Serum aminotransferase levels instead of etiology affects the accuracy of transient elastography in chronic viral hepatitis patients

Background and Aim: It is still uncertain whether the accuracy of transient elastography (TE) in predicting the fibrosis stage is similar in chronic hepatitis B (CHB) and chronic hepatitis C (CHC). The present study was carried out to evaluate whether the underlying cause of chronic viral hepatitis affects the predictive accuracy of TE. Methods: Patients with CHB or CHC who were admitted for a liver biopsy were enrolled. Patients underwent TE and laboratory tests on the same day as the liver biopsy. The predictive accuracy was analyzed by comparing the areas under the receiver‐operating characteristic curves (AUCs). Results: Two‐hundred and seven patients were enrolled, comprising 121 CHB patients and 86 CHC patients). The patients were aged 44 ± 14 years, and 121 (58.5%) of them were men. AUCs for predicting significant fibrosis were significantly lower in CHB patients than in CHC patients (P = 0.043). The serum alanine aminotransferase (ALT) level was associated with overestimation and underestimation of the fibrosis stage, while the cause of chronic hepatitis was not. AUCs for predicting significant fibrosis were significantly lower in patients with ALT levels >70 IU/L (AUC, 0.830; 95% CI, 0.742–0.898) than in patients with ALT levels ≤70 IU/L (0.944; 0.882–0.979; P = 0.015). Conclusions: Although the predictive accuracy of TE in predicting significant fibrosis differed significantly with the cause of chronic hepatitis, this difference was due to the degree of serum ALT levels rather than to the cause of hepatitis itself. Avoiding performing TE in patients with elevated ALT levels is recommended to guarantee the predictive accuracy of TE.     

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.     

Correlation of liver biochemistry with liver stiffness in chronic hepatitis B and development of a predictive model for liver fibrosis

Aim: To correlate liver stiffness with demographical factors and routine liver biochemistry and to assess the predictive value of these as potential markers of fibrosis. Methods: Transient elastography was performed in 1268 chronic hepatitis B (CHB) patients. According to a previous validated study for CHB, liver stiffness of >8.1 and >10.3 kPa were used as cut‐off values for defining severe fibrosis and cirrhosis respectively. Results: Liver stiffness correlated positively with bilirubin, alkaline phosphatase (ALP), γ‐glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), globulin, α‐fetoprotein (AFP) and HBV DNA levels and negatively with albumin and platelet levels (P<0.05 for all correlations). From 13 parameters (age, sex, platelet, AST, ALT, GGT, AFP, albumin, globulin, bilirubin, ALP, HBV DNA and hepatitis B e‐antigen), four best parameters (AST, platelet, GGT and AFP) were used to derive a liver stiffness model. Using log (index)=1.44+0.1490(GGT)+0.3308 log (AST)−0.5846 log (platelets)+0.1148 log (AFP+1) to predict both severe fibrosis and cirrhosis had area under the receiver operating characteristics curve of 0.85. Conclusion: Routine liver biochemistry correlated well with liver stiffness in Asian CHB patients. A model using simple serum markers can predict liver stiffness, and further studies are required to validate the usefulness of these simple tests as non‐invasive markers of fibrosis in CHB.     

丙氨酸转氨酶和天冬氨酸转氨酶是反映HBeAg阴性慢性乙型肝炎肝组织炎性分级的敏感指标

目的 分析HBeAg阴性慢性乙型肝炎(CHB)自然病程中血清ALT和AST水平,以及由相同肝实质细胞体积分摊的血清ALT和AST水平与肝组织炎症活动度分级的关系.方法 检测HBeAg阴性CHB患者肝组织病理学不同炎症活动度分级患者血清ALT和AST水平,以及相同肝实质细胞体积分摊的血清ALT和AST水平.数据经ANOVA检验.结果 145例CHB肝组织炎症活动度分级G1～G4级患者血清ALT水平分别为(35.3±29.1)、(91.6±120.4)、(111.6±116.1)和(118.0±122.1)U/L,用相同肝脏实质细胞体积分摊后的血清ALT水平分别为(54.0±45.1)、(144.2±184.9)、(191.3±204.8)和(215.1±226.5)U/L,G1级分别与G2～G4两两比较,差异有统计学意义(P＜0.05);G1～G4的AST水平分别为(35.5±29.0)、(64.9±71.7)、(96.0±81.9)和(102.8±77.0)U/L,相同肝脏实质细胞体积分摊后的血清AST水平分别为(54.3±44.6)、(102.3±107.9)、(165.2±148.7)和(189.4±145.4)U/L,G1与G3、G1与G4、G2与G3、G2与G4比较,差异有统计学意义(P＜0.05).结论 HBeAg阴性CHB自然病程中,ALT和AST均是反映肝组织炎症活动度分级严重性的较为敏感的指标.

