Alpha-fetoprotein changes in the course of chronic hepatitis: relation to bridging hepatic necrosis and hepatocellular carcinoma

To examine the frequency and significance of alpha-fetoprotein (AFP) elevation, radioimmunoassay for AFP was performed every 3-6 months in a prospective follow-up study on 432 hepatitis B surface antigen (HBsAg)-positive and 105 HBsAg-negative patients with clinicopathologically proven chronic hepatitis. In a period of 6-85 months (mean 26.9 +/- 16.8), AFP elevation (greater than 20 ng/ml) was recorded in 45.6% of the HBsAg-positive patients. In addition, 19.4% of the HBsAg-positive patients had AFP levels greater than 100 ng/ml, with a highest level of 2520 ng/ml in the absence of hepatocellular carcinoma (HCC). All these figures were much greater than those for HBsAg-negative patients (P less than 0.001). Most episodes of AFP elevation were transient, with parallel moderate SGPT elevation (greater than 200 IU/L). The AFP levels in such episodes correlated closely with the presence of bridging hepatic necrosis, only weakly with peak SGPT levels, but not with age, sex or hepatitis B e antigen/antibody status. None of the transient episodes was followed by subsequent development of HCC. On the other hand, AFP elevation (greater than 100 ng/ml) without parallel SGPT elevation could predict the presence of HCC with very high specificity (98.7%). However, the sensitivity was not high enough (66.7%) for one to rely solely on AFP for the detection of HCC at its earlier stage.     

Alpha-L-fucosidase as a serum marker of hepatocellular carcinoma in Thailand

To evaluate the role of serum alpha-L-fucosidase (AFU) in the diagnosis of hepatocellular carcinoma (HCC), we simultaneously studied both AFU activity and alpha-fetoprotein (AFP) level in 60 patients with HCC, 60 patients with cirrhosis and chronic hepatitis each, 30 patients with other liver tumors and 60 healthy subjects. Serum AFU activity in patients with HCC (1,418.62 +/- 575.76 nmol/ml/hr) was significantly higher than that found in cirrhosis (831.25 +/- 261.13 nmol/ml/hr), chronic hepatitis (717.71 +/- 205.86 nmol/ ml/hr) or other tumors (706.68 +/- 197.67 nmol/ml/hr) and in controls (504.18 +/- 121.88 nmol/ml/hr, p < 0.05). With 870 nmol/ml/hr (mean value of controls plus 3 standard deviations) considered as the cut-off point, AFU was more sensitive (81.7 vs 39.1%) but less specific (70.7 vs 99.3%) than AFP at a level of > 400 ng/ml as a tumor marker of HCC. With both markers combined, the sensitivity was improved to as much as 82.6%. AFU activity in HCC patients was correlated to tumor size (r = 0.3529, p = 0.006) but not associated with tumor staging classified by Okuda's criteria (p = 0.1). The AFU activity in the viral hepatitis group (hepatitis B or C) was also significantly higher than in the non-viral group (p = 0.0005). We conclude AFU to be a useful marker, in conjunction with AFP and ultrasonography, for detecting HCC, particularly in patients with underlying viral hepatitis and cirrhosis.     

Simultaneous measurements of serum alpha-fetoprotein and protein induced by vitamin K absence for detecting hepatocellular carcinoma. South Tohoku District Study Group

