(DCP) is considered a complementary biomarker to alpha-fetoprotein(AFP) in the diagnosis of hepatocellular carcinoma(HCC), its cut-off value has not been recommended in any guideline. This study aimed to explore the diagnostic efficacy of DCP on HCC.

Short Term Prediction of Infectious Diseases Patients from Prescription Surveillance

In Japan, the incidence of almost all common pediatric infectious diseases has been monitored, with 7 - 10 day delays, at medical institutions through the National Official Sentinel Surveillance of Infectious Diseases (NOSSID). On the other hand, based on prescriptions filled at external pharmacies, Prescription Surveillance (PS) collects information and provides estimated numbers of influenza, varicella, and gastroenteritis infectious (GI) patients to the public the following morning. For precise, and real-time estimation of incidences of common pediatric infectious diseases, we evaluated predictive power of PS for diseases other than influenza, varicella, and GI. Results demonstrated that PS information has sufficient predictive power for pharyngoconjunctival fever, group A streptococcal pharyngitis, exanthem subitum, and mumps, some predictive power for RS virus infection, erythema infectiosum and herpangina, but insufficient predictive power for hand, foot and mouth disease.

Stability and variability of molecular subtypes:comparative analysis of primary and metastatic triple-negative breast cancer

Objective:Triple-negative breast cancer(TNBC)is a heterogeneous and aggressive cancer.Although our previous study classified primary TNBC into four subtypes,comprehensive longitudinal investigations are lacking.Methods:We assembled a large-scale,real-world cohort comprised of 880 TNBC patients[465 early-stage TNBC(eTNBC)and 415 metastatic TNBC(mTNBC)patients]who were treated at Fudan University Shanghai Cancer Center.The longitudinal dynamics of TNBC subtypes during disease progression were elucidated in this patient cohort.Comprehensive analysis was performed to compare primary and metastatic lesions within specific TNBC subtypes.Results:The recurrence and metastasis rates within 3 years after initial diagnosis in the eTNBC cohort were 10.1%(47/465).The median overall survival(OS)in the mTNBC cohort was 27.2 months[95%confidence interval(CI),24.4–30.2 months],which indicated a poor prognosis.The prognostic significance of the original molecular subtypes in both eTNBC and mTNBC patients was confirmed.Consistent molecular subtypes were maintained in 77.5%of the patients throughout disease progression with the mesenchymal-like(MES)subtype demonstrating a tendency for subtype transition and brain metastasis.Additionally,a precision treatment strategy based on the metastatic MES subtype of target lesions resulted in improved progression-free survival in the FUTURE trial.Conclusions:Our longitudinal study comprehensively revealed the clinical characteristics and survival of patients with the original TNBC subtypes and validated the consistency of most molecular subtypes throughout disease progression.However,we emphasize the major importance of repeat pathologic confirmation of the MES subtype.

Detecting the distribution of and public attitudes to charismatic alien species based on media coverage

Charismatic species are often reported by the media,providing information for detecting population status and public perception.To identify the number and distribution of free-living Black Swan(Cygnus atratus),a charismatic alien species in Chinese mainland and to detect the public and the media attitudes to the species,we analyzed the reports and emotional tendency from media coverage in 2000-2022 using manual reading,crawler extraction and latent Dirichlet allocation.A total of 6654 Black Swans were reported at 711 sites,including 147 individuals at 30 nature reserves.Successful breeding was reported at one-fourth of the total sites,including five nature reserves.The proportion of positive emotional tendency to Black Swans was overwhelming in the reports and was higher than that to alien species in general,suggesting that the public and the media are unaware of the risk of biological invasion.Effective management of invasive species requires the media clarifies the invasion risk of charismatic alien species.Promoting the unity between the harmfulness of abstract concept of alien species and the charisma of a specific alien species among the public help effective management.

