Increased Aminotransferase Levels Research Articles

Efficacy of Upadacitinib As a Second-line JAK Inhibitor in Ulcerative Colitis: A Case Series.

Upadacitinib, a recently approved Janus kinase (JAK) inhibitor specific for JAK1, may be a promising candidate in patients with ulcerative colitis (UC) who present no response or intolerance to first-line JAK inhibitors. We assessed the therapeutic impact of upadacitinib on six UC patients who demonstrated an inadequate response or intolerance to tofacitinib or filgotinib. After 2 months of treatment, 5 patients (83.3%) achieved clinical remission, and all patients experienced decreased levels of C-reactive protein. One patient had coronavirus disease 2019 pneumonia and showed a mild increase in transaminase levels. This case series highlights the potential utility of a rotation strategy among JAK inhibitors.

Real-world experience of thrombopoietin receptor agonists in pediatric immune thrombocytopenia: a report from a Chinese tertiary children's hospital.

Primary immune thrombocytopenia (ITP) is the most common bleeding disorder in children. There are approximately 20% pediatric ITP patients respond poor to corticosteroids as first-line treatment. Recently thrombopoietin receptor agonists (TPO-RAs) have been used to treat refractory ITP and have achieved certain therapeutic effects. To investigate the efficacy and safety of TPO-RAs in the treatment of pediatric ITP, we conducted this real-world study. Fifty-three pediatric patients with ITP who did not respond well to corticosteroids were treated with TPO-RAs. Clinical data, including therapeutic response rate, changes in platelet (PLT) count, and adverse events (AEs) were collected. Of the 51 evaluable patients, 37 (72.5%) responded to TPO-RAs. Patients aged >4 years had a higher response rate than those aged ≤4 years (81.1% vs. 50.0%, P=0.04). There was no effect of sex, duration of disease, prior therapy, Mycoplasma pneumoniae (MP) immunoglobulin M (IgM) positivity, antinuclear antibody (ANA) positivity, CD4/CD8 ratio or baseline PLT count on the response rate (P>0.05). Other than 10 patients with PLT counts that exceeded the upper limit of normal, AEs were sporadic, including increased aminotransferase levels, cough, headache, and vomiting. TPO-RAs exhibited good clinical efficacy in pediatric ITP patients who failed to respond to first-line treatment, especially patients aged >4 years, and the side effects were minor.

DRESS as a rare differential diagnosis in eosinophilia, skin rash and acute hepatitis

A 21-year-old female patient presented with fever, pharyngitis, lymphadenopathy and generalized exanthema that had started 2 weeks prior. Allergies were not known, the family and travel history were negative. Due to depression, Duloxetine had been taken for 1.5 years, and due to bipolar disorder, a treatment with Lamotrigine was started four weeks prior but was stopped because of increased transaminase levels. Laboratory findings on admission showed eosinophilia (1.327 /nl), lymphocytosis and acute hepatitis (GOT 428 U/l, GPT 438 U/l) with deranged coagulation. Inflammatory parameters were increased. Ultrasound revealed hepatosplenomegaly with ascites. Acute viral or parasitic infection was excluded serologically. A skin biopsy showed a perivascular inflammatory infiltrate, compatible with a drug reaction. An inflammatory infiltrate was found in the liver biopsy, consistent with drug-induced hepatitis. Cough, dyspnea and pleural effusion occurred. In summary of the findings and with the help of the RegiSCAR-Score, the diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) could be made. Under high-dose prednisolone therapy, a gradual decrease of transaminases and reconstitution of liver synthesis could be observed.In patients with eosinophilia, lymphadenopathy, acute hepatitis and generalized exanthema, DRESS is a rare but-due to its potentially life-threatening consequences-important differential diagnosis. The most important measure is to stop the suspected inducing medication immediately. Severe cases should be treated with high-dose systemic corticosteroids.

