Objective: To study the protective and therapeutic antitumor immunity against hepatocellular carcinoma (HCC) with the fixed-tumor vaccine.Methods: A tumor vaccine consisting of fixed tumor cells or fixed tumor fragmen...Objective: To study the protective and therapeutic antitumor immunity against hepatocellular carcinoma (HCC) with the fixed-tumor vaccine.Methods: A tumor vaccine consisting of fixed tumor cells or fixed tumor fragments combined with sustained-releasers of cytokines and a non-toxic adjuvant was developed. C57BL/6J mice were immunized intra-dermally with the vaccine on day 0 and 7, followed by intrahepatic challenge with live Hepa 1–6 cells.Results: All of 15 nonimmunized control mice developed the hepatoma. Protection of mice immunized with fixed Hepa 1–6 cells and both of IL-2/GM-CSF microspheres or further mixed with TiterMax Gold reached 80% and 87%, respectively. Mass growth of the established tumors, vaccinated twice at 5 mm in diameter, the tumor of control animals continued to grow. However, 7–10 days after the second injection of the tumor vaccine, the tumor growth was suppressed in 9 of 10 mice and then markedly reduced. Complete tumor regression was observed in 60% (6/10) of mice. Splenocytes from the control mice were not able to lyse target Hepa 1–6 cells and other tumor cells. In contrast splenocytes from the vaccinated mice exhibited a 41% lytic activity against the Hepa 1–6 cells tested at an effector/target (E/T) ratio of 5, whereas they did not exhibited such activity against the melanoma cells (B16-F1), Lewis lung carcinoma cells (LLC), renal carcinoma cells (Renca), and bladder carcinoma cells (MBT-2). The cytotoxic activity was inhibited by the treatment with anti-CD3, anti-CD8, and anti-MHC-class I monoclonal antibodies but not with anti-CD4 and anti-MHC-class II antibodies. In the Phase-I clinical trial, vaccination of HCC patients with the autologous vaccine is a well-tolerated treatment and induces fixed tumor fragment-specific immunity.Conclusion: Fixed HCC vaccination elicited protective and therapeutic antitumor immunity against HCC. The tumor vaccine elicited antigen specific CTL response lysis of the target HCC was mediated by the typical MHC-class I restricted CD8+ T cells. Key words cancer vaccine - cytotoxic T lymphocyte - immunotherapy - hepatoma展开更多
AIM: To identify a multi serum protein pattern as well as single protein markers using surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF-MS) for detection and differentiation ...AIM: To identify a multi serum protein pattern as well as single protein markers using surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF-MS) for detection and differentiation of liver fibrosis (F1-F2), liver cirrhosis (F4) and hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV). METHODS: Serum samples of 39 patients with F1/F2 fibrosis, 44 patients with F4 fibrosis, 34 patients with HCC were applied to CM10 arrays and analyzed using the SELDI-TOF ProteinChip System (PBS-Ⅱc; Ciphergen Biosystems) after anion-exchange fractionation. All patients had chronic hepatitis C and histologically confirmed fibrosis stage/HCC. Data were analyzed for protein patterns by multivariate statistical techniques and artificial neural networks. RESULTS: A 4 peptide/protein multimarker panel (7486, 12843, 44293 and 53598 Da) correctly identified HCCs with a sensitivity of 100% and specificity of 85% in a two way-comparison of HCV-cirrhosis versus HCV-HCC training samples (AUROC 0.943). Sensitivity and specificity for identification of HCC were 68% and 80% for random test samples. Cirrhotic patients could be discriminated against patients with F1 or F2 fibrosis using a 5 peptide/protein multimarker pattern (2873, 6646, 7775, 10525 and 67867 Da) with a specificity of 100% and a sensitivity of 85% in training samples (AUROC 0.976) and a sensitivity and specificity of 80% and 67% for random test samples. Combination of the biomarker classifiers with APR/score and alfa-fetopotein (AFP) improved the diagnostic performance. The 6646 Da marker protein for liver fibrosis was identified as apolipoprotein C-I. CONCLUSION: SELDI-TOF-MS technology combined with protein pattern analysis seems a valuable approach for the identification of liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis C. Host probably a combination of different serum markers will help to identify liver cirrhosis and early-stage hepatocellular carcinomas in the future.展开更多
