弹性成像、B超、肝纤维化指标与肝纤维化程度的相关性研究

目的分析B超、肝纤维化指标与肝纤维化程度的相关性。方法随机选取医院收治的2012年1月到2015年1月60例乙型肝炎病毒感染患者,并且依据随机数字表方法分为研究组(20例)、观察组(20例)和对照组(20例)。给予对照组患者,应用B超检测;研究组患者,进行弹性成像检测;观察组,应用肝纤维化指标检测;对三组进行弹性成像、B超、肝纤维化指标检测的临床效果进行比较,分析不同检测方法与患者肝纤维化程度的相关性。结果乙型肝炎病毒感染患者在临床检测中,研究组与对照组检测结果与肝纤维化程度呈正相关,且随着患者肝组织炎症坏死以及纤维化程度的升高而升高;且在三组中随着肝纤维化程度的不同,患者肝功能总胆红素(TBil)、血清透明质酸(HA)、Ⅲ型胶原蛋白(PCⅢ)存在差异,有统计学意义(P0.05)。结论临床针对乙型肝炎病毒感染患者进行弹性成像检测,在反映肝纤维化程度方面具有相关性,与B超、肝纤维化指标发挥较好一致性,对临床评估肝纤维化程度具有较好的诊断价值。     

肝得健联合丹参注射液治疗慢性乙型肝炎肝纤维化疗效观察

目的观察肝得健联合丹参注射液治疗肝纤维化的疗效。方法选择慢性乙型肝炎肝纤维化患者68例。分为肝得健加丹参组、肝得健组、丹参组及对照组。治疗前后检测肝功能、肝纤维化血清学指标（HA、PCⅢ、LN、IV-C）。结果治疗后肝纤维化指标均有不同程度的好转。各组治疗前后及组间比较差异均有统计学意义。结论肝得健联用丹参治疗慢性乙型肝炎肝纤维化能增强抗肝纤维化效应。为临床治疗慢性肝炎和抗肝纤维化治疗提供依据。     

肝康Ⅱ号治疗慢性乙型肝炎肝纤维化的临床观察

观察肝康Ⅱ号治疗慢性乙型肝炎肝纤维化的临床疗效。76例慢性乙型肝炎肝纤维化患者随机分为两组,治疗组(40例)口服肝康Ⅱ号,对照组(36例)口服复方丹参滴丸,疗程均为3个月。观察两组用药前后肝功能、血清肝纤维化指标及肝组织病理等方面的改变。结果显示治疗组肝功能和血清肝纤维化指标均有明显改善(P< 0．01或P<0．05),也优于对照组(P<0．01或P<0．05)。肝脏组织病理检查显示治疗组炎症活动度减轻,肝纤维化程度明显下降。说明肝康Ⅱ号对慢性乙型肝炎肝纤维化有较好的抗肝纤维化作用。     

恩替卡韦联合氧化苦参碱治疗对肝纤维化患者肝功能及肝纤维化指标的影响

目的:探讨恩替卡韦联合氧化苦参碱治疗对肝纤维化患者肝功能及肝纤维化指标的影响。方法:选取2018年1月至2019年12月在我院消化科住院的慢性乙型肝炎肝纤维化患者98例,分为联合治疗组和恩替卡韦组各49例,两组患者均进行常规治疗,恩替卡韦组患者口服恩替卡韦治疗,联合治疗组患者采用恩替卡韦联合氧化苦参碱治疗,观察两组患者治疗前后肝功能、肝纤维化、炎症指标的变化及不良反应发生情况。结果:与恩替卡韦组相比,联合治疗组患者肝功能、肝纤维化、炎症指标好转时间、IL-6、IL-8、IL-10、TGF-β1、IFN-γ、TNF-α、肝功能指标、肝纤维化指标水平明显降低(P<0.05);与恩替卡韦组相比,联合治疗组IL-2水平明显下降(P<0.05),治疗总有效率较高(P<0.05);两组患者不良反应发生情况无明显差异(P>0.05)。结论:应用恩替卡韦联合氧化苦参碱治疗肝纤维化患者,可有效改善肝功能及肝纤维化程度,效果显著。     

肝纤维化发生的机制

各种致病因子作用于肝组织后,可直接导致肝细胞不同程度的损害,引起肝细胞的损伤、再生及肝纤维化等,最终导致肝功能不全,晚期则发展为肝功能衰竭。关于肝纤维化机制及对其防治的研究,近年来已成为国内外生物学、医学研究的热点之一。本文综述了肝纤维化发生的机制,并对其作用机制进行探讨。     

