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Coagulation management in the patient with cirrhosis has undergone a significant transformation since the beginning of this century, with the concept of a rebalancing between procoagulant and anticoagulant factors. The paradigm that patients with cirrhosis have a greater bleeding tendency has changed, as a result of this rebalancing. In addition, it has brought to light the presence of complications related to thrombotic events in this group of patients.These guidelines detail aspects related to pathophysiologic mechanisms that intervene in the maintenance of hemostasis in the patient with cirrhosis, the relevance of portal hypertension, mechanical factors for the development of bleeding, modifications in the hepatic synthesis of coagulation factors, and the changes in the reticuloendothelial system in acute hepatic decompensation and acute-on-chronic liver failure. They address new aspects related to the hemorrhagic complications in patients with cirrhosis, considering the risk for bleeding during diagnostic or therapeutic procedures, as well as the usefulness of different tools for diagnosing coagulation and recommendations on the pharmacologic treatment and blood-product transfusion in the context of hemorrhage. These guidelines also update the knowledge regarding hypercoagulability in the patient with cirrhosis, as well as the efficacy and safety of treatment with the different anticoagulation regimens. Lastly, they provide recommendations on coagulation management in the context of acute-on-chronic liver failure, acute liver decompensation, and specific aspects related to the patient undergoing liver transplantation. Resumen: El manejo de la coagulación en el paciente con cirrosis ha sufrido una transformación significativa a partir de principios de este siglo, con el concepto de un rebalanceo entre factores procoagulantes y anticoagulantes. Esto ha cambiado el paradigma de que los pacientes con cirrosis tienen una mayor tendencia a la hemorragia, ya que existe un rebalanceo entre factores procoagulantes y anticoagulantes. Además, ha traído a la luz la presencia de complicaciones relacionadas a eventos trombóticos en este grupo de pacientes.En estas guías se detallan aspectos relacionados con los mecanismos fisiopatológicos que intervienen en el mantenimiento de la hemostasia en el paciente con cirrosis, la relevancia de la hipertensión portal, factores mecánicos para el desarrollo de sangrado, modificaciones en la síntesis hepática de factores de coagulación, y los cambios en el sistema reticuloendotelial en la descompensación hepática aguda e insuficiencia hepática aguda sobre crónica (IHAC). Se abordan nuevos aspectos relacionados a las complicaciones hemorrágicas en pacientes con cirrosis, considerando el riesgo de hemorragia durante procedimientos diagnósticos o terapéuticos, así como la utilidad de diferentes herramientas diagnósticas de la coagulación y recomendaciones en el tratamiento farmacológico y transfusión de hemoderivados en el contexto de hemorragia. En estas guías se actualiza el conocimiento respecto al diagnóstico y abordaje de complicaciones relacionadas a hipercoagulabilidad en el paciente con cirrosis, así como la eficacia y seguridad del tratamiento con diferentes esquemas de anticoagulación. Finalmente, se mencionarán recomendaciones en el manejo de la coagulación en el contexto de IHAC, descompensación hepática aguda y aspectos específicos relacionados al paciente en protocolo de trasplante hepático.

La enfermedad hepática crónica y sus complicaciones, la cirrosis y el carcinoma hepatocelular, presentan una elevada mortalidad. Los tratamientos curativos, como la hepatectomía parcial o el trasplante hepático, tienen una aplicación limitada en pacientes con cirrosis, por su escasa capacidad de regeneración hepática. Son necesarias otras alternativas diagnósticas y terapéuticas para prevenir la progresión de la enfermedad y mejorar la supervivencia. Diversos estudios preclínicos demuestran el importante papel de la proteína quinasa B(Akt) en la disfunción hepática, aunque aún se desconoce el estado de Akt y sus dianas en las patologías hepáticas crónicas. El principal objetivo es determinar el estado de activación de la vía Akt y su relación con la función hepática en pacientes cirróticos.

