化肝纤方联合恩替卡韦对慢乙肝肝纤维化患者的血清壳多糖酶3样蛋白1及临床疗效观察

目的:基于以壳多糖酶3样蛋白1(chitinase-3-like protein 1,CHI3L1)为主要评价指标,观察化肝纤方联合恩替卡韦治疗慢性乙型肝炎肝纤维化的临床疗效。方法:将80例确诊为慢性乙型肝炎肝纤维化的患者采用随机数字表法的方式分为对照组和治疗组各40例,2组均采用一般西医综合治疗,治疗组在此基础上仅加用化肝纤方,疗程为8周,比较2组治疗前后的血清CHI3L1水平、肝功能(转氨酶、总胆红素)、肝纤4项、Fibrosis 4 Score(FIB-4指数)、肝脏硬度值(liver stiffness measurement,LSM)、乙肝病毒DNA(hepatitis B virus-DNA,HBV-DNA)转阴率、中医症状评分等观察指标。结果:治疗后治疗组血清CHI3L1水平、肝功能(转氨酶、总胆红素)、肝纤4项、FIB-4指数、肝脏硬度值、HBV-DNA转阴率、中医症状评分均低于对照组,差异有统计学意义。结论:化肝纤方联合恩替卡韦治疗慢性乙型肝炎相关肝纤维化有较好的临床疗效,可改善慢性乙型肝炎肝纤维化患者肝脏生理水平及肝纤维化程度,降低血清CHI3L1、肝纤4项、FBI-4指数、肝脏硬度值,提高乙肝病毒DNA转阴率,改善肝功能及临床症状,延缓疾病的进展,提高患者生存质量。

Transient elastography for the assessment of chronic liver disease: Ready for the clinic?

Transient elastography is a recently developed non- invasive technique for the assessment of hepatic fi brosis. The technique has been subject to rigorous evaluation in a number of studies in patients with chronic liver disease of varying aetiology. Transient elastography has been compared with histological assessment of percutaneous liver biopsy, with high sensitivity and specificity for the diagnosis of cirrhosis, and has also been used to assess pre-cirrhotic disease. However, the cut-off values between different histological stages vary substantially in different studies, patient groups and aetiology of liver disease. More recent studies have examined the possible place of transient elastography in clinical practice, including risk stratifi cation for the development of complications of cirrhosis. This review describes the technique of transient elastography and discusses the interpretation of recent studies, emphasizing its applicability in the clinical setting.

FEASIBILITY OF DIAGNOSING AND STAGING LIVER FIBROSIS WITH DIFFUSION WEIGHTED IMAGING

Objective To assess the clinical feasibility of diagnosing and staging liver fibrosis by apparent diffusion coefficient (ADC). Methods Totally, 43 patients (mean age 29.3 years) with chronic hepatitis by liver biopsy and 7 healthy controls (mean age 39.9 years) underwent liver diffusion weighted imaging (DWI) with four b values: 0, 200, 500, and 1000 s/mm2 respectively. The liver fibrosis was staged according to Ishak fibrosis stage. The ADC value of liver fibrosis patients and healthy controls was compared. The correlation of ADC value and liver fibrosis staging was analyzed. Result The histological staging showed 8 stage 1 patients, 10 stage 2 patients, 6 stage 3 patients, 9 stage 4 patients, 8 stage 5 patients and 2 stage 6 patients. The mean ADC value of liver fibrosis patients was significantly lower than that of healthy controls except for stage 1 group (P < 0.05). There was a negative correlation between liver fibrosis staging and ADC value (r = -0.697 with b=500 s/mm2, P < 0.01). Receiver operating characteristic (ROC) curve of ADC value of advanced liver fibrosis (Ishak stage F3 and higher) showed that area under curve = 0.913, 0.825, and 0.794 with b = 500, 1000, and 200 s/mm2, respectively (95% confidence interval: 83.6%-99.0%, 70.7%-94.3%, 66.5%- 92.4%; P < 0.05). When b value was 500 s/mm2, the sensitivity (84%) and specificity (80%) of DWI for diagnosis of advanced liver fibrosis were the highest. Conclusion DWI is proved to be a useful clinical tool in the quantitative evaluation of liver fibrosis and in the prediction of the process of liver fibrosis with the recommendable b value (500 s/mm2).

