BACKGROUND/AIMS: Glypican-3 (GPC3) protein is highly expressed in hepatocellular carcinoma (HCC) tissue. It has been suggested as a diagnostic biomarker, but its inconsistent performance means that it requires further assessment. We therefore investigated the diagnostic value of the plasma GPC3 level compared to the alpha-fetoprotein (AFP) level as a diagnostic biomarker of HCC. METHODS: We enrolled 157 consecutive patients with newly diagnosed HCC and 156 patients with liver cirrhosis (LC) as the control group. GPC3 plasma levels were measured using two commercially available enzyme-linked immunosorbent assays (ELISAs, named as Assay 1 and 2), and AFP levels were measured using an enzyme-linked chemiluminescent immunoassay. The diagnostic accuracy was analyzed using the receiver operating characteristics (ROC) curve. RESULTS: Plasma GPC3 levels in HCC patients were very low (0–3.09 ng/mL) in Assay 1, while only 3 of the 157 patients (1.9%) showed detectable GPC3 levels in Assay 2. The median GPC3 level was not significantly elevated in the HCC group (0.80 ng/mL) compared with the LC group (0.60 ng/mL). The area under the ROC curve (AUC) for GPC3 was 0.559 in Assay 1. In contrast, the median AFP level was significantly higher in HCC (27.72 ng/mL) than in LC (4.74 ng/mL), with an AUC of 0.729. CONCLUSION: The plasma level of GPC3 is a poor diagnostic marker for HCC, being far inferior to AFP. The development of a consistent detection system for the blood level of GPC3 is warranted.
Aged ; Aged, 80 and over ; Area Under Curve ; Biomarkers, Tumor/blood ; Carcinoma, Hepatocellular/*diagnosis/pathology ; Enzyme-Linked Immunosorbent Assay ; Female ; Glypicans/*blood ; Humans ; Liver Neoplasms/*diagnosis/pathology ; Male ; Neoplasm Staging ; ROC Curve ; alpha-Fetoproteins/*analysis

BACKGROUND/AIMS: The aim of this study was to evaluate the feasibility of alpha-fetoprotein (AFP) as a diagnostic tool for hepatocellular carcinoma (HCC) in Korean patients. METHODS: We retrospectively reviewed the medical records of HCC and cirrhosis patients at three hospitals. For each HCC patient, a cirrhosis patient matched for age, sex, etiology, and Child-Pugh classification was selected by simple random sampling. The performance of AFP in the diagnosis of HCC was determined using receiver operating characteristic curve analysis. RESULTS: A total of 732 patients with HCC or cirrhosis were selected for each case and the control groups. The mean age was 54 years, and 72.4% of patients were male. The mean serum AFP levels in the HCC group and cirrhosis group were 3,315.6 and 117.2 ng/mL, respectively (p < 0.001). The area under the receiver operating characteristic curve for all HCC patients was 0.757. The sensitivity, specificity, and positive predictive value of AFP was 50.55%, 87.70%, and 80.43%, respectively, at a cut-off of 20 ng/mL; 37.70%, 95.90%, and 90.20%, respectively, at a cut-off of 100 ng/mL, and 30.05%, 97.27%, and 91.67%, respectively, at a cut-off of 200 ng/mL. A cut-off of 100 ng/mL was more sensitive than one of 200 ng/mL with equivalent specificity and positive predictive value. CONCLUSIONS: The cut-off AFP value for early-stage HCC was 17.4 ng/mL. Our study cautiously suggests that AFP has a role in the diagnosis of HCC, and that the appropriate value of AFP for the diagnosis of HCC may be 100 ng/mL rather than 200 ng/mL.
Aged ; Area Under Curve ; Carcinoma, Hepatocellular/*blood/*diagnosis/pathology ; Feasibility Studies ; Female ; Humans ; Liver Neoplasms/*blood/*diagnosis/pathology ; Male ; Middle Aged ; Neoplasm Staging ; Predictive Value of Tests ; ROC Curve ; Republic of Korea ; Retrospective Studies ; alpha-Fetoproteins/*analysis

OBJECTIVETo assess the value of detecting peripheral blood circulating tumor cells (CTCs) in the diagnosis and treatment of hepatocellular carcinoma (HCC).