The Asociación Mexicana de Hepatología A.C. carried out the Consensus on the Management of Complications of Cirrhosis of the Liver in Pediatrics to provide physicians with useful information for treating said complications. A group of pediatric gastroenterologists and experts in nutrition, nephrology, and infectious diseases participated and reviewed the medical literature. The Delphi method was applied to obtain the level of agreement on the statements that were formulated. The statements were sent to the participants to be analyzed and voted upon, after which they were discussed in virtual sessions, and the final versions were produced. The aim of the consensus results was to issue indications for the management of pediatric patients with liver cirrhosis, to prevent or control complications. Resumen: La Asociación Mexicana de Hepatología A.C. llevo a cabo el Consenso del manejo de las complicaciones de la cirrosis hepática en población pediátrica con el fin de proveer a los médicos de información útil para su tratamiento. Participaron un grupo de gastroenterólogos pediatras y expertos en nutrición, nefrología y enfermedades infecciosas, quienes revisaron la literatura médica. El método Delphi fue aplicado para obtener el nivel de acuerdo de los enunciados emitidos; estos fueron enviados a los participantes para ser analizados, votados y en sesiones virtuales fueron discutidos, obteniendo así, las declaraciones finales. Los resultados del consenso fueron emitir las indicaciones para el manejo de un niño con cirrosis hepática, con el fin de prevenir o controlar las complicaciones.

Introduction and aims: Cirrhosis is the common outcome of liver diseases. It can be decompensated and lead to the development of complications, such as encephalopathy. Hyperammonemia that develops due to liver dysfunction is etiopathologically related to hepatic encephalopathy. Caffeine increases the activity of the urea cycle in the liver, augmenting ammonia degradation. By antagonizing adenosine receptors, it also has a hepatoprotective effect, impeding the formation of fibrosis, as well as having a stimulating effect on the central nervous system. The present study analyzed the effects of caffeine on the progression of cholestatic liver fibrosis and hepatic encephalopathy. Materials and methods: An experimental model of cholestatic liver fibrosis, through common bile duct ligature, and of hepatic encephalopathy, through the administration of a high-protein diet, was constructed. Male Wistar rats (n = 32) were equally divided into 4 groups. The experiment lasted 28 days, with the administration of 50 mg/kg/day of caffeine. Laboratory tests, histologic analyses of the liver and encephalon, open field tests (OFTs), and daily behavioral analyses were carried out. Results: The ligated animals treated with caffeine had lower mean transaminase levels and improved histologic aspects of the liver and encephalon. The untreated ligated animals were clearly lethargic and apathetic at the last week of the experiment, confirmed by reduced exploratory activity during the OFT. Conclusion: Caffeine improved the microarchitecture of the liver and encephalon of the cirrhotic animals and prevented the decrease in exploratory behavior of the animals during the OFT. Resumen: Introducción y objetivos: La cirrosis es el desenlace común de las enfermedades hepáticas. Puede ser descompensada y llevar al desarrollo de complicaciones como la encefalopatía. La hiperamonemia que se desarrolla debido a la disfunción hepática está etiopatológicamente relacionada con la encefalopatía hepática. La cafeína (CAF) aumenta la actividad del ciclo de la urea en el hígado, aumentando la degradación del amonio. Además, al antagonizar receptores de adenosina, ejerce un efecto hepatoprotector, impidiendo la formación de fibrosis y tiene un efecto estimulante en el sistema nervioso central. El objetivo del presente estudio fue el análisis de los efectos de la cafeína sobre la evolución de la fibrosis hepática colestásica y de la encefalopatía hepática. Material y métodos: Se construyó un modelo experimental de fibrosis hepática colestásica, por medio de la ligadura del conducto biliar común, y de encefalopatía hepática, con la administración de una dieta hiperprotéica. Treinta y dos ratas Wistar machos fueron divididas igualmente en 4 grupos. El experimento duró 28 días, con administración de CAF 50 mg/kg/día. Se realizaron pruebas de laboratorio, análisis histológicos de hígado y encéfalo, pruebas de campo abierto (PCA) y análisis conductuales diarios. Resultados: Los animales ligados tratados con CAF presentaron menores medias de transaminasas y mejorías histológicas en hígado y encéfalo. El grupo ligado sin tratamiento se presentó claramente letárgico y apático en la última semana de experimento, lo cual fue comprobado por la disminución de la actividad exploratoria durante la PCA. Conclusión: La CAF mejoró la microarquitectura hepática y encefálica de los animales cirróticos. Además, impidió la disminución de la actividad exploratoria de los animales durante la PCA.

