e抗原阴性慢性乙型肝炎合并肝脂肪变的预测指标及炎性反应和纤维化诊断

目的 研究HBeAg阴性慢性乙型肝炎(CHB)合并肝脂肪变患者的临床和病理关系,探讨预测此类患者肝组织炎性反应和纤维化的指标.方法 分别收集经临床与病理检查确诊的HBeAg阴性CHB合并和不合并肝脂肪变患者56例和60例,分别研究并比较其空腹血糖(FBG)、空腹血胰岛素(FINS)、三酰甘油(TG)、胆固醇(TC)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、谷氨酰转肽酶(GGT)、碱性磷酸酶(ALP)、白蛋白(Alb)、球蛋白(Glb)、胰岛素抵抗指数(HOMA-IR)、HBV DNA水平、体重指数(BMI),并就上述指标与肝组织脂肪变、炎性反应和纤维化的关系进行统计学分析.结果 与HBeAg阴性CHB不合并肝脂肪变者相比,合并肝脂肪变患者BMI、FBG、FINS、TG、TC、GGT、ALP、Glb和HOMA-IR明显增高(P值均<0.05),HBV DNA、AST、ALT、Alb明显降低(P值均<0.05),此外炎性反应程度和纤维化程度亦明显增强.可预测HBeAg阴性CHB者是否存在肝脂肪变的参数有BMI,FBG、FINS、TG、TC、GGT和HOMA-IR(P值均<0.05).可预测HBeAg阴性CHB合并肝脂肪变者肝组织是否存在炎性反应的参数有ALT、AST、Glb和HBVDNA(P值均<0.05),可预测其是否存在肝组织纤维化的参数有ALT,AST、Alb、Glb和HBV DNA(P值均<0.05).结论 肝脂肪变在HBeAg阴性CHB患者中较常见,其肝组织脂肪变与BMI、FBG、FINS、TG、TC、GGT和HOMA-IR有关.此类患者除肝脂肪变明显增加外,肝组织炎性反应和纤维化程度亦明显加重.     

e抗原阴性慢性乙型肝炎合并肝脂肪变的预测指标及炎性反应和纤维化诊断

目的 研究HBeAg阴性慢性乙型肝炎(CHB)合并肝脂肪变患者的临床和病理关系,探讨预测此类患者肝组织炎性反应和纤维化的指标.方法 分别收集经临床与病理检查确诊的HBeAg阴性CHB合并和不合并肝脂肪变患者56例和60例,分别研究并比较其空腹血糖(FBG)、空腹血胰岛素(FINS)、三酰甘油(TG)、胆固醇(TC)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、谷氨酰转肽酶(GGT)、碱性磷酸酶(ALP)、白蛋白(Alb)、球蛋白(Glb)、胰岛素抵抗指数(HOMA-IR)、HBV DNA水平、体重指数(BMI),并就上述指标与肝组织脂肪变、炎性反应和纤维化的关系进行统计学分析.结果 与HBeAg阴性CHB不合并肝脂肪变者相比,合并肝脂肪变患者BMI、FBG、FINS、TG、TC、GGT、ALP、Glb和HOMA-IR明显增高(P值均<0.05),HBV DNA、AST、ALT、Alb明显降低(P值均<0.05),此外炎性反应程度和纤维化程度亦明显增强.可预测HBeAg阴性CHB者是否存在肝脂肪变的参数有BMI,FBG、FINS、TG、TC、GGT和HOMA-IR(P值均<0.05).可预测HBeAg阴性CHB合并肝脂肪变者肝组织是否存在炎性反应的参数有ALT、AST、Glb和HBVDNA(P值均<0.05),可预测其是否存在肝组织纤维化的参数有ALT,AST、Alb、Glb和HBV DNA(P值均<0.05).结论 肝脂肪变在HBeAg阴性CHB患者中较常见,其肝组织脂肪变与BMI、FBG、FINS、TG、TC、GGT和HOMA-IR有关.此类患者除肝脂肪变明显增加外,肝组织炎性反应和纤维化程度亦明显加重.     

