Liver phenotypes in PCOS: Analysis of exogenous and inherited risk factors for liver injury in two European cohorts

Background & Aims Fatty liver disease (FLD) is common in women with polycystic ovary syndrome (PCOS). Here, we use non-invasive tests to quantify liver injury in women with PCOS and analyse whether FLD-associated genetic variants contribute to liver phenotypes in PCOS. Methods Prospectively, we recruited women with PCOS and controls at two university centres in Germany and Poland. Alcohol abuse was regarded as an exclusion criterion. Genotyping of variants associated with FLD was performed using TaqMan assays. Liver stiffness measurements (LSM), controlled attenuation parameters (CAP) and non-invasive HSI, FLI, FIB-4 scores were determined to assess hepatic steatosis and fibrosis. Results A total of 42 German (age range 18–53 years) and 143 Polish (age range 18–40 years) women with PCOS, as well as 245 German and 289 Polish controls were recruited. In contrast to Polish patients, Germans were older, presented with more severe metabolic profiles and had significantly higher LSM (median 5.9 kPa vs. 3.8 kPa). In the German cohort, carriers of the PNPLA3 p.I148M risk variant had an increased LSM (p = .01). In the Polish cohort, the minor MTARC1 allele was linked with significantly lower serum aminotransferases activities, whereas the HSD17B13 polymorphism was associated with lower concentrations of 17-OH progesterone, total testosterone, and androstenedione (all p < .05). Conclusions FLD is common in women with PCOS. Its extent is modulated by both genetic and metabolic risk factors. Genotyping of variants associated with FLD might help to stratify the risk of liver disease progression in women suffering from PCOS.Peer Reviewe

Liver phenotypes in PCOS : Analysis of exogenous and inherited risk factors for liver injury in two European cohorts

Background & Aims Fatty liver disease (FLD) is common in women with polycystic ovary syndrome (PCOS). Here, we use non-invasive tests to quantify liver injury in women with PCOS and analyse whether FLD-associated genetic variants contribute to liver phenotypes in PCOS. Methods Prospectively, we recruited women with PCOS and controls at two university centres in Germany and Poland. Alcohol abuse was regarded as an exclusion criterion. Genotyping of variants associated with FLD was performed using TaqMan assays. Liver stiffness measurements (LSM), controlled attenuation parameters (CAP) and non-invasive HSI, FLI, FIB-4 scores were determined to assess hepatic steatosis and fibrosis. Results A total of 42 German (age range 18–53 years) and 143 Polish (age range 18–40 years) women with PCOS, as well as 245 German and 289 Polish controls were recruited. In contrast to Polish patients, Germans were older, presented with more severe metabolic profiles and had significantly higher LSM (median 5.9 kPa vs. 3.8 kPa). In the German cohort, carriers of the PNPLA3 p.I148M risk variant had an increased LSM (p = .01). In the Polish cohort, the minor MTARC1 allele was linked with significantly lower serum aminotransferases activities, whereas the HSD17B13 polymorphism was associated with lower concentrations of 17-OH progesterone, total testosterone, and androstenedione (all p < .05). Conclusions FLD is common in women with PCOS. Its extent is modulated by both genetic and metabolic risk factors. Genotyping of variants associated with FLD might help to stratify the risk of liver disease progression in women suffering from PCOS

Metoda agregacji impedancyjnej w ocenie funkcji płytek krwi – czy tylko dla kardiologów?

