Signa Vitae - A Journal In Intensive Care And Emergency Medicine, 2015
At the University Hospital Centre Zagreb, 37 patients underwent liver transplantation in the peri... more At the University Hospital Centre Zagreb, 37 patients underwent liver transplantation in the period from 2010 to 2014. Six patients had fatal complications in the early post-transplantation period and deceases in the surgical intensive care unit (ICU). All other patients (31) were transferred to the medical ICU and later to the medical ward. The most common indications for liver transplantation were alcoholic liver disease (9 patients) and hepatitis C (8 patients). Two-thirds of the patients were male (67.7%) with an average age of 51 years. Thirty patients were discharged alive from the hospital. Infections developed in nine patients, mostly pneumonia and peritonitis. Only one patient experienced infection caused by multi-drug resistant bacteria, namely peritonitis due to methicillin-resistant Staphylococcus aureus (MRSA). All infections were successfully treated with antibiotics and none of them caused graft rejection.
Until the beginning of the 90ies, it was believed that patients with liver cirrhosis were auto-an... more 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...
European Journal of Gastroenterology & Hepatology, 2006
Background Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract ... more Background Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with variations in localization and behaviour. Mutations in the NOD2/CARD15 gene on chromosome 16q have been implicated in the pathogenesis of the disease and three main sequence variants, all single nucleotide polymorphisms (SNPs), have been identified in North American and European populations. Aims and methods As no data exist in the Croatian population, we consecutively collected a cohort of 136 CD patients and 91 healthy controls to determine the prevalence of NOD2/CARD15 mutations and their association with phenotypic expression of the disease. All patients and controls were genotyped for Arg702Trp (Hugot SNP8), Gly908Arg (Hugot SNP12), and Leu1007fsinsC (Hugot SNP13) and allele frequencies were compared between the Crohn's patients and controls. The correlation of NOD2/CARD15 genotypes with the phenotypic expression of Crohn's disease was further assessed by logistic regression analysis. Results NOD2/CARD15 variants were found in 38/136 CD patients (27.9%) compared to 10/91 (10.9%) healthy controls (P = 0.0022). Allele frequencies in patients with CD were 13.97%, 4.4% and 11.76%, respectively, for SNP8, 12 and 13, compared to 5.49%, 1.12% and 4.40% in controls (P = 0.041, P = 0.162, P = 0.055). Six CD patients carried double mutations and, remarkably, we identified two homozygous mutants amongst the healthy control group. Surgery over the course of the disease and a younger age at onset of the disease were significantly more frequent in patients who were carriers of NOD2/CARD15 mutations. Conclusions This report on NOD2/CARD15 mutations in Croatian patients with CD demonstrates that this gene is also implicated in susceptibility to CD in the Croatian population. Phenotypic association showed a younger age at diagnosis and a higher need for surgery in patients carrying NOD2/CARD15 mutations. However, the prevalence is somewhat lower compared to other reports, likely due to a more prominent colonic inflammation.
European Journal of Gastroenterology & Hepatology, 2009
Currently, magnetic resonance cholangiography is being used for establishing the diagnosis of pri... more 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. 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. 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 (chi = 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 (chi = 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). Endoscopic ultrasound elastography might be a useful noninvasive method in diagnosing primary sclerosing cholangitis.
Basic & Clinical Pharmacology & Toxicology, 2009
Vanishing bile duct syndrome is a severe cholestatic disease associated with toxic effects of med... more Vanishing bile duct syndrome is a severe cholestatic disease associated with toxic effects of medications. Stevens-Johnson syndrome is a hypersensitivity disorder that may also be caused by medications. We present a case of a 62-year-old male patient who developed vanishing bile duct syndrome a month after Stevens-Johnson syndrome. These adverse drug reactions were associated with the use of azithromycin (500 mg daily for 3 days). The patient was initially treated for Stevens-Johnson syndrome with steroids, antihistamines and proton pump inhibitors and fully recovered. However, a month after the beginning of Stevens-Johnson syndrome, he developed vanishing bile duct syndrome and was treated with steroids, ursodeoxycholic acid, antihistamines and tacrolimus. Unfortunately, the treatment was unsuccessful and he was listed for liver transplantation which was performed 7 months after the beginning of jaundice. This is the first case of vanishing bile duct syndrome associated with the use of azithromycin and one of few that reports vanishing bile duct syndrome and Stevens-Johnson syndrome co-occurrence.