重组肝再生增强因子对大鼠肝纤维化的保护作用

目的　观察重组肝再生增强因子 (rALR)对大鼠肝纤维化的保护作用。方法　构建表达ALR的质粒 ,将得到的rALR用于CCl4 致肝纤维化的大鼠 ,观察rALR对肝纤维化动物模型肝功能、血清细胞外基质水平及肝组织纤维化程度的影响。结果　rALR可显著改善CCl4 肝纤维化模型大鼠肝功能 ,降低血清细胞外基质水平和肝组织纤维化程度。结论　rALR对实验大鼠肝功能具有显著的改善作用 ,对抗肝纤维化亦有一定的作用。     

γ-干扰素抗肝纤维化临床疗效的初步观察

本文报道用γ－干扰素治疗慢性肝炎肝纤维化２０例的结果。另有２０例以一般常规治疗为对照。治疗前，后做肝功能，肝纤维化血清指标。治疗后，肝功能均有不同程度好转，尤以白蛋白升高；ＨＡ、Ⅳ－Ｃ，ＰＣⅢ和ＬＮ均有明显下降，差异非常显著。初步证明ＩＦＮ－γ有一定的抗肝纤维化作用，且无严重副作用。     

抗纤软肝胶囊联合阿德福韦酯治疗慢性乙型肝炎肝纤维化的临床研究

目的:评价抗纤软肝胶囊联合阿德福韦酯治疗慢性乙型肝炎肝纤维化的疗效.方法:将104例慢性乙型肝炎肝纤维化患者随机分为3组:抗纤软肝胶囊治疗组、阿德福韦酯治疗组和抗纤软肝胶囊联合阿德福韦酯治疗组,治疗前后分别进行肝功能、肝纤维化血清学指标检测及超声影像学检查.结果:治疗1年后,①3组患者肝功能、肝纤维化指标和超声影像学指标均有不同程度的好转;②阿德福韦酯组和联合治疗组ALT降低和Alb升高幅度与抗纤软肝胶囊组相比较,差异有显著性意义(P＜0.05);③联合治疗组在肝纤维化指标(HA、LN、C-Ⅳ)和超声影像学指标(门脉主干内径、脾厚度)方面的改善与其他两组比较,差异有显著性意义(P＜0.05).结论:抗纤软肝胶囊和阿德福韦酯均有一定的抗慢性乙型肝炎肝纤维化的作用,两者联用时抗纤维化疗效更好.     

血清肝纤维化指标与慢性肝炎肝纤维化程度的相关性

目的:评价血清肝纤维化指标与慢性肝炎肝纤维化程度病理分期的关系.方法:采用放射免疫技术对113例慢性肝炎患者的血清进行肝纤维化指标检测,包括透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原蛋白(PCⅢ)、Ⅳ型胶原蛋白(Ⅳ-C).并按肝穿刺活检进行组织纤维化分期(S),对这些指标的诊断价值进行分析.结果:血清肝纤维化指标HA、PcⅢ、Ⅳ-C与肝组织纤维化程度相关(r=0.677,0.395,O.454,P<0.01或0.05).除LN外(r=0.053,P>0.05),HA、PCⅢ、Ⅳ-C均随着肝纤维化程度的加重而呈上升趋势.结论:血清肝纤维化指标对判断肝纤维化程度有一定指导意义,对于难以开展肝穿刺活检的单位可以帮助肝纤维化诊断.     

强力宁合用丹参抗肝纤维化的疗效观察

本研究选择了７２例慢性乙型肝炎（ＣＨＢ）病人，分强力宁加丹参组，强力宁组，丹参组及对照组。治疗前后检测肝功能，病毒指标及肝纤维化血清学指标（ＨＡ，ＰＣⅢ，ＬＮ及ＩＶ－Ｃ）。结果表明，治疗后肝纤维化指标均有不同程度好转，各治疗组与治疗前及对照组治疗后差比较差异显著，且强力宁与丹参联用抗肝纤维化作用优于单用强力宁或丹参。     

