Hepatocellular carcinoma occurring in a Crohn��s disease patient

We report a case of hepatocellular carcinoma (HCC) occurring in a patient with Crohn’s disease (CD) without chronic hepatitis or liver cirrhosis, and review the clinicopathological features of HCC in CD patients. A 37-year-old Japanese man with an 8-year history of CD and a medication history of azathioprine underwent resection of a liver tumor. The histopathology of the liver tumor was pseudoglandular type HCC. In the non-neoplastic liver, focal hepatocyte glycogenosis (FHG) was observed, however, there was no evidence of liver cirrhosis or primary sclerosing cholangitis. Only nine cases of HCC in CD patients have been reported previously in the English-language literature. Eight of 10 cases (including the present case) had received azathioprine treatment, and four of these cases also showed FHG, which is considered a preneoplastic liver lesion, within the non-neoplastic liver. Although the precise mechanism of the development of HCC in CD patients is controversial, these results suggest that azathioprine therapy and FHG in the non-neoplastic liver contribute to the development of HCC. These findings also indicate that it is important to survey CD patients treated with prolonged azathioprine therapy for potential liver tumors.     

Hepatocellular Carcinoma Occurring in a Patient with Crohn’s Disease Treated with Both Azathioprine and Infliximab

Hepatocellular carcinoma is known to be associated with underlying liver diseases, such as cirrhosis, hemochromatosis, and chronic viral hepatitis. All reported cases of hepatocellular carcinoma in association with Crohn’s disease involve patients treated previously with azathioprine or both azathioprine and steroids. However, hepatocellular carcinoma associated with the use of azathioprine and infliximab has not been reported. In this report, we describe an unusual case of hepatocellular carcinoma and focal hepatic glycogenosis (FHG) occurring in a non-cirrhotic Crohn’s disease patient who has been treated with both azathioprine and infliximab.     

Elevation of endoglin (CD105) concentrations in serum of patients with liver cirrhosis and carcinoma

OBJECTIVE: Liver cirrhosis is considered as a premalignant state, as about 80% of hepatocellular carcinoma (HCC) is associated with liver cirrhosis. Although alpha-fetoprotein (AFP) has a high negative predictive value, its sensitivity for detecting HCC is poor. The aim of this study was to evaluate circulating endoglin (CD105) in the serum of patients with liver cirrhosis and at high risk for HCC. METHODS: CD105 and AFP serum concentrations were measured in 70 healthy and 94 nonliver-diseased controls and 130 patients with chronic liver diseases and HCC, respectively. RESULTS: Fifty-seven liver cirrhotic patients, 45 patients with liver cirrhosis plus HCC, 19 liver fibrosis patients and nine patients with HCC only were studied. Serum CD105 is significantly elevated in liver cirrhotic patients compared with healthy (P<0.0001) and nonliver-diseased controls (P<0.0001). Patients with liver cirrhosis and HCC show the highest CD105 concentrations being significantly elevated in comparison to liver cirrhosis (P=0.0006) and HCC only (P=0.0134). A stronger positive correlation exists between CD105 and AFP in the patient group suffering from liver cirrhosis and HCC (r=0.479, P=0.0015) than the obtained correlation between both markers in the group of patients diagnosed with liver cirrhosis alone (r=0.358, P=0.0073). The logistic regression model identified CD105 as an independent marker (P=0.0077, odds ratio 1.3). CONCLUSION: CD105 has the potential to be a novel complementary biomarker that has some important bearing on the risk assessment for development of HCC in cirrhotic patients.     

Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis

We describe six patients with non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). From 1990 to 2001, we treated 82 patients with NASH and observed six patients (three men and three women, aged 56-72 years) in this group who were referred with HCC or developed the complication during follow-up. In five of these six patients, NASH was associated with obesity (cases 3, 4 and 5), hyperlipidemia (case 5), or diabetes mellitus (cases 1, 3 and 6). We confirmed the presence of HCC by ultrasonography-guided tumor biopsy or surgery except in case 3 where we diagnosed the tumor by ultrasonography, computed tomography and selective hepatic arteriography. The carcinomas measured 1.5-6.0 cm in diameter and three were well differentiated. When HCC was diagnosed, cirrhosis was present in all instances. Four of the six tumor patients also had esophageal varices but only one patient had a history of variceal bleeding and ascites. Treatment of HCC consisted of surgery (cases 1 and 5), transcatheter arterial embolization or infusion and/or percutaneous ethanol injection (cases 2, 3, 4, and 6). In patients with NASH cirrhosis, the development of treatable HCC is sufficiently common to warrant regular screening for this grave complication.     

