Cholestasis Syndrome Research Articles

Cholestasis syndrome in a newborn child with congenital hypopituitarism

The purpose of the work is comprehensive examination of a newborn with cholestasis syndrome to determine congenital hypopituitarism. Materials and methods. The child was hospitalized on the 30th day of his life. At admission, complaints were noted about the ictericity of the skin, low body weight gain, convulsive syndrome (history). Differential diagnosis was carried out between diseases such as: impaired liver function, against the background of the course of the infectious-inflammatory process; diseases of the liver and bile ducts of hereditary nature; congenital malformations of the bile tract; metabolic and hormonal disorders. Results. During the survey, the following deviations from the norm were obtained: in the biochemical analysis there was an increase in the level of transaminases, alkaline phosphatase, total and direct bilirubin, hypoglycemia. When evaluating the hormonal profile, an increase in the level of prolactin, thyroid hormone, a decrease in the level of T4 free, insulin, and a complete absence of cortisol were revealed. Magnetic resonance imaging (MRI) of the brain - a picture of subependymal nodes of gray matter heterotopia, ectopia of the neurophysis. Conclusions. Lowering glucose levels, especially when combined with cholestasis syndrome, may be an early but nonspecific sign of congenital hypopituitarism. Hypoglycemia in newborns occurs as a result of intrauterine insufficiency of somatotropic hormone and cortisol related to contrinsular hormones. Cortisol deficiency also contributes to the development of cholestasis syndrome by reducing the expression of tubule transport proteins that regulate bile secretion into bile tubules. In addition to studying the hormonal profile, a brain MRI is performed to verify the diagnosis. Patients with congenital hypopituitarism are characterized by the detection of characteristic signs: the picture of the “empty” or “partially empty” Turkish saddle, as well as the classic triad of symptoms: hypoplasia/pituitary leg aplasia, neurophysis ectopia, adenohypophysis hypoplasia. This clinical case demonstrates that cholestasis syndrome may lie in the debut of a more severe pathology. At the same time, early diagnosis and adequately selected hormone replacement therapy leads to a rapid cessation of life-threatening conditions and an improvement in the quality of life of the child.

Жовчнокам’яна хвороба, ускладнена холедохолітіазом: сучасні аспекти діагностики

Choledocholithiasis is an urgent problem of modern hepatobiliary surgery and accounts for 60% of all obstructive jaundice. Stones of the common bile duct cause cholestasis and mechanical jaundice syndrome and in case of untimely diagnostics lead to the development of such severe complications as acute cholangitis and biliary sepsis. The criteria for determining the sequence, stages and volume of diagnostic measures with choledocholithiasis have not been determined by now. The purpose of the study. Optimization of the instrumental stage of the diagnostics of patients with choledocholithiasis. Materials and methods. 56 patients with choledocholithiasis were studied. The diagnostic program was expanded due to the instrumental stage using ultrasound, duodenopapiloscopy, endoscopic retrograde cholangiopancreatography and magnetic resonance tomography. The criterion for the patients selection was the syndrome of distal choledochal patency violation and the presence of stones in it according to echosonography and endoscopic cholangiopancreatography. Results and discussion. At sonography bilious hypertension was established in all 72 (100%) patients. Mechanical jaundice was present in 54 (96.4%) patients. Hepatic dysfunction with 84±9.6 mmol/l hyperbilirubinemia and an increase in AST and ALT levels to 1.2±0.9 mmol/l and 1.5±1.1 mmol/l, were verified respectively. At endoscopic retrograde cholangiopancreatography choledocholithiasis was found in 54 (96.4%) patients. Single stones were present in 18 (32.1%) and multiple – in 38 (67.9%) patients. In 52 (92.9%) cases, stones up to 1.5 cm in diameter were removed with a Dormia basket at one time or after mechanical lithotripsy. In 4 (7.1%) patients stones from 1.7 to 2.0 cm could not be removed endoscopically. Choledoch stenting was performed in 12 (21.4%) patients. One-stage transpapillary treatment was carried out in 38 (67.9%) patients, two and three stage treatment – in 14 (25%) cases, and «open» choledocholithotomy – in 4 (7.1%) cases. Conclusion. The program of choledocholithiasis diagnostics with the gradual use of clinical, laboratory, radiological and endoscopic data allows carrying out correct detailing of the cause, level, degree of common bile duct obstruction and the complicated course of the disease in 100% of cases