Changes in zonulin levels and possibilities for its correction in patients with liver cirrhosis and hepatic encephalopathy after COVID-19

Background. The liver is frequently affected in coronavirus disease 2019 (COVID-19), which can range from a simple increase in transaminase levels to the development of acute liver failure. The study of the peculiarities of the course of liver cirrhosis (LC) and its complications, especially hepatic encephalopathy (HE), in COVID-19 and the study of possible markers indica­ting the progression of the disease and the development of effective methods for their correction is an urgent task today. Aim of the research: to study the features of changes in serum and faecal zonulin levels and its dynamics in patients with LC and HE after COVID-19 on the background of a comprehensive therapy with a butyric acid preparation. Materials and methods. The study was conducted in two stages. At the first stage, 126 patients with LC were examined to determine the features of HE course, colonic dysbiosis, and zonulin levels in blood serum and faeces at discharge from the hospital after COVID-19, as well as after 1 month of outpatient follow-up. At the second stage of the study, patients with LC and HE after COVID-19 were divided into two groups depending on the treatment: group I (n = 56) received only basic therapy for LC, which included constant use of the β-blocker bisoprolol, lactulose, as well as a combined hepatoprotective agent, melatonin and rifaximin; group II (n = 70) in addition to basic therapy took a combined probiotic preparation containing butyric acid. Results. During the first month after COVID-19, progression of the HE severity was diagnosed in patients with LC. Among participants with LC classes B and C, an increase in the number of patients with grade II HE (up to 57.2 and 72.2 %, respectively) was found a month after COVID-19, and in 16.7 % of patients with decompensated LC, grade III HE was diagnosed. Colonic dysbiosis progression was detected in patients with LC and HE after COVID-19. In one month of the follow-up, a repeated microbiological exami­nation of faeces revealed a significant increase in the number of patients with LC and HE after COVID-19 with grade III colonic dysbiosis, regardless of the stage of the disease, which, accordingly, occurred against the background of a decrease in patients with grade I and II colonic dysbiosis. Among patients with LC and HE after COVID-19, a significant increase in serum and faecal zonulin was found with maximum values in patients with class C according to the Child-Pugh score, which also tended to increase during the first month of observation (up to (171.4 ± 2.2) ng/ml in serum and up to (198.2 ± 3.4 ng/ml) in faeces). The administration of a probiotic complex containing butyric acid contributed to a decrease in both blood and faecal zonulin levels in patients with LC and HE after COVID-19 during a one-month course of treatment. Conclusions. In patients with LC after COVID-19, a progression of HE and colonic dysbiosis severity was diagnosed during the first month of outpatient follow-up. Participants with LC and HE after COVID-19 reported an increase in the level of zonulin in the blood serum and faeces (up to (102.7 ± 1.4) ng/ml, p < 0.01, and up to (131.4 ± 2.6), p < 0.001, respectively), which tends to increase depending on the progression of the disease severity. Comprehensive therapy with the use of a drug containing butyric acid is an effective method to reduce the level of blood and faecal zonulin in patients with LC and HE after COVID-19.

Comparing the adverse effects of ketamine and esketamine between genders using FAERS data.

Ketamine was developed as an anesthetic. Esketamine is the isolated S-enantiomer of racemic ketamine. They provide new avenues for the treatment of depression, especially treatment-resistant depression. Considering differences in the pharmacokinetics and hormonal status of ketamine in patients of different genders, sex-based differences in esketamine adverse drug events (ADE) may also be observed. This study presents data mining and safety analysis of adverse events of ketamine and esketamine between genders, promoting the individualization of clinical practice. Adverse drug reactions to ketamine and esketamine reported between the first quarter of 2004 and the second quarter of 2023 in the U.S. Food and Drug Administration on Adverse Event Reporting System (FAERS) were extracted. Thereafter, the reporting odds ratio (ROR) with 95% confidence interval (CI) was calculated. A total of 2907 female reports and 1634 male reports on esketamine were included in the analysis. ROR mining showed that completed suicide, decreased therapeutic product effects, urinary retention, and hypertension were common in men. Additionally, 552 female and 653 male ketamine reports were recorded. ROR mining revealed that toxicity to various agents, bradycardia, cystitis and agitation, were more likely to occur in men, whereas women were more likely to develop suicidal ideation, increased transaminase levels, sclerosing cholangitis, and sterile pyuria. The adverse events of esketamine and ketamine differ across genders, which should be considered in clinical practice to provide individualized treatment.