碱性成纤维细胞生长因子与慢性乙型肝炎及肝纤维化临床检测指标的关系

目的观察碱性成纤维细胞生长因子(b-FGF)在不同肝纤维化分期(S)肝组织中表达的差异性及其与临床检测常用的肝功能指标、肝纤维化指标、HBV DNA复制水平以及肝硬化Child-Pugh分级之间的关系。方法选取122例HBV引起的慢性肝炎及肝硬化患者,空腹静脉血检测:(1)肝功能指标:ALT、TBil、Alb;(2)肝纤维化指标:透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、层粘连蛋白(LN)、Ⅳ型胶原(CⅣ);(3)HBV DNA复制水平;(4)对临床诊断肝硬化患者计算其Child-Pugh评分。行肝脏穿刺活检术后,经病理作纤维化分期(S1～S4)。免疫组织化学法测定肝组织中b-FGF在不同病理分期的表达及定位特点,半定量分析法计算b-FGF值,观察b-FGF与肝功能指标、肝纤维化指标、HBV DNA水平以及肝硬化Child-Pugh分级之间的关系。结果 (1)肝纤维化S1～S4期肝组织中b-FGF的表达部位及水平不同;(2)肝纤维化S1～S4期肝细胞中b-FGF的表达与肝纤维化分期(S1～S4)呈显著正相关(r=0.542,P<0.01);(3)不同肝纤维化分期中b-FGF的表达差异与患者ALT、TBil及Alb进行比较,其差异无统计学意义(P>0.05),不同肝纤维化分期患者,进行HBV DNA检测,其差异无统计学意义(P>0.05);(4)不同肝纤维化分期中,b-FGF与血清纤维化指标HA、PCⅢ、LN、CⅣ之间呈正相关;(5)b-FGF的表达与临床Child-Pugh分级无明显相关性。结论 b-FGF的表达与肝脏纤维化程度、肝纤维化指标有正相关关系,与患者ALT、TBil、Alb、Child-Pugh评分、及HBV DNA水平无关。     

Efficacy of AST to platelet ratio index in predicting severe hepatic fibrosis and cirrhosis in chronic hepatitis B virus infection]

BACKGROUND/AIMS: An ideal noninvasive diagnostic test for hepatic fibrosis should be simple, inexpensive, and accurate. We aimed to find the simple marker for predicting hepatic fibrosis and to compare the accuracy of AST, platelet, AST/ALT ratio and AST to platelet ratio index (APRI) in chronic hepatitis B patients without clinical evidence of cirrhosis. METHODS: A total of one hundred and twenty-six chronic hepatitis B patients who underwent liver biopsy at the Ajou University Hospital from August 1998 to December 2003 were enrolled. Hepatic fibrosis was assessed using the Ludwig classification. Significant fibrosis was defined as fibrosis score of 3 or more. The AST/ALT ratio and APRI were calculated and correlations with hepatic fibrosis were analyzed. RESULTS: APRI showed a significant correlation (r=0.501, p=0.000) with hepatic fibrosis, and was superior to AST, AST/ALT ratio and platelet in predicting fibrosis. Patients with significant fibrosis (fibrosis stage 3, 4) can be identified to have APRI = 1 with sensitivity 71.2% and specificity 70.3%. The sensitivity and specificity of an APRI = 1.5 for cirrhosis (stage 4) were 83.3% and 75.0%. CONCLUSIONS: Simple index using AST and platelet value can predict the presence of significant fibrosis and cirrhosis in chronic hepatitis B patients without clinical evidence of cirrhosis.     

门冬氨酸鸟氨酸对肝纤维化大鼠的实验研究

目的通过大鼠肝纤维化动物模型，研究门冬氨酸鸟氨酸防止肝纤维化的作用。方法采用0．03％的硫代乙酰胺溶液腹腔注射制备大鼠肝纤维化模型，观察门冬氨酸鸟氨酸对大鼠肝功能指标、组织病理学改变和脯氨酸羟化酶表达的影响。结果门冬氨酸鸟氨酸能降低大鼠AST，ALT水平（P〈0．05），减轻肝纤维化的病理改变进程。结论门冬氨酸鸟氨酸具有一定的抗肝纤维化作用。     

Assessment of hepatic fibrosis and necroinflammation among inactive HBsAg carriers in Egypt

