Molecular mechanism of hepatitis B virus X protein function in hepatocarcinogenesis

Many factors are considered to contribute to hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),including products of HBV,HBV integration and mutation,and host susceptibility. HBV X protein(HBx) can interfere with several signaling pathways associated with cell proliferation and invasion,and HBx C-terminal truncation has been suggested to impact the development of HCC. This review focuses on the pathological functions of HBx in HBV-induced hepatocarcinogenesis. As a transactivator,HBx can affect regulatory non-coding RNAs(nc RNAs),including micro RNAs and long nc RNAs. HBx is also involved in epigenetic modification and DNA repair. HBx interacts with various signal-transduction pathways,such as the p53,Wnt,and nuclear factor-κB pathways. We conclude that HBx hastens the development of hepatoma.

Nonalcoholic fatty liver disease and hepatic cirrhosis: comparison with viral hepatitis-associated steatosis

Nonalcoholic fatty liver disease(NAFLD) including nonalcoholic steatohepatitis(NASH) is globally increasing and has become a world-wide health problem. Chronic infection with hepatitis B virus or hepatitis C virus(HCV) is associated with hepatic steatosis. Viral hepatitis-associated hepatic steatosis is often caused by metabolic syndrome including obesity,type 2 diabetes mellitus and/or dyslipidemia. It has been reported that HCV genotype 3 exerts direct metabolic effects that lead to hepatic steatosis. In this review,the differences between NAFLD/NASH and viral hepatitis-associated steatosis are discussed.

Serum hepatitis B surface antigen levels predict treatment response to nucleos(t)ide analogues

Quantification of hepatitis B surface antigen(HBsAg)has been suggested to be helpful in the management of chronic hepatitis B(CHB)patients.Nucleos(t)ide analogs(NAs)are the therapy of choice for CHB and are used in the majority of CHB patients.NAs are able to induce hepatitis B virus(HBV)viral suppression,normalization of alanine aminotransferase(ALT)levels,and improvement in liver histology.Automated quantitative assays for serum HBsAg have recently become available,facilitating standardized quantification of serum HBsAg.This has led to increased interest in the clinical application of quantitative serum HBsAg for predicting therapeutic response to NAs.Recent studies have shown that a decline in serum HBsAg levels in patients receiving peginterferon may signal successful induction of immune control over HBV,and can therefore be used to predict therapeutic response.NA treatment typically induces a less rapid decline in HBsAg than interferon treatment;it has been estimated that full HBsAg clearance can require decades of NA treatment.However,a rapid HBsAg decline during NA therapy may identify patients who will show clearance of HBsAg.Currently,there is no consensus on the clinical utility of serum HBsAg monitoring for evaluating patient responses to NA therapy.This review focuses on recent findings regarding the potential application of HBsAg quantification in the management of CHB patients receiving NA therapy.

Application of nucleoside analogues to liver transplant recipients with hepatitis B

Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus(HBV) core antibody(HBc Ab) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues(NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBc Ab-positive liver grafts.

Urinary nuclear magnetic resonance spectroscopy of a Bangladeshi cohort with hepatitis-B hepatocellular carcinoma: A biomarker corroboration study