Background: Acute-on-chronic liver failure (ACLF) is a severe clinical entity associated with elevated short-term mortality. We aimed to characterize patients with decompensated cirrhosis according to presence of ACLF, their association with active alcohol intake, and long-term survival in Latin America., Methods: Retrospective cohort study of decompensated cirrhotic in three Chilean university centers (2017-2019). ACLF was diagnosed according EASL-CLIF criteria. We assessed survival using competing-risk and time-to-event analyses. We evaluated the time to death using accelerated failure time (AFT) models., Results: We included 320 patients, median age of 65.3±11.7 years old, and 48.4% were women. 92 (28.7%) patients met ACLF criteria (ACLF-1: 29.3%, ACLF-2: 27.1%, and ACLF-3: 43.4%). The most common precipitants were infections (39.1%), and the leading organ failure was kidney (59.8%). Active alcohol consumption was frequent (27.7%), even in patients with a prior diagnosis of non-alcoholic fatty liver disease (NAFLD) (16.2%). Ninety-two (28.7%) patients had ACLF (ACLF-1: 8.4%, ACLF-2: 7.8%, and ACLF-3: 12.5%). ACLF patients had a higher MELD-Na score at admission (27 [22-31] versus 16 [12-21], p<0.0001), a higher frequency of alcohol-associated liver disease (36.7% versus 24.9%, p=0.039), and a more frequent active alcohol intake (37.2% versus 23.8%, p=0.019). In a multivariate model, ACLF was associated with higher mortality (subdistribution hazard ratio 1.735, 95%CI: 1.153-2.609; p<0.008). In the AFT models, the presence of ACLF during hospitalization correlated with a shorter time to death: ACLF-1 shortens the time to death by 4.7 times (time ratio [TR] 0.214, 95%CI: 0.075-0.615; p<0.004), ACLF-2 by 4.4 times (TR 0.224, 95%CI: 0.070-0.713; p<0.011), and ACLF-3 by 37 times (TR 0.027, 95%CI: 0.006-0.129; p<0.001)., Conclusions: Patients with decompensated cirrhosis and ACLF exhibited a high frequency ofactive alcohol consumption. Patients with ACLF showed higher mortality and shorter time todeath than those without ACLF., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

BACKGROUND: The administration of vitamin K are restricted to situations such as an antidote for vitamin K antagonists and hemorrhagic disease of the newborn, but due to its role in hemostasis, its use has been extended to other diseases, such as terminal chronic liver disease. OBJECTIVE: To identify the efficacy of adding vitamin K to the management of patients with terminal hepatic insufficiency with some state of decompensation. MATERIAL AND METHOD: A retrospective case-control study was done between 2016-2017 in patients with Child-Pugh C chronic liver disease during an episode of decompensation. Vitamin K (menadione sodium bisulfite) was administered at a dose of 10 mg intramuscular every 12 h for three days. RESULTS: A total of 60 patients were studied, 30 received vitamin K, in the case of a hemorrhagic event, replacement therapy with fresh frozen plasma and cryoprecipitates were administered together. The mean age was 60 (25-86) years; all were male. Hemorrhage (85%) was the main cause of complication. Five cases (8.3%) died due to reactivation of the hemorrhage. The administration of vitamin K did not shorten the coagulation tests (TP, aPTT, INR) nor showed a mortality benefit. Only thrombosis such as encephalopathy showed an association on mortality. CONCLUSION: The addition of vitamin K does not influence the complications in patients with terminal liver disease. [ABSTRACT FROM AUTHOR]

