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.
Fibropolycystic liver diseases (FLDs) is a rare genetic disorder, including bile duct hamartomas, congenital hepatic fibrosis, polycystic liver disease, Caroli’s disease, and choledochal cysts. Fibropolycystic liver diseases has received little clinical attention and exhibits a variety of imaging manifestations, leading to a high likelihood of missed diagnosis and misdiagnosis. Through this case, we delineate the characteristic imaging manifestations of the disease and its underlying pathological mechanisms. Our objective is to enhance readers' comprehension of the disease and thereby reduce the rate of missed diagnosis and misdiagnosis of the disease.
【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.
ObjectiveTo investigate the differentiation potential of human umbilical cord mesenchymal stem cells (HUCMSCs) into hepatocytes induced by rat fibrotic liver tissue extracts. MethodsLiver fibrosis was induced in the Sprague Dawley rats (weighting, 180-220 g) by repeated intraperitoneal injections of 3% thioacetamide-saline at a dose of 200 mg/kg twice a week for 4 weeks;fibrotic liver tissues were used to prepare liver homogenate supernatants. The HUCMSCs at passage 3 were cultured in DMEM/F12 with 10% fetal bovine serum (FBS) (control group) and in DMEM/F12 with 10%FBS and 50 g/L liver homogenate supernatants (experimental group) for 7 days. The morphological changes of the cells were recorded;the protein levels of cytokeratin 18 (CK18), alpha fetoprotein (AFP), and CYP3A4 were measured using Western blot. The glycogen storing ability of the cells was detected by periodic acid-schiff (PAS) staining. Furthermore, the synthesis of albumin (ALB) and blood urea nitrogen (BUN) was measured. ResultsIn experimental group, after 1 day of induction, the stem cells of fusiform shape began to lose sharp edges and progressively shrunk, and then they changed into hepatocyte-like cells with round and irregular shape at 7 days. Positive expressions of AFP, CK18, and CYP3A4 were observed in the experimental group, but negative expression in the control group. The concentrations of BUN and ALB were (0.43±0.07) mmol/L and (8.08±0.41) μg/mL in the control group and were (2.52±0.20) mmol/L and (41.48±4.11) μg/mL in the experimental group, showing significant differences (t=24.160, P=0.000;t=19.810, P=0.000). PAS staining results showed navy blue nucleus and lavender cytoplasm in the control group, but dark purple cell body and visible nucleus in the experimental group. ConclusionHUCMSCs could differentiate into hepatocyte-like cells induced by rat fibrotic liver tissue extracts, which have hepatocyte biomarkers (AFP, CK18, and CYP3A4) and hepatocyte-specific functions of glycogen storage, urea production and ALB secretion, so they could partially replace the function of hepatocytes, that may be one of the therapeutic mechanisms of stem cell transplantation.
