Morbidity and mortality of elderly patients with pancreaticobiliary disease according to age and comprehensive geriatric assessment: A prospective observational study / Morbilidad y mortalidad de pacientes de edad avanzada con enfermedad pancreaticobiliar con relación a su edad y la evaluación geriátrica integral: un estudio prospectivo observacional

Background This study was designed to analyze the influence of age and comprehensive geriatric evaluation on clinical results of pancreaticobiliary disease management in elderly patients. Methods A prospective observational study has been undertaken, including 140 elderly patients (over 75 years) with benign pancreaticobiliary disease. Patients were divided according to age in the following groups: group 1: 75–79 years old; group 2: 80–84 years old; group 3: 85 years and older. They underwent a comprehensive geriatric assessment with different scales: Barthel Index, Pfeiffer Index, Charlson Index, and Fragility scale, at admission and had been follow-up 90 days after hospital discharge to analyze its influence on morbidity and mortality. Results Overall, 140 patients have been included (group 1=51; group 2=43 and group 3=46). Most of them, 52 cases (37.8%), had acute cholecystitis, followed by 29 cases of acute cholangitis (20.2%) and acute pancreatitis with 25 cases (17.9%). Significant differences has been observed on complications in different age groups (p=0.033). Especially in patients with a Barthel Index result ≤60, which suggests that these less functional patients had more severe complications after their treatment (p=0.037). The mortality rate was 7.1% (10 patients). Conclusions No significant differences were found between age, morbidity and mortality in elderly patients with pancreaticobiliary disease. Comprehensive geriatric scales showed some utility in their association with specific complications. (AU)

Antecedentes Este estudio fue diseñado para analizar la influencia de la edad y la evaluación geriátrica integral en los resultados clínicos del manejo de la enfermedad pancreatobiliar en pacientes de edad avanzada. Métodos Se ha realizado un estudio observacional prospectivo en el que se incluyeron 140 pacientes de edad avanzada (mayores de 75 años) con enfermedad pancreatobiliar benigna. Los pacientes se dividieron según la edad en los siguientes grupos: Grupo 1: 75-79 años; Grupo 2: 80-84 años; Grupo 3: 85 años y más. Se les realizó una valoración geriátrica integral con diferentes escalas: Barthel Index, Pfeiffer Index, Charlson Index y Fragility scale, al ingreso y seguimiento 90 días después del alta hospitalaria para analizar su influencia en la morbimortalidad. Resultados En total, se incluyeron 140 pacientes (Grupo 1=51; Grupo 2=43 y Grupo 3=46). La mayoría de ellos, 52 casos (37,8%), presentaron colecistitis aguda, seguido de colangitis aguda con 29 casos (20,2%) y pancreatitis aguda con 25 casos (17,9%). Se han observado diferencias significativas en las complicaciones en diferentes grupos de edad (p=0,033). Especialmente en pacientes con un índice de Barthel ≤60, lo que sugiere que estos pacientes menos funcionales tuvieron complicaciones más severas después de su tratamiento (p=0,037). La tasa de mortalidad fue de 7,1% (10 pacientes). Conclusiones No se encontraron diferencias significativas entre la edad, la morbilidad y la mortalidad en pacientes ancianos con enfermedad pancreatobiliar. Las escalas geriátricas integrales mostraron cierta utilidad en su asociación con complicaciones específicas. (AU)

Depression and hepatobiliary diseases: a bidirectional Mendelian randomization study.