Unfortunately, there is a gap of understanding in the pathophysiology of chronic liver disease due to the lack of experimental models that exactly mimic the human disease. Additionally, the diagnosis of patients is very poor due to the lack of biomarkers than can detect the disease in early stages. Thus, it is of utmost interest the generation of a multidisciplinary consortium from different countries with a direct translation. The present reports the meeting of the 2021 Iberoamerican Consortium for the study of liver Cirrhosis, held online, in October 2021. The meeting, was focused on the recent advancements in the field of chronic liver disease and cirrhosis with a specific focus on cell pathobiology and liver regeneration, molecular and cellular targets involved in non-alcoholic hepatic steatohepatitis, alcoholic liver disease (ALD), both ALD and western diet, and end-stage liver cirrhosis and hepatocellular carcinoma. In addition, the meeting highlighted recent advances in targeted novel technology (-omics) and opening therapeutic avenues in this field of research., (Copyright © 2022 Elsevier España, S.L.U. All rights reserved.)

Background: There is a pro-atherogenic trend in patients with chronic liver disease (CLD). The carotid intima media thickness (CIMT) by Doppler is useful for early diagnosis of subclinical atherogenesis, which correlates with cardiovascular risk factors. This study assessed the relation between subclinical atherogenesis and ankle to brachial index (ABI) in patients with CLD. Material and methods: CLD patients attending to Internal Medicine, General Hospital of Xoco from March 2014 to February 2015 were included. ABI and CIMT were measured by conventional methods. The sample was divided into two groups according to the determination of CIMT (CIMT ≤0.05cm and CIMT >0.05cm). The results were compared using mean difference, risk analysis (odds ratio), and standardization for variables of potential interaction (logistic regression). Results: Sixty patients, 53 (88.3%) males and 7 (11.6%) females, mean age 47 years-old were recruited. The ABI mean was 1.012 ± 0.144 in the group of CIMT >0.05. The ABI <0.9 was associated with CIMT risk OR = 12.42; 95% CI 1.46 - 105.7, p = 0.012. This association was modified when variables of potential interaction were added to the logistic regression, mainly uric acid (>5.2mg/dl) OR 5.3 (95% CI, 1.28-22.09), VSG (>20sec) OR 6.9 (95% CI, 1.68-28.9), age >50 years-old OR 7.1 (95% CI, 1.10-47.03). Conclusions: We found that ABI<0.9 increased by 10 times the risk of advanced subclinical atherogenesis (CIMT >0.05cm). This suggests the value of ABI as a non-invasive marker of subclinical atherogenesis and possibly also for cardiovascular events in patients with CLD. [ABSTRACT FROM AUTHOR]

The Asociación Mexicana de Hepatología A.C. carried out the Consensus on the Management of Complications of Cirrhosis of the Liver in Pediatrics to provide physicians with useful information for treating said complications. A group of pediatric gastroenterologists and experts in nutrition, nephrology, and infectious diseases participated and reviewed the medical literature. The Delphi method was applied to obtain the level of agreement on the statements that were formulated. The statements were sent to the participants to be analyzed and voted upon, after which they were discussed in virtual sessions, and the final versions were produced. The aim of the consensus results was to issue indications for the management of pediatric patients with liver cirrhosis, to prevent or control complications., (Copyright © 2022 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.)

Hepatic osteodystrophy is a frequent late complication in chronic liver diseases in which patients usually present bone mineral density reduction, osteopenia, osteoporosis and fractures. Strategies to decrease incidence, avoid comorbidity and improve patient quality of life have yet to be implemented in clinical practice. Hepatic osteodystrophy's pathophysiology is poorly understood. There is controversy about the use of screening tests especially regarding which patients are eligible, at what moment of the disease and with what frequency. Risk factors which are dependent on liver disease and other risk factors which are not liver disease dependent have been identified, all of which affect the natural history of hepatic osteodystrophy and all of which must be taken into account for screening, checkups and treatment. Recommendations for treatment are widely discussed but focus mainly on reduction of risk factors, antiresorptive drugs, calcium supplements and vitamin D. [ABSTRACT FROM AUTHOR]

