血清高尔基体蛋白73在慢性肝病患者中的临床应用

高尔基体蛋白73（GP73）是细胞高尔基体上的一种跨膜蛋白,可被切割释放入血。近年来,越来越多的临床研究表明,血清GP73的升高与肝脏疾病密切相关,有望作为评估慢性肝脏疾病进展的新型血清学标志物。现围绕血清GP73对不同病因引起的慢性肝炎、肝纤维化、肝硬化和肝细胞癌中的临床应用进行综述,并对未来研究进行展望。     

Identification of a new marker of hepatocellular carcinoma by serum protein profiling of patients with chronic liver diseases

Surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS) is a proteomic technique that enables the profiling of proteins present in any biological material studied. We used this approach to identify new biomarkers of hepatocellular carcinoma (HCC) in the sera of patients with cirrhosis. Sera from 82 patients with cirrhosis, either without (n = 38) or with (n = 44) HCC, were analyzed by SELDI-TOF MS, and the results of the two groups were compared. The most efficient protein peaks leading to discrimination of patients with HCC were selected (receiver operative characteristic curves). The highest-scoring peak combination was established in a first group of serum samples (multinomial regression) and was tested in an independent group. The protein corresponding to the highest discrimination was purified and characterized further. The intensity of 30 protein peaks significantly differed between cirrhotic patients with and without HCC. An algorithm including the six highest-scoring peaks allowed correct classification (presence or absence of HCC) of 92.5% of patients in the test sample set and 90% in the validation sample set. The highest discriminating peak (8900 Da) was purified further and was characterized as the C-terminal part of the V10 fragment of vitronectin. An in vitro study suggested that the increase of the 8900-Da fragment in the serum of patients with HCC may proceed from the cleavage of native vitronectin with metalloproteases, a family of enzymes whose activity is enhanced in HCC. In conclusion, global protein profiling is an efficient approach that enabled us to identify a catalytic fragment ofvitronectin as a new serum marker of HCC in patients with chronic liver diseases.     

Health-related quality of life of chronic liver disease patients with and without hepatocellular carcinoma

BACKGROUND AND AIM: Impaired health-related quality of life has been reported in patients with cirrhosis and chronic hepatitis. However, only limited data are available concerning the influence of hepatocellular carcinoma. METHODS: Health-related quality of life was assessed in 97 patients with hepatocellular carcinoma who had been treated successfully with percutaneous ablation therapy, and 97 patients with chronic liver disease without hepatocellular carcinoma matched for age and sex, using the Japanese version of Short-Form 36. Raw scores were transformed using norm-based scoring. The relations with objective variables including status of hepatocellular carcinoma and laboratory data were analyzed. RESULTS: Health-related quality of life was lower in both groups than in the general population. Patients with hepatocellular carcinoma and patients in the control group showed similar scores. By multivariate analysis, liver function, especially serum albumin, strongly predicted health-related quality of life, but status of hepatocellular carcinoma did not. CONCLUSIONS: Impaired health-related quality of life was not associated with the presence of hepatocellular carcinoma but dependent on the level of liver function, indicating the importance of preserving liver function in following up patients. Serum albumin level was a useful objective variable to assess health-related quality of life of patients with chronic liver disease.     

慢性肝病患者脾硬度值与肝硬度值的相关分析

目的 研究慢性肝病患者脾脏硬度(SSM)值与肝脏硬度(LSM)值的相关性.方法 选择200例慢性肝病患者,其中肝硬化组120例,肝炎组80例.采用瞬时弹性成像技术检测两组SSM及LSM程度,并对其SSM值和LSM值进行相关分析.结果 肝硬化组、肝炎组的SSM值与LSM值均有显著相关性(r分别为0.377、0.314,P分别为0.000、0.005).结论 慢性肝病患者的SSM值与LSM值显著相关,临床联合检测SSM及LSM,可全面地评价慢性肝病患者的病情.     