Multiple electrode aggregometry is one of the newest technologies in platelet function monitoring. The idea of this assay is based on whole blood impedance aggregometry measurements. The main advantages of this device are rapid and easy use, no necessity of sample pre-processing or requiring a specialized laboratory. These features allow one to include this methodology in point-of-care testing methods that can be performed at the patient bedside. Five different pathways of platelet activation can be investigated by adding specific reaction agonists. Antiplatelet drugs, such as acetylsalicylic acid or clopidogrel, inhibit arachidonic acid-dependent and adenosine diphosphate-dependent pathways of platelet activation. Individual patient response to these drugs can be estimated using multiple electrode aggregometry. The identification of low-responders may result in reducing thrombosis events in this group and make antiplatelet treatment more effective. Furthermore, it is supposed to be a reliable method of estimating the risk of perioperative bleeding in adults undergoing cardiac surgery. Other potential clinical applications for this technology are being found. Many studies report its use in determining prognosis in severe sepsis, detecting heparin-induced thrombocytopenia and diagnosing von Willebrand disease. Although multiple electrode aggregometry seems to have great diagnostic potential, more tests need to be performed before it becomes standard hospital equipment.Metoda agregacji impedancyjnej jest jedną z najnowszych technik stosowanych w ocenie funkcji płytek krwi, wykorzystującą krew pełną jako środowisko reakcji. Zasada jej działania opiera się na pomiarach zmian impedancji, jakie następują na skutek agregacji płytek krwi po dodaniu egzogennego aktywatora. Najważniejszymi zaletami tej metody są: łatwość jej wykonania bez specjalistycznego laboratorium, brak konieczności wcześniejszego przetwarzania pobranej do badania próbki oraz szybkość w uzyskaniu wyników. Wszystkie te cechy pozwalają na wykonanie tego badania przy łóżku pacjenta. Metoda agregacji impedancyjnej pozwala na ocenę pięciu różnych szlaków aktywacji płytek krwi w zależności od zastosowanego agonisty. Leki przeciwpłytkowe, takie jak kwas acetylosalicylowy czy klopidogrel, powodują blokadę aktywacji trombocytów zależną kolejno od kwasu arachidonowego i adenozynodifosforanu. Zastosowanie tych związków, jako aktywatorów agregacji płytek krwi, pozwala na ocenę indywidualnej odpowiedzi pacjentów na terapię tymi lekami. Identyfikacja osób „odpornych” na leczenie przeciwpłytkowe może spowodować zmniejszenie liczby powikłań zakrzepowych u tej grupy chorych oraz pozwoli na zwiększenie efektywności leczenia. Obecnie poszukiwane są także inne kliniczne zastosowania agregacji impedancyjnej. Technika ta może być również stosowana do oceny ryzyka krwawienia okołooperacyjnego w kardiochirurgii. Trwają badania dotyczące jej potencjalnego użycia przy określaniu rokowania u pacjentów z ostrą sepsą, wykrywaniu trombocytopenii indukowanej heparyną czy diagnostyce choroby von Willebranda. Pomimo że technika ta ma potencjał, aby stać się metodą przyszłości w ocenie funkcji płytek krwi, wiele badań musi potwierdzić jej przydatność zanim stanie się standardową procedurą szpitalną

Pochodne 1,4&#8722;dihydropirydyny jako &#8222;struktury uprzywilejowane&#8221; i ich potencjał farmakologiczny

Derivatives of 1,4-dihydropyridine belong to group of calcium channel blockers and remain large group of antihypertensive agents. Particular chemical structure and presence of highly reactive binding groups make 1,4-dihydropyridines &#8220;privileged structures&#8221;, which can be modified and change their pharmacological effects. This fact applies to new derivatives as well as metabolites of those drugs. Particularly interesting are outcomes of experiments with metabolites of furnidypine, which tend to cause different pharmacological effect, as well as have different profile of adverse effects from mother drug. Our paper concerns with potential new possibilities of using derivatives of 1,4-dihydropyridines, as well as their metabolites, as agents of more &#8220;optimised&#8221; effect. Kardiol Pol 2011; 69, supl. III: 100&#8211;103Pochodne 1,4-dihydropirydyny należą do grupy antagonistów kanału wapniowego i stanowią liczną rodzinę leków o potwierdzonej skuteczności w terapii nadciśnienia tętniczego. Szczególna struktura cząsteczkowa i obecność wysoce reaktywnych grup podstawnikowych sprawia, że 1,4-dihydropirydyny zalicza się do tzw. &#8222;struktur uprzywilejowanych&#8221;, cechujących się możliwością ingerencji w ich budowę i zmiany właściwości farmakologicznych. Dotyczy to nie tylko nowych pochodnych, ale również metabolitów tych leków. Szczególnie interesującym przykładem są wyniki prac eksperymentalnych nad metabolitami furnidypiny, które wykazują odmienny profil działania oraz są pozbawione niektórych działań niepożądanych leku macierzystego. Artykuł zwraca uwagę na potencjalne, nowe możliwości wykorzystania pochodnych 1,4-dihydropirydyny, a także ich metabolitów jako środków o bardziej &#8222;celowanym&#8221; efekcie terapeutycznym. Kardiol Pol 2011; 69, supl. III: 100&#8211;10

Hepatosplenomegaly in the course of the primary myelofirosis in 49-year-old female patient – a case report

