Rajko Ostojić

Endoscopic ultrasound elastography as a method for screening the patients with suspected primary sclerosing cholangitis.

Objectives Currently, magnetic resonance cholangiography is being used for establishing the diagnosis of primary sclerosing cholangitis, whereas endoscopic retrograde cholangiography is reserved for therapeutic interventions. The aim of this study was to determine the role of endoscopic ultrasound elastography in the detection of inflammatory and fibrotic lesions of the common bile duct. Methods Linear endoscopic ultrasound elastography of the common bile duct was performed in 41 patients. The patients were divided into two groups: disease group (20 patients with both, primary sclerosing cholangitis and inflammatory bowel disease) and control group (21 patients). Main outcome measurements were diameter, wall thickness and wall qualitative Elasto Score of the common bile duct. Results The disease group consisted of nine females and 11 males, whereas the control group consisted of 13 females and eight males, with no sex differences observed (χ2 = 0.6, d.f. = 1, P = 0.443). There was no significant difference in the diameter of common bile duct between the studied groups: 4.67±1.83 mm in the disease group and 5.88±2.47 mm in controls (t = −1.77, d.f.  = 39, P = 0.085). Hard or mixed Elasto Score was found in 16 patients and four controls, being significantly different compared with the soft Elasto Score found in four patients and 17 controls (χ2 = 1.8, d.f.  = 1, P<0.001). A significant difference was observed in the common bile duct wall thickness: 0.89±0.59 mm in the disease group and 0.39±0.14 mm in controls (t = 3.75, d.f.  = 39, P<0.001). Conclusion Endoscopic ultrasound elastography might be a useful noninvasive method in diagnosing primary sclerosing cholangitis.

Hypervariable Region 1 of Hepatitis C Virus Genome and Response to Interferon Therapy

Abstract The relationship between the complexity of the hypervariable region 1 (HVR1) quasispecies of hepatitis C virus (HCV) and responsiveness to interferon-α (IFN) therapy was studied in patients with chronic hepatitis C. Twelve HCV-RNA-positive patients were treated daily with high dose IFN and ribavirin for 4 weeks, and then with IFN 3 MIU (Million International Units) TIW (three times per week) and ribavirin for 6 months. The HVR1 quasispecies complexity was analyzed by nested polymerase chain reaction-mediated single-strand conformation polymorphism (SSCP). The baseline HCV-RNA levels in the study group ranged from 106 to 107 copies/ml. All patients exhibited HCV genotype 1 b. Initial SSCP analysis revealed four (33.3%) patients with a low complexity pattern (SSCP bands ≤4) and eight (66.6%) patients with high complexity pattern (SSCP bands >4). After 4 weeks of IFN therapy, one patient became HCV negative, and among those remaining positive, the HCV-RNA levels decreased by 2 to 3 logs and the number of SSCP decreased by 2 to 3 bands per sample. After 6 months of IFN therapy, five (41.7%) patients became HCV-RNA-negative. Seven (58.3%) patients did not respond to IFN therapy with sustained viral load from 103 to 105 copies/ml, and high complexity SSCP patterns. Our data support the HVR quasispecies complexity to be an independent predictive factor for IFN responsiveness in patients infected with HCV.

Pegylated interferon for treatment of chronic hepatitis C in hemodialysis patients in Croatia

Background and Aims: Hepatitis C virus (HCV) infection is a frequent complication among long-term dialysis patients. The aim of the present study was to evaluate the efficacy and side effects of pegylated interferon-α2a (PEG-IFN-α2a) treatment in hemodialysis patients. Methods: We retrospectively reviewed charts of 16 HCV-RNA-positive hemodialysis patients. Results: There were 11 male and 5 female patients treated with dialysis for 6–28 years. Twelve patients had HCV genotype 1b, 2 patients had 3a, and 1 patient had genotype 2a. Although only 10 out of 16 patients completed 48 weeks of treatment, early virological response and end-of-treatment virological response were achieved in 9 and 13 patients, respectively. Sustained virological response was recorded in 9 patients. The most common side effect was anemia. A flu-like syndrome was documented in 6, myalgia in 4, and arthralgia in 5 patients. Rectorrhagia, endocarditis and severe cough were recorded in 1 patient each. Nine patients received a renal transplant, and all 6 responders remained HCV-RNA-negative. Conclusions: PEG-IFN-α2a has limited efficacy in dialysis patients. A significant proportion of patients discontinued treatment because of side effects. Additional studies with long-term follow-up are needed to determine the optimal treatment of HCV infection in the dialysis population.