METHODSA total of 296 patients diagnosed with HCC admitted in our department from July 2013 to January 2015 were analyzed, with 39 patients with benign liver disease serving as the control group. The distribution of CTCs in the peripheral blood of HCC patients were detected by CanPatrol(TM) CTCs, and its relationship with the clinical features and prognosis of the patients were analyzed.

RESULTSs CTCs were detected in 64.5% (191/296) of the HCC patients but in none of the control group (P<0.05). Positive CTCs in peripheral blood of HCC patients were significantly correlated with serum AFP level, tumor number, TNM stage, BCLC stage, portal vein tumor thrombus and metastasis (P<0.05). In 127 HCC patients receiving radical surgery, the patients positive for CTCs showed significantly shorter relapse-free survival time (P<0.05).

CONCLUSIONPositive CTCs in the peripheral blood may indicate a poor prognosis in HCC patients. CTCs may serve as a indicator for monitoring the prognosis of HCC.

Carcinoma, Hepatocellular ; blood ; diagnosis ; Case-Control Studies ; Humans ; Liver Neoplasms ; blood ; diagnosis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neoplastic Cells, Circulating ; Portal Vein ; pathology ; Prognosis

Recent studies have shown that circulating microRNAs are a potential biomarker in various types of malignancies. The aim of this study was to investigate the feasibility of using serum exosomal microRNAs as novel serological biomarkers for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We measured the serum exosomal microRNAs and serum circulating microRNAs in patients with CHB (n=20), liver cirrhosis (LC) (n=20) and HCC (n=20). Serum exosomal microRNA was extracted from 500 mul of serum using an Exosome RNA Isolation kit. The expression levels of microRNAs were quantified by real-time PCR. The expression levels of selected microRNAs were normalized to Caenorhabditis elegans microRNA (Cel-miR-39). The serum levels of exosomal miR-18a, miR-221, miR-222 and miR-224 were significantly higher in patients with HCC than those with CHB or LC (P<0.05). Further, the serum levels of exosomal miR-101, miR-106b, miR-122 and miR-195 were lower in patients with HCC than in patients with CHB (P=0.014, P<0.001, P<0.001 and P<0.001, respectively). There was no significant difference in the levels of miR-21 and miR-93 among the three groups. Additionally, the serum levels of circulating microRNAs showed a smaller difference between HCC and either CHB or LC. This study suggests that serum exosomal microRNAs may be used as novel serological biomarkers for HCC.
Adult ; Aged ; Biomarkers, Tumor/blood/genetics ; Carcinoma, Hepatocellular/blood/diagnosis/*genetics ; Exosomes/genetics ; Female ; Gene Expression Profiling ; Humans ; Liver/pathology ; Liver Neoplasms/blood/diagnosis/*genetics ; Male ; MicroRNAs/blood/*genetics ; Middle Aged

Tumor lysis syndrome is rare in hepatocellular carcinoma (HCC), but it has been reported more frequently recently in response to treatments such as transcatheter arterial chemoembolization (TACE), radiofrequency thermal ablation (RFTA), and sorafenib. Tumor lysis syndrome induced by low-dose steroid appears to be very unusual in HCC. We report a patient with hepatitis-C-related liver cirrhosis and HCC in whom tumor lysis syndrome occurred due to low-dose steroid (10 mg of prednisolone). The patient was a 90-year-old male who presented at the emergency room of our hospital with general weakness and poor oral intake. He had started to take prednisolone to treat adrenal insufficiency 2 days previously. Laboratory results revealed hyperuricemia, hyperphosphatemia, and increased creatinine. These abnormalities fulfilled the criteria in the Cairo-Bishop definition of tumor lysis syndrome. Although the patient received adequate hydration, severe metabolic acidosis and acute kidney injury progressed unabated. He finally developed multiple organ failure, and died 3 days after admission. This was a case of tumor lysis syndrome caused by administration of low-dose steroid in a patient with HCC.
Acute Kidney Injury/pathology ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Carcinoma, Hepatocellular/*pathology/therapy ; Chemoembolization, Therapeutic ; Creatinine/blood ; Humans ; Liver Neoplasms/*pathology/*therapy ; Male ; Niacinamide/analogs & derivatives/therapeutic use ; Phenylurea Compounds/therapeutic use ; Steroids/adverse effects/therapeutic use ; Tomography, X-Ray Computed ; Tumor Lysis Syndrome/*diagnosis/drug therapy

