Aim
s :. This study evaluated the use and efficacy of chronic oral etoposide plus tamoxifen as a palliative treatment in 30 patients with far-advanced HCC in whom surgical resection, percutaneous ethanol injection or transarterial chemoembolization(TACE) was not possible. Methods : To be eligible for the study, patients had to have
objective
ly measurable or evaluable tumors, adequate hematologic profiles and hepatorenal functions, had to be between 20 and 75 years of age, and had to have an ECOG performance status of less than or equal to 2. The treatment included etoposide, 50 mg/m2/day, taken orally for 21 days, and tamoxifen, 40 mg/day, taken orally for 21 days. Each cycle was repeated every 5 weeks. Results : Two patients(7%) achieved a partial response(PR) and 16 patients(53%) achieved a stable disease(SD) with a median time-to-progression of 5 months(range: 2-24). Median of patients survival with the response of PR or SD and those patients with the response of progressive disease(PD) was 10 months and 7 months, respectively(p=0.0004). Of the 20 patients with initial elevated serum alpha-fetoprotein(≥500 ng/ml), 9 patients(45%) experienced a significant(≥50%) decrease in their values after chemotherapy and all 9 patients achieved
objective
tumor response of more than or equal to SD. Among the 30 patients in the study, 10 patients(33%) achieved performance status improvements of grade according to the ECOG criteria and 6 patients(20%) experienced improvements of subjective symptoms, such as abdominal pain, abdominal fullness and anorexia. Conclusion : Based on our results, the use of chronic oral etoposide plus tamoxifen as a palliative treatment for the far-advanced hepatocellular carcinoma are beneficial. A randomized two-arm study may be warranted to validate the results of this study.(Korean J Hepatol 2000;6:41-51)

Background/Aims
: Hepatocellular carcinoma (HCC) is a malignant tumor with very poor prognosis if left untreated after diagnosis. However, recent advances in digital subtraction imaging techniques and superselective catheterization seem to have somewhat increased the survival rate in patients with HCC after transarterial chemoembolization (TACE). This study analyzed the relationship between prognostic factors and recurrence after TACE, an aspect which has not attracted much attention. Methods : This investigation included 258 cases of HCC with 100% lipiodol uptake who received TACE for a duration of 13 years from 1985 to 1997. Clinical characteristics, biochemical factors, tumoral factors, angiographic characteristics, embolization technique, degree of lipiodol uptake, response, and recurrence factors were analyzed retrospectively. Results : Significant differences in survival were noted among 3 groups according to cancer-free interval (p<0.01). The different factors between early recurrence group (within 6 months) and late recurrence group (after 18 months) were initial tumor size (8.8±4.1/6.1±3.7cm, p<0.01), tumor type (multinodular,massive/single nodule, p<0.01), ill-defined margin (51.4/22.0%, p<0.01), response after TACE (NC/CR,PR, p<0.01), ALP level (196.1±124.5/144.4±72.0 IU/L, p<0.05), absence of encapsulation (42.3/25.0%, p<0.05), portal vein thrombosis (64.3/14.3%, p<0.05), nonsegmental embolization (46.6/25.0%, p<0.05), post-TACE AFP level (180.5±252.1/76.6±329.8 ng/mL, p<0.05), and recurrence pattern (revascularization of initial lesion/single nodule, p<0.05). Conclusions : Recurrence factors were significant in the survival of patients with HCC after TACE. Therefore, an understanding of the relationship between prognostic factors and recurrence is very important for early detection of recurrence and the timely provision of further TACE treatment. (Korean J Hepatol 2000;6:111－123)

Background/Aims
Des-γ-carboxy prothrombin(DCP), a protein induced by vitamin K absence or antagonist-II(PIVKA-II), and Lens culinaris agglutinin-A reactive AFP-L3 have been reported to be useful markers for the diagnosis of hepatocellular carcinoma (HCC). In the present study, both the PIVKA-II and AFP-L3 were analyzed and compared with a conventional AFP to determine its usefulness, specificity and sensitivity in the diagnosis of HCC. Methods: Sera were collected from 108 patients consisting of 17 patients with chronic hepatitis, 22 patients with liver cirrhosis and 69 patients with HCC. The AFP-L3 was determined by an lectin affinity electrophoresis coupled with an antibody-affinity blotting. Level of DCP was measured by an enzyme immunoassay with an anti-DCP monoclonal antibody. Results: The sensitivity and specificity of PIVKA-II and AFP L3 were 49.3% and 89.5%, and 32.5% and 85.7%, respectively. No significant correlation was found between the PIVKA-II or AFP L3 and serum AFP. No correlation was found between the PIVKA-II or AFP L3 and the characteristics of HCC. Conclusion: The determination of plasma DCP and AFP L3 levels combined with AFP levels may be useful especially for the differential diagnosis between HCC and chronic liver diseases without HCC.(Korean J Hepatol 2000;6:205-214)

