中药复方861对慢性肝炎肝纤维化治疗作用的病理研究

目的和方法：已证明中药复方８６１能逆转实验性肝纤维化，可改善慢性肝炎患者临床症状，恢复肝功，使纤维化血清指标明显好转。为了从组织学改变进一步明确疗效，我们对临床确诊慢性乙型肝炎病例３４例，８６１治疗组２２例，对照药组１２例，治疗前及治疗６个月后分别肝穿。作石蜡切片。ＨＥ、网织纤维、狼红及免疫组化染色，按９５方案进行分级、分期，按改进的炎症活动度及纤维化计分方案评分，对比治疗前后组织学改变。结果：８６１治疗组２２例治疗后炎症及纤维化好转，对照药组１２例的炎症纤维化程度治疗后大部变化不明显。８６１组炎症活动度计分：由治疗前９１４—治疗后５４５％（Ｐ＜００１）纤维化程度计分：由治疗前８９８—治疗后５８（Ｐ＜００５）对照药组炎症活动度计分：由８６７—７５（Ｐ＞００５）纤维化程度计分：由４８８—５５４（Ｐ＞００５）结论：中药复方８６１治疗对慢性肝炎、肝硬化有明显减轻炎症，减少或逆转纤维化（包括早期肝硬化）的作用     

肝纤维化组织学量化诊断的实验研究

目的探讨肝纤维化组织学量化诊断方法。方法用二甲基亚硝氨（ＤＭＮ）诱导ＳＤ大鼠肝纤维化模型，常规肝组织切片，Ｍａｓｏｎ三色和苦味酸天狼红染色，苦味酸固绿－天狼红染色比色测定，图像定量处理和半定量计分分析及羟脯氨酸（Ｈｙｐ）含量测定。结果切片胶原比色测定、图像定量处理和半定量计分分析均与肝纤维化程度变化相一致，与肝组织Ｈｙｐ含量具有良好的相关性，ｒ分别为０９４、０８９和０８８，Ｐ均＜００１。结论切片胶原测定、图像定量处理和半定量计分可作为确定肝纤维化程度的量化指标     

慢性肝炎患者肝组织胶原半定量测定方法的研究

目的:探讨慢性肝炎患者肝组织胶原半定量测定方法对肝纤维化量化诊断的临床价值.方法:对40例慢性肝炎和6例正常对照组的肝脏穿刺组织标本,常规组织切片,HE、Masson三色和苦味酸-天狼红染色,苦味酸-天狼红染色与洗脱液进行比色测定,并观察胶原定量与炎症活动度(G)、炎症半定量计分(SSG)和纤维化分期(S)、纤维化半定量计分(SSS)的相关性.结果:急性肝炎组、慢性肝炎轻度、中度、重度组的G、SSG的计分均值和S、SSS的计分均值呈上升趋势;肝组织切片胶原半定量检测结果,正常对照组为(42.15±1.87)μg/mg、急性肝炎组为(49.04±11.89)μg/mg、慢性肝炎轻度组为(56.24±9.16)μg/mg、慢性肝炎中度组为(87.09±21.81)μg/mg、慢性肝炎重度组为(121.69±10.03)μg/mg,从正常对照组到慢性肝炎重度组胶原半定量也呈上升趋势;且切片胶原含量与其他指标存在较好的相关性,与G、SSG、S、SSS的r分别是0.91、0.89、0.97、0.89,其P均＜0.01.结论:肝脏组织切片胶原测定方法可客观反映肝脏纤维化的程度,而且是一个简单而且敏感的量化诊断指标.     