Noninvasive serum markers in the diagnosis of structural liver damage in chronic hepatitis C virus infection.

AIM: Several noninvasive markers are being used to assess the structural liver damage in patients with chronic hepatitis C (CHC). We evaluated the capacity of serum hyaluronic acid (HA), aspartate aminotransferase (AST)/ALT ratio, the AST to platelet ratio index (APRI) and gamma-glutamyltransferase (GGT) levels to predict the intensity of hepatic fibrosis in patients with CHC. PATIENTS AND METHODS: In a total of 206 hepatitis C virus RNA-positive biopsied patients, AST, ALT, GGT levels, platelet count and serum HA concentration were determined. The APRI was calculated as the ratio of AST to platelets. RESULTS: HA levels were best correlated with disease stage (r=-0.694; P<0.001). In the diagnosis of significant fibrosis (F2-F4), HA levels [AUC=0.879, 95% CI (0.832-0.927)] and APRI [AUC=0.824 (0.772-0.903)] were the markers with the best diagnostic accuracy. These parameters also best identified the presence of cirrhosis (F4), with an AUC of 0.908 (0.868-0.949) for HA and of 0.837 (0.772-0.903) for APRI. CONCLUSION: Serum HA was the parameter that alone presented the best diagnostic accuracy in the assessment of hepatic fibrosis in CHC. The APRI showed a better diagnostic sensitivity than GGT levels or the AST/ALT ratio. Its simple determination and low cost make this index a valid alternative for the noninvasive staging of CHC.     

Significant variation of traditional markers of liver injury after a half-marathon run

Background

While the promotion of health-related fitness is thereby widespread, less focus is currently being given on the biological influence that physical activity might exert on results of laboratory testing. As such, this study was undertaken to assess the kinetics of liver injury markers following physical exercise.

Design and methods

Total and direct bilirubin as well as the activity of biochemical markers of liver injury including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT) and creatine kinase (CK), were measured before and after a half-marathon.

Results

Significant increases occurred for GGT, AST, LDH, CK, total and direct bilirubin immediately after the run. AST, LDH, CK, total and direct bilirubin were still increased 24 h thereafter, whereas GGT decreased after 6 h. None of the athletes exceed the upper reference limit for ALT, ALP and GGT, whereas significant variations were instead observed for LDH, AST, CK, total and direct bilirubin.

Conclusions

Taken together, the results of our prospective investigation clearly attest that an acute bulk of aerobic physical exercise, such as a half-marathon, might produce significant changes in the activity of traditional biomarkers of liver injury, which should be carefully considered when investigating physically active individuals undergoing laboratory testing.     

慢性乙型肝炎病毒感染合并非酒精性脂肪性肝病动物模型的建立与鉴定

目的 采用高脂饮食喂饲HBV转基因小鼠,建立慢性HBV感染合并非酒精性脂肪性肝病(NAFLD)的动物模型。 方法 将携带HBV全基因组的小鼠随机分为雄性对照组、雄性模型组、雌性对照组、雌性模型组。各模型组给予高脂饮食(含胆固醇2％、猪油l0％、基础饲料88％),对照组则喂饲基础饲料。分批于第8、16、24周末处死小鼠,检测体质学指标、肝肾功能、糖脂代谢等NAFLD相关指标;血清HBV分型、HBeAg、HBV DNA,以及肝组织HBsAg免疫组织化学染色等病毒学指标;并通过HE、Mason及油红O染色评价肝脏组织的病理学改变。组间均数的比较采用t检验,P＜0.05为差异有统计学意义。结果 与对照组相比,不同造模时间的雌性和雄性模型组小鼠体质量、肝脏质量、肝指数均明显升高;ALT、AST、碱性磷酸酶、γ-谷氨酰转移酶、总胆红素、胆汁酸等肝功能指标受损;总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和空腹血糖等糖脂代谢指标也有不同程度升高。然而,各组间血清HBV DNA、HBeAg水平和肝细胞HBsAg阳性率无明显差异。组织病理学检查结果提示,造模第8周时,雌、雄模型组小鼠均可见不同程度的肝细胞脂肪变,伴小叶内散在的点状坏死及炎症细胞浸润;第24周时肝脏脂肪变及炎症虽未明显加重,但有窦周纤维化和中央静脉周围纤维化。结论 成功建立慢性HBV感染合并NAFLD动物模型,为进一步研究慢性乙型肝炎合并NAFLD发病机制、药物筛选及疗效评价等提供了可靠的实验平台。     