Coagulation alterations in patients with chronic liver disease occur frequently, although they are usually described as auto-anticoagulation phenomena. Changes in hemostasis are broad and diffuse. They include changes in procoagulant and anticoagulant substances, hemodynamic modifi cations, endothelial dysfunction and platelet malfunction which are the causes of different clinical conditions varying from hemorrhaging to thrombosis. Given the complexity of theses alterations, laboratory tests do not correlate well with the clinical events. Treatment for these patients has been controversial. Currently we do not have objective methods for determining the hemostatic balance between bleeding and thrombosis in patients with chronic liver disease. In addition to this, the medical literature does not include guidelines for dealing with this special population. Also, the risk of thrombosis indicates the need to consider the use of thromboprophylaxis. [ABSTRACT FROM AUTHOR]

Introduction and Aims: Cirrhosis is the common outcome of liver diseases. It can be decompensated and lead to the development of complications, such as encephalopathy. Hyperammonemia that develops due to liver dysfunction is etiopathologically related to hepatic encephalopathy. Caffeine increases the activity of the urea cycle in the liver, augmenting ammonia degradation. By antagonizing adenosine receptors, it also has a hepatoprotective effect, impeding the formation of fibrosis, as well as having a stimulating effect on the central nervous system. The present study analyzed the effects of caffeine on the progression of cholestatic liver fibrosis and hepatic encephalopathy., Materials and Methods: An experimental model of cholestatic liver fibrosis, through common bile duct ligature, and of hepatic encephalopathy, through the administration of a high-protein diet, was constructed. Male Wistar rats (n=32) were equally divided into 4 groups. The experiment lasted 28 days, with the administration of 50mg/kg/day of caffeine. Laboratory tests, histologic analyses of the liver and encephalon, open field tests (OFTs), and daily behavioral analyses were carried out., Results: The ligated animals treated with caffeine had lower mean transaminase levels and improved histologic aspects of the liver and encephalon. The untreated ligated animals were clearly lethargic and apathetic at the last week of the experiment, confirmed by reduced exploratory activity during the OFT., Conclusion: Caffeine improved the microarchitecture of the liver and encephalon of the cirrhotic animals and prevented the decrease in exploratory behavior of the animals during the OFT., (Copyright © 2021 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.)

Introducción: Los errores innatos en la síntesis de ácidos biliares son un grupo de defectos genéticos que representan del 1 al 2% de las enfermedades colestásicas crónicas en lactantes, niños y adolescentes. La deficiencia de 3b-Δ5-C27-hidroxiesteroide oxidoreductasa (3b-HSDH) es el defecto más comúnmente reportado. El cuadro clínico característico consiste en hepatitis neonatal, hepatomegalia, esplenomegalia, malabsorción, desnutrición y enfermedad hepática de aparición tardía., Caso Clínico: Lactante masculino con antecedente de ictericia en escleras a los 4 meses que se resolvió espontáneamente; posteriormente, a los 18 meses, presentó enfermedad colestásica. Durante su abordaje se documentó gamma-glutamil transpeptidasa normal, hallazgo que es altamente sugestivo de alteración en la síntesis de ácidos biliares. El diagnóstico se realizó con espectrometría de masas en orina. Se inició tratamiento con ácido cólico oral, y presentó mejoría inmediata., Conclusiones: El resultado en los ácidos biliares urinarios es definitivo para el defecto genético y consistente con mutaciones homocigotas en el gen HSD3B7. Este padecimiento constituye un diagnóstico de exclusión en las enfermedades colestásicas de la infancia, particularmente el hallazgo de gamma-glutamil transpeptidasa normal o levemente aumentada, y responde adecuadamente al tratamiento oral, por lo que debe identificarse de forma temprana., Background: Inborn errors in bile acid synthesis are a group of genetic defects accounting for 1 to 2% of chronic cholestatic diseases in infants, children and adolescents. Deficiency of 3b-Δ5-C27-hydroxysteroid dehydrogenase (3β-HSDH) is the most common defect in this disease. Clinical features consist of neonatal hepatitis, hepatomegaly, splenomegaly, malabsorption, malnutrition, and late-onset liver disease., Case Report: A male infant who presented jaundice in sclera at 4 months that resolved spontaneously, later presented cholestatic disease at 18 months. During his approach, normal gamma-glutamyl transpeptidase was documented, a finding that is highly suggestive of alteration in the synthesis of bile acids. The diagnosis was made using urine mass spectrometry. Oral colic acid treatment was started, presenting immediate improvement., Conclusions: The result in urinary bile acids is definitive for the genetic defect and consistent with homozygous mutations in the HSD3B7 gene. This condition is a diagnosis of exclusion in childhood cholestatic diseases, particularly in the presence of normal or mildly enlarged gamma-glutamyl transpeptidase, and responds adequately to oral treatment; it should be identified early., (Copyright: © 2018 SecretarÍa de Salud.)

