CROATIAN GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF NONALCOHOLIC FATTY LIVER DISEASE.

Nonalcoholic fatty liver disease (NAFLD) is a term describing excessive accumulation of fat in hepatocytes, and is associated with metabolic syndrome and insulin resistance. NAFLD prevalence is on increase and goes in parallel with the increasing prevalence of metabolic syndrome and its components. That is why Croatian guidelines have been developed, which cover the screening protocol for patients with NAFLD risk factors, and the recommended diagnostic work-up and treatment of NAFLD patients. NAFLD screening should be done in patients with type 2 diabetes mellitus, or persons with two or more risk factors as part of metabolic screening, and is carried out by noninvasive laboratory and imaging methods used to detect fibrosis. Patient work-up should exclude the existence of other causes of liver injury and determine the stage of fibrosis as the most important factor in disease prognosis. Patients with initial stages of fibrosis continue to be monitored at the primary healthcare level with the management of metabolic risk factors, dietary measures, and increased physical activity. Patients with advanced fibrosis should be referred to a gastroenterologist/hepatologist for further treatment, monitoring, and detection and management of complications.

[ABNORMALITIES OF HEMOSTASIS IN PATIENTS WITH LIVER CIRRHOSIS].

Until the beginning of the 90ies, it was believed that patients with liver cirrhosis were auto-anticoagulated and thus protected from thromboembolic events. However, new discoveries have broken the longstanding paradigm. In deranged hepatic function there is a reduced synthesis of procoagulants and endogenous anticoagulants, however, extrahepatally synthesized hemostatic and fibrinolytic factors are disproportionately affected. In stable disease hemostatic system is "rebalanced'' but fragile, therefore, even a minimal stress can promote bleeding or thrombosis. Also, there are many concomitant factors, such as hemodynamic changes, other organ affection, namely kidney, and predisposition to infection, that shift the balance towards either bleeding or thrombosis. Conventional laboratory tests are not sufficient for evaluation of the bleeding risk, prothrombotic risk factors are not clearly identified, and safety profile of antithrombotic drugs is not precisely evaluated since cirrhotic patients are mainly excluded from big clinical trials. For all that is said, the diagnostic and therapeutic approach in this context is complex and requires teamwork of a hepatologist, hematologist and in a phase of operative treatment, the anesthesiologist. In this review article, we will discuss mechanisms of hemostatic and fibrinolytic abnormalities of liver cirrhosis, the incidence of thromboembolic events as well as prophylactic and therapeutic options in the setting of conservative treatment.

Liver steatosis replaced with non-invasive viral and host parametars can serve as negative predictive model in patients with chronic hepatitis-C.

Almost 70% of chronic hepatitis C (CHC) patients will have concomitant hepatic steatosis (HS) usually determined with invasive method. HS serve as negative predictive factor for lower sustained viral response (SVR) in CHC patients treated with standard of care (SOC) (PEG-IFN and Rib). Retrospective analysis of biochemical, virological and histological data in CHC patients treated with PEG-IFN and Ribavarin. Statistical analysis was carried out by Biometriha Healthcare Research. Level of significance was set to 95% (p < 0.05). 72 patients (43 M; 29 F; median age 41 y) with CHC (60 G1; 12 G3) with no concomitant metabolic syndrome were analyzed. HS ranged from 5 to 30% (median 15%). Overall accuracy of prediction of SVR based on the levels of HS was AUC=0.71 (95% CI=0.58-0.84; p=0.005). When HS was split regarding cut-off value of 5% significant difference was found between responders and non-responders to treatment (chi2 = 10.025; df = 1; p = 0.002). Overall sensitivity was 48% and specificity 91%. Conventional predictive variables (gender, age, fibrosis and genotype) where combined with HS (>5%) and all together achieved Nagelherke R squared of 34.0% in prediction of SVR, with accuracy rate of 75.0%. Further, invasive variables (fibrosis and HS) where replaced with vire mia and body mass index (BMI). All noninvasive variables together achieved Nagelkerke R squared of 26.5% in prediction of SVR with 74% accuracy rate of the logistic regression model. Very low HS (<5%) is negative predictor of SVR and can be replaced with noninvasive variables (gender, age, viremia and BMI) with same accuracy rate of the logistic regres- sion model.

[Breast cancer metastases to the stomach and colon: two case reports]. / Metastaze karcinoma dojke u zeludac i debelo crijevo: prikaz dviju bolesnica.

Summary. Breast cancer has a high potential for metastasis, usually to the lungs, bones, liver and lymph nodes. Metastases in the holow organs of the digestive system are rare and mainly affectes the stomach and colon. They are characterized by very different clinical and radiological manifestations. We have warned that the initial unrecognized breast cancer can appear as a primary tumor of the stomach and colon, and onlya histopathological analysis reveales that it is a metastatic breast cancer. Metastases to the stomach or intestine involve deep layer of the mucosa and pathohistological findings of standard biopsy sample can be falsely negative, despite positive imaging technique (abdominal ultrasound and MSCT, endoscopic ultrasound) that indicate the tumor process. That's,why we emphasize the importance of endoscopic mucosal resection in the detection of malignant process of deeper layers of the gastric mucosa and deep intestinal mucosal biopsies with postoperative analysis of its walls.