POS-231 Renal impairment during sarcoidosis: About 3 cases

Sarcoidosis is an inflammatory, multisystemic granulomatous disease of unknown etiology that affects the lung and lymphatic system. Renal involvement during sarcoidosis is rare. It may progress to renal failure in about 3% of cases. This is a retrospective study involving all patients with sarcoidosis with renal involvement observed over a period of 22 years in the internal medicine department of the Hédi Chaker University Hospital in Sfax. The diagnosis of sarcoidosis was based on a combination of clinical, biological, radiological and histological arguments. We only collected 3 cases of sarcoidosis with renal damage among a series of 84 cases, i.e. a frequency of 3.5%, and these were 3 women with a mean age of 51 years, with extremes of 43 and 68 years. Renal failure was present in all our patients at the time of diagnosis. Two of the patients had renal insufficiency with a median creatinine level of 160 umol/L. Proteinuria was positive greater than 1g/24 h, with two normal sized kidneys without kidney stones on ultrasound. In both cases, renal failure was functional secondary to hypercalcemia, without hypercalcuria. The third case, renal failure was associated with aseptic leucocyturea disease without proteinuria, without hypercalcemia or hypercalcuria, with cytolysis and cholestasis syndrome, and ultrasonography showed two normal sized kidneys. The most likely cause was renal failure by interstitial infiltration. A renal biopsy was indicated but was not performed due to the altered general status of the patient . Treatment was initiated with high-dose corticosteroids in 2 cases. The evolution was marked by hemodialysis in 1 case and stabilization of renal function in 2 patients, We emphasize the severity of kidney damage during sarcoidosis. The treatment is mainly based on corticosteroid therapy and early treatment allows a better prognosis and avoids the evolution towards chronic renal failure.

Функціональний стан гепатобіліарної системи в новонароджених дітей з проявами гіпербілірубінемії при перинатальній патології

Neonatal jaundice in most cases is a benign condition in the newborn that does not require additional interventions other than observation. However, the manifestations of hyperbilirubinemia under certain conditions may be one of the first clinical signs of disorders of the functional state of the hepatobiliary system (HBS), in which case this process is not considered physiological and requires appropriate clinical observation and additional examination. Contributing factors to the development of HBS dysfunction in newborns may be: concomitant perinatal pathology, isoimmunization, congenital defects in the metabolism of enzymes involved in the transformation and excretion of bilirubin, and so on. Purpose — based on a comprehensive analysis of specific clinical and laboratory indicators to determine the most characteristic pathogenetic syndromes, which are the basis for the formation of disorders of the functional state of the hepatobiliary system in the presence of clinical manifestations of jaundice in newborns. Materials and methods. 164 full-term infants were included in the study. The main study group І (92 children with clinical manifestations of jaundice on the background of perinatal pathology) was divided into 2 subgroups depending on the severity of the newborn in the early neonatal period: IA subgroup (46 pers.) — children with moderate severity and IB subgroup (46 people) — children whose condition was assessed as severe. Group II (comparison group) consisted of 72 healthy full-term newborns. Biochemical studies of serum in newborns were performed using an analyzer «ULTRA» company «Kone» (Finland, reagents of the company) and an apparatus for electrophoresis «PARAGON» company «Bekman» (Austria, reagents of the company) in the biochemical laboratory of the maternity hospital. For reliable analysis of statistical data, the assessment was performed using the software SpssStatistica, 2010; Excel, 2016. Procedures, logic and interpretation of the obtained analysis results were based on the main provisions of medical and biological statistics. The comparison of quantitative indicators with the normal distribution was performed using Student's t-test. Results. Analysis of the functional status of HBS in newborns with hyperbilirubinemia with perinatal pathology showed the following clinical signs of dysfunction: jaundice, hepatosplenomegaly, intestinal dysfunction, manifestations of hypoglycemia, anemic and hemorrhagic syndrome. Disorders of bilirubin metabolism were confirmed by an increase in the blood serum level of bilirubin due to the indirect fraction. Indicators of ALT and AST activity tended to increase considering the severity of perinatal pathology. The value of LDH also correlated with the severity of the condition and was highest in children of the IB subgroup. The activity of ALP tended to increase in children of the IA subgroup, while children of the IB subgroup showed lower activity compared to control. GGT activity in neonates of the observation subgroups showed a tendency to decrease compared with the control. Analysis of the white blood spectrum revealed a decrease in the level of both total protein and albumin levels in children of IA and IB subgroups compared with the control, with more expressed changes observed in newborns with severe perinatal pathology. It was found that the main pathogenetic syndromes and formation of dysfunction of the hepatobiliary system in the presence of clinical signs of hyperbilirubinemia in perinatal pathology are: cytolysis syndrome, cholestasis and protein-synthetic insufficiency, the severity and prevalence of which corresponds to the clinical symptoms and severity of the disease. Conclusions. The main clinical manifestations of disorders of the functional state of the hepatobiliary system in hyperbilirubinemia in perinatal pathology in newborns are: jaundice, hepatosplenomegaly, intestinal dysfunction, in more severe cases — hypoglycemia, anemia and hemorrhagic disorders. In-depth analysis of biochemical parameters of blood in newborns showed that the main syndromes of the pathogenesis of HBS dysfunction are: cytolysis syndrome, which is characterized by increased activity of AST, ALT and LDH; cholestasis syndrome, which is manifested by an increase in blood levels of total bilirubin, cholesterol, increased activity of ALP enzymes, GGT and protein — synthetic deficiency syndrome, which is confirmed by a decrease in total protein, albumin, cholinesterase, urea and glucose. Significant violations of the functional state of the hepatobiliary system in the presence of jaundice in severe perinatal pathology in newborns that were discovered indicate the need for timely diagnosis for appropriate therapeutic correction. The research was carried out according to the principles of the Declaration of Helsinki. The study protocol was approved by the BSMU LEK for all the participants. Examination of children was conducted with the consent of parents after a preliminary explanation of the purpose, methods and scope of laboratory research methods. No conflict of interest was declared by the authors. Key words: newborn, jaundice, hepatobiliary system.

