Do Semaphorins Play a Role in Development of Fibrosis in Patients with Nonalcoholic Fatty Liver Disease?

Nonalcoholic fatty liver disease (NAFLD) is associated with systemic changes in immune response linked with chronic low-grade inflammation and disease progression. Semaphorins, a large family of biological response modifiers, were recently recognized as one of the key regulators of immune responses, possibly also associated with chronic liver diseases. The aim of this study was to identify semaphorins associated with NAFLD and their relationship with steatosis and fibrosis stages. In this prospective, case-control study, serum semaphorin concentrations (SEMA3A, -3C, -4A, -4D, -5A and -7A) were measured in 95 NAFLD patients and 35 healthy controls. Significantly higher concentrations of SEMA3A, -3C and -4D and lower concentrations of SEAMA5A and -7A were found in NAFLD. While there was no difference according to steatosis grades, SEMA3C and SEMA4D significantly increased and SEMA3A significantly decreased with fibrosis stages and had better accuracy in predicting fibrosis compared to the FIB-4 score. Immunohistochemistry confirmed higher expression of SEMA4D in hepatocytes, endothelial cells and lymphocytes in NAFLD livers. The SEMA5A rs1319222 TT genotype was more frequent in the NAFLD group and was associated with higher liver stiffness measurements. In conclusion, we provide the first evidence of the association of semaphorins with fibrosis in patients with NAFLD.

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.

Imprint cytology of gastric mucosa biopsy--fast, simple and reliable method for detection of Helicobacter pylori infection.

The aim of the study was to determine the value of gastric mucosa imprint cytology in the detection of Helicobacter pylori infection. A total of 182 biopsy specimens, from 182 randomly selected patients undergoing gastroscopy with gastric mucosa biopsy, were analyzed. Specimens were first submitted to slide imprinting and then formalin fixed for further routine histopathology. One-hundred and fifty-five specimens proved adequate for definitive comparison of the methods used for detection of Helicobacter pylori infection. Helicobacter pylori was detected by histopathology in 51 specimens and by cytology in 54 specimens. Agreement between the findings obtained by the two methods was recorded in 130 of 155 (83.1%) specimens. Positive cytology and negative histology findings were obtained in 14, and vice versa in 11 specimens. Gastric mucosa imprint cytology provides a useful method for the detection of Helicobacter pylori infection. The method is advantageous for being fast, simple and inexpensive. When the sample is obtained exclusively for confirmation of the presence of Helicobacter pylori infection, cytology reduces the time and cost of the procedure, at the same time providing data on morphological changes of gastric mucosa. Every finding suspect of malignant transformation of the mucosa can also be verified by histopathology because imprint manipulation causes no damage to the sample.

[Cytomorphological characteristics of thyroid papillary carcinoma and their prognostic value]. / Citomorfoloske karakteristike klasicnog papilarnog karcinoma stitnjace i njihovo prognosticko znacenje.

OBJECTIVE: The aim of this study was to determine cytomorphological characteristics of classic papillary carcinoma that could point to a higher likelihood of intraglandular or paraglandular dissemination of the disease. METHODS: Morphological characteristics of classic thyroid papillary carcinoma and the size and ultrasonography characteristics of thyroid nodules were semiquantitatively analyzed in 100 patients diagnosed with papillary carcinoma by cytology and verified by histology. Data on the presence of intraglandular and paraglandular dissemination, established by histologic examination of postoperative material, were collected and analyzed. RESULTS: There were 16 male and 84 female patients aged 4-78 (mean 48.8) years. Polymorphism, multinucleation, intranuclear inclusions, psammoma bodies, presence of follicles, Hürthle like cells and connective tissue elements were present in 31%, 62%, 88%, 19%, 16%, 26%, 10% of cases, respectively. Thyroid nodule size was 4-80 mm (mean 14.5 mm) and up to 10 mm in 50% of cases; 76% of nodules were hypoechoic, 96% had irregular margins, and calcifications were present in 71% of nodules. Intraglandular dissemination and neck lymph node metastases were found in 16% of patients. Paraglandular dissemination was observed in 15% of cases. Statistical analysis showed no significant cytologic characteristic that would imply a higher or lower likelihood of intraglandular dissemination. Older age was found to be a risk factor for paraglandular but not intraglandular dissemination, while nodule size and neck lymph node metastases were not important for the presence of intraglandular or paraglandular dissemination. CONCLUSION: Since no marker that could indicate a higher or lower likelihood of intraglandular and/or paraglandular dissemination of thyroid papillary carcinoma has yet been identified, it is advisable to perform total thyroidectomy when papillary carcinoma is diagnosed by cytologic examination, irrespective of the nodule size or tumor subtype.