Background: More and more evidence suggests a close association between depression and hepatobiliary diseases, but its causal relationship is not yet clear. Method: Using genome-wide association studies (GWAS) to summarize data, independent genetic variations associated with depression were selected as instrumental variables. Firstly, we designed a univariate Mendelian randomization (UVMR) analysis with two samples and simultaneously conducted reverse validation to evaluate the potential bidirectional causal relationship between depression and various hepatobiliary diseases. Secondly, we conducted a multivariate Mendelian randomization (MVMR) analysis on diseases closely related to depression, exploring the mediating effects of waist to hip ratio, hypertension, and daytime nap. The mediating effects were obtained through MVMR. For UVMR and MVMR, inverse variance weighted method (IVW) is considered the most important analytical method. Sensitivity analysis was conducted using Cochran'Q, MR Egger, and Leave-one-out methods. Results: UVMR analysis showed that depression may increase the risk of non-alcoholic fatty liver disease (OR, 1.22; 95% CI, 1.03-1.46; p=0.0248) in liver diseases, while depression does not increase the risk of other liver diseases; In biliary and pancreatic related diseases, depression may increase the risk of cholelithiasis (OR, 1.26; 95% CI, 1.05-1.50; p=0.0120), chronic pancreatitis (OR, 1.61; 95% CI, 1.10-2.35; p=0.0140), and cholecystitis (OR, 1.23; 95% CI, 1.03-1.48; p=0.0250). In addition, through reverse validation, we found that non-alcoholic fatty liver disease, cholelithiasis, chronic pancreatitis, cholecystitis, or the inability to increase the risk of depression (p>0.05). The waist to hip ratio, hypertension, and daytime nap play a certain role in the process of depression leading to non-alcoholic fatty liver disease, with a mediating effect of 35.8%. Conclusion: Depression is a susceptibility factor for non-alcoholic fatty liver disease, and the causal effect of genetic susceptibility to depression on non-alcoholic fatty liver disease is mediated by waist-hip ratio, hypertension, and daytime nap.

Updated Insights into Probiotics and Hepatobiliary Diseases.

Hepatobiliary diseases have a high prevalence worldwide, with a wide range of diseases involved in the liver and biliary system. Modifications in gut microbiota have been proven to have an association with unbalanced intestinal homeostasis and the dysfunction of host metabolism and the immune system, which can be the risk factors for many hepatobiliary diseases, such as nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), nonalcoholic fatty steatohepatitis (NASH), hepatitis, cirrhosis, hepatocellular carcinoma (HCC) and cholestasis, as well as infection due to liver transplantation. Probiotics are commonly used gut microbiota-targeted strategies to treat dysbiosis and intestinal dysfunction, as well as the gut-liver axis, which can enhance the effectiveness of probiotics in the management of liver diseases. Recent studies have explored more potential single or mixed strains of probiotics, and bioinformatics methods can be used to investigate the potential mechanisms of probiotics on liver diseases. In this review, we summarize the preclinical and clinical studies on the role of probiotics in hepatobiliary diseases from 2018 to 2023, revealing the possible mechanism of probiotics in the treatment of hepatobiliary diseases and discussing the limitations of probiotics in treating hepatobiliary diseases. This review provides updated evidence for the development of probiotic products, exploration of new probiotic strains, and support for clinical studies. Further studies should focus on the safety, viability, and stability of probiotics, as well as medication dosage and duration in clinical practice.

Components from Curcuma longa (Turmeric) Against Hepatobiliary Diseases Based on Gut-Liver Axis: Pharmacotherapeutic Properties and Potential Clinical Applications.

Turmeric is widely used worldwide, and there are many examples of its use in treating hepatobiliary diseases. The gut-liver axis is a bidirectional relationship between gut microorganisms and the liver that is closely related to the pathogenesis of hepatobiliary diseases. This review systematically summarizes the components of turmeric. It links the studies on turmeric affecting gut microorganisms to its effects on liver and biliary diseases to explain the potential mechanism of turmeric's regulation of the gut-liver axis. Besides, ethnopharmacology, phytochemicals, and clinical adverse events associated with turmeric have been researched. Furthermore, turmeric is a safe agent with good clinical efficacy and without apparent toxicity at a certain amount. By summarizing the influence of turmeric on the liver by regulating the gut-liver axis, especially the gut microbiota, it provides a preclinical basis for using turmeric as a safe and effective therapeutic agent for the prevention and treatment of hepatobiliary diseases based on the gut-liver axis. However, more efforts should be made to exploit its clinical application further.

A retrospective study of variations in the kinds of diseases discharged from the Department of Infectious Diseases of a large general hospital in Central China during 2013-2019.