复方中药对肝纤维化治疗前后的血清学评价

目的通过对肝纤维化复方中药治疗的前后对比,结合肝病理组织学改变,进一步了解血清纤维化指标的诊断价值。方法对临床确诊为慢性乙肝及早期肝硬化的３４例患者,服用复方中药制剂半年,治疗前后各肝穿一次及采血４次,血清检测透明质酸（ＨＡ）,Ⅲ型前胶原（ＰＣⅢ）Ⅳ型胶原（ＣＩＶ）及层粘素（ＬＮ）。ＨＡ、ＰＣⅢ及ＬＮ用放免法,ＣＩＶ用酶免法。结果治疗前后对比,血清纤维化指标中,ＨＡ、ＰＣⅢ及ＩＮ变化非常显著（Ｐ＜０００１）;ＣＩＶ变化不明显（Ｐ＞００５）;血清纤维化四项指标与病理炎症及纤维化程度关系密切。与炎症计分的相关系数为：ＰＣⅢ：（０５２８５）、ＨＡ（０３８７７）、ＣＩＶ（０３４６４）和ＬＮ（０３３４１）;与纤维化计分的相关系数为：ＨＡ（０６２０３）、ＬＮ（０４２８９）、ＰＣⅢ（０４０９８）和ＣＩＶ（０３９７７）。结论血清纤维化指标为较好反映肝纤维化的指标,并随治疗有效而下降,其中ＨＡ对肝纤维化及早期肝硬化的诊断价值较大,ＰＣⅢ更倾向于反映活动性肝纤维化。     

慢性乙型肝炎临床与病理分级,分期的对比分析

目的评价１９９５年《病毒性肝炎防治方案（试行）》有关临床分度与病理分级、分期的一致性。方法对２６６例慢性乙型肝炎患者的临床表现、血清生化指标和临床分度的结果与病理分级、分期进行对比分析。结果临床症状的轻重和某些异常体征与病理分级显著相关（χ２分别为５２１５和２７８２，Ｐ＜０．０５）；血清总胆红素、白蛋白、白蛋白／球蛋白比值和凝血酶原活动度等的异常程度对判断轻度和重度慢性肝炎有较大的参考价值，而血清丙氨酸转氨酶和γ球蛋白水平与病理诊断并不符合；所有血生化指标的分度标准对病理重度慢性肝炎的漏诊率较高。慢性肝炎肝组织的炎症活动程度与纤维化程度显著相关（χ２＝３６２３７，Ｐ＜０．００１），而与ＨＢｅＡｇ阳性与否无明显关系（χ２＝６６５，Ｐ＞０．０５）。结论对１９９５年《病毒性肝炎防治方案（试行）》中的临床分度的标准应作适当的调整     

慢性乙型肝炎肝纤维化分期与血清肝纤维化标志物的相关性分析

目的 探讨血清透明质酸、Ⅲ型前胶原、层粘蛋白、Ⅳ型胶原等血清肝纤维化标志物与慢性肝炎肝组织炎症活动度及纤维化程度的相关性。方法 278例慢性肝炎患者经肝脏活栓后常规病理检查,肝活检前同时采血检测血清透明质酸、Ⅲ型前胶原、层粘蛋白、Ⅳ型胶原,结果应用x^2检验及t检验进行统计学处理。结果 肝组织纤维化程度与炎症活动度呈正相关关系,透明质酸可反映中度以上慢性肝炎炎症活动度及纤维化程度,且呈正相关;肝脏存在纤维化时层粘蛋白水平升高,与纤维化程度正相关;Ⅲ型前胶原、Ⅳ型胶原水平升高与炎症活动度有关。结论 血清透明质酸、Ⅲ型前胶原、层粘蛋白、Ⅳ型胶原可不同程度反映肝纤维纤维化程度,可作为血清肝纤维化检测指标,透明质酸更可反映肝硬化发展趋势。     

复方861对肝炎肝纤维化疗效的病理组织学分析

目的：以肝穿病理组织学研究中药复方８６１对慢性乙型肝炎及早期肝硬化的疗效。方法：中药８６１治疗慢性乙型肝炎及肝炎肝硬化１２例，另设对照组１０例，治疗前及治疗半年后行肝穿病理组织学检查。结果：肝炎症计分由治疗前１８．２５±７．４下降至治疗后８．５±２．７（Ｐ值＜０．００１），纤维化计分由１０±９．９２下降至２．５８±２．０７（Ｐ值＜０．０１）。对照组治疗后则无改变。平滑肌α－ａｃｔｉｎ染色见治疗前肝组织炎症区域中有较多肌成纤维细胞，治疗后显著减少。治疗前后血清乙肝指标无明显变化。结论：中药复方８６１治疗慢性肝炎肝纤维化半年，能明显减轻肝纤维化程度。肝组织炎症亦同步减退。     

