Outcome of patients with hepatitis C virus-related single, small hepatocellular carcinoma.

To clarify the cumulative recurrence-free interval and survival rate with hepatitis C virus (HCV)-related single, small hepatocellular carcinoma (HCC), we studied 32 patients with surgical resection, 61 with ablation therapy and 28 with transcatheter chemoembolization (TACE). A log-rank test revealed that there were no significant differences in the recurrence-free interval (p = 0.08) and survival (p = 0.279) between the resection and the ablation groups. Univariate analysis using the Cox proportional hazards regression model showed initial treatment (p = 0.0051) was associated with recurrence-free interval. Platelet count (p = 0.009), indocianine green retention rate at 15 minutes (p = 0.003), Child-Pugh classification (p = 0.001), serum albumin level (p = 0.0012) and serum total bililubin (p = 0.015) were associated with survival. Hence patients with HCV-related single, small HCC should be treated according to their hepatic reserve.

Aspirin induces hepatoma-derived cell apoptosis via a hydrogen peroxide-dependent pathway.

Here we studied whether aspirin (ASA) has any influence on viability of human hepatoma-derived SKHep-1 cells and whether hydrogen peroxide (H(2)O(2)) has any relation with this effect. ASA inhibited SKHep-1 cell proliferation dose- and time-dependently. Intracellular H(2)O(2) increased as early as 15 min after ASA supplementation. Cellular apoptosis correlated with an increase in intracellular H(2)O(2) level. Moreover, in the presence of a catalase inhibitor-aminotriazol, ASA showed more apoptotic effect on SKHep-1 cells with increasing intracellular H(2)O(2) level. In conclusion, the present results shows that ASA induced SKHep-1 cell apoptosis has a relation with an early increase in intracellular H(2)O(2) level and catalase inhibitor synergizes to induce this process.

Systemic combined chemotherapy with low dose of 5-fluorouracil, cisplatin, and interferon-alpha for advanced hepatocellular carcinoma: a pilot study.

The purpose of this pilot study was to evaluate the efficacy and adverse events of systemic combined chemotherapy with low dose of 5-fluorouracil (250 mg/m2, 5 days), cisplatin (10 mg/m2, 5 days), and interferon-alpha (2.5 million units, three times weekly) for advanced hepatocellular carcinoma (HCC) underlying liver cirrhosis. Six patients who had advanced HCC with tumor thrombi in the main portal trunk were enrolled in this study. Partial response was achieved in 2, stable disease in 1, and disease progressed in 3. Objective responses were achieved in 2 (33%), however, marked decreases of alpha-fetoprotein protein and protein-induced vitamin K antagonist or absence (PIVKAII) levels were also seen in one patient (stable disease). Four patients showed hematologic or renal toxicity, which were well tolerated and managed. Our systemic combined chemotherapy resulted in favorable response and was well tolerated in those with advanced HCC underlying liver cirrhosis, complicated by leukocytopenia and thromobocytopenia.

Risk factors for local recurrence of small hepatocellular carcinoma tumors after a single session, single application of percutaneous radiofrequency ablation.

BACKGROUND: The objectives of this study were to clarify risk factors for local tumor recurrence and to determine which patients with hepatocellular carcinoma (HCC) are most suitable for a single session, single application of percutaneous radiofrequency (RF) ablation. METHODS: Fifty-six consecutive patients with 65 HCC tumors measuring 2 cm (risk ratio [RR], 4.9; 95%CI, 1.3-16.4; P = 0.019) and subcapsular location (RR, 5.2; 95%CI, 1.7-16.6; P = 0.005) were associated independently with local recurrence. The other four factors were not associated with local recurrence in this study. CONCLUSIONS: A single session, single application of RF ablation produced favorable local control. Patients who have nonsubcapsular HCC tumors measuring

Inhibition by arsenic trioxide of human hepatoma cell growth.

Arsenic trioxide (As(2)O(3)) has been shown to be effective for treatment of patients with refractory or relapsed acute promyelocytic leukemia and a variety of other malignant hematopoetic disorders. We studied the effect of this agent on proliferation of human hepatoma-derived cell lines (SK-Hep-1, HepG2, and HuH7). In HuH7 cells, As(2)O(3) reduced proliferation time- and dose-dependently at 1 and 2 microM, while in SK-Hep-1 and HepG2 cells, As(2)O(3) inhibited proliferation at 2 and 4 microM respectively. Cell cycle analysis by flow cytometry showed that As(2)O(3) induced apoptosis in these hepatoma-derived cells as confirmed by appearance of sub-G(1) cells. Sensitivity of hepatoma-derived cells to As(2)O(3) was inversely related to their intracellular glutathione (GSH) and intensity of GSH synthesis. Arsenic sensitivity was restored to relatively resistant cell lines when GSH was depleted by L-buthionine sulfoximine (BSO). These results indicate that As(2)O(3) may have therapeutic potential for treatment of hepatocellular carcinoma.

Outcome of patients with hepatitis C virus-related hepatocellular carcinoma occurring after interferon therapy.

To determine whether previous IFN therapy for chronic hepatitis C (HCV) infection influences the outcome of patients with hepatocellular carcinoma (HCC), 143 patients were enrolled in this study. Of 143 patients, 48 had received previous IFN therapy (IFN group) and the remaining 95 had not (untreated group). We estimated distant intrahepatic recurrence-free intervals and disease-specific survivals of the two groups by the Kaplan-Meier method and analyzed the difference by the log-rank test. Factors determining distant intrahepatic recurrence-free interval and disease-specific survival were studied by univariate and multivariate analysis using Cox proportional hazards regression model. The proportion of patients with single tumors was significantly higher in the IFN group (p = 0.026). The IFN group showed a significantly higher distant intrahepatic recurrence-free interval (p = 0.001) and disease-specific survival (p = 0.003). Moreover, multivariate analysis indicated that previous IFN therapy for chronic HCV infection was a significant independent factor for distant intrahepatic recurrence-free interval and disease-specific survival. These results indicate that previous IFN therapy reduces multicentric hepatocarcinogenesis of HCV-related HCC and improves the patients' survival.