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.

THE OVER-THE-SCOPE-CLIP FOR THE TREATMENT OF THE DIGESTIVE TUBE LEAKS AND TEARS: A CASE-SERIES. / LIJECENJE OSTECENJA PROBAVNE CIJEVI PRIMJENOM ENDOSKOPSKE STEZALJKE: PRIKAZ SERIJE BOLESNIKA.

Digestive tube damages represent a therapeutic challenge for the gastrointestinal endoscopists. Recenty, a novel device ­ the-over-the-scope clip (OTSC) ­ has been introduced for non-surgical treatment of gastrointestinal perforations, fi stula, anastomotic leaks and refractory gastrointestinal bleeds. This study aimed to evaluate the therapeutic effi cacy of OTSC in our case series. A total of nine patients were included (six males, medain age 72 years, range 58-86). The indications were upper gastrointestinal bleeding (refractory to standard endoscopic treatment: fi ve patients, a vessel with a large caliber: one patient), fi stula in two patients, and iatrogenic perforation of the sigmoid colon in one patient. Atraumatic and traumatic versions of OTSCs with twin graspers were used. All of the patients were treated with only one OTSC, and none of the patients required additional endoscopic treatment. The OTSC procedure had 100% technical success. In a subgroup of patients with perforation and fi stulae, the clinical success was 67%, whereas in those with the bleedings it was 50%. The median follow-up was 34 days (range: 3-452). OTSC is a safe and effective device for closure of perforations and leaks. However therapeutic effi cacy was subopimal in patients with the upper gastrointestinal bleedings possibly due to the application of the sharp-teeth OTSC.

[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.

[PREDICTORS OF POOR BOWEL PREPARATION FOR COLONOSCOPY: A SINGLE-CENTRE PROSPECTIVE STUDY]. / PRETKAZATELJI LOSE PRIPREME BOLESNIKA ZA KOLONOSKOPIJU: MONOCENTRICNO PROSPEKTIVNO ISPITIVANJE.

Adequate bowel preparation is the key of a successful colonoscopy. The aim of the study was to analyze sociodemographic and clinical characteristics in our population of patients referred for colonoscopy. Bowel cleanness was evaluated using the Boston Bowel Preparation Scale (BBPS) where values 7 were considered a criterion of successful bowel preparation. The study involved 286 subjects (61.5% male, median 61 years, interquartile range 50-71). BBPS score 7 was found in 145 subjects (50.7%). Multivariate analysis indicated that subjects with severe comorbidity (ASA status 3, OR = 0,29; 95% CI: 0.12-0.72; p = 0,008) represented a risk factor for poor bowel preparation. Regimens with polyethyleneglycol (PEG) were superior compared with other protocols (OR = 2.54; 95% CI: 1.27-5.10; p = 0.008). Timing of the colonoscopy also contributed to better bowel preparation (OR = 5.50; 95% CI: 2.07-14.67; p = 0.001). This study confirms that presence of comorbidity and non-use of PEG regimens are predictors of poor bowel preparation in our population of patients referred for colonoscopy.

[Clinical characteristics of patients with a double pylori]. / Klinicke karakteristike bolesnika s dvostrukim pilorusom.

Double pylorus (DP), is a form of gastroduodenal fistula, which consists of a short accessory canal from the gastic antrum to the duodenal bulb, and mostly occrus in the background of peptic ulcer disease. Prevalence, as well long-term follow-up of patients with DP is less elucidated in western countries. Aim of our study was to analyse demografic, clinical and endoscopic characteristics in our case-series. During 2008-2013. a total of 23836 upper endoscopies were performed in 16759 patients. DP was diagnosed in 6 patients (prevalence of 0.04%). The follow-up period was f 8 to 72 months. In 87% DP was a complication of the upper gastrointestinal bleeding. In 83% cases opening of the fistula was on lesser curvature of gastric antrumu. During follow-up period the fistula healing did not occur in any of our patients. DP is a very rare entity, with a benign course of the disease Associated comorbidity and use of ulceriform medications plays important role in persistence of DP, wheras possible eradication of Helicobacter infection in this background remains elusive.

Endoscopic ligation ("Loop-And-Let-Go") is effective treatment for large colonic lipomas: a prospective validation study.

