Impact of sustained virus elimination on natural anticoagulant activity in patients with chronic viral hepatitis C.

Previous studies have reported reduced synthesis of various hemostatic factors in patients with chronic liver disease. Whether changes in plasma levels of these proteins reflect recovered liver synthetic function following virological eradication therapy has not been approved yet. The aim of the study was to determine the impact of sustained viral suppression achieved with pegylated interferon alpha and ribavirin on hemostatic parameters including natural anticoagulants in patients with chronic hepatitis C. The following coagulation screening tests were obtained in thirty patients with chronic viral hepatitis C before and after completion of antiviral treatment: activated partial thromboplastin time, prothrombin time, plasma fibrinogen and natural anticoagulant proteins antithrombin III, protein C (PC) and total protein S (PS) activity. Only patients who achieved durable virus suppression were included. The mean PC and PS levels were significantly lower in patients with chronic viral hepatitis C before antiviral therapy than in healthy controls (79.04 ± 16.19 % vs. 109.92 ± 21.33% and 54.04 ± 16.11% vs. 87.60 ± 8.15%, respectively; (p<0.001). Mean levels of PC exhibited a significant increase by 14.69 % after the completion of antiviral treatment (93.73 ± 14.18%, p<0.001) as well as PS levels, which significantly increased by 21.46% (75.50 ± 15.43, p<0.001) when compared with pre-treatment values. No remarkable fluctuations in other hemostatic parameters were noted. Protein C and protein S are sensitive markers of hepatocyte synthetic impairment and are valuable markers in monitoring the efficacy of antiviral treatment in chronic hepatitis C patients. Larger studies are needed to confirm our results.

Non-invasive liver fibrosis markers: use of serum levels of cytokines IL 1α and TGF ß1 in management of chronic liver diseases.

AIM: To analyze the usefulness of specified immunological parameters, proinflammatory IL-1α and profibrogenic, antiinflammatory TGF-ß1, along with routinely used laboratory tests, in the differential - diagnostic procedure of chronic hepatitis of infectious and noninfectious etiology. METHODS: A total of 150 subjects were divided into two groups, depending on the infectious or noninfectious etiology of liver damage, and the control group. Apart from standard laboratory tests, the analysis included serum levels of cytokines: IL-1α and TGF-ß1. RESULTS: A high degree of correlation of serum level of IL-1α with viral hepatitis has been found, especially with active replication of genetic material ( HBV-DNA or HCV-RNA-PCR positive), p less 0.01. The highest mean concentration of TGF-ß1 was noted in the group of malignant and toxic hepatitis, p less 0.0001. A negative correlation between the concentration of IL-1α and TGF-ß1 has been found (-0.18). For IL-1 α significant predictive parameters included a previous infection of hepatitis B, lower serum level of TGFß, age, use of alcohol, lower MELD and Chilld-Pugh scores. For TGF-ß1 significant predictive parameters were age, lower MELD and Child-Pugh scores, history of receiving transfusions, lower serum level of IL-1α, higher serum level of fibrinogen. A predictive model has been delivered MELD = (TGF-ß1) x 0,001- (IL-1 α) x 0,085 + CTP x 1,771-2,052; ( ± 2.04, R2=0,61; p less 0,001). CONCLUSION: Inflammatory and immune parameters, analyzed together could significantly contribute to the understanding of chronic liver damage and thus differential diagnostic procedure. IL-1α and TGF-ß1 are important parameters of inflammatory activity and fibrosis evaluation in chronic liver damage.

Tumor suppresser gene p53 expression in premalignant lesions and gastric carcinoma - prognostic value.

The aim of the study was to verify the presence of mutated tumor suppresser gene p53 in intestinal mucosa with histologically confirmed premalignant lesions and gastric carcinoma, and assess its prognostic value. The paper presents prospective study that included 50 patients with gastric adeno-carcinoma of intestinal type that were treated at Gastroenterohepatology Clinic, and 50 patients with histologically confirmed chronic atrophic H. pylori positive gastritis. In the mucosa biopsy samples, we analyzed presence, frequency and severity of inflammatory-regenerative, metaplastic and dysplastic changes. We typed intestinal metaplasia immunohistochemically and confirmed the presence of p53 onco-protein in antigen positive gastric carcinoma cells, and evaluated its prognostic value. Our results suggest that H. pylori acts as an initiator of inflammatory processes in gastric mucosa, which are followed by emergence of precancerous lesions. p53 is expressed late in carcinogenesis (14%) and as such, may be considered as an indicator of transformation of premalignant into malignant lesion.