Choledochal cyst in children in dakar: Diagnostic and therapeutic aspects.

Context:Choledochal cyst is a rare malformation that mainly affects girls.Aims:The aim of this work is to report the diagnostic, therapeutic and evolutionary aspects of bile duct cyst in children in Dakar.Subjects and Methods:we conducted a prospective monocentre descriptive study from 1 July, 2016, to 30 June, 2019, in the Pediatric Surgery Department of Albert Royer Children's Hospital in Dakar. The studied parameters featured clinical, biological, radiological, therapeutic and evolutionary data. Overall, ten patients, including eight girls and two boys, were selected.Results:Two patients presented the classic triple-syndrome complex featuring an abdominal pain, an abdominal mass and jaundice. Most of the patients presented a symptomatology associating abdominal pain and vomiting. Biological cholestasis syndrome was present in six cases and biological cytolysis syndrome in five cases. The abdominal ultrasound-computed tomography (CT) scan confirmed the diagnosis and helped to set the Todani classification with a predominance of Types 1 and 4. Surgical treatment by laparotomy consisted of total excision of the cyst followed by a Y-en-Roux hepatico-jejunal anastomosis in nine cases, whereas we performed a drainage of the cyst in one case. Two patients presented a morbidity of anastomotic suture release and evisceration and had a good outcome after surgical repair. There was no mortality.Conclusions:The diagnosis of choledochal cyst dilatation (CCD) can be suspected in the postnatal period on the basis of a gastro-intestinal symptomatology with or without associated to jaundice. The combination ultrasound-abdominal CT-scan helps set the diagnosis. The laparatomic approach always has its place for the management of CCD, especially in our context.

Vitamin K deficiency-induced spontaneous haemopericardium and cardiac tamponade in an infant with alpha-1 antitrypsin deficiency: a case report.

Background Vitamin K deficiency bleeding is a life-threatening complication in early infancy. Exclusive breastfeeding and neonatal cholestasis syndromes, most notable α-1-antitrypsin deficiency, have been reported to be risk factors. Intracranial haemorrhage is most common. No association to haemopericardium has been reported before.Case summary We report on an 11 weeks old at term-born infant, who presented with severe anaemia and signs of cardiogenic shock. Immediately echocardiography was done and depicted cardiac tamponade. Pericardiocentesis was performed and a significant amount of haemorrhagic fluid was removed. Further workup revealed deranged coagulation parameters, cholestatic liver disease, and reduced α-1-antitrypsin levels. Despite normal brain sonography, a small cerebral haemorrhage was detected on magnetic resonance imaging. A genetic test finally proofed homozygotic mutation of the SERPINA1-gene and confirmed the diagnosis of α-1-antitrypsin deficiency as the underlaying cause. After initial replacement of coagulation factors, erythrocytes and vitamin K, the infant recovered. Eighteen weeks after discharge, the infant is still on vitamin K supplementation. She did not have any further bleedings and no neurologic or developmental impairment.Discussion Alpha-1-antitrypsin deficiency can lead to vitamin K deficiency in young infants even with adequate prophylaxis. Spontaneous haemorrhagic pericardial effusion was a new manifestation of vitamin K deficiency bleeding in our patient and should be considered and ruled out in young infants who present with acute anaemia and poor clinical condition.

Correction possibilities of drug-induced liver toxicity in the treatment of patients with blood system tumors