Model to estimate survival in ambulatory patients with hepatocellular carcinoma

Survival of patients with hepatocellular carcinoma (HCC) is determined by the extent of the tumor and the underlying liver function. We aimed to develop a survival model for HCC based on objective parameters including the Model for Endstage Liver Disease (MELD) as a gauge of liver dysfunction. This analysis is based on 477 patients with HCC seen at Mayo Clinic Rochester between 1994 and 2008 (derivation cohort) and 904 patients at the Korean National Cancer Center between 2000 and 2003 (validation cohort). Multivariate proportional hazards models and corresponding risk score were created based on baseline demographic, clinical, and tumor characteristics. Internal and external validation of the model was performed. Discrimination and calibration of this new model were compared against existing models including Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), and Japan Integrated Staging (JIS) scores. The majority of the patients had viral hepatitis as the underlying liver disease (100% in the derivation cohort and 85% in the validation cohort). The survival model incorporated MELD, age, number of tumor nodules, size of the largest nodule, vascular invasion, metastasis, serum albumin, and alpha-fetoprotein. In cross-validation, the coefficients remained largely unchanged between iterations. Observed survival in the validation cohort matched closely with what was predicted by the model. The concordance (c)-statistic for this model (0.77) was superior to that for BCLC (0.71), CLIP (0.70), or JIS (0.70). The score was able to further classify patient survival within each stage of the BCLC classification. CONCLUSION: A new model to predict survival of HCC patients based on objective parameters provides refined prognostication and supplements the BCLC classification.     

艾滋病合并肝细胞癌与非艾滋病肝细胞癌患者肝切除术后并发症及肝功能的比较分析

目的通过对比艾滋病合并肝细胞癌与非艾滋病肝细胞癌患者肝切除术后并发症及肝功能,分析根治性肝切除术治疗艾滋病合并肝细胞癌的可行性,探讨围手术期死亡率增高的原因。 方法回顾性分析在广州医科大学附属市八医院接受根治性肝切除术的26例艾滋病合并肝细胞癌患者的临床资料,与同期接受根治性肝切除术的75例非艾滋病肝细胞癌患者对比。根据是否合并艾滋病分为艾滋病合并肝细胞癌组即HIV+组与非艾滋病肝细胞癌组即HIV-组。比较两组的并发症、肝功能及围手术期死亡率。计量资料用（±s）表示,组间比较用t检验。计数资料以病例数[n (%)]表示,组间比较采用χ²检验。 结果HIV+组与HIV-组手术方式选择差异无统计学意义（P=0.071）。两组间感染性并发症（P=0.259）、非感染性并发症（P=0.357）发生率差异无统计学意义。两组间术前、术后1 d、3 d、7 d谷丙转氨酶（ALT）、白蛋白、总胆红差异无统计学意义,术前天冬氨酸转氨酶（AST）差异有统计学意义（P<0.001）,HIV+组65.4%患者术前AST≥40 U/L。单因素分析术前AST、术后3 d总胆红素、术后7 d白蛋白是预后的影响因素。围手术期3例患者死亡,均为HIV+患者,其中肝功能衰竭死亡2例,出血死亡1例;两组围手术期死亡率差异有统计学意义（P=0.016）。 结论对艾滋病合并肝细胞癌患者行根治性肝切除术是可行的,但更易发生围手术期死亡,肝功能衰竭是围手术期死亡的主要原因,对其肝切除术应更加严格的选择患者。     

Hepatic resection with and without surgical margins for hepatocellular carcinoma in patients with impaired liver function.

BACKGROUND/AIMS: The significance of a surgical margin for hepatic resection of hepatocellular carcinoma (HCC) in patients with impaired liver function was evaluated. METHODOLOGY: Sixty-eight patients, each with a solitary HCC, who had not received any prior treatments were divided into 2 groups, according to surgical margin: Group A included 25 patients who underwent resection with no margin (although the tumor was not exposed) and Group B included 43 patients with a sufficient surgical margin (mean distance: 9 mm). There were no significant differences in clinicopathologic variables between the 2 groups. The rate of stump recurrence, survival and recurrence-free survival were analyzed. RESULTS: Among the 38 patients who had cancer recurrence after a median follow-up of 58 months, 9 (Group A, n=4; Group B, n=5) (24%) had recurrent lesions at the stump. The surgical margin was not a significant factor related to survival or recurrence, irrespective of cirrhosis, capsule formation, cancer spread, or tumor size. CONCLUSIONS: Our results indicated that the HCC-free surgical margin is unlikely to be related to the survival of patients with impaired liver function unless the tumor is exposed on the raw liver surface.     