AIM: To establish if a distinct urinary metabolic profile could be identified in Bangladeshi hepatitis-B hepatocellular carcinoma(HCC) patients compared to cirrhosis patients and controls. METHODS: Urine samples from 42 Bangladeshi patients with HCC(39 patients with hepatitis-B HCC), 47 with cirrhosis on a background of hepatitis B, 46 with chronic hepatitis B, and seven ethnically-matched healthy controls were analyzed using nuclear magnetic resonance(NMR) spectroscopy. A full dietary and medication history was recorded for each subject. The urinary NMR data were analyzed using principal component analysis(PCA) and orthogonal partial leastsquared discriminant analysis(OPLS-DA) techniques. Differences in relative signal levels of the most discriminatory metabolites identified by PCA and OPLSDA were compared between subject groups using an independent samples Kruskal-Wallis one-way analysis of variance(ANOVA) test with all pairwise multiple comparisons. Within the patient subgroups, the MannWhitney U test was used to compare metabolite levels depending on hepatitis B e-antigen(HBe Ag) status and treatment with anti-viral therapy. A BenjaminiHochberg adjustment was applied to acquire the level of significance for multiple testing, with a declared level of statistical significance of P < 0.05.RESULTS: There were significant differences in age(P < 0.001), weight(P < 0.001), and body mass index(P < 0.001) across the four clinical subgroups. Serum alanine aminotransferase(ALT) was significantly higher in the HCC group compared to controls(P < 0.001); serum α-fetoprotein was generally markedly elevated in HCC compared to controls; and serum creatinine levels were significantly reduced in the HCC group compared to the cirrhosis group(P = 0.004). A threefactor PCA scores plot showed clustering of the urinary NMR spectra from the four subgroups. Metabolites that contributed to the discrimination between the subgroups included acetate, creatine, creatinine, dimethyamine(DMA), formate, glycine, hippurate, and trimethylamine-N-oxide(TMAO). A comparison of relative metabolite levels confirmed that carnitine was significantly increased in HCC; and creatinine, hippurate, and TMAO were significantly reduced in HCC compared to the other subgroups. HBe Ag negative patients showed a significant increase in creatinine(P = 0.001) compared to HBe Ag positive patients in the chronic hepatitis B subgroup, whilst HBe Ag negative patients showed a significant decrease in DMA(P = 0.004) in the cirrhosis subgroup compared to HBe Ag positive patients. There were no differences in metabolite levels in HCC patients who did or did not receive antiviral treatment. CONCLUSION: Urinary NMR changes in Bangladeshi HCC were identified, corroborating previous findings from Egypt and West Africa. These findings could form the basis for the development of a cost-effective HCC dipstick screening test.

Use of endoscopic ultrasound for diagnosis of cholangiocarcinoma in auto-immune hepatitis

In this report, a patient was exposed to an herbal remedy for hypercholesterolemia. She became acutely jaundiced while taking the remedy and presented for medical care. Endoscopic ultrasound was utilized, and found a distal common bile duct mass. Endoscopic retrograde cholangiopancreatography guided bile duct biopsies revealed that the mass was cholangio-carcinoma (CCA). This case highlights a unique association between autoimmune hepatitis and CCA. It also highlights that EUS can be safely used in patients with cirrhosis to spare invasive evaluation such as exploratory laporotomy for diagnosis and staging of cholangio-carcinoma.

Chinese Consensus on Antiviral Treatment of Chronic Hepatits B Patients with Nucleos(t)ide Analogues

Antiviral treatment is the main method for chronic hepatitis B(CHB).After antiviral treatment,some patients may obtain satisfactory therapeutic effect,but some patients still show primary non-response,suboptimal response,even resistance to nucleos(t)ide analogues or relapse,which are becoming the key problems and confusing the clinical staffs.Thus,in January 2013,editorial department of Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition),Chinese Journal of Liver Diseases(Electronic Edition)

Four-year follow up of hepatitis C patients vaccinated against hepatitis B virus

AIM: Patients with chronic hepatitis C have been recommended to receive vaccinations against hepatitis B. Our study aimed at evaluating the hepatitis B immunogenicity and efficacy against hepatitis B virus infection 4 years after primary immunization series in a group of patients with chronic hepatitis C.METHODS: We recruited 36 out of 48 hepatitis C virus (HCV) infected individuals who were vaccinated against hepatitis B virus (20 μg of recombinant HBsAg at 0-1-6mo schedule) in 1998. Here we measured anti-HBs titers and anti-HBc 4 years after delivery of the third dose of primary immunization series.RESULTS: After 4 years a total of 13/36 (36%) HCV infected patients had seroprotective titers of anti-HBs compared with 9/10 (90%) in the control group, (P＜0.05).Similarly the mean concentration of anti-HBs found in hepatitis C patients was significantly lower than that found in healthy subjects (18.3 and 156.0 mIU/mL respectively (P＜0.05). None of the HCV infected patients or controls became infected with HBV during the study period as confirmed by anti-HBc negativity.CONCLUSION: We demonstrated that 4 years after HBV immunizations' more than 60% of vaccinated HCV patients did not maintain seroprotective levels of anti-HBs, which might put them at risk of clinically significant breakthrough infections. Further follow-up studies are required to clarify whether memory B and T lymphocytes can provideprotection in chronic hepatitis C patients in the absence or inadequate titers of anti-HBs.