Abstract：

Objective To investigate the relationship between serum levels of alanine aminotransferase (ALT)or aspartate aminotransferase (AST)apportioned by the same hepatic parenchyma cell volume and liver histological necroinflammation grades in HBeAg-negative chronic hepatitis B (CHB)patients.Methods A total of 145 CHB patients were divided into four groups:Gl,G2,G3 and G4 based on the liver histological necroinflammation grade.The serum ALT and AST levels were determined by automatic biochemical instrument in these four groups.Furthermore,serum ALT and AST levels were then apportioned by the same hepatic parenchyma cell volume.The data were analyzed by ANOVA.Results Mean serum ALT levels in G1,G2,G3 and G4 groups were (35.3±29.1),(91.6±120.4),(111.6± 116.1)and (118.0±122.1)U/L,respectively,and the serum ALT levels apportioned by same hepatic parenchyma cell volume were ( 54.0 ± 45.1 ),( 144.2 ± 184.9 ),(191.3± 204.8)and (215.1 ± 226.5)U/L,respectively.The pairwise comparison between G1 and other three groups all showed statistically significant difference (P＜0.05).Meanwhile,AST levels in G1 to G4 groups were (35.5± 29.0),(64.9±71.7),(96.0±81.9)and (102.8±77.0)U/L,respectively and the serum AST levels apportioned by the same hepatic parenchyma cell volume were (54.3±44.6),(102.3± 107.9),(165.2±148.7)and (189.4±145.4)U/L,respectively.The pairwise comparison between G1 and G3,G1 and G4,G2 and G3,G2 and G4 all showed statistically significant difference (P＜0.05).Conclusion Both AST and ALT levels are sensitive indicators for liver inflammation grading in HBeAg-negative CHB patients during the natural history of the disease.     

Soluble programmed death‐1 is a useful indicator for inflammatory and fibrosis severity in chronic hepatitis B

Elevated programmed death‐1 (PD‐1) has been found in immune cells in viral infections and plays an important role in infection persistence. The soluble form of PD‐1 (sPD‐1) is involved in tumours and viral infections. The aim of this study was to investigate the role of sPD‐1 in chronic hepatitis B (CHB). A total of two hundred and eighteen CHB patients and sixty healthy controls (HC) were enrolled. Demographic data and clinical parameters were collected. An ELISA assay was used to measure serum sPD‐1 levels, and the relationships between sPD‐1 and clinical/virological characteristics was analysed. sPD‐1 levels in CHB patients were higher (median 4.409 IQR 3.435‐5.306 pg/mL) than those of HC individuals (median 0.3665 IQR 0.2425‐0.5010 pg/mL). Among patients at various disease stages, patients with immune activity showed the highest sPD‐1 levels (median 5.138 IQR 4.329‐5.406 pg/mL). sPD‐1 concentration was associated with HBV markers (HBsAg, HBV DNA and HBeAg) and biochemical parameters (serum aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin [TBil] and gamma glutamyl transferase [γ‐GT] levels) (all P < 0.05). sPD‐1 levels were higher in CHB patients with moderate‐to‐severe inflammation or fibrosis than in those with mild inflammation or fibrosis, regardless of ALT levels. The association between sPD‐1 and disease progression of CHB suggests that sPD‐1 could serve as a new indicator in assessing liver fibrosis. These findings may further aid in determining the initiation of antiviral treatment in patients with normal ALT levels.     

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.     

