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

Kвантитативно одредување на калпротектин во асцит кај пациенти со спонтан бактериски перитонитис

Spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis is a newly developed, spontaneous bacterial infection of sterile ascites fluid, in the absence of intraabdominal sources of infection or malignancy. The most sensitive indicator of diagnosis is when the polymorphonuclear cell count (PMNC) is ≥250 in 1 ml ascites fluid (manual microscopic or automated counting) and/or when a bacterial strain is isolated in microbiological culture. The objectives of our pilot study were to determine the concentration of calprotectin in ascites in patients with SBP and non-SBP with BíœHLMANN Quantum Blue®Reader, whether there was a significant difference between the average values "‹"‹of Turcotte-Pugh II and MELD score and to determine average values for CRP serum and ascites in the studied groups. Materials and methods. This prospective analytical observational pilot study included 30 patients with liver cirrhosis and ascites, divided into two groups, SBP and non-SBP. The quantitative measurement of calprotectin in ascites was performed with the Quantum Blue Calprotectin Ascites (LF-ASC25) test. The test is designed to selectively measure calprotectin antigen (MRP8/14) with direct sandwich immunoassay. The ascites samples were diluted with Chase Buffer 1:5 and after 12 minutes incubation at room temperature, the test line signal intensity and the control line were quantitated with BíœHLMANN Quantum Blue®Reader. The collected data were processed using the SPSS 23 statistical software for Windows. Results. In our study the average value of calprotectin in patients with SBP was 1.4 µg/mL. The lowest value of calprotectin in the study group was recorded in one patient at 0.61 µg/mL, while the highest value was 1.81 µg/mL in four patients. The results showed higher values "‹"‹of calprotectin in ascites in patients with alcoholic liver disease compared to other etiologies. Refractive ascites was reported in 60.0% of the subjects and only one patient (6.7%)was reported with Klepsiella pneumoniae in the microbiological analysis of ascites. According to the Child-Turcotte-PughII classification, all patients in the study group were class C, while the mean MELD score was 29.8±6.14. The difference between the average values of CRP in serum and ascites in patients with SBP was statistically significant compared to non-SBP. Conclusion. The quantitative determination of calprotectin in ascites by the Quantum Blue Calprotectin Ascites (LF-ASC25) assay can be used as an alternative to the determination of PMNC in ascites. SBP occurs in patients with severe hepatic dysfunction calculated according to the Child-Pugh II score and the MELD score. Serum and ascites C-reactive protein values were not significantly elevated in patients with SBP, but were significantly different from non-SBP patients.Спонтаниот бактериски перитонитис (СБП) кај пациентите со црнодробна цироза е новонастаната, спонтана бактериска инфекција на стерилна асцитна течност, во отсуство на интраабдоминални извори на инфекција или малигнитет. Најсензитивен показател за поставување на дијагнозата е бројот на полиморфонуклеарни клетки (ПМНК) ≥250 во 1 мл асцитна течност (рачно микроскопско или автоматизирано пребројување) и/или кога во микробиолошката култура биде изолиран еден бактериски вид. Цел на трудот е да се одреди концентрацијата на калпротектин во асцит кај пациентите со СБП и не-СБП, да се споредат просечните вредности на Turcotte-Pugh II и MELD скорот кај пациентите со СБП и не-СБП  и просечните вредности на C-реактивниот протеин во серум и во асцит во испитуваните групи. Материјали и методи. Во оваа проспективно-аналитичко-опсервациска пилот студија беа вклучени 30 пациенти со црнодробна цироза и асцит, поделени во две групи, СБП и не-СБП. Квантитативното мерење на калпротектин во асцит се вршеше  со тестот Quantum Blue Calprotectin Ascites (LF-ASC25). Тестот е дизајниран за селективно мерење на антигенот на калпротектинот (MRP8/14) со директен сендвич имуноесеј. Примероците од асцитот се разредуваа со  Chase Buffer во однос 1:5 и по 12 минути инкубација на собна температура,  интензитетот на сигналот на линијата за тестирање и контролната линија се мереа квантитативно со BÜHLMANN Quantum Blue®Reader. Собраните податоци се обработија со помош на статистичкиот програм SPSS 23 за Windows. Резултати. Во нашата студија просечната вредност на калпротектин кај пациентите со СБП изнесуваше 1,4 μg/mL. Најниската вредност на калпротектин во испитуваната група беше регистрирана кај еден пациент со вредност од 0,61 μg/mL,  додека највисока вредност од 1,81μg/mL кај четири пациенти. Резултатите покажаа повисоки вредности на калпротектин во асцит кај пациентите со алкохолна болест на црниот дроб во споредба со останатите етиологии. Рефракторен асцит се регистрира кај 60,0% од испитаниците, а само кај еден пациент (6,7%) се регистрира Klepsiella pneumoniae во  микробиолошката анализа на асцитот. Според Child-Turcotte-PughII класификација сите пациенти од испитуваната група беа класа C, додека просечната вредност на MELD скорот изнесуваше 29,8±6,14. Разликата помеѓу просечните вредности наC-реактивниот протеин во серум и во асцит кај пациентите со СБП  беше статистички сигнификантна во споредба со не-СБП.  Заклучок. Kвантитативното одредување на калпротектинот во асцит со тестот Quantum Blue Calprotectin Ascites(LF-ASC25) може да се користи како алтернатива наполиморфонуклеарните клетки (ПМНК) во асцит. СБП се јавува кај пациенти со сериозна црнодробна дисфункција пресметана според Child-Pugh II скорот и MELD скорот. Вредноста на C-реaктивниот протеин во серум и во асцит кај пациентите со СБП немаше високи вредности ,но сепак беше утврдена сигнификантна разлика во споредба со пациентите со не-СБП

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

PORTAL VEIN THROMBOSIS-ULTRASOUND IMAGING

Portal venous system, apart from the main portal vein, includes its tributaries: superior and inferior mesenteric vein, as well as splenic vein, so the term portal venous thrombosis encompasses a broad spectrum of pathological conditions. Usually, one or more causative factors can be recognized, either local endothelial/ flow disturbances, or systemic inherited /acquired conditions. Portal vein thrombosis can be associated with benign or malignant disorders. Weather we are speaking about acute or chronic thrombosis, the clinical presentation is different. Acute thrombosis can be presented in a wide range, from mild abdominal discomfort to a state of intestinal ischemia and life-threatening infarction. Chronic thrombosis is usually recognized when variceal bleeding or other symptoms of portal hypertension express. Fast and accurate diagnosis sometimes is a life-saving procedure, especially in acute vascular alterations. Recently, due to the improvement of imaging procedures the number of patients with diagnosed portal vein thrombosis is increasingly growing. With a negative predictive value of 98% color Doppler ultrasound is considered as imaging modality of choice in detecting portal vein thrombosis. Based on large studies it is presumed that overall risk of getting portal vein thrombosis during lifetime is 1% in general population, but much bigger 5%-15% in cirrhotic patients. Existence of specific ultrasound criteria, if fulfilled, has ensured that diagnosis of portal vein thrombosis is fast and non-invasive. Procedure is convenient for the patient and healthcare providers, and above all, allows prompt treatment preventing further deterioration