Pierwotne włóknienie szpiku (primary myelofirosis – PMF) należy do grupy rzadkich, Filadelfi-ujemnych nowotworów mieloproliferacyjnych. Istotą choroby jest włóknienie szpiku kostnego, któremu towarzyszy pojawienie się pozaszpikowych ognisk hemopoezy. Ogniska krwiotworzenia mogą lokalizować się w obrębie każdego narządu, jednak zdecydowanie najczęściej zajmują wątrobę i śledzionę. Tworzenie alternatywnych centrów hemopoezy w tych narządach prowadzi do powiększenia ich rozmiarów wraz z rozwojem nadciśnienia wrotnego i jego powikłań. W pracy przedstawiamy rzadki przypadek hepatosplenomegalii w przebiegu pierwotnego włóknienia szpiku u 49-letniej pacjentki.Primary myelofirosis (primary myelofirosis – PMF) belongs to group of rare, Philadelphia-negative myeloproliferative neoplasms. The essence of the disease is a bone marrow fibrosis, which is accompanied by the appearance of extramedullary hemopoiesis foci. Hematopoietic foci may be located within various organs, but by far the most occupied the liver and spleen. Creating alternative centers of hemopoiesis in these organs leads to increase their size with the development of portal hypertension and its complications. We present a rare case of hepatosplenomegaly in the course of primary myelofirosis in 49-year-old female patient

Clinical Usefulness of Non-Invasive Metabolic-Associated Fatty Liver Disease Risk Assessment Methods in Patients with Full-Blown Polycystic Ovary Syndrome in Relation to the MRI Examination with the Ideal IQ Sequence

The coexistence of polycystic ovary syndrome (PCOS) and liver steatosis has been studied for years. The gold standards for the diagnosis of liver steatosis are liver biopsy and magnetic resonance imaging (MRI), which are invasive and expensive methods. The main aim of this study is to check the usefulness of lipid accumulation product (LAP) and free androgen index (FAI) in the diagnosis of liver steatosis. The Ideal IQ MRI was performed in 49 women with PCOS phenotype A to assess the degree of liver steatosis, which was expressed with the proton density fat fraction (PDFF). Anthropometric examination and laboratory tests were performed, and the LAP and FAI were calculated. The correlation between MRI results and LAP, FAI, and one of the FAI components, sex hormone binding globulin (SHBG), was checked using statistical tests. There is a statistically significant correlation between PDFF and LAP and also between PDFF and FAI. LAP = 70.25 and FAI = 5.05 were established as cut-offs to diagnose liver steatosis. The SHBG is not a statistically significant parameter to predict liver steatosis. The study showed that especially LAP, but also FAI, can be used to predict liver steatosis with high specificity and sensitivity

Vaspin mRNA levels in the liver of morbidly obese women with nonalcoholic fatty liver disease

The aim of this study was to evaluate hepatic vaspin mRNA in morbidly obese women with nonalcoholic fatty liver disease (NAFLD) and to look for its relationships with metabolic and histopathological features. The study included 56 severely obese women who underwent intraoperative wedge liver biopsy during bariatric surgery. Hepatic vaspin mRNA was assessed by quantitative real-time PCR. Vaspin mRNA found in all included patients was markedly higher in patients with body mass index (BMI) ≥ 40 kg/m2 (4.59 ±3.09 vs. 0.44 ±0.33; p = 0.05). An evident but statistically insignificant difference in vaspin mRNA levels was observed between patients with and without hepatocyte ballooning (4.77 ±4.23 vs. 0.45 ±0.29, respectively), with and without steatosis (4.80 ±4.20 vs. 0.41 ±0.29, respectively), without and with fibrosis (0.25 ±0.80 vs. 6.23 ±7.2, respectively), and those without and with lobular inflammation (0.27 ±1.0 vs. 5.55 ±10.1, respectively). There was marked difference in vaspin mRNA between patients with simple steatosis/borderline nonalcoholic steatohepatitis (NASH) compared to those with definite NASH (0.24 ±0.96 vs. 10.5 ±10.4). Adiposity is an undoubted confounding factor influencing vaspin levels. Hepatic vaspin mRNA seems to be markedly elevated in morbidly obese patients with more advanced NAFLD and when hallmarks of NASH were observed. Pointing to non-linear mRNA levels within the NAFLD spectrum and an evident increase in patients with fibrosis and definite NASH, the detrimental action of vaspin cannot be excluded