Background/Aims
Chronic hepatitis has been divided into chronic persistent hepatitis, chronic lobular hepatitis and chronic active hepatitis. These terms should be discontinued in favor of etiologic terminology. The activity of necro-inflammation and the degree of fibrosis should be evaluated for grading the severity and the stage of the disease. In this study, we sought to evaluate the long-term outcome and prognostic factors of chronic hepatitis B according to the new histological classification of chronic hepatitis proposed by the Korean Study Group for the Pathology of Digestive Diseases. Method: One hundred and eighty-eight patients (mean age, 35.0 years; male/female 3.9:1) with biopsy-proven chronic hepatitis B were retrospectively assessed with a mean follow-up of 80.6 months. The patients were divided into a biochemically-active group and a biochemically-inactive group according to serum alanine aminotransferase (ALT) changes during follow-up periods. The development of compensated cirrhosis and hepatocellular carcinoma were investigated during follow-up periods. As well, the liver biopsy specimens of the patients were reviewed according to the new histological classification of chronic hepatitis (grade of lobular activity and porto-periportal activity, stage of fibrosis). Results: Lobular activity and porto-periportal activity correlated with the serum ALT level at the time of biopsy (p<0.05). The development of compensated cirrhosis correlated with porto-periportal activity and stage of fibrosis (p<0.05). The probability of the development of compensated cirrhosis, decompensated cirrhosis and hepatocellular carcinoma increased significantly in the older age group (≥40 years) and the biochemically-active hepatitis group (p<0.01). The risk factors for the development of compensated cirrhosis and decompensated cirrhosis were old age (≥40 years) and biochemically-active hepatitis during follow-up periods. For hepatocellular carcinoma they were old age (≥40 years), male gender and biochemically-active hepatitis during follow up periods by multivariate analysis. Conclusions: The present study suggests that the new histological classification of chronic hepatitis indicates hepatitis activity and the prospect for progression to cirrhosis in chronic hepatitis B. The biochemical hepatitis activity during follow-up periods is the independent prognostic factor for the development of cirrhosis and hepatocellular carcinoma in chronic hepatitis B. Therefore, effective treatment to decrease hepatitis activity may reduce the develoment of cirrhosis and hepatocellular carcinoma.

Purpose
There have been studies concerning prognostic factors in patients with hepatocellular carcinoma (HCC) undergoing transcatheter arterial chemoembolization (TACE) but they reported different prognostic factors from each other. The aim of this study is to determine which prognostic factors contribute to long-term survival after TACE of hepatocellular carcinoma. Material and Method: Two hundred and forty-one patients with HCC who had been treated by TACE were analyzed retrospectively. TACE was accomplished by hepatic arterial infusion of a suspension of lipodol and anticancer drugs (Mitomycin-C and Adriamycin), either alone or followed by gelfoam embolization. Results: Male to female ratio was 4.7:1. Mean survival was 13.98 months. Maximum survival was 101 months. The overall cumulative survival rates at the end of the first and second years were, respectively, 41.54% and 20.06%. According to univariate analysis (log-rank scale test), variables significantly associated with survival were: sex, liver cirrhosis, Child-Pugh classification, gross type of the tumor, location of the tumor, size of the tumor, TNM stage, metastasis, portal vein thrombosis, arterioportal shunt, ascites, AFP, protein, albumin, alkaline phosphatase, AST, AST/ALT ratio, total bilirubin, and sodium. Multivariate analysis (Cox proportional hazard model) for the significant variables in a univarariate analysis revealed that the gross type of the tumor, portal vein thrombosis, and Child-Pugh classification were statistically significant independent prognostic factors. Conclusion: The prognosis of patients with HCC treated with TACE was affected favorably by the nodular type tumor, the patent main and the first-order portal vein, and the good liver function (Child-Pugh class A).

Transcatheter arterial chemoembolization (TACE) is a therapeutic option for unresectable hepatocellular carcinoma. Supraumbilical skin rash is a rare complication of TACE caused by patent hepatic falciform artery. We report herein two cases of supraumbilical skin rash developed after TACE for hepatocellular carcinoma, with discussion on the pathogenesis, prophylaxis, and treatment.