Is it better to use two elastographic methods for liver fibrosis assessment?

AIM:To find out if by combining 2 ultrasound based elastographic methods:acoustic radiation force impulse(ARFI)elastography and transient elastography(TE),we can improve the prediction of fibrosis in patients with chronic hepatitis C.METHODS:Our study included 197 patients with chronic hepatitis C.In each patient,we performed,in the same session,liver stiffness(LS)measurements by means of TE and ARFI,respectively,and liver biopsy(LB),assessed according to the Metavir score.10 LS measurements were performed both by TE and ARFI;median values were calculated and expressed in kilopascals(kPa)and meters/second(m/s),respectively.Only TE and ARFI measurements with IQR<30%andSR≥60%were considered reliable.RESULTS:On LB 13(6.6%)patients had F0,32(16.2%) had F1,52(26.4%)had F2,47(23.9%)had F3,and 53(26.9%)had F4.A direct,strong correlation was found between TE measurements and fibrosis(r=0.741),between ARFI and fibrosis(r=0.730)and also between TE and ARFI(r=0.675).For predicting significant fibrosis(F≥2),for a cutoff of 6.7 kPa,TE had 77.5% sensitivity(Se)and 86.5%specificity(Sp)[area under the receiver operating characteristic curve(AUROC)0.87] and for a cutoff of 1.2 m/s,ARFI had 76.9%Se and 86.7%Sp(AUROC 0.84).For predicting cirrhosis(F=4),for a cutoff of 12.2 kPa,TE had 96.2%Se and 89.6% Sp(AUROC 0.97)and for a cutoff of 1.8 m/s,ARFI had 90.4%Se and 85.6%Sp(AUROC 0.91).When both elastographic methods were taken into consideration,for predicting significant fibrosis(F≥2),(TE≥6.7 kPa and ARFI≥1.2 m/s)we obtained 60.5%Se,93.3% Sp,96.8%positive predictive value(PPV),41.4%negative predictive value(NPV)and 68%accuracy,while for predicting cirrhosis(TE≥12.2 kPa and ARFI≥1.8 m/s) we obtained 84.9%Se,94.4%Sp,84.9%PPV,94.4% NPV and 91.8%accuracy.CONCLUSION:TE used in combination with ARFI is highly specific for predicting significant fibrosis;therefore when the two methods are concordant,liver biopsy can be avoided.

Rosiglitazone prevents murine hepatic fibrosis induced by Schistosoma japonicum

AIM: To evaluate the effect of rosiglitazone in a murine model of liver fibrosis induced by Schistosoma japonicum infection. METHODS: A total of 50 mice were randomly and averagely divided into groups A, B, C, D and E. The mice in group A served as normal controls, while those in the other four groups were infected with Schistosoma japonicum to induce the model of liver fibrosis. Besides, the mice in groups C, D and E were treated with praziquantel, rosiglitazone and praziquantel plus rosiglitazone, respectively. NF-κB binding activity and expression of PPARγ-mRNA were determined by Western blot assay and real-time quantitative PCR. Radioimmunonassay technique was used to detect the serum content changes of TNF-α and IL-6. Histological specimens were stained with HE. Expression of TGF-β1, a-smooth muscle actin and type ?Ⅰ?and type Ⅲ collagen was detected by immunohistochemistry and multimedia color pathographic analysis system. RESULTS: Inflammation and fibrosis in the rosiglitazone plus praziquantel treatment group (group E) were lightest among the mice infected with Schistosoma (P < 0.05). To further explore the mechanism of rosiglitazone action, we found that rosiglitazone can significantly increase the expression of PPARγ [E: -18.212 ± (-3.909) vs B: -27.315 ± (-6.348) and C: -25.647 ± (-5.694), P < 0.05],reduce the NF-κB binding activity (E: 88.89 ± 19.34 vs B: 141.11 ± 15.37, C: 112.89 ± 20.17 and D: 108.89 ± 20.47, P < 0.05), and lower the serum level of TNF-α (E: 1.613 ± 0.420 ng/mL vs B: 2.892 ± 0.587 ng/mL, C: 2.346 ± 0.371 ng/mL and D: 2.160 ± 0.395 ng/mL, P < 0.05) and IL-6 (E: 0.106 ± 0.021 ng/mL vs B: 0.140 ± 0.031 ng/mL and C: 0.137 ± 0.027 ng/mL, P < 0.05) in mice with liver fibrosis. Rosiglitazone can also substantially reduce the hepatic expression of TGF-β1, α-SMA type Ⅰand type Ⅲ collagen in mice with liver fibrosis. CONCLUSION: The activation of PPARγ by its ligand can retard liver fibrosis and suggest the use of rosiglitazone for the treatment of liver fibrosis due to Schistosoma japonicum infection.

