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.
ObjectiveTo systematically review the efficacy and safety of Heluo Shugan capsule in the treatment of hepatitis B fibrosis. MethodWe searched PubMed, The Cochrane Library (Issue 8, 2015), CBM, CNKI, VIP and WanFang Data from their inception to August 2015, to collect randomized controlled trials (RCTs) on Heluo Shugan capsule for hepatitis B fibrosis. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed using RevMan 5.3 software. ResultsA total of 15 RCTs involving 1 840 patients were included. The results of meta-analysis showed that: (1) As for reduced level of serum hyaluronic acid (HA), Heluo Shugan capsule was superior to placebo (MD=82.31, 95%CI 37.44 to 127.19, P=0.000 3), but worse than Fuzheng Huayu capsule (MD=-137.45, 95% CI-196.29 to-78.62, P < 0.000 01), Fufang Biejia Ruangan tablet (MD=-51.19, 95% CI-67.58 to-34.81, P < 0.000 01) and Anti-fibrosis decoction (MD=-82.13, 95% CI-102.37 to-61.88, P < 0.000 01). (2) As for reduced level of serum laminin (LN), Heluo Shugan capsule was superior to placebo (MD=36.83, 95% CI 11.84 to 61.82, P=0.004), but worse than Fufang Biejia Ruangan tablet (MD=-36.00, 95% CI-64.29 to-7.71, P=0.01), Ganfujian capsule (MD=-22.14, 95% CI-37.28 to-7.00, P=0.004) and Anti-fibrosis decoction (MD=-38.64, 95% CI-75.00 to-2.29, P=0.04). (3) As for reduced level of serum procollagen type III peptide (PCIII), Heluo Shugan capsule was superior to placebo (MD=47.17, 95% CI 32.68 to 61.66, P < 0.000 01), but worse than Fuzheng Huayu capsule (MD=-4.80, 95% CI-9.08 to-0.51, P=0.03), Dahuang Zhechong pills (MD=-53.77, 95% CI-105.01 to-2.53, P=0.04), Ganfujian capsule (MD=-46.82, 95% CI-66.30 to-27.34, P < 0.000 01) and Anti-fibrosis decoction (MD=-28.68, 95% CI-55.59 to-1.77, P=0.04). (4) As for reduced level of serum type-IV-collagen (IV-C), Heluo Shugan capsule was superior to placebo (MD=72.77, 95% CI 47.65 to 97.89, P < 0.000 01), but worse than Fuzheng Huayu capsule (MD=-34.69, 95% CI-56.65 to-12.73, P=0.002), Dahuang Zhechong pills (MD=-21.26, 95%CI-38.79 to-3.73, P=0.02), Fufang Biejia Ruangan tablet (MD=-69.04, 95%CI-124.38 to-13.69, P=0.01), Ganfujian capsule (MD=-19.84, 95% CI-37.41 to-2.27, P=0.03) and Anti-fibrosis decoction (MD=-37.98, 95% CI-72.99 to-2.96, P=0.03). ConclusionCurrent evidence shows that, Heluo Shugan capsule was superior to placebo, but worse than Fufang Biejia Ruangan tablet, Fuzheng Huayu capsule, Dahuang Zhechong pills, Ganfujian capsule and Anti-fibrosis decoction in reducing the level of serum hepatic fibrosis. Due to the limited quantity and quality of included studies, more high-quality, large-scale RCTs are need to verify the above conclusion.
Evidence from numerous animal models and clinical studies in recent years has demonstrated that macrophages play an important role in the regulation of liver fibrosis regression. The safety and efficacy of utilizing autologous macrophages for the treatment of liver fibrosis have been demonstrated in patients and shows promising application prospects, but the therapeutic effects need to be improved. Cirrhotic liver undergoes a process of marked extracellular matrix degradation after partial hepatectomy surgery, and single-cell sequencing identified multiple restorative macrophage subsets that express different matrix metalloproteinases (MMPs) at high levels. Future efforts to further characterize this population of macrophages and improve their enrichment in the liver may allow macrophage therapy to be a highly effective strategy to reverse liver fibrosis.
Trying to provide ultrasonic image-aid measures for quantitative diagnosis and dynamic monitoring of liver fibrosis, we propose two scoring methods for liver fibrosis tissue in vivo, based on ultrasound radio frequency (RF) time series in this paper. Firstly, RF echo signals of human liver were recorded in this study. Then one of the recorded frame RF data was demodulated to be B model image. After that, a region of interest (ROI) in the B model image was selected. For each point in the ROI, its all frame data were acquired so that RF time series were formed. An SMR (size measure relationship) fractal dimension and six spectral features were extracted from RF time series in the ROI. With relative deviation and Fisher's discriminant ratio, seven features were weighted and summed so that the liver tissues' scores were obtained, Score-rd and Score-fisher, respectively. Area under ROC curve (AUC) and a support vector machine (SVM) were used to evaluate whether these scoring methods would be useful in distinguishing normal and cirrhosis tissues. Experimental results are shown as follows: Score-rd's AUC was 0.843, while Score-fisher was 0.816, SVM classification accuracies were both up to 87.5%. This proved that our proposed scoring methods were effective in distinguishing normal and cirrhosis tissues. Score-rd and Score-fisher have potential for clinical applications. They can also provide quantitative references for liver fibrosis diagnosis.