Background/Aims
The incidence of hepatocellular carcinoma has been universally lower in female than in male. The aims of our study are to define whether there are any difference between female and male patients with hepatocellular carcinoma in terms of clinical characteristics and results of treatment. Methods: Retrospective analyses of medical history, physical findings, laboratory results, etiological factors, characteristics of tumor, and therapeutic results were performed in 80 female patients with hepatocellular carcinoma compared to 160 male patients. Results: Asymptomatic presentation and family history of liver disease were found more frequently in female patients than in male patients. A history of smoking and alcohol drinking were found less frequently in female patients than in male patients. The detection rate of spider angioma was significantly lower in female patients than in male patients. There was no difference in laboratory results, characteristics of tumor, and therapeutic results between female and male patients. Conclusions: Environmental factors such as smoking and alcohol drinking could contribute the sexual difference of hepatocarcinogenesis. However, clinical characteristics at the time of diagnosis and therapeutic results were not significantly different between female and male patients with hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE) is widely used to treat inoperable hepatocellular carcinoma and metastatic tumor of the liver. Among the complications occurring after TACE, liver abscess formation in HCC is a fatal complication. The reported incidence of this complication ranges from 0% to 3.3%. Moreover, liver abscess formation in non-tumorous parenchyma is very rare. The pathogenic mechanism of this complication has been linked to several factors but retrograde enteric bacterial contamination of the biliary tract appears to be the most commonly implicated cause. The major risk factors of the biliary tract infection are pneumobilia, portal vein thrombosis, bilo-enteric anastomosis and biliary obstruction. We report a rare case of liver abscess formation in non-tumorous liver parenchyma after TACE for the treatment of hepatocellular carcinoma in a patient with pneumobilia. (Korean J Hepatol 2001;7:189-194)

Combined hepatocellular and cholangiocarcinoma (cHCC-CC) is an uncommon form of primary liver cancer having features of both hepatocellular and billiary epithelial differentiation. We report a case of cHCC-CC that separately developed in a patient who was serologically positive for hepatitis B virus. A 36-year-old woman was diagnosed by ultrasonography with an asymptomatic tumor in the left lobe of the liver. Based on radiologic and serologic findings of elevated serum alpha-fetoprotein (AFP) level, a preoperative diagnosis of hepatocellular carcinoma was made. A left lobectomy of the liver was done. On histological examination, the resected tumor was shown to consist of two separated masses. One was hepatocellular carcinoma that showed immunoreactivity for AFP. The other was cholangio- carcinoma that showed immunoreactivity for cytokeratin-19 (CK-19) in a separate form. (Korean J Hepatol 2001;7:201-205)

Background/Aims
It has been acknowleged that diverse factors such as Hepatitis B or C virus, alcohol, food carcinogens, and environmental or genetic factors are involved in hepatocellular carcinogenesis. In the molecular biologic aspect, suppression of tumor suppressor gene or amplification of oncogene, abnormal regulation of cell cycle-related proteins, abnormal apoptosis mechanism, and diverse growth factors are reported to be factors that contribute to hepatocellular carcinogenesis. In this study, the genetic difference between hepatocellular carcinoma tissue and surrounding non-hepatocellular carcinoma tissue has been investigated to identify genes that are deleted, diminished, amplified, or newly developed in hepatocellular carcinoma using differential gene expression.Method:We studied each of 12 biopsy samples of hepatocellular carcinoma and surrounding non-hepatocellular carcinoma tissues obtained during surgical resections. Random arbitrarily primed-polymerase chain reaction(RAP-PCR) was applied for differential gene expression. The genes that are deleted, diminished, or amplified, newly developed in hepatocellular carcinoma are cloned, sequenced, and then identified by BLAST search, some genes are characterized by eletrophoresis motility shift assay(EMSA) and in situ hybridization. Results:We identified the various, diverse genes classified as tumor suppressor genes, oncogenes, growth factor genes, and some kinds of transcription factors. Some of these genes were identified to be repressed, deleted or diminished, others were amplified, or newly developed in hepatocellular carcinoma tissues.Conclusions:RAP-PCR is a good method in the identification of the gene associated with hepatocellular carcinoma. The result in this study shows that so many genes are different between hepatocellular carcinoma and surrounding non- hepatocellular carcinoma tissues, and that the genes related with hepatocellular carcinogenesis may be predicted. Further studies are necessary for analyzing the relationship between the identification of the gene associated with hepatocellular carcinoma and the diverse factors involved in hepatocellular carcinogenesis. (Korean J Hepatol 2001;7:265-272)