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) may be one of the important causes of cryptogenic hepatocellular carcinoma (HCC). The aim of this study was to evaluate whether patients with cryptogenic HCC share clinical features similar to that of NAFLD. METHODS: Cryptogenic HCC was defined as HCC that occurs in patients with the following conditions: HBsAg(-), anti-HCV(-), and alcohol ingestion of less than 20 g/day. All patients diagnosed with cryptogenic HCC from 2005 to 2012 (cryptogenic HCC group), and all patients diagnosed with HBV associated HCC between 2008 and 2012 (HBV-HCC group) were enrolled in the present study. Clinical features, BMI, lipid profiles, presence of diabetes mellitus, hypertension, and metabolic syndrome were compared between the two groups. RESULTS: Cryptogenic HCC group was composed of 35 patients (19 males and 16 females) with a mean age of 70+/-11 years. HBV-HCC group was composed of 406 patients (318 males and 88 females) with a mean age of 56+/-7 years. Patients in the cryptogenic HCC group were older (p=0.001) and female dominant (p=0.042) than those in the HBV-HCC group. There were no differences in the laboratory test results including lipid profiles and Child-Turcotte-Pugh class between the two groups. Patients in the cryptogenic HCC group had higher prevalence of diabetes (37% vs. 17%, p=0.015), hypertension (49% vs. 27%, p=0.051), metabolic syndrome (37% vs. 16%, p=0.001), and higher BMI (25.3 kg/m2 vs. 24.1 kg/m2, p=0.042) than those in the HBV-HCC group. The tumor stage was more advanced (stage III and IV) at diagnosis in the cryptogenic HCC group than in the HBV-HCC group (60% vs. 37%, p=0.007). CONCLUSIONS: Cryptogenic HCC has clinical features similar to that of NAFLD and is diagnosed at a more advanced tumor stage.
Age Factors ; Aged ; Body Mass Index ; Carcinoma, Hepatocellular/*diagnosis/etiology/pathology ; Diabetes Complications ; Diabetes Mellitus/pathology ; Female ; Hepatitis B/complications ; Humans ; Hypertension/complications ; Lipids/blood ; Liver Neoplasms/*diagnosis/etiology/pathology ; Male ; Metabolic Syndrome X/complications ; Middle Aged ; Neoplasm Staging ; Non-alcoholic Fatty Liver Disease/*diagnosis/pathology ; Risk Factors ; Severity of Illness Index ; Sex Factors

BACKGROUND/AIMS: We compared the accuracy and usefulness of clinical diagnostic criteria for hepatocellular carcinoma in a hepatitis B virus (HBV)-endemic area. METHODS: We reviewed the medical records of 355 patients who had undergone liver resection or biopsy at our institution between January 2008 and December 2009. These patients were reevaluated using four noninvasive diagnostic criteria for hepatocellular carcinoma proposed by the European Association for the Study of the Liver (EASL), the American Association for the Study of Liver Diseases (AASLD), the Korean Liver Cancer Study Group and the National Cancer Center (KLCSG/NCC), and National Comprehensive Cancer Network (NCCN) guidelines. RESULTS: The overall sensitivity was highest using the KLCSG/NCC criteria (79.8%), followed by the AASLD (51.5%), EASL (38.4%), and NCCN (10.1%; P<0.001) criteria, whereas the specificity (84.5-98.3%) and positive predictive value (96.2-98.3%) were similar for all of the criteria. The KLCSG/NCC criteria had an acceptable false-positive rate and the highest sensitivity among all of the patients, including those positive for HBsAg, those without liver cancer, and those with a tumor of at least 2 cm. CONCLUSIONS: The KLCSG/NCC and AASLD criteria exhibited the highest sensitivity, and all four guidelines had a high specificity among all of the patients. Based on the sensitivity and false-positive rate, the KLCSG/NCC criteria was the most useful in the majority of patients. Inclusion of HBV infection in the clinical diagnostic criteria for hepatocellular carcinoma would be reasonable and may lead to an improvement in the sensitivity, with acceptable false-positive rates, in HBV-endemic areas.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular/*diagnosis/etiology/pathology ; Female ; Hepatitis B/complications/*diagnosis/epidemiology ; Hepatitis B Surface Antigens/blood ; Hepatitis C/diagnosis/epidemiology ; Humans ; Liver/pathology ; Liver Neoplasms/*diagnosis/etiology/pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Practice Guidelines as Topic ; Predictive Value of Tests ; Retrospective Studies ; Risk Factors ; Tomography, X-Ray Computed ; Young Adult ; alpha-Fetoproteins/analysis