ObjectiveTo observe the survival, migration, and effect of human amniotic epithelial cells (hAECs) on hepatic fibrosis in immune rats so as to provide the experimental theory for the clinical treatment with hAECs. MethodsSixty-four 10-week-old male Sprague Dawley rats (weighing, 220-280 g) were randomly divided into 4 groups, sixteen rats in each group. Rat hepatic fibrosis model was induced in groups A, B, and C; hepatic fibrosis rats were injected with 4×106 hAECs in group A, and with normal saline in group B, and no treatment was given in group C; group D served as control group. After 2 weeks of transplantation, the expression of human Alu gene repeat sequence was detected by DNA-PCR method and human leucocyte antigen G (HLA-G) by immunohistochemical staining in heart, liver, spleen, kidney, lung, and brain in group A, and then the percentage of positive expression was compared between organs except spleen. Semi-quantitative analysis was done for liver fibrosis with HE staining according to Chevallier semi-quantitative histological liver fibrosis scoring system, and immunohistochemical staining for TGF-β1 was used to record immunohistochemical score (ISH), the concentrations of aspartate transaminase (AST), alanine aminotransferase (ALT), and albumin (ALB) were determined to analyze hepatic fibrosis. ResultsAlu gene repeat sequence and HLA-G could be detected in liver, heart, brain, lung, and kidney in group A, the percentage of positive expression in the liver was significantly higher than that in the other organs (P<0.05). The histological semi-quantitative score of group A (10.47±3.20) was significantly lower than that of groups B and C[(13.84±3.46) and (13.85±3.16)](P<0.05), but no significant difference was found between groups B and C (P>0.05). The ISH scores in groups A, B, C, and D were 3.60±1.50, 5.38±2.60, 5.50±2.40, and 1.87±1.36, respectively; groups A, B, and C were significantly higher than group D, and group A was significantly lower than groups B and C (P<0.05), but there was no significant difference between groups B and C (P>0.05). The concentrations of ALT and AST in groups A, B, and C were significantly higher than those in group D, and group A was significantly lower than groups B and C (P<0.05), but there was no significant difference between groups B and C (P>0.05). The concentration of ALB in groups A, B, and C was significantly lower than that in group D, and group A was significantly higher than groups B and C (P<0.05), but there was no significant difference between groups B and C (P>0.05). ConclusionhAECs can survive in immune rats by intrasplenic transplantation and migrate to liver, heart, brain, lung, and kidney, and the liver shows the largest migration. The transplantation of hAECs in immune rat with cirrhosis can alleviate hepatic fibrosis and improve the serum indexes of liver function.
【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.
Early diagnosis and accurate stage of liver fibrosis are important for conducting the clinic therapy and assessing the therapeutic outcome. Functional magnetic resonance imaging (fMRI), as a noninvasive and effective method, plays an important role in diagnosis and stage of liver fibrosis. This review focuses on the advances in fMRI evaluation of liver fibrosis.
ObjectiveTo summarize the research progress on the role of exosomes derived from different sources in hepatic stellate cells.MethodThe experimental studies and clinical applications of exosomes from different cell sources effected on hepatic stellate cells were reviewed.ResultsIn the occurrence and development of liver fibrosis pathological physiological process, the activation, proliferation, migration, apoptosis of hepatic stellate cells played the important roles on the development of liver fibrosis. In recent years, the study found that the exosomes derived from different sources contained active protein, mRNA, microRNA, long noncoding RNA, and lipid components involved in the biological function of hepatic stellate cells, realized the communication between cells, which played the important regulatory role in the formation of liver fibrosis.ConclusionsExosomes derived from different sources and their contents play an important regulatory role in occurrence and development of liver fibrosis. In the future, exosomes might become a new non-invasive diagnostic method for liver fibrosis to help its early diagnosis, and might also be used as a biological active carrier to achieve its targeted therapy for targeted tissues and cells.
【Abstract】 Objective To review the study of noninvasive imaging methods for evaluating liver fibrosis. Methods The current literatures on the use of the ultrasonography， CT and MRI for the evaluation of liver fibrosis were reviewed. The principles, applications and advancement of each imaging methods were described and summarized respectively. The features of the newly developed imaging techniques were also discussed. Results In addition to the morphologic information， the imaging examinations can also provide functional information about the circulation status， diffusion and metabolism features of liver. The potential diagnostic value of MR elastography for liver fibrosis has been addressed. Conclusion The imaging examinations, especially the functional MRI techniques, are reliable noninvasive alternatives for the evaluation of hepatic fibrosis, with bright potentiality for clinical application.