Noninvasive predictors for liver fibrosis in patients with nonalcoholic steatohepatitis

AIM: To evaluate certain anthropometric, clinical and laboratory features indicating liver fibrosis in nonalcoholic steatohepatitis and to establish the noninvasive markers for liver fibrosis.METHODS: Eighty-one patients (40 male, 41 female) who were diagnosed with fatty liver by ultrasonographic examination and fulfilled the inclusion criteria participated in the study. Anamnesis, anthropometric, clinical and laboratory features of all cases were recorded and then liver biopsy was performed after obtaining patient consent. Steatosis, necroinflammation and liver fibrosis were examined according to age ≥ 45, gender, body mass index, central obesity, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 1, γ-glutamyltransferase (GGT)/ALT > 1, platelet count, insulin, c-peptide levels and the presence of hypertension, diabetes, hypertriglyceridemia and insulin resistance.RESULTS: Eighty-one patients with non-alcoholic steatohepatitis (NASH) enrolled in the study. 69 of 81 patients were diagnosed with NASH, 11 were diagnosed with simple fatty liver and 1 was diagnosed with cirrhosis. AST/ALT > 1, GGT/ALT > 11, high serum ferritin and fasting insulin levels, the presence of diabetes, hypertension, hypertriglyceridemia and insulin resistance seemed to enhance the severity of steatosis, necroinflammation and fibrosis but these results were not statistically significant.CONCLUSION: Liver steatosis and fibrosis can occur in individuals with normal weight. There was no significant concordance between severity of liver histology and the presence of predictors for liver fibrosis including metabolic risk factors.     

Relationships among viral diagnostic markers and markers of liver function in acute hepatitis E

Background  Diagnosis of acute hepatitis E has been based in many clinics predominantly on detection of anti-HEV (hepatitis E virus) antibody. Now, new assays have been developed to detect other HEV markers. Our aim was to investigate the relationships among HEV diagnostic markers and liver function markers in acute hepatitis E. Methods  Seventy serum samples were collected from non-A, non-B, non-C acute hepatitis patients and tested for HEV markers (HEV antigen and RNA and anti-HEV IgM) and markers of liver function [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total iron binding capacity (TBA), γ-glutamyl transferase (GGT), total bilirubin (TBIL), and direct bilirubin (DBIL)]. Partial open reading frame (ORF) 2 sequences from HEV RNA-positive samples were cloned and analyzed. Results  The concordances between HEV antigen and HEV RNA and between HEV antigen and anti-HEV IgM were 77.1% and 72.9%, respectively, with significant correlations, while that between HEV RNA and anti-HEV IgM was 61.4% with no significant correlation. Eleven of 25 samples negative for anti-HEV IgM were positive for HEV antigen. The ALT, AST, ALP, TBA, GGT, TBIL, and DBIL levels did not differ significantly between the anti-HEV IgM-positive and -negative groups. However, the ALT, AST, ALP, TBA, and GGT levels were significantly higher in the HEV antigen-positive group than in the HEV antigennegative group. All of the HEV isolates cloned belonged to genotype 4. Conclusions  HEV antigen was highly correlated with HEV RNA and elevated ALT, AST, ALP, TBA, and GGT levels. Testing for HEV antigen in combination with anti-HEV IgM is useful for the diagnosis of HEV infection.     

Non-invasive models for predicting histology in patients with chronic hepatitis B.

