Background:Human hepatocellular carcinoma (HCC) cells are largely deficient of argininosuccinate synthetase and thus auxotrophic for arginine. This study aims to investigate the efficacy and pharmacodynamics of pegylated arginine deiminase (ADI-PEG 20), a systemic arginine deprivation agent, in Asian HCC patients.Methods:Patients with advanced HCC who were not candidates for local therapy were eligible and randomly assigned to receive weekly intramuscular injections of ADI-PEG 20 at doses of 160 or 320 IU m−2. The primary end point was disease-control rate (DCR).Results:Of the 71 accruals, 43.6% had failed previous systemic treatment. There were no objective responders. The DCR and the median overall survival (OS) of the intent-to-treat population were 31.0% (95% confidence interval (CI): 20.5–43.1) and 7.3 (95% CI: 4.7–9.9) months respectively. Both efficacy parameters were comparable between the two study arms. The median OS of patients with undetectable circulating arginine for more than or equal to and <4 weeks was 10.0 (95% CI: 2.1–17.9) and 5.8 (95% CI: 1.4–10.1) months respectively (P=0.251, log-rank test). The major treatment-related adverse events were grades 1–2 local and/or allergic reactions.Conclusions:ADI-PEG 20 is safe and efficacious in stabilising the progression of heavily pretreated advanced HCC in an Asian population, and deserves further exploration.

Background:Interferon (IFN)-based therapies could eradicate hepatitis C (HCV) and reduce the risk of hepatocellular carcinoma (HCC). However, HCC could still happen after sustained virological response (SVR). We aimed to develop a simple scoring system to predict the risk of HCC development among HCV patients after antiviral therapies.Methods:From 1999 to 2009, 1879 patients with biopsy-proven HCV infection treated with IFN-based therapies were analyzed.Results:Multivariable analysis showed old age (adjusted HR (aHR)=1.73, 95% CI=1.13–2.65 for aged 60–69 and aHR=2.20, 95% CI=1.43–3.37 for aged ⩾70), Male gender (aHR=1.74, 95% CI=1.26–2.41), platelet count <150 × 109/l (HR=1.91, 95% CI=1.27–2.86), α-fetoprotein ⩾20 ng ml−1 (HR=2.23, 95% CI=1.58–3.14), high fibrotic stage (HR=3.32, 95% CI=2.10–5.22), HCV genotype 1b (HR=1.53, 95% CI=1.10–2.14), and non SVR (HR=2.40, 95% CI=1.70–3.38) were independent risk factors for HCC. Regression coefficients were used to build up a risk score and the accuracy was evaluated by using the area under the receiver operating characteristic curve (AUC). Three groups as low-, intermediate-, and high-risk are classified based on the risk scores. One hundred sixty patients (12.78%) in the derivation and 82 patients (13.08%) in the validation cohort developed HCC with AUC of 79.4%, sensitivity of 84.38%, and specificity of 60.66%. In the validation cohort, the 5-year HCC incidence was 1.81%, 12.92%, and 29.95% in low-, intermediate-, and high-risk groups, with hazard ratios 4.49 in intermediate- and 16.14 in high-risk group respectively. The risk reduction of HCC is greatest in patients with SVR, with a 5-year and 10-year risk reduction of 28.91% and 27.99% respectively.Conclusion:The risk scoring system is accurate in predicting HCC development for HCV patients after antiviral therapies.

A high prevalence of HBeAg among HBsAg-positive mothers at the time of delivery results in a high prevalence of hepatitis B vertical transmission. From 1990 to 1995, 896 pregnant HBsAg-positive women, including 411 (46 per cent) HBeAg-positive subjects, were enrolled in our study to analyse the secular change in HBeAg prevalence. Their mean age, number of pregnancies and parity were 29.5 +/- 4.1 years, 2.0 +/- 1.2, and 0.6 +/- 0.7, respectively. The prevalence rates of HBeAg were 48, 54, 49, 47, 40, and 40 per cent among the subjects enrolled in 1990, 1991, 1992, 1993, 1994, and 1995, respectively. In univariate analyses, prevalence of HBeAg decreased by the calendar year of pregnancy (p = 0.01), and also by age (p < 0.00001), number of pregnancies (p < 0.0001) and parity (p < 0.0002). After adjusting for age in multiple logistic regression, the calendar year of pregnancy was still the independent variable, while gravida and parity became insignificant. The odd ratios (95 per cent confidence interval) of HBeAg negative-seroconversion in the equations were 1.09 (1.00-1.19) per calendar year and 1.14 (1.10-1.18) per year of age. Our results have shown a secular decrease in HBeAg-prevalence among pregnant HBsAg-positive women in Taiwan.

To assess the usefulness of alpha-fetoprotein (AFP) in monitoring treatment effects of transcatheter arterial embolization (TAE) in hepatocellular carcinoma (HCC) patients, a total of 31 sets of AFP levels after TAE in 21 HCC patients were analysed by linear regression between logarithmic AFP levels and days. Eleven sets of AFP data with poor linear declination were accompanied with poor TAE results except in one patient who had chronic hepatitis with acute exacerbations. Twenty sets of data with good linear declination in the first month after TAE indicated good TAE results. Seven of them showed no evidence of tumour recurrence nor elevated AFP levels within a follow-up of 6 months. The mean, standard deviation and range of half-lives of AFP in the non-recurrent group were 5.0, 1.6 and 2.9-7.2 days, respectively. The others experienced late tumour recurrence that was detected by rebound of AFP levels except one who had another non-AFP-secreting HCC. Thus, the results might be used as a reference in monitoring the treatment effects of TAE and the timing selection of repeated TAE.