Гликогеновая болезнь, IX тип у детей: клинические наблюдения

Orphan diseases are of increasing scientific and practical interest due to the difficulties of diagnosis which in its turn is caused by their rare occurrence and, accordingly, delayed actions aimed at improving the patient’s quality of life and in some situations the impossibility of preserving it. The clinical observations presented in this Article demonstrate emerging problem: many diseases have similar symptoms, and correct vision and interpretation of these symptoms and syndromes require time and specific diagnostic methods. Analyses of the observed clinical situations are useful from the perspective of medical education and alertness to rare genetic diseases. The Article presents clinical observations of a glycogen disease type IX case in siblings, of a familiar and hereditary nature. For the first time, hepatomegaly and increased transaminase levels were accidentally detected in an older boy at the age of 2 years old during an outpatient check-up. As a result of a thorough long-term examination of the child, a number of diseases accompanied by liver damage were excluded and a hereditary metabolic pathology was suggested. Molecular genetic research made it possible to establish a diagnosis by identifying a genetic defect when the child was 4 years and 3 months old. Similar complaints and clinical manifestations in the younger brother of the described patient prompted the disease, as a result of which an identical gene mutation was discovered. The study of the genotype of the children's mother made it possible to confirm both the familiar and the hereditary nature of transmission of the disease from a clinically healthy carrier-mother to her sons. The clinical observations of glycogen disease, type IX, presented in the Article attract attention due to the non-obviousness of the clinical diagnosis when detected in siblings. Timely examination and diagnostic research made it possible to verify the diagnosis and develop a rational diet that contributes to the achievement of the main life characteristics - its quality and expectancy. Thus, a prognostically favorable prognosis was ensured. Conclusion: a genetic defect may be hidden behind the nonspecific manifestations of almost any disease. From this perspective, it becomes obvious that it is necessary to inform physicians of all specialties, especially within the primary care healthcare system, about the possibility of medical genetic counseling, the increasing availability of molecular genetic examinations and biochemical tests aimed at identifying hereditary pathologies. Timely examination and treatment, early medical intervention helped changing the course of the disease in terms of minimizing symptoms and improving the quality of life, reducing the rate of progression of the pathology.

MTOR inhibitors a potential predisposing factor for chronic hepatitis E: Results from the prospective collaborative CHES study (Chronic Hepatitis EScreening in patients with immune impairment and increased transaminases levels)

BackgroundChronic hepatitis E virus (HEV) in persons with immune impairment has a progressive course leading to a rapid progression to liver cirrhosis. However, prospective data on chronic HEV is scarce. The aim of this study was to determine the prevalence and risk factors for chronic HEV infection in subjects with immune dysfunction and elevated liver enzymes. Patients and methodsCHES is a multicenter prospective study that included adults with elevated transaminases values for at least 6 months and any of these conditions: transplant recipients, HIV infection, haemodialysis, liver cirrhosis, and immunosuppressant therapy. Anti-HEV IgG/IgM (Wantai ELISA) and HEV-RNA by an automated highly sensitive assay (Roche diagnostics) were performed in all subjects. In addition, all participants answered an epidemiological survey. ResultsThree hundred and eighty-one patients were included: 131 transplant recipients, 115 cirrhosis, 51 HIV-infected subjects, 87 on immunosuppressants, 4 hemodialysis. Overall, 210 subjects were on immunosuppressants. Anti-HEV IgG was found in 94 (25.6%) subjects with similar rates regardless of the cause for immune impairment. HEV-RNA was positive in 6 (1.6%), all of them transplant recipients, yielding a rate of chronic HEV of 5.8% among solid-organ recipients. In the transplant population, only therapy with mTOR inhibitors was independently associated with risk of chronic HEV, whereas also ALT values impacted in the general model. ConclusionsDespite previous abnormal transaminases values, chronic HEV was only observed among solid-organ recipients. In this population, the rate of chronic HEV was 5.8% and only therapy with mTOR inhibitors was independently associated with chronic hepatitis E.