Abstract: Background and aim: In contrast to chronic hepatitis C (CHC), few studies had been performed in assessing non‐invasive models for predicting significant fibrosis or cirrhosis in chronic hepatitis B (CHB) patients. We aimed to evaluate non‐invasive markers for diagnosing significant fibrosis/cirrhosis in patients with CHB, and to evaluate accuracy of models from CHC in CHB patients. Patients and methods: Liver biopsies from consecutive treatment‐naïve CHB patients were evaluated histologically by a pathologist blindly, using the Ishak score. Patients were divided randomly into a training (65%) and a validation sets (35%). Markers of fibrosis were evaluated by univariate followed by multivariate analysis in the training set. Area under receiver operating characteristics curve (AUROC) was assessed and validated in the training set. AUROC of aspartate aminotransferase (AST), AST/alanine aminotransferase (ALT) ratio, and AST‐platelets ratio index (APRI) (derived from studies from CHC) in diagnosing significant fibrosis/cirrhosis were also assessed. Results: Two‐hundred and eighteen CHB patients were evaluated: 83% male, 86% Chinese, 47% having significant fibrosis, 19% having cirrhosis. Platelets were the only factor significantly associated with significant fibrosis and cirrhosis at multivariate analysis but the AUROC was only modest at 0.63 and 0.73, respectively. Models derived from studies from CHC were even less accurate. Conclusion: Models with non‐invasive markers in predicting histology from CHC patients were unsuitable for CHB patients. No variables consisting of simple and readily available markers were able to predict cirrhosis accurately in patients with CHB.     

Characteristics of peripheral blood Gamma-glutamyl transferase in different liver diseases

Gamma-glutamyl transferase (GGT) is a marker of oxidative stress and cholestasis. Because of its low specificity, clinicians usually ignore its diagnostic value.To compare and analyze the clinical features of GGT in primary biliary cholangitis (PBC), drug-induced liver injury (DILI), alcoholic liver disease (ALD), and non-alcoholic fatty liver disease (NAFLD) from the perspective of different causes instead of the severity of the disease.We observed the distribution characteristics and the rate of abnormality of GGT in the above 4 diseases. The relationship between GGT and alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total serum bilirubin, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol was analyzed using Spearman correlation.The highest level of GGT was up to 1000.00 to 2000.00 U/L in PBC and DILI, and the highest level of GGT was more than 2000.00 U/L in ALD, yet the difference was not statistically significant (P > .05). The highest level of GGT was only about 200.00 U/L in NAFLD and was the lowest in 4 liver diseases. Also, GGT was positively correlated with ALP, TC in PBC and DILI. Also, in ALD, GGT was positively correlated with ALT, AST, ALP, TG, and TC. In NAFLD, GGT was positively correlated with ALT, AST, and TG.The abnormal GGT in PBC and cholestasis DILI was associated with cholestasis; in ALD, it was associated with oxidative stress and cholestasis, and in NAFLD, it was associated with oxidative stress. GGT levels had different characteristics in different liver diseases, which were closely related to the pathogenesis of liver diseases.     

慢性乙型肝炎患者ALT、HBV DNA及血清肝纤维化标志物与肝纤维化程度的关系

目的探讨ALT、HBV DNA以及血清纤维化标志物透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原肽(PⅢP)、Ⅳ型胶原(CⅣ)与慢性乙型肝炎肝纤维化程度的关系。方法检测281例慢性乙型肝炎患者血清中ALT、HBV DNA和纤维化标志物(HA、LN、PⅢP及CⅣ)的水平,并行肝活检检测肝组织病理纤维化分期。结果 HBeAg阴性慢性乙型肝炎患者HBV DNA水平较低、纤维化程度较高。HBeAg阳性患者纤维化程度与HBV DNA呈负相关(r=-0.251,P<0.001),S≥3组水平最低。慢性乙型肝炎患者纤维化程度与PⅢP水平呈正相关,其水平随着纤维化程度的加重而明显升高。结论 PⅢP水平可能作为评估慢性乙型肝炎患者肝纤维化程度的血清学指标,血清HBV DNA与肝脏纤维化严重程度的关系仍需进一步深入探讨。     

A novel liver stiffness measurement‐based prediction model for cirrhosis in hepatitis B patients