[Endoscopic mucosal resection of sessile polypoid colorectal lesions: a two-year retrospective study, technique description, indications and complications]. / Endoskopska mukozna resekcija sesilnih polipoidnih lezija debelog crijeva: dvogodisnja retrospektivna analiza, prikaz tehnike, indikacija i komplikacija.

INTRODUCTION: Endoscopic mucosal resection (EMR) is a therapeutic method for removal of sesile premalignant lesions and intramucosal carcinoma of the gastrointestinal tract. No reports on EMR data in Croatia have been published yet. MATERIALS AND METHODS: All patients included in the study were managed at the University Hospital Centre Zagreb between December 2006 and December 2008. EMR was performed using strip technique with submucosal injection of epinephrine (dilution with saline 1:5000-10000). RESULTS: EMR of sessile polypoid colorectal lesions was performed in 95 patients. The most common localisation of the disease was rectum (52 pts - 54.7%). In most patient size of the lesion was between 16-25 mm (43 pts - 45%). En-bloc resection was performed in 75 patients and piecemeal resection in the rest. Bleeding occurred immediately during the EMR in 5 pts (5.3%). Patohistological diagnosis revealed tubulovillous adenoma in 67 pts (70%). Invasive carcinoma was observed in 6 pts (6.3%) and intramucosal carcinoma in 20 pts (21%). On follow up, 73 pts (77%) did not show and sign of disease recurrence. Surgery was needed in 6 pts (6.3%) due to the diagnosis of invasive carcinoma. CONCLUSION: EMR is safe and reliable method with low risk of serious complications and acceptable recurrence rate.

Hepatocellular Carcinoma Surveillance-Experience from Croatian Referral Centre for Chronic Liver Diseases.

PURPOSE: For patients at high-risk of developing hepatocellular carcinoma (HCC), biannual ultrasound surveillance has long been recommended, in order to detect the tumor in the early, potentially curative stages. However, globally reported HCC surveillance rates vary greatly, ranging from as low as 1.7 to as high as 80%. Our aim was to assess the utilization of surveillance with biannual ultrasound in high-risk Croatian patients and to identify the factors that impact the implementation of the recommended protocol. METHODS: This retrospective study included 145 newly diagnosed HCC patients in the period from January 2010 to September 2015. We identified low-risk and high-risk patients. The latter were further subdivided into the regular biannual ultrasound surveillance group and the non-surveillance group. The groups were compared according to demographic characteristics and BCLC stage at the time of HCC diagnosis. RESULTS: Among 145 patients, 80 patients were classified as high-risk according to EASL criteria. During the relevant period, 28.7% underwent regular surveillance, while 71.25% did not. Younger patients were more likely to undergo surveillance (OR 0.935 CI 0.874-0.999; p = 0.05). The patients who underwent regular surveillance had a higher chance of being diagnosed at a curative stage (BCLC 0 or A) (OR 3.701 CI 1.279-10.710; p < 0.05).Gender was not a predictor of participation in the regular surveillance protocol. Among the high-risk patients who did not undergo regular surveillance, 56.1% were not aware of the chronic liver disease prior to the HCC diagnosis. CONCLUSION: HCC surveillance is still underutilized in high-risk Croatian patients despite its obvious benefits possibly due to the untimely diagnosis of the chronic liver disease.

Nutritional Status and Nutrition Quality in Patients with Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is becoming a major health burden with increasing prevalence worldwide due to its close association with the epidemic of obesity. Currently there is no standardized pharmacological treatment, and the only proven effective therapeutic strategy is lifestyle modification, therefore it is important to determine the potential dietary targets for the prevention and treatment of NAFLD. We assessed nutritional status in 30 patients diagnosed with NAFLD using anthropometric parameters, hand grip strength, and lifestyle and dietetic parameters (physical activity, NRS2002 form and three-day food diary). The mean body mass index was 29.62±4.61 kg/m2, yielding 86.67% of obese or overweight patients. Physical activity results indicat-ed poorly active subjects. Excessive energy intake was recorded in 27.78% of patients. The mean in-take of macronutrients was as follows: 15.5% of proteins, 42.3% of carbohydrates and 42.2% of fat, with -deficient micronutrient intake of calcium, magnesium, iron, zinc, and vitamins A, B1 and B2. The -results showed that the quality of nutrition in study subjects was not accordant to current rec-ommendations and that they consumed a high proportion of fat, especially saturated fatty acids, along with low micronutrient intake. The results obtained might point to the importance of unbalanced diet as a contributing factor in NAFLD development.

Clinical analysis of propofol deep sedation for 1,104 patients undergoing gastrointestinal endoscopic procedures: a three year prospective study.