Background/Aims
TRAIL-induced apoptosis was believed to occur in tumor cell lines, while not in normal cells, which suggested that TRAIL might be safe as an antitumor therapy. Some authors advocate that this exclusive TRAIL-induced apoptosis depended on whether or not TRAIL-R3 mRNA was expressed. In this study we investigated the difference in the expression of TRAIL and its receptors mRNA between human hepatocellular carcinoma(HCC) and surrounding liver tissues.Methods:Intra-operative sampling of HCC and paired surrounding liver tissue was performed in 12 patients who underwent hepatic resection due to HCC. After RT-PCR, using total RNA extracts from the tissues, amplified RT-PCR, products were analyzed qualitatively for the expression of TRAIL and its receptors mRNA. Both tissues were compared semi-quantitatively for the expression of TRAIL-R3 mRNA with β-actin using the method of Nicoletti et al.Results:1)TRAIL mRNA was expressed in HCC and surrounding liver tissues in all cases. 2)TRAIL-R1, -R2, and -R3 mRNA were also expressed in HCC and surrounding liver tissues in all cases. 3)The ratio of the expression of TRAIL-R3 mRNA to β-actin mRNA was 0.22±0.15 in HCC and 0.34±0.21 in surrounding liver tissues(p=0.124, paired t-test). 4) TRAIL, TRAIL-R1, -R2 and -R3 mRNA were expressed in all HCC cases irrespective of the degree of tumor cell differentiation.Conclusions:TRAIL, TRAIL-R1, -R2, and TRAIL-R3 mRNA were expressed in all of the HCC and surrounding liver tissues. There was no quantitative difference in the expression of TRAIL-R3 mRNA between both tissues. (Korean J Hepatol 2001;7:273-280)

In hepatocellular carcinoma distant metastasis after curative surgical resection without intrahepatic metastasis is very rare. A 55-year old man presented with a huge pelvic bone mass. Eight years ago he underwent posterior hepatic segmentectomy following diagnosis of hepatocelluar carcinoma. He has received regular check-ups with abdominal ultrasonography and serum alpha-fetoprotein. On admission an MRI on the pelvic area showed an 18×10cm sized lobulated mass invading the pelvic bone and acetabulum. Microscopic examination revealed that the tumor was a well differentiated hepatocellular carcinoma. There was no evidence of intrahepatic recurrence. He was treated with transarterial chemoembolization, external radiotherapy(total 3750 cGy), and systemic chemotherapy using 5-fluorouracil. (Korean J Hepatol 2001;7:315-319)

Hepatocellular carcinoma(HCC) usually spreads to lung, regional lymph node, bone and the other organs by hematogenous, lymphatic route and direct extention at the advanced stage. Extrahepatic metastases from small HCC are, however, rare events. The frequent involving bony metastases are spine, rib and long bone. These are rare in cranial bone. Therefore, a case of small HCC diagnosed by first manifestation of cranial bone metastasis is very rare. We report a case of cranial bone metastasis with left eyelid ptosis from small HCC and review the literature pertaining to this condition.(Korean J Hepatol 2001;7:320-324)

The tumor seeding after percutaneous ethanol injection (PEI) therapy has been considered to be a rare complication in hepatocellular carcinoma. We report a case of needle tract implantation of hepatocellular carcinoma following PEI manifested as subcutaneous nodule. A 57-years old male patient had been treated with PEI for hepatocellular carcinoma. Thirteen months after completion of the PEI session, a subcutaneous nodule was palpated at the site of the needle puncture. A CT scan showed that the subcutaneous nodule was 1.7 cm in size and enhanced in the early phase. The nodule was surgieally removed. Microscopic examination showed hepatocellular carcinoma. (Korean J Hcpatol 2001;7:325 329)

Spontaneous regression of hepatocellular carcinoma is an extraordinarily rare phenomenon. Fewer than 20 occasions have been reported in the English medical literature. There have only been 5 case reports in Korea. Understanding of the mechanism of spontaneous regression of hepatocellular carcinoma will help us to establish new treatments for the disease. In this case report, we present a 53 year-old Asian male who showed spontaneous necrosis of hepatocellular carcinoma confirmed with pathology. He developed a febrile condition secondary to pneumonia for 2 weeks. After that hepatocellular carcinoma was observed to have been necrosed on an MRI scan and hepatic angiography. A right lobectomy of the liver was done because the possibility of residual microscopic cancer cells could not be ruled out. The pathologic finding confirmed the spontaneous near-total necrosis of hepatocellular carcinoma. The patient has recovered uneventfully and has been followed up for 7 months.(Korean J Hepatol 2001;7:330-335)