Background. In modern oncohematology achieved notable success due to the intensification and development of new chemotherapy regimens. However, the side effects of anticancer drugs, due to low selectivity of most of them, are a serious limitation to achieve their maximal therapeutic effect. Although doctors are aware of the possibility of hepatotoxic reactions to various drugs, in clinical practice, the diagnosis of drug-induced liver injury is formulated unreasonably rarely. This speculation is due to several factors: in some cases, the latent course of drug-induced liver injury, often inadequate interpretation of clinical symptoms and laboratory parameters, and sometimes insufficiently thorough collection of anamnesis. A particularly difficult problem for a doctor is the development of drug-induced hepatotoxicity in patients for whom the “causal” drug is prescribed for vital indications, in particular, polychemotherapy in cancer patients, complex antimicrobial therapy and antiviral therapy for febrile neutropenia or sepsis, etc. In these situations, on the one hand, treatment cancellation is impossible due to the risk of disease progression, on the other hand, its continuation is undesirable due to the risk of severe hepatitis. In addition, multicomponent therapy, which is a complex of potentially hepatotoxic substances, often does not allow specifying the substance that caused the pathological reaction. At the same time, it is obvious that the hepatocyte, the main cell of the hepatic parenchyma, remains the center of the organ pathology. The variety of biochemical processes occurring with ademetionine participation served as the basis for conducting clinical studies in order to correct drug-induced liver toxicity in the treatment of patients with blood system tumors.The objective of the study is to assess laboratory and clinical parameters of drug-induced liver injury (DILI), intrahepatic cholestasis in the study of homeostasis disorders in patients with hematological malignancies and chemotherapy-induced hepatotoxicity.Materials and methods. The study involved 45 patients with blood system tumors, who had chemotherapy-induced hepatocellular failure. To describe the population of DILI patients, we collected demographic data, clarified the underlying liver disease in each patient, and analyzed the diagnostic criteria for chronic liver disease due to DILI. Clinical signs and symptoms of cholestasis (jaundice, pruritus, weakness), as well as manifestations of a depressive state and asthenic syndrome – mood (mild, moderate and severe), normalization of sleep rhythm, memory improvement, general health were assessed. Changes in laboratory parameters of liver function were studied. In 20 patients with blood system tumors, the biochemical parameters associated with cell metabolism were analyzed – lipid peroxidation, nitric oxide (NOx ) level, impaired liver detoxification capacity by glutathione level and glutathione-S-transferase activity. The treatment regimens for drug-induced hepatotoxicity included the Heptral, which was prescribed until stable normalization of liver function.Results. All patients with developed liver failure showed metabolic disorders. The use of ademetionine has shown significant effect. The NO and superoxide dismutase in most patients decreased significantly and almost corresponded to the norm. Normalization of the glutathione system parameters was also observed. One of the mechanisms of Heptral protective effect is an increase in the glutathione synthesis. The improvement in laboratory parameters was accompanied by the disappearance of DILI and intrahepatic cholestasis symptoms. This is confirmed by significant statistical correlations between them and indicates the ademetionine efficacy to recovery of hepatocytes function. When using ademetionine, the most pronounced reduction among biochemical parameters was observed in alkaline phosphatase and γ-glutamyl transpeptidase, markers of cholestasis syndrome. In addition, serum bilirubin concentration and alanine and aspartic transaminases activity (albeit to a lesser extent) decreased significantly. Clinical and biochemical effects, as a rule, persisted for several months after completion of therapy. Decrease in biochemical parameters characterizing cholestasis and cytolysis (positive dynamics of alanine and aspartic transaminases, alkaline phosphatase, γ-glutamyl transpeptidase, bilirubin) was accompanied by an improvement and normalization of patients’ well-being. When assessing the depression and asthenic syndrome, it was noted that the duration of Heptral therapy is important.Conclusion. The results obtained were the basis for the development of supportive therapy programs to prevent and reduce liver toxicity during chemotherapy. Rational approaches to the liver metabolic disorders correction – a real way to increase the treatment efficacy and improve the quality of life of patients with blood system tumors.

Possibilities of ademetionine in treatment of patients with alcoholic liver disease

Introduction. Alcoholic liver disease (ALD) is the most common liver disease, the terminal stage of which is alcoholic liver cirrhosis (ALC), which ranks first in terms of prevalence and frequency of lethal outcomes in hospital patients. The pathogenesis of alcoholic liver disease is based on direct damage to the hepatocyte membrane, oxidative stress, hepatic parenchyma inflammation with hyperproduction of inflammatory mediators, immune mechanisms, hepatic parenchyma fibrosis. S-adenosyl-L-methionine (ademetionine) is able to affect the different parts of the pathogenesis of ALD. One of the new ademetionine drugs is Samelix (manufacturer – Canonfarma Production JSC, Russia).Aim of the study. Evaluation of Samelix efficacy and safety in patients with chronic alcoholic liver disease with cholestasis syndrome at the inpatient stage of treatment.Materials and methods. 23 patients (men – 11, women – 12) were admitted to the study. The average age was 51.8 ± 3.4 years. Duration of the disease in the remaining patients averaged 3.5 ± 1.9 years (from 0.5 to 8 years). All patients received detoxification therapy, vitamin therapy, and Verospiron was used in patients with liver cirrhosis. Within 10-12 days the therapy with Samelix was carried out: 800 mg/day intravenous drip. The dynamics of biochemical indices (ALT, AST, GGT, bilirubin, ALP); clinical manifestations; life quality according to the SF-36 questionnaire; side effects were assessed.Conclusions. There was a significant reduction in the number of patients with skin itching, increased fatigue and depressed mood, positive dynamics of biochemical indicators in the form of a decrease in AST, ALT, alkaline phosphatase, GGT, total and direct bilirubin. Thus, the therapy allows to effectively reduce symptoms in patients with alcoholic liver disease, resulting in an improvement on all scales and summary indicators – psychological and physical component of health.