Comparison of FIB‐4 and APRI in Chinese HBV‐infected patients with persistently normal ALT and mildly elevated ALT

Significant liver disease has been reported in chronic hepatitis B patients with normal alanine aminotransferase (ALT). Liver biopsy (LB) is the current gold standard for assessing hepatic inflammation and fibrosis in patients with chronic HBV. However, associated risks have led to the development of noninvasive models. Their utility in patients with normal ALT is unknown. FIB‐4 and aspartate aminotransferase (AST)‐to‐platelet ratio index (APRI) were calculated for patients with chronic HBV infection undergoing biopsy. The performance of each model and AUROC for predicting significant fibrosis (Scheuer's score ≥ S2) were determined for the entire cohort and stratified by elevated (≥50 U/L) and normal ALT. Two‐hundred and thirty‐one liver biopsies were included. The number of patient with normal ALT was 140, and 22.1% had significant fibrosis. The AUROC curve for patients with normal ALT was 0.81 for FIB‐4 and 0.80 for APRI, compared with 0.71 for FIB‐4 and 0.72 for APRI for those with mildly elevated ALT level. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of FIB‐4 were 0.63, 0.88, 0.61 and 0.93, for patients with normal ALT; the values for APRI were 0.40, 0.88, 0.33 and 0.93. Both FIB‐4 and APRI are useful for identification of those without significant fibrosis. However, because they have poor PPV, LB will continue to be used for assessment of HBV‐infected patients with normal ALT and mildly elevated ALT.     

Selected Cytokines Serve as Potential Biomarkers for Predicting Liver Inflammation and Fibrosis in Chronic Hepatitis B Patients With Normal to Mildly Elevated Aminotransferases

Previous studies of small cohorts have implicated several circulating cytokines with progression of chronic hepatitis B (CHB). However, to date there have been no reliable biomarkers for assessing histological liver damage in CHB patients with normal or mildly elevated alanine aminotransferase (ALT).The aim of the present study was to investigate the association between circulating cytokines and histological liver damage in a large cohort. Also, this study was designed to assess the utility of circulating cytokines in diagnosing liver inflammation and fibrosis in CHB patients with ALT less than 2 times the upper limit of normal range (ULN).A total of 227 CHB patients were prospectively enrolled. All patients underwent liver biopsy and staging by Ishak system. Patients with at least moderate inflammation showed significantly higher levels of CXCL-11, CXCL-10, and interleukin (IL)-2 receptor (R) than patients with less than moderate inflammation (P < 0.001). Patients with significant fibrosis had higher levels of IL-8 (P = 0.027), transforming growth factor alpha (TGF-α) (P = 0.011), IL-2R (P = 0.002), and CXCL-11 (P = 0.032) than the group without significant fibrosis. In addition, 31.8% and 29.1% of 151 patients with ALT < 2 × ULN had at least moderate inflammation and significant fibrosis, respectively. Multivariate analysis demonstrated that CXCL-11 was independently associated with at least moderate inflammation, and TGF-α and IL-2R independently correlated with significant fibrosis in patients with ALT < 2 × ULN. Based on certain cytokines and clinical parameters, an inflammation-index and fib-index were developed, which showed areas under the receiver operating characteristics curve (AUROC) of 0.75 (95% CI 0.66–0.84) for at least moderate inflammation and 0.82 (95% CI 0.75–0.90) for significant fibrosis, correspondingly. Compared to existing scores, fib-index was significantly superior to aspartate aminotransferase (AST) to platelet ratio index (APRI) and FIB-4 score for significant fibrosis.In conclusion, CXCL-11 was independently associated with at least moderate inflammation, whereas IL-2R and TGF-α were independent indicators of significant fibrosis in both, total CHB patients and patients with normal or mildly elevated ALT. An IL-2R and TGF-α based score (fib-index) was superior to APRI and FIB-4 for the diagnosis of significant fibrosis in patients with normal or mildly elevated ALT.     

