目的:观察CCl4攻击小鼠致肝纤维化血清IL4、IL6、IL8的动态变化规律及其表达的影响。方法:将小鼠分为4组:雌、雄性小鼠对照组、雌、雄性小鼠体积分数为30%四氯化碳花生油组(皮下注射)。用ELISA及酶标仪方法检测小鼠血清IL4、IL6、IL8的含量及肝脏、脾脏的表达情况。结果: CCl4攻击可使小鼠血清IL6、IL8含量增加,IL4的表达进一步减少。结论:CCl4可能通过攻击小鼠IL4、IL6、IL8的表达参与抗炎反应过程,细胞因子在肝纤维化发病过程中起重要的作用。检测血清IL4、IL6、IL8浓度的变化可作为了解其与肝纤维化的关系。
ObjectiveTo investigate the effect of indocyanogen green retention rate (ICGR) measurement and Child-Pugh classification of liver function in the preoperative evaluation of hepatic functional reservation. MethodsThe level of ICGR at 15 min (ICGR15) and the percentage of liver fibrosis in 103 patients with liver cancer were measured before hepatectomy, and the Child-Pugh classification of liver function was evaluated before and after the operations, and their connections were analyzed. ResultsAs the rise of Child-Pugh classification of liver function, the percentage of liver fibrosis increased gradually, there were significant differences between any two Child-Pugh classification (Plt;0.05). There was a linear correlation between the ICGR15 and the liver fibrosis percentage (rs=0.960, Plt;0.05). The value of preoperative ICGR15 in patients with postoperative Child-Pugh classification from grade A to grade B or grade B to grade C was gnificantly higher than that in patients with stabilization of Child-Pugh classification before and after operations (Plt;0.05). ConclusionICGR15 combined with Child-Pugh classification can improve the accuracy for the evaluation of preoperative hepatic functional reservation.
Immunohistochemical study on 39 specimens of hepatobilibary duct stricture due to stones were performed. Collagen types Ⅲ and Ⅳ were studied by quantitative analysis. The results showed that significant increase of type Ⅲ collagen was found in the stenotic bile duct wall, the portal area and liver sinusoid with fibrosis. Abnormal increasing of type Ⅳ collagen was found in the liver sinusoid of the stenotic bile duct.
Objective To evaluate the effectiveness and safety of treatment with Fuzheng Huayu capsule for liver fibrosis of chronic hepatitis B (CHB). Methods We searched MEDLINE, EMBASE, Cochrane Database of Controlled Trials (CCTR), CBMweb and CNKI up to March 2008. The references of retrieved literature were also hand searched. Randomized controlled trials (RCTs) which compared Fuzheng Huayu capsule with placebo or other drugs were collected. Data extraction and quality assessment were performed by two reviewers independently. The Cochrane Collaboration’ s software RevMan 4.2.10 was used for data analyses. Results Seven RCTs involving 590 cases of liver fibrosis of CHB were included. As for their methodological quality, one was graded A, one was graded B and the others were graded C. We carried out subgroup analyses based on treatment course and intervention measures. In terms of reducing haluronic acid, Fuzheng Huayu capsule was more effective than Huoluo Shugan capsule when the treatment course was 3 months (WMD=–61.75, 95%CI –105.20 to –18.30); significant differences were also noted between Fuzheng Huayu capsule and placebo (WMD=–187.72, 95%CI –244.23 to –31.21) or Huoluo Shugan capsule (WMD=–120.03, 95%CI –158.41 to –81.65) when the treatment course was 6 months. In terms of reducing IV-C, Fuzheng Huayu capsule was more effective than Gantaile when the treatment course was 6 months (WMD=–72.32, 95%CI –84.30 to –60.34). As for improving liver fibrosis at stage S, significant differences were observed between Fuzheng Huayu capsule and Gantaile (RR=2.33, 95%CI 1.37 to 3.96) or Huoluo Shugan capsule (RR=1.30, 95%CI 1.03 to 1.65). Except a very small number of gastrointestinal reactions, no significant adverse reactions were reported. Conclusion Fuzheng Huayu capsule is effective in reducing haluronic acid and improving liver fibrosis at stage S, especially when the treatment course is prolonged from 3 months to 6 months. No significant adverse reactions are reported. Because most of the included trials are of poor quality and small sample size, more high-quality RCTs are needed.