Ferritinophagy: A new idea for liver diseases regulated by ferroptosis

Background:The discovery of regulatory cell death has led to a breakthrough in the therapeutic field.Various forms of cell death,such as necrosis,apoptosis,pyroptosis,autophagy,and ferroptosis,play an important role in the development of liver diseases.In general,more than one form of cell death pathways is responsible for the disease state.Therefore,it is particularly important to study the regulation and interaction of various cell death forms in liver diseases.Data sources:We performed a PubMed search up to November 2022 with the following keywords:ferritinophagy,ferroptosis,and liver disease.We also used terms such as signal path,inducer,and inhibitor to supplement the query results.Results:This review summarized the basic characteristics of ferritinophagy and ferroptosis and the regulation of ferroptosis by ferritinophagy and reviewed the key targets and treatment strategies of ferroptosis in different liver diseases.Conclusions:Ferritinophagy is a potential therapeutic target in ferroptosis-related liver diseases.

HBV genotype characterization and distribution in patients with HBV-related liver diseases in Zhejiang Province, P. R. China: possible association of co-infection with disease prevalence and severity

BACKGROUND: There are 8 well-documented genotypes of hepatitis B virus (HBV) at this time point. Genotyping can be accomplished based on a partial sequence of hepatitis B virus (HBV) genome such as the pre-S or S gene. Several methods have been developed and used for HBV genotyping including direct sequencing, restriction fragment length polymorphism, line probe assay and enzyme-linked immunoassay. Recently, a novel, rapid and cost-effective genotyping method based on PCR amplification assay using type-specific primers that can identify all six major genotypes has been developed. This study was undertaken to characterise HBV genotypes and investigate the association between the prevalence of different genotypes and the severity of HBV-induced liver diseases. METHODS: Serum samples from carriers of HBV and patients with HBV-related liver diseases from Zhejiang Province were screened for viral serological markers using commercially available radioimmunoassay (RIA) and enzyme linked immunosorbent assay (ELISA) kits. Serum HBV DNA load was determined by real-time detection PCR. A type-specific primer based the nested-PCR method was employed in the HBV genotyping. The genotype results obtained were confirmed by direct sequencing of nested PCR amplicons of the pre-S region. Ten samples of each genotype (B and C) were sequenced. RESULTS: The survey on a cohort of 125 HBV carriers in and around Hangzhou City, Zhejiang Province showed the existence of HBV genotypes A (0.8%), B (48%), C (40.8%), D (0.8%), mixed B and C (9.6%) and an absence of E and F genotypes. Distribution of HBV genotypes in patients with liver diseases revealed a statistically insignificant higher prevalence of genotype B in mild chronic hepatitis (CH). Among the three genotypes B, C and mixed B/C infections 11 (73.3%), 3 (20%) and 1 (6.7%), (P< 0.05), respectively in subjects with moderate CH, genotype B was significantly predominant. The infection patterns for genotypes B, C and B/C mixed in (i) liver cirrhosis (LC) 4 (23.5%), 10 (58.8%) and3 (17.7%) and (ii) hepatocellular carcinoma (HCC) 2 (28.6%), 5(71.4%) and 0 (0.0%) respectively revealed a marked association of C genotype with liver disease; however, the association was statistically insignificant (P >0.05). Differences in positive rate of HBeAg for the three genotypes B, 16(30.8%), C, 27(51.9%), and mixed B/C, 9(17.3%) were significant (P < 0. 05 ) , with genotype C showing predominance. CONCLUSIONS : These findings show an interesting distribution of HBV A-D genotypes in Zhejiang Province. Furthermore, our results indicate a novel and markedly high prevalence of mixed B/C genotype infections in subjects with severe CH and LC, and a possible association of mixed B/C infections with the severity of liver diseases in this region of China's Mainland.

Frequency and Absolute Number of FoxP3^+ Regulatory T Cells Correlate with Disease Progression of Chronic HIV-1 Infection

CD4^＋CD25^＋ Regulatory T cells （Treg） have been found to down-regulate immune activation in HIV-1 infection. However, whether the depletion of Treg benefits to the disease status of HIV infection remains undefined. To address this issue, we enumerated the Treg absolute counts and frequency in 75 antiviral-naive HIV-1-infected individuals in this study. It was found that HIV-infected patients displayed a significant decline in Treg absolute counts but a significant increase in Treg frequency. In addition, with disease progression indicated by CD4 T-cell absolute counts, circulating Treg frequency gradually increased; while Treg absolute counts were gradually decreased, suggesting that the alteration of Treg number closely correlated with disease progression in HIV infection Functional analysis further showed that Treg efficiently inhibit both CD4 and CD8 T cell proliferation in vitro. Thus, our findings indicates that Treg actively participate in pathogenesis of chronic HIV infection, influencing the disease progression.

