拉米夫定联合复方鳖甲软肝片治疗慢性乙型肝炎肝纤维化60例临床观察

慢性乙型肝炎肝纤维化尚无特效治疗,目前认为抗病毒和抗纤维化治疗为两大重点.2005年1月至2007年1月,我们采用拉米夫定联合复方鳖甲软肝片治疗60例慢性乙型肝炎肝纤维化患者,取得良好效果,现报告如下.     

拉米夫定联合复方鳖甲软肝片治疗慢性乙型肝炎肝纤维化60例临床观察

慢性乙型肝炎肝纤维化尚无特效治疗,目前认为抗病毒和抗纤维化治疗为两大重点.2005年1月至2007年1月,我们采用拉米夫定联合复方鳖甲软肝片治疗60例慢性乙型肝炎肝纤维化患者,取得良好效果,现报告如下.     

抗肝纤冲剂治疗慢性乙型肝炎肝纤维化前后临床及病理研究

目的观察抗肝纤冲剂治疗慢性乙型肝炎肝纤维化的临床疗效，探讨其可能的作用机制。方法随机将57例慢性乙型肝炎肝纤维化患者分为两组。治疗组45例采用抗肝纤冲剂配合常规护肝药物治疗；对照组12例仅用常规护肝药物治疗。观察两组患者治疗前后血清肝功能、肝纤维化指标，并观察治疗前后肝组织病理及肝内Ⅳ型胶原免疫组化的改变。结果治疗组患者肝功能、肝纤维化指标、肝组织病理及肝内IV型胶原恢复程度均好于对照组（P〈0．05或P〈0．01）。结论抗肝纤冲剂配合常规护肝药物治疗慢性乙型肝炎肝纤维化患者疗效显著，为临床治疗慢性肝炎肝纤维化开辟了新的治疗途径。     

康宁胶囊联合谷膛甘肽治疗慢性乙型肝炎的疗效观察

目的 观察康宁胶囊联合谷胱甘肽治疗慢性乙型肝炎的临床疗效。方法 对照组79例用谷胱甘肽治疗,治疗组93例用谷胱甘肽加用康宁胶囊治疗,通过肝功能指标及纤维化指标评价疗效。结果 经4－8周治疗后,治疗组及对照组肝功能指标及纤维化指标均有明显改善,但在部分指标下,治疗组优于对照组。结论 康宁胶囊联合谷胱甘肽治疗慢性乙型肝炎有较好作用。     

苦参素和甘利欣对慢性乙型肝炎患者肝纤维化指标的影响

目的:探讨苦参素联合甘利欣治疗慢性乙型肝炎的疗效,及对肝纤维化指标的影响。方法:选择我院200-01/2009-01收治的80例慢性乙型肝炎合并肝纤维化患者作为研究对象,随机分成治疗组和对照组各40例,治疗组给予甘利欣加苦参素,对照组应用复方丹参治疗,3个月为一个疗程。观察比较两组的临床疗效及肝功能指标与肝纤维化指标的改变。结果:治疗组40例的总有效率90.0%;对照组40例的总有效率为57.5%,两组总有效率比较,差异有统计学意义(P0.05)。治疗前两组的肝纤维化指标HA、LN、PCⅢ、Ⅳ-C比较,差异无显著性,治疗3个月后,肝纤维化指标HA、LN、PCⅢ、Ⅳ-C均较治疗前明显下降,且治疗组与对照组比较,差异有统计学意义(P0.05)。治疗前两组的肝功能指标ALT、AST、TBIL、ALB比较,差异无显著性,治疗3个月后,肝功能指标ALT、AST、TBIL、ALB比较均较治疗前明显下降,但治疗组与对照组比较,差异无显著性(P0.05)。结论:苦参素和甘利欣对慢性乙型肝炎患者肝纤维化具有协同作用,阻止或改善肝纤维化有疗效明显,无明显副作用,值得临床推广和应用。     