Liver fibrosis in chronic liver disease refers to the body’s repair response to sustained repeated necrosis or inflammation of liver cells, which results in fibrosis accompanied by relative or absolute lack of fiber degradation and deposition of extracellular matrix in the liver. Early and timely diagnosis and treatment of hepatic fibrosis are of great importance to patients with liver disease. A rational and complete diagnostic model of liver fibrosis should involve clinical pathology and histology, imaging, and serum biochemical markers. Liver biopsy has been regarded as the "gold standard" for the diagnosis of liver fibrosis and as a reference standard for other non-invasive diagnostic tests of liver fibrosis. Since it is invasive, liver biopsy is difficult to implement in clinical practice and a second liver biopsy is even more difficult. As for the non-invasive diagnosis of liver fibrosis, clinical symptoms and signs are not specific. The sensitivity and specificity of individual serum biochemical markers are still very weak, and imaging studies also lack specificity. The mathematical model “FibroTest” of serum biochemical markers has better diagnostic accuracy, but the calculation is complicated, making it difficult to achieve widespread use. There is insufficient evidence to suggest that the "gold standard" of liver biopsy can be replaced. Therefore, further research is needed to investigate how best to balance the benefits and harms of different tests, to identify the best combination, to simplify any calculation steps, to reduce costs, to avoid liver biopsy, and to find new, more specific and sensitive markers.
Objective To evaluate the quality of studies assessing the value of serum hyaluronic acid in the diagnosis of liver fibrosis, to analyze the sources of bias and variation, and to estimate the accuracy of serum hyaluronic acid in diagnosing early liver cirrhosis and liver fibrosis in patients with chronic viral hepatitis.Methods We searched MEDLINE (1966 to June 2006), EMbase (1974 to June 2006), CBMdisc (1978 to April 2005), CNKI (2005 to June 2006) and VIP (2005 to June 2006) for studies assessing the diagnostic value of serum hyaluronic acid for liver fibrosis in patients with chronic viral hepatitis. We checked the references in the reports of included studies. QUADAS items were used for quality assessment. Meta-disc software was used to analyze sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic test odds ratio for the pooled analysis and heterogeneity test. DPS2005 software was used to draw SROC curves for those without heterogeneity. Results In total 24 studies were included: 12 published in Chinese and 12 published in English. Results of the pooled analysis showed that, as for radioimmunoassay (RIA), the pooled LR+ of the studies involving the diagnosis of liver cirrhosis and the differentiation of absent/present liver fibrosis were 7.029 and 3.608; and the pooled LR- were 0.198 and 0.319, respectively. As for enzyme-linked immunosorbent assay (ELISA), the pooled LR+ of the studies involving the diagnosis of liver cirrhosis, the differentiation of mild/severe and absent/present liver fibrosis were 6.093, 9.806 and 4.308; and the pooled LR- were 0.354, 0.347 and 0.563, respectively. Conclusion The biases identified from the 24 studies are mainly due to reference standard review bias. By both RIA and ELISA methods, serum hyaluronic acid has a sound value in diagnosing live cirrhosis. Its value in differentiating absent/present liver fibrosis is also acceptable. However, its value in differentiating mild/severe liver fibrosis needs to be further studied.
Objective To assess the effectiveness and safety of Jiuweirougan granule in the treatment of chronic hepatitis with hepatic fibrosis. Methods A double-blind, double dummy and randomized controlled method was adopted. Forty-six patients were selected by using the inclusion and exclusion criteria and were randomizedly allocated to the treatment group (n=23, Jiuweirougan 10 g, twice a day) and the control group (n=23, treated with Biejiaruangan 4 pills, three times a day). The duration of treatment for both groups lasted for 6 months. Results Two patients in the treatment group dropped out halfway through the study, while one patient in the control group was withdrawal for irregular treatment. Analysis according to intention-to-treat (ITT) and per-protocol (PP) was conducted. In the treatment group, the effective rates of TCM (Traditional Chinese Medicine) on the syndrome were 82.61% (19/23) (ITT) and 90.48% (19/21) (PP), while in the control group, there were 86.96% (20/23) (ITT) and 86.36% (19/20) (PP). There was no significant difference between the two groups (P＞0.05). The improvement rate of serum parameters in the treatment group such as hyaluronic acid (HA), type Ⅲ procollagen (PCⅢ), type Ⅳ collagewn (CⅣ) and laminin (LN) were 28.57% (6/21), 23.81% (5/21), 28.57% (6/21) and 4.76% (1/21), respectively, while in control group, the rates were 36.37% (8/22),13.64% (3/22), 36.37% (8/22) and 9.09% (2/22), respectively. No significant difference was seen between the two groups (P＞0.05). ITT and PP analysis revealed similar results. No obvious adverse effects were noted. Conclusion Jiuweirougan granule may improve chronic hepatitis with fibrosis, and its effect is equal to that of Biejiaruangan. No obvious toxic-adverse effects were seen.