对慢性肝炎的分类、分级与分期的浅见

对慢性肝炎的分类、分级与分期的浅见巫协宁洛杉矶、墨西哥坎肯大会关于慢性肝炎的分类、分级与分期新方案，是以病原为基础命名慢性肝炎，以炎症坏死活动程度进行分级，以纤维化程度为分期标准，这一新方案确实比以往１９６８年制订的方案前进一大步。炎症、坏死的活动度...     

慢性肝炎临床与病理对照分析

为提高慢性肝炎临床诊断的正确性，按2000年“病毒性肝炎防治方案”对774例慢性肝炎患者临床表现、七项血液生化学指标ALT、AST、总胆红素(TSB)、白蛋白(ALB)、白蛋白／球蛋白比值(A／G)、γ—球蛋白(γ—G)、凝血酶原活动度(PTA)及门静脉内径(MPV)、脾静脉内径(SPV)、脾厚与病理对照分析。结果临床表现如乏力、腹胀、纳差、恶心、厌油、黄疸、鼻／牙龄出血、蜘蛛痣及血液指标ALT、TSB、PTA、ALB、A／G均能较好反映肝组织炎症活动程度，PTA、ALB、γ—GT、A／G能较好反映肝纤维化进程，脾厚是反映早期肝纤维化较敏感指标。     

血清生化指标对慢性肝炎病变程度的评价

目的:分析临床肝病常用血清生化指标与慢性肝炎病变程度的相关性.方法:检测慢性肝炎患者142例的丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、谷氨酰转肽酶(GGT)、白蛋白(ALB)、总胆红素(TBIL)和凝血酶原活动度(PTA),并将其结果与肝炎病变程度(病理分级和分期)对比分析.结果:ALT、AST、ALB和PTA在不同病理分级(炎症)之间均有显著性差异( F = 6.812,6.592,10.131,3.247,P<0.05或0.01); ALT、AST、ALP、GGT、ALB、TBIL和PTA在不同病理分期(纤维化)之间无显著性差异;TBIL、PTA和病理分级呈正相关,ALB和病理分级分期呈负相关.结论:常用血清生化指标ALT、AST、ALB、PTA能反映慢性肝炎的炎症程度,但不能反映慢性肝炎的纤维化程度.     

超声检查对慢性病毒性肝炎肝纤维化诊断价值的评估

目的 探索超声二维图像和多普勒血流显像对慢性病毒性肝炎患者中纤维化程度和早期肝硬化的诊断价值。方法 324例慢性病毒性肝炎患者根据肝穿刺活检组织学结果分为无肝纤维化(SO)到肝硬化(S4)五期。活检组织按炎症分级为G1～G4四级。比较各组间超声指标的差异。结果 在超声定性指标中，肝表面回声，肝实质光点形态和分布异常等指标都与肝纤维化分期和炎症分级有相关性。但这些定性指标对具体患者的诊断判断变异很大。在不同纤维化程度分组间，脾长径，脾门静脉内径在各组间差异有统计学意义。根据脾长径界限值12．1cm，诊断早期肝硬化的敏感度为60．0％，特异性为75．3％；脾静脉内径以8mm作为界限值，诊断早期肝硬化的敏感度为60．0％，特异性为78．1％；门静脉主干内径12mm，诊断早期肝硬化的敏感度76．7％，特异性44．6％。门静脉最大流速界限值为30．5cm／s时，诊断早期肝硬化的敏感度为78．6％，特异性为66．9％。结论 超声检查是诊断早期肝硬化的有效工具，是临床实用的方法，并适用于随访复查。     