Chagas heart disease:An overview of diagnosis,manifestations,treatment,and care

Chagas heart disease(CHD)affects approximately 30%of patients chronically infected with the protozoa Trypanosoma cruzi.CHD is classified into four stages of increasing severity according to electrocardiographic,echocardiographic,and clinical criteria.CHD presents with a myriad of clinical manifestations,but its main complications are sudden cardiac death,heart failure,and stroke.Importantly,CHD has a higher incidence of sudden cardiac death and stroke than most other cardiopathies,and patients with CHD complicated by heart failure have a higher mortality than patients with heart failure caused by other etiologies.Among patients with CHD,approximately 90%of deaths can be attributed to complications of Chagas disease.Sudden cardiac death is the most common cause of death(55%–60%),followed by heart failure(25%–30%)and stroke(10%–15%).The high morbimortality and the unique characteristics of CHD demand an individualized approach according to the stage of the disease and associated complications the patient presents with.Therefore,the management of CHD is challenging,and in this review,we present the most updated available data to help clinicians and cardiologists in the care of these patients.We describe the clinical manifestations,diagnosis and classification criteria,risk stratification,and approach to the different clinical aspects of CHD using diagnostic tools and pharmacological and non-pharmacological treatments.

Providing Infectious Disease Information to Child-Rearing Families and Its Evaluation

Background: Earlier study without actual trial indicated that caregivers needed delivery of information about outbreak situations independently of their job status. This report describes, for about two months in winter, actual delivery outbreak information to families with preschool children. The study objective was to confirm the usefulness of this information delivery. Method: Participants receiving outbreak information were recruited from the Child Care Support Service in a ward in Tokyo, Japan. Outbreak information was obtained from the Nursery School Absenteeism Surveillance System (NSASSy) covering approximately 40% of all nursery schools in Japan, prescription surveillance and other resources. Delivery of outbreak information started in December 2017 and ceased at the end of February in 2018. After the delivery period, a questionnaire survey was administered to participants. Results: For this area, NSASSy showed the most dominant disease was influenza, with 707 patients, followed by group A streptococcal pharyngitis with 98 patients. The outbreak peak was inferred to be as Monday, 22 January, and it was announced by e-mail on 23 January. Of the 202 persons joined this trial, 60 participants responded to the questionnaire survey after the delivery period. Of those respondents, 98% wanted delivery of that information to continue. Conclusion: We found that almost all respondents confirmed usefulness of the information about infectious diseases which was delivered.

Does Family with Children Need Information about Infectious Disease?

This paper reports a study of the necessity of providing information that is of the most concern of caregivers: health management, responses to sudden onset, and outbreaks of infectious diseases. We asked users and providers of Child Care Support Service in ward A of Tokyo, as respondents, whether they would like to receive information related to infectious diseases. Of questionnaires sent by mail to 383 providers and 3101 users, we received 18 responses from providers and 88 responses from users. All providers and users were required to provide information related to infectious diseases. The most often reported responses were “straight-out hand washing, mask wearing, gargling, and disinfection”, followed by “voluntary restraint of outside activities”, and “measures for illnesses of the family or children.” Results show that caregivers would like to receive information about infectious diseases because they have many health management concerns about their children.

