Puerarin protects the fatty liver from ischemia-reperfusion injury by regulating the PI3K/AKT signaling pathway

Abstract The incidence of non-alcoholic fatty liver (NAFLD) remains high, and many NAFLD patients suffer from severe ischemia-reperfusion injury (IRI). Currently, no practical approach can be used to treat IRI. Puerarin plays a vital role in treating multiple diseases, such as NAFLD, stroke, diabetes, and high blood pressure. However, its role in the IRI of the fatty liver is still unclear. We aimed to explore whether puerarin could protect the fatty liver from IRI. C57BL/6J mice were fed with a high‐fat diet (HFD) followed by ischemia reperfusion injury. We showed that hepatic IRI was more severe in the fatty liver compared with the normal liver, and puerarin could significantly protect the fatty liver against IRI and alleviate oxidative stress. The PI3K-AKT signaling pathway was activated during IRI, while liver steatosis decreased the level of activation. Puerarin significantly protected the fatty liver from IRI by reactivating the PI3K-AKT signaling pathway. However, LY294002, a PI3K-AKT inhibitor, attenuated the protective effect of puerarin. In conclusion, puerarin could significantly protect the fatty liver against IRI by activating the PI3K-AKT signaling pathway.

Descripción de polimorfismos genéticos en CYP3A5 y MDR-1 y su impacto en el rechazo agudo clínico de pacientes trasplantados de hígado del Hospital San Vicente Fundación Rionegro / Description of genetic polymorphisms in CYP3A5 and MDR-1 and their impact on clinical acute rejection in liver transplant patients at Hospital San Vicente Fundación Rionegro

Introducción. El tacrolimus es un medicamento inmunosupresor ampliamente usado en trasplante hepático, que presenta una gran variabilidad interindividual la cual se considera asociada a la frecuencia de polimorfismos de CYP3A5 y MDR-1. El objetivo de este estudio fue evaluar la frecuencia de los polimorfismos rs776746, rs2032582 y rs1045642 y su asociación con rechazo clínico y toxicidad farmacológica. Métodos. Se incluyeron pacientes inmunosuprimidos con tacrolimus a quienes se les realizó trasplante hepático en el Hospital San Vicente Fundación Rionegro entre 2020 y 2022, con supervivencia mayor a un mes. Se evaluaron las variables clínicas, rechazo agudo y toxicidad farmacológica. Se secuenciaron los genes de estudio mediante PCR, comparando la expresión o no en cada uno de los pacientes. Resultados. Se identificaron 17 pacientes. El 43 % de los pacientes se clasificaron como CYP3A5*1/*1 y CYP3A5*1/*3, entre los cuales se encontró asociación con aumento en la tasa de rechazo agudo clínico, al comparar con los pacientes no expresivos (100 % vs. 44 %, p=0,05); no hubo diferencias en cuanto a la toxicidad farmacológica u otros desenlaces. Se encontró el polimorfismo rs2032582 en un 50 % y el rs1045642 en un 23,5 % de los pacientes, sin embargo, no se identificó asociación con rechazo u otros eventos clínicos. Conclusiones. Se encontró una asociación entre el genotipo CYP3A5*1/*1 y CYP3A5*1/*3 y la tasa de rechazo clínico. Sin embargo, se requiere una muestra más amplia para validar estos datos y plantear modelos de medicina personalizada.

Introduction. Tacrolimus is an immunosuppressive drug widely used in liver transplantation, which presents great interindividual variability which is considered associated with the frequency of CYP3A5 and MDR-1 polymorphisms. The objective of this study was to evaluate the frequency of the rs776746, rs2032582 and rs1045642 polymorphisms and their association with clinical rejection and drug toxicity. Methods. Immunosuppressed patients with tacrolimus who underwent a liver transplant at the Hospital San Vicente Fundación Rionegro between 2020 and 2022 were included, with survival of more than one month. Clinical variables, acute rejection and pharmacological toxicity were evaluated. The study genes were sequenced by PCR, comparing their expression or not in each of the patients. Results. Seventeen patients were identified. 43% of the patients were classified as CYP3A5*1/*1 and CYP3A5*1/*3, among which an association was found with increased rates of clinical acute rejection when compared with non-expressive patients (100% vs. 44%, p=0.05). There were no differences in drug toxicity or other outcomes. The rs2032582 polymorphism was found in 50% and rs1045642 in 23.5% of patients; however, no association with rejection or other clinical events was identified. Conclusions. An association was found between the CYP3A5*1/*1 and CYP3A5*1/*3 genotype and the clinical rejection rate. However, a larger sample is required to validate these data and propose models of personalized medicine.