丙氨酸氨基转移酶升高小于2倍正常值上限的慢性乙型肝炎患者肝组织学变化的预测指标

目的 分析ALT升高小于2倍正常值上限(ULN)的慢性乙型肝炎患者肝组织学改变的相关因素,并探讨各因素对临床抗病毒治疗适应证的指导价值.方法选择ALT升高<2×ULN,且经肝活组织检查的152例慢性乙型肝炎患者.用Spearman相关分析、单因素方差分析、受试者工作特征曲线下面积、Logistic逐步回归等方法分析临床上常规指标与肝脏炎症分级(G)和纤维化分期(S)的相关性及其诊断价值.分析指标包括年龄、总胆红素、直接胆红素、球蛋白、白蛋白、总蛋白、ALT、AST、碱性磷酸酶、γ-谷氨酰转肽酶(GGT)、白细胞计数、血小板计数(BPC)和血清HBV DNA载量.结果152例患者均有不同程度肝组织学异常,炎症G2、G3及G4者分别为42例(27.6%)、46例(30.3%)和14例(9.2%);纤维化S2、S3及S4者分别为16例(10.5%)、25例(16.5%)和41例(27.0%).血清白蛋白、白蛋白/球蛋白比值、BPC、白细胞计数和GGT与明显肝组织炎症(G2～4)及明显纤维化(S2～4)显著相关(P值均<0.05).年龄≥40岁组患者明显纤维化与中、重度肝损害者均达70.4%(38/54),高于<40岁组的44.9%(44/98)和38.8%(38/98),x2值分别为18.83和9.09,P值均<0.01.建立Logistic逐步回归方程:预测值P=1/[(1+e-(9.3625-0.1626×白蛋白水平-0.0234×BPC].GGT≥65 U/L判断有无明显肝组织炎症的阳性预测值最高(92.7%),回归方程中预测值≥0.500判断有无明显肝组织炎症的灵敏度最高(83.3%).结论 ALT轻度升高的慢性乙型肝炎的患者大部分存在明显的肝脏组织学改变,年龄≥40岁者发生明显肝纤维化与中、重度肝损害的可能性大.GGT及由BPC和白蛋白构成的Logistic回归方程是预测明显肝组织炎症的较好指标.

Abstract：

Objective To investigate the relevant factors of liver histological changes in chroonic hepatitis B(CHB)patients with mildly elevated ALT and to explore the clinical values of these factors on anti-viral treatment.Methods A total of 152 CHB patients with mildly elevated ALT(less than 2×ULN)who underwent liver biopsy were included in the study.Correlations between routine laboratory markers,liver histological inflammation grade and fibrosis stage were statistically assessed by Spearman correlation analysis,one-way ANOVA,area under the curve(AUC)of the receiver operating characteristic curves(ROC)and Logistic regression statistical analysis.Results All patients in the study showed various hepatic histological damages. Among the 152 patients 50 (32.9%) were found with inflammation grade 1 (G1),42 (27.6%) with G2,46 (30.3%) with G3 and 14 (9.2%) with G4. 16 patients (10.5%) were found with fibrosis stage 2 (S2),25(16.5%) with S3 and 41 (27.0%) with S4. Routine laboratory markers Alb,BPC and WBC were significantly correlated with hepatic histological inflammation grade and fibrosis stage. Marked liver fibrosis and moderate to severe liver damage were significantly higher in patients aged more than 40 years as compared to those less than 40 years of age (P = 0.002,P = 0.010). The regression equation P = 1/[1+e-(9.3625-0.1625Alb-0.0234BPC)]was established with sensitivity and specificity of 83.3% and 65.0%,respectively. Conclusion 67.8% of CHB patients with mildly elevated ALT have significant injury to the liver tissue. CHB patients aged more than 40 years have a significant increase of marked liver fibrosis and moderate to severe liver damage. The regression equation is valuable to predict whether CHB patients need antiviral therapy or not.     

Metabolic factors are associated with serum alanine aminotransferase levels in patients with chronic hepatitis C

Background

Although serum alanine aminotransferase (ALT) activity is an important marker for the management of chronic hepatitis C (CHC), the factors associated with serum ALT levels remain to be fully understood. This study aimed to clarify the association between serum ALT levels and clinical, histological, and virological factors in patients with CHC.