Pharmaceutical Principles of Acid Inhibitors: Unmet Needs

Despite the well-established benefits of currently approved delayed-release proton pump inhibitors (PPIs) in the treatment of acid-related diseases, the unmet needs are still present and although often frustrating, they challenge clinicians. The unmet needs relate to the lack of complete control of acid secretion with oral PPI administration in the management of patients with gastroesophageal symptoms. These substantial groups of patients, who do not respond completely to standard doses of PPIs, are nonresponders, and their lack of response should be considered as PPI failure. Several mechanisms could explain PPI failure: differences in pharmacokinetics, PPI formulation, dosing time and diet, noncompliance, transient lower esophageal sphincter relaxations, esophageal hypersensitivity, and nocturnal acid breakthrough. To increase the quality of life of these patients and avoid multiple medical consultations and unnecessary investigations, we have to go one step forward and use combined therapy or look towards new treatments beyond acid suppression.

POLITIKA LIJEKOVA I UGRADBENIH MATERIJALA U ZEMLJAMA EUROPSKE UNIJE I REPUBLICI HRVATSKOJ

Sažetak: Osnovni cilj provedenog istraživanja bio je dobiti uvid u znacajke politike lijekova i ugradbenih materijala zemalja clanica Europske unije (EU) i Republike Hrvatske te donijeti zakljucke i potencijalne smjernice za buduce djelovanje. Istraživanje je provedeno metodom polustrukturiranih intervjua na uzorku od 49 ispitanika iz podrucja zdravstva. Identificirani su kljucni problemi politike lijekova u zemljama clanicama EU proizasli iz razlicitih i visokih cijena lijekova i ugradbenih materijala, nedostatka inovacija, nejednake dostupnosti lijekova, dugog cekanja na odobrenje lijeka te slabe konkurentnosti farmaceutske industrije EU. Najvažniji problemi politike lijekova u Hrvatskoj povezuju se s procedurom nabave i registracijom lijekova, troskovima i nedovoljnom informiranoscu struke. Potrebno je poboljsanje klinicke prakse te promicanje propisivanja generickih lijekova. Povecanje dostupnosti kvalitetnih i sigurnih lijekova moguce je putem komplementarnog djelovanja javnog i privatnog sektora. Nadalje, nužno je kontinuirano i sistematsko pracenje propisivanja i analiza potrosnje lijekova te okrupnjavanje nabave istih. U buducnosti se ocekuju bolji uvjeti za primjenu novih tehnologija, stroža kontrola te ujednacenost standarda s onima u EU.

T2001 Quasispecies Changes Detected in Hypervariable Region 1 of Hepatitis C Genome With High-Resolution DNA Melting Analysis in Treated and Untreated Chronic Hepatitis C Patients

HCV exists in an individual as pool of closely related but genetically distinct variants. Development of resistant variants can be the reason of treatment failure. Aim of this study was to determine the changes in HCV quasispecies in region susceptible for mutations. Quasispecies were detected by new method, highresolution DNA melting analysis, in hypervariable region-1 at two points: 1. forty untreated patients: at baseline and after 6 months ; 2. sixty-nine treated patients: at baseline and at the end of treatment. Second sample was collected for all untreated and for 24 treated patients (45 had ETVR). For each sample result was shown as melting curve with 4 parameters: Tm (melting temperature), H (high), W (wide) and A (area). The most common genotype was 1 in both groups (57.5% in untreated and 83.3% in treated). Obtained baseline Tm was statistically significantly correlated with genotype obtained with commercial kits (p = 0.05). No significance was found for other baseline parameters. No statistical significances have been found in Tm, H, W and A for untreated and treated patients between paired samples but medians have changed in both groups (table 1 and 2).Trend of changes differed between groups, in untreated patients W and H raised while in treated declined. Without treatment, quasispecies become more heterogeneous while therapy makes them more homogeneous, towards resistant variants. Since no significant changes have been found in Tm it might be concluded that all observed changesdeveloped between same genotype at baseline.

Viral kinetic study of induction dosing with interferon alpha and ribavirin in the treatment of chronic hepatitis C

Viral kinetic study of induction dosing with interferon alpha and ribavirin in the treatment of chronic hepatitis C

The efficacy of injection slerotherapy, fibrin glue and hemoclips in stopping bleeding from gastroduodenal ulcers

The efficacy of injection sclerotherapy, fibrin glue and hemoclips in stopping bleeding from gastroduodenal ulcers