Introduction: Vitamin D (VD) is known to have multiple extra-skeletal health functions. There is emerging interest in exploring the relationship between vitamin D and chronic liver disease (CLD)., Objectives: To determine the prevalence of VD deficiency in patients with CLD in our setting and to assess whether VD supplementation influences plasma levels and is associated with improved liver function., Material and Methods: We conducted a study in 2 phases. First, we analysed clinical and epidemiological characteristics in 94 patients with CLD; second, different doses of calcifediol (25-OH-VD) were administered to patients with VD deficiency (<20ng/mL) and insufficiency (20-30ng/mL). Plasma concentrations and liver function (Child-Pugh and MELD) at the end of treatment were compared with baseline data., Results: Deficient or insufficient VD levels were found in 87% of the patients, with an average concentration of 18.8ng/mL. Levels were lower in patients with cirrhosis (15.9ng/mL) (P=.002) and in alcoholic liver disease. VD levels were inversely proportional to the degree of liver function: Child A (16.52ng/mL) vs C (7.75ng/mL). After VD supplementation, optimal serum levels were achieved in 94% of patients and significant improvements were observed in platelet count, albumin levels (P<.05) and functional status assessed by the Child-Pugh scale (P<.05)., Conclusion: Given the high prevalence of VD deficiency or insufficiency, the need for screening should be considered in the population with CLD. VD supplementation could be safe and effective., (Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.)

Unlabelled: Health-Related Quality of Life (HRQL) assessed by a specific, validated, brief test is an important measure of the health status perceived by patients diagnosed with chronic liver disease., Aim: To prospectively validate the SF-LDQOL (Short Form-Liver Disease Quality of Life) instrument in Spanish, in patients diagnosed with liver disease of diverse etiologies and distinct severity levels, attended at the Hospital Universitari de Bellvitge (Barcelona)., Methods: This observational, longitudinal study was conducted by using the SF-LDQOL in outpatients diagnosed with chronic liver disease. This instrument contains the generic SF-36 test, and 9 liver disease-specific dimensions. We also evaluated socio-demographic features, the number of missing responses, and internal consistency (Cronbach's alpha), as well as Pearson's correlation between SF-36 and SF-LDQOL scores on specific dimensions by means of a multi-trait multi-method technique. The sample consisted of 340 patients., Results: In 6 out of 9 liver disease-specific dimensions, reliability coefficients for internal consistency exceeded 0.70. The convergent validity of these items was acceptable in 8 out of 9 dimensions, with a scaling success of 100% in each item. Missing items were under 1.5% in all dimensions, except for Sexual Functioning., Conclusions: The Spanish version of the SF-LDQOL has, in general, good psychometric properties, making it a useful instrument for clinical practice in a population of patients diagnosed with chronic liver disease, with or without liver transplantation., (Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.)

Obesity is sharply rising worldwide and is increasingly recognized in patients with cirrhosis. This review summarizes the available data documenting a detrimental role of obesity and insulin-resistance on the risk of appearance of clinical events in patients with cirrhosis. Molecular pathways explaining the harmful effect of obesity and insulin resistance in the natural history of cirrhosis are largely unknown. Increasing knowledge of mechanisms leading to white adipose tissue dysfunction on one side, and to portal hypertension on the other side, allow hypothesizing that a link between the pathophysiology of obesity, insulin resistance and portal hypertension in cirrhosis exists. Mechanisms likely involved in this interplay are discussed in this article., (Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.)