Sonographic and Anatomical Evaluation of the Liver and Portal Vein Reference Values / Evaluación Ecográfica y Anatómica de los Valores de Referencia del Hígado y la Vena Porta

SUMMARY: This paper's aim is a morphometric evaluation of liver and portal vein morphometry using ultrasonography in healthy Turkish population. This study was carried out with 189 subjects (107 females, 82 males). The demographic data and the body surface area were calculated. The longitudinal axis of the liver for two lobes, diagonal axis or liver span, anteroposterior diameter of the liver and portal vein, portal vein transverse diameter, caudate lobe anteroposterior diameter, and portal vein internal diameters as well as longitudinal liver scans in an aortic plane, sagittal plane, transverse plane, and kidney axis were measured. All measurements were analyzed according to age, sex, body mass index, obesity and alcohol consumption. The mean values of the age, height, weight and body mass index were calculated as 44.39 years, 167.05 cm, 74.23 kg, and 27.06kg/m2 in females, respectively. The same values were 44.13 years, 167.70 cm, 75.93 kg and 26.71 kg/m2 in males, respectively. There was significant difference between demographic characteristics, gender, and alcohol consumption in terms of anteroposterior diameter of the liver, portal vein transverse diameter of the right side and liver transverse scan. Also, some measurements including portal vein transverse diameter, liver transverse scan and at kidney axis longitudinal scan of liver showed significant difference between the age groups. There was significant difference in diagonal axis and anteroposterior diameter of liver, portal vein internal diameter, and longitudinal liver scans of the aortic plane parameters between obesity situation. The findings obtained will provide important and useful reference values as it may determine some abnormalities related liver diseases. Also, age, sex, obesity and body mass index values can be effective in the liver and portal vein morphometry related parameters.

El objetivo de este artículo fue realizar una evaluación de la morfometría del hígado y la vena porta mediante ecografía en una población turca sana. Este estudio se llevó a cabo en 189 sujetos (107 mujeres, 82 hombres). Se calcularon los datos demográficos y la superficie corporal. Se midió eleje longitudinal del de dos lóbulos del hígado, el eje diagonal o la extensión del hígado, los diámetros anteroposterior del hígado y de la vena porta, el diámetro transversal de la vena porta, anteroposterior del lóbulo caudado y los diámetros internos de la vena porta, así como las exploraciones longitudinales del hígado en un plano aórtico. Se midieron el plano sagital, el plano transversal y el eje del riñón. Todas las mediciones se analizaron según edad, sexo, índice de masa corporal, obesidad y consumo de alcohol. Los valores medios de edad, talla, peso e índice de masa corporal se calcularon como 44,39 años, 167,05 cm, 74,23 kg y 27,06 kg/m2 en las mujeres, respectivamente. Las mismas variable fueron 44,13 años, 167,70 cm, 75,93 kg y 26,71 kg/m2. Hubo diferencias significativas entre las características demográficas, el sexo y el consumo de alcohol en términos de diámetro anteroposterior del hígado, diámetro transversal de la vena porta del lado derecho y exploración transversal del hígado. Además, algunas mediciones, incluido el diámetro transversal de la vena porta, la exploración transversal del hígado y la exploración longitudinal del hígado en el eje del riñón, mostraron diferencias significativas entre los grupos de edad. Hubo diferencias significativas en el eje diagonal y el diámetro anteroposterior del hígado, el diámetro interno de la vena porta y los parámetros de las exploraciones hepáticas longitudinales del plano aórtico entre situaciones de obesidad. Los hallazgos obtenidos proporcionarán valores de referencia importantes y útiles ya que pueden determinar algunas anomalías relacionadas con enfermedades hepáticas. Además, los valores de edad, sexo, obesidad e índice de masa corporal pueden ser eficaces en los parámetros relacionados con la morfometría del hígado y la vena porta.

Aplicabilidad del índice de fragilidad hepática en pacientes cirróticos evaluados para trasplante / Applicability of the liver frailty index in cirrhotic patients evaluated for transplantation

