Peginterferon alpha-2a and ribavirin versus peginterferon alpha-2a monotherapy in early virological responders and peginterferon alpha-2a and ribavirin versus peginterferon alpha-2a, ribavirin and amantadine triple therapy in early virological nonresponders: the SMIEC II trial in naïve patients with chronic hepatitis C.

OBJECTIVE: The objective of this study was to compare the efficacy of anti-hepatitis C virus (anti-HCV) treatment schedules on the basis of an early virological response (EVR), defined as undetectable serum HCV-RNA (<50 IU/ml) after a 12-week induction course of peginterferon alpha-2a (PEG-IFN) 180 mcg/week. METHODS: A total of 210 interferon-naïve patients (69% male; median age, 42 years) with histologically proven chronic hepatitis C infection (genotype 1: 62%) received PEG-IFN 180 mcg/week for 12 weeks. Patients with EVR (58%) were randomized to continue PEG-IFN monotherapy (n=64) or to add ribavirin (RBV), 800 mg/day (n=57), for 36 additional weeks. Patients without EVR (42%) were randomized to add RBV (n=42), or RBV plus amantadine, 200 mg/day (n=47), for 36 additional weeks. Sustained virological response (SVR, undetectable HCV-RNA 24 weeks after treatment completion) was compared among treatment groups. RESULTS: Patients with EVR: SVR rate was 60.3% in the PEG-IFN group versus 67.2% in the PEG-IFN+RBV group (NS). In genotypes 2/3, SVR rates were 66.7 versus 73.1% (NS); in genotypes 1/4, SVR rates were 51.6 versus 61.3%, respectively (NS). Patients without EVR: SVR was 16.7% in the PEG-IFN+RBV group versus 31.9% in the triple therapy group (P=0.07). In patients with genotypes 1/4, SVR rates were 9.4 versus 29.7% (P=0.041). CONCLUSION: In genotypes 1/4 patients without EVR, triple therapy results in higher SVR rates than standard dual therapy. This study confirms that addition of amantadine is beneficial in early-recognized 'difficult-to-treat' patients.

Analysis of factors predicting survival in patients with hepatocellular carcinoma treated with percutaneous laser ablation.

BACKGROUND/AIMS: The factors which predict the long-term outcome in patients with hepatocellular carcinoma who are treated with percutaneous laser ablation (PLA) are not well established. METHODS: We prospectively analyzed treatment and survival parameters of 148 cirrhotic patients with nonsurgical hepatocellular carcinoma who had undergone PLA at a single institution during an 11-year period. RESULTS: Single tumors were seen in 129 of 148 (87%) patients, and 2-3 nodules were seen in 19 (13%) patients, for a total of 169 tumors. The median overall time survival was 39 months (95% confidence interval [CI], 30-47 months). The 1-, 2-, 3-, 4-, and 5-year cumulative survival rates were 89, 75, 52, 43, and 27%, respectively. From multiple regression analysis, the independent predictors of survival were found to be tumor grading (P=0.002; risk ratio [RR] 0.37, 95% CI 0.20-0.70), bilirubin levels < or =2.5mg/dl (P=0.014; RR 1.58, 95% CI 1.09-2.28), and the achievement of complete tumor ablation (P=0.020; RR 0.53, 95% CI 0.31-0.90). An initial complete tumor ablation was the only factor associated with longer survival in patients with Child-Turcotte-Pugh class A cirrhosis (P=0.012; hazard ratio [HR] 0.48, 95% CI 0.23-1.03). CONCLUSIONS: A complete tumor ablation results in improved survival in all patients with nonsurgical hepatocellular carcinoma. Ideal candidates for PLA are those with a well-differentiated histology, and normal bilirubin levels.

Percutaneous laser ablation in the treatment of hepatocellular carcinoma with small tumors: analysis of factors affecting the achievement of tumor necrosis.

PURPOSE: To identify the factors that affect the achievement of tumor necrosis with percutaneous laser ablation (PLA) in patients with hepatocellular carcinoma (HCC) and tumor size no larger than 4.0 cm. MATERIALS AND METHODS: Ultrasound-guided biopsy results were retrospectively studied in 99 lesions (range, 0.5-4.0 cm; mean, 2.7 cm) from 82 patients (44 men, 38 women; age range, 50-80 years; median, 68 y) who had undergone PLA. RESULTS: Complete tumor ablation was obtained in 90 lesions (90.9%). Of the nine cases in which complete tumor necrosis was not achieved, six had tumors located in sites that did not allow the optimal placement of fibers, and five of these had a tumor diameter greater than 3 cm. Early discontinuation of PLA as a result of decompensation of liver cirrhosis was the reason for not achieving a complete tumor ablation in three other cases. There was a clear relationship between the energy delivered and the volume of necrosis achieved (r = 0.56; P < .001) regardless of the initial size of HCC tumors. The number of illuminations required, and consequently the amount of energy delivered, was also affected by tumor location. In fact, lesions adjacent to large vessels (> or = 3 mm) required a greater number of illuminations than the other lesions to achieve complete ablation (2.9 +/- 1.4 vs 2.3 +/- 0.9; P = .043). The eight cases with undifferentiated histology required more illuminations than the cases with other histologic types (3.4 +/- 0.9 vs 2.2 +/- 0.9; P < .001). However, these cases were located in sites that did not allow the optimal placement of fibers, therefore requiring multiple treatments. CONCLUSION: PLA is a highly effective treatment in HCC with a tumor size of 4.0 cm or smaller. In this setting, two variables, tumor size and tumor location, affect the achievement of complete tumor ablation and the number of treatments required to obtain tumor necrosis.