Methods

We retrospectively analyzed 256 patients with CHC who underwent liver biopsy, and classified them into three groups according to serum ALT levels: normal to minimal (<40?IU/L), mild (40?C80?IU/L), and moderate to severe elevation (??80?IU/L). All demographic and laboratory data were collected at the time of liver biopsy. All biopsies were evaluated for fibrosis, inflammation, and steatosis. Glucose metabolism was assessed by various indices derived from oral glucose tolerance tests, including the homeostasis model assessment for insulin resistance (HOMA-IR). In 180 patients, visceral fat area was measured at the umbilical level by abdominal computed tomography.

Results

Ordered logistic regression analysis showed that higher serum ALT levels were significantly associated with male sex, lower high-density lipoprotein cholesterol (HDL-C), higher HOMA-IR, and higher grades of histological inflammation and steatosis. HOMA-IR, HDL-C, and hepatic steatosis were associated with visceral fat accumulation.

Conclusions

Metabolic factors, as well as sex and hepatic inflammation, are independent risk factors for serum ALT elevation in hepatititis C virus (HCV)-infected patients. Metabolic factors may offer targets to decrease serum ALT levels.     

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.     

Role of quantitative hepatitis B core antibody levels in predicting significant liver inflammation in chronic hepatitis B patients with normal or near‐normal alanine aminotransferase levels

Aim

Chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) levels are not free from significant hepatic lesions. Recently, there has been an improved understanding of the clinical significance of quantitative hepatitis B core antibody levels (qAnti‐HBc) during CHB management. In this cross‐sectional study, we evaluated the utility of qAnti‐HBc in identifying significant liver inflammation in CHB patients.

Methods

A total of 469 patients (training set, n = 363; validation set, n = 106) who underwent liver biopsy (LB) were included. The qAnti‐HBc levels were quantified and the relationship between histology and serum markers was systematically analyzed.

Results

In the training set, qAnti‐HBc levels were found to have significant diagnostic value for moderate to severe liver inflammation (≥G2) in all patients (area under the receiver operating characteristic curve [AUROC] = 0.768; 95% confidence interval [CI], 0.721–0.810; P < 0.001) and in patients with normal or near‐normal ALT levels (AUROC = 0.767; 95% CI, 0.697–0.828; P < 0.001). Our novel index (AC index) for the identification of ≥G2 inflammation, which combined the qAnti‐HBc and ALT levels, significantly improved diagnostic performance (AUROC = 0.813; 95% CI, 0.768–0.852) compared to the use of ALT alone (AUROC = 0.779; 95% CI, 0.732–0.821) in all patients. In the validation set, the AC index showed an improved AUROC of 0.890 (95% CI, 0.814–0.942) and 0.867 (95% CI, 0.749–0.943) in all patients and patients with normal ALT levels, respectively.

Conclusions

The qAnti‐HBc level predicts significant liver inflammation well, even in patients with normal or near‐normal ALT levels. Compared with the conventional ALT level, the AC index is a more reliable non‐invasive biomarker for significant liver inflammation in CHB patients.     