OBJECTIVE: We evaluated the measurements of serum alpha-fetoprotein (AFP) and the protein induced by vitamin K absence (PIVKA-II) in 734 patients with chronic hepatitis (CH) and liver cirrhosis (LC) who had been followed-up for the development of hepatocellular carcinoma (HCC). METHODS: Serum AFP and PIVKA-II were measured every month and abdominal ultrasonography was performed every 3 months. Youden's index (sensitivity + specificity -1) was calculated. RESULTS: On an average follow-up period of 374.5 days, HCC was detected in three HBsAg-positive LC patients (10.0%/yr), four anti-HCV-positive CH patients (1.35%/yr), 21 anti-HCV-positive LC patients (7.8%/yr), and one patient with both HBsAg- and anti-HCV-positive LC (22.7%/yr). At the time of HCC detection, the size of HCC was 4.7+/-0.6 (mean +/- SD) cm in HBsAg-positive patients and 2.4+/-1.3 cm in anti-HCV-positive patents. Cut-off values of 20 ng/ml for AFP (Youden's index = 0.422) and 60 mAU/ml for PIVKA-II (Youden's index = 0.316) gave the highest index for each marker. When these two markers were combined, cut-off values of 40 ng/ml for AFP and 80 mAU/ml for PIVKA-II gave the highest index (Youden's index = 0.500, sensitivity = 65.5%, specificity = 85.5%, positive predictable value = 14.8%, negative predictable value = 98.3%). The levels of AFP or PIVKA-II increased within three months before the detection of HCC. CONCLUSIONS: Simultaneous measurements of serum AFP and PIVKA-II levels that are performed every 3 months are useful for detecting a developing HCC. The optimal cut-off values for AFP and PIVKA-II may be 40 ng/ml and 80 mAU/ml, respectively.     

α-Fetoprotein and Its Concanavalin A Affinity in Acute Exacerbation of Chronic Hepatitis B

Serum samples from 20 patients with acute exacerbation of chronic hepatitis due to hepatitis B virus and 20 patients with hepatocellular carcinoma arising from B viral cirrhosis with elevated levels of alpha-fetoprotein (AFP) were analyzed by affinity column chromatography for concanavalin A binding. Serum AFP was tested at regular intervals in all of these patients. Acute exacerbation was defined as elevation of serum transaminase greater than 300 IU/L in patients with chronic hepatitis B. In hepatocellular carcinoma, serum AFP levels fluctuated but remained higher than 92 ng/ml, whereas, in acute exacerbation of chronic hepatitis B, serum AFP levels returned to normal within 3-12 months of follow-up. The results of concanavalin A-binding assay revealed that AFP from both these groups had a high affinity for concanavalin A, and this assay could not be used to discriminate between the two conditions.     

Racial differences in effectiveness of alpha-fetoprotein for diagnosis of hepatocellular carcinoma in hepatitis C virus cirrhosis

alpha-Fetoprotein (AFP) is frequently used as a diagnostic marker for hepatocellular carcinoma (HCC). Most available data concerning AFP come from studies of patients with chronic hepatitis B or other chronic liver diseases of mixed etiologies. Limited data concerning the diagnostic value of AFP for hepatitis C virus (HCV)-related HCC have to date come only from Asian and European studies, and results are conflicting. There may be significant differences in AFP levels depending on racial backgrounds and etiologies of primary liver disease. We conducted a multicenter, retrospective, case-control study of 163 HCC patients with HCV infection and 149 control patients with HCV-related cirrhosis. The positive likelihood ratios for AFP at 0 to 20, 21 to 50, 51 to 100, and 101 to 200 ng/mL were 0.46, 1.31, 1.15, and 6.90, respectively. No controls had AFP greater than 200 ng/mL. The sensitivity of AFP for the diagnosis of HCC in African Americans with HCV infection was lower than that of patients of all other ethnic groups combined (57.1% vs. 81.6% for AFP > 10 ng/mL, P =.02, and 42.9% vs. 66.0% for AFP > 20 ng/mL, P =.05). The area under the receiver operating characteristics curve was 0.81 for non-African Americans but only 0.56 for African Americans. In conclusion, AFP greater than 200 ng/mL can be used to confirm HCC in patients with HCV-related cirrhosis and a hepatic mass. However, AFP is insensitive for the diagnosis of HCC in African Americans.     

Early detection of hepatocellular carcinoma associated with cirrhosis by ultrasound and alfafetoprotein: a prospective study

A prospective surveillance of hepatocellular carcinoma (HCC) associated with cirrhosis, using alfafetoprotein (AFP) and real-time ultrasonography (US) was carried out in 157 patients with histologically proven cirrhosis. During a two-year follow-up, 15 asymptomatic HCCs were identified. HCCs detected by these methods were at a relatively early stage, as most tumors were small (13 out of 15 less than 5 cm). US was more sensitive than AFP in the diagnosis of HCC when values greater than 400 ng/ml were considered. Patients with initial AFP values greater than 20 ng/ml developed HCC within two years more frequently than patients with values less than 20 ng/ml. A combined approach using US and AFP is suggested in our geographical area.     

Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size

OBJECTIVES: Serum levels of des-gamma-carboxy prothrombin (DCP) and alpha-fetoprotein (AFP) are known to be useful tumor markers for the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to examine the diagnostic efficacy of DCP and AFP in differentiating HCC from chronic liver diseases. METHODS: We examined 1,377 HCC patients and 355 patients with chronic hepatitis or cirrhosis (non-HCC) who visited our institute and affiliated hospitals between June 1997 and September 2003. RESULTS: The median values of DCP and AFP were 60 mAU/mL and 34 ng/mL in HCC patients, respectively, and 18 mAU/mL and 3 ng/mL in non-HCC patients, respectively. The areas under the receiver operating characteristic (ROC) curves of DCP and AFP were 0.812 and 0.887, respectively (p < 0.0001). The area under the DCP ROC curve was significantly smaller than that of AFP in tumors less than 3 cm in diameter (p < 0.0001). However, the ROC area of DCP was significantly larger than that of AFP in tumors greater than 5 cm in diameter (p < 0.0001). CONCLUSIONS: The utility of DCP for the diagnosis of HCC was lower than that of AFP for small tumors, but higher than that of AFP for large tumors.     

The diagnostic value of the assay of des-gamma-carboxy prothrombin in the detection of small hepatocellular carcinoma.

Des-gamma-carboxy prothrombin (DCP) assay was performed by a staphylocoagulase method in 35 consecutive patients with small (less than 5 cm), resectable hepatocellular carcinoma (HCC). They also simultaneously received serum alpha-fetoprotein (AFP) assay. According to diagnostic strategy, patients were divided into two groups. Group I consisted of eight patients who were candidates for a mass screening project for HCC with elevated AFP levels (greater than 20 ng/ml). Five of these patients had an increased DCP level (greater than 6 U/l). Group II included 27 victims of chronic hepatitis B or cirrhosis whose tumors were detected by ultrasonography during regular follow-up. In this group, increased DCP and AFP levels were observed in 11 and 16 cases, respectively. Of 14 patients with smaller HCC (less than 3 cm), only three had elevated DCP levels, while eight patients had an abnormal AFP level. When these two assays were combined, 18 of 27 patients in group II and nine of 14 patients with smaller HCC (less than 3 cm) revealed elevation of one or both of the two markers. A total of 16 out of 35 patients with small HCC had abnormal DCP levels. In conclusion, DCP assay is less sensitive than AFP assay in the detection of small HCC, and the combination of both markers has little complementary effect.     

Elevation of serum riboflavin carrier protein in hepatocellular carcinoma.

Early detection of hepatocellular cancer (HCC), makes it surgically resectable with a potential for cure. The test most commonly used to detect HCC is the measurement of serum alpha-fetoprotein (AFP) levels. However, the AFP test is negative in HCC detection in more than 30% of the cases. Riboflavin carrier protein (RCP) is a growth and developmental protein, synthesized and secreted by the liver and hence was of interest to measure its levels in HCC. A prospective double blind evaluation of RCP levels in serum from 93 subjects was undertaken. These included 22 proven cases of HCC, 25 normal controls, 20 cases of alcoholic hepatitis, 20 cirrhotics, and 6 cases of primary biliary cirrhosis (PBC). RCP was measured by a sensitive and specific radioimmunoassay (RIA). RCP was immunohistochemically localized in paraffin sections of liver specimens using standard methods. Mean serum RCP levels in HCC were 21.75+/-14.66ng/ml and were significantly higher (p<0.0001) than those in normal controls (0.73+/-0.25ng/ml), alcoholic hepatitis (1.92+/-0.82ng/ml), PBC (2.16+/-0.74ng/ml), or cirrhosis (5.02+/-1.52ng/ml). Serum RCP levels were elevated in all 22 HCC cases. In contrast serum AFP levels were elevated in 11 of 22 HCC cases. Immunohistochemical analyses revealed positive staining for RCP in liver tumors. We have previously demonstrated elevation of serum RCP levels in breast adenocarcinoma. Our results suggest that serum RCP levels are significantly elevated in HCC also and could potentially serve as a marker for HCC detection under conditions where breast cancer is ruled out. In combination with AFP, serum RCP levels have the potential of serving as a panel of markers for better detection of HCC.     