Efficacy of pegylated interferon-alpha-2a plus ribavirin for patients aged at least 60 years with chronic hepatitis C

Background In China, patients with hepatitis C virus （HCV）-associated liver disease are getting older, and thus the number of deaths due to such disease is increasing. The efficacy of combination therapy with ribavirin and interferon for chronic HCV infection in elderly patients has not been fully clarified. The aim of the present study was to evaluate the efficacy and tolerability of the combination therapy in the elderly patients. Methods Sixty-eight chronic hepatitis C patients, who received the combination therapy, were classified into two age groups： elderly group （〉60 years, n=25） and non-elderly group （〈60 years, n=43）. Rapid virological response, complete early virological response, sustained virological response, relapse, non-response rate, and safety were compared between the elderly group and non-elderly group. Results Overall sustained virological response was lower in the elderly group than non-elderly group （44% vs. 75%, P=0.012, OR=0.270, and 95% CI 0.095-0.768）. Among patients with HCV genotype 1, sustained virological response was lower in the elderly group than non-elderly group （45% vs. 77%, P=0.015, OR=0.247, 95% CI 0.078-0.781）. The proportions of dose reduction due to laboratory abnormalities were significantly higher in the elderly group than non-elderly group （60.0% vs. 32.6%, P=0.027）. Multiple binary Logistic regression analysis confirmed that patient age was an associated factor for sustained virological response. Conclusion Among patients with HCV genotype 1, the elderly patients had lower sustained virological response than non-elderly patients during pegylated interferon-alpha-2a plus ribavirin combination therapy.

Clinical Observation on Effect of Ruangan Granule (软肝颗粒剂) in Treating Chronic Hepatitic Liver Fibrosis

Objective: To observe the clinical effect of Ruangan granule (RGG) in treating liver fibrosis.Methods: One hundred and twenty patients of chronic viral hepatitis B were randomly divided into two groups, 60 patients in the treated group and 60 patients in the control group. They were treated with RGG or composite Biejia Ruangan tablet (复方鳖甲软肝片) respectively for three months. The changes of liver function, liver fibrosis indices, including fibronectin (FN), laminin (LN) and hyaluronic acid (HA), as well as liver morphology by B ultrasonic examination were observed after treatment. A three month follow up study was also conducted. Results: In the treated group, the markedly effective rate was 50.0% and effective rate was 41.7%, while in the control group, the corresponding rates were 26.7% and 55.0% respectively. Comparison of the markedly effective rate between the two groups showed significant difference ( P <0.01). The serum levels of FN, LN, HA as well as splenomegaly and portal vein widening in the treated group after treatment were significantly improved ( P <0.05), as compared with those in the control group after treatment; significant difference was shown in comparison of serum FN, LN and HA. Conclusion: RGG could improve effectively serum liver fibrosis indices and liver function in patients of chronic hepatitic fibrosis. It is helpful in alleviating and inhibiting the genesis and development of liver fibrosis so as to block the progression of liver cirrhosis.

Traditional Chinese Medicine Diagnosis and Evaluation of the Clinical Effect in Post-hepatitic Cirrhosis based on Fuzzy Analysis

In view of the problem of traditional Chinese medicine (TCM) diagnosis, fuzzy comprehensive evaluation is introduced to the diagnosis and evaluation of the clinical effect of hepatitis. A new diagnosis and evaluation model of the TCM clinical effect standard was presented. The old disputed evaluation model by subjective analysis can be displaced by this objective method in its evaluation system. The foundation of this method is the fuzzy diagnosis model. This method has been realized to diagnose hepatitis and its values in practice has been validated through examples of clinical syndromes of post-hepatitic cirrhosis.