Introducción. En las últimas décadas se han desarrollado diferentes scores y modelos para predecir el pronóstico en pacientes con enfermedad hepática crónica avanzada. Los más reconocidos y utilizados son el sistema de estadificación de Child-Pugh (CP) y el score de MELD, pero estos carecen de herramientas para evaluar objetivamente otros factores pronósticos. Por este motivo, se ha incorporado el concepto de fragilidad a la hepatología clínica. El objetivo de este artículo es examinar la aplicabilidad del índice de fragilidad hepática (IFH) en pacientes con cirrosis evaluados para trasplante hepático en Uruguay. Metodología. Estudio observacional, descriptivo y retrospectivo en el Servicio de Enfermedades Hepáticas del Hospital Central de las Fuerzas Armadas (HCFFAA) de enero de 2018 a diciembre de 2021. Resultados. Se evaluaron un total de 78 pacientes, excluyéndose 19 de estos, culminando con una muestra final de 59 pacientes. La edad media fue de 52 años, siendo el 66 % hombres. La principal etiología de la cirrosis fue la alcohólica, y la comorbilidad más frecuente fue el sobrepeso/obesidad (66 %). La media de IFH fue de 4,03 ± 0,45. El 90 % de los pacientes eran prefrágiles, el 10 % frágiles y ningún paciente fue clasificado como no frágil. El 76 % presentaba un estadio avanzado de la enfermedad al momento de la evaluación 42 % CP estadio B, 34 % CP C, 24 % CP A, con una media de MELD-Na de 17,8 ± 7,6. El 17 % tuvo complicaciones infecciosas. La mortalidad global (n=78) fue del 12 %, y la de los pacientes con IFH calculado fue del 22 %. Conclusiones. El cálculo del IFH es realizable en cirróticos como herramienta objetiva que brinda una mirada integral del paciente. A mayor severidad de la cirrosis, mayor es el IFH. Sin embargo, este índice no parece ser un predictor de la eventual realización del trasplante hepático, ni de muerte en lista de espera en nuestros pacientes.

Introduction. In recent decades, several scores and models have been proposed to predict prognosis in patients with advanced chronic liver disease. The most recognized and used are the Child-Pugh (CP) and the Model for End-stage Liver Disease (MELD) scores, but they lack tools to objectively evaluate other prognostic factors. For this reason, the concept of fragility has been incorporated into clinical hepatology. The objective of this study was to evaluate the applicability of the liver frailty index (LFI) in patients with cirrhosis evaluated for liver transplantation in Uruguay. Methodology. Observational, descriptive and retrospective study at the Hospital Central de las Fuerzas Armadas (HCFFAA) Liver Disease Service from January 2018 to December 2021. Results. A total of 78 patients were evaluated, 19 were excluded, culminating in a final sample of 59 patients. The mean age was 52 years, with 66% being men. The main etiology of cirrhosis was alcoholic and the most frequent comorbidity was overweight/obesity (66%). The mean LFI was 4.03 ± 0.45. 90% of patients were pre-fragile, 10% were fragile, and no patient was classified as non-fragile. 76% had an advanced stage of the disease at the time of evaluation: 42% CP stage B, 34% CP C, 24% CP A, with a mean MELD-Na of 17.8 ± 7.6. 17% had infectious complications. Overall mortality (n=78) was 12%, and that of patients with calculated LFI was 22%. Conclusions. The LFI can be calculated in cirrhotic patients, and it is an objective tool that provides a comprehensive view of the patient. LFI depends on the severity of the cirrhosis. However, this index is not a predictor of liver transplantation or death on the waiting list in our patients.

Cohorte descriptiva de pacientes adultos con hipertensión portal en una institución de tercer nivel en Colombia / Descriptive cohort of adult patients with portal hypertension at a tertiary care institution in Colombia

Introducción. La hipertensión portal (HTP) se define como una elevación anormal de la presión venosa en el sistema portal que lleva al desarrollo de vías colaterales para desviar el flujo sanguíneo de la zona. Dentro de su etiología están las relacionadas con la cirrosis hepática y otras causas denominadas no cirróticas. El objetivo de este estudio fue evaluar los principales hallazgos demográficos, clínicos y paraclínicos en un grupo de pacientes con HTP, y determinar el uso de ayudas invasivas y no invasivas, y su disponibilidad para el diagnóstico y seguimiento de los pacientes en los centros que no cuentan con laboratorio de hemodinamia hepática, reflejando la dinámica de múltiples escenarios en Colombia. Metodología. Se realizó un estudio descriptivo de corte transversal, retrospectivo, en pacientes atendidos en una institución de tercer nivel del sur de Colombia, entre enero del año 2015 y diciembre del año 2020. Resultados. Se obtuvo una muestra de 61 pacientes en donde la mayoría de casos correspondían a hombres en la séptima década de la vida, procedentes del área urbana. La principal causa de consulta fue el sangrado digestivo (39,3 %), asociado a la presencia de telangiectasias (arañas vasculares) en el 37,2 %, seguido de circulación colateral (31,3 %) e ictericia (19,7 %). En la ecografía abdominal (realizada en el 57,4 % de los pacientes) predominaron la cirrosis (68 %) y la presencia de esplenomegalia (14,2 %), y en lospacientes con Doppler portal (realizado en el 16,4 %) se encontró hígado cirrótico (80 %) y dilatación portal (40 %). Con respecto a los hallazgos en la esofagogastroduodenoscopia predominó la presencia de várices esofágicas y gastritis crónica. Conclusión. El principal motivo de consulta fue el sangrado digestivo, en tanto que la cirrosis fue el antecedente y el hallazgo imagenológico más frecuente, seguido de las várices esofágicas. Se encontró que el uso de paraclínicos, ecografía abdominal, ecografía con Doppler portal y esofagogastroduodenoscopia fueron los más utilizados en el contexto clínico de los pacientes con el diagnóstico de HTP.