Clinical features and potential mechanism of coronavirus disease 2019-associated liver injury

Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2,has posed a serious threat to global public health security.With the increase in the number of confirmed cases globally,the World Health Organization has declared the outbreak of COVID-19 an international public health emergency.Despite atypical pneumonia as the primary symptom,liver dysfunction has also been observed in many clinical cases and is associated with the mortality risk in patients with COVID-19,like severe acute respiratory syndrome and Middle East respiratory syndrome.Here we will provide a schematic overview of the clinical characteristics and the possible mechanisms of liver injury caused by severe acute respiratory syndrome coronavirus 2 infection,which may provide help for optimizing the management of liver injury and reducing mortality in COVID-19 patients.

Difference and clinical value of metabolites in plasma and feces of patients with alcohol-related liver cirrhosis

BACKGROUND Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis(ALC).AIM To explore the common and different metabolites in the plasma and feces of patients with ALC and evaluate their clinical implications.METHODS According to the inclusion and exclusion criteria,27 patients with ALC and 24 healthy controls(HCs)were selected,and plasma and feces samples were collected.Liver function,blood routine,and other indicators were detected with automatic biochemical and blood routine analyzers.Liquid chromatography-mass spectrometry was used to detect the plasma and feces metabolites of the two groups and the metabolomics of plasma and feces.Also,the correlation between metabolites and clinical features was analyzed.RESULTS More than 300 common metabolites were identified in the plasma and feces of patients with ALC.Pathway analysis showed that these metabolites are enriched in bile acid and amino acid metabolic pathways.Compared to HCs,patients with ALC had a higher level of glycocholic acid(GCA)and taurocholic acid(TCA)in plasma and a lower level of deoxycholic acid(DCA)in the feces,while L-threonine,L-phenylalanine,and L-tyrosine increased simultaneously in plasma and feces.GCA,TCA,L-methionine,L-phenylalanine,and L-tyrosine in plasma were positively correlated with total bilirubin(TBil),prothrombin time(PT),and maddrey discriminant function score(MDF)and negatively correlated with cholinesterase(CHE)and albumin(ALB).The DCA in feces was negatively correlated with TBil,MDF,and PT and positively correlated with CHE and ALB.Moreover,we established a P/S BA ratio of plasma primary bile acid(GCA and TCA)to fecal secondary bile acid(DCA),which was relevant to TBil,PT,and MDF score.CONCLUSION The enrichment of GCA,TCA,L-phenylalanine,L-tyrosine,and L-methionine in the plasma of patients with ALC and the reduction of DCA in feces were related to the severity of ALC.These metabolites may be used as indicators to evaluate the progression of alcohol-related liver cirrhosis.

FibroScan-aspartate transaminase:A superior non-invasive model for diagnosing high-risk metabolic dysfunction-associated steatohepatitis

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)with hepatic histological NAFLD activity score≥4 and fibrosis stage F≥2 is regarded as“at risk”non-alcoholic steatohepatitis(NASH).Based on an international consensus,NAFLD and NASH were renamed as metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH),respectively;hence,we introduced the term“high-risk MASH”.Diagnostic values of seven non-invasive models,including FibroScan-aspartate transaminase(FAST),fibrosis-4(FIB-4),aspartate transaminase to platelet ratio index(APRI),etc.for high-risk MASH have rarely been studied and compared in MASLD.AIM To assess the clinical value of seven non-invasive models as alternatives to liver biopsy for diagnosing high-risk MASH.METHODS A retrospective analysis was conducted on 309 patients diagnosed with NAFLD via liver biopsy at Beijing Ditan Hospital,between January 2012 and December 2020.After screening for MASLD and the exclusion criteria,279 patients wereincluded and categorized into high-risk and non-high-risk MASH groups.Utilizing threshold values of each model,sensitivity,specificity,positive predictive value(PPV),and negative predictive values(NPV),were calculated.Receiver operating characteristic curves were constructed to evaluate their diagnostic efficacy based on the area under the curve(AUROC).RESULTS MASLD diagnostic criteria were met by 99.4%patients with NAFLD.The MASLD population was analyzed in two cohorts:Overall population(279 patients)and the subgroup(117 patients)who underwent liver transient elastography(FibroScan).In the overall population,FIB-4 showed better diagnostic efficacy and higher PPV,with sensitivity,specificity,PPV,NPV,and AUROC of 26.9%,95.2%,73.5%,72.2%,and 0.75.APRI,Forns index,and aspartate transaminase to alanine transaminase ratio(ARR)showed moderate diagnostic efficacy,whereas S index and gamma-glutamyl transpeptidase to platelet ratio(GPR)were relatively weaker.In the subgroup,FAST had the highest diagnostic efficacy,its sensitivity,specificity,PPV,NPV,and AUROC were 44.2%,92.3%,82.1%,67.4%,and 0.82.The FIB-4 AUROC was 0.76.S index and GPR exhibited almost no diagnostic value for high-risk MASH.CONCLUSION FAST and FIB-4 could replace liver biopsy as more effectively diagnostic methods for high-risk MASH compared to APRI,Forns index,ARR,S index,and GPR;FAST is superior to FIB-4.