[Evaluation of hepatitis C virus genotype and its influence on therapeutical respond on combined therapy with pegilated interferon A 2a (40)kD and ribavirin]. / Evaluacija genotipa hepatitis C virusa i njegov utjecaj na terapijski odgovor pegiliranim interferonom alpha 2a (40)kD u kombinaciji sa ribavirinom.

The aim of our study was to determine the genotypes of viral hepatitis C. We examined 54 patients with chronic hepatitis C who were treated at Gastroenterohepatology Department University of Sarajevo. We also monitored effects of therapeutical results in same group of patients. Polymerasa chain reaction (PCR) was used to quantified the number of HCV-RNA copies in 1 ml of blood. Genotype of virus was determined as well. We created therapeutical protocols based on genotype and quantity of virus that contained pegilated interferon alpha2a(40) kD and ribavirin. The result of our investigation presented that the highest number of patients, 25 had genotype 1a; 13 patients had genotype lb; 11 patients had genotype 3; 4 patients had genotype 4 and 1 patients with genotype 2a. At the end of therapy, 42 patients were HCV-RNA PCR negative; 7 female and 35 male. Four women with genotype 1a, responded on therapy; two with genotype 1b and one with genotype 3. Within the male group of patients (35 patients), 16 patients had a genotype 1a, 3 patients had a genotype 1b, 11 patients had a genotype 3, 4 patients had genotype 4 and one patient had genotype 2a. Patients who did not respond on therapy or were HCV-RNA-PCR positive at the end of therapy were genotype 1a and 1b. According to result of our investigation, genotype 1 is the most frequent among our patients, and the most severe damages in liver parenchyma are associated with genotype 1a and 1b. Genotype 1b also had less respond on therapy.

Incomplete intestinal metaplasia as an indicator for early detection of gastric carcinoma in the events of helicobacter pylori positive chronic atrophic gastritis.

The aim of the study was to ascertain the existence of intestinal metaplasia in gastric mucosa of patients with gastric carcinoma coupled with H. pylori positive chronic atrophic gastritis and possible connection of IM with the development of gastric carcinoma. The paper presents prospective study that included 50 patients with gastric carcinoma and 50 patients with chronic atrophic H. pylori positive gastritis. All the patients were subjected to gastroscopy as well as biopsy targeted at antrum, lesser curvature and corpus and at the area 1-2 cm removed from tumor lesion. Biopsy samples were sliced by microtome and stained. We analyzed presence, frequency and severity of inflammatory-regenerative, metaplastic and dysplastic changes in the mucosa and evaluated their prognostic value. We typed IM immunohistochemically. This study confirmed responsibility of H. pylori for inflammatory events in gastric mucosa in patients with gastric carcinoma. According to our findings incomplete IM of types IIa and IIb as precancerous lesion is responsible for the development of gastric carcinoma and is associated with chronic atrophic gastritis grade I and II (92% of subjects, p=0.0097, h=1, p=0.01). Thus, the finding of incomplete intestinal metaplasia may be used as an indicator for early gastric carcinoma detection. Patients with patho-histologically verified incomplete intestinal metaplasia associated with active chronic atrophic gastritis of levels I and II represent risk group for the development of gastric carcinoma of intestinal type.

Helicobacter pylori as a promoter of accelerated regeneration, pathological differentiation and transformation of normal gastric mucosa into cancerous type.