Background/Aims
About 15% of Korean hepatocellular carcinoma(HCC) are negative both of Hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (anti-HCV)in their sera. They can be classified as a non-B, non-C hepatocellular carcinoma group(NBNC group). The aims of our study were, firstly, to describe the clinical characteristics of Korean NBNC HCC and compare them with those of HBsAg-positive HCC(HBV group) and anti-HCV-positive HVV(HCV group). Secondly we wanted to assess the frequency of viremia of HBV, HCV and transfusion-transmitted virus(TTV)in NBNC HCC patients. Methods : we prospectively collected clinical data and sera from 113 NBNC HCC patients and performed PCR for HBV DNA, HCV RNA and TTV DNA. We also collected clinical data from 125 HBsAg-positive HCC patients during a similar period. Results : The mean age of the NBNC HCC group was 59 years, in-between that of the HBV and the HCV groups. A History of heavy alcohol drinking was found in 48% of the NBNC HCC group. This was significantly higher than that of the HBV group, but similar to that of the HCV group. Serum α FP level in the NBNC HCC group was more frequently in the normal range compared to that in the HBV and HCV groups. The detection rates of HBV DNA, HCV RNA and TTV DNA in the NBNC HCC group were 17%, 13% and 67% respectively. Conclusions : The NBNC HCC patients seemed to comprise a heterogeneous group of various etiologies and clinical presentations. About one third of these patients displayed evidence of viremia of HBV or HCV. (Korean J Hepatol 2001;7 :439- 448)

Background
/ Aim : We identified risk factors for hepatocellular carcinoma(HCC)through a nine-year follow-up study, ending last year, of 4,339 patients with chronic liver disease. The aim of this study was to establish an individual prediction model according to risk factors for the development of HCC. Methods : We studied a total of 1994 patients who had regular check-ups from January 1990 to December 1998. We analyzed the risk factors and established the individual prediction model to predict the risk rate for HCC using logistic regression analysis. We applied the model to patients who were enrolled over the next two years. Results : 90(9.05%) out of 994 patients developed HCC during a mean of 33 months of follow-up. The risk index for individual patients was made by considering the relative risk level of statistically significant risk factors. From 1999 to 2000, 480 patients were newly enrolled and divided into a low risk group(less than 5% probability), an intermediate risk group(5% to 10% probability), and a high risk group(more than 10% probability). According to this classification, 1 of 191 patients in the low risk group(0.523%), 5 of 176 patients intermediate risk group(2.84%), and 21 of 113 patients in the high risk group(18.6%) were diagnosed with HCC. Conclusion : We confirmed the reliability of the newly established individual prediction model for the screening of HCC. This model may help screening programs to be done effectively by focusing on high risk groups for HCC. (Korean J Hepatol 2001;7 :449- 458)

Background
/Aim: Although hepatocellular carcinoma(HCC) shows poor prognosis, transcatheter hepatic arterial chemoembolization(TACE) can improve survival rate in some patient groups. This study investigated the synergy effect of the different clinical indices on the survival time in patients with HCC underwent TACE. Materials and Methods: A retrospective study of 241 patients with HCC who underwent TACE with a mixture of lipiodol, mitomycin-C and driamycin, alone or followed by gelfoam was conducted. Three different survival groups (A, less than 6 months; B, between between 6 and 23 months; and C, over 24 months) were compared. Results: Alkaline phosphatase was lowest in group C(p=0.0001). The longer the survival, the lower (p=0.027, p=0.007) the AST and AST/ALT ratio were. Albumin was higher (p=0.032), GGT and LDH were lower (p=0.003, p=0.002) in the long-term survival group. The long-term survival group revealed an absence of both ascites(p<0.002) and portal vein thrombosis(p<0.001), and lower TNM stage (P<0.0001). The single nodular type of HCC was more frequent (P<0.0001) and the size of tumor was smaller in the long-term survival group (P<0.0001). Child-Pugh class was lower in the long-term survival group (p=0.017). The higher serum albumin and elder age, the higher albumin and the lower alkaline phosphatase or alpha-fetoprotein, represented synergic effects on a long term survival. The higher albumin and the smaller size or the lower tumor stage, the higher albumin and platelet revealed similar synergy effects. Although the age or platelet is high, low albumin showed poor prognosis. Conclusion: Patients with small-sized single, nodular HCC in a low Child-Pugh class without evidence of ascites and portal vein thrombosis, and the higher level of serum albumin but lower levels of alpha-fetoprotein, alkaline phosphatase, GGT, and LDH, can expect a long-term survival over 24 months by the treatment of TACE. There are meaningful synergies of the different clinical variables affecting the survival times in the patients with HCC undergoing TACE.(Korean J Hepatol 2002;8:189-200)