Introduction. Portal hypertension (PHT) is defined as an abnormal elevation of venous pressure in the portal system that leads to the development of collateral pathways to divert blood flow from the area. Within its etiology are those related to liver cirrhosis and other so-called non cirrhotic causes. The aim of this study was to evaluate the main demographic, clinical and paraclinical findings in a group of patients with PHT, and to determine the use of invasive and non-invasive aids, and their availability for the diagnosis and follow-up of patients in centers that do not have a hepatic hemodynamics laboratory, reflecting the dynamics of multiple scenarios in Colombia. Methodology. A descriptive, retrospective, cross-sectional, retrospective study was conducted in patients attended in a third level institution in Southern Colombia, between January 2015 and December 2020. Results. A sample of 61 patients was obtained where the majority of cases corresponded to men in the seventh decade of life, from the urban area. The main cause of consultation was digestive bleeding (39.3%), associated with the presence of telangiectasias (spider veins) in 37.2%, followed by collateral circulation (31.3%) and jaundice (19.7%). In abdominal ultrasound (performed in 57.4% of the patients), cirrhosis (68%) and the presence of splenomegaly (14.2%) predominated, and in patients with portal Doppler (performed in 16.4%), cirrhotic liver (80%) and portal dilatation (40%) were found. With respect to the findings in the esophagogastroduodenoscopy, esophageal varices and chronic gastritis were predominant. Conclusion. The main reason for consultation was gastrointestinal bleeding, while cirrhosis was the most frequent history and imaging finding, followed by esophageal varices. It was found that the use of paraclinics, abdominal ultrasound, ultrasound with portal Doppler and esophagogastroduodenoscopy were the most used in the clinical context of patients diagnosed with PHT.

Caracterización clínico-epidemiológica de pacientes con enfermedad hepática esteatósica asociada a disfunción metabólica previa al trasplante en un hospital de cuarto nivel / Clinical-epidemiological characterization of patients with steatotic liver disease associated with metabolic dysfunction prior to transplantation in a fourth level hospital

Introducción. La enfermedad hepática esteatósica asociada a disfunción metabólica (MASLD) se ha convertido en la enfermedad hepática crónica más frecuente en los países occidentales, causando un aumento en los costos y en la ocupación hospitalaria. La caracterización integral previa al trasplante hepático en pacientes con MASLD es una gran interrogante, especialmente en nuestro medio. El objetivo del presente estudio fue realizar la caracterización clínico-epidemiológica de pacientes trasplantados por cirrosis hepática (CH) descompensada o carcinoma hepatocelular (CHC) asociado a MASLD. Metodología. Se desarrolló un estudio observacional retrospectivo, descriptivo, de corte transversal en el Servicio de Hepatología del Hospital Pablo Tobón Uribe en Medellín, Colombia. Se incluyeron pacientes mayores de 17 años, con diagnóstico de CH o de CHC asociado a MASLD que fueron trasplantados entre los años 2004 a 2017. Resultados. Se encontraron 84 pacientes que fueron trasplantados con esas características. La edad promedio de los pacientes fue de 59±10,5 con una mayor proporción significativa de hombres sobre mujeres, llegando casi al 70 %. Con relación a las comorbilidades, se encontró que el sobrepeso/obesidad, la hipertensión arterial y la diabetes mellitus tipo 2 fueron un hallazgo en el 44,1 %, 33,3 % y 33,3 %, respectivamente. Por otro lado, el 14,5 %, el 33,7 % y el 51,8 % presentaron un Child-Pugh A, B y C, respectivamente. La media del puntaje MELD fue de 18,9±6,26. Con respecto a las complicaciones de la cirrosis, el 77,4 % de los pacientes presentó ascitis, el 61,9 % encefalopatía hepática, el 36,9 % hemorragia del tracto digestivo superior y el 29,8 % peritonitis bacteriana espontánea. Conclusión. Los resultados expuestos mostraron nuestra experiencia en trasplante hepático en pacientes con CH y CHC asociado a MASLD. Se debe realizar una evaluación multidisciplinaria antes y después del trasplante en estos pacientes, haciendo especial énfasis en el manejo de la disfunción metabólica y sus componentes, entre los que se destacan la obesidad y la diabetes mellitus.