The aim of the study was to ascertain presence of Helicobacter pylori in gastric carcinoma as a responsible promoter of inflammatory-regenerative changes, which lead to pathological differentiation and transformation of normal epithelial cells into intestinal type and, in progression, cause epithelial dysplasia that develops into early gastric carcinoma. The paper presents prospective study that includes clinical, pathohistological and microbiological aspects of carcinogenesis initiation in gastric mucosa. The subjects are patients treated at Gastroenterohepatology Clinic divided into two groups. One group included 50 patients with gastric carcinoma while the control group included 50 patients with chronic atrophic H. pylori positive gastritis. All the patients were subjected to endoscopy as well as biopsy targeted at antrum, lesser curvature and corpus and at the region 1-2 cm removed from tumor lesion. We used HUT test to verify H. pylori presence in biopsy samples. We analyzed the samples for presence, frequency and severity of inflammatory-regenerative, metaplastic and dysplastic changes in gastric mucosa and evaluated their meaning for the prognosis. Our study confirmed Helicobaster pylori responsibility for inflammatory events in gastric mucosa in patients with gastric carcinoma. Slight and mild epithelial dysplasia with chronic atrophic gastritis grade I and II coupled with intestinal metaplasia may be considered an indicator for early detection of carcinoma. Such patients represent risk group for gastric carcinoma development.

[Imaging procedures in gastroenterology]. / Slikovne procedure u gastroenterologiji.

Recent achievements in fields of physics, microelectronical devices and informatical sciences opened huge possibilities of applications in medical specialities. Spread imaging over routine high-resolution instruments continue to be in focus of scientific researches varying from simple staining techniques to most sophisticated photodynamical techniques. Magnetic resonance imaging and computed tomography are radiological specialties, however; we mentioned them for promising achievements in computed data analysis and further improvements of virtual colonoscopy. During the last few years techniques of magnifying endoscopy have been improved including trials with narrow band endoscopy, autoflourescence endoscopy, elastic scattering spectroscopy and laser confocal microscopy. In many indications capsula endoscopy have been applied successfully.

[Four different treatment protocols for Helicobacter pylori infection--a clinical pilot study]. / Cetiri razlicita protokola lijecenja Helicobacter pylori infekcije--pilotska klinicka studija.

A pilot clinical trial specially designed to test four different treatment regimens of Helicobacter pylori infection was performed among hospitalized and outpatient based patients in Clinical Centre University of Sarajevo, Gastroenterohepatology Clinics. Another objective was to assess Helicobacter pylori total cradication rates, partial cradication rates and after treatment persistent Helicobacter pylori infection rates among patients with clinically proven peptic ulcer disease (PUS). All patients randomly assigned into four groups had endoscopically and Helicourcasa test (HUT Astra) proven peptic ulcers. Each group was treated with one of the following four triple regimens: ranitidine + amoxicillin + metronidazole (RAM); ranitidine + clarithromycin + metronidazole (RCM); omeprazole + amoxicillin + metronidazole (OAM) and omeprazole + clarithromycin + m etronidazole (OCM). All triple regimens were given twice-a-day for one week following either ranitidine or omeprazole for two weeks depending of basic regimens. The highest Helicobacter pylori eradication was produced with OCM regimens (91.7%). Using same regimens we found the lowest partial eradication rate of all regimens (8.3%) and no persistency of H. pylori after the treatment. The lowest total eradication rate was found using RCM regimens (67.7%), while there was no difference in the cure rate between OAM (76.9%) and RAM (77.3%) regimens. If it is applicable, recommended treatment regimen as a first choice for proven H. pylori infection is OCM.

[Endoscopic ultrasonography of the upper digestive tract]. / Endoskopska ultrasonografija gornje probavne cijevi.

Endoscopic Ultrasonography, or EUS, has joined medical techniques of endoscopy with high frequency ultrasound technique, known as ultrasound. This removable achievement allows physician for microscopic tissue examination, not only in digestive system, but also in its surroundings by highly frequent technique. Endoscopic ultrasonography detects all kinds and nature of possible abnormalities, including and information, which are necessary for proper diagnosis and optimal treatment. In experience hands, EUS can detect abnormalities, which are undetectable during any other techniques of examination. EUS is applied from inside the body, near or even touching the examined surface, so the precise, highly frequent energy of showing the images can be used. The sonography, MRI, CT techniques must show the inner organs through outside surface of body, loosing the resolution during process. The superior resolution of EUS shows 5 layers of digestive tract, almost equally good as by microscope; none of other techniques allows showing of intestinal wall equally good as this one. By EUS liquid has been proved with 90% of precision in diagnosis of operative degrees of pancreas tumours. CT in this case has shows only 50% of precision. Highly skilled surgeons are aware of application of these diagnostics techniques in preoperative cases so the surgical removement of tumours is going to be more effective. The precision of EUS findings are of critical importance for the utilisation of maximum of new treatment having in mind that abnormalities could be diagnosed and characterised without operative intervention. To be able to focus on specific anatomic surfaces, there is need of great knowledge, skillfulness and praxis during the manipulation with EUS instrument. The years of experience are needed to be able to achieve high standard of expertise. The accuracy of results varies, depending on physicians diagnostic experience, sub-optimal results are not going to be a good guide during treatment planning. Endosonographist must be in position to document at least 80% of accuracy in diagnosis and determination of disease stage in order to achieve 30-60% changes in plans treatment.