Hepatocellular Carcinoma Associated with AlcoholicLiver Disease: A Clinicopathological Study and Genetic Polymorphism of Aldehyde Dehydrogenase 2

In this paper, we describe a clinicopathological study of primary hepatocellular carcinoma (HCC) associated with alcoholic liver disease without hepatitis virus infection. In 180 HCC patients who were admitted to Asahikawa Medical College Hospital from 1987 to 1995, 10 patients (6%) had HCC associated with pure alcoholic liver disease (AI-HCC), whereas the HCC in 165 patients was associated with chronic viral liver diseases, in 2 with primary biliary cirrhosis, in 1 each with coexistence of the hepatitis C virus infection and hemochromatosis, and in 2 with cirrhosis of unknown origin. In the AI-HCC group, all patients were male. The diagnosis of HCC was obtained at the age of 54 to 67 years old, and the duration of ethanol intake was 33 to 40 years. Four cases had a history of temperance. As an underlying liver disease, liver fibrosis was found in three cases and liver cirrhosis in seven cases. HCC was diagnosed histologically in all cases. Serum α-fetoprotein and PIVKA-II were positive in patients with advanced HCC. In cases with small HCC, the tumor was resected surgically in three cases and percutaneous ethanol injection was performed in two cases. In four cases with small HCC, the patients were alive without tumor recurrence during the observation period. In advanced HCC, transcatheter arterial chemolipiodolization was performed. In the analysis of genetic polymorphism of ALDH 2, all AI-HCC had ALDH 2¹/2¹.     

Transforming growth factor α immunoreactivity. A study in hepatocellular carcinoma and in non-neoplastic liver tissue

Background. Transforming growth factor alpha (TGFα) is an important mitogen that binds to epidermal growth factor receptor and is associated with the development of several tumors.Aims. Assessment of the immunoexpression of TGFα in hepatocellular carcinoma (HCC) and in non-neoplastic liver tissue and its relationship to morphological patterns of HCC.Material and methods. The immunohistochemical expression of TGFα was studied in 47 cases of HCC (27 multinodular, 20 nodular lesions). Five lesions measured up to 5 cm and 15 lesions above 5 cm. Thirty-two cases were graded as I or II and 15 as III or IV. The non-neoplastic tissue was examined in 40 cases, of which 22 had cirrhosis. HBsAg and anti-HCV were positive in 5/38 and 15/37 patients, respectively. The statistical analysis for possible association of immunostaining of TGFα and pathological features was performed through chi-square test.Results. TGFα was detected in 31.9% of the HCC and in 42.5% of the non-neoplastic. There was a statistically significant association between the expression of TGFα and cirrhosis (OR = 8.75, 95% CI = [1.93, 39.75]). The TGFα was detected more frequently in patients anti-HCV(+) than in those HBsAg(+). The immunoexpression of TGFα was not found related to tumor size or differentiation. In conclusion the TGFα is present in hepatocarcinogenesis in HBV negative patients. Further analysis is needed to examine the involvement of TGFα in the carcinogenesis associated with HCV and other possible agents. In addition, TGFα has an higher expression in hepatocyte regeneration and proliferation in cirrhotic livers than in HCC.     

