The Features of GGT in Patients with ATP8B1 or ABCB11 Deficiency Improve the Diagnostic Efficiency

MethodsThis study enrolled 207 patients with chronic cholestasis who were ordered to test for ATP8B1 and/or ABCB11 from January 2012 to December 2015. Additional 17 patients with ATPB81 or ABCB11 deficiency diagnosed between January 2004 and December 2011 were also enrolled in this study. 600 population-matched children served as controls. Clinical data were obtained by retrospectively reviewing medical records.ResultsA total of 26 patients were diagnosed with ATP8B1 deficiency and 30 patients were diagnosed with ABCB11 deficiency. GGT levels were similar between the two disorders at any observed month of age, but varied with age. The peak GGT value was <70U/L in the 2nd~6th month of life, <60U/L in the 7th~12th month and <50U/L beyond one year. GGT levels in patients with a genetic diagnosis were different from that in patients without a genetic diagnosis and controls. Larger ranges for GGT were found in patients without a genetic diagnosis. Some controls had GGT≥70U/L in the 2nd~6th month. Of the 207 patients, 39 (18.8%) obtained a genetic diagnosis. 111 patients met the ranges described above, including all the 39 patients with ATP8B1 or ABCB11 deficiency. The sensitivity was 100.0%. The rate of a positive molecular diagnosis increased to 35.1% (39/111 vs. 39/207, X² = 10.363, P = 0.001). The remaining 96 patients exceeded the ranges described above and failed to receive a genetic diagnosis. These patients accounted for 43.8% of sequencing cost.ConclusionsGGT levels in patients with ATP8B1 or ABCB11 deficiency varied with age. The peak GGT value was <70U/L in the 2nd~6th month of life, <60U/L in the 7th~12th month and <50U/L beyond one year.     

Mutational Analysis of Patients with Neurofibromatosis 2

Neurofibromatosis 2 (NF2) is a genetic disorder characterized by the development of multiple nervous-system tumors in young adulthood. The NF2 gene has recently been isolated and found to encode a new member of the protein 4.1 family of cytoskeletal associated proteins, which we have named merlin. To define the molecular basis of NF2 in affected individuals, we have used SSCP analysis to scan the exons of the NF2 gene from 33 unrelated patients with NF2. Twenty unique SSCP variants were seen in 21 patients; 10 of these individuals were known to be the only affected person in their kindred, while 7 had at least one other known affected relative. In all cases in which family members were available, the SSCP variant segregated with the disease; comparison of sporadic cases with their parents confirmed the de novo variants. DNA sequence analysis revealed that 19 of the 20 variants observed are predicted to lead to a truncated protein due to frameshift, creation of a stop codon, or interference with normal RNA splicing. A single patient carried a 3-bp deletion removing a phenylalanine residue. We conclude that the majority of NF2 patients carry an inactivating mutation of the NF2 gene and that neutral polymorphism in the gene is rare.     

Predictors of Osteodystrophy in Patients with Chronic Nonalcoholic Pancreatitis with or without Diabetes

ObjectiveTo study bone mineral content (BMC), bone mineral density (BMD), vitamin D status, and bone mineral variables in patients with chronic nonalcoholic pancreatitis and to determine the relationship between pancreatic dysfunction and these variables.MethodsThirty-one eligible nonalcoholic men with proven chronic pancreatitis and 35 male control subjects were studied. Biochemical data, variables of malabsorption, and BMD of the lumbar spine were evaluated.ResultsIn patients with chronic pancreatitis, the mean body mass index (BMI) was 18.46 kg/m² and the median 25-hydroxyvitamin D value was 15.5 (range, 5.0 to 52.0) ng/mL. A T-score of less than -2.5 was found in a higher proportion of study patients (9 of 31, 29%) than of control subjects (3 of 35, 9%). BMI correlated significantly with BMC (r = 0.426; P = .017). There was an inverse correlation between stool fat and BMC (r = -0.47; P = .03) in patients with chronic pancreatitis and steatorrhea. There was no significant correlation between serum 25-hydroxyvitamin D or biochemical variables and BMD. Patients with steatorrhea had a significantly lower BMC than did those without steatorrhea, and this difference could not be accounted for by differences in BMI, presence of diabetes, or hypovitaminosis D.ConclusionPancreatic osteodystrophy is a novel entity consisting of osteopenia, osteoporosis, and osteomalacia in patients with chronic pancreatitis. The inverse correlation between stool fat and BMC in patients with chronic pancreatitis, the strong positive correlation between BMI and BMC, and the lack of difference in BMC between subjects with vitamin D sufficiency and those with vitamin D deficiency suggest that long-standing malabsorption with attendant chronic undernutrition is the major factor contributing to the changes in BMC. (Endocr Pract. 2011;17:897-905)     