联合超声学指标无创诊断慢性乙型肝炎早期肝硬化

目的找出区别于肝纤维化（S0-3）及早期肝硬化（S4）的超声学指标,建立一个无创诊断早期肝硬化的模型,并评估模型的诊断效果。方法选取肝穿刺活检确诊的慢性乙型肝炎（CHB）患者99例,其中男性79例,女性20例;年龄18～61岁,平均年龄41.83岁。均行超声检查。收集的指标包括反映肝、脾的大小和血流动力学的指标,患者的年龄和性别,找出有意义的指标,建立一个诊断模型。统计分析的方法包括单因素分析、logistic多因素分析及接受者操作特征（ROC）曲线等。结果脾脏的厚径和脾动脉收缩期峰速/舒张期末流速之比（S/D）2个指标最后经筛选进入了模型,该数学模型诊断早期肝硬化（S4）指数（ECI）=logit P（y=肝硬化）=-14.965＋1.401×脾脏厚径＋2.883×脾动脉S/D,选取合适的阈值,灵敏度和特异度分别为100.00%和78.10%。结论超声学指标的数学模型对早期肝硬化的诊断有一定的临床价值,但尚需进一步验证。     

复方鳖甲软肝片治疗慢性乙型肝炎肝纤维化的临床研究

目的验证复方鳖甲软肝片治疗慢性乙型肝炎肝纤维化的临床疗效和安全性。方法将420例慢性乙型肝炎肝纤维化患者随机分为两组：治疗组300例，口服复方鳖甲软肝片，对照组120例，口服和络舒肝胶囊，6个月为1疗程。结果治疗组的患者在改善症状和体征，恢复肝功能总疗效方面，显效率和总有效率分别为55．67％和81．67％，对照组分别为15．80％和60．00％，治疗组明显优于对照组（P〈0．01）。结论复方鳖甲软肝片在改善中医症状，血清学肝纤维化及肝组织病理指标等方面疗效确切，可以有效治疗慢性乙型肝炎肝纤维化。     

甘利欣联合苦参素治疗慢性乙型病毒性肝炎肝纤维化指标的变化

目的观察联合应用甘利欣和苦参素治疗慢性乙型病毒性肝炎患者血清肝纤维化指标的变化。方法选择39例慢性乙型病毒性肝炎中度患者,随机分成：治疗组19例,联合应用甘利欣和苦参素治疗;甘利欣组20例,给予甘利欣治疗。分别于治疗前后一周内检测血清肝纤维化指标HA、LN、ⅣP。结果两组治疗前血清HA、LN、ⅣP均明显高于正常对照组（P〈0.05）。两组患者治疗后的血清HA、LN、ⅣP水平较治疗前降低,治疗组血清HA、LN、ⅣP水平治疗前后存在统计学差异,且明显低于甘利欣组治疗后水平（P〈0.05）。结论苦参素和甘利欣合用较与单纯应用甘利欣治疗慢性乙型肝炎可明显改善肝纤维化指标,说明苦参素有较强的抗肝纤维化作用。     

慢性乙型肝炎患者血清HBV-DNA病毒载量与血清肝纤维化指标变化

目的：探讨慢性乙型肝炎患者血清HBV-DNA病毒载量与血清肝纤维化指标变化的关系。方法：以慢性乙型病毒性肝炎患者20例为对象,分为应用抗病毒药有效抑制组10例与未进行抗病毒药治疗组10例,跟踪调查治疗情况5年（2002～2007年）,用荧光定量聚合酶链反应（FQ-PCR）检测HBV-DNA病毒载量,采用放射免疫分析对20例慢性乙肝患者检查血清肝纤维化指标透明质酸（HA）、层黏蛋白（LN）、Ⅳ型胶原（Ⅳ-C）、Ⅲ型前胶原（PCⅢ）水平。结果：5年来,抗病毒药有效抑制组10例患者平均HBV-DNA病毒载量对数水平3.56±1.12,未进行抗病毒药治疗组10例平均HBV-DNA病毒载量对数水平7.76±1.23,有显著差异（P〈0.05）。2002年抗病毒药有效抑制组血清肝纤维化指标分别为HA（82.72±30.62）μg/ml、LN（71.18±26.71）μg/ml、Ⅳ-C（93.77±69.87）μg/ml、PCⅢ（91.4±18.64）μg/ml,2002年未进行抗病毒药治疗组血清肝纤维化指标分别为HA（79.32±31.34）μg/ml、LN（70.25±28.23）μg/ml、Ⅳ-C（90.35±67.81）μg/ml、PCⅢ（85.77±20.56）μg/ml,两组间各项指标统计学无显著差异（P〉0.05）。2007年抗病毒药有效抑制组血清肝纤维化指标分别为HA（85.72±29.52）μg/ml、LN（70.18±25.4）μg/ml、Ⅳ-C（94.2±70.92）μg/ml、PCⅢ（93.4±19.32）μg/ml,2007年未进行抗病毒药治疗组血清肝纤维化指标分别为HA（105.67±28.54）μg/ml、LN（97.75±26.25）μg/ml、Ⅳ-C（132±72.13）μg/ml、PCⅢ（120.72±19.87）μg/ml,两组间各项指标比较均有显著差异（P〈0.05）。结论：有效控制慢性乙肝患者HBV-DNA病毒载量可能是控制患者肝纤维化进展的重要因素。     