MicroRNA-185-5p mediates regulation of SREBP2 expression by hepatitis C virus core protein

AIM: To investigate the molecular mechanism for regulation of cholesterol metabolism by hepatitis C virus(HCV) core protein in Hep G2 cells.METHODS: HCV genotype 1b core protein was cloned and expressed in Hep G2 cells. The cholesterol content was determined after transfection. The expression of sterol regulatory element binding protein 2(SREBP2) and the rate-limiting enzyme in cholesterol synthesis(HMGCR) was measured by quantitative real-time PCR and immunoblotting after transfection. The effects of core protein on the SREBP2 promoter and 3'-untranslated region were analyzed by luciferase assay. We used different target predictive algorithms, micro RNA(mi RNA) mimics/inhibitors, and site-directed mutation to identify a putative target of a particular mi RNA.RESULTS: HCV core protein expression in Hep G2 cells increased the total intracellular cholesterol level(4.05 ± 0.17 vs 6.47 ± 0.68, P = 0.001), and this increase corresponded to an increase in SREBP2 and HMGCR m RNA levels(P = 0.009 and 0.037, respectively) and protein expression. The molecular mechanism studyrevealed that the HCV core protein increased the expression of SREBP2 by enhancing its promoter activity(P = 0.004). In addition, mi R-185-5p expression was tightly regulated by the HCV core protein(P = 0.041). Moreover, overexpression of mi R-185-5p repressed the SREBP2 m RNA level(P = 0.022) and protein expression. In contrast, inhibition of mi R-185-5p caused upregulation of SREBP2 protein expression. mi R-185-5p was involved in the regulation of SREBP2 expression by HCV core protein. CONCLUSION: HCV core protein disturbs the cholesterol homeostasis in Hep G2 cells via the SREBP2 pathway; mi R-185-5p is involved in the regulation of SREBP2 by the core protein.

Parthenolide protects human lens epithelial cells from oxidative stress-induced apoptosis via inhibition of activation of caspase-3 and caspase-9

The apoptosis of lens epithehal cells has been proposed as the common basis of cataract formation, with oxidative stress as the major cause. This study was performed to investigate the protective effect of the herbal constituent parthenolide against oxidative stress-induced apoptosis of human lens epithelial （HLE） cells and the possible molecular mechanisms involved. HLE cells （SRA01-04） were incubated with 50 μM H2O2 in the absence or presence of different doses of parthenolide （10, 20 and 50 μM）. To study apoptosis, the cells were assessed by morphologic examination and Annexin V-propidium iodide double staining flow cytometry; to investigate the underlying molecular mechanisms, the expression of caspase-3 and caspase-9 were assayed by Western blot and quantitative RT-PCR, and the activities of caspase-3 and caspase-9 were measured by a Chemicon caspase colorimetric activity assay kit. Stimulated with H202 for 18 h, a high fraction of riLE cells underwent apoptosis, while in the presence ofparthenolide of different concentrations, dose-dependent blocking of HLE cell apoptosis was observed. The expression of caspase-3 and caspase-9 induced by H202 in HLE cells was significantly reduced by parthenolide both at the protein and mRNA levels, and the activation ofcaspase-3 and caspase-9 was also suppressed by parthenolide in a dose-dependent manner. In conclusion, parthenolide prevents HLE cells from oxidative stress-induced apoptosis through inhibition of the activation ofcaspase-3 and caspase-9, suggesting a potential protective effect against cataract formation.