AIM: To investigate the expression of programmed death (PD)-1,PD ligand 1 (PD-L1) and PD-L2 in liver tissues in the context of chronic hepatitis and hepatocellular carcinoma (HCC).METHODS: Liver biopsies and HCC speci...AIM: To investigate the expression of programmed death (PD)-1,PD ligand 1 (PD-L1) and PD-L2 in liver tissues in the context of chronic hepatitis and hepatocellular carcinoma (HCC).METHODS: Liver biopsies and HCC specimens from patients were collected and histologically examined.The expression of PD-1,PD-L1,and PD-L2 in biopsy specimens of chronic hepatitis and HCC specimens was evaluated by immunohistochemical staining.The association between the expression level of PD-1,PD-L1,and PD-L2 and clinical and pathological variables was analyzed statistically.RESULTS: Expression of PD-1 was found in liverinfiltrating lymphocytes.In contrast,PD-L1 and PD-L2 were expressed in non-parenchyma liver cells and tumor cells.The expression of PD-L1 was significantly correlated with hepatitis B virus infection (1.42 ± 1.165 vs 0.50 ± 0.756,P = 0.047) and with the stage of HCC (7.50 ± 2.121 vs 1.75 ± 1.500 vs 3.00 ± 0.001,P = 0.018).PD-1 and PD-Ls were significantly up-regulated in HCC specimens (1.40 ± 1.536 vs 5.71 ± 4.051,P = 0.000;1.05 ± 1.099 vs 4.29 ± 3.885,P = 0.004;1.80 ± 1.473 vs 3.81 ± 3.400,P = 0.020).CONCLUSION: PD-L1 may contribute to negative regulation of the immune response in chronic hepatitis B.PD-1 and PD-Ls may play a role in immune evasion of tumors.展开更多
AIM: To study the expressions of p27^kip1 protein and p27mRNA, the hypermethylation of p27^kip1 and the relation between them in various stages of hepatocarcinogenesis. METHODS: p27 protein and p27mRNA were detected...AIM: To study the expressions of p27^kip1 protein and p27mRNA, the hypermethylation of p27^kip1 and the relation between them in various stages of hepatocarcinogenesis. METHODS: p27 protein and p27mRNA were detected by immunohistochemical staining and in situ hybridization respectively in 68 cases of normal liver, liver cirrhosis, pericancerous cirrhosis and hepatocellular carcinoma (HCC). The hypermethylation of p27^kip1 was detected by methylation-specific PCR (MSP) in 44 cases of normal liver, liver cirrhosis, and HCC. RESULTS: The positive rate of p27 protein was 66.7% (4/6) in normal liver, 60.0% (6/10) in liver cirrhosis, 50.0% (12/24) in pericancerous cirrhosis and 21.4% (6/28) in HCC. There were no statistical differences in normal liver, liver cirrhosis and pericancerous cirrhosis, but the positive rate of p27 protein significantly decreased in HCC compared to that in the other groups (P = 0.006, %2 = 7.664). The positive rate of p27^kip1 mRNA was 83.3% (5/6) in normal liver, 70.0% (7/10) in liver cirrhosis, 75.0% (18/24) in pericancerous cirrhosis and 25.0% (7/28) in HCC. There were no statistical differences in normal liver, liver cirrhosis and pericancerous cirrhosis, but the positive rate of p27^kip1 mRNA also significantly decreased in HCC compared to that in the other groups (P = 0.000, %2 = 16.600). In addition, there was a significant correlation between the expression of p27 protein and p27mRNA in the integrated group of normal liver and liver cirrhosis. However, no significant correlation was found between pericancerous cirrhosis and HCC. Using MSP, we found that 1 HCC in 44 cases (including 6 cases of normal liver, 10 cases of liver cirrhosis and 28 cases of HCC) was methylated, whose p27 protein and p27mRNA were negative. CONCLUSION: The reduction or loss of p27 protein and p27mRNA are potentially involved in hepatocarcinogenesis. The hypermethylation of p27 might lead to the loss of p27mRNA transcription.展开更多