Liver fibrosis identification based on ultrasound images captured under varied imaging protocols

Diagnostic ultrasound is a useful and noninvasive method in clinical medicine. Although due to its qualitative, sub- jective and experience-based nature, ultrasound image interpretation can be influenced by image conditions such as scanning frequency and machine settings. In this paper, a novel method is proposed to extract the liver features using the joint features of fractal dimension and the entropies of texture edge co-occurrence matrix based on ultrasound images, which is not sensitive to changes in emission frequency and gain. Then, Fisher linear classifier and support vector machine are employed to test a group of 99 in-vivo liver fibrosis images from 18 patients, as well as other 273 liver images from 18 normal human volunteers.

Non-invasive assessment of liver fibrosis in chronic liver diseases:Implementation in clinical practice and decisional algorithms

Chronic hepatitis B and C together with alcoholic and non-alcoholic fatty liver diseases represent the major causes of progressive liver disease that can eventually evolve into cirrhosis and its end-stage complications,including decompensation,bleeding and liver cancer.Formation and accumulation of fibrosis in the liver is the common pathway that leads to an evolutive liver disease.Precise definition of liver fibrosis stage is essential for management of the patient in clinical practice since the presence of bridging fibrosis represents a strong indication for antiviral therapy for chronic viral hepatitis,while cirrhosis requires a specif ic follow-up including screening for esophageal varices and hepatocellular carcinoma.Liver biopsy has always represented the standard of reference for assessment of hepatic fibrosis but it has some limitations being invasive,costly and prone to sampling errors.Recently,blood markers and instrumental methods have been proposed for the non-invasive assessment of liver fibrosis.However,there are still some doubts as to their implementation in clinical practice and a real consensus on how and when to use them is not still available.This is due to an unsatisfactory accuracy for some of them,and to an incomplete validation for others.Some studies suggest that performance of non-invasive methods for liver fibrosis assessment may increase when they are combined.Combination algorithms of non-invasive methods for assessing liver fibrosis may represent a rational and reliable approach to implement non-invasive assessment of liver fibrosis in clinical practice and to reduce rather than abolish liver biopsies.

Intravenous injection of mesenchymal stem cells is effective in treating liver fibrosis

AIM: To compare the influence of different transplant sites in bone marrow mesenchymal stem cell (MSC)-based therapy for liver fibrosis. METHODS: MSCs isolated from Sprague Dawley (SD) rats were induced into hepatocyte-like cells. Liver fibrosis in SD rats was induced with carbon tetrachloride. Following hepatocyte induction in vitro, 4',6-diamidino- 2-phenylindole (DAPI)-labeled MSCs were transplanted by intravenous, intrahepatic, and intraperitoneal injection. Histopathological staining, immunohistochemistry, and biochemical analysis were used to compare the morphological and functional liver regeneration among different MSC injection modalities. The expression differences of interleukins, growth factor, extracellular matrix, matrix metalloproteinases, and tissue inhibitor of metalloproteinase were examined by real-time reverse transcription-polymerase chain reaction (RT-PCR) andenzyme linked immunosorbent assay (ELISA). RESULTS: Four days after exposure to hepatocyte differentiation medium, MSCs that did not express hepatocyte markers could express α-fetoprotein, albumin, and cytokeratin 18. The results of histopathological staining, immunohistochemistry, and biochemical analysis indicated that intravenous injection is more effective at rescuing liver failure than other injection modalities. DAPI-labeled cells were found around liver lobules in all three injection site groups, but the intravenous group had the highest number of cells. PCR and ELISA analysis indicated that interleukin-10 (IL-10) was highest in the intravenous group, whereas il1β, il6, tnfα and tgfβ, which can be regulated by IL10 and are promoters of liver fibrosis, were significantly lower than in the other groups. CONCLUSION: MSC administration is able to protect against liver fibrosis. Intravenous injection is the most favorable treatment modality through promotion of IL10 expression.