Strain Background Modifies Phenotypes in the ATP8B1-Deficient Mouse

Background

Mutations in ATP8B1 (FIC1) underlie cases of cholestatic disease, ranging from chronic and progressive (progressive familial intrahepatic cholestasis) to intermittent (benign recurrent intrahepatic cholestasis). The ATP8B1-deficient mouse serves as an animal model of human ATP8B1 deficiency.

Methodology/Principal Findings

We investigated the effect of genetic background on phenotypes of ATP8B1-deficient and wild-type mice, using C57Bl/6 (B6), 129, and (B6-129) F1 strain backgrounds. B6 background resulted in greater abnormalities in ATP8B1-deficient mice than did 129 and/or F1 background. ATP8B1-deficient pups of B6 background gained less weight. In adult ATP8B1-deficient mice at baseline, those of B6 background had lower serum cholesterol levels, higher serum alkaline phosphatase levels, and larger livers. After challenge with cholate-supplemented diet, these mice exhibited higher serum alkaline phosphatase and bilirubin levels, greater weight loss and larger livers. ATP8B1-deficient phenotypes in mice of F1 and 129 backgrounds are usually similar, suggesting that susceptibility to manifestations of ATP8B1 deficiency may be recessive. We also detected differences in hepatobiliary phenotypes between wild-type mice of differing strains.

Conclusions/Significance

Our results indicate that the ATP8B1-deficient mouse in a B6 background may be a better model of human ATP8B1 deficiency and highlight the importance of informed background strain selection for mouse models of liver disease.     

Cluster Analysis in Patients with GOLD 1 Chronic Obstructive Pulmonary Disease

Background

We hypothesized that heterogeneity exists within the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 spirometric category and that different subgroups could be identified within this GOLD category.

Methods

Pre-randomization study participants from two clinical trials were symptomatic/asymptomatic GOLD 1 chronic obstructive pulmonary disease (COPD) patients and healthy controls. A hierarchical cluster analysis used pre-randomization demographics, symptom scores, lung function, peak exercise response and daily physical activity levels to derive population subgroups.

Results

Considerable heterogeneity existed for clinical variables among patients with GOLD 1 COPD. All parameters, except forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC), had considerable overlap between GOLD 1 COPD and controls. Three-clusters were identified: cluster I (18 [15%] COPD patients; 105 [85%] controls); cluster II (45 [80%] COPD patients; 11 [20%] controls); and cluster III (22 [92%] COPD patients; 2 [8%] controls). Apart from reduced diffusion capacity and lower baseline dyspnea index versus controls, cluster I COPD patients had otherwise preserved lung volumes, exercise capacity and physical activity levels. Cluster II COPD patients had a higher smoking history and greater hyperinflation versus cluster I COPD patients. Cluster III COPD patients had reduced physical activity versus controls and clusters I and II COPD patients, and lower FEV₁/FVC versus clusters I and II COPD patients.

Conclusions

The results emphasize heterogeneity within GOLD 1 COPD, supporting an individualized therapeutic approach to patients.

Trial registration

www.clinicaltrials.gov. NCT01360788 and NCT01072396.     