Pathological observations of sinusoid lining endothelial cells and the basement membrane in human hepatocellular carcinoma

OBJECTIVE : To observe changes in sinusoid lining endothelial cells (SEC), type IV collagen (CoIV) and laminin (LM) in chronic liver disease and hepatocellular carcinoma (HCC). To assess the clinicopathological significance of these changes in HCC. METHODS : Thirty specimens were taken from 30 cases of HCC (together with corresponding non‐cancerous tissues), 10 cases of liver cirrhosis, five cases of mild chronic hepatitis and and four cases of normal liver tissues. The specimens were tested for CD34, CoIV and LM by using immunohistochemical methods. CD34, CoIV and LM were semiquantitatively analyzed and assessed in the context of the clinical and pathological features of HCC. RESULTS : CD34 and LM were not present along the sinusoidal walls in normal human liver, however, CoIV was weakly and discontinuously distributed along the sinusoidal walls. In cirrhosis, positive expression of CoIV increased significantly in the sinusoidal walls and became continuous and homogeneous. CD34 and LM were weakly present in the perinodules in a few cases of cirrhosis with obvious inflammatory infiltration. Hepatocellular carcinoma showed a diffuse capillarization, with overexpression of CD34, CoIV and LM. CoIV and LM expression were reduced in poorly differentiated HCC and HCC with portal vein thrombosis. This was frequently accompanied by breaks and losses in the basement membrane. The expression of CD34 in tumors of < 2 cm in diameter was significantly lower than that in tumors of > 5 cm in diameter. The expression of CD34 and LM was markedly increased in HCC compared with non‐cancerous liver tissues. CONCLUSIONS : Diffuse capillarization with overexpression of CD34, CoIV and LM are features of HCC. Frequent breaks in, loss of and decrease of the basement membrane in poorly differentiated tumors and tumors with portal vein infiltration suggests potential metastasis of tumor cells and may play a major role in the metastasis of HCC. CD34 is a useful marker for distinguishing HCC from non‐cancerous liver tissues.     

Two cases of patients with hepatocellular carcinoma (HCC) that developed in cryptogenic cirrhosis suggestive of nonalcoholic steatohepatitis (NASH) as background liver disease after clinical courses of 26 years]

We report two cases of patients with hepatocellular carcinoma (HCC) that developed in cryptogenic cirrhosis suggestive of nonalcoholic steatohepatitis (NASH) as background liver disease. Case 1 was a 68-year-old woman, and case 2 was a 46-year-old man. They were admitted to our department for evaluation and treatment of HCC. The causes of the underlying liver disease were not determined from blood tests. However, histological analysis of non-tumor tissues of the liver revealed cirrhosis with few fat droplets. Both patients had undergone liver biopsy 26 years before the treatment of HCC. Histological review of the biopsy specimens revealed NASH (case 1) and fatty liver (case 2), respectively. It was suggested that these cases progressed from NASH and fatty liver, respectively, to NASH-related cirrhosis (so called burned-out NASH), eventually, developing HCC. These findings suggest that substantial number of burned-out NASH cases may be included in those with cryptogenic cirrhosis. These two patients are indicative cases that may reveal the long-term natural course of fatty liver and NASH.     

Diarrhea as a presenting symptom of hepatocellular carcinoma

The clinical manifestations of hepatocellular carcinoma (HCC) are highly nonspecific since they usually mimic those of hepatic cirrhosis, which frequently underlies this neoplasm. The fact that some HCC patients present with severe diarrhea, an unusual symptom in liver cirrhosis, prompted us to determine the prevalence of diarrhea in a series of 23 consecutive HCC patients and compare it with that of a control group formed by cirrhotic patients without HCC, matched by age, sex, and etiology of the liver disease. All the patients were interviewed about the existence of diarrhea (defined as the presence of three or more loose stools per day appearing over three or more days) in the three months prior to admission. Both groups of patients were similar in regards to the degree of liver failure and presence of diarrhea-favoring factors. By contrast, diarrhea was significantly more frequent among HCC cases than among cirrhotics without HCC (47.8% vs 8.7%, P less than 0.005). HCC patients with diarrhea exhibited higher alkaline phosphatase and bilirubin levels and worse liver function, assessed by the Child-Pugh's classification, than patients without diarrhea. However, neither tumor size, vascular invasion, or the degree of tumor differentiation were significantly different between these two groups of HCC patients. These results show that diarrhea is a frequent manifestation of HCC in patients with cirrhosis. Therefore, the development of HCC in these patients should be suspected upon the appearance of diarrhea.     