BACKGROUND: Colonic lipomas (CL) are rare benign adipose tumours usually found incidentally during colonoscopy. Endoscopic resection of symptomatic large CL remains controversial, since significant rates of perforation have been reported. In recent years, a novel technique for removal of large CL has been described, consisting of looping and ligating the lipoma with a nylon snare. The aim of our study was to evaluate the safety and efficacy of the "loop and let go" technique for large colon lipomas in a large case series. METHODS: Consecutive patients referred to our institution for colonoscopy were eligible for the study. The diagnosis of CL was confirmed endoscopically by "pillow" and "naked fat" signs. Following diagnosis, lipomas were looped and ligated by endoloop. Follow-up colonoscopies were scheduled at 1- and 3-months interval. RESULTS: A total of 11 patients with large CL were enrolled in study. The indications for the colonoscopy included altered bowel habits (7 patients, 64%), screening for colorectal neoplasm (3 pts, 27%) and lower gastrointestinal bleeding (1 pts, 9%). The median lesion size was 3 cm (range 2,5-6 cm). Lesions were located at the hepatic flexure in 4 patients (36%), cecum and ascending colon (4 pts, 36%), rectosigmoid (2 pts, 18%) and transverse colon (1 pts, 9%). There were no immediate and late complications. On follow-up (median follow-up time 11.9 months, range 8-24), there was one small residual lipoma (<1 cm). CONCLUSION: The results of this study confirm that "loop-and-let-go" technique is safe and efficacious treatment of large colonic lipomas.

[Treatment of non-1 genotype chronic hepatitis C patients]. / Lijecenje bolesnika s kronicnim hepatitisom C genotipa 2, 3, 4, 5 i 6.

Infection with non-1 genotype in Croatia is detected in 41.2% of patients with chronic hepatitis C. Since the last treatment guidelines for hepatitis C patients, little has been changed. With today's standard of care, sustained viral response can be achieved in 43% to 85% of non-1 CHC patients, which is not satisfactory at all. The lowest cure rate is usually found among patients with genotype 3 and 4 infection. The grouping of genotype 2 and genotype 3 patients to "easy to treat" genotypes was an unfortunate consequence of their underrepresentation in previous large registration clinical trials. Careful re-examination of the data obtained shows clearly enough that patients with genotype 3 infection respond less to treatment than genotype 2 patients. They sometimes behave more like patients with genotype 1 infection. Small progress is found in treatment approach and viral kinetics might be a useful tool for tailoring therapy to improve efficacy. Rapid virologic response is the best parameter to predict success of therapy. For patients who achieve a rapid viral response, consideration of shortened therapy (< 24 weeks) may be reasonable although sustained viral response is still slightly higher with 24 weeks of therapy. Nevertheless, the presence of poor prognostic factors (high viral load, advanced fibrosis, obesity, increased age, insulin resistance and liver non-viral steatosis) may discourage a shortened course of therapy. Extending therapy (> 24 weeks) in patients who do not achieve a rapid viral response would be beneficial, particularly in patients with genotype 3 infection and poor prognostic factors, but formal recommendation should be confirmed in prospective trails. New data suggest a prognostic role for IL28B polymorphisms mostly in genotype 3 patients not achieving a rapid viral response and these could also be considered for improved tailoring of therapy. In conclusion, new treatments are urgently needed for non-1 genotype chronic hepatitis C patients. So far, telaprevir and boceprevir have failed to show a satisfactory activity in these genotypes. Evaluation of many promising molecules such as second generation of protease inhibitors or NS5B nucleos(t)ide inhibitors, NS5A inhibitors, cyclophilin inhibitors or their combinations with or without pegylated interferon or ribavirin is still in progress.

[Monitoring of patients with chronic hepatitis during and after therapy]. / Pracenje lijecenih i nelijecenih bolesnika s virusnim hepatitisom.