Backgrounds/aims: While liver stiffness measurement (LSM) predicts histological cirrhosis accurately, complementary methods are needed for better performance. Furthermore, alanine aminotransferase (ALT) influences LSM, making it necessary to modify its use in patients with high ALT levels. We developed a new LSM‐based prediction model for cirrhosis and estimated the thresholds for different ALT levels. Methods: From 2008 to 2009, we prospectively enrolled 330 consecutive patients who were diagnosed with chronic hepatitis B (CHB) and underwent a liver biopsy and LSM on the same day. For detection of cirrhosis, we performed univariate and multivariate analyses, using the χ²‐test/t‐test and logistic regression respectively. Thereafter, a prediction model was derived from multivariate predictors. Results: In multivariate analyses of patients with and without cirrhosis, we found significant differences in the LSM, spleen diameter and platelet count. Then, we developed an LSM–spleen diameter to platelet ratio index (LSPI): (LSM × spleen diameter/platelet count) × 100. The area under the receiver operating curve was 0.956, significantly higher than LSM alone (0.919, P=0.032). We suggested different thresholds in patients with ALT≤upper limit of normal (ULN) (normal‐ALT group, 164 patients) and ALT>ULN (high‐ALT group, 166 patients). In the normal‐ALT group, LSPI thresholds of 38 and 62 provided 95.7% negative predictive value (NPV) and a 95.5% PPV (positive predictive value), while in the high‐ALT group, thresholds of 42 and 94 yielded 95.1% NPV and 96.4% PPV respectively. Therefore, liver biopsy could be avoided in 76.7% of the subjects. Conclusions: LSPI is a useful, non‐invasive tool that can replace liver biopsy in the assessment of liver fibrosis in the majority of CHB patients.     

非酒精性脂肪性肝病临床和病理学研究

目的研究非酒精性脂肪性肝病(NAFLD)的临床与病理特征。方法分析41例NAFLD患者的肝组织脂肪变程度、炎症分级和纤维化分期,并研究其与体重指数(BMI)、血清生物化学和B超检查结果的关系。结果41 例NAFLD患者中,肝组织脂肪变分级:Ⅰ级21例(51．2％),Ⅱ级15例(36．6％),Ⅲ级5例(12．2％);肝组织炎症活动度分级:G0级2例(4．9％),G1级25例(61．0％),G2级10例(24．4％),G3级3例(7．3％),G4级1例(2．4％); 肝组织纤维化分期:S0期20例(48．8％),S1期14例(34．2％),S2期4例(9．8％),S3期2例(4．9％),S4期1例(2．4％)。肝脂肪变程度与肝炎症分级(r=-0．131 3,P=0．413)和肝纤维化分期(r=-0．179 2,P=0．262 3)均无显著的相关性。肝细胞脂肪变程度与BMI(r=0．669,P<0．01)和B超检测到的脂肪肝程度(r=0．366,P<0．01) 呈正相关,炎症活动度与丙氨酸氨基转移酶(ALT)(r=0．669,P=0．019)、天冬氨酸氨基转移酶(AST)(r= 0．438,P=0．005)和B超检测到的脂肪肝程度(r=0．562,P<0．001)呈正相关,而与血小板数呈负相关(r= -0．344,P=0．040);肝纤维化分期与ALT(r=0．449,P=0．003)、AST(r=0．477,P=0．002)、γ-谷氨酰转肽酶(r=0．373,P=0．025)和碱性磷酸酶(r=0．346,P=0．039)呈正相关,而与甘油三酯(r=-0．324, P=0．042)和血小板数(r=-0．375,P=0．024)呈负相关。结论肝脂肪变程度与炎症分级和肝纤维化分期均无显著的相关性,BMI、AST、ALT、血小板和B超检测到的脂肪肝程度等与肝组织病理学有关,肝活组织检查有助于明确诊断。     