血清高尔基体蛋白73诊断肝细胞癌价值探讨

目的评价血清高尔基体蛋白73（GP73）在肝细胞癌（HCC）诊断中的价值。方法选择400例HCC、100例肝硬化（LC）、100例慢性乙型肝炎（CHB）患者和200例健康对照者（HC）,分别采用ELISA和电化学发光法检测血清GP73和甲胎蛋白（AFP）水平;采用受试者工作特征曲线下面积（ AUROC）评估两者对HCC的诊断效能。结果 HCC、CHB和LC患者血清GP73水平分别为243.6±163.1ng/ml、85.6±35.3ng/ml和81.9±36.4ng/ml,均显著高于健康对照组（78.2±33.9ng/ml,P〈0.05）,但在CHB和LC组及HC三组间无统计学差异;GP73和AFP的最佳诊断临界值分别为150.7ng/ml和19.7ng/ml,GP73的AUROC为0.846,灵敏性为69.2%,特异度为90.5%,均显著优于AFP（AUROC为0.828,灵敏性为57.6%,特异度为88.1%,P〈0.05）;GP73与AFP两者联合检测可以进一步提高对HCC的诊断准确性（AUROC为0.887,灵敏性为73.5%,特异度为88.0%）;在AFP阴性与阳性的两组HCC患者中,GP73灵敏性和特异度无显著性差异。结论血清GP73对HCC的诊断效能高于AFP,两者联合检测可以进一步提高诊断效能。     

Evaluation of serum clusterin as a surveillance tool for human hepatocellular carcinoma with hepatitis B virus related cirrhosis

Background and Aim: Hepatocellular carcinoma (HCC) is a common human cancer worldwide. The levels of serum clusterin in HCC patients and its potential diagnostic significance is not clear. We aimed to evaluate the clinical use of serum clusterin levels as a surveillance tool for HCC with hepatitis B virus (HBV) related cirrhosis. Methods: Twenty‐two cases of healthy subjects, 31 cases of HBV carriers, 26 patients with chronic hepatitis B, 29 patients with cirrhosis, and 76 patients with HCC were enrolled in this study. Serum levels of clusterin were measured by a sandwich enzyme‐linked immunosorbent assay. Results: The serum clusterin levels in HCC patients were significantly lower than that in healthy, HBV carriers and chronic hepatitis B, but statistically higher than in cirrhosis patients. Receiver operator characteristic (ROC) curve indicated that a serum clusterin value of 50 µg/mL yielded the best sensitivity (91%) and specificity (83%) for differentiating HCC patients with HBV‐related cirrhosis from those with HBV‐related cirrhosis. The optimal alpha fetoprotein (AFP) cutoff value was 15 ng/mL and was inferior to the clusterin value of 50 µg/mL, the area under the ROC curves being 0.937 versus 0.781, respectively (P < 0.05). Conclusions: Serum clusterin was more sensitive and specific than serum AFP for differentiating HCC patients with HBV‐related cirrhosis from those with HBV‐related liver cirrhosis, and may be a useful surveillance tool of HCC based on HBV‐related cirrhosis.     

Utility of alpha-fetoprotein (AFP) in the screening of patients with virus-related chronic liver disease: does different viral etiology influence AFP levels in HCC? A study in 350 western patients

