Non-alcoholic fatty liver disease in lean individuals or another rare differential diagnosis - a clinical case

Въведение: Неалкохолната Мастна Чернодробна Болест (НАМЧБ) е значим обществен здравен проблем, засягаща  близо един милиард хора по цял свят. НАМЧБ е най-честата причина за чернодробно увреждане в световен мащаб и представлява чернодробна изява на метаболитния синдром. НАМЧБ е основно свързана със затлъстяването и свързаните му коморбидности, но също така би могло да се наблюдава и при индивиди с нормален или граничен BMI. Това е т.н. НАМЧБ „при слаби“ и представлява субфенотипна изява на Неалкохолната мастна чернодробна болест. Слабите индивиди с НАМЧБ показват по-леки признаци на Метаболитния синдром, сравнено с тези със затлъстяване, но са с по-висока честота на метаболитни промени, като дислипидемия, артериална хипертония, инсулинова резистентност и диабет сравнено със здрави контроли. Поставянето на диагнозата на НАМЧБ изисква изключване на вторични причини за чернодробна стеатоза, както и изключване на дневна алкохолна консумация ≥ 30 гр. абсолютен алкохол за мъже и ≥ 20 гр. абсолютен алкохол за жени.Клиничен случай: Представяме клиничен случай на мъж на 29 години, постъпил в клиниката с оглед диагностично уточняване във връзка с ехографски данни за изразена чернодробна стеатоза, съпроводена с лекостепенна хепатоспленомегалия. Липсват данни за известен Захарен диабет, ХБ или затлъстяване. Пациента е с наднормено тегло, но без затлъстяване: ръст 187 см, телесно тегло 108 кг, BMI – 30, коремна обиколка 111 см. От лабораторните изследвания нормална ПКК, CRP, нормални АСАТ, АЛАТ, АФ  и билирубин, леко повишен ГГТ, нормална синтетична чернодробна функция. Изследването на липидната обмяна показва повишени нива на LDL холестерол и ниско ниво на HDL холестерол. Проведен е лабораторен хепатологичен скрининг, при който са изключени – хронични вирусни хепатити, Болест на Уилсън и хемохроматоза, автоимунна чернодробна болест. Неинвазивните cкоровете за доказване наличие на стеатоза показаха високи стойности. NAFLD fibrosis score: -3,35 и FIB-4 index: 0,52, отхвърлят наличието на значима  фиброза. При ехографското изследване данни за изразена чернодробна стеатоза – 3 ст, горно-граничен размер на черния дроб и лекостепенна спленомегалия. Фиброскан еластографията показва нормална плътност на черния дроб – 4,8 кРа, при САР – 304 db/m, което доказва наличие на високостепенна стеатоза. Имайки предвид физикалните данни, категоричните резултати от неинвазивните скорове за стеатоза,  ехографското изследване, данните от фиброскан еластографията и след изключване на алкохолна консумация и на други по-чести причини за стеатоза се прие диагноза Неалкохолна мастна чернодробна болест при слаби.  Направи се и изследване на суха капка кръв  за лизозомални ензими, при което се изключи Болест на Гоше. Установи се ниско ниво на кисела сфингомиелиназа, което е индикация за Niemann Pick A/B болест, която представлява рядка наследствена автозомно-рецесивна болест засягаща липидния метаболизъм.Заключение: Клиничният случай представя пациент без затлъстяване, с категорични лабораторни, ехографски и фиброскан данни за Неалкохолна мастна чернодробна болест. В диференциално диагностичен план установихме данни за рядка наследствена болест – Болестта на Niemann Pick, протичаща с нарушение в обмяната на мазнините. Клиничният случай доказва широкия спектър от диференциални диагнози при слаби пациенти с НАМЧБ.abstractIntroduction:    Non-alcoholic    fatty    liver    disease    (NAFLD)  is  a  significant  health  problem  in  society  and it affects around a billion people on a global scale. NAFLD is the most common reason for liver damage worldwide and is considered the hepatic manifestation of the metabolic syndrome.. Nonalcoholic fatty liver disease (NAFLD) is generally associated with obesity and the related comorbidities but it can also develop in subjects with a normal body mass index (BMI). This sub-phenotype of NAFLD is so-called “lean” NAFLD. Lean subjects with NAFLD have milder features of the metabolic syndrome when compared with obese patients. Nonetheless they have a higher prevalence of metabolic alterations (e.g.,dyslipidemia, arterial hypertension, insulin resistance, and diabetes) compared with healthy controls. The diagnosis of NAFLD requires the exclusion of both secondary causes and of a daily alcohol consumption ≥ 30 g for men and ≥ 20 g for women.Clinical case: We present the clinical case of a 29-year-old man, who was admitted to the hospital because of diagnostic evaluation of ultrasound findings of severe liver steatosis accompanied with mild hepatosplenomegaly. No evidence of known Diabetes mellitus, Hypertensive disease or Obesity. The patient is overweight but without obesity: height – 187 sm., weight – 108 kg, BMI - 30, waist circumference – 111 sm. Laboratory