Objective To investigate the effect of blood microenvironment of rats with hepatic fibrosis on differentiation of human umbilical cord mesenchymal stem cells (HUCMSCs) into hepatocytes and its mechanisms. Methods Eighteen male adult Sprague Dawley rats [weighing, (200±20) g] were used, liver fibrosis was induced in 12 rats by repeated intraperitoneal injections of thioacetamide. The serum was separated after successful model preparation, and the serum of 6 normal rats was collected. ELISA assay was used to detect the concentrations of epidermal growth factor (EGF), hepatocyte growth factor (HGF), oncostatin M (OSM), and basic fibroblastic growth factor (bFGF). Passage 3 HUCMSCs were divided into 3 groups: cells were cultured for 7 days in DMEM/F12 containing 10% fetal bovine serum and 5 mL/ L serum from rats with hepatic fibrosis (group A), in DMEM/F12 containing 10% fetal bovine serum and 5 mL/ L serum from normal rats (group B), and in DMEM/F12 containing 10% fetal bovine serum (group C). The morphological changes of the cells were observed. The expressions of α-fetoprotein (AFP) and cytokeratin 18 (CK18) were detected by immunofluorescence. The protein levels of albumin (ALB), tryptophan 2, 3-dioxygenase (TPH2), and CYP3A4 and MAPK/ERK signal pathway protein (P-ERK) were detected using Western blot. The content of blood urea nitrogen (BUN) was measured by diacetyl m onoxime method. Results HE staining showed that the liver tissue of rats was in accordance with the change of fibrosis, indicating successful model preparation. In serum of normal rats and rats with hepatic fibrosis, the concentrations of EGF were (21.42±0.32) pg/mL and (17.57±0.31) pg/mL respectively, showing significant difference (t=14.989, P=0.000); the concentrations of OSM were (129.96±0.65) pg/mL and (98.44±1.32) pg/mL respectively, showing significant difference (t=37.172, P=0.000); the concentrations of HGF were below the detection limit and (1.03±0.12) ng/ mL respectively; and the concentrations of bFGF were lower than the detection limit in both groups. No morphological changes of cells were observed in both groups at 7 days, and there was no significant difference between groups. At 7 days after culture, the cells in group A could express human hepatocyte biomarkers of AFP, CK18 and hepatocyte-specific-function proteins of ALB, TPH2, and CYP3 A4 while cells in groups B and C did not. Western blot showed that cells in each group could express P-ERK protein. The relative level of P-ERK protein in group A was significantly higher than that in groups B and C (P < 0.05), but no significant difference was found between groups B and C (P > 0.05). The BUN concentration of group A [(0.74±0.07) mmol/ L] was significantly higher than that of groups B [(0.40±0.04) mmol/ L] and C [(0.38±0.04) mmol/L] (P < 0.05), but no significant difference was shown between groups B and C (P > 0.05). Conclusion Under the condition of hepatic fibrosis, the level of HGF will increase while EGF and OSM will decrease. The formed blood microenvironment will activate MAPK/ERK signal pathway in HUCMSCs, induce them differentiate into hepatocytes.
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.
ObjectiveTo summarize mechanism of DNA methylation and histone methylation in liver fibrosis.MethodThe literatures on the DNA methylation and histone methylation during the liver fibrosis were reviewed and analyzed.ResultsThe DNA methylation and histone methylation were the important components of epigenetics. The up-regulation or down-regulation of genes during the liver fibrosis leaded to the activation or inactivation of the subsequent pathways. For example, the PTEN, SEPT9, Smad7, etc. were hypermethylated and the expressions were decreased in the liver fibrosis. The Spp1 was hypomethylated and the expression was increased in the liver fibrosis.ConclusionsMethylation affects expression of genes by altering epigenetics of genes. Systematic and in-depth study of role and mechanism of methylation in liver diseases provides a new direction and locations for some target treatments for liver disease.
ObjectiveTo summarize the role of ionized free calcium/calmodulin/calmodulin-dependent protein kinase Ⅱ (Ca2+/CaM/CaMKⅡ) signaling pathway in liver fibrosis so as to provide a theoretical basis for the treatment of liver fibrosis. MethodThe recent literature relevant research on the role of Ca2+/CaM/CaMKⅡ signaling pathway in the process of liver fibrosis both domestically and internationally was reviewed. ResultsThe Ca2+/CaM/CaMKⅡ signaling pathway played a bidirectional regulatory role in the process of liver fibrosis, potentially facilitating the activation of hepatic stellate cells and triggering hepatocyte apoptosis through synergistic transforming growth factor-β1 and platelet-derived growth factor pathways. ConclusionsAt present, there is very little research on the role of Ca2+/CaM/CaMKⅡ signaling pathway in the process of liver fibrosis, and there is still insufficient understanding. Future research should focus on the mechanism of this signaling pathway in liver fibrosis, especially its upstream genes or downstream target proteins, which will aid to develop targeted and effective treatment strategies, achieve the reversal of liver fibrosis and even liver cirrhosis, and provide more effective treatment options for patients with liver fibrosis.