Clinical significance of serum procalcitonin levels in patients with acute or chronic liver disease

OBJECTIVE: To evaluate the diagnostic value of serum procalcitonin levels in patients with acute or chronic liver disease, with or without bacterial infections and to correlate the results with the clinical outcome and the laboratory findings for these patients. METHODS: One hundred and six consecutive hospitalized patients with liver disease were evaluated for procalcitonin levels on admission. Fifteen of them (14.2%) had acute alcoholic hepatitis on cirrhotic background (group A), 20 (18.9%) had alcoholic cirrhosis without hepatitis and/or bacterial infection (group B), 16 (15.1%) had decompensated cirrhosis with proved bacterial infection (group C), 42 (39.6%) had uncomplicated viral hepatitis-related cirrhosis (group D) and 13 (12.3%) had acute icteric viral hepatitis (group E). Serum procalcitonin levels were measured using an immunoluminometric assay. Statistical analysis was based on Student's t-test and the non-parametric Kruskall-Wallis test (P<0.05). RESULTS: Serum procalcitonin levels were significantly higher in cirrhotic patients with bacterial infection (9.80+/-16.80 ng/ml) than in those without bacterial infection (0.21+/-0.13 ng/ml, P=0.001), whereas they were within normal range (<0.5 ng/ml) in all patients with uncomplicated cirrhosis, irrespective of the cause of cirrhosis. Seven of 15 group A patients (46.2%) and 4/13 group E patients (30.8%), all of them cirrhotics, had procalcitonin levels higher than 0.5 ng/ml on admission, without established bacterial infection. CONCLUSION: Serum procalcitonin levels remain below the threshold of 0.5 ng/ml in all patients with uncomplicated cirrhosis, irrespective of the cause of the disease, while they are significantly elevated when bacterial infection complicates the course of the disease. A significant proportion of patients with acute alcoholic hepatitis on a cirrhotic background as well as of patients with acute on chronic viral hepatitis, without bacterial infection, exhibit serum procalcitonin levels above 0.5 ng/ml, suggesting that this cut-off value is probably not enough to discriminate between patients with or without bacterial infection within these subgroups of patients with liver disease.     

Plasma and urine levels of urinary trypsin inhibitor in patients with chronic liver diseases and hepatocellular carcinoma

BACKGROUND AND AIM: Because urinary trypsin inhibitor (UTI) is synthesized by hepatocytes and excreted into the urine, plasma and urine levels of UTI may alter in liver diseases. However, there are few reports on the changes in these levels in chronic liver diseases and hepatocellular carcinoma (HCC). The aim of the present study was to evaluate the relationships between plasma and urine UTI levels and the severity of liver damage or progression of HCC in patients with chronic liver diseases and HCC. METHODS: Plasma and urine UTI levels were measured by a newly developed enzyme-linked immunosorbent assay in 16 patients with chronic hepatitis (CH), 19 patients with liver cirrhosis (LC) and 39 patients with HCC. RESULTS: Plasma UTI level exhibited a significant positive correlation with the urine UTI level. Plasma and urine UTI levels significantly decreased in LC patients compared with those of normal controls. In contrast, the plasma UTI level in HCC patients was higher than that in LC patients, but there was no difference between the groups in the urine UTI level. Plasma and urine UTI levels in LC and HCC patients were significantly correlated with the degree of liver damage according to the Child-Pugh classification. Although neither the plasma nor urine level of UTI in HCC patients were related to the clinical stage of HCC, both levels were closely associated with the level of protein induced by vitamin K absence or antagonist-II. CONCLUSIONS: The present findings indicate that the levels of plasma and urine UTI in patients with LC reflect the severity of liver damage. In HCC patients, these levels may also reflect progression of HCC, although further study is required.     