慢性乙肝患者的心理健康情况调查分析

目的:本文针对乙肝患者存在的心理障碍,提出相应的干预方法,为提高乙肝患者的心理健康水平及治疗效果提供理论依据。方法:选取2011年1月-2012年11月在我院接受治疗的慢性乙型肝炎患者80例作为研究组,另选取80位同期在我院接受体检的健康人群为对照组。针对两组对象的焦虑、抑郁、偏执等心理问题设计问卷调查,统计并分析调查结果。结果:观察组患者的焦虑及抑郁评分明显高于对照组,差异具有统计学意义(P0.05);观察组中,病情重的患者焦虑及抑郁评分高于病情轻、中度的患者,差异具有统计学意义(P0.05)。结论:慢性乙型肝炎患者的心理压力对治疗有影响,医护人员应积极的对乙肝患者进行心理疏导,帮助其树立自信、摆脱心理障碍,以积极的心态配合治疗,从而获得良好的疗效。     

拉米夫定联合胸腺肽A1 治疗慢性乙型肝炎的疗效观察

目的:探讨拉米夫定(LAM)联合胸腺肽α1(Tα1)治疗慢性乙型肝炎的长期疗效和安全性。方法:72例慢性乙肝患者(HBV-DNA和HBeAg均阳性),按1:1随机分配进入联合治疗组(LAM+Tα1组)和单用拉米夫定组(LAM组)。结果:治疗1年时LAM+Tα1组HBeAg血清转换率(44.4%,16/36例)明显高于LAM组(5.6%,2/36例),P<0.01。停药1年后,持续的HBeAg血清转换率分别为36.1%(13/36例)和8.3%(3/36例),P<0.01。治疗过程中及停药后,两组HBV-DNA水平均明显下降,但两组的HBV-DNA转阴率相仿。治疗后1年ALT复常率联合治疗组与拉米夫定组相似,分别为75%(27/36例)和66.7%(24/36例)、随访1年时ALT复常率联合治疗组明显高于拉米夫定组,分别为58.3%(21/36例)和16.7%(6/36例)。在治疗过程中,未发现严重的不良反应。结论:LAM联合Tα1治疗慢性乙肝,不良反应少,疗效优于单一LAM用药组。     

Increased Risk of Acute Pancreatitis in Patients with Chronic Hemodialysis: A 4-Year Follow-Up Study

Background

The risk of acute pancreatitis in patients on long-term peritoneal dialysis is higher as compared to the general population. However, the relationship between long-term hemodialysis and acute pancreatitis has never been established.

Objectives

We investigated the incidence of acute pancreatitis among patients on long-term hemodialysis in Taiwan to evaluate if there is a higher risk of acute pancreatitis in comparison to the general population.

Methods

We utilized a National Health Insurance (NHI) claims data sample containing one million beneficiaries. We followed all adult beneficiaries from January 1, 2007 until December 31, 2010 to see if they had been hospitalized for acute pancreatitis during this period. We further identified patients on chronic hemodialysis and compared their risk of acute pancreatitis with the general population.

Results

This study included 2603 patients with long-term hemodialysis and 773,140 patients without hemodialysis. After controlling for age, gender, Charlson Comorbidity Index Score, geographic region, socioeconomic status and urbanization level, the adjusted hazard ratio was 3.44 (95% Confidence interval, 2.5–4.7).

Conclusions

The risk of acute pancreatitis in patients on long-term hemodialysis is significantly higher in comparison to the general population.     

IL28B Polymorphism Correlates with Active Hepatitis in Patients with HBeAg-Negative Chronic Hepatitis B

Background & Aims

The clinical relevance of single nucleotide polymorphisms (SNPs) near the IL28B gene is controversial in patients with hepatitis B virus (HBV) infection. This study aimed to investigate the role of viral and host factors, including IL28B genotypes, in the natural course of chronic hepatitis B (CHB).

Methods

The study enrolled consecutive 115 treatment-naive CHB patients. HBV viral loads, genotypes, precore and basal core promotor mutations, serum hepatitis B surface antigen (HBsAg) and interferon-gamma inducible protein 10 (IP-10) levels as well as four SNPs of IL28B were determined. Serial alanine transaminase (ALT) levels in the previous one year before enrollment at an interval of three months were recorded. Factors associated with active hepatitis, defined as persistent ALT >2× upper limit of normal (ULN) or a peak ALT level >5× ULN, were evaluated.

