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Aim To analyse the impact of the length of antiviral therapy with tenofovir disoproxil fumarate (TDF) on the renal function in patients with chronic hepatitis B (CHB). Methods A cross-sectional study included 75 patients with CHB treated with tenofovir, who had a normal renal function at the beginning of the treatment. Renal function was determined based on glomerular filtration rate (eGFR) value using the Modification of Diet in Renal Disease formula (MDRD). Measurement of serum creatinine concentration and urinary protein excretion were performed using standard laboratory analyses. Viral load quantification (HBV-DNA) was determined by polymerase chain reaction (PCR). The degree of liver fibrosis was determined using fibrosis4 (FIB-4) and aspartate transaminase to platelet ratio index (APRI) fibrosis score. Results Out of 75 CHB patients, 37 were on antiviral treatment for up to 2 years (group 1) and 38 patients on antiviral treatment longer than two years (group 2). Mean age of patients was not significantly different between the groups (p=0.076), nor was the gender distribution. There was no statistically significant difference between the mean values of the eGFR in the two groups (91.89±9.24 vs. 88.42±7.84 mL/min/1.73m2; p=0.42), as well as between the mean values of serum creatinine (p=0.360) and 24-hour urine protein excretion (p=0.380). There was no statistically significant correlation between renal parameters and viral load, APRI and FIB-4 fibrosis score. Conclusion Results of our study did not show significant changes in the measured parameters of renal function in group 1 and group 2 of patients, regardless of the length of antiviral treatment, indicating a good renal safety profile of TDF.

Nerma Čustović, Aida Saray, Samra Ćato-Mehmedbašić, Ira Tančica, S. Sprečkić, N. Tokić, N. Herenda

OBJECTIVE The aim of our study was to determine the etiological factors, treatment and outcome of patients with non-variceal bleeding from upper gastrointestinal tract. MATERIALS AND METHODS This study enrolled 200 patients admitted to Sarajevo University Clinical Center with signs and symptoms of upper gastrointestinal bleeding, from January 2019 to July 2020. All patients had undergone gastroscopy, confirming the cause of gastrointestinal bleeding. Clinical and laboratory data were collected retrospectively, including previous non-steroid antiinflammatory drugs (NSAIDs) and anticoagulant therapy, comorbidities, risk factors, as well as endoscopic findings, laboratory findings, treatment and clinical follow-up. RESULTS The majority of patients were men (59%) with an average age of 53±6 years. Duodenal and gastric ulcers were the most common cause, followed by other etiologies. In our study, previous NSAIDs therapy had been registered in 29.5% of patients, anticoagulants in 8%, and proton pump inhibitors (PPI) in 2.9% of patients. Endoscopic intervention was required in 34% of patients. The need for transfusion occurred in 44.5% of cases. Rebleeding during hospitalization was observed in 7.5% of patients, mortality in 1.5% and surgery in 3% of patients. CONCLUSION The patients admitted to our hospital with symptoms of acute nonvariceal upper gastrointestinal bleeding were elderly, predominantly males, with significant comorbidities and a higher incidence of NSAID use. Gastroprotection is underutilized during NSAID treatment in patients with other coexisting risk factors, with a low rate of concomitant use of PPI during NSAIDs therapy. Endoscopic therapy, together with PPI, significantly reduces rebleeding rates, mortality and the number of emergency surgical interventions.

There is accumulating evidence that the coagulation system is involved in the process of fibrogenesis in chronic liver disease. Recent studies postulated a possible connection between plasmatic hypercoagulability and progression of fibrosis. The aim of the study was to investigate disorders of the coagulation system in patients with chronic hepatitis C having different extent of hepatic fibrosis well defined by liver histology. A total of 62 patients with chronic hepatitis C were recruited and categorized into 2 groups according to their histological fibrosis stage : mild/moderate fibrosis group (F0-F3 group, n = 30) and extensive fibrosis/cirrhosis group (F4-F6 group, n = 32). The control group consisted of 31 healthy individuals. The following hemostatic assays were evaluated: antithrombin III (AT), protein C (PC) activity, activated partial thromboplastin time, prothrombin time, plasma fibrinogen as well as conventional liver function test. The PC level exhibited a significant reduction in both patient groups when compared to the normal control group (89.25% ± 10.05% and 48.33% ± 15.86% vs 111.86 ± 10.90; P < .001 and P < .001). The PC was found to be the strongest associated factor to histological fibrosis stage (r = –.834; P < .0001). Univariate and multivariate analysis showed that AT (P = .003) and PC (P = .0001) were the most important factors associated with advanced fibrosis. The PC (P = .001) was found to be the only predictor of mild fibrosis. In conclusion, PC deficiency occurs in an early stage of liver fibrosis. The severity of deficiency is proportional to extent of fibrosis. The PC may have a key role in linking hypercoagulability with hepatic fibrogenesis in chronic liver disease.