Background/Aims
E-cadherin is involved in intercellular binding and cellular polarity formation. β-catenin plays a fundamental role in regulation of the E-cadherin cell adhesion complex. The abnormalities of the components of the complex may disrupt this adhesive function. We investigated the expression patterns of E-cadherin and β-catenin to determine the clinical significance of these proteins in hepatocellular carcinoma. Materials/Methods: Thirty-six hepaticellular carcinoma tissues and adjacent non-tumor specimens were analyzed. Subcellular distribution of E-cadherin and β-catenin was examined by immunohistochemistry staining. We evaluated the patterns of the expression, and investigated the relationship with the cause of HCC; level of AFP; TNM stage; tumor size; growth types; metastasis; differentiation grade of HCC; and presence of portal vein thrombosis. Results: Immunohistochemistry showed that all non-tumor tissues had membranous type staining of E-cadherin. All non-tumor tissues showed cytoplasmic type staining of β-catenin, but no β -catenin accumulation in nuclei was found. 58% (21/36) of HCC showed positive expression of E-cadherin in cytoplasmic membrane. The cytoplasmic expression of β-catenin in HCC was 83% (30/36); nuclear expression in 14% (5/36); and no staining in 3% (1/36). Nuclear β-catenin expression was observed in none (0/4) of the well-differentiated HCC; 17%(3/9) of moderate-differentiated HCC; and 17%(2/6) of poorly-differentiated HCC. There were no relationships between E-cadherin and β-catenin expression with other clinicopathologic factors. Conclusions: Loss of cytoplasmic staining of E-cadherin and nuclear accumulation of β-catenin were observed in HCC. Nuclear accumulation of β-catenin was not found in well differentiated HCC but was found in poorly differentiated HCC. (Korean J Hepatol 2002;8:297-303)

Background/Aims
Protein induced by vitamin K absence or antagonist II (PIVKA-II) appears to be a useful tumor marker for the evaluation of patients with hepatocellular carcinoma (HCC). But the usefulness of PIVKA-II was not yet clear in Korea where hepatitis B-virus is endemic. We investigated the usefulness of PIVKA-II in the diagnosis and follow-up after treatment of HCC. Methods: We studied patients with HCC which was pathologically confirmed. PIVKA-II was measured by enzyme immunoassay. PIVKA-놳 levels before and after treatment, in correlation with imaging studies, were analyzed for the comparison of treatment responses. Kappa index was obtained. Results: A total of 129 patients were included. 93 patients (72%) were HBsAg positive. 86 patients (67%) were PIVKA-II >40 mAU/mL. 52 patients (40%) were AFP >20 ng/mL and 77 patients (60%) were AFP 20 ng/mL. Of 77 patients, 40 patients (52%) showed PIVKA-II >40 mAU/mL. 68 of 129 patients were evaluated treatment response. On the basis of radiologic response, CR was 33, PR 17, SD 12, and PD 6. Of the 33 radiologic CR patients, 30 patients were CR and 3 patients were PR by means of PIVKA-II response. Of the 17 radiologic PR patients, 6 patients were CR and 7 patients were PR. Therefore, tumor responses by radiologic and PIVKA-II were well correlated (Kappa index was 0.59). Conclusions: PIVKA-II can be used as a useful tumor marker for patients with HCC, especially those with low levels of AFP, before and after treatment in Korea. (Korean J Hepatol 2002;8:465-471)

Background/Aims
[¹⁸F]FDG-PET is a functional imaging modality reflecting cellular glucose metabolism. In most malignant cells, accumulation and trapping of [¹⁸F]FDG allows the visualization of increased uptake compared with normal cells. The aim of this study was to assess the value of PET in differentiating benign from malignant hepatic lesions and to determine in which types of hepatic tumors PET can help evaluate stage, monitor response to therapy, and detect recurrence. Methods: Eighty patients with liver lesions were enrolled (hepatocellular carcinoma 34, cholangiocarcinoma 8, metastatic liver cancer 25, hemangioma 6, liver abscess 7). Liver metastases were 22 adenocarcinoma, 2 lymphoma, 2 squamous cell carcinoma. The PET images of these patients were analyzed. SUV and lesion-to-normal liver background SUV ratio were obtained and compared among the disease groups. Results: All liver metastases and all cholangiocarcinomas had increased uptake value, with SUV ratios greater than 2. Hepatocellular carcinoma had SUV ratios greater than 2 in 20 of 34 patients (59%). All hemangiomas had poor uptake, a SUV ratio of less than 2. All liver abscesses showed definite uptake. Conclusions: The PET technique using FDG static imaging was useful in differentiating malignant from benign lesions of the liver in limited situations. Limitations included false negative results in some patients with hepatocellular carcinoma. Liver abscesses raised problems in differential diagnosis from malignant liver tumors. The findings of this study suggest that the PET technique might be applied in tumor staging and the detection of recurrence, as well as monitoring responses to therapy for all adenocarcinomas and some hepatocelluar carcinomas. (Korean J Hepatol 2002;8:472-480)