Results

The prevalence of rs8105790 TT, rs12979860 CC, rs8099917 TT, and rs10853728 CC genotypes were 88.3%, 87.4%, 88.4% and 70.9%, respectively. In HBeAg-positive patients (n = 48), HBV viral load correlated with active hepatitis, while in HBeAg-negative patients (n = 67), rs10853728 CC genotype (p = 0.032) and a trend of higher IP-10 levels (p = 0.092) were associated with active hepatitis. In multivariate analysis, high viral load (HBV DNA >10⁸ IU/mL, p = 0.042, odds ratio = 3.946) was significantly associated with HBeAg-positive hepatitis, whereas rs10853728 CC genotype (p = 0.019, odds ratio = 3.927) was the only independent factor associated with active hepatitis in HBeAg-negative population.

Conclusions

HBV viral load and IL28B rs10853728 CC genotype correlated with hepatitis activity in HBeAg-positive and HBeAg-negative CHB, respectively. Both viral and host factors play roles in disease activity during different phases of CHB.     

FIC1, a P-type ATPase linked to cholestatic liver disease,has homologues (ATP8B2 and ATP8B3) expressed throughout the body

ATP8B1/FIC1 is a member of the Type IV P-type ATPase family, which function as ATP dependent aminophospholipid translocases (APLT). We identified two familial intrahepatic cholestasis type 1 (FIC1) homologues, ATP8B2 and ATP8B3, with 53% and 45% amino acid identity, respectively. The expression profile for each gene was determined using a 73-tissue human RNA expression array. The subfamily of FIC1-like proteins is expressed in a wide range of tissues. Given that mutations in FIC1 result in liver disease, these proteins may have important roles in other organs in which they are candidates for genetic and acquired diseases.     

FIC1, a P-type ATPase linked to cholestatic liver disease,has homologues (ATP8B2 and ATP8B3) expressed throughout the body

ATP8B1/FIC1 is a member of the Type IV P-type ATPase family, which function as ATP dependent aminophospholipid translocases (APLT). We identified two familial intrahepatic cholestasis type 1 (FIC1) homologues, ATP8B2 and ATP8B3, with 53% and 45% amino acid identity, respectively. The expression profile for each gene was determined using a 73-tissue human RNA expression array. The subfamily of FIC1-like proteins is expressed in a wide range of tissues. Given that mutations in FIC1 result in liver disease, these proteins may have important roles in other organs in which they are candidates for genetic and acquired diseases.     

Common Variants in CLDN2 and MORC4 Genes Confer Disease Susceptibility in Patients with Chronic Pancreatitis

A recent genome-wide association study (GWAS) identified association with variants in X-linked CLDN2 and MORC4, and PRSS1-PRSS2 loci with chronic pancreatitis (CP) in North American patients of European ancestry. We selected 9 variants from the reported GWAS and replicated the association with CP in Indian patients by genotyping 1807 unrelated Indians of Indo-European ethnicity, including 519 patients with CP and 1288 controls. The etiology of CP was idiopathic in 83.62% and alcoholic in 16.38% of 519 patients. Our study confirmed a significant association of 2 variants in CLDN2 gene (rs4409525—OR 1.71, P = 1.38 x 10^-09; rs12008279—OR 1.56, P = 1.53 x 10^-04) and 2 variants in MORC4 gene (rs12688220—OR 1.72, P = 9.20 x 10^-09; rs6622126—OR 1.75, P = 4.04x10^-05) in Indian patients with CP. We also found significant association at PRSS1-PRSS2 locus (OR 0.60; P = 9.92 x 10^-06) and SAMD12-TNFRSF11B (OR 0.49, 95% CI [0.31–0.78], P = 0.0027). A variant in the gene MORC4 (rs12688220) showed significant interaction with alcohol (OR for homozygous and heterozygous risk allele -14.62 and 1.51 respectively, P = 0.0068) suggesting gene-environment interaction. A combined analysis of the genes CLDN2 and MORC4 based on an effective risk allele score revealed a higher percentage of individuals homozygous for the risk allele in CP cases with 5.09 fold enhanced risk in individuals with 7 or more effective risk alleles compared with individuals with 3 or less risk alleles (P = 1.88 x 10^-14). Genetic variants in CLDN2 and MORC4 genes were associated with CP in Indian patients.     