Pharmacogenetic Markers of Favipiravir Safety in COVID-19 Treatment

The aim of the study was to evaluate the associations of different variants of AOX1 and CYP1A2 genes with safety parameters of favipiravir therapy in patients with COVID-19. Material and Methods. The study included 86 patients hospitalized at Moscow Clinical Hospital No. 15 with a COVID-19 diagnosis who received favipiravir as etiotropic therapy. Frequency of adverse reactions (bradycardia, dyspeptic disorders, increased transaminase levels) and various laboratory parameters (levels of ALT, AST, leukocytes) were compared between the carriers of «wild» and polymorphic variants of the genes studied after administration of the drug. The dynamics of these indicators before and after the therapy depending on the carriage of the variants of the genes studied were also compared. Results. There was no significant difference in the frequency of ad- verse reactions and laboratory parameters between the carriers of various variants of the studied genes. Haplotype analysis of the combination of different gene variants also did not reveal associations with therapy safety parameters. Upon the comparison of the parameters before and after treatment, an increase in the level of AST was noted in carriers of the AA genotype for both studied loci of the AOX1 gene (P=0.018 и P=0.009). At the same time, the level of AST increased in carriers of polymorphic variants of the CYP1A2*F1 gene (P=0.024). Leukocyte number increase was noted in carriers of polymorphic variants of AOX1 (rs10931910) (P=0.044), as well as «wild» genotypes AOX1 (rs55754655) (P=0.002) and CYP1A2*F1 (P=0.05). Conclusion. The associations of carriers of different AOX1 and CYP1A2 gene variants on the dynamics of AST and leukocytes in patients with COVID-19 after favipiravir therapy were revealed.

Increase in transaminase levels during COVID-19 infection and its association with poor prognosis.

Increase in transaminase levels during COVID-19 infection and its association with poor prognosis.

Liver Damage Associated with SARS-CoV-2 Infection—Myth or Reality?

(1) Introduction: While the primary impairment in COVID-19 is pulmonary, the ubiquitous distribution of angiotensin-converting enzyme 2 (ACE2) demonstrates the possible presence of systemic disease with involvement of the heart, kidneys, liver and other organs. (2) Methods: We retrospectively studied the observation sheets of patients diagnosed with SARS-CoV-2 infection hospitalized in the "Sf. Parascheva" Clinical Hospital of Infectious Diseases from Iasi for a period of 3 months. The aim of the study was to identify the frequency of liver injury due to SARS-CoV-2 infection among patients and its impact on the course of the disease. (3) Results: Out of the total number of hospitalized cases (1552), 207 (13.34%) were the subjects of our analysis. The severe form of SARS-CoV-2 infection predominated (108 cases; 52.17%) and in terms of liver damage, in all cases increased transaminase levels predominated and were determined to be secondary to the viral infection. We divided the lot into two groups, A (23 cases; 23.19%) and B (159 cases; 76.81%), depending on the time of onset of liver dysfunction, either at the time of hospitalization or during hospitalization. The evolution of liver dysfunction was predominant in most cases, with an average time of onset at 12.4 days of hospitalization. Death occurred in 50 cases. (4) Conclusions: This study revealed that high AST and ALT at hospital admission was associated with a high mortality risk in COVID-19 patients. Therefore, abnormal liver test results can be a significant prognostic indicator of outcomes in COVID-19 patients.

MTOR inhibitors a potential predisposing factor for chronic hepatitis E: Results from the prospective collaborative CHES study (Chronic Hepatitis EScreening in patients with immune impairment and increased transaminases levels)

BackgroundChronic hepatitis E virus (HEV) in persons with immune impairment has a progressive course leading to a rapid progression to liver cirrhosis. However, prospective data on chronic HEV is scarce. The aim of this study was to determine the prevalence and risk factors for chronic HEV infection in subjects with immune dysfunction and elevated liver enzymes. Patients and methodsCHES is a multicenter prospective study that included adults with elevated transaminases values for at least 6 months and any of these conditions: transplant recipients, HIV infection, haemodialysis, liver cirrhosis, and immunosuppressant therapy. Anti-HEV IgG/IgM (Wantai ELISA) and HEV-RNA by an automated highly sensitive assay (Roche diagnostics) were performed in all subjects. In addition, all participants answered an epidemiological survey. ResultsThree hundred and eighty-one patients were included: 131 transplant recipients, 115 cirrhosis, 51 HIV-infected subjects, 87 on immunosuppressants, 4 hemodialysis. Overall, 210 subjects were on immunosuppressants. Anti-HEV IgG was found in 94 (25.6%) subjects with similar rates regardless of the cause for immune impairment. HEV-RNA was positive in 6 (1.6%), all of them transplant recipients, yielding a rate of chronic HEV of 5.8% among solid-organ recipients. In the transplant population, only therapy with mTOR inhibitors was independently associated with risk of chronic HEV, whereas also ALT values impacted in the general model. ConclusionsDespite previous abnormal transaminases values, chronic HEV was only observed among solid-organ recipients. In this population, the rate of chronic HEV was 5.8% and only therapy with mTOR inhibitors was independently associated with chronic hepatitis E.