BACKGROUND/AIMS: Dosage of serum AFP (alpha-fetoprotein) is widely used for HCC screening in patients with chronic liver disease. Virus-related chronic liver disease is the main cause of cirrhosis and HCC in Western and Far Eastern countries, but the relationship between viral etiology and AFP levels in HCC is still unclear. The aim of this study was to verify, in Western patients with post-viral chronic liver disease, the usefulness of AFP dosage for the detection of HCC, and the influence of viral etiology on AFP levels in HCC. METHODOLOGY: The study population included 350 patients with post viral chronic liver disease that underwent liver biopsy, serum AFP determination and ultrasound liver evaluation. Seven patients had normal liver histology, 197 had chronic hepatitis, 72 had cirrhosis, and 74 had cirrhosis and HCC. ROC (receiver operating characteristic) analysis was used to assess the best diagnostic AFP threshold value for HCC detection. Logistic regression analysis was performed to individuate independent predictors of HCC diagnosis. RESULTS: No difference was observed in AFP levels between HCV- and HBV-positive patients, neither in the whole population nor in the HCC patients only. ROC area under curve for AFP was 0.801 (95% CI: 0.721-0.867). The analysis individuated a best accurate AFP threshold value for HCC diagnosis of 50 ng/mL. HCC was detected with specificity > or = 95% only for AFP > 100 ng/mL. The sensitivity however was poor (25%). Male sex, age > 60, and AFP were independent predictors of HCC diagnosis. CONCLUSIONS: Serum AFP levels in HCC patients are not influenced by virus B or C hepatitis pattern. AFP dosage should not be used for HCC diagnosis in non-cirrhotic patients. Male patients with cirrhosis should be regarded with a more "aggressive" screening program compared to females.     

肝细胞癌患者血清Dickopff 1水平对TACE治疗后预后的影响

目的 探讨肝细胞癌患者血清Dickopff相关蛋白1(Dickopff-1)水平对TACE治疗后预后的影响。方法 2016年1月～2018年1月在我院住院经导管动脉化疗栓塞术(TACE)治疗的HCC患者90例,选择同期在我院进行健康体检者90例,慢性乙型肝炎(CHB)患者86例,乙型肝炎肝硬化患者81例,采用ELISA法检测血清Dickopff-1和AFP水平,对HCC患者进行为期24个月的随访,绘制研究对象受试者工作特征曲线(ROC)并计算曲线下面积(AUC),确定血清Dickopff-1和AFP诊断HCC的效能,应用Kaplan-Meier曲线进行生存分析。结果 HCC组血清Dickopff-1和AFP水平显著高于肝硬化组 或CHB组【分别对(0.8±0.1)ng/ml和(12.3±3.0)ng/ml,P<0.05】或健康人【分别对(0.7±0.1)ng/ml和(11.5±2.5)ng/ml,P<0.05】; TACE治疗后HCC患者血清Dickopff-1水平降至(1.6±0.6)ng/ml(P<0.05);有癌栓的HCC患者血清Dickopff-1水平显著高于无癌栓患者;死亡患者血清Dickopff-1水平显著高于生存患者;血清Dickopff-1和AFP单独诊断HCC的AUC分别为0.860和0.618,对HCC都有一定的诊断价值( Z=6.297,P<0.05);血清Dickopff-1和AFP联合应用能提高诊断效能(AUC=0.892),其诊断的灵敏度、特异度和准确度均最高;Kaplan-Meier生存分析显示,高血清Dickopff-1水平患者总体生存率显著低于低水平组(x²=8.418,P<0.05)。结论 HCC患者血清Dickopff-1水平升高,其水平越高,在TACE治疗后预后越差,是否可以作为HCC患者在TACE治疗后疗效和预后判断的指标,值得研究。     

Clinical usefulness of des-γ-carboxy prothrombin assay in early diagnosis of hepatocellular carcinoma

Des--carboxy prothrombin (DCP) was evaluated as a serological marker for hepatocellular carcinoma (HCC), particularly in patients with early HCC. In 1192 patients with various diseases, plasma DCP levels were measured by a newly developed enzyme immunoassay method using an anti-DCP monoclonal antibody. Of the 254 patients with HCC, 143 (56%) had abnormal DCP levels of greater than 0.1 AU/ml. In contrast, elevated DCP levels were rarely observed in patients with chronic hepatitis, liver cirrhosis, metastatic liver cancer, and other malignant tumors. Because no correlation was observed between DCP and -fetoprotein (AFP), the combined measurement of these two complementary markers appears to be useful in the diagnosis of HCC. Since normal levels were observed in 29 of 30 patients (97%) with small liver tumors measuring 2 cm or less in diameter, the diagnostic application of the DCP assay to small liver tumors is limited. However, in patients with tumors larger than 2 cm, the plasma DCP assay may even be more useful than AFP. Among 46 patients with liver cirrhosis or chronic hepatitis who subsequently developed HCC, significantly increased DCP and AFP levels were observed in nine patients (20%) and 14 patients (30%), respectively, when a tumor was detected. When the results of both assays were combined, 19 patients (41%) had elevated levels of one or both markers. Although the plasma DCP assay alone is not sensitive enough to detect early small liver cancers, it could be applied as a complementary tumor marker together with AFP. The use of both these markers together with imaging modalities in the regular follow-up of patients with chronic liver disease who are at high risk for HCC might be of great benefit.This work was supported in part by a grant from the Japanese Society of Hepatology.     