肝细胞脂肪变导致HBV DNA载量慢性乙型肝炎患者转氨酶增高

目的 分析HBV DNA低载量HBsAg阳性患者转氨酶异常的原因.方法 研究对象为血清HBsAg阳性时间持续1年以上、HBV DNA(PCR法)<103拷贝/ml和ALT>1.25×ULN超过6个月的患者,剔除合并HCV和HIV等病毒感染及其他慢性肝病.患者均进行肝活组织检查并结合临床资料分析转氨酶增高的原因. 结果有119例患者纳入研究,男性102例,HBeAg阴性88例(73.9%);平均年龄(33.9±9.7)岁,体重指数(23.4±3.7)kg/m2,ALT(150.0±166.6)U/L,AST(102.4±193.2)U/L.肝活组织检杏有32例(26.9%)为肝细胞脂肪变,64例(53.8%)为慢性肝炎,7例(5.9%)为两者并存,15例(12.6%)为非特异性改变,1例为止常肝组织.30例接受核苷类似物抗病毒治疗的患者,17例有肝脂肪变,占56.7%;89例未进行抗病毒治疗的患者,有22例有肝脂肪变,占24.7%,两组比较x2=10.394,P<0.01,差异有统计学意义.单因素分析显示,肝脂肪变组(n=39)体重指数、甘油三酯、总胆固醇、载脂蛋白B以及尿酸水平显著高十尢肝脂肪变组(n=64);而ALT、AST和载脂蛋白-A水半则显著低于无肝脂肪变组,t值分别为5.369、4.276、3.216、4.223、2.438以及-2.234、-3.877和-2.956,P值均<0.05.肝脂肪变组男性的比例.超重和肥胖,高尿酸血症和高脂血症的患病率亦显著高于无肝脂肪变组;而肝组织炎症和纤维化程度却显著降低,x2分别为3.829、7.659、13.389、0.549和20.978、17.550,P值均<0.05.与肝脏非特异性改变患者相比较,慢性肝炎患者ALT、AST、GGT水平显著升高,P值均<0.05;但其他相关指标无统计学差异. 结论代谢紊乱及其相关肝细胞脂肪变为HBV DNA低载量HBsAg阳性患者转氨酶升高的原因之一.     

Glucose intolerance and serum aminotransferase activities in Japanese men

BACKGROUND/AIMS: Elevated activities of serum aminotransferase are commonly observed in patients with diabetes mellitus. Few studies have addressed the relation between glucose intolerance and serum activities of aminotransferase in free-living populations. METHODS: Using a 75 g oral glucose tolerance test, we examined the association of impaired fasting glycemia (IFG), impaired glucose tolerance (IGT), and type 2 diabetes mellitus with serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) among 4621 men aged 49-59 years of the Japan Self-Defense Forces. Statistical adjustment was made for body mass index, waist-hip ratio, and other possible confounding factors. RESULTS: Proportions of an elevated ALT (>50 IU/l) in men with normal glucose tolerance, IFG, IGT, and newly diagnosed diabetes mellitus were 3.5%, 9.5%, 7.7%, and 18.0%, respectively. Adjusted odds ratios of an elevated ALT for IFG, IGT, and newly diagnosed diabetes mellitus were 2.2 (95% confidence interval 1.1-4.3), 1.7 (1.2-2.4), and 4.4 (3.0-6.6), respectively. IGT and diabetes mellitus were also significantly positively associated with elevated AST (>40 IU/l) and GGT (>50 IU/l). CONCLUSIONS: Glucose intolerance is associated with elevated serum aminotransferase independent of obesity, but even a mildly elevated ALT is relatively uncommon in free-living men with glucose intolerance.     

High prevalence of significant histology in asymptomatic chronic hepatitis B patients with genotype C and high serum HBV DNA levels

Summary.  Current treatment guidelines suggest that antiviral therapy be considered for chronic hepatitis B (CHB) patients with high viral load if a biopsy shows significant liver disease despite alanine aminotransferase (ALT) levels two times or less than the upper limit of normal (ULN). We evaluated the histological findings in CHB patients with high viral load and persistently normal or slightly elevated serum ALT levels. Between January 2003 and June 2006, 105 consecutive treatment-naive patients with CHB who underwent ultrasonography-guided percutaneous liver biopsy, had detectable serum HBV DNA (>10⁵ copies/mL) in a direct hybridization assay and normal or slightly elevated serum ALT levels (≤2 × ULN) for at least 12 months were included in a prospective study. Histological assessment was based on the METAVIR scoring system. Significant histology was defined as fibrosis stage ≥F2 or necroinflammation grade ≥A2. Among the 105 CHB patients with high viral load and persistently normal or slightly elevated serum ALT levels for at least 12 months, significant fibrosis (F2–F4 fibrosis) was observed in 63 patients (60.0%) and the actual significant histology was found in 65 patients (61.9%). On multivariate analysis, serum ALT levels and age at which they entered the study were independent factors associated with significant histology. Odds ratios for significant histology increased progressively according to serum ALT levels and age. In conclusion, a large proportion of CHB patients with genotype C, high viral load and ALT ≤2 × ULN had significant liver disease on liver biopsy and should be considered for antiviral therapy.     