Liver fibrosis in chronic viral hepatitis： An ultrasonographic study

AIM: To select valuable ultrasonographic predictors for the evaluation of hepatic inflammation and fibrosis degree in chronic hepatitis, and to study the value of ultrasonography in the evaluation of liver fibrosis and compensated liver cirrhosis in comparison with serology and histology. METHODS: Forty-four ultrasonographic variables were analyzed and screened using color Doppler ultrasound system in 225 patients with chronic viral hepatitis and compensated liver cirrhosis. The valuable ultrasonographic predictors were selected on the basis of a comparison with histopathological findings. The value of ultrasonography and serology in the evaluation of liver fibrosis degree and the diagnosis of compensated liver cirrhosis was also studied and compared. Meanwhile, the influencing factors on ultrasonographic diagnosis of compensated liver cirrhosis were also analyzed. RESULTS: By statistical analysis, the maximum velocity of portal vein and the degree of gall-bladder wall smoothness were selected as the valuable predictors for the inflammation grade (G), while liver surface, hepatic parenchymal echo pattern, and the wall thickness of gall-bladder were selected as the valuable predictors for the fibrosis stage (S). Three S-related independent ultrasonographyic predictors and three routine serum fibrosis markers (HA, HPCIII and CIV) were used to discriminate variables for the comparison of ultrasonography with serology. The diagnostic accuracy of ultrasonography in moderate fibrosis was higher than that of serology (P<0.01), while there were no significant differences in the general diagnostic accuracy of fibrosis as well as between mild and severe fibrosis (P<0.05). There were no significant differences between ultrasonography and serology in the diagnosis of compensated liver cirrhosis. However, the diagnostic accuracy of ultrasonography was higher in inactive liver cirrhosis and lower in active cirrhosis than that of serology (both P<0.05). False positive and false negative results where found when the diagnosis of compensated liver cirrhosis was made by ultrasonography. CONCLUSION: There are different ultrasonographic predictors for the evaluation of hepatic inflammation grade and fibrosis stage of chronic hepatitis. Both ultrasonography and serology have their own advantages and disadvantages in the evaluation of liver fibrosis and compensated liver cirrhosis. Combined application of the two methods is hopeful to improve the diagnostic accuracy.     

Application of a numerical scoring system for assessment of histological outcome in patients with chronic posttransfusion non-A, non-B hepatitis with or without antibodies to hepatitis C

A numerical scoring system was applied and compared to the conventional histological classification to assess the histological status of liver specimens from 37 patients with chronic posttransfusion non-A, non-B hepatitis followed for 7 to 105 months (mean 35 months). Four histological categories of alterations were assessed and scored: piecemeal necrosis (PMN), fibrosis and cirrhosis, lobular necrosis and portal inflammation. Sequential liver biopsies were obtained from 19 patients. PMN was generally mild but still predictive of progressing fibrosis. Thus, in none of the biopsies from four patients with initial PMN score 0 was there any increase in the fibrosis score in the follow-up biopsy, while in 10/15 (67%) patients with an initial PMN score of greater than or equal to 1 the fibrosis score increased with time (p = 0.033). Lobular necrosis and portal inflammation were not predictive of progressing fibrosis. Judging from the scoring method, 22% of all the 37 patients displayed cirrhosis and 27% bridging fibrosis in the latest liver biopsy performed. Patients with antibodies to hepatitis C did not differ in histological status or outcome from those without antibodies to hepatitis C. It is concluded that the scoring system can be used to monitor the histological long-term follow-up in patients with chronic posttransfusion non-A, non-B hepatitis, and offers a means of predicting the histological outcome.     