Introduction. Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most frequent chronic liver disease in Western countries, causing increased costs and hospital occupancy. The comprehensive pre-transplant characterization in patients with MASLD is a major question, especially in our setting. The aim of the present study was to perform the clinical-epidemiological characterization of transplanted patients with decompensated liver cirrhosis (LC) or hepatocellular carcinoma (HCC) associated with MASLD. Methodology. A retrospective, descriptive, cross-sectional observational study was carried out in the Hepatology Department of the Pablo Tobón Uribe Hospital in Medellin, Colombia. Patients over 17 years of age, with a diagnosis of LC or HCC associated with MASLD who were transplanted between 2004 and 2017 were included. Results. We found 84 patients who were transplanted with these characteristics. The mean age of the patients was 59±10.5 with a significantly higher proportion of men over women, reaching almost 70%. Regarding comorbidities, overweight/obesity, arterial hypertension, and type 2 diabetes mellitus were found in 44.1%, 33.3%, and 33.3%, respectively. On the other hand, 14.5%, 33.7%, and 51.8% had Child-Pugh A, B, and C, respectively. The mean MELD score was 18.9±6.26. Regarding complications of cirrhosis, 77.4% of patients developed ascites, 61.9% hepatic encephalopathy, 36.9% upper gastrointestinal tract hemorrhage, and 29.8% spontaneous bacterial peritonitis. Conclusion. The above results showed our experience of liver transplantation in patients with LC and HCC associated with MASLD. A multidisciplinary evaluation should be performed before and after transplantation in these patients, with special emphasis on the management of metabolic dysfunction and its components, including obesity and diabetes mellitus.

La piel como reflejo de trastornos hepáticos subyacentes / The skin as a reflection of underlying liver disorders

La piel es el órgano más grande y visible del cuerpo humano; en ella se pueden reflejar diversos hallazgos de enfermedades sistémicas, incluidas las hepatopatías crónicas y agudas, las cuales se asocian a múltiples lesiones dermatológicas como principal manifestación extrahepática. Las manifestaciones cutáneas son comunes pero inespecíficas y pueden encontrarse en diferentes enfermedades; por lo tanto, la piel funciona como una ventana a nuestra salud general, de ahí que el examen clínico de la piel, las uñas y el cabello pueda permitir el reconocimiento adecuado, el diagnóstico y tratamiento temprano de las enfermedades hepáticas y la mejoría de la calidad y esperanza de vida de los pacientes afectados.

La piel es el órgano más grande y visible del cuerpo humano; en ella se pueden reflejar diversos hallazgos de enfermedades sistémicas, incluidas las hepatopatías crónicas y agudas, las cuales se asocian a múltiples lesiones dermatológicas como principal manifestación extrahepática. Las manifestaciones cutáneas son comunes pero inespecíficas y pueden encontrarse en diferentes enfermedades; por lo tanto, la piel funciona como una ventana a nuestra salud general, de ahí que el examen clínico de la piel, las uñas y el cabello pueda permitir el reconocimiento adecuado, el diagnóstico y tratamiento temprano de las enfermedades hepáticas y la mejoría de la calidad y esperanza de vida de los pacientes afectados.

Manifestaciones dermatológicas de la cirrosis hepática: revisión de la literatura / Dermatological manifestations of liver cirrhosis: review of the literature

La piel y sus anexos tienen amplia relación con todos los órganos y sistemas. Los cambios presentes en estos pueden ser el primer hallazgo en un paciente con enfermedad hepática, encontrándose hasta en el 20 % de los casos, por lo que las manifestaciones extrahepáticas adquieren importancia, y aunque muchas de estas no son específicas, algunos marcadores dermatológicos pueden ayudar al diagnóstico de la enfermedad y se pueden correlacionar con su severidad. El desarrollo de las lesiones cutáneas en los pacientes con cirrosis hepática se genera principalmente por hipertensión portal y exceso de estrógenos circulantes, por lo tanto, su tratamiento se basa en el manejo de la patología hepática subyacente. En el presente artículo se hace una revisión de la literatura y se describe un amplio espectro de manifestaciones dermatológicas asociadas a cirrosis hepática, con sus características y etiopatogénesis, siendo las más frecuentes la ictericia, el prurito, los nevus en araña, el eritema palmar, las venas en cabeza de Medusa, y los cambios de uñas y del vello, entre otras.

The skin and its annexes have a broad relationship with all organs and systems. Changes present in these can be the initial finding in a patient with liver disease, occurring in up to 20% of cases, therefore the extrahepatic manifestations become important, and although many of these are not specific, some dermatological markers can help in the diagnosis of the disease and may correlate with its severity. The development of cutaneous lesions in patients with liver cirrhosis is mainly generated by portal hypertension and excess of circulating estrogens, therefore their treatment is based on managing the underlying liver pathology. This article reviews the literature and describes a wide range of dermatological manifestations associated with liver cirrhosis, with their characteristics and etiopathogenesis, being the most frequent jaundice, pruritus, spider nevus, palmar erythema, caput Medusae veins, nail and hair changes, among others.