核苷(酸)类似物对ALT正常或轻度升高的HBeAg阴性慢性乙型肝炎患者的疗效分析

目的分析核苷/核苷酸类似物(NAs)对丙氨酸氨基转移酶(ALT)正常或轻度升高的HBeAg阴性慢性乙型肝炎(CHB)患者的疗效。方法纳入2018年6月-2021年7月期间淮安市第四人民医院肝病科收治的HBeAg阴性CHB患者102例,其中男性68例,女性34例,年龄(41.7±9.2)岁。根据血清ALT基线水平将纳入病例分为ALT正常组(n=59)和ALT轻度升高组(n=43)[ALT低于2倍正常值上限(ULN)]。比较NAs治疗后两组病毒应答(VR)率、HBV DNA、ALT以及肝脏硬度值(LSM)变化。结果ALT正常组男性比例、ALT、AST及HBV DNA为34例(57.6%)、(25.4±8.0)U/L、(24.2±8.3)U/L及(4.4±1.0)log_(10) IU/mL,分别显著低于ALT轻度升高组[34例(79.1%)、(70.3±17.5)U/L、(52.3±16.2)U/L及(5.2±1.3)log_(10) IU/mL,P<0.05]。正常ALT组VR率在第12、24、36、48、72和96周分别为49.2%(29/59)、66.1%(39/59)、81.4%(48/59)、84.7%(50/59)、93.2%(55/59)及93.2%(55/59),对应的ALT轻度升高组VR率分别为41.9%(18/43)、58.1%(25/43)、69.8%(30/43)、76.7%(33/43)、86.0%(37/43)及95.3%(41/43)。对数秩检验得出两组VR率差异无统计学意义(P>0.05)。NAs抗病毒治疗期间,HBV DNA载量显著降低。ALT正常组在治疗48周和96周后HBV DNA水平分别下降(2.8±1.2)log_(10) IU/mL、(3.7±1.1)log_(10) IU/mL;对应的ALT轻度升高组HBV DNA水平分别下降(3.6±1.5)log_(10) IU/mL、(4.3±1.5)log_(10) IU/mL。两组患者HBV DNA平均下降程度比较差异无统计学意义(P>0.05)。正常ALT组在第12、24、36、48、72和96周时ALT复常率分别为71.2%(42/59)、86.4%(51/59)、91.5%(54/59)、94.9%(56/59)、96.6%(57/59)及96.6%(57/59),对应的ALT轻度升高组ALT复常率分别为53.5%(23/43)、76.7%(33/43)、83.7%(36/43)、88.4%(38/43)、95.3%(41/43)及100%(43/43)。两组ALT复常率比较差异无统计学意义(P>0.05)。有37例ALT正常、轻度升高HBeAg阴性CHB患者在NAs治疗48周时接受FibroScan检查,发现LSM值显著改善[(7.9±3.2)kPa比(6.6±2.9)kPa,P<0.05];NAs治疗96周后对25例患者进行FibroScan检查,结果显示治疗后LSM值显著改善[(8.1±3.3)kPa比(6.2±2.7)kPa,P<0.05]。结论NAs有效抑制了ALT正常或轻度升高的HBeAg阴性CHB患者HBV DNA水平,并改善了肝脏组织学表现。因此,即便是ALT正常的HBeAg阴性CHB也建议行抗病毒治疗。此外ALT正常或轻度升高的HBeAg阴性CHB患者中显著肝纤维化病例并不少见,应该对他们常规进行肝纤维化评估。

干扰素治疗慢性乙型肝炎研究进展

乙型肝炎病毒(hepatitis B virus,HBV)感染是全球性的公共卫生问题,中国是感染HBV人数最多的国家。HBV感染后,免疫系统不能及时有效地清除病毒,机体免疫耐受导致慢性乙型肝炎(chronic hepatitis B,CHB)。CHB可导致肝硬化、肝衰竭、肝癌等,严重危害人群健康。干扰素(interferon,IFN)是治疗CHB的一线药物,具有提高功能性治愈率、可安全停药、实现持续的非治疗性免疫反应、降低肝癌发生率及避免耐药的发生等优势,可延缓CHB患者病程进展,改善患者生活质量。本文将从IFN的作用机制、优势、治疗模式、治疗前景等方面进行综述,以期为临床实践提高干扰素抗病毒疗效提供依据。