Detection of PERV by polymerase chain reaction and its safety in bioartificial liver support system

AIM： To establish a method detecting porcine endogenous retrovirus （PERV） in China experimental minipigs and to evaluate the safety of PERV in three individuals treated with bioartificial liver support systems based on porcine hepatocytes. METHODS： Porcine hepatocytes were isolated with two-stage perfusion method, then cultured in the bioreactor, which is separated by a semipermeable membrane （0.2μm） from the lumen through which the patients＇ blood plasma was circulated. After posthemoperfusion, patients＇ blood was obtained for screening. Additionally, samples of medium collected from both intraluminal and extraluminal compartments of the laboratory bioreactor and culture supernate in vitro was analyzed. The presence of viral sequences was estimated by polymerase chain reaction （PCR） and reverse transcriptase-polymerase chain reaction （RTPCR）. Finally, the infection of virus in the supernate of common culture was ascertained by exposure to the fetal liver cells. RESULTS： PERV-specific gag sequences were found in the porcine hepatocytes using RT-PCR. and were detected in all samples from the intraluminal, extraluminal samples and culture supernate. However, culture supernatant from primary porcine hepatocytes （cleared of cellular debris） failed to infect human fetal liver cells. Finally, RT-PCR detected no PERV infection was found in the blood samples obtained from three patients at various times post-hemoperfusion. CONCLUSION： The assays used are specific and sensitive, identified by second PCR. PERVs could be released from hepatocytes cultured in bioreactor without the stimulation of mitogen and could not be prevented by the hollow fiber semipermeable membrane, indicating the existence of PERV safety in extracorporeal bioartificial liver support system （EBLSS）.

Influence of TBX21 T-1993C variant on autoimmune hepatitis development by Yin-Yang 1 binding

AIM To investigated the mechanism of the association between the TBX21 T-1993 C promoter polymorphism and autoimmune hepatitis type 1(AIH-1) development.METHODS In vivo,In vivo,and reporter analyses were performed to determine the function of transcription factors binding to the T-1993 C element of the TBX21 promoter in human CD4+ T and B cell lines. Flow cytometry and quantitative real-time PCR were used to analyze T-box transcription factor(T-bet) and interferon-γ(IFN-γ) expressions in CD4+ T cells,B cells and monocytes from the peripheral blood of AIH-1 patients including 5-1993 TC and 15-1993 TT genotype carriers,and healthy controls including 10-1993 TC and 25-1993 TT genotype carriers. Furthermore,a range of biochemical indices was measured simultaneously in the blood of AIH-1 patients.RESULTS TBX21-1993 C allele created a strong Yin-Yang 1(YY1)-binding site and decreased transcriptional activity of TBX21 promoter in human CD4+ T and B cells.Higher levels of T-bet and IFN-γ were detected in the circulating CD4+ T cells and B cells of AIH-1 patients carrying the TBX21-1993 TT genotype compared with the patients carrying the-1993 TC genotype and controls with the-1993 TC genotype. T-bet expression levels of circulating T cells and B cells were positively correlated with AIH-1 disease activity. Knockdown of YY1 with si RNA caused increased expression of T-bet and IFN-γ in peripheral blood mononuclear cells in AIH-1 patients. CONCLUSION The repression of TBX21 expression by high-affinity binding of YY1 to the-1993 C allele may contribute to a decreased development of AIH-1 via suppression of type 1 immunity.