Usefulness of serum alpha-fetoprotein (AFP) as a marker for hepatocellular carcinoma (HCC) in hepatitis C virus related cirrhosis: analysis of the factors influencing AFP elevation without HCC development]

BACKGROUND/AIMS: Serum alpha-fetoprotein (AFP) is frequently used for the diagnosis of hepatocellular carcinoma (HCC). Most available data concerning AFP came from studies of patients with chronic hepatitis B or mixed etiologies. Studies concerning the diagnostic value of AFP for HCV-related liver cirrhosis (LC) are limited. We evaluated the factors influencing AFP elevation in the absence of HCC and analyzed the diagnostic value of serum AFP in HCC surveillance of HCV-related LC patients. METHODS: We enrolled 55 patients of HCV-related LC with HCC and 62 patients without HCC as a case-control study were analyzed. The sensitivity and specificity were calculated and the clinical and biochemical factors influencing serum AFP levels. RESULTS: The sensitivities and specificities of serum AFP for the detection of HCC in HCV-related LC were 72.7% and 59.7% for AFP>or=20 ng/mL, and 47.3% and 92.5% for AFP>or=100 ng/mL, respectively. Elevated serum AST was independently associated with elevated serum AFP level in HCV-related LC. In cases of ASTor=100 ng/mL for the diagnosis of HCC was 100%. However, in case of AST>2 ULN, the specificity was 85.0% for AFP>or=100 ng/mL and 95.0% for AFP>or=200 ng/mL. CONCLUSIONS: Serum AST levels influence serum AFP level in HCV-related LC. In cases of AST2 ULN.     

Risk factors for hepatocellular carcinoma in patients with liver cirrhosis.

OBJECTIVE: Although cirrhosis is known to predispose toward hepatocellular carcinoma (HCC), there is no agreement on the factors that can influence the risk for HCC in patients with cirrhosis. This study was designed to identify differences in cirrhosis-related risk factors for developing HCC in relation to epidemiological characteristics, stage of the disease and etiology. METHODS: 512 patients from southwestern Spain with Child-Pugh stage A or B cirrhosis were examined periodically by ultrasonography, and alpha-fetoprotein (AFP) concentration was measured. RESULTS: The average length of follow-up was 37 months. A total of 52 cases of HCC were detected, which represented a risk of 17% after 5 years of follow-up. The Cox model showed that the risk of HCC increased by 8% per year of increasing age. Male sex (relative risk: 3.4), hepatitis C virus infection (relative risk: 4.6), hepatitis B virus infection (relative risk: 2.9) and AFP levels higher than 15 ng/ml (relative risk: 2.5) were also shown to be risk factors. Among alcoholic patients, only age (risk increased by 15% per year), and hepatitis C virus infection (relative risk: 5.4) were risk factors for HCC. However, in patients infected by hepatitis C virus, the main risk factors were age (relative risk increased by 8% per year), male sex (relative risk: 3.9), co-infection with hepatitis B virus (relative risk: 4.9), and increased AFP (relative risk: 2.8). Of the patients with HCC, 71% were infected with hepatitis C virus. Alcoholism, Child-Pugh stage and duration of cirrhosis did not increase the risk of the appearance of HCC. CONCLUSIONS: The risk of HCC increased to 17% after 5 years of follow-up in patients with Child-Pugh stage A or B cirrhosis. Hepatitis C virus infection was the main risk factor in patients with cirrhosis. Other risk factors were age, male sex, hepatitis B virus infection and altered AFP level.     