肝癌、肝硬化组织中GrB、CD57、CD3阳性细胞的表达研究

目的探讨颗粒酶B(GrB)+、CD+57、CD+3细胞在原发性肝细胞癌(HCC)、癌旁、肝硬化及正常肝组织中的数量、分布及意义.方法 HCC60例、单纯性肝硬化62例、正常肝组织23例,以免疫组化SP法进行GrB、CD57、CD3染色,对阳性细胞数进行定量分析.结果①各组GrB+细胞平均数从高到低为癌旁、HCC、正常肝、肝硬化(P＜0.05);各组CD+57细胞平均数从高到低为HCC、癌旁、正常肝、肝硬化(P＜0.05);各组CD+3细胞平均数从高到低为癌旁、HCC、肝硬化、正常肝(P＜0.05).②HCC中CrB+细胞、CD+57细胞、CD+3细胞与组织学分级均无明显关系.③HCC中CrB+细胞、CD+57细胞随临床分期的发展有下降趋势(P＜0.05);HCC中CD+3细胞平均数与临床TNM分期无关.④HCC中15月内有转移组的CrB+、CD+57、CD+3细胞数均少于无转移组(P＜0.01).结论 GrB+、CD+57、CD+3细胞可作为反映机体抗肿瘤特异性细胞免疫状态及判断预后的重要指标.     

Hepatocellular carcinoma with nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) was originally believed to be a benign disease. However, it has been recently revealed that NASH could lead to irreversible liver disease in some patients. We report an unusual case of hepatocellular carcinoma (HCC) in a 76-year-old man with NASH. He had no history of alcohol consumption, drug use, or blood transfusion. He was negative for all serological viral markers and autoantibodies. In addition, he was obese (body mass index [BMI], 30.75kg/m²) and had type 2 diabetes mellitus. A liver biopsy specimen showed moderate steatosis with necroinflammatory changes, ballooning degeneration, Mallory bodies, pericellular fibrosis, and evidence of nodular regeneration. He was diagnosed with NASH with cirrhosis. Simultaneously, a liver tumor, measuring 19mm in diameter, was detected in segment 6. A tumor biopsy specimen revealed well-differentiated HCC, and imaging modalities confirmed the characteristics of HCC. To our knowledge, ten patients who had HCC with NASH were reported. In all patients with NASH and HCC, cirrhosis was present. Patients with NASH and cirrhosis may progress to HCC, and regular screening, based on tumor markers and imaging modalities, is needed to detect HCC in patients with NASH and cirrhosis.     

Expression of vascular endothelial-cadherin in human hepatocellular carcinoma tissues

Aim: Angiogenesis is important in tumor growth and progression to metastasis. Vascular endothelial (VE)-cadherin is an endothelial cell-specific cadherin required for angiogenesis, but its expression in hepatocellular carcinoma (HCC) tissues has not been examined. Methods: Expression of VE-cadherin was analyzed in 31 HCC frozen tissue specimens by immunohistochemical and immunoelectron microscopic procedures. In addition, the association of its expression with clinicopathological parameters was investigated to determine the possible diagnostic or predictive value of VE-cadherin expression in neoplastic and non-neoplastic liver lesions. Results: Immunoreactive VE-cadherin expression was faint or barely detectable on sinusoidal endothelial cells of normal liver but was evident on sinusoidal or capillary endothelium of chronic hepatitis, cirrhosis, and HCC tissues. VE-cadherin expression was more intense on capillary endothelium of HCC tissues in 26 (84%) of 31 patients than on sinusoidal endothelium of surrounding non-tumorous liver tissues with chronic liver diseases. The intensity or intracapillary extent of positive stain for VE-cadherin on capillary endothelium of HCC tissues was significantly associated with tumor size, capsular invasion and tumor cell differentiation in HCC. Conclusions: Intense VE-cadherin expression was evident in capillary endothelium of HCC tissues, giving the first indication of association with clinicopathological features of HCC patients.     