ABSTRACT Introduction: Gastric cancer is the fourth most common cancer and the second leading cause of death from cancer. Only complete resection of all gross disease with negative microscopic margins (R0 resection) provides a long-term survival benefit, and the overall 5-year relative survival rate is approximately 20%. To improve survival and quality of life, new therapeutic approaches have been introduced. Material and methods: A total of 277 patients (171 men, 106 women) were included in this analysis. The results from the preoperative EUS and MDCT were compared to the postoperative pathological findings. A radial scanning ultrasonic endoscope was used. In patients with early gastric cancer, especially in cases confined to mucosa, endoscopic resection is performed to avoid unnecessary surgical procedures. To achieve R0 resection for locally-advanced gastric cancer, neoadjuvant treatments have been investigated. Results and discussion: Laparoscopic surgery has been shown to improve quality of life for both early and locally advanced gastric cancer. Endoscopic ultrasonography (EUS), which is considered to be the most precise method for locoregional staging, was commonly used for differentiating mucosal lesions from submucosal lesions. By contrast, computed tomography (CT) was used to detect the presence of distant metastasis. The difference in accuracy between the ≤20-mm group and other groups was statistically significant for both EUS and MDCT (P = 0.026 and P = 0.044, respectively). Conclusion: However, recent technological advances with the helical and multi-detector scanners have provided better CT performance.

Introduction: Gastric cancer is one of the most common tumors in humans and is on the 14th place by frequency in the United States and it is at the 8th place by the mortality rate. In the world it takes seventh place by incidence. Today prevail the opinion and the surveys show, that it is twice as common in men as compared to women. Although there are advancements in diagnostics it must be noted that gastric cancer is still discovered late and when it already has metastasized, so that the therapeutic approach is limited and low survival rate. Patients and Methods: The study was retrospective-prospective, which covered the period from 2011 to 2012 and was performed at the Clinic of Gastroenterohepatology, Clinical Center of Sarajevo University. The study included 50 patients with gastric cancer, 34 men and 16 women. All patients underwent gastroscopy and according to tumor lesions localization divided into 3 regions: cardia, corpus and antropyloric region. Tumor lesions were biopted with histologically confirmation of gastric wall cancer. All patients underwent CT of gastric wall, CT of the abdomen and in some cases EUS was performed also. Goal: To prove by available diagnostic methods (endoscopy, CT and EUS) the presence of gastric cancer, histologically validate it and determine localization according to regions. To determine by CT the thickness of the stomach wall or the penetration of tumor lesions, the presence of enlarged lymph nodes and possible metastases. Record by EUS the progression of malignant processes in depth to layers of the wall, surrounding tissue metastases and enlarged lymph nodes. Determine the correlation between the measured parameters. Results: Our study showed that the localization of tumors at the cardia was represented in 15.31%, corpus in 17.36% and antropyloric region 16.33%. Median age he was 65.5 years with a standard deviation of 11.04. We failed to demonstrate a statistically significant difference in verified findings by EUS and age as well as endoscopic findings and age. Also there is no statistically significant difference between the CT scan and endoscopy XT = 5.99 and α = 0.05 = 0.63 XE, XE XT) and endoscopic findings and age (XT = 3.84 at α = 0.01, = 0.01 XE, XE> XT). Conclusion: Our study showed that gastric cancer are more common in men than women, metastases were more common in the elderly population, there were no significant deviations from the endoscopic findings and CT findings. EUS was performed in a small number of patients and showed as a good method because it gave accurate information about the penetration depth. Endoscopy, EUS and CT are ideal methods in diagnostic and staging of gastric cancer before the surgery.

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.

AIM To analyze the usefulness of specified immunological parameters, proinflammatory IL-1α and profibrogenic, antiinflammatory TGF-β1, 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-β1. 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-β1 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-β1 has been found (-0.18). For IL-1 α significant predictive parameters included a previous infection of hepatitis B, lower serum level of TGFβ, age, use of alcohol, lower MELD and Chilld-Pugh scores. For TGF-β1 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-β1) 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-β1 are important parameters of inflammatory activity and fibrosis evaluation in chronic liver damage.