Different effective treatments, which are today available for chronic virus hepatitis C and B, reduce the rate of adverse outcomes but HCV and HBV infections are still one of the major health and public medical problems. Screening for HCV and HBV is performed only in high-risk groups with diagnostic tests with high sensitivity and specificity. In HCV antibody positive patients, serum HCV RNA has to be determined by quantitative assay and virus genotype identified. Liver fibrosis is determined by liver biopsy or widely accepted elastography and different serum fibrosis markers. In patients with HCV cirrhosis, HCC has to be detected by expert ultrasound performer or MSCT, MR, and liver transplantation performed according to indications. The current hepatitis B vaccination policy is universal neonatal vaccination. The risk population undergo screening for HBsAg, antiHBc and antiHBs antibodies. The HBsAg, HBeAg and antiHBe positive individuals undergo quantitative testing for HBsAg and HBV DNA. According to the stage of their liver disease, patients are treated with interferon or nucleos(t)ide analogues. The optimal treatment with oral antivirals are entecavir and tenofovir, but the duration of treatment with nucleos(t)ide analogues is generally life-long. In HBV cirrhosis and HBsAg inactive carriers, detection of HCC is essential, and liver transplantation is successfully performed in these patients.

[Liver transplantation in hepatitis B viral infection]. / Terapija hepatitisa B nakon transplantacije jetre.

Hepatitis B infection (HBV) causes liver cirrhosis and hepatocellular carcinoma that are indications for orthotopic liver transplantation (OLT). The outcome of OLT depends on the prevention of HBV reinfection and disease relapses. Out of 692 liver transplantations performed at Merkur University Hospital, 30 were done for HBV infection. These patients were treated with HBIG post OLT and lamivudine, entecavir, adefovir, tenofovir prior and post OLT. All patients became HBsAg and HBV DNA negative but four of them became HbsAg positive one year post OLT. The patients survived for 2 months to 7 years post OLT. With the introduction of HBIG immunoprophylaxis and new efficient antiviral treatment, the risk of relapse is only < 10%, and survival is the same as in other indications for OLT. Because of the high cost and long-term treatment, efforts have been made to prevent recurrent HBV disease by using the schedules according to pre- and post-transplant HBV viremia and introducing the new potent antiviral analogue nucleos(t)ides.

[Treatment of recurrent HCV infection after liver transplantation]. / Terapija HCV infekcije nakon transplantacije jetre.

Recurrent infection with HCV after liver transplantation (LT) is almost universal and is associated with substantial morbidity, mortality and graft loss. In contrast to immunocompetent individuals, HCV infection in immunosuppressed transplant recipients usually has an accelerated course. Acute hepatitis develops in approximately 75% of HCV recipients in the first six months following LT. Within the five years after LT, over 80% of HCV-infected liver transplant recipients develop histologic evidence of chronic allograft injury secondary to HCV, with up to 30% of cirrhosis. While the choice of calcineurin inhibitors has not clearly shown to affect the histologic HCV recurrence or the frequency of rejection in HCV-infected recipients, the cumulative exposure to corticosteroids is associated with increased mortality, higher levels of HCV viremia, and more severe histologic recurrence. Successful therapy has been shown to have a positive impact on both graft and patient survival. Combination therapy with interferon (pegylated and non-pegylated forms) plus ribavirin appears to provide maximum benefits. Drug therapy is usually administered for recurrent disease. No prophylactic therapy is available. Preemptive regimens offer no distinctive advantages over treatments for recurrent disease. Overall, treatment is poorly tolerated, with frequent need for dose reductions, especially due to cytopenias, and drug discontinuation in up to 50% of patients. Optimizing drug doses is important in maximizing sustained virologic response rates (SVR). The SVR achieved is between 33% and 42% in randomized studies treating patients with histologic recurrence. The potential factors that influence this low SVR rate are:1) genotype 1 virus; 2) high viral load; 3) prior nonresponding to therapy; 4) side effects of antiviral treatment; 5) use of growth factors; and 6) effect of immunosuppression. In post-transplant patients with recurrent HCV disease, combination peg alpha-2b or alpha-2a in standard dose and ribavirin (800-1200 mg either ab initio or as an increasing dose) regimen for 48 weeks was significantly better than no therapy but not than any other therapy.

[Viralhepatitis. Croatian Consensus Statement 2013]. / Virusni hepatitis. Hrvatska konsenzus konferencija 2013.