血清纤维化指标的影响因素分析

目的 探讨慢性乙型肝炎恢复期患者血清纤维化4项指标[血清透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(CIV)和层黏连蛋白(LN)]的影响因素及意义。方法用放射免疫法检测141例慢性乙型肝炎患者血清HA、PCⅢ、LN、CⅣ,并将他们分为不一致组和一致组。肝活检标本行常规病理检查,自动生物化学分析仪检测肝功能,B超检查肝门静脉主干内径、脾门部脾静脉内径及腋中线处脾脏厚度。结果血清纤维化指标与肝纤维化程度不一致患者16例(14.16％),血清纤维化指标不一致的产生与肝纤维化程度分期无关,与肝脏炎症活动度有关(X2=12.07,P<0.05)。不一致组患者血清丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、γ-谷氨酰基转移酶、球蛋白水平明显下降,分别从89.28±64.25、66.10±42.30、86.26±70.36、32.13±5.18下降至49.31±26.75(t=2.45,P<0.05)、40.83±22.40(t=2.33,P<0.05)、48.99±29.96(t=2.08,P<0.05)、28.05±3.47(t=3.03,P<0.01)。白蛋白和白蛋白/球蛋白比值则明显升高,分别从42.34±4.81、1.35±0.28上升至46.19±3.61(t=3.06,P<0.01)、1.63±0.26(t=3.70,P<0.01)。血清碱性磷酸酶、总胆红素、总蛋白无明显改变,肝门静脉主干内径、脾门部脾静脉内径及腋中线处脾脏厚度也无明显改变。结论 在评价某些患者血清纤维指     

Ceruloplasmin,a reliable marker of fibrosis in chronic hepatitis B virus patients with normal or minimally raised alanine aminotransferase

AIM To develop a non-invasive model to evaluate significant fibrosis and cirrhosis by investigating the association between serum ceruloplasmin(CP) levels and liver fibrosis in chronic hepatitis B(CHB) patients with normal or minimally raised alanine aminotransferase(ALT).METHODS Serum samples and liver biopsy were obtained from 193 CHB patients with minimally raised or normal ALT who were randomly divided into a training group(n = 97) and a validation group(n = 96). Liver histology was evaluated by the METAVIR scoring system. Receiver operator characteristic curves were applied to the diagnostic value of CP for measuring liver fibrosis in CHB patients. Spearman rank correlation analyzed the relationship between CP and liver fibrosis. A noninvasive model was set up through multivariate logistic regression analysis.RESULTS Serum CP levels individualized various fibrosis stages via area under the curve(AUC) values. Multivariate analysis revealed that CP levels were significantlyrelated to liver cirrhosis. Combining CP with serum GGT levels, a CG model was set up to predict significant fibrosis and liver cirrhosis in CHB patients with normal or minimally raised ALT. The AUC, sensitivity, specificity, positive predictive value, and negative predictive value were 0.84, 83.1%, 78.6%, 39.6%, and 96.5% to predict liver cirrhosis, and 0.789, 80.26%, 68.38%, 62.25%, and 84.21% to predict significant fibrosis. This model expressed a higher AUC than FIB-4(age, ALT, aspartate aminotransferase, platelets) and GP(globulin, platelets) models to predict significant fibrosis(P = 0.019 and 0.022 respectively) and revealed a dramatically greater AUC than FIB-4(P = 0.033) to predict liver cirrhosis.CONCLUSION The present study showed that CP was independently and negatively associated with liver fibrosis. Furthermore, we developed a novel promising model(CG), based on routine serum markers, for predicting liver fibrosis in CHB patients with normal or minimally raised ALT.     

Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B

Summary.  The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty-one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1–4), bridging fibrosis (F0–2 vs F3–4) and liver cirrhosis (F0–3 vs F4) was 0.80 (95% CI: 0.68–0.92), 0.87 (95% CI: 0.82–0.93) and 0.93 (95% CI: 0.89–0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.     