Introduction. The inactive hepatitis B surface antigen (HBsAg) carrier state is usually characterized by minimal or absent liver pathology. However, in developing countries, owing to the very early age of infection with hepatitis B virus (HBV), this state is reached after a very prolonged immune tolerant and immune reactive phase, during which considerable liver damage may have occurred. The extent of liver damage in inactive HBsAg carriers has not been thoroughly assessed in developing countries. We thus sought to characterize liver pathology among Egyptian inactive HBsAg carriers.Material and methods. Liver biopsy was conducted on 30 inactive HBsAg carriers [positive for HBsAg; negative for HBeAg; positive for antibody to HBeAg (anti-HBe); HBV-DNA levels < 2,000 IU/mL; persistently normal serum alanine aminotransferase (ALT)]. Liver histopathology was assessed according to the Ishak scoring system.Results. Among the studied carriers, 6.7% had no hepatic fibrosis, 73.3% had stage 1 fibrosis, and 20% had stage 2 fibrosis. The majority (80%) of carriers had minimal hepatic necroinflammation (grades 2-4), while 20% had mild hepatic necroinflammation (grade 5). All patients with stage 2 fibrosis were males, while no gender predilection was observed for necroinflammation. Age, ALT and HBV-DNA levels did not differ significantly according to fibrosis or ne-croinflammatory scores. Conclusion. Our study findings do not support the presence of significant hepatic fibrosis or necroinflammation among Egyptian inactive HBsAg carriers. However, follow-up studies on these carriers may be required to monitor any further pathological progress of the disease.     

Quantitative testing of liver function in relation to fibrosis in patients with chronic hepatitis B and C.

BACKGROUND/AIM: Quantitative tests of liver function may be superior to conventional tests to assess the prognosis of patients with liver diseases. There are insufficient data from quantitative testing of liver function (QTLF) for patients with chronic hepatitis B and C, particularly with regard to fibrosis. Therefore, we applied a broad panel of QTLF to these patients. METHODS: Three hundred and sixty-seven consecutive patients with chronic hepatitis B or C underwent liver biopsy and QTLF, which included tests for hepatic metabolism (aminopyrine breath test, galactose elimination capacity) and for hepatic perfusion (sorbitol clearance, indocyanine green clearance). QTLF values were correlated with liver histology (grading and staging for inflammation and fibrosis) and Child-Pugh classification for liver cirrhosis. RESULTS: In patients with no and moderate fibrosis, metabolic liver function was significantly decreased, whereas hepatic perfusion remained normal. Severe fibrosis and cirrhosis showed a significant decline in all QTLFs. Hepatic inflammation only reduced metabolic liver function, irrespective of the inflammatory grade. Viral etiology and HCV genotypes did not change QTLF. CONCLUSIONS: In summary, viral damage compromises hepatic metabolism before perfusion. Therefore, tests of metabolic liver function (aminopyrine breath test, galactose elimination capacity) should be useful to search for drugs that restore liver function in viral hepatitis irrespective of the fibrosis stage.     

林蛙油对大鼠肝纤维化的影响

目的 探讨林蛙油对大鼠肝纤维化的治疗效果.方法 用林蛙油治疗CCl4诱导的肝纤维化模型,观察它对肝细胞实验室检查及氧化和抗氧化能力指标的影响.结果 林蛙油能降低肝纤维化大鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、γ-谷氨基转移酶(GGT)、羟脯氨酸(Hyp)及丙二醛(MAD),增加超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GSH-Px).结论 林蛙油能改善其肝脏损伤程度,减少肝纤维化大鼠肝组织中胶原的增生,增加抗氧化能力,延缓肝硬化的形成,对大鼠肝纤维化有很好的治疗作用.     

Noninvasive parameters and hepatic fibrosis scores in children with nonalcoholic fatty liver disease

AIM: To evaluate the noninvasive parameters and hepatic fibrosis scores in obese children with nonalcoholic fatty liver disease (NAFLD).METHODS: A total of 77 children diagnosed with NAFLD via liver biopsy were included and divided into 2 subgroups according to the histopathologic staging of hepatic fibrosis: mild (stage 0-1) vs significant fibrosis (stage 2-4). Clinical and laboratory parameters were evaluated in each patient. The aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, AST/platelet ratio index (APRI), PGA index, Forns index, FIB-4, NAFLD fibrosis score, and pediatric NAFLD fibrosis index (PNFI) were calculated.RESULTS: No clinical or biochemical parameter exhibited a significant difference between patients with mild and significant fibrosis. Among noninvasive hepatic fibrosis scores, only APRI and FIB4 revealed a significant difference between patients with mild and significant fibrosis (APRI: 0.67 ± 0.54 vs 0.78 ± 0.38, P = 0.032 and FIB4: 0.24 ± 0.12 vs 0.31 ± 0.21, P = 0.010). The area under the receiving operating characteristic curve of FIB4 was 0.81, followed by Forns index (0.73), APRI (0.70), NAFLD fibrosis score (0.58), AST/ALT ratio (0.53), PGA score (0.45), and PNFI (0.41).CONCLUSION: APRI and FIB4 might be useful noninvasive hepatic fibrosis scores for predicting hepatic fibrosis in children with NAFLD.     