加强慢性乙型肝炎的抗病毒治疗

我国“慢性乙型肝炎防治指南”指出:“慢性乙型肝炎治疗主要包括抗病毒、免疫调节、抗炎保肝、抗纤维化和对症治疗,其中抗病毒治疗是关键,只要有适应证,且条件允许,就应进行规范的抗病毒治疗[1]。”但据调查,我国仅有19%慢性乙型肝炎患者接受抗病毒治疗;45%医务人员不知道慢性乙型肝炎规范化抗病毒治疗;73%医师仅用中成药和保肝降酶药治疗慢性乙型肝炎患者;38%慢性乙型肝炎患者轻信虚假广告。因此,多数慢性乙型肝炎患者未能得到及时、规范的抗病毒治疗,从而延误了病情,甚至发展成为肝硬化和肝细胞癌(HCC)。值得指出的是:我国一方面是大多…     

慢性乙型肝炎组织中肝前体细胞的免疫组化特征

目的研究肝前体细胞（hepatic progenitor cells,HPCs）、小管样反应、中间型肝细胞在慢性乙型肝炎组织中的分布特征和数量变化,以及与肝细胞再生之间的可能联系。方法对42例慢性乙型肝炎组织行常规病理HE染色,按炎症活动度（G）分为轻、中、重三度,免疫组织化学方法观察肝胆细胞标记（AFP、GST-π、CK7、CK19）和造血干细胞标记（c-kit、CD34）的表达,并以Ki-67标记增殖的肝细胞,用CK7／CK19作为标记物对符合定义的HPCs、中间型肝细胞进行计数,小管样反应程度的判定利用彩色病理图象分析系统。结果慢性乙型肝炎的早期阶段即存在HPCs的活化和小管样反应,其数量随着炎症活动度的增加而增加,均表达CK7、CK19、GST-π和AFP,肝细胞增殖指数在轻、中度肝炎中逐渐增加,重度肝炎、肝硬化患者增殖的肝细胞数下降,而中间型肝细胞数量显著增加。小管样反应面积百分比与HPCs数目正相关（r=0．739,P〈0．05）,中间型肝细胞数目与HPCs数目正相关（r=0．614,P〈0．05）。结论慢性乙型肝炎中不仅有成熟肝细胞增殖,也存在肝前体细胞活化和分化,可能参与肝脏损伤后的再生修复。     

Transmission routes of hepatitis B virus infection in chronic hepatitis B patients in The Netherlands

The Netherlands is a low endemic country for hepatitis B virus (HBV). Rotterdam, a city in The Netherlands harbors a large group of chronic hepatitis B (CHB) patients of which most are born abroad. The study included 464 consecutive CHB patients who were reported to the Municipal Public Health Service in Rotterdam from January 1, 2002 to September 15, 2005. The HBV genotypes, possible transmission routes of infection and travel history of CHB patients born in The Netherlands, were compared with those CHB patients living in The Netherlands but who were foreign-born, taking into account the ethnicity of the mother. Of the 464 patients with CHB infection, 14% were Dutch-born and 86% were foreign-born. The CHB patients in the Dutch-born group had genotypes A (35%), B (15%), C (11%), D (37%), and G (2%). In the foreign-born group, the distribution of genotypes was A (20%), B (15%), C (11%), D (40%), and E (15%). In the Dutch-born group, sexual transmission accounted for a larger proportion of infections (P < 0.0001) compared to the foreign-born group, whereas perinatal transmission is reported to be higher in the foreign-born group and in the Dutch-born group with a foreign mother. The genotypes of the chronic HBV strains determined corresponded well with the HBV genotypes expected from the countries of origin of the patients or their mothers. Genotypes A and D are predominant in CHB patients in The Netherlands.     