S2643 Hepatic Sarcoidosis Manifesting With Severe Hypercalcemia in an Elderly Woman: A Rare Presentation

INTRODUCTION: Sarcoidosis is a chronic, multisystemic non-caseous granulomatous disease of unknown origin. Exclusive liver involvement without lung disease is less frequent, documented in only about 13% of patients with systemic sarcoidosis. The diagnosis of liver sarcoidosis is difficult, because symptoms or functional derangement due to involvement of the liver are uncommon in sarcoidosis. CASE DESCRIPTION/METHODS: An 83 year old woman presented with fever, chills and fatigue of 1 week duration. She further reported no alcohol or drug use, prior blood transfusions and use of herbal supplements. Her exam was unremarkable and initial laboratory data was significant for eosinophilia of 0.6 k/uL and the following liver tests: ALP 613 U/L, AST 234 U/L, ALT 224 U/L, total bilirubin 0.8 mg/dL, INR 1.0 and Gamma Glutamyl Transferase (GGT) 518 U/L. Infectious workup was negative for HBV, HCV, CMV, EBV and Quantiferon. Magnetic resonance imaging of the liver was negative for masses and biliary dilation. Chest CT was negative for pulmonary fibrosis and hilar adenopathy. Immunological workup came back negative. The patient’s ALP was of macrohepatic source and peaked to 1251 U/L over the following week, serum calcium rapidly increased to 13.6 mg/dl and Angiotensin-1 converting enzyme (ACE) was >80 U/L. At this point a liver biopsy was conducted which showed non-necrotic granulomata in a lobular and periportal distribution consistent with sarcoidosis of the liver. The patient was placed on oral prednisone after which her liver tests and severe fatigue improved rapidly. She continues to follow up outpatient and is doing well. DISCUSSION: Sarcoid hepatic granulomas are usually asymptomatic and associated with normal liver function or mild derangement. Fever, interestingly, correlates with hepatic sarcoid, like in our patient. Clinical manifestations of liver involvement are rare and may include chronic cholestasis, portal hypertension or Budd Chiari syndrome. In general, granulomas are found in 4% of all liver biopsy specimens, of these only 13.5%-22% are due to sarcoidosis. An optimal therapeutic regimen for hepatic sarcoidosis remains ill defined. In patients with symptoms or significant hepatic dysfunction, corticosteroids have been used as a first line treatment. Prednisone daily for 8-12 weeks and then gradual tapering over a period of 6-12 months is usually recommended.Figure 1.: Lobular granuloma.Figure 2.: Periportal granuloma.Figure 3.: Periportal granuloma (magnified).

SOME FEATURES OF THE PATHOGENESIS OF ALCOHOLIC HEPATITIS AND ALCOHOLIC CIRRHOSIS OF THE LIVER IN COMBINATION WITH ARTERIAL HYPERTENSION

Purpose - to study the features of the combined course of chronic alcoholic hepatitis (CAH) and alcoholic liver cirrhosis (ALC) with arterial hypertension (AH) by determining the main clinical and laboratory parameters. Material and methods. 13 patients with CAH (group I), 22 patients with CAH in combination with arterial hypertension (group II), 22 patients with ADC (group III) and 40 patients with ADC in combination with arterial hypertension (group IV) were examined. Serum content of C-reactive protein, tumor necrosis factor-α (TNFα), transforming growth factor-β1 (TGFβ1 ), interleukin-10 (IL-10), 8-isoprostane, D-dimer, stable metabolites of nitric oxide (nitrites / nitrates), endothelin-1 (ET-1), intercellular adhesion molecules-1 (ICAM-1); plasma recalcification time (PRT), prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), plasma fibrinogen levels, antithrombin III (ATIII) activity, factor XIII activity, platelet aggregation. Liver function and blood lipid spectrum were also examined. Results. It was found that the manifestations of cytolysis and cholestasis syndromes were mostly more pronounced in patients with alcoholic liver disease (ALD) due to its combination with hypertension. At the same time, there was an increase in the levels of CRP, TNFα, TGFβ1 , IL-10, ceruloplasmin and 8-isoprostane. In the presence of concomitant hypertension, the content of IL-10 (in patients with CAH), CRP (in patients with ALC), as well as the content of 8-isoprostane and ceruloplasmin (in patients with CAH and AlC) probably (p <0.05) exceeded that in patients without hypertension. At the same time, in both CAH and ALC, the presence of endothelial dysfunction was established. Disorders of the endothelial functional state were accompanied by changes in the hemocoagulation of homeostasis and the blood lipid spectrum. When evaluating the quality of the LAL test, it was found that the positive test was in 97.5% of patients with ALC with hypertension compared with CAH with hypertension, where this test was positive in 68.2% of cases. When comparing groups of patients with ALC and CAH, it was found that in 77.2% of cases it was positive in group III and in 38.5% - in group I. In patients with ALC with and without hypertension, this test had the following distribution: 39 patients out of 40 had a positive test in group IV and 17 out of 22 - in group III. Conclusion. The occurrence of cytolytic, cholestatic, mesenchymal-inflammatory syndromes and hepatocellular insufficiency in patients with ALD with hypertension is associated with the direct action of ethanol on the liver, the development of systemic inflammation, oxidative stress, dyslipoproteinemia, endothelial dysfunction with hemocoagulation disorders and endotoxemia..

Pituitary stalk interruption syndrome broadens the clinical spectrum of the TTC26 ciliopathy.