Croatian Consensus Conferences on Viral Hepatitis took place in 2005 and 2009. Considering the numerous novel concepts on the epidemiology, diagnosis and management of viral hepatitis (chronic hepatitis C genotype 1 in particular) that have emerged in the past four years, a new Croatian Consensus Conference on Viral Hepatitis was held in Zagreb on February 28, 2013. The abridged text of the Croatian Consensus Conference on Viral Hepatitis 2013 presents the new concepts on the epidemiology of viral hepatitis, serologic and molecular diagnosis of viral hepatitis, determination of the IL-28 gene promoter polymorphism, fibrosis grading, algorithm for patient diagnostic follow up, treatment of chronic hepatitis C (genotypes 1-6) and hepatitis B, treatment of special populations (children, dialysis patients, transplanted patients, individuals with HIV/HCV co-infection), and therapy side effects.

Challenges for health care development in Croatia.

The main aim of the research done in this paper was to establish key challenges and perspectives for health care development in the Republic of Croatia in the next two decades. Empirical research was conducted in the form of semi-structured interviews involving 49 subjects, representatives of health care professionals from both, public and private sectors, health insurance companies, pharmaceutical companies, drug wholesalers, and non-governmental organisations (patient associations). The results have shown that key challenges and problems of Croatian health care can be divided into three groups: functioning of health care systems, health care personnel, and external factors. Research has shown that key challenges related to the functioning of health care are inefficiency, financial unviability, inadequate infrastructure, and the lack of system transparency. Poor governance is another limiting factor. With regard to health care personnel, they face the problems of low salaries, which then lead to migration challenges and a potential shortage of health care personnel. The following external factors are deemed to be among the most significant challenges: ageing population, bad living habits, and an increase in the number of chronic diseases. However, problems caused by the global financial crisis and consequential macroeconomic situation must not be neglected. Guidelines for responding to challenges identified in this research are the backbone for developing a strategy for health care development in the Republic of Croatia. Long-term vision, strategy, policies, and a regulatory framework are all necessary preconditions for an efficient health care system and more quality health services.

Implications of the accession of the Republic of Croatia to the European Union for Croatian health care system.

The Republic of Croatia's accession to the European Union (EU) will affect all segments of economy and society, including the health care system. The aim of this paper is to establish the potential effects of joining the EU on Croatian health care, as well as to assess its readiness to enter this regional economic integration. The paper identifies potential areas of impact of EU accession on Croatian health care and analyzes the results of the conducted empirical research. In this research, a method of in-depth interviews was applied on a sample of 49 subjects; health professionals from public and private sectors, health insurance companies, pharmaceutical companies, drug wholesalers, and non-governmental organisations (patient associations). Once Croatia joins the EU, it will face: new rules and priorities in line with the current European health strategy; the possibilities of drawing funds from European cohesion funds; labour migrations; new guidelines on patient safety and mobility. From the aspect of harmonising national regulations with EU regulations in the area of health care, Croatian system can be assessed as ready to enter the EU. Croatia's accession to the EU can result in a better information flow, growth of competitiveness of Croatian health care system, enhanced quality, inflow of EU funds, development of health tourism, but also in increased migration of health care professionals, and potential increase in the cost of health care services. Functioning within the EU framework might result in adaptation to the EU standards, but it could also result in the concentration of staff and institutions in larger cities.

[Croatian guidelines for the management of pancreatic exocrine insufficiency]. / Hrvatske smjernice za lijecenje egzokrine pankreasne insuficijencije.

Pancreatic exocrine insufficiency is a major consequence of pancreatic diseases (e. g. chronic pancreatitis and cystic fibrosis), extrapancreatic diseases like celiac disease and Crohn's disease, and gastrointestinal and pancreatic surgical resections. Recognition of this entity is highly relevant to avoid malnutrition-related morbidity and mortality. The main clinical consequence of PEI is fat maldigestion and malabsorption, resulting in steatorrhoea. Pancreatic exocrine function should be assessed by measuring levels of faecal elastase-1. Pancreatic enzyme replacement therapy is the mainstay of treatment for PEI. Administration of enzymes in form of enteric-coated minimicrospheres avoids acid-mediated lipase inactivation and ensures gastric emptying of enzymes in parallel with nutrients. In adults, the initial recommended dose of pancreatic enzymes is 25.000 units of lipase per meal, titrating up to a maximum of 80000 units of lipase per meal. Large meals require 25.000 - 80.000 units of lipase per meal while snacks require 10.000 - 40.000 units of lipase per meal. Oral pancreatic enzymes should be taken with meals to ensure adequate mixing with the chyme. Adjunct therapy with acid-suppressing agents may be useful in patients who continue to experience symptoms of PEI despite high-dose enzyme therapy. Patients with PEI should be encouraged to consume small, frequent meals and to abstain from alcohol. Dietary fat restriction is not recommended for patients with PEI.