Objective: To analyze the changing trend of the absolute number and constituent ratio of various in-patient diseases in the Department of Infectious Diseases of a large general hospital in Central China during 2013-2019. Methods: A retrospective study was conducted to analyze the diagnostic data of discharged patients for seven consecutive years, from 2013 to 2019. The first discharge diagnosis is used as the basis for the disease classification. The absolute number, constituent ratio, and changing trend of major diseases in hepatobiliary diseases and infectious diseases were analyzed. Results: The changing trend of the diseases during 2013-2019 showed that the absolute number of cases of hepatobiliary disease did not change significantly (p = 0.615), while the constituent ratio decreased significantly, from 68.01% in 2013 to 55.29% in 2019 (p<0.001). The absolute number (constituent ratio) of cases of infectious diseases increased significantly from 585 (21.91%) in 2013 to 1,244 (36.86%) in 2019 (p = 0.015, p<0.001). The major part of the increase was non-communicable infectious diseases (NCIDs). Conclusion: During 2013-2019, the proportion of cases of hepatobiliary disease gradually decreased. The absolute number and proportion of cases of infectious diseases, especially NCIDs, have increased rapidly.

Clinical Implementation of Dual-Energy CT Technical for Hepatobiliary Imaging.

Dual-energy computed tomography (DECT) applies two energy spectra distributions to collect raw data based on traditional CT imaging. The application of hepatobiliary imaging, has the advantages of optimizing the scanning scheme, improving the imaging quality, highlighting the disease characterization, and increasing the detection rate of lesions. In order to summarize the clinical application value of DECT in hepatobiliary diseases, we searched the technical principles of DECT and its existing studies, case reports, and clinical guidelines in hepatobiliary imaging from 2010 to 2023 (especially in the past 5 years) through PubMed and CNKI, focusing on the clinical application of DECT in hepatobiliary diseases, including liver tumors, diffuse liver lesions, and biliary system lesions. The first part of this article briefly describes the basic concept and technical advantages of DECT. The following will be reviewed:the detection of lesions, diagnosis and differential diagnosis of lesions, hepatic steatosis, quantitative analysis of liver iron, and analyze the advantages and disadvantages of DECT in hepatobiliary imaging. Finally, the contents of this paper are summarized and the development prospect of DECT in hepatobiliary imaging is prospected.

Morbidity and mortality of elderly patients with pancreaticobiliary disease according to age and comprehensive geriatric assessment: A prospective observational study.

BACKGROUND: This study was designed to analyze the influence of age and comprehensive geriatric evaluation on clinical results of pancreaticobiliary disease management in elderly patients. METHODS: A prospective observational study has been undertaken, including 140 elderly patients (over 75 years) with benign pancreaticobiliary disease. Patients were divided according to age in the following groups: group 1: 75-79 years old; group 2: 80-84 years old; group 3: 85 years and older. They underwent a comprehensive geriatric assessment with different scales: Barthel Index, Pfeiffer Index, Charlson Index, and Fragility scale, at admission and had been follow-up 90 days after hospital discharge to analyze its influence on morbidity and mortality. RESULTS: Overall, 140 patients have been included (group 1=51; group 2=43 and group 3=46). Most of them, 52 cases (37.8%), had acute cholecystitis, followed by 29 cases of acute cholangitis (20.2%) and acute pancreatitis with 25 cases (17.9%). Significant differences has been observed on complications in different age groups (p=0.033). Especially in patients with a Barthel Index result ≤60, which suggests that these less functional patients had more severe complications after their treatment (p=0.037). The mortality rate was 7.1% (10 patients). CONCLUSIONS: No significant differences were found between age, morbidity and mortality in elderly patients with pancreaticobiliary disease. Comprehensive geriatric scales showed some utility in their association with specific complications.

Alteración de la microbiota intestinal y su relación con enfermedades gastrointestinales y hepatobiliares / Disruption of the intestinal microbiota and its relationship with gastrointestinal and hepatobiliary diseases

La interrupción de la simbiosis que existe entre el cuerpo humano y su microbioma puede resultar en una disbiosis, un desequilibrio en la interacción huésped-microbiota, que puede asociarse al desarrollo de diversas enfermedades como el síndrome de intestino irritable, hígado graso no alco-hólico, enfermedad hepática alcohólica y cirrosis, entre otras. En ciertas condiciones patológicas y por múltiples factores de riesgo, la capacidad de autorregulación del intestino se puede alterar, contribuyendo al incremento de la permeabilidad con inflamación intestinal crónica. El diagnóstico y el tratamiento, así como la relación entre la permeabilidad intestinal, la disbiosis y las patologías gastrointestinales y hepatobiliares, todavía no tienen estudios clínicos validados o con el soporte científico adecuado, por lo que se realiza una revisión de la literatura con la finalidad de aportar conceptos que puedan orientar con respecto a la importancia del estudio del microbioma humano en estas enfermedades.