[Mucosal damage caused by nonsteroidal anti-inflammatory agents in H. pylori infection]. / Ostecenje sluznice uzrokovane nesteroidnim antiinflamatornim lijekovima kod prisustva H. pylori infekcije.

BACKGROUND: The pathogenic role of Helicobacter pylori (H. pylori) infection in the setting of NSAID use is still controversial. Aim of the study is to prove increased incidence of gastric mucosa damage in H. pylori positive NSAID users compared to H. pylori negative patients. METHODS: Patients with dyspeptic symptoms (n = 160, average age 62.13 +/- 6.24, ranged from 51 to 77 years) were divided in two groups: 80 patients (45 male, 35 female) with positive history of using NSAID and same group with negative history for NSAID. All patients underwent endoscopy, examined to H. pylori presence by rapid unease test. Patients with ulcer or erosions (> 5) were evaluated and grade of gastric mucosa damage were done according to Forrest classification of gastrointestinal bleeding. RESULTS: In first group 69/80 of examined patients were H. pylori positive, in second group 56/80 were H. pylori positive (X2 = 5.266; p = 0.022). In gastric mucosa bleeding, caused with NSAIDs, H. pylori was not diagnosed more often compared to other group (p > 0.05). CONCLUSION: Patients with NSAID induced gastric injury were significantly greater incidence of H. pylori infection compared to patients without history of NSAIDs abuse. H. pylori was not significantly present in complication of ulcer disease (bleeding) caused by NSAID.

[Proximal endoscopy--from diagnosis to therapy]. / Proksimalna endoskopija--od dijagnostike do terapije.

Gastroscopy is medical procedure which allows examination of esophagus, stomach and duodenum by flexible instrument named gastroscope. Procedure could be strictly diagnostical, with evidence of current state and interventional/therapeutical, by attempting of prompt action (haemostasis, mucosal resection of cancer "in situ", polypectomy, dilation of benign and malignant strictures of digestive tube, placing endoprosthesis over strictures) Despite of its invasive nature, endoscopy is daily routine, safe and accurate procedure.

[Endoscopy of the lower part of the digestive system]. / Endoskopija donjeg dijela probavnog sistema.

Examination of lower part of digestive system by colonoscopy is necessity in occult fecal hemorrhage occurrence, hematochesis, unresolved loss of blood iron and suspicious finding of large bowel X-ray barium study. By therapeutical colonoscopy, haemorrhage from neoplasms and angiodysplastic changes are controlled, foreign bodies are removed as well as routine polipectomics. Balloon dilation of large bowel stenosis, and palliative treatment of unoperable stenoses lead to improvement in quality of life with significant cost-benefit effects. Follow-up of patients on high-risk for colorectal neoplasms increased early diagnosis of neoplasms.

[Endoscopic retrograde cholangiopancreatograpy]. / Endoskopska retrogradna holangiopankreatografija.

Endoscopic retrograde cholangiopancreatography has been a "golden standard" in endoscopic radiological diagnosis and treatment of biliopancreatic pathology for a long time. Possibilities of biliary and pancreatic three imaging, with prompt conversion into therapeutical procedure--papillotomy, stone extraction, biliary and pancreatic stents placement over benign or malignant ductal strictures, is of outstanding value like very few other methods. Since time is measure by itself, "golden age" of ERCP has passed with non-invasive diagnostic procedures. However, in the endoscopic treatment of biliary and pancreatic pathology it still remains to be a golden standard.