慢性乙型肝炎患者肝组织学纤维化分期与血清肝纤维化相关指标的关系

目的 探讨慢性乙型肝炎(CHB)肝组织学纤维化程度与临床血清肝纤维化相关指标之间的关系.方法 对189例人院诊断为CHB的患者行肝穿刺.同时检测血清HA、LN、PCⅢ、ⅣC、肝功能和血常规,并按组织学的不同纤维化分期(S)进行比较和相关性回归分析.结果 从肝纤维化So至S4期,PC Ⅲ、γ-GT、TBil、γ-球蛋白和PT渐增,差异有统计学意义(F值分别为3.325、6.218、2.958、10.160和7.028,P＜0.05);胆碱酯酶(CHE)、总蛋白(TP)、Alb、PLT值渐减,差异有统计学意义(F值分别为15.984、3.786、14.919和4.737,P＜0.01);LN、ⅣC、ALT和AST值在S各期比较差异有统计学意义(F值分别为4.618、2.795、2.649和3.199,P＜0.05).S分期与LN、PCⅢ、ALT、AST、TBil、γ-GT、γ-球蛋白、PT呈正相关(rs值为0.200、0.306、0.1 72、0.273、0.153、0.402、0.415、0.269),与CHE、TP、Alb、PLT呈负相关(rs值为-0.502、-0.208、-0.413、-0.390);LN、ALT、CHE、PLT、γ-球蛋白为肝纤维化分期的独立影响因素(P＜0.05).结论 肝组织学纤维化分期与血清肝纤维化、肝功能、血常规指标有不同程度相关.综合多项临床资料可早期无创性诊断肝纤维化.     

Adeno-associated virus mediated interferon-gamma inhibits the progression of hepatic fibrosis in vitro and in vivo

AIM: To investigate the effects of adeno-associated virus (AAV) mediated expression of human interferon-γ for gene therapy in experimental hepatic fibrosis in vitro and in vivo. METHODS: We constructed the recombinant AAV encoding human INF-γ (rAAV- INF-γ) and took the primary rat hepatic stellate cells and carbon tetrachloride induced rats as the experimental hepatic fibrosis model in vitro and in vivo. Immunocytochemistry analysis was used to reveal the expression of α-SMA, the marker protein expressed in hepatic stellate cells. The mRNA expression of TGF-β, TIMP-1, and MMP-13 were analyzed by RT-PCR method. In vivo study, the hydroxyproline content in liver and serum AST, ALT were also detected. RESULTS: In vitro study, AAV vector could mediated efficient expression of human INF-γ, which inhibit the activation of hepatic stellate cells, decrease the expression of α-SMA and mRNA of TIMP-1, TGF-β, with the MMP-13 unchanged. In vivo study, the histological examination revealed that rAAV- INF-γ could inhibit the progression of the hepatic fibrosis. In the rAAV-INF-γ induced group, the hydroxyproline content and serum AST, ALT level were decreased to 177±28 μg/g wet liver, 668.5±140.0, 458.4±123.5 U/L, compare with the fibrosis control group 236±31 μg/g wet liver, 1 019.1±276.3, 770.5±154.3 U/L, respectively (P<0.01). mRNA expression of TIMP-1 in the rAAV-INF-γ induced rat liver was decreased while no significant change was observed in TGF-β and MMP-13. CONCLUSION: All these results indicated that rAAV-INF-γ has potential effects for gene therapy of hepatic fibrosis, which could inhibit the progression of hepatic fibrosis.     

大于40岁ALT正常慢性HBV感染者肝组织纤维化分期的研究

目的观察大于40岁ALT正常慢性HBV感染者的肝组织纤维化分期的情况。方法选择64例慢性HBV感染者,检测血清肝功能、HBeAg、HBVDNA、进行肝脏活检,提供肝组织纤维化分期情况。结果年龄大于40岁ALT正常慢性HBV感染者肝组织73.44%有2期及以上的纤维化。肝纤维分期与Ⅲ型前胶原、透明质酸具有相关性（P〈0.05）,HBVDNA、HBeAg与肝组织纤维化无相关性（P〉0.05）。结论大于40岁ALT正常的HBV慢性感染者有3/4肝组织纤维分期在2期以上,应关注其抗纤维化治疗。