探讨慢性肝炎患者血清肝纤维化指标的临床价值

探讨慢性肝炎患者血清肝纤维化指标（ＨＡ、ＰＣⅢ、Ⅳ－Ｃ、ＬＮ）的临床实用价值。对２５００例慢性肝炎患者，用放射免疫法进行血清ＨＡ、ＰＣⅢ、Ⅳ－Ｃ、ＬＮ的检测，其中２３７例进行肝穿刺及肝脏病理组织学检查。结果显示２５００例轻、中、重度慢性肝炎患者的ＨＡ、ＰＣⅢ、Ⅳ－Ｃ、ＬＮ指标均有明显差异（Ｐ＜０．０１）；４项肝纤维化指标水平与乙肝患者的肝脏炎症活动度分级、肝纤维化程度分期与病理组织学分度均存在显著相关（ｒ＝０．２５６－０．３９９）。血清肝纤维化指标对判断慢性肝炎的肝纤维化和肝硬化倾向具有临床实用意义。

抗乙肝新药阿德福韦的研究进展

阿德福韦 (adefovir)是新一代核苷类抗病毒药物 ,能够有效抑制逆转录病毒、嗜肝病毒和疱疹病毒等各种病毒的复制和表达。实验研究表明阿德福韦不仅对慢性乙型肝炎病毒有着显著的抑制作用 ,而且其对于拉米夫定等耐药的变异病毒株同样有效 ,是一种新型的核苷类抗病毒药 ,预期可望成为解决核苷类似物耐药问题的有效办法。在迄今为止的实验中 ,阿德福韦显示了良好的安全及有效性。本文主要对阿德福韦的药理作用机制、临床应用进展等作一综述。

慢性乙型肝炎患者心身症状和应对方式对生活质量的影响

目的 :研究慢性乙型肝炎患者的心身症状水平和应对方式对生活质量的影响。方法 :对 15 2名住院慢性乙肝病人用慢性肝病问卷 (CLDQ)、症状自评量表 (SCL - 90 )、医学应对问卷 (MCMQ)进行调查。结果 :慢性乙肝患者SCL - 90得分与常模和对照组有显著差异 ,各因子与CLDQ各维度呈负相关 ,以SCL - 90总均分 0 .4 4为划界分将病人分成阳性组和阴性组 ,阳性组CLDQ各维度得分均低于阴性组。患者面对应对低于常模 ,回避和屈服应对高于常模 ,阳性组比阴性组患者更倾向于采用回避和屈服应对 ,这两种消极的应对方式与生活质量呈负相关。结论 :慢性乙肝患者的心身症状及不良的应对方式对患者的生活质量有较大影响 ,要想通过心理干预减轻患者心身症状 ,提高患者的生活质量 。

乙型肝炎病毒垂直传播在人早期胚胎感染的检测

目的 探讨HBV的垂直传播途径,分析母亲血清的HBV复制水平与早期胚胎感染HBV的关系。方法 对31例进行人工流产的HBsAg阳性的早孕期母亲（同时父亲HBsAg阴性）用PCR法检测了血清及胚胎组织的HBVDNA,并以相应的子宫内膜组织作对照。血清HBV标志物用Elisa方法进行检测。结果 共检测出胚胎组织HBVDNA阳性而相应的子宫内膜组织阴性的7例（22.58％）,其中20例母血HBeAg和/或HBV DNA阳性的胚胎组织检出5例（25.00％）,11例母血HBeAg和HBV DNA均阴性的胚胎组织检测出2例（18.18％）,无显著性差异（P>0.05）。结论HBV的感染可以发生在胚胎早期,提示一部分HBV的垂直传播可能是经受精卵携带病毒DNA途径实现的,并且这种传播可能与母血HBV的复制水平无密切相关,即使母亲血清HBeAg和HBV DNA均阴性,其胚胎也存在着经受精卵途径感染的可能。加强对此类人群的免疫预防可能是今后减少传染源的关键。