AIM: To analyze the hemodynamic and respiratory effects of propofol on patients undergoing gastroscopy and colonoscopy. METHODS: In this prospective study, conducted over a period of three years, 1,104 patients referred for a same day GI endoscopy procedure were analyzed. All patients were given a propofol bolus (0.5-1.5 mg/kg). Arterial blood pressure (BP) was monitored at 3 min intervals and heart rate and oxygen saturation (SpO2) were recorded continuously by pulse oximetry. Analyzed data acquisition was carried out before, during, and after the procedure. RESULTS: A statistically significant reduction in mean arterial pressure was demonstrated (P < 0.001) when compared to pre-intervention values, but severe hypotension, defined as a systolic blood pressure below 60 mmHg, was noted in only 5 patients (0.5%). Oxygen saturation decreased from 96.5% to 94.4 % (P < 0.001). A critical decrease in oxygen saturation (< 90%) was documented in 27 patients (2.4%). CONCLUSION: Our results showed that propofol provided good sedation with excellent pain control, a short recovery time and no significant hemodynamic side effects if carefully titrated. All the patients (and especially ASA III group) require monitoring and care of an anesthesiologist.

[Syndrome of acute abdomen in gynaecology and obstetrics]. / Sindrom akutnog abdomena u ginekologiji i opstetriciji.

The syndrome of acute abdomen in gynecology and obstetrics can develop due to inflammatory, ischemic-obstructive and hemorrhagic intra-abdominal etiology as a complication of primary disease, pathologic processes on some organs or injuries (genital, gastrointestinal, urinary, vascular, neurologic and musculoskeletal systems). Clinical and ultrasound examination, x-ray diagnosis, laparoscopy (in early pregnancy) and laboratory findings are the basic diagnostic methods to evaluate etiology of acute abdomen syndrome in gynecology and obstetrics. Rare cases with atypical clinical pictures and etiology of acute abdomen syndrome in gynecologic and obstetric casuistic are described.

ATP7B Gene Mutations in Croatian Patients with Wilson Disease.

AIMS: Wilson disease (WD) is an autosomal recessive disorder of copper metabolism, characterized by its accumulation in tissues which results in hepatic, neurological, and/or psychiatric symptoms. The aim of this study was to investigate the genetics of WD in Croatian patients. METHODS: Correlation of the clinical presentation subtype and the age at onset of the diagnosis of WD with the ATP7B genotype was investigated in a group of Croatian WD patients. DNA from peripheral blood samples was tested for the p.His1069Gln by direct mutational analysis and other polymorphisms were identified by sequence analysis of coding and flanking intronic regions of ATP7B gene. RESULTS: In the group of 75 WD patients of Croatian origin, 18 different mutations in ATP7B gene were detected, three of which were novel. The p.His1069Gln mutation was most frequent, being detected in 44 Croatian WD patients (58.7%). Most ATP7B mutations (90.4%) were located in exons 5, 8, 13, 14, and 15. CONCLUSIONS: Clinical diagnosis of WD was confirmed in 59 patients by detecting mutations on both ATP7B alleles. The age at onset of WD and the type of WD clinical presentation showed no significant correlation with the ATP7B genotype.

[First online continuing tele-education in gastroenterology in Croatia]. / Prva "on-line" trajna teleedukacija iz gastroenterologije u Hrvatskoj.

The expansion and popularity of the Internet created the expansion of tele-medicine, with tele-education as its important part. Such on-line distance learning is especially important for diseases being in the focus of public health interest, as diseases of the gastrointestinal, hepatobiliary and pancreatic system due to their frequency. Therefore, in this study is shown the "TIGEL project of tele-interventional gastroenterology" that was launched in May 2001 at the Center for Interventional Gastroenterology, Department of Gastroenterology, University Department of Medicine, Zagreb University Hospital Center. The project includes creation of a web site at the server of the Zagreb University School of Medicine (www.mef.hr/edumed/gastro/index.html), and among the most important goals of the project is continuous medical tele-education in gastroenterology. Beside description of the project, one of the founders of continuous on-line medical education in Croatia, this work describes many advantages but also some still unsolved questions considering medical tele-education, a very promising but still developing way of education.

[Percutaneous endoscopic gastrostomy: 5-year experience at out center (1997-2002)]. / Perkutana endoskopska gastrostomija: petogodisnje iskustvo naseg centra (1997-2002).

Gauderer and Ponsky first described percutaneous endoscopic gastrostomy (PEG) in 1979. It was introduced as a routine method in the Division of Gastroenterology, University Hospital Rebro, Zagreb, in 1995. Over the years the number of PEG insertions has increased significantly. We reviewed the available literature and compared the results with our experience according to indications, complications and efficacy of the procedure. We inserted PEG in 86 patients from January 1, 1997 until January 31, 2002. There were 40 females and 46 males. The most frequent indication for PEG insertion was a neurological condition (60/86). There were no deaths directly related to the procedure. One patient had a leakage of PEG feeding into the peritoneal cavity that caused severe peritonitis and required urgent laparatomy within 24 hours of the PEG insertion. Two patients had local infection and the tube had to be removed. The antibiotic prophylaxis has been given to 65 patients. Our experience confirms that PEG is a relatively safe and well tolerated procedure.