Loss of Hematopoietic Cell-Derived Oncostatin M Worsens Diet-Induced Dysmetabolism in Mice.

Innate immune cells infiltrate growing adipose and propagate inflammatory clues to metabolically distant tissues, thereby promoting glucose intolerance and insulin resistance. Cytokines of the IL-6 family and gp130 ligands are among such signals. The role played by Oncostatin M (OSM) in the metabolic consequences of overfeeding is debated at least in part because prior studies did not distinguish OSM sources and dynamics. Here, we explored the role of OSM in metabolic responses and used bone marrow transplantation to test the hypothesis that hematopoietic cells are major contributors to the metabolic effects of OSM. We show that OSM is required to adapt during the development of obesity as OSM concentrations are dynamically modulated during high-fat diet (HFD) and Osm-/- mice displayed early-onset glucose intolerance, impaired muscle glucose uptake, worsened liver inflammation and damage. We found that OSM is mostly produced by blood cells, and that deletion of OSM in hematopoietic cells phenocopied glucose intolerance of whole-body Osm-/- mice on HFD, and recapitulated liver damage with increased aminotransferase levels. We thus uncover that modulation of OSM is involved in the metabolic response to overfeeding and that hematopoietic cell-derived OSM can regulate metabolism, likely via multiple effects in different tissues.

The Frequency and Characteristics of Severe Liver-Related Adverse Events in Patients with Chronic Liver Diseases after Vaccination against Severe Acute Respiratory Syndrome Coronavirus 2: A Retrospective Study

Background: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recommended for patients with chronic liver diseases as the vaccine can prevent and/or reduce the severity of SARS-CoV-2 infection. However, we have little information on the often-reported liver-related adverse events (LrAEs) caused by the mRNA vaccine. Methods: We retrospectively investigated the frequency and details of severe LrAEs and changes in liver function tests in patients with chronic liver diseases. Results: Among 431 patients with chronic liver diseases, 416 (96.5%) had received the SARS-CoV-2 vaccine ≥ 2 times. Among the 345 patients included in the analysis, 6 (1.7%) had severe LrAEs; 3 ascites, 2 increases in transaminases, and 1 an increase in total bilirubin. Multivariate analysis demonstrated that cirrhosis and autoimmune disease were risk factors for severe LrAEs. In contrast, the liver function reserve assessed by the Child–Pugh and ALBI scores did not markedly change after vaccination in patients with cirrhosis and/or autoimmune diseases despite a small increase in transaminase levels. Conclusion: SARS-CoV-2 mRNA vaccines, which were used in most of our patients, are safe in patients with chronic liver diseases, but the frequency of severe LrAEs is slightly increased in patients with cirrhosis and/or autoimmune diseases.

Portal Hypertension in Children: A Tertiary Center Experience in Turkey.

Portal hypertension (PH) and its complications have a significant impact on morbidity and mortality. This study aimed to evaluate the etiology; clinical, laboratory, and endoscopic findings; treatment approaches; long-term outcomes; and prognosis of pediatric PH. This retrospective study included 222 pediatric patients diagnosed with PH between 1998 and 2016, and data encompassing clinical, laboratory, and radiological features; treatments; and complications were analyzed. The most common causes of PH were portal vein thrombosis (20.3%), progressive familial intrahepatic cholestasis (18.9%), and biliary atresia (12.2%). Among the enrolled patients, 131 (59.0%) were included in the cirrhotic group and 91 (41.0%) in the non-cirrhotic group. Hepatomegaly and increased transaminase levels were more frequent in the cirrhotic group than in the non-cirrhotic group. Additionally, portal gastropathy, esophageal varices, and variceal bleeding were more frequent in the non-cirrhotic group, whereas ascites, hepatopulmonary syndrome and hepatic encephalopathy were more common in the cirrhotic group. The incidence of hepatomegaly was higher in the presinusoidal group than in the prehepatic group (p<0.001). Hyperbilirubinemia was more frequent in the prehepatic group (p=0.046). The frequency of esophageal varices was similar between the prehepatic and presinusoidal groups; however, variceal bleeding was more frequent in the prehepatic group (p=0.002). Extrahepatic portal vein obstruction, genetic-metabolic diseases, and biliary atresia were the most prevalent causes of PH in our country. In patients with PH, hepatomegaly, increased transaminase levels, and synthesis dysfunction were suggestive of cirrhotic PH. Notably, PH in patients without cirrhosis might be more severe than that in those with cirrhosis.