Ciliopathies are a heterogeneous group of disorders, related to abnormal ciliary function. Severe biliary ciliopathy, caused by bi-allelic mutations in TTC26, has been recently described in the context of a syndrome of polydactyly and severe neonatal cholestasis, with brain, kidney and heart involvement. Pituitary involvement has not been previously reported for patients with this condition. Pituitary stalk interruption syndrome (PSIS) is a congenital anomaly of the pituitary gland, diagnosed by characteristic MRI findings. We now describe four patients with TTC26 ciliopathy due to a homozygous c.695A>G p.Asn232Ser mutation and delineate PSIS as a novel clinical feature of this disorder, highlighting an important role of TTC26 in pituitary development.

Surgical diversion of enterohepatic circulation in pediatric cholestasis

Progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome (AS) are conditions caused by either an autosomal recessive or an autosomal dominant genetic defect, and they are both characterized by cholestasis, jaundice, and severe debilitating pruritus refractory to medical management. Before the advent of liver transplantation, most PFIC patients would die from end-stage liver disease in the first decade of life. Although liver transplantation has led to patients’ survival, disease recurrence (PFIC-2) and severe extra-hepatic manifestations of the disease (PFIC-1) occurred post transplant. In the late 1980s, Whitington described the use of partial external biliary diversion in PFIC and AS patients as a successful way to improve symptoms and decrease circulating bile acid serum concentrations. Since then, other diversion techniques have been described (ileal exclusion and partial internal biliary diversion). These techniques have the benefit of avoiding a stoma, but equivalent results have not been demonstrated (recurrence of cholestasis after ileal exclusion, limited follow up after internal biliary diversion). Overall, studies have showed that biliary diversions in children with cholestasis are safe procedures with low morbidity and mortality, and that they can reduce inflammation and ongoing liver injury, therefore delaying or avoiding the need for liver transplantation in some patients.

Вплив екстракту листя лепехи звичайної (Acorus calamus L.) на показники холестазу та жовчовидільну функцію печінки за експериментального гепатиту

Однією з складових уражень печінки є холестатичний синдром, який обумовлено порушенням утворення та відтоку жовчі в кишечник, накопиченням її компонентів у печінці та крові, що проявляється підвищенням активності в крові лужної фосфатази (ЛФ), γ-глутамілтранспептидази (γ-ГТТП), трансаміназ, вмісту холестерину, білірубіну, жовчних кислот тощо. Для корекції синдрому холестазу за алкогольної хвороби та інших уражень печінки часто використовують рослинні та синтетичні засоби з гепатопротекторною й жовчогінною активністю. Мета дослідження – вивчення впливу деалкоголізованого екстракту листя лепехи звичайної (Acorus calamus L.) на процеси жовчоутворення, жовчовиділення та холестазу за умов етанолтетрахлорметанового гепатиту в щурів. Встановлено, що використання деалкоголізованого екстракту листя лепехи звичайної в лікувально-профілактичному режимі за умов гепатиту в щурів, спричиненого введенням тетрахлорметану та етанолу, достовірно зменшує інтенсивність процесу холестазу, покращує жовчосектеторну та жовчоутворювальну функції печінки. Антихолестатичні властивості деалкоголізованого екстракту листя лепехи звичайної підтверджено достовірним зменшенням рівня непрямого та прямого білірубіну, зниженням активності ЛФ і γ-ГТТП. За показниками нормалізації швидкості секреції жовчі, вмісту в жовчі жовчних кислот і холестерину, зменшенням процесів холестазу деалкоголізований екстракт листя лепехи звичайної не поступався препаратам порівняння. Отримані дані свідчать про доцільність подальших поглиблених досліджень екстракту листя лепехи звичайної для створення на її основі ефективних гепатопротекторів.

Features of therapy of alcoholic liver disease in persons of young age

The aim of this study was to study the eff ects of using the infusion drug Remaxol in young patients with alcoholic liver disease.Materials and methods: the clinical and laboratory data of 80 young patients with alcoholic liver disease were analyzed, divided depending on the treatment regimen into 2 groups: the main (n = 44) who received Remaxol according to the scheme: 400 ml iv, drip, at a rate 40–60 drops per minute daily, course No. 5–10, and control (n = 36) — received basic therapy. In all patients, the dynamics in blood serum was studied: lipid peroxidation indices (malondialdehyde, diene conjugates), antioxidant protection enzymes (catalase, SOD, glutathione peroxidase), markers of cytolysis, cholestasis and lipid metabolism.Results: initially there was a significant increase in lipid peroxidation processes, accompanied by slight stimulation of the antioxidant system of the liver and pronounced signs of cytolysis and cholestasis. The inclusion of Remaxol in treatment regimens leads to a significant decrease in the level of malondialdehyde and diene conjugates, and the restoration of the antioxidant system (increase in catalase, SOD, and glutathione peroxidase). At the same time, a marked decrease in the syndromes of cytolysis and cholestasis was noted, which was accompanied by an improvement in the condition of the patients: cessation of nausea, restoration of appetite and sleep, and improvement of well-being.