Disruption of the symbiosis that exists between the human body and its microbiome can result in dys-biosis, an imbalance in the host-microbiota interaction, which may be associated with the develop-ment of various diseases such as irritable bowel syndrome, non-alcoholic fatty liver disease, alcoholic liver disease and cirrhosis, among others. In certain pathological conditions and due to multiple risk factors, the self-regulating capacity of the intestine may be lost, contributing to increased permeability with chronic intestinal inflammation. Its diagnosis and treatment as well as the relationship between intestinal permeability, dysbiosis and gastrointestinal and hepatobiliary pathologies have not been validated in clinical studies or have adequate scientific support, so a review of the literature is carried out in order to provide concepts that can guide with respect to the importance of the study of the human microbiome in these diseases

Manifestaciones hepatobiliares asociadas a la enfermedad inflamatoria intestinal / Hepatobiliary manifestations associated with inflammatory bowel disease

La enfermedad inflamatoria intestinal (EII) engloba dos entidades, la enfermedad de Crohn (EC) y la colitis ulcerativa (CU), las cuales son enfermedades inmunomediadas, crónicas y recurrentes que, aunque afectan al intestino, pueden ir acompañadas de manifestaciones extraintestinales de tipo hepatobiliar en el 5 % de los casos. Entre ellas, las más frecuentes son la enfermedad por hígado graso no alcohólico (EHGNA), la colelitiasis, la colangitis esclerosante primaria (CEP), la colangitis relacionada con IgG4, la hepatitis autoinmune (HAI), el síndrome de superposición HAI/CEP, así como la lesión hepática inducida por fármacos (DILI); y otras menos frecuentes como la colangitis biliar primaria (CBP), la trombosis de la vena porta, los abscesos hepáticos, la hepatitis granulomatosa, las hepatitis B y C, la reactivación de la hepatitis B por terapia inmunosupresora, y la amiloidosis. Estas manifestaciones hepatobiliares cursan con una fisiopatología similar o inclusive la misma de la EII, en la que participan el sistema inmune innato y adaptativo, alteración de la microbiota (disbiosis), permeabilidad intestinal, factores de riesgo genéticos (comunes para EII y manifestaciones hepatobiliares) y desencadenantes ambientales. La primera manifestación de un trastorno hepatobiliar es la alteración del perfil de función hepática, por lo que el abordaje diagnóstico se debe dirigir a evaluar y monitorizar las enzimas hepáticas y su asociación a algún patrón diferencial de alteración hepatocelular o colestásico, con el fin de tomar decisiones oportunas con respecto a la suspensión, indicación o modificación de algún medicamento, o cualquier otro abordaje que impida o retrase la evolución de la enfermedad hepatobiliar, y al mismo tiempo garantice el control de la EII, mejorando potencialmente el pronóstico de estos pacientes.

Inflammatory bowel disease (IBD) encompasses two entities, Crohn's disease (CD) and ulcerative colitis (UC), which are chronic, recurrent, immune-mediated inflammatory diseases that, although affect the gut, may be accompanied by extraintestinal hepatobiliary manifestations in 5% of the cases. Among them, the most frequent are non-alcoholic fatty liver disease (NAFLD), cholelithiasis, primary sclerosing cholangitis (PSC), IgG4-related cholangitis, autoimmune hepatitis (AIH), AIH/PSC overlap syndrome, as well as drug-induced liver injury (DILI); and other less frequent such as primary biliary cholangitis (PBC), portal vein thrombosis, liver abscesses, granulomatous hepatitis, hepatitis B and C, reactivation of hepatitis B due to different drugs, and amyloidosis. These hepatobiliary manifestations present with a pathophysiology similar or even the same as that of IBD, where several factors participate, including the innate and adaptive immune system, an interaction with the components of the microbiota, leaky gut, genetic risk factors (common for both IBD and hepatobiliary manifestations) and environmental triggers. The first manifestation of a hepatobiliary disorder is the alteration of the liver profile; therefore, the diagnostic approach should be aimed at evaluating and monitoring liver enzymes and their association with some differential pattern of hepatocellular or cholestatic changes, in order to make appropriate decisions regarding the suspension or modification of any medication, or any other approach that prevents or delays the evolution of hepatobiliary disease, and at the same time guarantees control of IBD, improving the prognosis of these patients.