Occurrence of HCC in asymptomatic HCV-related chronic hepatitis

Patients with persistently normal ALT affected with HCV-related chronic hepatitis exist. The natural history of liver disease in these patients was demonstrated to be very slow and progression to cirrhosis likely absent. The case we report describes the occurrence of hepatocellular carcinoma (HCC) in a patient with persistently normal ALT affected with mild chronic hepatitis. This observation suggests that asymptomatic carriers of HCV may develop HCC that is not related to underlying liver cirrhosis.     

Minor Role of Hepatitis B and C Virus Infection in the Etiology of Hepatocellular Carcinoma in a Low-Endemic Area

Background: The etiologic role of hepatitis B (HBV) and C virus (HCV) for hepatocellular carcinoma (HCC) in a low-endemicity area is obscure. Methods: Patients suspected of having primary liver cancer (PLC) in Göteborg, Sweden (n = 113), were tested serologically for HBV surface antigen and antibodies to HBV surface and core antigens. The presence of HBV surface and core antigens in cancer and non-neoplastic liver tissue in HCC cases was investigated immunohistochemically. Antibodies to HCV were tested by third-generation tests. The prevalence of HBV and HCV infection was compared in 73 patients with HCC and 32 patients with a final diagnosis other than PLC. Results: No patient had signs of chronic HBV infection. Seven of 64 (11%) HCC patients were anti-HCV-positive, compared with 1 of 31 (3%) without PLC. All seven patients with HCC and HCV infection had liver cirrhosis, and two were alcoholics. Alcoholism was judged the commonest (42%) cause of cirrhosis. Conclusion: Contrary to areas with a high incidence of HCC, chronic viral hepatitis, particularly HBV, seems to play a minor etiologic role for HCC in Sweden compared with alcohol-related cirrhosis.     

Increased levels of tissue inhibitor of metalloproteinase-1 in human hepatocellular carcinoma.

BACKGROUND: Invasion and metastasis of hepatocellular carcinoma (HCC) are regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). However, the role of TIMPs in these processes is not clear. AIM: To examine the potential involvement of TIMP-1 in HCC and the association between TIMP-1 and clinical outcome of patients with HCC. METHODS: The study included 91 patients who underwent surgical removal of HCC. TIMP-1 concentrations in the supernatant of tissue homogenates of HCC and non-neoplastic liver were measured by enzyme immunoassay. The relationships between TIMP-1 concentration and various clinicopathological features and recurrence of HCC after surgical operation were examined. RESULTS: The mean level of TIMP-1 in HCC (486 +/- 610 ng/mg protein, +/- SD) was significantly higher than in the non-neoplastic liver (75 +/- 69, P < 0.0001). The median level of TIMP-1 in poorly differentiated HCCs (701 ng/mg protein) was significantly higher than in well- (80) and moderately (172) differentiated HCCs (P = 0.0047 and P = 0.0082, respectively). TIMP-1 level in liver cirrhosis was higher than in chronic hepatitis (P = 0.0015). TIMP-1 levels in HCC did not influence the recurrence rate of HCC. CONCLUSIONS: TIMP-1 concentration in HCC was higher than in non-neoplastic liver and correlated with the differentiation grade of HCCs. However, tissue TIMP-1 concentration does not seem to be an important determinant of HCC recurrence.     

Hepatitis E virus re-infection accelerates hepatocellular carcinoma development and relapse in a patient with liver cirrhosis: A case report and review of literature

BACKGROUNDHepatitis E virus (HEV) superinfection is a suspected promoting factor for hepatocellular carcinoma (HCC) in patients with chronic hepatitis and cirrhosis. However, to date, very few cases of HEV-related HCC have been reported. Nevertheless, the role of HEV re-infection in cirrhotic liver without other chronic hepatitis infections has rarely been explored.CASE SUMMARYA 53-year-old male farmer was diagnosed with liver cirrhosis and splenomegaly in August 2016, accompanied with negative HEV-IgM and positive HEV-IgG. No evidence of hepatitis B virus or hepatitis C virus infection was found. Since then the patient was evaluated for liver function and viral parameters every 3 mo. In June 2017, the patient presented severe fatigue with whole body itching and was diagnosed with HCC. Afterwards this patient experienced quick HCC development, progression, relapse, and metastasis in the following 8 mo, and presented persistent dual positivity of HEV-IgM and HEV-IgG. This patient had a long history of smoking and alcohol consumption.CONCLUSIONThis unique case invokes the importance of HEV surveillance and treatment among cirrhotic patients, HCC cases, and blood donors.     