Histological outcome of chronic hepatitis B in children treated with interferon alpha

AIM: To evaluate the effect of interferon alpha (IFN-α) treatment on the liver histology in children with chronic hepatitis B and to evaluate the usefulness of various histological scoring systems of liver histology in this group of patients. METHODS: Fibrosis stage and inflammation grade were assessed according to Batts and Ludwig, Ishak et al., and METAVIR (only fibrosis stage) before and 12 mo after IFN-α treatment termination in 93 children aged 2-16 years with chronic hepatitis B. RESULTS: None of the three numerical scoring systems for liver fibrosis showed statistically significant differences in liver fibrosis, while evolution of inflammatory activity revealed statistically significant improvement in the whole group of children with chronic hepatitis B treated with IFN-α and in responders. Significantly positive correlations were found between fibrosis stage and inflammation grade in the respective scoring systems. CONCLUSION: Treatment with IFN-α did not improve histological fibrosis but decreased inflammatory activity in children with chronic hepatitis B. The three semiquantitative scoring systems seem to be comparable in the estimation of the inflammation grade and fibrosis stage in this group of children.     

Progression of fibrosis in chronic hepatitis C

BACKGROUND & AIMS: Fibrosis is the hallmark of hepatic cirrhosis, worsening of which is probably the best surrogate marker for progression of chronic liver disease. We evaluated a large cohort of patients with chronic hepatitis C (CHC) using liver histology to assess the rate and predictors of progression of fibrosis. METHODS: The cohort consisted of 123 patients with CHC who underwent 2 liver biopsies 4-212 months (mean, 44 months) apart without intervening treatment. Liver histology was graded using the histology activity index (score, 0-18) and fibrosis staged using a scoring system of 0 (no fibrosis) to 6 (cirrhosis). RESULTS: Among 123 patients, 48 (39%) showed progression in fibrosis scores, 46 (37%) showed no change, and 29 (24%) showed improvement. Of those with worsening fibrosis, 75% had a 1-point increase and 25% a 2-point or greater increase in scores, and 9% showed progression to cirrhosis. The overall rate of progression was 0.12 fibrosis units per year, a rate that predicts progression to cirrhosis in 50 years if progression was linear. The rate of fibrosis progression was variable, and it was higher among older patients, those with higher serum alanine and aspartate aminotransferase levels, and those with the most extensive periportal necrosis on initial liver biopsy. CONCLUSIONS: The best predictors of fibrosis progression in CHC are the extent of serum aminotransferase elevations and the degree of hepatocellular necrosis and inflammation on liver biopsy. These findings support the recommendation that patients with normal aminotransferase levels and mild liver histology can safely defer treatment.     

Advances in digital quantification technique enhance discrimination between mild and advanced liver fibrosis in chronic hepatitis C.

BACKGROUND AND AIMS: The necessity of liver biopsy for staging fibrosis and its quantification in patients with chronic hepatitis C (CHC) remains controversial. Semiquantitative scoring of fibrosis is considered more subjective and less objective than digital quantification by image analysis. However, measurement of fibrosis using digital image analysis is thought to be less reliable in determining early stage fibrosis as compared with advanced fibrosis or cirrhosis. Our aims were to correlate all Ishak stages of fibrosis (0-6) with fibrosis percentage (%) using computerized digital image analysis, and thereby seek to improve discrimination between varying levels of liver fibrosis. METHODS: Fibrosis % data were obtained by image analysis on 164 trichrome-stained liver biopsies from untreated patients with CHC, representing all Ishak stages of fibrosis. RESULTS: Digital analysis of fibrosis % was highly correlated with Ishak scores of fibrosis (Kendall's tau-beta=0.86, P<0.001). Receiver-operator characteristic curves showed reliable discriminative capability of our digital image measurement of fibrosis when compared with semiquantitative assessments of fibrosis. Excellent interobserver reliability was found. CONCLUSIONS: Recent advances in digital quantification of fibrosis have resulted in improved discrimination between the varying stages of liver fibrosis, including mild fibrosis. This method is reproducible, can detect early as well as advanced fibrosis or cirrhosis, may prove to be the best assessment of mild fibrosis, and may be more precise than semiquantitative estimation of changes for monitoring fibrosis progression or regression during clinical therapeutic trials.     