AIM:To labed Anti-hepatoma monoclonal antibody(mAb) fragment HAb18 F(ab')_2 was labeled with 188 Re for the pharmacokinetic model of ^(188)Re-HAb18 F(ab')_2 and to evaluate its pharmacokinetic parameters in he...AIM:To labed Anti-hepatoma monoclonal antibody(mAb) fragment HAb18 F(ab')_2 was labeled with 188 Re for the pharmacokinetic model of ^(188)Re-HAb18 F(ab')_2 and to evaluate its pharmacokinetic parameters in hepatoma- bearing nude mice. METHODS:HAb18 F(ab')_2 was directly labeled with ^(188)Re using 2-mercaptoethanol(2-ME)as reducing agents. Labeling efficiency and immunoreactivity of ^(188)Re-HAb18 F (ab')_2 were evaluated by Whatman 3MM paper chromatography and live cell assay,respectively. Biodistribution analysis was also conducted in nude mice bearing human hepatoma in which animals were sacrificed at different time points(1,4,18,24 and 24h)after ^(188)Re-HAb18 F(ab')_2 was injected through tail-vein into hepatoma-bearing nude mice.The blood and radioactivity of organs and mass were measured.The concentrations of ^(188)Re-HAb18 F(ab')_2 were evaluated with a pharrnacokinetic 3P97 software. RESULTS:The optimum labeling efficiency and immunoreactive fraction were 91.7% and 0.78%, respectively.The parameters of ^(188)Re-HAb18 F(ab')_2 were: T_(1/2),2.29h;Vd,1.49×10^(-9)L·Bq^(-1);AUC,20.49×10~9Bq·h· L^(-1);CL,0.45×10^(-3)L·h^(-1).^(188)Re-HAb18 F(ab')_2 could locate specially in hepatoma with high selective reactivity of HAb18 F(ab')_2.^(188)Re-HAbl8 F(ab')_2 was mainly eliminated by kidney.The maximal tumor to blood ratio was at 48h,and maximal tumor to liver ratio was at 18h. CONCLUTION:The pharmacokinetics of ^(188)Re-HAb18 F(ab')_2 fit a I-compartment model.^(188)Re-HAb18 F(ab')_2 can be uptaken selectively at the hepatoma site.展开更多
AIM: To study the expression of the inhibitor of apoptosis protein survivin in hepatocellular carcinoma (HCC), and its correlation with clinicopathological factors, cell proliferation, recurrence and prognosis afte...AIM: To study the expression of the inhibitor of apoptosis protein survivin in hepatocellular carcinoma (HCC), and its correlation with clinicopathological factors, cell proliferation, recurrence and prognosis after hepatectomy. METHODS: Immunohistochemical staining of survivin and Ki-67 was performed by the standard streptavidin- peroxidase technique on paraffin sections of 55 cases of HCC. RESULTS: The positive rate of survivin in HCC was 52.7% (29/55). Significant correlation was found between survivin expression with portal vein thrombi and intrahepatic matastasistic nodes (P 〈 0.05). The recurrent rate in survivin-positive HCC was significantly higher than that in survivin-negative HCC after hepatectomy, the 1- and 3-year survival rate in patients with survivin-positive tumors was significantly lower than that in patients with survivin-negative tumors (58.62 and 10.34% vs 76.92 and 30.77%, P 〈 0.05, log-rank test). The proliferation index (Ki-67) in survivin-positive HCC (33.83% ± 18.90%) was significantly higher than that in survivin-negative HCC (19.60% ± 19.35%) (P 〈 0.05). CONCLUSION: Survivin may play an important role in progression of HCC by promoting cell proliferation, and may be positively correlated with high risk of disease recurrence and poor prognosis in HCC. Its expression may serve as a prognostic factor for patients with HCC after hepatectomy.展开更多
A case of a 53-year-old female patient with reactive lymphoid hyperplasia (RLH), clinically designated as pseudolymphoma of the liver is described in this article. The patient was admitted to our hospital for furthe...A case of a 53-year-old female patient with reactive lymphoid hyperplasia (RLH), clinically designated as pseudolymphoma of the liver is described in this article. The patient was admitted to our hospital for further evaluation of hepatic tumors incidentally discovered at another hospital. Various diagnostic methods, including ultrasonography (US), computerized tomography (CT), magnetic resonance imaging (MRI) and hepatic angiography displayed three small lesions in the liver with outstanding findings consistent with hepatocellular carcinoma (HCC). Surgical resection was performed and the three lesions were microscopically diagnosed as RLH of the liver. The lesions comprised a massive infiltration of lymphoid cells with follicles and hyalinized inter- follicular spaces. Immunohistochemical examination revealed that infiltrating lymphocytes had no prominent nuclear atypia and polyclonality. RLH of the liver is a very rare condition and only twelve cases have been reported in the English literature. Majority of the reported cases were middle-aged women and about half of them had some immunologic abnormalities such as autoimmune thyroiditis, Sjogren's syndrome, primary immunodeficiency, primary biliary cirrhosis. Since they are olden clinically misdiagnosed as HCC, surgery is the choice of treatment for these patients. Although their pathology resembles malignant lymphoma, the clinical course is completely benign. The authors propose that RLH of the liver can be discriminated from HCC by its clinical features.展开更多