Updates in interaction of gastroesophageal reflux disease and extragastroesophageal digestive diseases.

INTRODUCTION: Gastroesophageal reflux disease (GERD) is one of the common chronic diseases with prevalence increasing in the last decades. Because of its prevalence and chronicity, GERD affects the quality of life and increases health-care costs. Gastroesophageal diseases leading to GERD have been thoroughly studied, while extragastroesophageal digestive diseases (EGEDDs) may coexist with GERD and affect the occurrence and persistence of GERD symptoms and therapeutic effect. AREAS COVERED: In this review, we aim to summarize the EGEDDs correlated with GERD and explore the potential mechanisms of this interaction. EXPERT OPINION: Individuals with troublesome GERD symptoms may have some common gastroesophageal etiologies, but EGEDDs may also overlap and impact on the progression of GERD, which are often ignored in clinic. The lesions in the small intestine, colon, and hepatobiliary tract as well as functional bowel disorders had positive or negative associations with GERD through potential mechanisms. These diseases aggravate GERD symptoms, increase the esophageal acid burden, cause esophageal hypersensitivity, and finally affect the response to therapy in GERD patients. Therefore, it is necessary to clear the interaction between GERD and EGEDDs and their mechanisms.

Adipose-derived stem cells in the treatment of hepatobiliary diseases and sepsis.

Determination of the mesenchymal stem cells is one of the greatest and most exciting achievements that tissue engineering and regenerative medicine have achieved. Adipose-derived mesenchymal stem cells (AD-MSC) are easily isolated and cultured for a long time before losing their stem cell characteristics, which are self-renewal and pluripotency. AD-MSC are mesenchymal stem cells that have pluripotent lineage characteristics. They are easily accessible, and the fraction of stem cells in the adipose tissue lysates is highest among all other sources of mesenchymal stem cells. It is also HLA-DR negative and can be transplanted allogenically without the need for immunosuppression. These advantages have popularized its use in many fields including plastic reconstructive surgery. However, in the field of hepatology and liver transplantation, the progress is slower. AD-MSC have the potential to modulate inflammation, ameliorate ischemia-reperfusion injury, and support liver and biliary tract regeneration. These are very important for the treatment of various hepatobiliary diseases. Furthermore, the anti-inflammatory potential of these cells has paramount importance in the treatment of sepsis. We need alternative therapeutic approaches to treat end-stage liver failure. AD-MSC can provide a means of therapy to bridge to definitive therapeutic alternatives such as liver transplantation. Here we propose to review theoretic applications of AD-MSC in the treatment of hepatobiliary diseases and sepsis.

The role and significance of matrix metalloproteinase-7 in hepatobiliary diseases / 国际儿科学杂志

Matrix metalloproteinases(MMPs)are a large family of zinc-dependent endopeptidases, which are mainly synthesized by connective tissues, it can degrade the extracellular matrix(ECM)and basement membrane, affect the regeneration and reconstruction of normal tissues, and participate in the pathological process of malignant tumors.Matrix metalloproteinase-7(MMP-7)is the smallest member of the metalloproteinase family.It is expressed in many tissues of the body, such as thyroid, breast, lung, digestive tract, reproductive system and hepatobiliary system.In recent years, the expression of MMP-7 in hepatobiliary diseases has attracted more and more attention.MMP-7 is not only involved in the growth, metastasis and invasion process of hepatobiliary malignant tumors, but also highly expressed in liver fibrosis, biliary atresia and other diseases.This paper reviews the expression of MMP-7 in the above diseases.

Cholangitis in three critically ill patients after a severe CoVID-19 infection.

Coronavirus disease 2019 (CoVID-19) is a viral disease. Although the predominant presentation is respiratory disease, other manifestations such as gastrointestinal manifestations are commonly reported. Nevertheless, it has not been associated with chronic cholangitis or hepatic injury. In this study, we report three cases of severe CoVID-19 infection that required ICU admission, intubation, and sedation with ketamine. All three patients had abnormal liver function despite recovery and were diagnosed with cholangitis in the context of CoVID-19.

Oral manifestations in paediatric patients with hepatobiliary diseases: a review.