Parvovirus B19 infection is known to cause chronic anemia in immunocompromised hosts, including organ transplant recipients. We report the first case of liver transplant recipient with parvovirus B19-induced pure red cell aplasia in Korea. A 57-yr-old female patient with hepatocellular carcinoma due to hepatitis C virus received a liver transplantation. Two months later, anemia developed and she received periodic red blood cell transfusions. However, chronic anemia persisted and bone marrow examination was performed 8 months after transplantation. Bone marrow aspiration smears showed markedly reduced erythroid precursors with atypical giant pronormoblasts and nuclear remnants with viral inclusions, and characteristic lantern cells were observed in biopsy sections. In addition, parvovirus B19 DNA PCR was positive. She was diagnosed as parvovirus B19-induced pure red cell aplasia and her anemia was improved following intravenous immunoglobulin therapy.
Blood Transfusion ; Bone Marrow/pathology ; Carcinoma, Hepatocellular/etiology/therapy ; DNA, Viral/analysis ; Female ; Hepatitis C/complications/diagnosis ; Humans ; Immunocompromised Host ; Immunoglobulins/therapeutic use ; Liver Neoplasms/etiology/therapy ; Liver Transplantation ; Middle Aged ; Parvoviridae Infections/complications/*diagnosis ; *Parvovirus B19, Human/genetics ; Red-Cell Aplasia, Pure/*diagnosis/therapy/virology

OBJECTIVETo study the correlation between hepatocellular carcinoma (HCC) and serum Golph2 protein.

METHODSGolph2 gene was cloned by RT-PCR using RNA from WBF44 cell line as template, the point mutations of the cloned sequence were corrected by PCR, then the gene (1206 bp) was cloned into pET-21 plasmid, and the resulted plasmid was transformed into E.coli DH5a. The expression of 6xHis and Golph2 fusion protein was induced by isopropylthio-beta-D-galactoside (IPTG). The expression of fusion protein was detected by SDS-PAGE and Western blot, and was purified by Ni NTA chelating agarose. The rabbit antibody against Golph2 protein was obtained by immunizing 2 rabbits with the purified Golph2 protein. The specificity and titer of the antibody was determined by Western-blot and ELISA respectively. Sandwich ELISA was used to detect the level of serum Golph2 protein.

RESULTSThere were two replacement mutation and 1 deletion mutation in the cloned sequence contrasted to NM177937 in Genbank, including 644(T-->C, L-->P) , 970 (G-->A, V-->I) and 802 G deletion. The sequence was completely reversed by PCR. The sequence of Golph2 gene cloned into expression vector was confirmed by DNA sequencing. SDS-PAGE and Western blot analysis showed that Golph2 protein was expressed in E.coli DH5a. The antiserum could bind to the 52 kD recombinant protein and serum 73 kD protein specifically. The mean A450 value of ELISA for serum Golph2 protein were significantly higher in HCC and other liver diseases than that in control groups. The sensitivity and specificity for HCC were 44.5% and 82.0%, respectively, at the cut off value is more than or equal to 0.40.

CONCLUSIONThe polyclonal antibody against Golph2 protein is specific. The level of serum Golph2 is significantly higher in patients with HCC and other liver diseases than that in healthy controls.

Animals ; Antibodies, Monoclonal ; analysis ; immunology ; Base Sequence ; Biomarkers, Tumor ; blood ; Carcinoma, Hepatocellular ; diagnosis ; metabolism ; pathology ; Cell Line, Tumor ; Cloning, Molecular ; Enzyme-Linked Immunosorbent Assay ; methods ; Escherichia coli ; genetics ; Genetic Vectors ; genetics ; Humans ; Liver Neoplasms ; diagnosis ; metabolism ; pathology ; Male ; Membrane Proteins ; biosynthesis ; blood ; genetics ; immunology ; metabolism ; Molecular Sequence Data ; Polymerase Chain Reaction ; Rabbits

Carcinoma, Hepatocellular ; diagnosis ; pathology ; DNA ; blood ; DNA Methylation ; Humans ; Liver Neoplasms ; diagnosis ; pathology ; Polymerase Chain Reaction ; methods