Prevalence of Hepatitis E Virus in Patients with Chronic Hepatopathy in a Reference Center of Bahia State, Brazil

Introduction: Hepatitis E virus infection can lead to severe liver disease and unregulated hepatitis in patients with a history of previous chronic liver disease of different etiologies. Objective: To determine the seroprevalence of hepatitis E in untreated carriers of hepatitis C virus, hepatitis B virus, autoimmune hepatitis and in patients with drug-induced liver disease. Materials and Methods: This is a cross-sectional study with a total sample of 301 outpatient hepatology volunteers. The detection of anti-HEV IgM and IgG antibodies was determined using the ELISA (RecomWell anti-HEV IgG and IgM, Mikrogen®, Germany), One-step real-time PCR was used for the detection of HEV-RNA (Taqman, Life Technologies TM, Foster City, CA, USA). Results: The overall prevalence of anti-HEV IgG and IgM in the population studied was 12.95% and 2.3%, respectively. The prevalence by group were: anti-HEV IgG: hepatitis C virus with 13.2%, hepatitis B virus with 13%, autoimmune hepatitis with 8.1 and drug-induced liver disease with 21.1. Patients with HCV chronic hepatitis and positive HCV IgG serology showed an increase in transaminase levels in 66.7% (10/15) of the cases, while in the seronegative patients this increase was present in 42.4% (42/99) of the cases (p&lt;0.05). Conclusions: A high seroprevalence of HEV was observed. Among the patients with serology concomitantly positive for anti HEV IgG and IgM, 57.1% (4/7) had higher levels of TGO and TGP, suggesting acute HEV infection. A relationship between hepatitis C and E virus co-infection and elevated transaminase levels has been demonstrated. Future studies with evaluation of several clinical parameters are necessary.

Eugenia gracillima essential oil has pharmaceutical applications in pain and inflammation without toxic effects in mice

Ethnopharmacological relevanceEugenia gracillima is widely used by the population in the manufacture of pulps and jellies, with popular reports of its use in the treatment of infections in the urinary system, respiratory and dermatological problems. A previous study reports that EO from E. gracillima leaves proved to be a promising antioxidant agent in combating the promastigote forms of protozoa. Despite this, this species has been little studied due to its pharmacological properties. Study objectiveIn this study, an essential oil extracted (EO) from Eugenia gracillima leaves was evaluated for its acute toxicity and anti-inflammatory, antinociceptive and behavioral effects in mice. MethodsThe EO was obtained by hydrodistillation, and the composition analysis was performed by gas chromatography coupled to mass spectrometry. Acute toxicity assessment was performed with observation of hematological parameters and histopathological evaluation, as well as tests to investigate antinociceptive, anti-inflammatory activities and behavioral effects. ResultsChromatographic analysis showed D-germacrene (16.10%), γ-muurolene-g (15.60%) and bicyclogermacrene (8.53%) as the majority of compounds. In the toxicity evaluation, no death or physiological changes were observed in mice treated with a single oral dose of up to 5000 mg/kg, and it did not lyse erythrocytes in vitro. The hematological parameters evaluated were not changed after treatment; however, 5,000 mg/kg promoted an increase in transaminase levels. In the histopathological evaluation, only the animals that received the dose of 5000 mg/kg showed discrete leukocyte infiltration around the centrilobular vein in the liver. Antinociceptive activity was detected through tests of acetic acid-induced writhing, formalin, and tail flick, promoted in part by the opioid receptor pathway. In the evaluation of anti-inflammatory activity, a reduction in inflammation was observed in the paw edema test and a decrease in the migration of leukocytes and neutrophils in the peritonitis test. The open field and elevated plus maze tests showed that EO did not affect the animals' motor functions or exploratory activity. ConclusionIt was concluded that the essential oil of E. gracillima has potential for the development of pharmaceutical formulations with analgesic and anti-inflammatory actions in non-toxic concentrations.

