Single-center randomized trial comparing conventional chemoembolization versus doxorubicin-loaded polyethylene glycol microspheres for early- and intermediate-stage hepatocellular carcinoma.

According to Barcelona Clinic Liver Cancer classification, transarterial chemoembolization (TACE) is preferred treatment for stage B and in certain cases for stage A hepatocellular carcinoma (HCC). Conventional TACE (c-TACE) and drug-eluting microspheres TACE (DEM-TACE) are available intraarterial therapies. Screening of patients with cirrhosis is of great importance for early detection of malignant liver nodules. Primary endpoint of this study was to compare DEM-TACE with c-TACE in terms of 12- and 24-month survival. Secondary endpoints were comparison of intensity and duration of the postembolization syndrome (PES) and severe adverse events. We randomized 60 patients with unresectable HCC one-to-one with c-TACE or DEM-TACE and followed them for at least 24 months or until death. TACE was repeated 'on-demand. Most patients underwent two TACE sessions and the median hospital stay was 3 days for c-TACE and 2 days for DEM-TACE group. The overall 12- and 24-month survival rates were 89.8 and 70.7%, respectively, precisely 85.7 and 63.6% after c-TACE and 90.2 and 75.8% after DEM-TACE, without any significant difference (P = 0.18). Median overall survival was 21.1 months. Significant difference in the overall 12- and 24-month survival was found in patients with Child-Pugh A compared to Child-Pugh B class (P = 0.001). Child-Pugh class, aspartate aminotransferase levels and ascites independently predicted survival (P = 0.003). Both, DEM-TACE and c-TACE showed excellent 12- and 24-month survival rates. No significant difference in terms of adverse events was found. PES was slightly more severe after c-TACE, because of elevated temperature. DEM-TACE requires shorter in-hospital stay.

Atorvastatin in Combination with Pegylated Interferon and Ribavirin Provided High Rate of Sustained Virological Response in Patients with Genotype 3 Hepatitis C Virus.

BACKGROUND: Chronic hepatitis C virus infection represents a more frequent cause of liver cirrhosis and hepatocellular carcinoma. Statins, inhibit HCV replication in vitro, enhance the antiviral effect of the already known antiviral drugs and reduce their resistance. AIM: To determine the impact of additional therapy (treatment with Atorvastatin 20 mg) to the standard antiviral therapy (pegylated interferon alpha-peg-IFN α and ribavirin) on achieving sustained virological response (SVR). MATERIAL AND METHODS: In the study which is comparative, open-label, prospective-retrospective, 70 patients diagnosed with chronic hepatitis C virus infection who met criteria for treatment with standard antiviral therapy combined with anti-lipemic therapy (Atorvastatin 20 mg) were included. Patients in the study were divided into two groups: one group of 35 patients receiving combination therapy (Atorvastatin + peg-IFN α + Ribavirin) and another group of 35 patients received only standard antiviral therapy. Those parameters were followed in all patients: genotyping, quantification of the virus, histological assessment of liver inflammation and fibrosis degree (before starting treatment), the presence of steatosis, laboratory analysis: hematology, liver, lipid and carbohydrate status, insulin blood level (the calculation of HOMA-IR) and body mass index (BMI) calculation. The overall treatment of the patients depends from the virus genotype, thus, patients with genotype 1 and 4 received 48 weeks standard antiviral therapy, but patients with genotypes 2 and 3 received 24 weeks of antiviral therapy. SVR was considered an undetectable level of HCV RNA levels 24 weeks after completion of antiviral therapy. The results were statistically analysed, and all results for p < 0.05 were considered statistically significant. RESULTS: Combination therapy leads to a slightly higher percentage of SVR (85.71%) in patients with chronic hepatitis C versus standard therapy (74.29%), but in a group of patients with genotype 3 this rate of SVR amounting to 95.83%. Combination therapy leads to significant improvement of lipid and glucose status after treatment, and in terms of side effects, there was no appearance of serious adverse events that would be a reason for discontinuation of the therapy. CONCLUSION: Combination therapy Atorvastatin + pegylated interferon alpha + Ribavirin leads to high rate of SVR of 95.83% in patients with chronic hepatitis C, genotype 3. Statins can be used safely in patients with chronic hepatitis C.

Safety Profile and Efficacy of Chemoembolization with Doxorubicin - Loaded Polyethylene Glycol Microspheres in Patients with Hepatocellular Carcinoma.

AIM: This study was designed as a preliminary investigation of safety and efficacy of LifePearl, polyethylene glycol microspheres loaded with doxorubicin for treatment of locally untreatable (i.e., unresectable and not suitable for local thermal ablation) hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Patients with locally untreatable HCC (mono- or bilobar disease, ECOG performance status 0-1, Chilg-Pugh score < 11) were analysed for this single arm Unicenter retrospective study. All the information were acquired through our local hospital information system. DEB-TACE was performed with 100-200 microns LifePearl loaded with 75-150 mg of doxorubicin depending on tumour size. One interventional radiologist with experience of more than 350 TACE procedures and one fellow in radiology performed all embolisations. RESULTS: Twenty subjects with 29 tumours were treated (mean age 66.2 years). Child-Pugh status was A for 12 pts. (60%), B for 6 pts. (30%) and C for 2 pts. (10%). Three patients had insignificant ascites. Most patients (70%) underwent < 3 DEB-TACE procedures. Average doxorubicin dose was 71.1 mg per procedure. One patient had procedure-related SAE (acute pancreatitis) within the postembolization period which was induced due to non-target embolisation of the superior pancreaticoduodenal artery. Six-month freedom from procedure-related SAE or death was 95% (one necrotizing pancreatitis). Tumor response or stable disease was achieved in 95% (19/20) of subjects. Freedom from tumor progression or death at 6 months was 95%. One-year survival rate was 90% overall. CONCLUSION: The results from this investigation suggest that LifePearl microspheres, Terumo loaded with doxorubicin can provide an excellent local tumour control with very few side effects in a relatively homogeneous group of patients with locally untreatable HCC.