Relationship between hepatitis B virus DNA levels and liver histology in patients with chronic hepatitis B

AIM： To study the relationship between hepatitis B virus （HBV） DNA levels and liver histology in patients with chronic hepatitis B （CHB） and to determine the prevalence and characteristics of hepatitis B e antigen （HBeAg） negative patients.
METHODS： A total of 213 patients with CHB were studied, and serum HBV DNA levels were measured by the COBAS Amplicor HBV Monitor test. All patients were divided into two groups according to the HBeAg status.The correlation between serum HBV DNA levels and liver damage （liver histology and biochemistry） was explored.
RESULTS： Of the 213 patients with serum HBV DNA levels higher than 10^5 copies/mL, 178 （83.6%） were HBeAg positive, 35 （16.4%） were HBeAg negative. The serum HBV DNA levels were not correlated to the age,history of CHB, histological grade and stage of liver disease in either HBeAg negative or HBeAg positive patients. There was no correlation between serum levels of HBV DNA and alanine aminotransferanse （ALT）,aspartate aminotrans-ferase （AST） in HBeAg positive patients. In HBeAg negative patients, there was no correlation between serum levels of HBV DNA and AST,while serum DNA levels correlated with ALT （r = 0.351, P = 0.042）. The grade （G） of liver disease correlated with ALT and AST （P 〈 0.05, r = 0.205, 0.327 respectively）in HBeAg positive patients. In HBeAg negative patients,correlations were shown between ALT, AST and the G （P 〈 0.01, and r = 0.862, 0.802 respectively）. HBeAg negative patients were older （35 ± 9 years vs 30 ±9 years, P 〈 0.05 ） and had a longer history of HBV infection （8 ± 4 years vs 6 ± 4 years, P 〈 0.05） and a lower HBV DNA level than HBeAg positive patients （8.4± 1.7 Log HBV DNA vs 9.8 ± 1.3 Log HBV DNA, P 〈0.001）. There were no significant differences in sex ratio,ALT and AST levels and liver histology between the two groups.
CONCLUSION： Serum HBV DNA level is not correlated to histological grade or stage of liver disease in CHB patients with HBV DNA mor     

FibroScan对慢性乙型肝炎肝纤维化患者的应用价值及ALT、AST对其诊断的影响

目的探讨瞬时弹性探测仪(FS)在慢性乙型肝炎肝纤维化患者中应用价值及ALT、AST对其诊断纤维化的影响。方法应用FS对90名慢性乙型肝炎肝纤维化患者进行肝穿前肝脏弹性测量值(LSM)的测定,同时进行血清ALT、AST的检测。以肝脏活检病理结果为金标准,对肝纤维化进行分期。结果 LSM在肝纤维化病理S1～4之间逐渐增高,组间差异有统计学意义(P<0.01);相邻两分期间LSM组间差异均有统计学意义(P<0.01)。肝脏LSM与病理分期呈正相关(r=0774,P<0.01)。S1～4各期的LSM与相应分期的ALT呈正相关,相关系数分别为0.672(P=0.000)、0.790(P=0.000)、0.845(P=0.001)和0.797(P=0.003),S1～4各期LSM与相应分期的AST呈正相关,相关系数分别为0.593(P=0.000)、0.762(P=0.001)、0.743(P=0.009)和0.872(P=0.000)。结论 FS在慢性乙型肝炎肝纤维化程度评估中有较好的应用价值,但是血清ALT和AST水平对其有一定影响。     