Diagnostic Performance of Noninvasive Tests for Advanced Hepatic Fibrosis in Young Age Population

Most noninvasive tests (NITs) for hepatic fibrosis are designed for middle-aged patients with chronic liver disease. We compared the diagnostic performance of major NITs (aspartate aminotransferase-to-platelet ratio index [APRI], Fibrosis-4 index, and nonalcoholic fatty liver disease fibrosis score) for a community-based cohort. This cross-sectional study analyzed 8775 participants who underwent magnetic resonance elastography at community health check-up centers. Advanced hepatic fibrosis (≥F3)was defined by magnetic resonance elastography thresholds of 3.6 kPa. Thediagnostic performance of 3 NITs was evaluated according to the etiology of liver disease, sex,metabolic syndrome, obesity, and increased aminotransferase levels in 4 age groups. The APRI generally showed the best area under the receiver operating characteristic curve in patients aged 45 years or younger, and it was statistically significant in patients with chronic viral hepatitis and alcoholic fatty liver disease (P < .043). The best APRI cut-off value for detecting advanced hepatic fibrosis was 0.4, with a sensitivity and specificity of 75.8% and 73.5%, respectively, in the community-based cohort. The APRI showed balanced sensitivity and specificity across all age groups, whereas the other metrics showed low sensitivity in those aged <45 and low specificity in those >65 years. The APRI showed better sensitivity and negative predictive value than the Fibrosis-4 index and the nonalcoholic fatty liver disease fibrosis score in community-based populations with mixed etiology, and, thus, can be performed as the primary test in young adults (age, ≤45 y).

Anorexia Nervosa and Liver Health

Sinirsel iştah kaybı anlamına gelen Anoreksiya Nervoza (AN), düşük vücut ağırlığı, devam eden besin kısıtlaması ve bozuk beden algısı ile karakterize psikiyatrik bir hastalıktır. Her yaş grubunda görülebilen AN, genellikle erken ve orta ergenlik döneminde başlamakta olup, kadınlarda erkeklere göre daha sık görülmektedir. Anoreksiya nervoza tanılı bireyler, enerji alımının kısıtlanması veya alınan enerjinin telafi edilmesi için birtakım davranışlar (kendini kusturma, laksatif-diüretik kullanma, aşırı egzersiz yapma gibi) sergilemektedir. Bunun sonucunda, vücut ağırlığı kaybıyla doğrudan ilişkili olarak tüm organları etkileyebilecek tıbbi komplikasyonlar gelişebilmektedir. Literatürde, AN’ya özgü hepatik komplikasyonların artış gösterdiği belirtilmektedir. Açlıkla uyarılan, hepatosit hasarına ve ölümüne neden olan otofajinin, AN’da karaciğer fonksiyon bozukluğuna neden olan temel mekanizma olduğu ileri sürülmektedir. Aminotransferaz düzeylerinin artması ve karaciğer hasarının ilerlemesi, ciddi bir komplikasyon olan hipoglisemiye neden olmaktadır. Anoreksiya nervoza tedavisinde, psikiyatri, beslenme ve tıbbi uzmanlardan oluşan ekiple ortak bir yaklaşım uygulanmalıdır. Tıbbi beslenme tedavisi, enerji alımını ve ağırlık kazanımını sağlayacak şekilde bireyin ihtiyaçlarına uygun olarak planlanmalıdır. Ayrıca, davranış değişikliği ve düzenli yeme alışkanlığı kazandırmak için bireye beslenme eğitimi verilmesi faydalı olmaktadır. Yapılan çalışmalar, AN tanılı bireylerde karaciğer fonksiyon bozuklukları ve hepatik komplikasyonlarla ilişkili tıbbi durumların iyileştirilebilmesinde tıbbi beslenme tedavisinin etkili olduğunu göstermektedir. Bu derlemede, AN’da yaygın olarak görülen hepatik komplikasyonlar ve tıbbi beslenme tedavisinin karaciğer fonksiyon bozukluğu üzerine etkileri incelenmiştir.