Hormonal profile of pubertal age girls with chronic viral hepatitis

Chronic viral hepatitis (CVH) is more than 70% of the total number of children with chronic hepatitis, and in the population - 0.5%. Adolescents are the most vulnerable group of the population due to the physiological and psychological characteristics of this age. The liver coordinates both adaptive and reproductive processes in the body, and during puberty is the formation of pituitary-gonadal relationships. The aim: to study the features of hormonal homeostasis in adolescent girls with CVH. Materials and methods. We examined 300 girls aged 12-17 years, of which 120 patients with CVH (60 patients with hepatitis B and 60 - with hepatitis C) and 180 relatively healthy patients with physiological sexual development. The diagnosis of CVH was established on the basis of medical history, clinical, virological, biochemical, morphological and instrumental examination. Results. Analysis of the obtained data of the functional state of the liver in the examined patients with CVH revealed disorders of the morphofunctional state of the liver, manifested by cytolysis syndrome, cholestasis, hepatocellular insufficiency and mesenchymal-inflammatory syndrome. In patients with CVH there was a decrease in the production of luteinizing hormone (4.35 ± 0.09 vs. 5.13 ± 0.08 mIU / ml, p<0.01); follicle-stimulating hormone (4.40 ± 0.15 vs. 5.40 ± 0.07 mIU / l, p<0.01); prolactin (215.56 ± 4.76 vs. 282.93 ± 8.36 mIU / ml, p <0.01); progesterone (2.09 ± 0.10 vs. 2.78 ± 0.08 nmol / l, p<0.01) on the background of increasing the average level of estradiol (468.65 ± 21.32 vs. 437.45 ± 9.59 pmol / l, p<0,01) and free testosterone (1,98 ± 0,08 vs. 1,16 ± 0,04 nmol / l, p <0,01). Thyroid status was characterized by a relative decrease in the production of thyroid-stimulating hormone (1.74 ± 0.04 vs. 2.15 ± 0.05 μIU / ml (p<0.01) and an increase in the secretion of free triiodothyronine (9.32 ± 0.09 vs. 5,46 ± 0.07 pmol / l, p<0.01) and free thyroxine (23.35 ± 0.76 vs. 18.55 ± 0.20 pmol / l, p<0.01). chronic infectious process, affects the morphofunctional state of the liver and leads to dysfunction of the hypothalamic-pituitary-ovarian and pituitary-thyroid systems, manifested by pathological changes in the secretion of gonadotropins, prolactin, thyroid-stimulating hormone, sex steroids and hormonal steroids.

Mutations in Myosin 5B in Children With Early-onset Cholestasis.

Mutations in Myosin 5B (MYO5B) are known to be associated with microvillous inclusion disease (MVID) a genetic cause of neonatal intractable diarrhoea. More recently, they have been reported in children with cholestasis but without typical gastrointestinal symptoms of MVID. We describe our series of children with cholestasis and mutations in MYO5B. Clinical, laboratory, and histological data were collected from patients with cholestasis and pathogenic mutations in MYO5B, found by next generation sequencing (NGS) but with minimal gastrointestinal disease. Six patients (3 boys) were identified. Median age at presentation was 19 months (range, 3-92). Presenting features were jaundice, pale stools, pruritus, and failure to thrive. Patients 5 and 6 had intractable diarrhoea until the age of 3 and 7 years, respectively, but currently are on full enteral diet with no intestinal symptoms. Median values for serum total bilirubin were 55 μmol/L (2-500), alanine aminotransferase 73I IU/L (32-114), γ-glutamyltransferase 7 IU/L (7-10), and serum bile acids 134 μmol/L (18-274). Three patients underwent 1 or more types of biliary diversion for symptom control. Median follow-up was 5 years (2-22). At most recent follow-up, they all reported pruritus while on antipruritics. Patient 1 had a liver transplant. We identified 6 patients, with mutations in MYO5B, early-onset cholestasis and pruritus, with variable response to biliary diversion without typical MVID.

Inherited Cholestatic Diseases in the Era of Personalized Medicine.

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-3-reading-mack a video presentation of this article.

Clinical course features of non-alcoholic steatohepatitis on obesity background in comorbidity with chronic obstructive pulmonary disease