Diabetes: One of Few Remarkable Differences in Clinicopathologic Features Between Cirrhotic and Noncirrhotic Swedes With Hepatocellular Carcinoma

The prognosis of hepatocellular carcinoma (HCC) is usually very poor, so increased knowledge of clinicopathologic characteristics and etiologic factors may improve the clinical handling. Because HCC in many patients is unrecognized before death, it is of particular interest to study cases from a period with a high autopsy frequency. The records and liver biopsies from all patients with a diagnosis of primary liver cancer in Göteborg, Sweden, during a 22-year period were scrutinized. Only patients with evaluable non-neoplastic liver tissue were included in the final analysis. The majority (95%) of 478 HCC cases were autopsied and cirrhosis of the liver could be established in 71%. At presentation, general paramalignant symptoms such as malaise, weight loss, anorexia, and hepatomegaly (84%) were common irrespective of cirrhosis. Alcoholism and diabetes mellitus were each significantly more common among cirrhotics (29% and 20%, respectively; P < .001), than among noncirrhotics, in which cholelithiasis was more common (54%; P < .001). The correlation between diabetes and cirrhosis was independent of reported alcoholism. In an unselected population in a low HCC incidence area, there are few differences in clinicopathologic features between cirrhotic and noncirrhotic patients. Diabetes mellitus seems to play an etiologic role in HCC in cirrhotics, and cholelithiasis in noncirrhotics.     

Clinicopathological study of juvenile hepatocellular carcinoma

Clinicopathological analyses were performed on 11 cases of juvenile (less than 40 years) hepatocellular carcinomas (HCC) and compared with those of 187 cases of nonjuvenile HCCs. 91% of juvenile HCC cases were positive for HBsAg in their sera and it was much higher than that of nonjuvenile group (p less than 0.05). Familial clustering of HBV carriers or advanced liver diseases was found in 50%. 73% of juvenile HCC cases had cirrhosis. Abdominal pain was found most frequently as initial symptom. All except one case, who had surgical resection of the tumor, were rapidly fatal. Interestingly the association of paraneoplastic syndrome (PNS) was more frequently seen in juvenile HCC cases (36.3%) than in nonjuvenile HCC ones (5.9%, p less than 0.05). In juvenile HCC cases with PNS, LC was less associated, serum alphafetoprotein tested higher and prognosis was worse than those without PNS. Therefore, these results imply that HBV plays an important role for the development of juvenile HCC and juvenile HCC patients with PNS show characteristic features in HCC patients in Japan.     

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。     

Leucocyte adherence inhibition assay for immunodiagnosis of hepatocellular carcinoma

Hematocytometer leucocyte adherence inhibition (LAI) assays were performed with hepatocellular carcinoma (HCC) tissue extract and liver cirrhosis extract as nonspecific antigens. Titration experiments revealed that the optimal extract concentration was 200 mu protein/ml. The LAI assays were positive in 28 of 39 HCC cases (71.8%). All three small liver carcinoma cases were positive. LAI assays were negative in all other cancer cases. In the false negative cases (n=11), serum total bilirubin was significantly elevated (p less than .05) and the number of peripheral blood lymphocytes significantly decreased (p less than .005) compared with the positive cases. LAI assays using extracts of human hepatocellular cell line (HUH-6) as antigen were positive in 18 of 27 (66.7%) patients. The results were negative in all liver cirrhosis patients and normal individuals. Furthermore, LAI assays were negative in all HCC and liver cirrhosis patients with extracts of Grawitz's tumor cell line. These results show that the hematocytometer LAI assay using a human culture cancer cell line as a tumor antigen might be useful for diagnosing HCC.