慢性乙型肝炎患者临床和肝组织病理学特点及影响肝纤维化因素分析*

目的 分析HBeAg阴性与阳性慢性乙型肝炎（CHB）患者临床和肝组织病理学特点,探讨影响CHB患者发生明显肝纤维化的危险因素。方法 回顾性分析250例CHB患者血清HBV DNA水平、Fibroscan检测肝脏硬度（stiffness）值和肝穿刺组织病理学特点,应用多因素Logistic回归模型分析影响CHB患者发生明显肝纤维化的独立危险因素。结果 160例HBeAg阴性患者血清HBV DNA ≥1×10⁵ copies/ml者所占比例显著低于HBeAg阳性组（66.9%对99.4%,P<0.05）;HBeAg阴性组血清ALT和AST水平显著低于HBeAg阳性组（P<0.05）;血清HBeAg阴性组与阳性组肝组织炎症分级和纤维化分期总体分布差异无统计学意义（P>0.05）;多因素Logistic回归分析结果显示年龄≥40岁、HBV DNA水平高、PTA低和Stiffness水平高为CHB患者存在明显肝纤维化的独立危险因素。结论 血清HBeAg阴性与阳性CHB患者存在一些临床和肝组织病理学特征的差异,血清HBeAg阴性患者可能存在更为严重的临床和预后问题,需要给予特别的关注和管理。     

血清HBsAg低水平患者肝组织炎症活动和纤维化程度及其相关影响因素分析*

目的 探讨血清HBsAg低水平的慢性乙型肝炎患者肝组织炎症活动和纤维化分期的相关影响因素。方法 2016年3月~2018年3月我院诊治的70例血清HBsAg低水平慢性乙型肝炎患者,行肝活检检查,采用Scheuer法对肝组织进行炎症分级和纤维化分期,采用单因素和多因素回归分析影响肝组织炎症活动和纤维化分期的因素。结果 本组肝组织无明显炎症(G₀-G₁)者26例（37.1%）,中重度炎症（G₂-G₃)者44例（62.9%）;无/轻度肝纤维化（S₀-S₁）者37例（52.8%）,中重度肝纤维化（S₂-S₃）者33例（47.2%）;经非条件单因素和多因素回归分析,发现感染时间[比值比（OR）=3.245,95 %可信区间（CI）:1.210~2.012,P=0.035]和脾静脉内径（OR=4.011,95% CI:1.248~6.514,P=0.025）是影响肝组织炎症分级的独立危险因素,而血清天冬氨酸氨基转移酶水平（OR=2.225,95% CI:0.895~1.211,P=0.048）和血小板计数（OR=3.014,95% CI:0.964~1.010,P=0.021）为影响肝纤维化程度的独立危险因素。结论 血清HBsAg低水平的慢性乙型肝炎患者肝组织仍然可能存在明显的炎症和纤维化,需要及时进行肝组织学检查,以明确病变程度,并给予相应的处理,以免延误了病情。     