文摘Objective: To study the protective and therapeutic antitumor immunity against hepatocellular carcinoma (HCC) with the fixed-tumor vaccine.Methods: A tumor vaccine consisting of fixed tumor cells or fixed tumor fragments combined with sustained-releasers of cytokines and a non-toxic adjuvant was developed. C57BL/6J mice were immunized intra-dermally with the vaccine on day 0 and 7, followed by intrahepatic challenge with live Hepa 1–6 cells.Results: All of 15 nonimmunized control mice developed the hepatoma. Protection of mice immunized with fixed Hepa 1–6 cells and both of IL-2/GM-CSF microspheres or further mixed with TiterMax Gold reached 80% and 87%, respectively. Mass growth of the established tumors, vaccinated twice at 5 mm in diameter, the tumor of control animals continued to grow. However, 7–10 days after the second injection of the tumor vaccine, the tumor growth was suppressed in 9 of 10 mice and then markedly reduced. Complete tumor regression was observed in 60% (6/10) of mice. Splenocytes from the control mice were not able to lyse target Hepa 1–6 cells and other tumor cells. In contrast splenocytes from the vaccinated mice exhibited a 41% lytic activity against the Hepa 1–6 cells tested at an effector/target (E/T) ratio of 5, whereas they did not exhibited such activity against the melanoma cells (B16-F1), Lewis lung carcinoma cells (LLC), renal carcinoma cells (Renca), and bladder carcinoma cells (MBT-2). The cytotoxic activity was inhibited by the treatment with anti-CD3, anti-CD8, and anti-MHC-class I monoclonal antibodies but not with anti-CD4 and anti-MHC-class II antibodies. In the Phase-I clinical trial, vaccination of HCC patients with the autologous vaccine is a well-tolerated treatment and induces fixed tumor fragment-specific immunity.Conclusion: Fixed HCC vaccination elicited protective and therapeutic antitumor immunity against HCC. The tumor vaccine elicited antigen specific CTL response lysis of the target HCC was mediated by the typical MHC-class I restricted CD8+ T cells. Key words cancer vaccine - cytotoxic T lymphocyte - immunotherapy - hepatoma
基金Supported by a research grant of the Jurgen Manchot Stiftung
文摘AIM: To identify a multi serum protein pattern as well as single protein markers using surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF-MS) for detection and differentiation of liver fibrosis (F1-F2), liver cirrhosis (F4) and hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV). METHODS: Serum samples of 39 patients with F1/F2 fibrosis, 44 patients with F4 fibrosis, 34 patients with HCC were applied to CM10 arrays and analyzed using the SELDI-TOF ProteinChip System (PBS-Ⅱc; Ciphergen Biosystems) after anion-exchange fractionation. All patients had chronic hepatitis C and histologically confirmed fibrosis stage/HCC. Data were analyzed for protein patterns by multivariate statistical techniques and artificial neural networks. RESULTS: A 4 peptide/protein multimarker panel (7486, 12843, 44293 and 53598 Da) correctly identified HCCs with a sensitivity of 100% and specificity of 85% in a two way-comparison of HCV-cirrhosis versus HCV-HCC training samples (AUROC 0.943). Sensitivity and specificity for identification of HCC were 68% and 80% for random test samples. Cirrhotic patients could be discriminated against patients with F1 or F2 fibrosis using a 5 peptide/protein multimarker pattern (2873, 6646, 7775, 10525 and 67867 Da) with a specificity of 100% and a sensitivity of 85% in training samples (AUROC 0.976) and a sensitivity and specificity of 80% and 67% for random test samples. Combination of the biomarker classifiers with APR/score and alfa-fetopotein (AFP) improved the diagnostic performance. The 6646 Da marker protein for liver fibrosis was identified as apolipoprotein C-I. CONCLUSION: SELDI-TOF-MS technology combined with protein pattern analysis seems a valuable approach for the identification of liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis C. Host probably a combination of different serum markers will help to identify liver cirrhosis and early-stage hepatocellular carcinomas in the future.