Clinical evaluation of plasma des-γ-carboxy prothrombin as a marker protein of hepatocellular carcinoma in patients with tumors of various sizes

We measured des--carboxyprothrombin (DCP) (prothrombin induced by vitamin K absence or antagonist-II, abbreviated as PIVKA-II) by a newly developed enzyme immunoassay using an anti-DCP monoclonal antibody in 665 human subjects, of which 112 were patients with hepatocellular carcinoma (HCC). PIVKA-II was elevated to more than 0.1 AU/ml in 54 of the 112 patients (48.2%) with HCC, while it was positive only in 7.1% of those with liver cirrhosis and 3.1% of those with chronic hepatitis. Three patients with elevated PIVKA-II greater than 0.1 AU/ml who had been diagnosed as having liver cirrhosis by ultrasonography and computed tomography at the start of this study developed a diffuse type of HCC three or six months later, which was detected by angiography. No obvious correlation was observed between plasma PIVKA-II concentration and serum -fetoprotein (AFP) level in HCC patients. Of the 112 HCC patients, 40.2% showed an increase in AFP to above 200 ng/ml. In the remaining patients, 32.8% had a PIVKA-II concentration greater than 0.1 AU/ml. In these patients with a negative or low serum AFP concentration, PIVKA-II proved to be a valuable tumor marker for laboratory diagnosis of HCC. Among them, 59.8% tested positive for PIVKA-II and/or AFP. Thus, combination assay with PIVKA-II and AFP seems useful for increasing the accuracy of laboratory diagnosis of HCC. None of patients with a solitary tumor smaller than 2 cm had elevated PIVKA-II. In patients with larger-sized and multiple HCC, positive results of elevated PIVKA-II were more frequent than those of increased AFP. Thus, the determination of PIVKA-II may be more useful than AFP assay in patients with larger-sized and multiple tumors. The levels of plasma PIVKA-II concentration were higher in patients with larger-sized and multiple tumors than in those with smaller ones. In 20 patients, PIVKA-II decreased significantly after transcatheter arterial embolization (TAE) therapy, and in eight of these 20 patients it normalized after TAE. In conclusion, plasma PIVKA-II might be used as a valuable marker for the diagnosis and screening of HCC, especially in patients with negative or low AFP and in those with larger-sized and multiple tumors. However, its usefulness for mass screening of small HCC is limited.     

血清寡糖链检测对HBV相关肝细胞癌的诊断价值

目的评价寡糖链检测(G-Test)试剂盒(荧光毛细管电泳法)辅助诊断HBV相关肝细胞癌(HCC)的临床价值。方法收集2017年8月-2018年6月就诊于北京佑安医院的患者血清样本310例,其中HBV相关HCC(HCC组)170例,乙型肝炎肝硬化(肝硬化组)50例,慢性乙型肝炎(肝炎组)85例,其他脏器恶性肿瘤(其他恶性肿瘤组)5例。检测血清寡糖链组分的相对浓度,计算并分析G-Test试剂盒在临床诊断中的灵敏度、特异度、总符合率和阳性预测值、阴性预测值,并与血清AFP进行方法学比较。非正态计量资料多组间比较采用Kruskal-Wallis H检验,进一步两两比较使用Dunn’s多重比较,计数资料两组间比较采用χ2检验。利用受试者工作特征曲线(ROC曲线)对诊断效能进行分析,利用logistic回归建立G-Test与AFP联合诊断模型,受试者工作特征曲线下面积(AUC)的比较采用Z检验。结果HCC组患者G值[6.46(5.73~7.07)]明显高于肝炎组[3.38(2.85~4.18)]及肝硬化组[3.99(3.13~5.21)]患者(H值分别为107.9、104.2,P值均<0.001)。HCC组患者AFP的水平明显高于肝炎组患者[0.77(0.45~1.77)log10 ng/ml vs 0.58(0.41~0.89)log10 ng/ml,H=33.65,P=0.025]。G-Test的灵敏度83.53%,特异度为74.29%,总体符合率为79.36%,阳性预测值79.78%,阴性预测值78.79%。G-Test与AFP单独诊断的AUC分别为0.846与0.611,G-Test的AUC明显高于AFP(Z=5.795,P<0.001),G-Test联合AFP诊断的AUC为0.870,明显优于G-Test(Z=2.523,P=0.012)与AFP(Z=6.943,P<0.001)单独诊断效能。HCC早期与中晚期组间G-Test检出率均高于AFP>400 ng/ml检出率(χ2值分别为26.441、38.379,P值均<0.001)。AFP分别以<20、<200、<400 ng/ml为阴性临界值,G-Test在AFP阴性的HCC患者中检出率分别为86.24%、85.93%、85.31%。结论G-Test的灵敏度和特异度较好,具有辅助诊断HCC的临床应用价值,联合AFP诊断效能更好。     