[Intraductal papillary mucinous neoplasm of the pancreas: case report and review of the literature]. / Intraduktalna papilarna mucinozna novotvorina gusterace: prikaz slucaja i pregled literature.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a relatively rare clinical entity with a main characteristic being mucus production. Extension of IPMN along pancretic ducts and mucus production lead to ductal obstruction and dilatation, resulting in recurrent episodes of acute pancreatitis. Molecular background of IPMN-a comprises several aberrations, with the K-ras gene mutation being the likely trigger that initiates further genetic changes. Due to its indolent nature, IPMN is most commonly diagnosed in the 7th decade of life. Depending on the histology type, IPMN has a malignant potential. Therefore, surgical therapy remains a "gold standard" of treatment. Insidious, slow progression of the disease and absence of symptoms in a certain number of patients makes diagnostic approach to this entity difficult. In this paper we present a patient with IPMN of the pancreas, in whom the episodes of acute pancreatitis had been present for 22 years.

A pilot study of transrectal endoscopic ultrasound elastography in inflammatory bowel disease.

BACKGROUND: Using standard diagnostic algorithms it is not always possible to establish the correct phenotype of inflammatory bowel disease which is essential for therapeutical decisions. Endoscopic ultrasound elastography is a new endoscopic procedure which can differentiate the stiffness of normal and pathological tissue by ultrasound. Therefore, we aimed to investigate the role of transrectal ultrasound elastography in distiction between Crohn's disease and ulcerative colitis. METHODS: A total 30 Crohn's disease, 25 ulcerative colitis, and 28 non-inflammatory bowel disease controls were included. Transrectal ultrasound elastography was performed in all patients and controls. In all ulcerative coltis patients and 80% of Crohn's disease patients endoscopy was performed to assess disease activity in the rectum. RESULTS: Significant difference in rectal wall thickness and strain ratio was detected between patients with Crohn's disease and controls (p = 0.0001). CD patients with active disease had higher strain ratio than patients in remission (p = 0.02). In ulcerative colitis group a significant difference in rectal wall thickness was found between controls and patients with active disease (p = 0.03). A significant difference in rectal wall thickness (p = 0.02) and strain ratio (p = 0.0001) was detected between Crohn's disease and ulcerative colitis patient group. Crohn's disease patients with active disease had a significantly higher strain ratio compared to ulcerative colitis patients with active disease (p = 0.0001). CONCLUSION: Transrectal ultrasound elastography seems to be a promising new diagnostic tool in the field of inflammatory bowel disease. Further study on a larger cohort of patients is needed to definitely assess the role of transrectal ultrasound elastography in inflammatory bowel disease.

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-α(2a) (PEG-IFN-α(2a)) 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-α(2a) 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.

[Chronic liver diseases in patients with chronic kidney disease]. / Kronicne bolesti jetre u bolesnika s kronicnom bolesti bubrega.