ATP8B1-mediated spatial organization of Cdc42 signaling maintains singularity during enterocyte polarization

During yeast cell polarization localization of the small GTPase, cell division control protein 42 homologue (Cdc42) is clustered to ensure the formation of a single bud. Here we show that the disease-associated flippase ATPase class I type 8b member 1 (ATP8B1) enables Cdc42 clustering during enterocyte polarization. Loss of this regulation results in increased apical membrane size with scattered apical recycling endosomes and permits the formation of more than one apical domain, resembling the singularity defect observed in yeast. Mechanistically, we show that to become apically clustered, Cdc42 requires the interaction between its polybasic region and negatively charged membrane lipids provided by ATP8B1. Disturbing this interaction, either by ATP8B1 depletion or by introduction of a Cdc42 mutant defective in lipid binding, increases Cdc42 mobility and results in apical membrane enlargement. Re-establishing Cdc42 clustering, by tethering it to the apical membrane or lowering its diffusion, restores normal apical membrane size in ATP8B1-depleted cells. We therefore conclude that singularity regulation by Cdc42 is conserved between yeast and human and that this regulation is required to maintain healthy tissue architecture.     

Mutational Analysis of Bacillus megaterium QM B1551 Cortex-Lytic Enzymes

Molecular-genetic and muropeptide analysis techniques have been applied to examine the function in vivo of the Bacillus megaterium QM B1551 SleB and SleL proteins. In common with Bacillus subtilis and Bacillus anthracis, the presence of anhydromuropeptides in B. megaterium germination exudates, which is indicative of lytic transglycosylase activity, is associated with an intact sleB structural gene. B. megaterium sleB cwlJ double mutant strains complemented with engineered SleB variants in which the predicted N- or C-terminal domain has been deleted (SleB-ΔN or SleB-ΔC) efficiently initiate and hydrolyze the cortex, generating anhydromuropeptides in the process. Additionally, sleB cwlJ strains complemented with SleB-ΔN or SleB-ΔC, in which glutamate and aspartate residues have individually been changed to alanine, all retain the ability to hydrolyze the cortex to various degrees during germination, with concomitant release of anhydromuropeptides to the surrounding medium. These data indicate that while the presence of either the N- or C-terminal domain of B. megaterium SleB is sufficient for initiation of cortex hydrolysis and the generation of anhydromuropeptides, the perceived lytic transglycosylase activity may be derived from an enzyme(s), perhaps exclusively or in addition to SleB, which has yet to be identified. B. megaterium SleL appears to be associated with the epimerase-type activity observed previously in B. subtilis, differing from the glucosaminidase function that is apparent in B. cereus/B. anthracis.Spores of the genera Bacillus and Clostridium emerge from dormancy via the process of germination. The germination process comprises a series of sequential biophysical and biochemical reactions that result irreversibly in the spore losing its properties of metabolic dormancy and extreme resistance to various chemical and physical treatments (24, 34). Germination is initiated by the presumed binding of small molecular germinants, commonly amino acids or sugars, to cognate receptors located within the spore inner membrane (25, 28). In a process that is poorly understood at the molecular level, this interaction leads to a change in the permeability of the inner membrane, resulting in the release of various solutes from the spore core, including metal ions, calcium dipicolinate (Ca-DPA), and some amino acids (32, 33, 35). A degree of rehydration of the core is evident at or around the same time, although this is insufficient to permit a significant degree of vegetative metabolism (9, 31). These events, which appear common to all Bacillus species where examined, comprise stage I of germination (31, 32, 34).The major event in stage II of the germination process from a biochemical perspective involves depolymerization of the spore cortex. The spore cortex is a thick layer of peptidoglycan, characterized by the spore-specific muramic acid lactam (MAL) moiety (37, 38), which, together with the thin inner layer of germ cell wall peptidoglycan (36), forms contiguous layers that entirely envelope the spore protoplast. While the germ cell wall forms the initial cell wall during vegetative outgrowth, the spore cortex serves primarily to maintain the relatively dehydrated status of the spore protoplast during dormancy (13). Dissolution of the cortex permits complete hydration of the spore core and resumption of vegetative metabolism, leading ultimately to shedding of the spore coat and the emergence of a new vegetative cell (34).A number of studies have indicated that spores of various Bacillus species employ two cortex-lytic enzymes (CLEs), SleB and CwlJ, to initiate hydrolysis of the cortex during stage II of the germination process (16, 19, 32). These enzymes are semiredundant; hence, strains bearing null mutations in either structural gene can still degrade the cortex