Immunohistochemical demonstration of transferrin receptor 1 and 2 in human hepatocellular carcinoma tissue.

BACKGROUND/AIMS: Recent studies have confirmed that iron overload is involved not only in liver carcinogenesis, but in its progression. Results in studies using liver cancer cell lines have suggested a relationship between transferrin receptor (TfR) expression and liver carcinogenesis, but TfR expression has not yet been analyzed in human hepatocellular carcinoma (HCC) tissues. METHODOLOGY: We immunohistochemically assessed the expression of TfR1 and TfR2 in tumor tissues and adjacent non-tumorous liver tissues from 41 HCC patients who underwent partial hepatectomy. We evaluated uptake of iron in hepatocytes and HCC cells using iron staining. RESULTS: The expression TfR was significantly higher in HCC samples than in adjacent non-tumor tissue (p < 0.001). TfR expression was significantly related to serum alpha-fetoprotein (p < 0.05) and des-gamma carboxy prothrombin (p < 0.05) concentrations. We also found iron deposition in non-tumor tissue from 25 patients, but in only two HCC samples, consistent with findings that hepatocellular iron uptake decreases with liver carcinogenesis. CONCLUSIONS: We investigated the expression of TfR1 and TfR2 in human HCC tissues by immunohistochemistry, the first report demonstrating TfR2 expression immunohistochemically in human HCC. These results suggest that TfR is expressed in response to iron deficiency during liver carcinogenesis.

Combination therapy of lamivudine and adefovir in Japanese patients with chronic hepatitis B.

PURPOSE: This study aimed to clarify the long-term efficacy of the lamivudine treatment in Japanese patients with chronic hepatitis B either with or without lamivudine resistance or with or without adefovir add-on treatment. METHODS: We followed 110 patients who received lamivudine for more than 12 months, including 67 hepatitis B e antigen (HBeAg)-positive and 43 HBeAg-negative patients. RESULTS: The median follow-up after the onset of lamivudine was 48 (range = 12-86) months. In all the patients with or without lamivudine resistance, the level of alanine aminotransferase (ALT) normalization decreased from 70.0% at 1 year to 36.4% at 5 years and the loss of serum HBV DNA level decreased from 72.7% at 1 year to 31.8% at 5 years. Sixty patients (54.6%) developed a lamivudine-resistant mutation, and this occurrence was more frequently observed in those who were HBeAg-positive (P < 0.01), those with a low level of ALT (P < 0.05), and those with a high level of serum HBV DNA (P < 0.01). Thirty-six of 60 patients received adefovir in addition to lamivudine to treat breakthrough hepatitis. A Cox proportional hazards model analysis revealed the level of baseline HBV DNA to be the best predictive factor for the virus recrudescence (risk ratio = 0.466, 95% confidence interval [CI]: 0.246-0.842, P = 0.011) and the breakthrough hepatitis (risk ratio = 0.444, 95% CI: 0.218-0.879, P = 0.019). We carefully monitored the efficacy of this treatment both in patients who received adefovir and in those who did not since the beginning of the lamivudine treatment. The normalization level of ALT was 61.4% at 5 years and the loss of serum HBV DNA was 61.4% at 5 years since lamivudine was started. A histologic improvement was observed in patients with ALT levels less than two times the upper limit of normal at the time of a second liver biopsy. CONCLUSIONS: Although the efficacy of lamivudine is limited because of breakthrough hepatitis, adefovir was used as a salvage treatment of patients with lamivudine-resistant chronic hepatitis B. In addition, lamivudine was used for the treatment of Japanese patients with chronic hepatitis B with or without lamivudine resistance, and was found to be useful regarding the long-term virologic and biochemical responses.

Hepatocellular carcinoma in a patient with liver cirrhosis associated with negative serum HCV tests but positive liver tissue HCV RNA.

A 70-year-old woman was admitted to our hospital because of a liver tumor. Laboratory data revealed mild liver dysfunction. Neither serum anti-HCV antibody nor HCV-RNA was detected. Computed tomography revealed a tumor lesion measuring 2 cm in diameter within the liver. Histological examination of the tumor revealed moderately differentiated hepatocellular carcinoma while the non-tumorous liver tissue demonstrated liver cirrhosis. By the RT-PCR method, HCV-RNA was detected from the non-tumorous liver tissue. We herein report a very rare case of hepatocellular carcinoma in a patient with liver cirrhosis associated with negative serum HCV findings, but positive finding for liver tissue HCV RNA.