肝硬变和原发性肝癌患者HCV与HBV标志物分析

目的探讨肝硬变（ＬＣ），原发性肝癌（ＨＣＣ）发生和发展与ＨＣＶ及ＨＢＶ感染的关系．方法ＨＣＣ２８例，ＬＣ４８例和对照组５０例，用ＥＬＩＳＡ法同步检测ＨＢＶ及ＨＣＶ的６项血清标志物（Ｍ）．结果ＨＣＣ，ＬＣ及对照组ＨＢＶ＿Ｍ的阳性率分别为７５０％，８１３％和４００％；ＨＣＶ＿Ｍ的阳性率分别为７１％，２０８％和２０％．ＨＣＣ，ＬＣ中ＨＢＶ＿Ｍ阴性患者ＨＣＶ＿Ｍ阳性率为１２５％．ＨＣＶ与ＨＢＶ重叠感染者占ＨＣＣ和ＬＣ全部患者的１３２％．结论ＨＣＣ，ＬＣ发生和发展与ＨＢＶ及ＨＣＶ病毒感染密切相关，重叠感染者肝功能损害及临床失代偿程度更严重．     

静息能量消耗测定在老年慢病人群中的应用

人体每日能量消耗的精确测定有助于个体化营养治疗方案的制定,防止出现营养过剩或营养不良,使营养治疗受益最大化。影响静息能量消耗的因素有很多,如体型与机体构成、性别、年龄、疾病、环境条件等,本文主要对静息能量消耗测定在不同慢病时期老年人群中的临床应用加以综述。     

Hyperasialoglycoproteinemia in patients with chronic liver diseases and/or liver cell carcinoma. Asialoglycoprotein receptor in cirrhosis and liver cell carcinoma

The pathogenesis of hyperasialoglycoproteinemia in cirrhosis and liver cell carcinoma was investigated by measuring the amount of asialoglycoprotein receptor in hepatic tissues from 30 patients with either cirrhosis or a malignancy. The asialoglycoprotein receptor activity in the cirrhotic liver was 770 +/- 423 U/g liver, i.e., 28% of the control value (2770 +/- 731 U/g liver). Receptor activity was negligible in tissues from patients with either liver cell carcinoma or metastatic tumor. The receptor levels in noncirrhotic and cirrhotic tissues in close proximity to liver cell carcinoma were 2281 +/- 659 and 1134 +/- 473 U/g liver, respectively. There was a close correlation between serum asialoglycoprotein levels and the size of the tumor mass in patients with liver cell carcinoma. Our results suggest that decreases in the asialoglycoprotein receptor levels may lead to an accumulation of serum asialoglycoproteins in patients with cirrhosis or liver cell carcinoma, or both.     

Nephrogenous cyclic AMP in primary hepatocellular carcinoma patients with or without hypercalcaemia

OBJECTIVE: To study the relationship between the excretion of nephrogenous cyclic AMP (NcAMP) and other blood and urine parameters as an index of PTH-like activity in patients with primary hepatocellular carcinoma. DESIGN: After overnight fast, a double voided urine and a blood sample were collected from each subject for determination of various analytes and results compared between various groups. PATIENTS: Fifty-five consecutive untreated patients with primary hepatocellular carcinoma, 14 healthy controls and eight patients with cirrhosis only. MEASUREMENTS: Serum calcium, phosphate, alkaline phosphatase, albumin, creatinine and urinary calcium, creatinine and hydroxyproline were measured by routine methods. cAMP was measured in plasma and urine by a radioimmunoassay (Diagnostic Products Corporation) and PTH measured in serum by an immunoradiometric assay (Nichols Institute). TmP/GFR, NcAMP etc. were calculated according to various published methods. RESULTS: Four out of 55 patients (7%) with primary hepatocellular carcinoma had hypercalcaemia. These four patients had significantly lower (P less than 0.05) phosphate, PTH and TmP/GFR and elevated NcAMP (P less than 0.001) compared with normocalcaemic hepatocellular carcinoma and cirrhotic patients, and healthy controls. The excretion of hydroxyproline and calcium was significantly elevated (P less than 0.001) in the hypercalcaemic patients. Bone resorption was found to be the major cause of hypercalcaemia in three of the four hypercalcaemic patients. Fifteen hepatocellular carcinoma patients (29%) with normocalcaemia had suppressed PTH. CONCLUSION: We conclude that a PTH-like humoral factor such as PTH related peptide is the cause of hypercalcaemia in patients with primary hepatocellular carcinoma, and that in some normocalcaemic patients with this tumour PTH is suppressed.