慢性乙型肝炎患者肝纤维化的危险因素分析

目的 探讨慢性乙型肝炎患者发生显著肝纤维化的危险因素。方法 2015年1月～2016年8月我院诊治且行肝穿刺病理学检查的慢性乙型肝炎患者80例,将肝组织病理学纤维化分期≥S2期定义为显著纤维化。采用荧光定量PCR法检测血清HBV DNA,采用酶联免疫吸附法检测HBV标记物,使用全自动生化分析仪检测肝功能,同时检测血常规和凝血功能等指标。结果 本组发现显著肝纤维化患者58例（72.50%）;显著纤维化患者血清HBV DNA、丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、谷氨酰转肽酶（GGT）、凝血酶原时间（PT）、红细胞体积分布宽度（RDW）和血小板平均容积（MPV）分别为（9.32±1.20）log10 IU/ml、（49.50±12.48）U/L、（48.91±10.11）U/L、（60.38±21.21）U/L、（15.52±1.28）s、（15.51±2.33）%和（12.20±3.05）fl,显著高于22例非显著肝纤维化患者[分别为（6.49±1.18）log10 IU/ml、（31.29±8.50）U/L、（28.47±6.77）U/L、（26.35±17.49）U/L、（14.10±2.31）s、（13.29±3.20）%和（10.13±3.22）fl,P<0.05];显著纤维化患者白细胞计数（WBC）、血红蛋白（Hb）和血小板计数（PLT）分别为（5.10±1.73）×10⁹/L、（123.47±12.10）g/L和（120.76±20.85）×10⁹/L,显著低于非显著纤维化患者[（6.51±1.52）×10⁹/L、（130.85±13.10）g/L、（213.75±23.48）×10⁹/L,P<0.05];HBV DNA、ALT、AST、GGT、PT、RDW、MPV与肝纤维化程度呈正相关性（r=0.642、r=0.411、r=0.411、r=0.447、r=0.397、r=0.538、r=0.486,P<0.05）,而WBC、Hb、PLT与肝纤维化程度呈负相关（r=-0.375、r=-0.362、r=-0.543,P<0.05）;Logistic回归分析发现PLT下降是慢性乙型肝炎患者显著肝纤维化的独立危险因素（OR=0.93,P<0.05）。结论 慢性乙型肝炎患者伴有血常规、肝功能、凝血功能指标异常是肝纤维化的高危人群。     

不同医院无创性肝纤维化指标预测慢性乙型肝炎患者肝纤维化效能差异分析*

目的 探讨应用谷草转氨酶/血小板比值（APRI）、基于4因子的纤维化指数（FIB-4）和瞬时弹性成像技术评判不同医院慢性HBV感染者肝纤维化的效能差异。方法 在2所大学附属医院收治的慢性HBV携带者或慢性乙型肝炎（CHB）行肝穿刺,并获得APRI、FIB-4和肝脏硬度检测（LSM）值,采用ROC曲线分析指标的诊断效能。结果 两组分别纳入327例（A组）和250例（B组）患者,两组患者肝组织病理学检查肝纤维化分期和LSM值存在极显著差异（P值均<0.001）,而APRI和FIB-4值无显著性统计学差异（P=0.547和0.578）;就区分S0-1和≥S2期肝纤维化而言,A组APRI分别为0.14和0.18,B组分别为0.15和0.24,A组FIB-4分别为0.98和1.26,B组分别为0.93和1.50,而A组LSM分别为5.2 kPa和6.8 kPa,B组分别为7.2 kPa和9.0 kPa（P<0.001）;A组和B组APRI诊断的截断点分别为0.105和0.145,FIB-4分别为0.675和0.775,而LSM分别为4.650和6.345,其诊断两家医院患者显著性肝纤维化的灵敏度在85%左右,而特异性在24%~46%之间。结论 可能由于一些不可控制的因素存在,导致临床数据的获得在不同医院间不可比,因此也需要经组织病理学检查,以确定APRI、FIB-4和LSM 诊断显著性肝纤维化的截断点,达到最佳诊断效果。     

α干扰素对慢性丙型肝炎患者血清肝纤维化指标的影响

丙型肝炎病毒(HCV)感染的最主要特征是慢性化,肝纤维化是这一慢性化过程中的一种极为重要的病变,因此,及早阻止肝纤维化的进程具有重要意义。α干扰素(IFN-α)的抗病毒疗效已得到肯定,关于其在慢性丙型肝炎中抗纤维化作用的报道尚不多见,为此,选取24例慢性丙型肝炎患者进行治疗前后的对比研究。     

普通杂合子血色病基因突变是慢性丙型肝炎炎症和纤维化的危险因素

背景：慢性丙型肝炎常常伴有肝脏铁储存的增加。长期争论的问题是血色病基因的杂合子突变是否影响肝纤维化的进展。因此作者的目的是评估德国的慢性丙性肝炎患者血色病基因的HFE突变与肝脏炎症和纤维化程度的关系。     