Manifestaciones cutáneas comunes de las principales enfermedades hepáticas / Common cutaneous manifestations of major liver diseases

Las enfermedades hepáticas presentan múltiples manifestaciones sistémicas, entre las cuales se destacan los hallazgos en piel, siendo los más comunes el prurito y la ictericia; así mismo, se pueden encontrar angiomas en araña, eritema palmar, xantomas, vasculitis y cambios en anexos. Este artículo tiene como objetivo describir los principales signos y síntomas cutáneos en las enfermedades hepáticas para brindar herramientas semiológicas al clínico en su práctica diaria

Liver disease present multiple systemic manifestations, among which skin findings stand out, being the most common pruritus and jaundice. Other findings can also be manifested like spider angiomas, palmar erythema, xanthomas, vasculitis and changes in skin appendages. The objective of this article is to describe the main skin signs and symptoms of liver diseases to provide semiological tools to the physician in his daily practice.

TIPS en pacientes cirróticos con trombosis venosa portal: una revisión de la literatura / TIPS in cirrhotic patients with portal vein thrombosis: A review of the literature

En los últimos años, la trombosis de la vena porta entre los pacientes cirróticos se ha comportado como una entidad reconocida y cada vez más estudiada, no solo por su creciente incidencia, sino por la asociación con gravedad y mal pronóstico en cirrosis. Asimismo, se hacen objeto de estudio las terapias disponibles para el manejo tanto médico como quirúrgico de estos pacientes, lo que ha dado un papel importante a la derivación portosistémica transyugular intrahepática (TIPS). El uso de TIPS en esta población se posiciona como una alternativa de manejo aceptable, no solo por brindar mejoría en las complicaciones derivadas de la hipertensión portal, sino también por sus resultados prometedores en diferentes estudios sobre el flujo y la recanalización portal, y por su perfil de seguridad. Sin embargo, la eficacia, los efectos adversos a largo plazo y el pronóstico de dicha intervención en la compleja fisiopatología de la cirrosis deben continuar en estudio. El objetivo de este artículo es revisar los avances del uso de TIPS en el manejo de pacientes con cirrosis hepática y trombosis portal.

In recent years, portal vein thrombosis among cirrhotic patients has been a well-recognized and continuously studied entity, not only because of its increasing incidence but also because of its association with severity and poor prognosis in cirrhosis. Likewise, therapies available for both medical and surgical management in these patients are being studied, which has given an important role to the transjugular intrahepatic portosystemic shunt (TIPS). The use of TIPS in this population is positioned as an acceptable management alternative, not only because it provides improvement in complications derived from portal hypertension, but also because of its promising results in different studies on portal flow and recanalization upgrade, and for its safety. However, the efficacy, long-term adverse effects, and prognosis of this intervention in the complex pathophysiology of cirrhosis must continue to be studied. The objective of this article is to review the advances in the use of TIPS in the management of patients with liver cirrhosis and portal vein thrombosis.

Albúmina en cirrosis: perspectiva inflamatoria / Albumin in cirrhosis: inflammatory perspective

La albúmina sérica humana es la proteína más abundante en el plasma, su estructura molecular le confiere estabilidad, pero también flexibilidad para ligar y transportar un amplio rango de moléculas. Su función oncótica es la propiedad más reconocida que la lleva a introducirse en la terapéutica médica como un expansor de volumen. Sin embargo, en los últimos años se le han adicionado funciones con carácter antioxidante, inmunomodulador y de estabilización endotelial, que hacen presumir que su impacto terapéutico está más allá de sus funciones volumétricas. En los últimos años, específicamente en la cirrosis y la falla hepática aguda sobre crónica, se ha tenido un cambio en el paradigma fisiológico, desde una perspectiva netamente hemodinámica hacia una perspectiva inflamatoria, en donde las funciones oncóticas y no oncóticas de la albúmina están alteradas y tienen un carácter pronóstico en estas entidades. Este conocimiento creciente, desde una perspectiva inflamatoria, hace que se fortalezca el uso terapéutico de la albúmina sérica humana desde las indicaciones tradicionales como prevención de la disfunción circulatoria posparacentesis, prevención y tratamiento de lesión renal aguda, hasta las discusiones para administración a largo plazo en pacientes cirróticos con ascitis.