Objective: to elucidate clinical, ultrasonographic, and biochemical features of the course of non-alcoholic steatohepatitis (NASH) for comorbidity with grade 1 obesity, chronic obstructive pulmonary disease (COPD) of 2–3 D stages compared with NASH during obesity without COPD by studying the frequency and intensity of leading clinical and biochemical syndromes of NASH, comparison of ultrasonographic (USG) characteristics of NASH depending on the presence of COPD. Material and methods. 105 NASH patients were examined: 52 NASH patients with grade 1 obesity (1 group) (there were 18 men, 24 women); 53 NASH patients with comorbid grade 1 obesity and COPD of 2–3 D stages (group 2) (there were 28 men, 13 women). In order to determine the dependence of NASH on the presence of COPD, groups of patients were randomized by the age and the degree of obesity. The average age of the patients was (55,7 ± 3,22) years. The functional condition of the liver was determined by the generally accepted lists of enzyme activity, markers of pigment and nitrogen metabolism, proteinograms, lipidograms, ionograms, calculation of de Ritis ratio, and the USG was performed. In order to quantify the changes in liver echogenicity we have used the method of echodensitometry with the calculation of the hepatorenal index. Results. The symptoms of astheno-vegetative syndrome, dyspepsia and feeling of heaviness or pain while palpating in the right hypochondrium were observed in 2,1 times, 1,7 times and 2,5 times (p<0,05) more often in patients of the 2nd group in comparison with patients of the 1st group. Clinically, in NASH patients the syndrome of cholestasis was found in 28.8%, in comparison with NASH patients and COPD (in 62,3%). In patients of the 2nd group, the frequency of splenomegaly exceeded the indicator in the 1st group, respectively, in 2.7 times (p<0.05). Among the biochemical syndromes in the examined patients of the 2nd group was found cytolytic (100,0%), cholestatic (73,6%) syndromes, which exceeded the frequency in the 1st group in 2,3 times (p<0,05), mesenchymal inflammatory, which occurred more often as compared to the 1st group — in 1.9 times (p<0,05), and hepatocellular failure (HF) syndrome (50,9%), which occurred more often in comparison with the 1st group — in 2,6 times (p<0,05). Conclusion. The clinical course of non-alcoholic steatohepatitis for comorbidity with obesity is characterized by a high frequency and intensity of clinical syndromes, the manifestation of which increases significantly with the addition of COPD 2–3 D namely: astheno-vegetative, abdominal pain, portal hypertension, splenomegaly, cholestasis, as well as the frequency and intensity of biochemical syndromes namely: mesenchymal inflammation, cholestasis, hepatocellular failure.

Diagnosis of Galactosemia by Simple Technique in a Resource-Constraint Country

Galactosemia is an autosomal recessive inheritance and there is cellular deficiency of enzymes leading to defective/impaired metabolism of galactose resulting in toxic byproducts like galactilol, galactose-1-phosphate and galactonate that affect mainly liver, brain, kidneys, lens and gonads. Galactosemia appears as a rare metabolic cause of neonatal cholestasis syndrome (NCS). The classic disease manifestation after the first milk feeding varies in severity from an acute fulminant illness to a more common subacute illness beginning within the first few days of life. Neonatal sepsis is one of the presentations. Galactokinase deficiency results primarily in cataract formation and galactosuria. The preliminary diagnosis of galactosemia in sick neonates and suspected infants is made by Benedict test in several urine specimens and followed by dipstick test to exclude glycosuria. Gold standard test is demonstration of low enzyme activity in erythrocyte. Galactosemia can be detected by newborn screening methods like the Guthrie test using filterpaper blood samples. Classical form of galactosemia should be treated with an absolute galactose restricted diet without waiting for confirmation of the diagnosis. Here we report a case of a 50-dayold boy with features of neonatal cholestasis, diagnosed as galactosemia by using a simple cost effective method.&#x0D; J Enam Med Col 2020; 10(1): 43-48

Клінічний випадок гострої форми панкреатиту у свійського собаки

At present the disease called pancreatitis has become widespread not only among humans, but also among animals, including dogs. It is not only difficult to diagnose, but also to treat. The main cause is considered to be improper feeding of the animal, which can include fatty feed, various spices, sweets, etc. Even the same irregular feeding regimen can lead to pancreatitis. To diagnose this disease, various scientists offer different methods of research: ranging from general and biochemical blood tests to ultrasound diagnostics of the abdominal cavity. We conducted a study of the clinical case of acute form of pancreatitis in the dog breed pug, aged 1 year and 3 months. The main clinical features of the disease were general weakness and frequent vomiting seen over several days. It was also found the main etiologic factor - the wrong feeding regimen of the young organism and formed as a result of this distorted appetite. Elevated hematocrit and erythrocytosis indicate dehydration. Moderate monocytosis and neutrophilia with a shift to the left, as well as lymphopenia are indicators of stress and significant inflammation. Concentration ability of the kidneys is not impaired, as evidenced by urine analysis. Hyperglycemia is possibly stress related. Hypercholesterolemia and increased ALP activity are the result of cholestasis syndrome. A decrease in the concentration of phosphorus, urea and creatinine may indicate a violation of feeding, namely a low-protein diet, possibly even starvation. A strong increase in the activity of the enzymes amylase and lipase, along with the history data and changes in the leukocyte formula, as well as ultrasound confirm the diagnosis of pancreatitis. The therapy included active intravenous infusion of solutions to maintain metabolic processes together with analgesics, namely 0.9 % sodium chloride solution - 300 ml per day (with the addition of 2 % lidocaine solution), Ringer's lactate solution - 154 ml per day, and drugs to reduce pain and the growth of pathogenic bacteria: serenia - 0.3 ml once a day, Sinulox - 0.3 ml, once a day. Infusion therapy was carried out at a constant rate using a perfuser. Diet therapy for pancreatitis is a fairly important link in any treatment regimen. At the end of the 3rd day in the hospital, Rocky began to drink water, it was recommended to give him a small amount (about a tablespoon) chopped and diluted with warm, boiled water, dietary food Gastro Intestinal Low Fat from Royal Canin.