Stress-Induced Premature Senescence Related to Oxidative Stress in the Developmental Programming of Nonalcoholic Fatty Liver Disease in a Rat Model of Intrauterine Growth Restriction

Metabolic syndrome (MetS) refers to cardiometabolic risk factors, such as visceral obesity, dyslipidemia, hyperglycemia/insulin resistance, arterial hypertension and non-alcoholic fatty liver disease (NAFLD). Individuals born after intrauterine growth restriction (IUGR) are particularly at risk of developing metabolic/hepatic disorders later in life. Oxidative stress and cellular senescence have been associated with MetS and are observed in infants born following IUGR. However, whether these mechanisms could be particularly associated with the development of NAFLD in these individuals is still unknown. IUGR was induced in rats by a maternal low-protein diet during gestation versus. a control (CTRL) diet. In six-month-old offspring, we observed an increased visceral fat mass, glucose intolerance, and hepatic alterations (increased transaminase levels, triglyceride and neutral lipid deposit) in male rats with induced IUGR compared with the CTRL males; no differences were found in females. In IUGR male livers, we identified some markers of stress-induced premature senescence (SIPS) (lipofuscin deposit, increased protein expression of p21WAF, p16INK4a and Acp53, but decreased pRb/Rb ratio, foxo-1 and sirtuin-1 protein and mRNA expression) associated with oxidative stress (higher superoxide anion levels, DNA damages, decreased Cu/Zn SOD, increased catalase protein expression, increased nfe2 and decreased keap1 mRNA expression). Impaired lipogenesis pathways (decreased pAMPK/AMPK ratio, increased pAKT/AKT ratio, SREBP1 and PPARγ protein expression) were also observed in IUGR male livers. At birth, no differences were observed in liver histology, markers of SIPS and oxidative stress between CTRL and IUGR males. These data demonstrate that the livers of IUGR males at adulthood display SIPS and impaired liver structure and function related to oxidative stress and allow the identification of specific therapeutic strategies to limit or prevent adverse consequences of IUGR, particularly metabolic and hepatic disorders.

Germline Mutations in CIDEB and Protection against Liver Disease

BackgroundExome sequencing in hundreds of thousands of persons may enable the identification of rare protein-coding genetic variants associated with protection from human diseases like liver cirrhosis, providing a strategy for the discovery of new therapeutic targets.MethodsWe performed a multistage exome sequencing and genetic association analysis to identify genes in which rare protein-coding variants were associated with liver phenotypes. We conducted in vitro experiments to further characterize associations.ResultsThe multistage analysis involved 542,904 persons with available data on liver aminotransferase levels, 24,944 patients with various types of liver disease, and 490,636 controls without liver disease. We found that rare coding variants in APOB, ABCB4, SLC30A10, and TM6SF2 were associated with increased aminotransferase levels and an increased risk of liver disease. We also found that variants in CIDEB, which encodes a structural protein found in hepatic lipid droplets, had a protective effect. The burden of rare predicted loss-of-function variants plus missense variants in CIDEB (combined carrier frequency, 0.7%) was associated with decreased alanine aminotransferase levels (beta per allele, −1.24 U per liter; 95% confidence interval [CI], −1.66 to −0.83; P=4.8×10−9) and with 33% lower odds of liver disease of any cause (odds ratio per allele, 0.67; 95% CI, 0.57 to 0.79; P=9.9×10−7). Rare coding variants in CIDEB were associated with a decreased risk of liver disease across different underlying causes and different degrees of severity, including cirrhosis of any cause (odds ratio per allele, 0.50; 95% CI, 0.36 to 0.70). Among 3599 patients who had undergone bariatric surgery, rare coding variants in CIDEB were associated with a decreased nonalcoholic fatty liver disease activity score (beta per allele in score units, −0.98; 95% CI, −1.54 to −0.41 [scores range from 0 to 8, with higher scores indicating more severe disease]). In human hepatoma cell lines challenged with oleate, CIDEB small interfering RNA knockdown prevented the buildup of large lipid droplets.ConclusionsRare germline mutations in CIDEB conferred substantial protection from liver disease. (Funded by Regeneron Pharmaceuticals.)