It is well known that greenish pigmentation of the teeth is seen in children following remission of severe jaundice and clinical and serum bilirubin, a degradation product of haemoglobin, may be permanently trapped in forming dental hard tissues causing discolouration and enamel and dentine hypoplasia. Neonatal jaundice is the most common cause of hyperbilirubinemia and pigmentation of the deciduous teeth is the consequence of this condition. Various hepatobiliary pathologies may have a clinical finding in the oral cavity; furthermore, oral manifestations of hepatic pathologies are not just limited to the pigmentation of the deciduous teeth but also the permanent dentition and the mucous membranes can be affected.

Somatic Mutations in Circulating Cell-Free DNA and Risk for Hepatocellular Carcinoma in Hispanics.

Hispanics are disproportionally affected by liver fibrosis and hepatocellular carcinoma (HCC). Advanced liver fibrosis is a major risk factor for HCC development. We aimed at identifying somatic mutations in plasma cell-free DNA (cfDNA) of Hispanics with HCC and Hispanics with advanced liver fibrosis but no HCC. Targeted sequencing of over 262 cancer-associated genes identified nonsynonymous mutations in 22 of the 27 HCC patients. Mutations were detected in known HCC-associated genes (e.g., CTNNB1, TP53, NFE2L2, and ARID1A). No difference in cfDNA concentrations was observed between patients with mutations and those without detectable mutations. HCC patients with higher cfDNA concentrations or higher number of mutations had a shorter overall survival (p < 0.001 and p = 0.045). Nonsynonymous mutations were also identified in 17 of the 51 subjects with advanced liver fibrosis. KMT2C was the most commonly mutated gene. Nine genes were mutated in both subjects with advanced fibrosis and HCC patients. Again, no significant difference in cfDNA concentrations was observed between subjects with mutations and those without detectable mutations. Furthermore, higher cfDNA concentrations and higher number of mutations correlated with a death outcome in subjects with advanced fibrosis. In conclusion, cfDNA features are promising non-invasive markers for HCC risk prediction and overall survival.

Bile acid indices as biomarkers for liver diseases II: The bile acid score survival prognostic model.

BACKGROUND: Cholestatic liver diseases are characterized by an accumulation of toxic bile acids (BA) in the liver, blood and other tissues which lead to progressive liver injury and poor prognosis in patients. AIM: To discover and validate prognostic biomarkers of cholestatic liver diseases based on the urinary BA profile. METHODS: We analyzed urine samples by liquid chromatography-tandem mass spectrometry and investigated the use of the urinary BA profile to develop survival models that can predict the prognosis of hepatobiliary diseases. The urinary BA profile, a set of non-BA parameters, and the adverse events of liver transplant and/or death were monitored in 257 patients with cholestatic liver diseases for up to 7 years. The BA profile was characterized by calculating BA indices, which quantify the composition, metabolism, hydrophilicity, formation of secondary BA, and toxicity of the BA profile. We have developed and validated the bile-acid score (BAS) model (a survival model based on BA indices) to predict the prognosis of cholestatic liver diseases. RESULTS: We have developed and validated a survival model based on BA (the BAS model) indices to predict the prognosis of cholestatic liver diseases. Our results demonstrate that the BAS model is more accurate and results in higher true-positive and true-negative prediction of death compared to both non-BAS and model for end-stage liver disease (MELD) models. Both 5- and 3-year survival probabilities markedly decreased as a function of BAS. Moreover, patients with high BAS had a 4-fold higher rate of death and lived for an average of 11 mo shorter than subjects with low BAS. The increased risk of death with high vs low BAS was also 2-4-fold higher and the shortening of lifespan was 6-7-mo lower compared to MELD or non-BAS. Similarly, we have shown the use of BAS to predict the survival of patients with and without liver transplant (LT). Therefore, BAS could be used to define the most seriously ill patients, who need earlier intervention such as LT. This will help provide guidance for timely care for liver patients. CONCLUSION: The BAS model is more accurate than MELD and non-BAS models in predicting the prognosis of cholestatic liver diseases.

Bile acid indices as biomarkers for liver diseases I: Diagnostic markers.