Characterization of viral kinetics in patients with hepatitis B e antigen-positive chronic hepatitis B

A study was conducted during a 1 year follow-up to characterize the viral kinetics in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B and to develop a model of predicting the probability of spontaneous HBeAg seroconversion. Fifty-seven patients with HBeAg-positive chronic hepatitis B were enrolled with monthly follow-ups from three Phase III clinical trial placebo groups. According to serial viral loads, 30 patients (52.6%) with the stationary pattern maintained stable HBV DNA levels with fluctuations of less than 1.5 log copies/ml. Twenty patients (35.1%) with the declining pattern exhibited a spontaneous decline of more than 1.5 log copies/ml without a following rebound of at least 1.5 log copies/ml. The remaining seven patients (12.3%) had the wavering pattern. Both declining and wavering patterns, when compared with the stationary pattern, had significantly higher hepatic necroinflammation in terms of ALT and Knodell scores at the baseline and peak ALT levels during the follow-up period. The declining pattern had a significantly better clinical outcome in terms of the lowest final HBV DNA and a reduction in the necroinflammatory score after 1 year. Furthermore, the declining pattern had a favorable HBeAg seroconversion rate (40%) compared with the wavering (14.3%) and stationary patterns (0%). A regression equation, incorporating simultaneous serum bilirubin, ALT, and HBV DNA levels, predicted the probability of HBeAg seroconversion with a sensitivity of 76.8% and a specificity of 74.7%. In conclusion, different viral kinetic patterns in patients with chronic hepatitis B implicate distinct clinical significance and immunologic perspective.     

The role of the hepatitis B virus infection in patients with chronic hepatitis in argentina

Over a seven-year period, we monitored 221 patients with chronic hepatitis from two medical centers. By using the counterelectrophoresis (CEP) test to detect the presence of HBsAg and anti-HBc, or both, we established that 87.7% of them had hepatitis B infection. Serum specimens originally found negative for HBsAg by CEP were further tested by reversed passive hemagglutination (RPH), and those originally found negative for anti-HBc by CEP were further tested by radioimmunoassay (RIA). Five patients were anti-HBc-positive and HBsAg-negative. No sex predominance was observed, but HBsAg incidence increased with increasing age. The HBeAg antigen was detected in 46.8% of the 161 cases tested for it; the most frequent subtype found was adw (63.7%). The present findings indicate that HBV infection largely contributes to the development of chronic hepatitis in Argentinian patients.     

Loss of hepatitis B surface antigen from the serum of patients with chronic hepatitis treated with lamivudine

Although loss of hepatitis B e antigen (HBeAg) from the serum is sought by treatment with lamivudine, clearance of hepatitis B surface antigen (HBsAg) is the eventual goal of any antiviral therapy. In a single hepatology center in the Metropolitan Tokyo, 486 patients with chronic hepatitis B were followed up for longer than 3 years after they started treatment with lamivudine. HBsAg disappeared from the serum in 17 (3.5%). Age >or=50 years and low HBsAg levels (hemagglutination titer or=50 years at the start of lamivudine was the only factor predicting the loss of HBsAg (hazard ratio: 2.96 [95% confidence interval: 1.14-7.68], P = 0.028). By the method of Kaplan-Meier performed on the 486 patients, the loss of HBsAg was estimated to occur in 3% and 13% of patients, respectively, who had received lamivudine therapy for 5 and 10 years. These results indicate that loss of HBsAg occurs in a minority (3.5%) of patients with chronic hepatitis B who receive lamivudine therapy and more frequently in those with lower HBsAg titers and older ages at the start of treatment.     

Changes in hepatitis B virus DNA-polymerase activity in patients with chronic infection

Levels of serum hepatitis B virus DNA-polymerase (HBV-DNAP) were studied longitudinally over variable periods of time in 16 HBV chronic carriers using a modified assay procedure developed to increase reproducibility. Ten patients were tested on a short-term basis at 3- to 6-hr intervals for 48 hr or at 24- to 48-hr intervals for 15 consecutive days, and all showed marked vacillations in enzyme levels although hospitalized and untreated. Patients with chronic active hepatitis on liver biopsy had larger fluctuations compared to cases of chronic persistent hepatitis. Six patients were longitudinally tested over a period of 12–32 months and those three receiving immunosuppressive drugs showed a progressive increase in DNAP levels during therapy, but two returned to pretreatment levels after therapy was withdrawn and one even cleared permanently the complete virus with seroconversion to anti-HBe. Such outcome was also observed in one patient with chronic active hepatitis who remained untreated.     