中国北方地区321例乙型肝炎病毒相关肝细胞癌患者的流行病学和临床特征分析

背景:我国是肝细胞癌(HCC)高发区,其中大部分HCC与乙型肝炎病毒(HBV)感染相关,有必要对其自然史和临床进程作大样本调查研究。目的:了解中国北方地区HBV相关HCC患者的流行病学和临床特征。方法:对中国北方地区321例HBV相关HCC患者作流行病学问卷调查,行肝功能、甲胎蛋白(AFP)、HBV血清标志物和HBV DNA水平检测,并进行统计分析。结果:321例HBV相关HCC患者中,仅7.2%接受过抗病毒治疗;46.4%和25.5%分别有肝硬化和肝癌家族史;38.3%有饮酒史。21.0%的患者乙型肝炎e抗原(HBeAg)阳性,62.3%乙型肝炎e抗体(HBeAb)阳性,HBeAg阳性者合并肝硬化的比例和HBV DNA水平较高。84.5%的患者HBV DNA阳性,但其中仅42.6%HBV DNA≥5.0log10,HBV DNA高水平者合并肝硬化的比例显著高于HBV DNA低水平者。无症状HBV感染、慢性乙型肝炎、代偿性和失代偿性肝硬化患者分别占4.1%、24.1%、39.0%和32.9%。71.0%的患者AFP升高,但其中仅33.8?P≥400ng/ml。结论:本组HBV相关HCC患者中,HBeAg阳性和高HBV DNA水平者不多,但病情常较重。肝硬化是HCC的重要危险因素,饮酒和肝癌家族史对HCC的发生有一定影响。血清AFP筛查有助于HCC的诊断。     

Serum alpha-fetoprotein levels and liver histology in patients with chronic hepatitis C

Objective: The clinical and morphological significance of a raised alpha-fetoprotein (AFP) level in patients with chronic hepatitis C is undefined. We sought to determine the relation between serum AFP level and liver histology in this population.
Methods: We reviewed the clinical and histological records of 200 consecutively evaluated patients with chronic hepatitis C whose serum AFP levels were recorded. Two groups were studied: group I = 125/200 (62%) patients with normal AFP, < 10 ng/ml; and group II = 75/200 (38%) patients with raised AFP, > 10 ng/ml. The groups were compared according to age, gender, duration of disease, histology, and history of alcohol abuse.
Results: There was no significant difference in serum AFP based on age, gender, alcohol consumption, or disease duration. Significant histological differences were observed: cirrhosis was present in 57 (45%) patients in group I versus 51 (68%) in group II (   p < 0.001  ). Hepatocellular carcinoma was more frequent in group II (14/75 [19%]) than in group I (1/125 [1%]) (   p < 0.001  ). Ten of 77 (13%) noncirrhotic patients and 51/108 (47%) cirrhotic patients had a raised AFP (   p < 0.002  ; relative risk, 3.262; confidence interval [C.I.], 1.912–5.564). A derived AFP level of 17.8 ng/ml maximized specificity for predicting histological outcome: one of 76 (1.3%), 29/108 (26.8%), and 14/15 (93.3%) patients were noncirrhotic, cirrhotic, or had HCC, respectively. This derived AFP value is 35% sensitive and 98.6% specific for cirrhosis, with a positive predictive value of 97.7%.
Conclusions: A serum AFP level >17.8 ng/ml strongly suggests the diagnosis of cirrhosis in a population of patients with chronic hepatitis C.