工业果糖与1型慢性丙型肝炎患者肝纤维化的严重程度相关

<正>【据《J Hepatol》2013年12月报道】题:工业果糖与1型慢性丙型肝炎患者肝纤维化的严重程度相关(作者Petta S等)在1型慢性丙型肝炎(CHC)患者中检测果糖摄入与肝组织细胞损伤严重程度之间的关系。研究涉及147名活检诊断为G1的CHC患者,对其人体学测量因素和代谢因素进行检测,所有的活检都由经验丰富的病理学家进行分期评定,并对脂肪肝进行定级,如果百分比≥20%就定义为重度。根据Bedossa分类对CHC患者NASH的特点进行了分析。结果显示:总果糖、工业果糖和水果果糖的平均每日摄入量分别为(18.0±8.7)、(6.0±4.7)和(11.9±7.2)g。工业果糖     

丙型肝炎肝纤维化诊治进展

丙型肝炎肝纤维化是丙型肝炎进展至肝硬化的关键病理过程,其诊断方法除常规肝脏活体组织检查及肝纤维化标志物检测外,无创性诊断方法包括影像学检查新技术及无创性诊断模型的研究取得重要进展,使丙型肝炎肝纤维化的诊断准确率及对治疗反应的预测效果显著提高.在抗病毒治疗基础上的中西医结合治疗可能成为未来防治丙型肝炎肝纤维化的发展方向.     

Assessment of FIBROSpect II to detect hepatic fibrosis in chronic hepatitis C patients

Background

The degree of liver fibrosis in patients with Hepatitis C (HCV) provides important prognostic information; however, the only current method available to obtain this information is by performing a liver biopsy. Liver biopsies are invasive, associated with complications, and costly. There has been recent interest in developing a panel of serum markers that can reliably predict the presence of fibrosis and, thus, obviate the need for a liver biopsy. Our objective was to prospectively validate a panel of serum fibrosis markers (FIBROSpect^SM II) that has been recently developed.

Methods

Serum was obtained from 108 consecutive HCV (15% with HCV/ETOH) patients seen in a hepatology clinic at a single tertiary care center at the time of liver biopsy. The performance of FIBROSpect II (consisting of 3 fibrosis markers: hyaluronic acid, tissue inhibitor of metalloproteinases 1, and alpha-2-macroglobulin) in differentiating mild (F0-F1) from significant (F2-F4) fibrosis was assessed by comparing the panel results with performed liver biopsy.

Results

The prevalence of significant fibrosis in the study group was 36.1%. The diagnostic value of the serum marker panel to detect significant fibrosis as assessed by area under the receiver operating characteristic (ROC) curve was 0.826. Performance characteristics are as follows: sensitivity 71.8%, specificity 73.9%, positive predictive value 60.9%, negative predictive value 82.3%, and overall accuracy of 73.1%.

Conclusion

This prospective study supports the clinical utility of serum markers in detecting fibrosis and validates the performance of FIBROSpect II in a prospective cohort of patients. The high negative predictive value of the test provides a reliable alternative to rule out severe fibrosis.     

Influence of iron on the severity of hepatic fibrosis in patients with chronic hepatitis C

AIM: To evaluate the association among hepatic fibrosis, serum iron indices, and hepatic iron stores in patients with Chronic Hepatitis C (CMC). METHODS: Thirty-two CHC patients were included in our study. The histological degree of fibrosis and inflammation activity was assessed according to the Metavir system. The serum iron indices including ferritin, iron and transferrin saturation were measured. Hepatic iron deposition was graded by Perls' stain. RESULTS: The CHC patients with severe hepatic fibrosis (n = 16) were significantly older than CHC patients with mild fibrosis (n = 16) (P = 0.024). The serum iron indices, increased serum iron store and positive hepatic iron stain were not significantly different between the two groups. In multivariate logistic regression analysis, the age at biopsy was an independent predictor of severe hepatic fibrosis (Odds ratio = 1.312; P = 0.035). The positive hepatic iron stain was significantly associated with the values of alanine aminotransferase (ALT) (P = 0.017), ferritin (P = 0.008), serum iron (P - 0.019) and transferrin saturation (P = 0.003). The ferritin level showed significant correlation with the value of ALT (r = 0.531; P = 0.003), iron (r = 0.467; P = 0.011) and transferrin saturation (r = 0.556; P = 0.002). CONCLUSION: Our findings suggest that the severity of hepatitis C virus (HCV)-related liver injury is associated with patient age at biopsy. Both serum iron indices and hepatic iron deposition show correlation with serum indices of chronic liver disease but are not related to grade and stage of liver histology.     