长效干扰素治疗慢性乙型肝炎e抗原阴性患者疗效研究

目的 观察长效干扰素对慢性乙型肝炎HBeAg阴性患者的临床疗效.方法 将46例HBeAg阴性慢性乙肝患者随机分为两组,其中长效干扰素组：派罗欣180μg,一周一次,皮下注射,疗程48周;普通干扰素组：赛诺金500MU,肌肉注射,隔日一次,疗程48周.治疗结束后随访24周.结果 长效干扰素组和普通干扰素组的ALT水平复常率在治疗结束和随访结束比较,差异有统计学意义（x2 =9.106,P＜0.05;x2=9.832,P＜0.05）.长效干扰素组和普通干扰素组的HBV-DNA阴转率在治疗结束和随访结束比较,差异有统计学意义（x2 =4.312,P＜0.05;x2=6.158,P＜0.05）.但两组在HBV-DNA下降程度上无明显差别（P＞0.05）.结论 长效干扰素治疗慢性乙型肝炎e抗原阴性患者可以明显提高疗效.     

Peroxidase-anti-peroxidase detection of hepatitis B surface and core antigen in liver biopsy specimens from patients with chronic type B hepatitis

Liver biopsy specimens from 58 American patients with chronic type B hepatitis were investigated for the presence and distribution of the hepatitis B core (HBcAg) and surface (HBsAg) antigens by peroxidase-anti-peroxidase techniques. HBsAg was detected in 43 (77%) and HBcAg in 52 (90%) patients. HBcAg was present in 50 of 51 (98%) patients with hepatitis B e antigen (HBeAg) but in only two of seven (29%) of patients with antibody to HBeAg (anti-HBe). There was no correlation between severity of hepatitis or height of aminotransferase activities and the amount of HBsAg or HBcAg in hepatocytes but there was a positive correlation between amount of HBcAg and height of HBV-DNA and DNA polymerase activity in serum. Follow-up liver biopsies, taken 1 to 3 yr later, were available from 39 patients. HBcAg remained detectable in 25 of 26 patients with persistence of HBeAg but disappeared in 12 patients who had lost HBeAg. In nine patients, HBcAg was cytoplasmic as well as nuclear in distribution. Seven of these patients had an intense lobular hepatitis with marked elevations in aminotransferase activities. These findings indicate that the amount of HBcAg in liver correlates with the amount of serum hepatitis B virus as quantified by serum levels of DNA polymerase and HBV-DNA. The amount of nuclear HBcAg does not correlate with the severity of the liver disease, but the presence of cytoplasmic HBcAg usually reflects an active and severe ongoing hepatitis.     

Characteristics of lamivudine-resistant hepatitis B virus (HBV) strains with and without breakthrough hepatitis in patients with chronic hepatitis B evaluated by serial HBV full-genome sequences

Lamivudine therapy often causes breakthrough of hepatitis B virus (HBV) DNA and breakthrough hepatitis. The aim of this study was to determine the viral factors that relate to HBV-DNA breakthrough with and without breakthrough hepatitis. Among 82 patients with chronic hepatitis B (CHB) who received lamivudine at a dose of 100 mg daily for more than 24 months, 23 patients had HBV-DNA breakthrough induced by a lamivudine-resistant mutant. Of these 23 patients, 16 had breakthrough hepatitis and 7 had only HBV-DNA breakthrough. Serial HBV-DNA full-genome sequences during therapy were examined in 10 (7 had breakthrough hepatitis and 3 did not) of these 23 patients by direct sequencing. Mutations in the S region were examined by cloning in representative patients. There were no significant differences in the baseline clinical backgrounds and virus marker between patients with and without breakthrough hepatitis. The HBV amino acid substitutions at breakthrough hepatitis were identical to those at HBV-DNA breakthrough. Cloning analysis revealed that monoclonal mutational strain appeared at breakthrough and no such mutations existed at baseline. Regarding HBV amino acid substitutions in the polymerase region, S region, X region, and precore-core region with breakthrough compared to baseline, there was no significant differences of the numbers of amino acid substitution between breakthrough hepatitis and non-breakthrough hepatitis. There were no common amino acid changes in patients with breakthrough hepatitis. Although monoclonal lamivudine-resistant strain emerged at HBV-DNA breakthrough in patients with CHB, there were no common amino acid changes, suggesting viral factor may have insignificant role in breakthrough hepatitis.