Human serum albumin is the most abundant protein in plasma, with a molecular structure that provides stability while also allowing flexibility to bind and transport a wide range of molecules. Its oncotic function is the most recognized property, leading to its introduction in medical therapy as a volume expander. However, in recent years, additional functions with antioxidant, immunomodulatory, and endothelial stabilization properties have been identified, suggesting that its therapeutic impact extends beyond its volumetric functions. Specifically, in cirrhosis and acute-on-chronic liver failure, there has been a shift in the pathophysiological paradigm from a purely hemodynamic perspective to an inflammatory perspective, where both oncotic and non-oncotic functions of albumin are altered and have prognostic significance in these conditions. This growing understanding from an inflammatory perspective strengthens the therapeutic use of human serum albumin, not only for traditional indications such as the prevention of post-paracentesis circulatory disfunction, prevention and treatment of acute kidney injury, but also for discussions regarding long-term administration in cirrhotic patients with ascites.

Efecto del confinamiento por COVID-19 en la prevalencia de la enfermedad hepática esteatósica asociada a disfunción metabólica / Effect of COVID-19 lockdown on the prevalence of metabolic dysfunction-associated steatotic liver disease

Introducción. La enfermedad hepática esteatósica asociada a disfunción metabólica (MASLD) es una condición clínica frecuente, relacionada con el sobrepeso, la dislipidemia y la diabetes. Como estos factores de riesgo están a su vez asociados al sedentarismo y la ganancia de peso, se esperaría un impacto como resultado del confinamiento por COVID-19 en la prevalencia de dicha condición. Metodología. Estudio longitudinal retrospectivo en un panel de datos de 132 pacientes de 2017 a 2022, en donde fueron incluidos pacientes con una ecografía hepática y una valoración médica y paraclínica 1,5 años antes y después del periodo de confinamiento (25 de marzo de 2020 a 28 de febrero de 2021). El desenlace primario fue un cambio significativo en la prevalencia de la MASLD, y se utilizó un modelo exploratorio de regresión logística de efectos fijos con panel de datos para hallar los predictores de cambio. Resultados. En un total de 132 pacientes analizados, la prevalencia global de la MASLD antes (31 %; IC95%: 23-39) y después (35,6 %; IC95%: 27,4-43,8) del confinamiento por COVID-19 no cambió significativamente, sin embargo, en las mujeres sí hubo un aumento significativo (RR: 4; IC95%: 1,0004-16). Se encontró una marcada diferencia de prevalencia entre sexos (17 % en mujeres y 46 % en hombres; p=0,001). El confinamiento se asoció a incrementos en la masa corporal (diferencia: +1 kg; IC95%: 0,1-1,9), el colesterol LDL (diferencia: +9,7 mg/dL; IC95%: 4,9-14,4) y al diagnóstico de prediabetes (RR: 2,1; IC95%: 1,4-3,1). La MASLD se asoció positivamente a la preferencia nutricional por la comida rápida (p=0,047). Solo el índice de masa corporal resultó predictor independiente de MASLD (RR: 1,49; IC95%: 1,07-1,93). Conclusión. La prevalencia global de la MASLD no varió después del confinamiento por COVID-19, pero sí se incrementó en mujeres, y algunos de sus factores de riesgo también aumentaron significativamente. Se encontró equivalencia numérica entre la MASLD y la definición previa de la enfermedad. Se requiere un estudio local más grande para desarrollar y validar un mejor modelo predictor del cambio de la MASLD a través del tiempo.

Introduction. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common clinical condition, related to overweight, dyslipidemia and diabetes. As these risk factors are in turn associated with sedentary lifestyle and weight gain, an impact as a result of the COVID-19 confinement on the prevalence of MASLD would be expected. Methodology. Retrospective longitudinal study in a data panel of 132 patients from 2017 to 2022. Patients with a liver ultrasound and a medical and paraclinical assessment 1.5 years before and after the confinement period (March 25, 2020 to February 28, 2021) were included. The primary outcome was a significant change in the prevalence of MASLD, and an exploratory fixed-effects logistic regression model with panel data was used to find predictors of change. Results. In a total of 132 patients analyzed, the overall prevalence of MASLD before (31%, 95%CI: 23-39) and after (35.6%, 95%CI: 27.4-43.8) confinement by COVID-19 did not change significantly, however, in women there was a significant increase (RR: 4, 95%CI: 1.0004-16). A marked difference in prevalence was found between sexes (17% in women and 46% in men; p=0.001). Confinement was associated with increases in body mass (difference: +1 kg, 95%CI: 0.1-1.9), LDL cholesterol (difference: +9.7 mg/dL, 95%CI: 4.9-14.4) and the diagnosis of prediabetes (RR: 2.1, 95%CI: 1.4-3.1). MASLD was positively associated with nutritional preference for fast food (p=0.047). Only body mass index was an independent predictor of MASLD (RR: 1.49, 95%CI: 1.07-1.93). Conclusion. The overall prevalence of MASLD did not change after the COVID-19 lockdown, but it did increase in women, and some of its risk factors also increased significantly. Numerical equivalence was found between MASLD and the previous definition of the disease. A larger local study is required to develop and validate a better predictor model of MASLD change over time.

