Sheng Shun Yang

Heparanase inhibitor PI-88 as adjuvant therapy for hepatocellular carcinoma after curative resection: A randomized phase II trial for safety and optimal dosage

BACKGROUND/AIMS Hepatocellular carcinoma recurrence after curative treatment adversely influences clinical outcome. It is important to explore adjuvant therapies. This phase II/stage 1 multi-center, randomized trial investigated the safety, optimal dosage and preliminary efficacy of PI-88, a novel heparanase inhibitor, in the setting of post-operative recurrence of HCC according to a Simons 2-stage design. METHODS Three groups were included: one untreated arm (Group A) and two PI-88 arms (Group B: 160 mg/day; Group C: 250 mg/day). Treatment groups received PI-88 over nine 4-week treatment cycles, followed by a 12-week treatment-free period. Safety and optimal dosage were assessed. RESULTS Overall, 172 patients were randomized and 168 were included in the intention-to-treat (ITT) population. Treatment-related adverse effects included cytopenia, injection site hemorrhage, PT prolongation, etc. Four serious adverse events were possibly related to PI-88 treatment. One (1.8%) group B patients and six (10.5%) group C had hepatotoxicity-related withdrawals. Among the ITT population, 29 patients (50%) in Group A, 35 (63%) in Group B, and 22 (41%) in Group C remained recurrence-free at completion. Calculated T(1) value suggested 160 mg/day treatment satisfied the criteria for the next stage of the trial. CONCLUSIONS PI-88 at 160 mg/day is optimal and safe, and shows preliminary efficacy as an adjunct therapy for post-operative HCC.

Long‐term trends and geographic variations in the survival of patients with hepatocellular carcinoma: Analysis of 11 312 patients in Taiwan

Background/Aims:  The survival rates of patients with hepatocellular carcinoma (HCC) were investigated over the past 20 years to clarify the long‐term survival trend.

Do young hepatocellular carcinoma patients have worse prognosis? The paradox of age as a prognostic factor in the survival of hepatocellular carcinoma patients

Abstract: Background/Aims: Our previous study showed that male hepatocellular carcinoma (HCC) patients below 40 years of age had the worst survival in the initial several years, but had the best prognosis thereafter. Thus, it seems that age has a paradoxical influence on the prognosis. To further clarify the issue of age on HCC prognosis, we initiated this study.

Four-year entecavir therapy reduces hepatocellular carcinoma, cirrhotic events and mortality in chronic hepatitis B patients.

Oral antiviral therapy may reduce the disease progression of chronic hepatitis B (CHB) patients. We aimed to further investigate the efficacy of long‐term entecavir therapy in reduction of the risk of hepatocellular carcinoma (HCC), cirrhotic events and mortality in a large group of CHB‐related cirrhosis patients.

Adjuvant heparanase inhibitor PI-88 therapy for hepatocellular carcinoma recurrence.

AIM To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma (HCC) recurrence for up to 3 year following curative resection. METHODS A total of 143 patients (83.1% of the 172 participants in the phase II study) participated in the follow-up study. Of these patients, 50 had received no treatment, 48 had received 160 mg/d PI-88, and 45 had received 250 mg/d PI-88 during the phase II trial. Safety parameters and the following efficacy endpoints were investigated: (1) time to recurrence; (2) disease-free survival; and (3) overall survival. RESULTS PI-88 at 160 mg/d delayed the onset and frequency of HCC recurrence, and provided a clinically significant survival advantage for up to 3 years after treatment compared with those of the control group: (1) the recurrence-free rate increased from 50% to 63%, and (2) time to recurrence at the 36th percentile was postponed by 78%. The efficacy of administering PI-88 at 250 mg/d was confounded by a high dropout rate (11 out of 54 patients). Additionally, subgroup analyses of patients with (1) multiple tumors or a single tumor ≥ 2 cm; and (2) hepatitis B or C revealed that administering PI-88 at 160 mg/d conferred the most significant survival advantage (56.8% improvement in disease-free survival, P = 0.045) for patients with both risk factors for recurrence. CONCLUSION Administering PI-88 at 160 mg/d is a safe and well-tolerated dosage that may confer significant clinical benefits for patients with HCC.

527 SUSTAINED HCV CLEARANCE AND INCREASED HBSAG SEROCLEARANCE IN PATIENTS WITH DUAL CHRONIC HEPATITIS C AND B POST-PEGINTERFERON ALFA-2A AND RIBAVIRIN TREATMENT: A 5-YEAR FOLLOW-UP

8 weeks than that of in placebo group, but there were no significant difference between lamivudine and entecavir group. The number of patients in lamivudine and entecavir group with undetectable HBV DNA was 30.5% and 36.6% at week 12 respectively, there was significant difference between two groups (P < 0.05). Among patients with HBeAg positive diseases, 45.3% patients in lamivudine group and 44.7% in entecavir group lost HBeAg at follow up week 12 respectively, whereas none in placebo group. 36.0% patients in lamivudine group and 34.2% in entecavir group had HBeAg seroconversion at week 12, while none of patient in placebo had HBeAg seroconversion at follow up period. Conclusion: Antiviral treatment therapy can significantly reduce the mortality of patients with chronic hepatitis B liver failure. Both lamivudine and entecavir can be prescribed as an initial treatment in patients with chronic hepatitis B liver failure to reduce the mortality.