Interobserver study of liver histopathology using the Ishak score in patients with chronic hepatitis C virus infection.

AIMS/BACKGROUND: Assessing the histopathological degree of liver damage is essential to the routine care of patients with chronic hepatitis C virus (HCV) infection. Several scoring systems have been proposed in attempts to standardize the histological assessment. One scoring system has been proposed by Ishak et al. Although widely endorsed, its interobserver reliability has not been evaluated. METHODS: 95 liver biopsies from patients with chronic HCV infection were scored by three independent observers. Interface hepatitis, confluent necrosis, focal necrosis, portal inflammation, and fibrosis were assessed. RESULTS: Confluent necrosis, which is more common in acute hepatitis, was not seen in any biopsy. For each of the remaining variables of inflammation (periportal hepatitis, focal necrosis, and portal inflammation) we found agreement in 95-96% for all three observers. Kappa scores ranged from 0.11 to 0.41 and weighted kappa scores from 0.18 to 0.53. For staging we noted 84% agreement, kappa scores of 0.26-0.47, and weighted kappa scores of 0.57-0.69. CONCLUSION: The Ishak system is associated with good interobserver reliability if a deviance of one categorical level in each variable of the system is accepted as agreement. Compared to the Knodell system it provides more detailed information but is less reliable regarding fibrosis.     

血清半胱氨酸蛋白酶裂解细胞角蛋白18预测慢性乙型肝炎转归

目的探讨血清半胱氨酸蛋白酶裂解细胞角蛋白18(CK18)对慢性乙型肝炎肝病严重程度的预测价值。方法选取2017年3月至2018年3月府谷县人民医院收治的122例慢性乙型肝炎患者。按照METAVIR评分系统肝纤维化分期分为轻度肝纤维化组(n=69)、重度肝纤维化组(n=53);根据METAVIR评分系统肝脏炎症活动度分级分为轻度肝脏炎症组(n=76)、重度肝脏炎症组(n=46)。通过酶联免疫吸附试验测定血清CK18水平。结果轻度肝纤维化组血清CK18[167.86(89.54~274.65)U/L]水平显著低于重度肝纤维化组[231.98(132.09~564.38)U/L],差异有统计学意义(Z=12.765,P=0.002)。轻度肝脏炎症组血清CK18水平[138.23(165.34~677.46)U/L)]显著低于重度肝脏炎症组[337.43(82.87~234.15)U/L],差异有统计学意义(Z=15.917,P=0.001)。血清CK18预测慢性乙型肝炎患者严重肝脏炎症程度的预测效能更佳。结论血清CK18水平可用于预测慢性乙型肝炎重度肝脏组织炎症。     

Older age at the time of liver biopsy is the important risk factor for advanced fibrosis in patients with chronic hepatitis C

BACKGROUND/AIMS: Progression of chronic hepatitis C depends on the host and viral characteristics, duration of infection, co-infection with other viruses, etc. In this study, some of demographic, epidemiological and viral data as risk factors for a degree of liver fibrosis were evaluated. METHODOLOGY: A total of 144 patients was investigated (89 males, ages from 16-65 years) classified into two groups, with fibrosis scores 0-3 and 4-6, using the Ishak scoring system. Significant variables were entered into univariate logistic regression model and further multivariate analysis was performed. RESULTS: There were 64% and 36% of patients with fibrosis scores 0-3 and 4-6, respectively. Gender, moderate to heavy alcohol abuse and high viral RNA were equally distributed between both groups. In univariate analysis, the age older than 40, history of intravenous drug abuse, and the genotype 1b were independently associated with different fibrosis scores. Multivariate regression analysis revealed ages older than 40 as the positive (p < 0.001), and younger than 40 as the negative predictive factors for fibrosis scores 4-6 and 0-3 (p < 0.001), respectively. CONCLUSIONS: Our results indicate the age over 40 at the time of liver biopsy as the important risk factor for advanced liver disease in chronic hepatitis C according to fibrosis scores.