Hepatocellular carcinoma is one of the most common causes of death in Koreans. Most cases of hepatocellular carcinoma are beyond the stage of curative resection at the time of diagnosis due to extrahepatic metastasis as well as wide distribution of tumor in the liver. The lung is the most common site of extrahepatic metastasis but metastasis to gingiva is very rare in hepatocellular carcinoma. We report a case hepatecellular carcinoma with gingival methststasis in a 59 year old male patient.(Korean J Hepatol 2002;8:495-499)

Background/Aims
Tamoxifen has been tried in patients with hepatocellular carcinoma (HCC), however, its inhibitory mechanism remains unknown. In this study, we evaluated the effects of tamoxifen on HCC cell growth and the expression of transforming growth factor-β1 (TGF-β1) which had been known as an important cytokine in growth of HCC. Methods: Hep 3B cells were cultivated in estrogen free media with 0.1μM, 0.5μM, 1μM, 5μM, and 10μM of tamoxifen for 6 days. Viable cells were counted daily and the TGF-β1 concentrations in supernatant were measured by ELISA method. Results: The number of viable HCC cells increased rather significantly after the treatment of tamoxifen of lower concentration (0.1μM) compared with that of the control (2.59×10⁷ vs. 1.97×10⁷; p<0.05). As the concentration of treated tamoxifen was higher, the number of viable HCC cells became gradually less, resulting in the significant decrease of it at the highest concentration (10μM) compared with that of the control (1.40×10⁷ vs. 1.97×10⁷; p<0.05). TGF-β1 concentration in supernatant of tamoxifen-treated samples was significantly decreased compared with those of controls, regardless of the amount of treated tamoxifen. Conclusions: These results suggest that tamoxifen may suppress TGF-β1 expression to an extent, although it has different effects on the proliferation of HCC cells, at the various concentrations of this agent in vitro. Such effects of tamoxifen on TGF-β1 expression may inhibit the growth and progression of HCCs over-expressing TGF-β1 in vivo.(Korean J Hepatol 2002; 9:10-16)

Background/Aims
It is still unclear whether Super Paramagnetic Iron Oxide-Magnetic Resonance Imaging (SPIO-MRI) is a clinically useful imaging modality for patients with hepatocellular carcinoma (HCC). This study searched for the clinical usefulness and limitations of SPIO-MRI with respect to tumor detection capacity, false positive and negative rate, and early recurrence rate. Methods: From December 1999 to February 2001, 218 patients who were surgical candidates by 3-phase dynamic helical CT (3dHCT) were enrolled. We reviewed the medical records and radiologic findings, retrospectively, and postulated the post-operative pathologic findings and the early recurrences within 3 months as the standards for the true positive lesion. Results: The mean number of nodules detected by SPIO-MRI was significantly more numerous than that of 3dHCT (p<0.01). Modifications of treatment strategy due to the discordant findings between SPIO-MRI and 3dHCT for tumor resectability were observed in 22 (10.1%) out of 218 patients. Early recurrences were observed in 10 patients (7.8%). The false positive and negative rates of SPIO-MRI were 6.3% and 13.3%, respectively. Conclusions: We demonstrated that the tumor detection rate of SPIO-MRI was better than that of 3dHCT. Given the relatively acceptable false positive and negative rates, SPIO-MRI could be an appropriate preoperative imaging modality for patients with HCCs.(Korean J Hepatol 2002;9:17-24)

It is our great pleasure to announce that the Taehan Kan Hakhoe Chi (The Korean Journal of Hepatology) was approved for listing, from 2002, in the Index Medicus, Medline/PubMed of the National Library of Medicine, NIH of USA. Herein, I review the searching tools employing a Medical Subject Heading (MeSH) such as liver disease and liver neoplasm or an author index for this Journal in the PubMed at a website. Of course, The Korean Journal of Hepatology should be continually striving to be upgraded. Dream comes true.(Korean J Hepatol 2003; 9:35-41)