40例慢性乙型肝炎轻度患者肝组织病理学变化研究

目的探讨40例成人谷丙酶正常或轻度升高的慢性HBV感染者肝组织病理学的变化。方法常规进行肝穿刺组织学检查,对肝组织进行炎症分级及纤维化分期;采用化学发光法对该组患者进行血清HA、LN、PCⅢ、cⅣ水平的检测;应用全自动生化仪检测主要血生化指标。分析上述血清学指标水平与肝组织炎症分级及纤维化分期之间的关系。结果在40例慢性HBV感染者中,G1S0 3例,G1S1 9例,G1S2 1例,G1S3 3例,G1S4 4例,G2S1 10例,G2S2 3例,G2S4 4例,G3S4 2例,G4S4 1例;肝组织炎症分级和纤维化分期〈G2S：组血清ALT、ALB及CHE水平较≥G2S2 组有所增加,血清AST、TBIL水平较≥G2S2组有所减少,其中仅血清AST水平在两组间有显著性差异（P〈0．05）,血清ALT、TBIL、ALB、CHE水平在组间均无统计学差异（P〉0．05）。肝组织纤维化分期≥S2组血清HA、LN、PCⅢ、CIV水平较〈S2组均有所增加,其中血清HA、PCⅢ、CIV水平在组间有统计学差异（P〈0．05）,而血清LN水平在组间无显著性差异（P〉0．05）。结论对成人ALT正常或轻度升高的HBV感染者应及时行肝穿刺活检,以便作出正确的诊断和及时处理,防止病情向肝硬化、肝癌的进展。     

Rotavirus Causes Hepatic Transaminase Elevation

Rotavirus is one of the leading causes of acute gastroenteritis among children. While clinical complaints are generally intestinal including vomiting and diarrhea, there is evidence to suggest that disease outside the gastrointestinal tract occurs. This study examines the frequency of hepatic transaminase elevation in children with rotavirus gastroenteritis. Patients identified with rotavirus gastroenteritis by stool antigen testing between November 2005 and March 2006 had available serum analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin, direct bilirubin, and creatinine phoshosphokinase (CPK). Chart review was conducted to identify patients with possible liver injury unrelated to rotavirus. Among the 92 patients identified with rotavirus during the study period, 75 had serum specimens available for testing. Fifteen patients (20%) had elevated ALT and AST, including one patient with an increase in AST, ALT, alkaline phosphatase, and total and direct bilirubin. The mean ALT elevation was 56 IU/L (range, 44 to 114 IU/L), and the mean AST elevation was 80 IU/L (range, 57 to 126 IU/L). Fifty-three patients (71%) had an increase in AST alone, and three patients (4%) had an increase in AST and alkaline phosphatase. The mean AST values in these groups were 61 IU/L (range, 42 to 110 IU/L) and 79 IU/L (range, 59 to 96 IU/L), respectively. In conclusion, rotavirus commonly causes elevation of liver transaminases.     

Effect of ursodeoxycholic acid on autoimmune-associated chronic hepatitis C

BACKGROUND: Hypergammaglobulinaemia and various auto-antibodies which are commonly seen in autoimmune hepatitis are also found in patients with chronic hepatitis C. We recently reported that ursodeoxycholic acid (UDCA) improved liver function tests and immunoserological markers in patients with type I autoimmune hepatitis. The aim of this study was to prospectively evaluate the efficacy of UDCA on autoimmune-associated chronic hepatitis C. METHODS: Immunoglobulin G (IgG), anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) were determined in 95 patients with chronic hepatitis C. All patients were positive for hepatitis C virus RNA. Autoimmune-associated chronic hepatitis C (C-AIH) was defined by elevated serum IgG level (> or = 2.0 g/dL) and high titres of ANA and/or ASMA (> or = 1 : 160). Nine (9%) of 95 patients were diagnosed as C-AIH. All the C-AIH patients and 30 of the remaining 86 chronic hepatitis C patients without autoimmune features (CHC) were treated with UDCA (600 mg/day) for 1 year. RESULTS: Autoimmune-associated chronic hepatitis C patients included one man and eight women and their AIH scores, as defined by the International Autoimmune Hepatitis Group, were significantly higher than the CHC patients. Before UDCA therapy, there were no significant differences in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and y-glutamyl transpeptidase (gamma-GTP) levels between C-AIH and CHC patients. However, after 1 year UDCA therapy, AST, ALT and gamma-GTP were significantly lower in C-AIH patients (P< 0.05) than in CHC patients. In C-AIH, ANA titres in seven of nine patients and ASMA titres in five of seven patients were reduced after 1 year UDCA treatment. CONCLUSIONS: These results suggest that UDCA is a useful therapeutic agent for autoimmune-associated chronic hepatitis C.