A novel index using routine clinical parameters for predicting significant liver inflammation in chronic hepatitis B

Identifying the degree of liver inflammation is critical for therapeutic judgement of patients with chronic hepatitis B (CHB). However, we lack indexes which can accurately predict significant liver inflammation in patients with CHB. This study aimed to develop a simple predictive index for liver inflammation in CHB using routine clinical parameters. A total of 519 patients with CHB who underwent liver biopsy were enrolled and randomly divided into training (n = 346) and validation cohorts (n = 173). Based on routine clinical parameters, gamma‐glutamyl transpeptidase (GGT; P = 0.031) and platelets (PLT; P < 0.001) were identified as independent predictors of significant inflammation by multivariable analysis in the training cohort. Accordingly, the GGT to PLT ratio (GPR) was developed to amplify the opposing effects for predicting liver inflammation. In the training cohort, the AUCs of GPR in predicting significant inflammation were 0.791 (95% CI: 0.742‐0.839), 0.783 (95% CI: 0.717‐0.849) and 0.791 (95% CI: 0.716‐0.867) in the entire patients with CHB, HBeAg‐positive CHB patients and HBeAg‐negative CHB patients, respectively. The diagnostic performance of GPR for significant inflammation was significantly superior to that of alanine aminotransferase (ALT), aspartate transaminase (AST) and GGT in all patients with CHB and HBeAg‐positive CHB patients, but was comparable with ALT, AST and GGT in HBeAg‐negative CHB patients. In the validation cohort, the diagnostic performance of GPR in assessing significant liver inflammation was also superior to other indexes in all patients with CHB and HBeAg‐positive CHB patients, but was comparable with GGT in HBeAg‐negative CHB patients. Thus, GPR can be a novel and simple index for predicting significant liver inflammation in CHB, especially for HBeAg‐positive CHB.     

肝移植临床化学指标实验诊断价值

目的:探讨临床化学指标对指导肝移植实验诊断价值.方法:分析98例肝移植受者病历,按出院诊断标准分为治愈组、治愈合并并发症组、死亡组3组.分析3组受者12项临床化学指标变化规律和特征.结果:ALT,AST, ALD,GLDH是预测缺血-再灌注损伤的良好指标.TB,DB,TBA是预测移植肝脏存活,恢复其胆汁分泌、排泄功能的指标.PA,CHE是反映移植肝脏存活、恢复其合成蛋白质功能的指标.急性排斥反应ALT,GGT, ALP, TB,DB有诊断价值.抗排异药物毒性反应ALT,AST, GGT, TB,DB有特异性.胆道狭窄/梗阻TB,DB有诊断价值.胆道感染时ALT, GGT有诊断特点.肺部感染时ALT,TB,DB有诊断意义.切口感染时ALT,GGT, GLDH有诊断价值.肝脏无功能临床化学指标3个特点:PA,CHE逐渐降低;TB,DB居高不降,甚至逐渐升高;ALD,GLDH进行性升高.结论:临床化学指标的变化规律和特点对判断肝脏存活、肝功能恢复,诊断、鉴别不同并发症以及指导临床治疗有诊断价值.     

Validation of FIB‐4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virus‐infected patients

Backgrounds: To optimize management and predict long‐term clinical courses in patients with chronic hepatitis B (CHB), noninvasive tests to determine the degree of hepatic fibrosis have been developed. Aims: This study aimed to validate a simple, noninvasive FIB‐4 index, which was first derived from an HCV–HIV‐co‐infected population, in patients with CHB and to compare it with other noninvasive tests for predicting cirrhosis. Methods: From 2006–2008, a total of 668 consecutive CHB patients who underwent liver biopsies were enrolled. The fibrosis stage was assessed according to the Batts and Ludwig system by a single pathologist blinded to patients' data. Results: For prediction of significant (F≥2) and severe (F≥3) fibrosis, and cirrhosis (F=4), the area under the receiver‐operating characteristic curves were 0.865, 0.910 and 0.926 respectively. In predicting cirrhosis, it demonstrated diagnostic values comparable to the age–spleen platelet ratio index (0.937, P=0.414) and age–platelet index (0.928, P=0.888), and better outcomes than spleen–platelet ratio index (0.882, P=0.007), aspartate aminotransferase (AST)–platelet ratio index (0.731, P<0.001) and AST–alanine aminotransferase ratio index (0.730, P<0.001). FIB‐4 cut‐offs of 1.6 and 3.6 provided 93.2% negative predictive value and 90.8% positive predictive value for detection of cirrhosis respectively. Based on these results, liver biopsy could be avoided in 70.5% of the study population. These cut‐offs were validated internally using bootstrap resampling methods, showing good agreement. Conclusions: FIB‐4 is a simple, accurate and inexpensive method of predicting cirrhosis, with outcomes comparable to other noninvasive tests and may reduce the need for liver biopsy in the majority of CHB patients.     