Background/Aims
To determine the treatment modalities and the prognosis of a patient with liver cirrhosis, quantitative estimation of liver function is important. We assessed the Child-Pugh score (CPS), the common method as a severity index for the cirrhosis, the Promthombin, -GT, and Apolipoprotein A1 (PGA) index and model for end-stage liver disease (MELD) score. The purpose of this study was to evaluate the correlation between these indices in the patients with cirrhosis only and hepatocellular carcinoma (PHC), according to underlying causes (HBV and alcohol). Methods: We reviewed medical records of 339 cirrhotic patients with/without hepatocellular carcinoma and divided patient groups by disease and underlying cause: cirrhosis caused by alcohol; LC-Al, cirrhosis caused by HBV; LC-B, hepatocellular carcinoma with cirrhosis caused by alcohol; HCC-Al, hepatocellular carcinoma with cirrhosis caused by HBV; HCC-B. We assessed the CPS, PGA index and MELD score and calculated the correlation coefficient between these scores. Results: Among the total of 339 patients, 201 patients were diagnosed on the liver cirrhosis only, and 138 patients on the hepatocellular carcinoma with cirrhosis. In each groups, mean score values were not significantly different in CPS, PGA index and MELD score. The correlation of CPS, PGA index and MELD score in all groups, except for the correlation of PGA index and MELD score in HCC-Al group, was significantly positive (p<0.05). Compared to correlation coefficients between three indices, the patients with cirrhosis only had higher tendencies than the patients with hepatocellular carcinoma. The patients by HBV had higher tendencies than by alcohol. Conclusions: The correlations between CPS, PGA index and MELD score showed significantly positive correlations in the patients with liver cirrhosis only and hepatocellular carcinoma with cirrhosis (except in HCC-Al group). The patients with cirrhosis only had higher correlation coefficients than the patients with PHC and the patients by HBV had higher than by alcohol.(Korean J Hepatol 2003;9:107-115)

Background/Aims
Screening for hepatocellular carcinoma (HCC) is a common practice in the endemic countries but its exact role has not been fully investigated. The purpose of this study was to determine whether screening can achieve early diagnosis and survival benefits. Methods: All HCC patients diagnosed at our hospital (September 1994∼April 2000) were enrolled; They were divided into two groups; a pre- screening group screened with alpha-fetoprotein and ultrasound for longer than 6 months before diagnosis and a non pre-screening group. We compared the tumor size, portal vein thrombosis, and stage at initial diagnosis and survival rate between the two groups. Results: A total of 247 patients were enrolled. 64 were in the non pre-screening group and 183 were in the non pre-screening group. The tumor size at initial diagnosis in the pre-screening group was smaller than in the non pre-screening group (2.6±2.0 cm vs. 5.7±4.1 cm, p<0.05). The percentages of patients with stage I, II, III, and IV were 42.2%, 20.3%, 14.1%, 23.4% in the pre-screening group and 8.7%, 19.7%, 36.6%, 35.0% in the non pre-screening group. A significantly higher proportion in the pre-screening group had earlier stage compared with the non pre-screening group (p<0.05). Portal vein thrombosis in the pre-screening group was noticed as significantly less than in the non pre-screening group (9.4% vs. 26.8%, p<0.05). Among Child A patients, the cumulative survival rate in the pre-screening group was significantly higher than in the non pre-screening group (1 year; 91.4% vs. 70.7%, 2 year; 71.5% vs. 59.9%, p<0.05). Conclusions: Screening with AFP and US is a useful tool for early diagnosis of HCC, especially with improved survival in Child A patients.(Korean J Hepatol 2003;9:116-123)

Background/Aims
Immunogene therapy is extensively studied for a therapeutic modality of various cancers. This study was conducted to investigate the efficacy of immunogene therapy using the T-cell costimulatory molecule and human B7-1 (CD80, hB7-1) in an in vivo human hepatocellular carcinoma (HCC) model. Methods: The stable HCC cell line expressing hB7-1 gene was established using retroviral vector (Huh-7/hB7-1). Of fourteen BALB/c nude mice, 7 were subcutaneously injected with 2×10⁶Huh-7/hB7-1 cells, while the other 7 were injected with 2×10⁶Huh-7/mock cells as a control group. After the injection, the mice were observed weekly for three months for subcutaneous tumor formation. Assay for natural killer (NK) cell cytotoxicity and serum IFN-γ was performed at 1 and 2 weeks after inoculation. Results: In BALB/c nude mice inoculated with Huh-7/hB7-1 cells, no tumor growth was observed. BALB/c nude mice inoculated with Huh-7/hB7-1 cells showed significantly increased NK cell activities of splenocytes compared with those with Huh-7/mock cells. Serum IFN-γ was not measurable at 1 week, but significantly increased at 2 weeks after inoculation to the level of 470 pg/ml in BALB/c nude mice with Huh-7/mock cells and 521 pg/ml in BALB/c nude mice with Huh-7/hB7-1. Conclusions: Our results demonstrate the in vivo anti-tumor immunity and NK cell activation by transfer of hB7-1 gene into human HCC in xenogeneic BALB/c nude mice model. This approach may provide a tool for the development of immunogene therapies against human malignant tumors.(Korean J Hepatol 2003;9:124-134)