sufficiently to complete germination, whereas double mutant strains do not appear capable of degrading the cortex at all, resulting typically in a decrease of several orders of magnitude in colony-forming ability (15, 19, 32). Other enzymes, including Bacillus cereus/Bacillus anthracis SleL, are also involved in stage II of germination, apparently hydrolyzing peptidoglycan products of SleB and/or CwlJ to smaller peptidoglycan fragments that can more easily permeate through the spore coats to the surrounding germination medium (21).Studies with SleB and SleL purified from dormant and germinating spores indicate that whereas the latter enzyme degrades only cortical fragments of peptidoglycan (7), SleB has a requirement for intact peptidoglycan that has adopted the precise architecture present within the spore (12, 22). These substrate requirements appear to be important in maintenance of the respective autolysins, which are present in the spore in a mature form, in an inactive state during dormancy. Additionally, whereas the molecular mechanism of activation of SleB remains unclear—a change in cortical stress/architecture induced by stage I events has been hypothesized (12)—the efflux of Ca-DPA from the spore core to the cortex/coat boundary where CwlJ is localized (5) appears to be the mechanism by which this CLE is activated. CwlJ can also be activated by high concentrations of exogenous Ca-DPA, presenting an alternative germination pathway that bypasses the germinant receptors (27).The hydrolytic bond specificity of various CLEs has been examined by both direct and indirect biochemical means. Direct assays are typically conducted by incubation of purified or recombinant enzymes with peptidoglycan fragments or suspensions of spores in which the cortex is rendered accessible by first chemically compromising the permeability of the spore coats (7, 12, 22). Subsequent assays for the generation of reducing groups and/or free amino groups can yield information on the probable hydrolytic bond specificity of the respective enzyme(s) being assayed.More recently, the high-performance liquid chromatography/mass spectrometry (HPLC/MS)-based muropeptide analysis technique has been applied to characterize CLE activity during germination of various spore-forming species (2, 4, 10). This methodology has the resolution to reveal fine structural changes that occur to the peptidoglycan in vivo during germination, and when used in combination with CLE null mutant strains, it can be used to indirectly correlate the generation of certain classes of muropeptides, and therefore the hydrolytic bond specificity, with defined CLEs. Muropeptide analysis has revealed, for example, that an intact copy of the sleB gene in B. subtilis and B. anthracis is required for the presence of anhydromuropeptides in the germination exudates of these respective species, indicating that SleB is a lytic transglycosylase or generates substrate for subsequent lytic transglycosylase activity (6, 16). Conversely, B. cereus SleB was characterized as a probable amidase after enzyme purified from germinating spores was found to liberate a large amount of free amino groups when incubated with coat-stripped spores as a substrate (22). The hydrolytic bond specificity of SleB therefore remains ambiguous and perhaps varies between different species.Contrary to these observations, the overall structural architecture of SleB appears to be well conserved between different Bacillus species. Alignment of the primary amino acid sequence from different species indicates that the mature protein comprises an N-terminal domain that is connected to the C-terminal domain by a linker region that is variable in length and amino acid composition (Fig. ​(Fig.1).1). The N-terminal domain is thought to comprise the peptidoglycan binding domain by virtue of two direct sequence repeats that are reminiscent of cell wall-binding motifs observed in other proteins (26). The C-terminal domain shows homology with that of the other major Bacillus CLE, CwlJ, which lacks a corresponding peptidoglycan binding domain and is therefore thought to comprise the catalytic domain (19), although there is as yet no experimental evidence to substantiate this idea.Open in a separate windowFIG. 1.ClustalW alignment of SleB from various Bacillus species. Residues predicted to comprise putative structural domains are denoted. Stars indicate charged residues that were subjected to amino acid substitution in this work. BM, B. megaterium QM B1551; BC, B. cereus W; BCl, B. clausii KSM-K16; BS, B. subtilis 168.In the current study, we have investigated the molecular function of SleB during germination of Bacillus megaterium QM B1551 spores, employing engineered SleB N- and C-terminal deletion strains, site-directed mutagenesis (SDM), and muropeptide analyses. In addition to revealing several cortex-modifying activities during germination of this species, the presented data indicate that while the presence of either the N- or C-terminal domain of SleB is sufficient for the generation of anhydromuropeptides during germination, this may be an indirect effect, and at least a degree of lytic transglycosylase activity may result from the activity of another as yet unidentified enzyme.     