基金Supported by Grants from the National Mega Research Program of China,No.2008ZX10002-011the National Key Basic Research Program of China,No.2001CB510008,2005CB522901,2007CB512804 and 2009CB522500the Deutsche Forschun-gsgemeinschaft (SFB/Transregio 60)
文摘AIM: To investigate the expression of programmed death (PD)-1,PD ligand 1 (PD-L1) and PD-L2 in liver tissues in the context of chronic hepatitis and hepatocellular carcinoma (HCC).METHODS: Liver biopsies and HCC specimens from patients were collected and histologically examined.The expression of PD-1,PD-L1,and PD-L2 in biopsy specimens of chronic hepatitis and HCC specimens was evaluated by immunohistochemical staining.The association between the expression level of PD-1,PD-L1,and PD-L2 and clinical and pathological variables was analyzed statistically.RESULTS: Expression of PD-1 was found in liverinfiltrating lymphocytes.In contrast,PD-L1 and PD-L2 were expressed in non-parenchyma liver cells and tumor cells.The expression of PD-L1 was significantly correlated with hepatitis B virus infection (1.42 ± 1.165 vs 0.50 ± 0.756,P = 0.047) and with the stage of HCC (7.50 ± 2.121 vs 1.75 ± 1.500 vs 3.00 ± 0.001,P = 0.018).PD-1 and PD-Ls were significantly up-regulated in HCC specimens (1.40 ± 1.536 vs 5.71 ± 4.051,P = 0.000;1.05 ± 1.099 vs 4.29 ± 3.885,P = 0.004;1.80 ± 1.473 vs 3.81 ± 3.400,P = 0.020).CONCLUSION: PD-L1 may contribute to negative regulation of the immune response in chronic hepatitis B.PD-1 and PD-Ls may play a role in immune evasion of tumors.
基金Supported by the Natural Science Foundation of Yunnan Province, China, No. 2000C0058M, and Scientific Research Foundation of the Education Department of Yunnan Province, No. 0011010
文摘AIM: To study the expressions of p27^kip1 protein and p27mRNA, the hypermethylation of p27^kip1 and the relation between them in various stages of hepatocarcinogenesis. METHODS: p27 protein and p27mRNA were detected by immunohistochemical staining and in situ hybridization respectively in 68 cases of normal liver, liver cirrhosis, pericancerous cirrhosis and hepatocellular carcinoma (HCC). The hypermethylation of p27^kip1 was detected by methylation-specific PCR (MSP) in 44 cases of normal liver, liver cirrhosis, and HCC. RESULTS: The positive rate of p27 protein was 66.7% (4/6) in normal liver, 60.0% (6/10) in liver cirrhosis, 50.0% (12/24) in pericancerous cirrhosis and 21.4% (6/28) in HCC. There were no statistical differences in normal liver, liver cirrhosis and pericancerous cirrhosis, but the positive rate of p27 protein significantly decreased in HCC compared to that in the other groups (P = 0.006, %2 = 7.664). The positive rate of p27^kip1 mRNA was 83.3% (5/6) in normal liver, 70.0% (7/10) in liver cirrhosis, 75.0% (18/24) in pericancerous cirrhosis and 25.0% (7/28) in HCC. There were no statistical differences in normal liver, liver cirrhosis and pericancerous cirrhosis, but the positive rate of p27^kip1 mRNA also significantly decreased in HCC compared to that in the other groups (P = 0.000, %2 = 16.600). In addition, there was a significant correlation between the expression of p27 protein and p27mRNA in the integrated group of normal liver and liver cirrhosis. However, no significant correlation was found between pericancerous cirrhosis and HCC. Using MSP, we found that 1 HCC in 44 cases (including 6 cases of normal liver, 10 cases of liver cirrhosis and 28 cases of HCC) was methylated, whose p27 protein and p27mRNA were negative. CONCLUSION: The reduction or loss of p27 protein and p27mRNA are potentially involved in hepatocarcinogenesis. The hypermethylation of p27 might lead to the loss of p27mRNA transcription.