Signa Vitae - A Journal In Intensive Care And Emergency Medicine, 2015
At the University Hospital Centre Zagreb, 37 patients underwent liver transplantation in the peri... more At the University Hospital Centre Zagreb, 37 patients underwent liver transplantation in the period from 2010 to 2014. Six patients had fatal complications in the early post-transplantation period and deceases in the surgical intensive care unit (ICU). All other patients (31) were transferred to the medical ICU and later to the medical ward. The most common indications for liver transplantation were alcoholic liver disease (9 patients) and hepatitis C (8 patients). Two-thirds of the patients were male (67.7%) with an average age of 51 years. Thirty patients were discharged alive from the hospital. Infections developed in nine patients, mostly pneumonia and peritonitis. Only one patient experienced infection caused by multi-drug resistant bacteria, namely peritonitis due to methicillin-resistant Staphylococcus aureus (MRSA). All infections were successfully treated with antibiotics and none of them caused graft rejection.
Until the beginning of the 90ies, it was believed that patients with liver cirrhosis were auto-an... more 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...
European Journal of Gastroenterology & Hepatology, 2006
Background Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract ... more Background Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with variations in localization and behaviour. Mutations in the NOD2/CARD15 gene on chromosome 16q have been implicated in the pathogenesis of the disease and three main sequence variants, all single nucleotide polymorphisms (SNPs), have been identified in North American and European populations. Aims and methods As no data exist in the Croatian population, we consecutively collected a cohort of 136 CD patients and 91 healthy controls to determine the prevalence of NOD2/CARD15 mutations and their association with phenotypic expression of the disease. All patients and controls were genotyped for Arg702Trp (Hugot SNP8), Gly908Arg (Hugot SNP12), and Leu1007fsinsC (Hugot SNP13) and allele frequencies were compared between the Crohn's patients and controls. The correlation of NOD2/CARD15 genotypes with the phenotypic expression of Crohn's disease was further assessed by logistic regression analysis. Results NOD2/CARD15 variants were found in 38/136 CD patients (27.9%) compared to 10/91 (10.9%) healthy controls (P = 0.0022). Allele frequencies in patients with CD were 13.97%, 4.4% and 11.76%, respectively, for SNP8, 12 and 13, compared to 5.49%, 1.12% and 4.40% in controls (P = 0.041, P = 0.162, P = 0.055). Six CD patients carried double mutations and, remarkably, we identified two homozygous mutants amongst the healthy control group. Surgery over the course of the disease and a younger age at onset of the disease were significantly more frequent in patients who were carriers of NOD2/CARD15 mutations. Conclusions This report on NOD2/CARD15 mutations in Croatian patients with CD demonstrates that this gene is also implicated in susceptibility to CD in the Croatian population. Phenotypic association showed a younger age at diagnosis and a higher need for surgery in patients carrying NOD2/CARD15 mutations. However, the prevalence is somewhat lower compared to other reports, likely due to a more prominent colonic inflammation.
European Journal of Gastroenterology & Hepatology, 2009
Currently, magnetic resonance cholangiography is being used for establishing the diagnosis of pri... more 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. 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. 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 (chi = 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 (chi = 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). Endoscopic ultrasound elastography might be a useful noninvasive method in diagnosing primary sclerosing cholangitis.
Basic & Clinical Pharmacology & Toxicology, 2009
Vanishing bile duct syndrome is a severe cholestatic disease associated with toxic effects of med... more Vanishing bile duct syndrome is a severe cholestatic disease associated with toxic effects of medications. Stevens-Johnson syndrome is a hypersensitivity disorder that may also be caused by medications. We present a case of a 62-year-old male patient who developed vanishing bile duct syndrome a month after Stevens-Johnson syndrome. These adverse drug reactions were associated with the use of azithromycin (500 mg daily for 3 days). The patient was initially treated for Stevens-Johnson syndrome with steroids, antihistamines and proton pump inhibitors and fully recovered. However, a month after the beginning of Stevens-Johnson syndrome, he developed vanishing bile duct syndrome and was treated with steroids, ursodeoxycholic acid, antihistamines and tacrolimus. Unfortunately, the treatment was unsuccessful and he was listed for liver transplantation which was performed 7 months after the beginning of jaundice. This is the first case of vanishing bile duct syndrome associated with the use of azithromycin and one of few that reports vanishing bile duct syndrome and Stevens-Johnson syndrome co-occurrence.
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