慢性乙型肝炎患者血清HBV基因分型

为了解长春市慢性乙型肝炎患者血清中的乙型肝炎病毒(HBV)基因型情况及其与临床特点的相关性,应用型特异性引物进行巢式PCR方法对长春市69例慢性乙型肝炎患者血清HBV进行基因分型检测。在69例血清标本中,B型10例(占14.5%);C型41例(占59.4%);B C混合型8例(占11.6%);未分型的患者共10例(占14.5%)。C基因型患者的HBV-DNA定量、HBeAg阳性率明显高于B基因型患者(HBV-DNA:P<0.01;HBeAg:χ2=3.98,P<0.05),C基因型患者肝功检查指标谷丙转氨酶(ALT)和总胆红素(TB IL)均较B基因型患者高(P<0.01)。长春地区存在HBV B基因型、C基因型、B C混合基因型及未分型,C基因型为优势基因,引起的肝脏活动性炎症较B基因型明显。     

聚乙二醇干扰素α-2a对慢性乙型肝炎患者树突状细胞B7-H1表达的影响

目的：观察聚乙二醇干扰素α-2a对慢性乙型肝炎患者外周血树突状细胞功能及B7-H1的影响,探讨慢性乙型肝炎病毒逃逸的的机制。方法：慢性乙型肝炎患者31例,给予聚乙二醇干扰素α-2a180txg抗病毒治疗52周,分别于0、12、26、52周检测肝功能、HBV-DNA;流式细胞术检测外周血mDC表面HLA-DR、CD80、CD86、CD83、CDla、B7一H1水平。根据患者HBV—DNA水平,将患者分为应答组（A组）、非应答组（B组）,10例健康志愿者作正常对照组（C组）。结果：慢性乙肝患者的树突状细胞膜表面分子HLA-DR、CD80、CD86、CD83、CDla的表达均降低。聚乙二醇干扰素α-2a治疗后应答组膜表面分子HLA-DR、CD80、CD86、CD83、cDla的表达高于非应答组65．3±6．2％VS44．2±5．5％,67．2±7．4％VS37.3±7．2％,68．4±3．6％VS42．5±7．3％,65．6±6．8％VS43．2±3．9％,49．4±9．5％VS37．5±7．9％,（P〈0．05）。应答组B7-H1表达水平较治疗前下降,非应答组B7-H1水平无明显变化12．73±3．8％VS25．24±2．92％,（P〈0．05）。结论：慢性乙型肝炎患者树突状细胞功能低下,聚乙二醇干扰素α-2a治疗可以提高树突状细胞功能,降低B7-H1表达,促进HBV-DNA的清除。树突状细胞功能低下及B7-H1高表达是乙型肝炎病毒免疫逃逸的因素之一。