BACKGROUND Anaemia has been recognised as a key symptom of IBD. Although efficient therapeutic options have been developed for the treatment of IBD associated anaemia, treating anaemia often has a low priority for gastroenterologists. Compared with other manifestations of the disease, such as arthritis or osteopathy, anaemia in IBD has been given scant attention. AIM To evaluate prevalence of anaemia in patients treated for IBD in the Department of Gastroenterology and Hepatology, Clinical Centre, University of Sarajevo. PATIENTS AND METHODS The study was conducted between January 2010 and November 2012 as a retrospective observational clinical trial. Total of 210 patients were recruited. All patients with histopatological verification of IBD were divided into three groups, according to CDAI (Chronic Disease Activity Index): Biochemical parameters were recorded: full blood count, haemoglobin, haematocrit, RBC, WBC, proteinogram, fibrinogen, CRP. RESULTS Most of patients had haemoglobin serum level in range 100-120 g/l. Lower haemoglobin serum levels were measured in 40% of pts (CDAI>220). Lower haematocrit levels were detected in 38% of subjects with verified IBD ( CDAI>220). In the comparison of haematocrit level in the group of patients with CDAI>220 (moderate activity: 220-450 and high activity: >450) and CDAI<220 (low activity: 150-220) the statistical difference was at level p<0.04. In the comparison of haemoglobin level in the group of patients with moderate or high activity and low activity, by Student t-test the statistical difference was at level p<0.03. Hypoalbuminaemia was detected in 37.6% of patients. A significantly lower albumin level was in the group of moderate and high activity of IBD, at p<0.05 (ANOVA). Increased parameters of inflammation (CRP, fibrinogen and SE) were present in 35% of cases. CONCLUSION Anaemia could be the most common systemic complication of acute IBD. In our study 40 % of patients with IBD had anaemia; increased parameters of inflammation were present in 35% of cases. The control of inflammation is a key point, but often is not enough to treat anaemia. Patients should be followed up after completing treatment, and anaemia and iron deficiency actively assessed in the standard investigations.

Introduction: Colorectal cancer is the third most common tumor which causes high percentage of mortality in the general population. Etiologic factors which cause this disease are various, while diagnostic methods involve very complex protocols from detection of tumor markers to a combination of endoscopic and imaging methods. Goal: To determine the number of patients suffering from colon cancer for a period of two years and with endoscopic methods to verify and localize the tumor and its spread. Histopathological determination of the tumor type. Determine the concentration of CEA and CA 19-9 in the serum. Depending on the tumor location asses its progression, severity and extent by radiological imaging methods. Material and Methods: The study was prospective and retrospective, performed at the Gastroenterohepatology Clinic of the Clinical Center of Sarajevo University. During the two-year follow-up, 91 patients were hospitalized underwent endoscopy, targeted biopsy and histologically proven adenocarcinoma of the colon in which a pathologist determined grade of the cancers. Samples were eosin stained and underwent pathological histological analyzes. All patients according to tumor localization underwent CT scan and MRI of the rectum and pelvis. Results: The most common location of the cancer regardless of sex was in the recto sigmoid colon. Prevalence of colorectal cancer spread to other organs was not related to location. No significant dependence of the localization of the tumor by gender was found (p-value = 0.313). Ca 19-9 had the highest value in localization of tumors in the rectum. There was no statistically significant difference in age between men and women. The largest number of patients has adenocarcinoma grade 2 and the localization at the rectum. Conclusion: The combination of laboratory parameters (CEA and CA 19-9) with endoscopic and radiological imaging methods is essential in diagnosis of colorectal cancer and assessment of the process progression. There is a need to impose additional diagnostic parameters to detect the disease at an earlier stage.

Aims: Since its description in 1980, percutaneous endoscopic gastrostomy has become the modality of choice for providing enteral access to patients who require long-term enteral nutrition. This study aimed to evaluate current indications and complications associated with PEG feeding. Methods: We conducted a retrospective analysis of all patients who referred to our endoscopic unit of the Department of Gastroenterology and Hepatology of the Medical Center University of Sarajevo for PEG tube placement over a period of 7 years. Medical records of 359 patients dealing with PEG tube placement were reviewed to assess indications, technical success, complications and the need for repeat procedures. Results: The indications for enteral feeding tube placement were malignancy in 44% (n=158), of which 61% (n=97) patients were suffering of head and neck cancer and 39% (n=61) of other malignancy. Central nervous disease was the indication in 48.7 % (n=175) of patients. Cerebrovascular accidents (CVA) accounted for 20% (n=73), head injury for 16% (n=59) and cerebral palsy for 11% (n=38). In 6.13% (n=22) of patients minor complications occur which included wound infection (0.8%), inadvertent PEG removal (2.5%) and tube blockage (1.1%). 11 patients experienced major complications including hemorrhage, tube migration and perforation. There were no deaths related to PEG procedure placement and the overall 30-day mortality rate due to primary disease was 15.8%. Oral feeding was resumed in 23% of the patients and the tube was removed subsequently after 6 -12 months. Conclusions: Percutaneous endoscopic gastrostomy is a save and minimally invasive endoscopic procedure associated with a low morbidity (9.2%) rate, easy to follow-up and to replace when blockage occurs. Over a seven-year period we noticed an increase of 63% in PEG placement at our department.

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