湖北汉族人群对乙肝疫苗免疫应答能力与HLA-DRB1等位基因相关性的研究

目的分析HLA-DRB1等位基因型别与个体乙肝疫苗免疫应答水平的相关性。方法对37名湖北汉族健康自愿者进行HBV血源型疫苗标准全程接种,共3次(0,1,6月),末次接种后8周用酶免疫法(EIA)检测血清抗-HBs抗体水平(S/N≥2.1为应答者,S/N<2.1为无应答者);同时,对全部受试者进行HLA-DRB1基因分型。结果37名个体中无应答者7名(19%),应答者30名(81%),无应答与HLA-DRB*1001等位基因具有显著相关性,RR=21.75,X2=5.55,P<0.05。结论在湖北汉族人群中。

甲肝减毒活疫苗(L-A-1)免疫持久性观察

对接种甲肝减毒活疫苗的222名志愿者进行了连续5年的免疫持久性观察，二批疫苗免后6周抗体阳转率分别为97.36％和97.22％，抗体GMT分别为5．134和5．408；免后3年抗体阳性率为88.89％和89.42％，GMT为2．764和2．406；兔后5年抗体阳性率为80．76％和81．69％，GMT为1．746和1．823。疫苗批间抗体阳性率、GMT差异无显著性意义，表明该疫苗具有良好的免疫原性及免疫持久性。

APRI、FIB-4和GPR对慢性乙型肝炎肝脏炎症程度的诊断价值

目的评价AST/PLT指数(APRI)、纤维化指数(FIB-4)、GGT/PLT比值(GPR)对慢性乙型肝炎(CHB)患者肝组织炎症分级的诊断价值。方法选取2016年10月—2019年10月在上海市公共卫生临床中心住院期间接受经皮肝组织活检及常规实验室检查的CHB患者545例。依据Scheuer方法进行炎症分级(G),并依据临床指标分别计算APRI、FIB-4、GPR。正态分布计量资料2组间比较采用t检验;非正态分布计量资料2组间比较采用Mann-Whitney U检验。计数资料2组间比较采用χ2检验。两变量间相关性应用Spearman相关分析。血清无创诊断模型对肝组织炎症活动度分级的诊断性能评价采用受试者工作特征曲线法(ROC曲线)。采用Delong检验比较血清无创模型的ROC曲线下面积(AUC)。结果545例患者中肝组织炎症分级G0~1级224例,G2级209例,G3级112例。Spearman相关分析结果显示,APRI、FIB-4和GPR值与肝组织炎症分级均呈正相关(r值分别为0.611、0.470、0.563,P值均<0.001)。APRI、FIB-4和GPR诊断肝炎症分级G≥2的AUC分别为0.820、0.719、0.782;临界值分别为0.53、1.48和0.20;GPR诊断G≥2的效能优于FIB-4(P=0.01),但略低于APRI(P=0.048)。基于ALT水平分层分析,在ALT≤1×ULN组、1~2×ULN组和2~5×ULN组,APRI诊断G≥2的AUC分别为0.847、0.786和0.724,FIB-4分别为0.777、0.729和0.626,GPR分别为0.801、0.781和0.607;亚组结果显示除在2~5×ULN组GPR诊断效能低于APRI(P=0.042),其余ALT分层组GPR和APRI、FIB-4诊断性能相似。APRI、FIB-4和GPR诊断肝炎症分级G≥3的AUC分别为0.791、0.725、0.801;临界值分别为0.66、1.49和0.25;GPR诊断炎症分级G≥3的效能与APRI相似,但优于FIB-4(P=0.006)。基于ALT水平分层分析,在ALT≤1×ULN组、1~2×ULN组和2~5×ULN组,APRI诊断G≥3的AUC分别为0.900、0.742和0.693,FIB-4分别为0.874、0.683和0.644,GPR分别为0.890、0.805和0.668。亚组结果显示除在1~2×ULN组GPR诊断效能优于FIB-4(P=0.015),其余ALT分层组GPR和APRI、FIB-4诊断性能相似。结论APRI、FIB-4和GPR可较准确地诊断CHB肝脏炎症坏死程度,有助于监测CHB疾病进展,并对抗病毒治疗时机的确定有重要意义。