BACKGROUND: Hepatobiliary diseases result in the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues which may contribute to an unfavorable prognosis. AIM: To discover and validate diagnostic biomarkers of cholestatic liver diseases based on the urinary BA profile. METHODS: We analyzed urine samples by liquid chromatography-tandem mass spectrometry and compared the urinary BA profile between 300 patients with hepatobiliary diseases vs 103 healthy controls by statistical analysis. The BA profile was characterized using BA indices, which quantifies the composition, metabolism, hydrophilicity, and toxicity of the BA profile. BA indices have much lower inter- and intra-individual variability compared to absolute concentrations of BA. In addition, BA indices demonstrate high area under the receiver operating characteristic curves, and changes of BA indices are associated with the risk of having a liver disease, which demonstrates their use as diagnostic biomarkers for cholestatic liver diseases. RESULTS: Total and individual BA concentrations were higher in all patients. The percentage of secondary BA (lithocholic acid and deoxycholic acid) was significantly lower, while the percentage of primary BA (chenodeoxycholic acid, cholic acid, and hyocholic acid) was markedly higher in patients compared to controls. In addition, the percentage of taurine-amidation was higher in patients than controls. The increase in the non-12α-OH BA was more profound than 12α-OH BA (cholic acid and deoxycholic acid) causing a decrease in the 12α-OH/ non-12α-OH ratio in patients. This trend was stronger in patients with more advanced liver diseases as reflected by the model for end-stage liver disease score and the presence of hepatic decompensation. The percentage of sulfation was also higher in patients with more severe forms of liver diseases. CONCLUSION: BA indices have much lower inter- and intra-individual variability compared to absolute BA concentrations and changes of BA indices are associated with the risk of developing liver diseases.

Association of Arterial Hypertension with Hepatobiliary Pathology: The Occurrence of Comorbidity and Features of Metabolic Processes.

Comorbidity of hypertension and hepatobiliary pathology has negative medical and social consequences, including an increase in the indicators of hospital admissions, disability and mortality. OBJECTIVE: The aim was to study the occurrence of hypertension combined with hepatobiliary diseases depending on social status, gender and age in 2003-2017 and their influence on indicators of metabolic processes in patients with a therapeutic profile. METHODS: A cross-sectional study using the inpatients' medical record database of the clinic of Federal Research Centre for Basic and Translational Medicine (Novosibirsk, Russia), which collects demographics, diagnoses (using ICD-10 codes), procedures and examinations of all inpatients from 2003-2017 was conducted. The incidence of comorbidity of hypertension and hepatobiliary pathology depending on age, gender and social status, based on the analysis of 13496 medical records was examined. A comparative analysis of biochemical parameters characterizing the main types of metabolism (lipid, protein, carbohydrate and purine) was carried out in 3 groups of patients: with hypertension; with hepatobiliary pathology, and with a combined pathology. RESULTS: During the years 2003-2005, there was the greatest frequency of this comorbidity in workers, in women, in the age group 60 years and older. In 2009-2017, the highest incidence was observed in the male administrative staff. In patients with this comorbidity, more pronounced changes in carbohydrate, protein, lipid and purine metabolism were found in comparison with groups of patients with isolated diseases. CONCLUSION: The results highlight the need to improve the system of prevention and treatment of comorbidity taking into account sex, age, occupation and features of metabolism.

Study of the relationship between vitamin D deficiency, sunlight incidence and skeletal/extra skeletaldiseases

It is estimated that more than 1 billion people worldwide have vitamin D insufficiency or deficiency. Vitamin D participates in bone mineralization, and is therefore important in osteoporosis, osteomalacia and rickets prevention. However, vitamin D deficiency could also be associated with several other pathologies. The present study aimed to investigate the relationships between vitamin D deficiency and vitamin D deficiency-related disorders in patients. In addition, this study aims to verify if countries with low solar incidence have higher extraskeletal disease death rates when compared to countries with high solar incidence. The vitamin D concentrations were obtained from the Heart Hospital database (Natal/Brazil). The relationship between solar incidenceand death rate for vitamin D deficiency-related disorders was verified. Death rate data were extracted from the 'World Life Expectancy' repository and data about solar incidence were obtained from NASA's Surface Meteorology and Solar Energy project. Thesedata were statistically processed with IBM SPSS v23.0 software and R programming language. Our results showed that patients with vitamin D insufficiency/deficiency showed significantly more bone diseases, thyroid diseases, hypercholesterolemy, hypertriglyceridemia, cancers, diabetes, hepatobiliary diseases, and urinary system diseases. Moreover, countries with high solar incidence have low cancer and multiple sclerosis death rates. This work suggests the participation of vitamin D and sunlight incidence inseveral diseases.