Non-invasive fibrosis markers for assessment of liver fibrosis in chronic hepatitis delta

Assessment of liver fibrosis by non-invasive means is clinically important. Studies in chronic hepatitis delta (CHD) are scarce. We evaluated the performance of eight serum fibrosis markers [fibrosis-4 score (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), age-platelet index (API), AST-to platelet-ratio-index (APRI), Goteborg University Cirrhosis Index (GUCI), Lok index, cirrhosis discriminant score (CDS) and Hui score] in CHD and chronic hepatitis B (CHB). Liver stiffness was assessed by transient elastography (TE) in CHD. The ability of fibrosis markers to detect significant fibrosis and cirrhosis were evaluated in 202 CHB and 108 CHD patients using published and new cut-offs through receiver operating characteristics (ROC) analysis. The latter was also applied to obtain cut-offs for TE. APRI, Fib-4, API and Hui score were assessed for significant fibrosis, and APRI, GUCI, Lok index, CDS and AAR for cirrhosis determination. Fibrosis markers displayed weak performance in CHB for significant fibrosis with area under ROC (AUROC) curves between 0.62 and 0.71. They did slightly better for CHD. TE displayed an AUROC of 0.92 and performed better than serum fibrosis markers (p < 0.05 for fibrosis markers). For cirrhosis determination, CDS and Lok Index displayed an AUROC of 088 and 0.89 in CHB and GUCI, Lok index and APRI displayed AUROCs around 0.90 in CHD. TE displayed the best AUROC (0.95). Hence TE is superior to serum fibrosis markers for diagnosing significant liver fibrosis and cirrhosis. GUCI, Lok index and APRI displayed a reasonable performance in CHD, which needs further confirmation.     

临床诊断的肝细胞型急性药物性肝损伤患者血清ALT/ALP比值变化特点与组织病理学特征分析

目的 探讨药物性肝损伤(DILI)患者临床分型的变化及其组织病理学特征。方法 2018年8月～2019年8月入院临床诊断为肝细胞型DILI患者43例,在入院治疗2周后行肝穿活检,在病理学检查当日再次根据临床指标确定临床分型,观察组织病理学特征。结果 43例临床诊断的肝细胞型DILI患者在肝穿时血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、血清总胆红素(TBIL)、碱性磷酸酶(ALP)、γ-谷氨酰转肽酶(GGT)和总胆汁酸(TBA)水平已显著降低,其R值较入院时也显著下降(19.6±13.6对3.29±3.26),差异具有统计学意义(P<0.05);组织病理学检查诊断急性炎症型21例,炎症淤胆型22例;在入院时,急性炎症型与炎症淤胆型患者血清ALT、AST、TBIL、ALP和GGT水平无显著性差异(P>0.05),仅急性炎症型患者R值显著小于炎症淤胆型(13.8±6.2对25.5±16.5,P=0.004),血清TBA水平显著低于炎症淤胆型(61.0±60.8 μmol/L对115.3±80.9μmol/L,P=0.017);入院时诊断为肝细胞型DILI的43例患者在肝穿时仅9例符合肝细胞型临床分型;经ROC曲线分析,以R值等于14.9为截断点,其曲线下面积(AUC)为0.708,具有一定的诊断意义。结论 药物性肝损伤的临床分型会随着病情的变化而呈动态变化,入院时以较高的R值诊断胆汁淤积具有一定的指导意义,值得进一步观察。