Relationship between HLA-DR gene polymorphisms and outcomes of hepatitis B viral infections:A meta-analysis

AIM:To assess the rigorous relationship between human leukocyte antigens(HLA)-DR alleles and outcomes of hepatitis B virus(HBV) infections by means of metaanalysis.METHODS:Medline/PubMed,EMBASE,CNKI and VIP were searched to identify relevant studies.Study quality was evaluated using the Newcastle-Ottawa Scale.Odds ratios(OR) and 95% confidence interval(95% CI) were pooled using Stata 11.0.Subgroup analyses were performed by ethnicity.Heterogeneity and publication bias analyses were performed to validate the credibility.RESULTS:A total of 2609 patients with chronic hepatitis B and 2606 controls spontaneously recovering from prior HBV infection were included.Meta-analysis showed that HLA-DR*04(OR = 0.72,95% CI:0.60-0.85) and DR*13(OR = 0.27,95% CI:0.19-0.37) alleles were significantly associated with HBV clearance while patients carrying HLA-DR*03(OR = 1.47,95% CI:1.16-1.87) or DR*07(OR = 1.59,95% CI:1.24-2.03) alleles had a significantly increased risk of chronic HBV persistence.For the HLA-DR*01 polymorphism,a significantly association with HBV clearance was found in Chinese Han group(OR = 0.48,95% CI:0.26-0.86),but not found in other ethnic groups(P = 0.191).For other polymorphisms,no association with the HBV infection outcome was found.CONCLUSION:HLA-DR*04 and DR*13 alleles may be the protective factors for HBV clearance and HLADR*03,and DR*07 alleles may be the risk factors for HBV persistence.

Clinical features of chronic hepatitis B patients with YMDD mutation after lamivudine therapy

Objective: To study the clinical features of chronic hepatitis B (CHB) patients with tyrosine-methionine-aspartateaspartate (YMDD) mutation after lamivudine therapy. Methods: This investigation was a retrospective study of 63 CHB patients with YMDD mutation during lamivudine therapy. Clinical data, including period and types of YMDD mutation; hepatitis B virus (HBV) DNA levels and alanine aminotransferase (ALT) levels before and after YMDD mutation were measured. YMDD mutation in the HBV DNA polymerase gene was determined using polymerase chain reaction (PCR) and direct sequencing. HBV DNA quantification was determined using real-time PCR. Relevant serum markers of HBV were measured. The follow-up period was 12 months after YMDD mutation. Results: YMDD mutation occurred 7～44 months (median, 21.5 months) after the start of lamivudine therapy. The majority of the cases (42/63, 66.6%) had YMDD mutants detected between 12 and 24 months. Four types of YMDD mutation were observed in this study, rtL180M/M204V mutation was the predominant type (26/63, 41.3%). A proportion of patients (16/63, 25.4%; 12/63, 19.1%) had higher HBV DNA levels and ALT levels (after mutation vs before mutation),respectively. Conclusion: The majority of patients with YMDD mutants had similar or lower HBV DNA levels and ALT levels compared with baseline values. This subset of patients might have benefited from the continued lamivudine therapy. The patients with increased ALT and HBV DNA levels (breakthrough hepatitis) should benefit from the addition of a newer nucleotide analogue (e.g. adefovir).

Character of HBV (hepatitis B virus) polymerase gene rtM204V/I and rtL180M mutation in patients with lamivudine resistance

Objectives: To investigate the relationship between HBV (hepatitis B virus) polymerase gene 180 and 204 sites mutation and lamivudine resistance. Methods: One hundred forty-one patients with lamivudine resistance after lamivudine treatment and 60 chronic hepatitis B patients without lamivudine treatment were enrolled in this study. The serum HBV DNA mutation was analyzed by sequence detection via polymerase chain reaction (PCR). The sequences of the same patient were analyzed before and after lamivudine treatment. Results: One hundred and nine lamivudine resistance patients had HBV YMDD (tyrosine-methionine-aspartate-aspartate) mutation. Among them, 45 patients had rtL 180M/M204V mutation (41.28%), 28patients had rtL180M/M204I mutation (25.70%) and 36 patients had rtM204I mutation (33.02%). There were 6 patients with rtL180M mutation in 32 lamivudine resistance patients. Sixty chronic hepatitis patients without lamivudine treatment had no mutations. Conclusions: HBV mutations, which play an important role in lamivudine resistance usually locate at polymerase gene 204 site; 180 site mutation was also observed in these patients. Evaluation of the anti-virus therapy by surveillance of the two sites mutations is of importance.