基金the National Natural Science Foundation of China,No.39700175
文摘AIM:To labed Anti-hepatoma monoclonal antibody(mAb) fragment HAb18 F(ab')_2 was labeled with 188 Re for the pharmacokinetic model of ^(188)Re-HAb18 F(ab')_2 and to evaluate its pharmacokinetic parameters in hepatoma- bearing nude mice. METHODS:HAb18 F(ab')_2 was directly labeled with ^(188)Re using 2-mercaptoethanol(2-ME)as reducing agents. Labeling efficiency and immunoreactivity of ^(188)Re-HAb18 F (ab')_2 were evaluated by Whatman 3MM paper chromatography and live cell assay,respectively. Biodistribution analysis was also conducted in nude mice bearing human hepatoma in which animals were sacrificed at different time points(1,4,18,24 and 24h)after ^(188)Re-HAb18 F(ab')_2 was injected through tail-vein into hepatoma-bearing nude mice.The blood and radioactivity of organs and mass were measured.The concentrations of ^(188)Re-HAb18 F(ab')_2 were evaluated with a pharrnacokinetic 3P97 software. RESULTS:The optimum labeling efficiency and immunoreactive fraction were 91.7% and 0.78%, respectively.The parameters of ^(188)Re-HAb18 F(ab')_2 were: T_(1/2),2.29h;Vd,1.49×10^(-9)L·Bq^(-1);AUC,20.49×10~9Bq·h· L^(-1);CL,0.45×10^(-3)L·h^(-1).^(188)Re-HAb18 F(ab')_2 could locate specially in hepatoma with high selective reactivity of HAb18 F(ab')_2.^(188)Re-HAbl8 F(ab')_2 was mainly eliminated by kidney.The maximal tumor to blood ratio was at 48h,and maximal tumor to liver ratio was at 18h. CONCLUTION:The pharmacokinetics of ^(188)Re-HAb18 F(ab')_2 fit a I-compartment model.^(188)Re-HAb18 F(ab')_2 can be uptaken selectively at the hepatoma site.
文摘AIM: To study the expression of the inhibitor of apoptosis protein survivin in hepatocellular carcinoma (HCC), and its correlation with clinicopathological factors, cell proliferation, recurrence and prognosis after hepatectomy. METHODS: Immunohistochemical staining of survivin and Ki-67 was performed by the standard streptavidin- peroxidase technique on paraffin sections of 55 cases of HCC. RESULTS: The positive rate of survivin in HCC was 52.7% (29/55). Significant correlation was found between survivin expression with portal vein thrombi and intrahepatic matastasistic nodes (P 〈 0.05). The recurrent rate in survivin-positive HCC was significantly higher than that in survivin-negative HCC after hepatectomy, the 1- and 3-year survival rate in patients with survivin-positive tumors was significantly lower than that in patients with survivin-negative tumors (58.62 and 10.34% vs 76.92 and 30.77%, P 〈 0.05, log-rank test). The proliferation index (Ki-67) in survivin-positive HCC (33.83% ± 18.90%) was significantly higher than that in survivin-negative HCC (19.60% ± 19.35%) (P 〈 0.05). CONCLUSION: Survivin may play an important role in progression of HCC by promoting cell proliferation, and may be positively correlated with high risk of disease recurrence and poor prognosis in HCC. Its expression may serve as a prognostic factor for patients with HCC after hepatectomy.
文摘A case of a 53-year-old female patient with reactive lymphoid hyperplasia (RLH), clinically designated as pseudolymphoma of the liver is described in this article. The patient was admitted to our hospital for further evaluation of hepatic tumors incidentally discovered at another hospital. Various diagnostic methods, including ultrasonography (US), computerized tomography (CT), magnetic resonance imaging (MRI) and hepatic angiography displayed three small lesions in the liver with outstanding findings consistent with hepatocellular carcinoma (HCC). Surgical resection was performed and the three lesions were microscopically diagnosed as RLH of the liver. The lesions comprised a massive infiltration of lymphoid cells with follicles and hyalinized inter- follicular spaces. Immunohistochemical examination revealed that infiltrating lymphocytes had no prominent nuclear atypia and polyclonality. RLH of the liver is a very rare condition and only twelve cases have been reported in the English literature. Majority of the reported cases were middle-aged women and about half of them had some immunologic abnormalities such as autoimmune thyroiditis, Sjogren's syndrome, primary immunodeficiency, primary biliary cirrhosis. Since they are olden clinically misdiagnosed as HCC, surgery is the choice of treatment for these patients. Although their pathology resembles malignant lymphoma, the clinical course is completely benign. The authors propose that RLH of the liver can be discriminated from HCC by its clinical features.