【摘要】 目的 评价九味柔肝颗粒治疗慢性乙肝肝纤维化的疗效和安全性。 方法 根据纳入与排除标准，选取2007年2-8月入院的慢性乙肝肝纤维化（气滞血瘀兼湿热未净证）患者96例，按3∶1随机分为两组进行随机双盲双模拟对照试验。试验组72例，口服九味柔肝颗粒， 2次/d，每次10 g；阳性对照药鳖甲软肝片组（对照组）24例，口服鳖甲软肝片，4片/次，3次/d；两组疗程均为6个月。 结果 试验组完成治疗66例，对照组完成21例。符合方案数据分析（PPS）结果显示，试验组治疗后中医证侯积分及B超积分分别下降了0.50±1.04和8.61±3.62，对照组分别下降了0.32±1.01和8.63±3.15，均较治疗前显著下降（Plt;0.05），两组比较无统计学意义（Pgt;0.05）。在血清肝纤维化四项指标方面，试验组除LN外，其余指标治疗后均较治疗前明显下降（Plt;0.05），对照组中仅PⅢP有显著下降（Plt;0.05），其余指标下降不明显，两组比较无统计学意义（Pgt;0.05）。两组患者治疗期间均未观察到明显不良反应，不良反应发生率分别为5.56%和4.17%。 结论 九味柔肝颗粒能明显改善慢性肝炎肝纤维化患者的症状和部分肝纤维化指标，其疗效与鳖甲软肝片相当，安全性良好。【Abstract】 Objective To assess the safety and therapeutic effect of Jiuweirougan grandule on chronic hepatitis B with hepatic fibrosis. Methods A double-blind, double dummy and randomized controlled method was adopted. Ninety-six patients from February to August 2007 selected by including and excluding criteria were distributed randomly in accordance with the 3∶1 ratio into the test group (n=72, treated with Jiuweirougan 10 g, two times per day) and the control group (n=24, treated with Biejiaruangan 4 tablets, three times per day). The period of treatment for both groups lasted for half a year. Results A total of 66 cases in the test group and 21 cases in the control group completed the experiment. The results of per-protocol population (PPS) suggested that the accumulated score of B ultrasound and symptom decreased 0.50±1.04 and 8.61±3.62 in the test group and 0.32±1.01 and 8.63±3.15 in the control group, respectively. The score decreased remarkably compared with pre-treatment(Plt;0.05). There was no significant difference between the two groups (Pgt;0.05). For serum liver fibrotic parameters, all parameters except laminin (LN) in the test group decreased remarkably compared with pre-treatment(Plt;0.05). But in the control group, besides type Ⅲ procollagen (PCⅢ) decreased remarkably(Plt;0.05), other parameters showed no obvious changes. There was no significant difference between the two groups (Pgt;0.05). At the same time, no obvious adverse effect was found in the two groups. The incidence of adverse reactions was 5.56% and 4.17% respectively. Conclusion Jiuweirougan granule may improve the syndrome and part of fibrotic index of chronic hepatitis B with fibrosis, and the effect is equal to that of Biejiaruangan with good security.
Objective To find a new specific marker that can be used to early diagnose hepatic fibrosis by detecting the change of serum protein in patients with hepatic fibrosis. Methods This research adopted 50 SD rats (25 males and 25 females), and from which 6 rats were selected randomly (3 males and 3 females) as control group, last 44 rates were divided into four groups according to four pathological stages as hepatic fibrosis model group (experimental group). Distinct proteins in serum were detected by surface-enhanced laser desorption/ionization-time of flight-mass spectra (SELDI-TOF-MS). Radioimmunoassay was used to measure four parameters of hepatic fibrosis which were hyaluronidase (HA), precollagen Ⅲ (PCⅢ), laminin (LN) and collagen Ⅳ (Ⅳ-C). Results Distinct proteins in serum were detected in 8 cases of stage Ⅰ of hapatic fibrosis, 5 cases of stage Ⅱ, 5 cases of stage Ⅲ, 6 cases of stage Ⅳ, and 5 cases of control by SELDI-TOF-MS. Three protein peaks were found (M/Z: 4 203, 4 658, and 7 400). The peaks of M/Z 4 658 and 4 700 proteins were obviously increased in the stage Ⅰ of hepatic fibrosis （Plt;0.05）, while the changes of hepatic fibrosis four parameters appeared in stage Ⅳ of hepatic fibrosis. Conclusion This method shows great potential for early diagnosing of hepatic fibrosis and finding better biomarkers to hepatic fibrosis.