Significance of serum leptin and adiponectin levels in Egyptian patients with chronic hepatitis C virus associated hepatic steatosis and fibrosis

AIM: To study serum levels of leptin and adiponectin in patients with chronic hepatitis C virus infection genotype-4 (HCV-4) related steatosis and fibrosis. METHODS: We prospectively studied 45 untreated men with chronic HCV-4, with proven steatosis (group I, 30 patients), and fibrosis (group II, 15 patients), on liver biopsy. In addition, 15 healthy men (group III), matched for age, and body mass index were included. However, we excluded another five patients with steatohepatitis, and six patients with cirrhosis. We measured total serum leptin and adiponectin levels, as potential predictors for liver steatosis and fibrosis. Also, a correlation between these adipokines and various clinical and laboratory data were evaluated. All subjects were selected from Tropical and Internal medicine departments, Menoufiya University Hospital, Menoufiya, Egypt, during the period from February 2010 to August 2011. RESULTS: In group I, severity of hepatic steatosis was mild, moderate, and severe, in 19 patients (63.5%), 8 patients (26.5%), and 3 patients (10%), respectively. In contrast, in group II, hepatic fibrosis was found to be in stage 1, 2, and 3, in 6 patients (40%), in 6 patients (40%), and in 3 patients (20%), respectively. On comparing group I with group II, there was a significant decrease in serum adiponectin levels (131.4 ± 7.91 pg/mL vs 436 ± 9.75 pg/mL, P < 0.001), while there was no significant difference between both groups regarding serum leptin levels (34.69 ± 7.69 ng/mL vs 35.17 ± 1.06 ng/mL, P > 0.05). However, in the same group, when compared with group III, there was a significant increase in serum leptin levels (34.69 ± 7.69 ng/mL vs 10.69 ± 0.84 ng/mL, P < 0.001), while there was a significant decrease in serum adiponectin levels (131.4 ± 7.91 pg/mL vs 342.4 ± 44.48 pg/mL, P < 0.001). In contrast, in group II, when compared with group III, there was a significant increase in serum leptin and adiponectin levels (35.17 ± 1.06 ng/mL vs 10.69 ± 0.84 ng/mL, P < 0.001, and 436 ± 9.75 pg /mL vs 342.4 ± 44.48 pg/mL, P < 0.05, respectively), while there was no significant difference between both groups regarding serum creatinine (0.83 ± 0.34 vs 0.89 ± 0.24, P > 0.05). On the other hand, serum leptin was not correlated with serum adiponectin in group I and in group II (r = 0.09, P > 0.05, and r = -0.1, P > 0.05, respectively). However, serum adiponectin was significantly negatively correlated with serum aspartate transaminase in group I, but no correlation detected in group II (r =-0.39, P > 0.05, and r = -0.03, P > 0.05). CONCLUSION: In male patients with chronic HCV-4, serum adiponectin levels are elevated in hepatic fibrosis, but decreased in steatosis. Therefore, in contrast to leptin, adiponectin may be used as a non-invasive marker.     

拉米夫定治疗慢性乙型肝炎对血清肝纤维化指标影响的临床观察

目的探讨拉米夫定治疗慢性乙型肝炎对患者血清肝纤维化指标的影响。方法对42例慢性乙型肝炎患者在拉米夫定治疗前和治疗1年后测定血清透明质酸(HA)、层粘蛋白(LN)、Ⅲ型前胶原(PCⅢ)和Ⅳ型胶原(ⅣC)水平,并与39例对照组进行比较。结果治疗组治疗后4项血清肝纤维化指标明显下降(P均<0.01);治疗后治疗组与对照组相比也有显著性差异(P均<0.01)。结论拉米夫定治疗慢性乙型肝炎对血清肝纤维化指标有明显降低作用。     