The morphological and functional integrity of the liver is vital to human health in general as well as to patients with renal disease. Any chronic liver disease will eventually lead to liver insufficiency. Liver enzymes are routinely measured to assess liver function in patients with or without renal failure. The use of standard reference values of aminotransferases to help detect liver disease is less useful in patients on chronic dialysis therapy. Some investigators have suggested that, to increase the sensitivity of liver function tests among dialysis patients, lower "normal" values of aminotransferases should be adopted. Liver biopsy may be helpful for assessing the activity and severity of liver disease, especially in chronic viral liver diseases. The most widely used scores are Ishak (6-point scale) and METAVIR (4-point scale). The most important chronic liver diseases associated with chronic renal disease are hepatitis B and C. Several types of renal disease have been recognized: mixed cryoglobulinemia, membranoproliferative glomerulonephritis, membranous nephropathy and polyarteritis nodosa. In any patient first ever diagnosed with any of the mentioned features, serologic and molecular tests for hepatitis B and/or C should be done. There is limited information on the treatment of HBV-associated renal diseases. Nonrandomized studies suggest that antiviral therapy may be beneficial in patients with glomerular disease or vasculitis due to HBV. According to Croatian National Guidelines for Hepatitis B and C, treatment with antiviral drug is recommended for patients with chronic renal disease, especially those on the waiting list for kidney transplantation. Decision on the type and duration of treatment is based on the level of viremia and biochemical and histological activity of liver disease. Several antiviral drugs are currently used for hepatitis B: pegylated interferon alpha-2a and nucleot(z)id analogues. The choice of analogues is based on their genetic barrier and resistance. The probability to develop resistance is much higher in prolonged treatment, more than 1 year. To avoid it, regular check-ups are mandatory. First check-up is recommended after 12 weeks of treatment to detect the possible primary resistance to treatment. Similar approach is used in patients with hepatitis C. Today's standard of care is treatment with a combination of pegylated interferon alpha and ribavirin. Serum concentration of both drugs rises in patients with impaired renal function. The dosage should be corrected according to the glomerular filtration rate. Treatment with pegylated interferon alpha is not recommended in patients with glomerular filtration rate less than 15 mL/min and ribavirin less than 50 mL/min. Recent evidence suggest that nonalcoholic fatty liver disease is associated with an increased prevalence and incidence of chronic renal disease. Current treatment recommendations for nonalcoholic fatty liver disease are limited to weight reduction and treatment of any component of the metabolic syndrome. Liver cirrhosis is the terminal stage of any chronic liver disease. Mortality differs according to the stage of cirrhosis evaluated with Child-Turcotte-Pugh score. The worst prognosis have patients with grade C cirrhosis, which should be borne in mind when evaluating patients with terminal renal disease for treatment with kidney transplantation.

[Consensus guidelines for diagnosis, treatment and follow-up of patients with gastrointestinal stromal tumors]. / Prijedlog postupnika za dijagnostiku, lijecenje i pracénje oboljelih od gastrointestinalnih stromalnih tumora.

Gastrointestinal stromal tumors are the most common mesenchymal tumors in gastrointestinal tract. They are often asymptomatic and discovered incidentally during endoscopic or barium studies. About 80% GISTs have a KIT (CD 117 antigen) gene mutation. Most affect exon 11, less commonly exon 9,13 or 17, that results in uncontrolled KIT signaling. This led to effective systemic therapies in the form of small molecule inhibitors of the receptor tyrosine kinase such as imatinib mesylat. With the purpose of providing standardized approach to rational and effective diagnostic and treatment algorithm in Croatia, a multidisciplinary session was organized. Results of the session are given in the form of Consensus guidelines.

FibroScan-AST Score Predicts 30-Day Mortality or Need for Mechanical Ventilation among Patients Hospitalized with COVID-19.

BACKGROUND: Liver involvement in Coronavirus disease 2019 (COVID-19) has been recognised. We aimed to investigate the correlation of non-invasive surrogates of liver steatosis, fibrosis and inflammation using transient elastography (TE) and FibroScan-AST (FAST) score with (a) clinical severity and (b) 30-day composite outcome of mechanical ventilation (MV) or death among patients hospitalized due to COVID-19. METHOD: Patients with non-critical COVID-19 at admission were included. Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were assessed by TE. Clinical severity of COVID-19 was assessed by 4C Mortality Score (4CMS) and need for high-flow nasal cannula (HFNC) oxygen supplementation. RESULTS: 217 patients were included (66.5% males, median age 65 years, 4.6% with history of chronic liver disease). Twenty-four (11.1%) patients met the 30-day composite outcome. Median LSM, CAP and FAST score were 5.2 kPa, 274 dB/m and 0.31, respectively, and neither was associated with clinical severity of COVID-19 at admission. In multivariate analysis FAST > 0.36 (OR 3.19, p = 0.036), 4CMS (OR 1.68, p = 0.002) and HFNC (OR 7.03, p = 0.001) were independent predictors of adverse composite outcome. CONCLUSION: Whereas LSM and CAP failed to show correlation with COVID-19 severity and outcomes, FAST score was an independent risk factor for 30-day mortality or need for MV.