examination revealed: normal blood count, normal level of CRP, AST, ALT, AF, total bilirubin, mild elevation of GGT and normal synthetic liver function tests. Lipid profile showed elevated level for LDL cholesterol and low HDL cholesterol. Underlying chronic viral hepatitis, autoimmune liver diseases, Wilson's disease and Hemohromatosis were ruled out. Calculated non-invasive scores for steatosis were high. NAFLD fibrosis score: -3,35 and FIB-4 index: 0,52, ruled out presence of significant fibrosis. Abdominal ultrasound examination showed liver steatosis grade 3, upper limit of normal size, mild splenomegaly. Liver transient elastography (TE) with fibroscan revealed normal liver stiffness - 4,8 kPa and CAP – 304 db/m, that proved presence of severe steatosis. Based on physical examination data, definite results of non-invasive scores for steatosis, ultrasound examination and fibroscan elastography, and after excluding of alcohol consumption and other common causes for steatosis we established the diagnosis „lean“ Non-alcoholic fatty liver disease. We performed an examination for Lysosomal Enzymes from dried blood, that rule out classical Gaucher disease. Low activity of acid sphingomyelinase was found, which is indicative of Niemann Pick disease A/B – rare inherited autosomal recessive condition involving lipid metabolism.Conclusion: Clinical case represents a patient without obesity, with definite laboratory, ultrasound and fibroscan data for Non-alcoholic fatty liver disease. As a differential diagnosis we found a rare inherited condition - Niemann Pick disease, characterized with impaired lipid metabolism. Our clinical case proves the broad spectrum of differential diagnosis of patients with NAFLD. Introduction:  Non-alcoholic  fatty  liver  disease  (NAFLD) is a socially significant health problem and it affects around a billion people on a global scale. NAFLD is the most common reason for liver damage worldwide and is considered the hepatic manifestation of the metabolic syndrome. Non-alcoholic fatty liver disease is generally associated with obesity and the related comorbidities, but it can also develop in subjects with a normal body mass index (BMI). This sub-phenotype of NAFLD is called lean NAFLD. Lean subjects with NAFLD have milder features of the metabolic syndrome when compared with obese patients. Nonetheless, they have a higher prevalence of metabolic alterations (e.g., dyslipidemia, arterial hypertension, insulin resistance, and diabetes) compared with healthy controls. The diagnosis of NAFLD requires the exclusion of both secondary causes and of a daily alcohol consumption ≥ 30 g for men and ≥ 20 g for women.Clinical Case: We present the clinical case of a 29-year-old man, who was admitted to the hospital because of diagnostic evaluation of ultrasound findings of severe liver steatosis accompanied with mild hepatosplenomegaly. There was no evidence of diabetes mellitus, hypertensive disease or obesity. The patient was overweight but without obesity: height – 187 cm., weight – 108 kg, BMI – 30, waist circumference – 111 cm. Laboratory examination revealed: normal blood count, normal level of CRP, AST, ALT, AF, total bilirubin, mild elevation of GGT and normal synthetic liver function tests. The lipid profile showed elevated level for LDL cholesterol and low HDL cholesterol. Underlying chronic viral hepatitis, autoimmune liver diseases, Wilson's disease and hemochromatosis were ruled out. The calculated non-invasive scores for steatosis were high. The NAFLD fibrosis score: -3.35 and FIB-4 index: 0.52, ruled out presence of significant fibrosis. Abdominal ultrasound examination showed liver steatosis grade 3, upper limit of normal size, mild splenomegaly. Liver transient elastography (TE) with fibroscan revealed normal liver stiffness – 4.8 kPa and CAP – 304 db/m that proved the presence of severe steatosis. Based on physical examination data, definite results of non-invasive scores for steatosis, ultrasound examination and fibroscan elastography, and after excluding alcohol consumption and other common causes for steatosis, we established the diagnosis lean non-alcoholic fatty liver disease. We performed an examination for lysosomal enzymes from dried blood that ruled out classic Gaucher disease. Low activity of acid sphingomyelinase was found, which was indicative of Niemann-Pick disease A/B – rare inherited autosomal recessive condition involving lipid metabolism.Conclusion: The clinical case presents a patient without obesity, with definite laboratory, ultrasound and fibroscan data for non-alcoholic fatty liver disease. As a differential diagnosis we found a rare inherited condition – Niemann-Pick disease, characterized by impaired lipid metabolism. Our clinical case proves the broad spectrum of differential diagnoses of patients with NAFLD