男性慢性乙型肝炎患者肝细胞脂肪变危险因素分析

目的：比较男性慢性乙型肝炎（CHB）合并肝脂肪变患者与单纯 CHB 患者临床特征，寻找影响肝细胞脂肪变的危险因素。方法2010年3月～2013年3月期间，住院初治且有肝活检病理学检查的男性 CHB 患者209例，根据肝组织中有无脂质沉积分为 CHB 合并脂肪变组及单纯 CHB 组，比较两组患者血脂、血尿酸、血糖、饮酒、体质量指数和病毒载量情况，进行二元 Logistic 回归分析，了解肝脂肪变的危险因素。结果在209例男性 CHB 患者中，合并脂肪变121例（57.9%），单纯 CHB 88例（42.1%）；CHB 合并脂肪变患者尿酸、低密度脂蛋白和甘油三酯分别为（352.5±87.1）mmol/L、（2.8±0.8）mmol/L 和（1.8±0.1）μmol/L，均显著高于单纯 CHB 患者[（310.3±69.1） mmol/L、（2.2±0.6） mmol/L 和（1.2±0.7）μmol/L，P〈0.01）]；体质量指数和低密度脂蛋白水平升高是男性 CHB 患者合并肝脂肪变的危险因素（P〈0.05）。结论肥胖、血脂紊乱等代谢综合征相关表现是男性 CHB 患者肝组织脂肪变的危险因素，而饮酒或病毒载量可能不是肝脂肪变的危险因素。     

Accuracy of a predictive model for severe hepatic fibrosis or cirrhosis in chronic hepatitis C

AIM: To assess the accuracy of a model in diagnosing severe fibrosis/cirrhosis in chronic hepatitis C virus (HCV) infection. METHODS: The model, based on the sequential combination of the Bonacini score (BS: ALT/AST ratio, platelet count and INR) and ultrasonography liver surface characteristics, was applied to 176 patients with chronic HCV infection. Assuming a pre-test probability of 35%, the model defined four levels of post-test probability of severe fibrosis/cirrhosis: <10% (low), 10-74% (not diagnostic), 75-90% (high) and >90% (almost absolute). The predicted probabilities were compared with the observed patients' distribution according to the histology (METAVIR). RESULTS: Severe fibrosis/cirrhosis was found in 67 patients (38%). The model discriminated patients in three comparable groups: 34% with a very high (>90%) or low (<10%) probability of severe fibrosis, 33% with a probability ranging from 75% to 90%, and 33% with an uncertain diagnosis (i.e., a probability ranging from 10% to 74%). The observed frequency of severe fibrosis/ cirrhosis was within the predefined ranges. CONCLUSION: The model can correctly identify 67% of patients with a high (>75%) or low (<10%) probability of cirrhosis, leaving only 33% of the patients still requiring liver biopsy.     

病毒性肝炎肝纤维化形成影响因素的研究

目的　调查病毒性肝炎肝纤维化的流行病学，探讨其影响因素。方法对５０例肝纤维化患者和患者住地附近非肝纤维化者作病例对照研究。结果表明感染乙型肝炎病毒后大量饮酒、营养不足与肝纤维化形成关系密切、其ＯＲ值分别为２５和３倍。结论　感染乙型肝炎病毒后过量饮酒在病毒性肝炎肝纤维化形成中的作用远高于其他危险因素。     

MRI联合血清维生素D预测慢性丙型肝炎患者肝纤维化临床价值探讨*

目的 探讨慢性丙型肝炎(CHC)患者MRI检查指标和血清维生素D水平变化的意义。方法 200例CHC患者接受肝活检和MRI检查,测量扩散加权成像(DWI)值,采用ELISA法检测血清维生素D。结果 在200例CHC患者中,经肝穿组织病理学检查,发现存在肝纤维化80例(40.0%);80例存在肝纤维化患者血清维生素D水平为(22.1±12.5) nmol/L,显著低于120例无明显肝纤维化患者的(32.1±13.2) nmol/L(P <0.05);80例肝纤维化患者MRI表观弥散系数(ADC)为(1322.8±82.6),T₁变化率为(0.35±0.17),均显著低于120例无肝纤维化患者的(1542.5±80.7)和(0.52±0.21)。结论 伴有肝纤维化的CHC患者血清维生素D降低,MRI检查显示ADC值和T₁变化率也显著降低,了解这些变化可能对判断肝纤维化有帮助。