User Software for Numerical Study of Josephson Junction with Magnetic Momenta

A user software for numerical study of a Josephson junction model with magnetic momenta is presented. Computer implementation has been done by means of Wolfram Mathematica using the extensive capabilities of this system to create interactive dynamic objects. Two methods for numerical solution of the respective system of ordinary differential equations are implemented: the four-step Runge-Kutta algorithm and the Runge-Kutta-Fehlberg method with predetermined accuracy. Results of numerical simulation are presented to confirm the correctness of the calculations done with the developed software

User Software for Numerical Study of Josephson Junction with Magnetic Momenta

A user software for numerical study of a Josephson junction model with magnetic momenta is presented. Computer implementation has been done by means of Wolfram Mathematica using the extensive capabilities of this system to create interactive dynamic objects. Two methods for numerical solution of the respective system of ordinary differential equations are implemented: the four-step Runge-Kutta algorithm and the Runge-Kutta-Fehlberg method with predetermined accuracy. Results of numerical simulation are presented to confirm the correctness of the calculations done with the developed software

Parallel Numerical Simulation of the Magnetic Moment Reversal within the

The φ0-Josephson Dushanbe, Tajikistanjunction model with a coupling between the magnetic moment and the Josephson current in the “superconductor–ferromagnet–superconductor” system has been investigated. Numerical solution of the respective system of nonlinear differential equations is based on the two-stage Gauss–Legendre algorithm. For numerical simulation in a wide range of parameters which requires a significant computer time, a parallel MPI=C++ computer code has been developed. Results of numerical study of the magnetization effect depending on physical parameters, as well as results of methodological calculations demonstrating the efficiency of the parallel implementation, are presented. Calculations have been carried out at the Heterogeneous Platform “HybriLIT” and on the supercomputer “Govorun” of the Multifunctional Information and Computing Complex of the Laboratory of Information Technologies, JINR (Dubna)

Parallel Numerical Simulation of the Magnetic Moment Reversal within the φ0-Josephson Junction Spintronic Model

The φ0-Josephson Dushanbe, Tajikistanjunction model with a coupling between the magnetic moment and the Josephson current in the “superconductor–ferromagnet–superconductor” system has been investigated. Numerical solution of the respective system of nonlinear differential equations is based on the two-stage Gauss–Legendre algorithm. For numerical simulation in a wide range of parameters which requires a significant computer time, a parallel MPI=C++ computer code has been developed. Results of numerical study of the magnetization effect depending on physical parameters, as well as results of methodological calculations demonstrating the efficiency of the parallel implementation, are presented. Calculations have been carried out at the Heterogeneous Platform “HybriLIT” and on the supercomputer “Govorun” of the Multifunctional Information and Computing Complex of the Laboratory of Information Technologies, JINR (Dubna)

Simulation of Collective Excitations in Long Josephson Junction Stacks

The phase dynamics of a stack of long Josephson junctions has been studied. Both inductive and capacitive couplings between Josephson junctions have been taken into account in the calculations. The IV-curve, the dependence on the bias current of the radiation power and dynamics of each JJs of the stack have been investigated. The coexistence of the charge traveling wave and fluxon states has been observed. This state can be considered as a new collective excitation in the system of coupled Josephson junctions. We demonstrate that the observed collective excitation leads to the decrease of radiation power from the system

Effect of Selenium Supplementation on Redox Status of the Aortic Wall in Young Spontaneously Hypertensive Rats

Selenium (Se) is an exogenous antioxidant that performs its function via the expression of selenoproteins. The aim of this study was to explore the effect of varying Se intake on the redox status of the aortic wall in young spontaneously hypertensive rats (SHR). Sixteen male Wistar Kyoto (WKY) rats and nineteen male SHR, 16-week-old, were tested after being given diets with different Se content for eight weeks. They were divided into 4 groups: control groups of WKY NSe and SHR NSe on an adequate Se diet and groups of WKY HSe and SHR HSe that received Se supplementation. The Se nutritional status was assessed by measuring whole blood glutathione peroxidase-1 (GPx-1) activity. Serum concentration of lipid hydroperoxides and serum level of antibodies against advanced glycation end products (anti-AGEs abs) were determined. Expression of GPx-1 and endothelial nitric oxide synthase (eNOS) were examined in aortic wall. Se supplementation significantly increased GPx-1 activity of whole blood and in the aortas of WKY and SHR. Decreased lipid peroxidation level, eNOS-3 expression in the aortic wall, and serum level of anti-AGEs abs were found in SHR HSe compared with SHR NSe. In conclusion, Se supplementation improved the redox status of the aortic wall in young SHR

Simulation of Collective Excitations in Long Josephson Junction Stacks

The phase dynamics of a stack of long Josephson junctions has been studied. Both inductive and capacitive couplings between Josephson junctions have been taken into account in the calculations. The IV-curve, the dependence on the bias current of the radiation power and dynamics of each JJs of the stack have been investigated. The coexistence of the charge traveling wave and fluxon states has been observed. This state can be considered as a new collective excitation in the system of coupled Josephson junctions. We demonstrate that the observed collective excitation leads to the decrease of radiation power from the system