Hepatic alveolar echinococcosis simulating metastatic malignancy

ABSTRACT Echinococcosis is a parasitic disease caused by infection with tiny tapeworms of the genus Echinococcus. Echinococcosis is classified as either cystic echinococcosis or alveolar echinococcosis. The common form is a zoonosis from goats and sheep that tends to cause liver lesions. The larval stage of Echinococcus multilocularis causes alveolar echinococcosis/alveolar hydatid disease. It is a zoonosis with field mice and tundra voles as intermediate and wild carnivores like foxes and wolves as definitive hosts. This zoonosis is highly uncommon compared to the other form known as cystic echinococcosis but poses a great human threat if untreated. We report the case of a young man who was working in the Kashmir Valley, North India, and presented with jaundice and right upper quadrant abdominal pain. Computed tomography revealed a large solid-cystic intrahepatic lesion measuring 125x118x123 mm, suggestive of a malignant tumor with central necrosis. A liver biopsy showed necrosis with PAS-positive membranes morphologically consistent with echinococcosis. Alveolar echinococcosis can present as a solid-cystic mass in the liver and can simulate metastatic malignancy.

Relationship between skeletal muscle mass loss and metabolic dysfunction-associated fatty liver disease among Chinese patients with metabolic dysregulation

SUMMARY OBJECTIVE: The aim of this study was to explore the correlation between skeletal muscle content and the presence and severity of metabolic dysfunction-associated fatty liver disease in patients with metabolic dysregulation in China. METHODS: A cross-sectional study was conducted among patients from the endocrinology outpatient department at Ningbo First Hospital, in Ningbo, China, in April 2021. Adult patients with metabolic dysregulation who accepted FibroScan ultrasound were included in the study. However, those without clinical data on skeletal muscle mass were excluded. FibroScan ultrasound was used to noninvasively evaluate metabolic dysfunction-associated fatty liver disease. The controlled attenuation parameter was used as an evaluation index for the severity of liver steatosis. Bioelectrical impedance analysis was used to measure the skeletal muscle index. RESULTS: A total of 153 eligible patients with complete data were included in the final analysis. As the grading of liver steatosis intensifies, skeletal muscle index decreases (men: Ptrend<0.001, women: Ptrend=0.001), while body mass index, blood pressure, blood lipid, uric acid, aminotransferase, and homeostatic model assessment of insulin resistance increase (Ptrend<0.01). After adjusting for confounding factors, a negative association between skeletal muscle index and the presence of metabolic dysfunction-associated fatty liver disease was observed in men (OR=0.691, p=0.027) and women (OR=0.614, p=0.022). According to the receiver operating characteristic curve, the best cutoff values of skeletal muscle index for predicting the metabolic dysfunction-associated fatty liver disease presence were 40.37% for men (sensitivity, 87.5%; specificity, 61.5%) and 33.95% for women (sensitivity, 78.6%; specificity, 63.8%). CONCLUSION: Skeletal muscle mass loss among patients with metabolic dysregulation was positively associated with metabolic dysfunction-associated fatty liver disease severity in both sexes. The skeletal muscle index cutoff value could be used to predict metabolic dysfunction-associated fatty liver disease.

Histological findings and NAFLD/NASH Status in liver biopsies of patients subjected to bariatric surgery

ABSTRACT Objective: To investigate nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) and hepatic fibrosis in biopsies of people with obesity who underwent bariatric surgery and examine the possible association of different variables with a diagnosis of NAFLD and NASH. Materials and methods: Epidemiological, clinical and laboratory data from 574 individuals with obesity of both genders seen by the same physician between 2003 and 2009 who had a liver biopsy during bariatric surgery were examined. Results: Of the 437 patients included, 39.8% had some degree of liver fibrosis, 95% had a histologic diagnosis of NAFLD, and the risk factors were age ≥ 28 years and Homeostatic Model Assessment (HOMA) ≥ 2.5 (p = 0.001 and p = 0.016, respectively). In the NAFLD group, NASH was present in 26% of patients and the associated factors were aspartate aminotransferase and alanine aminotransferase index (AST/ALT) > 1, high-density lipoprotein cholesterol (HDL-c) < 40 mg/dL, total cholesterol (TC) ≥ 200 mg/dL, gamma-glutamyl transferase (GGT) > 38 U/L and triglycerides (TG) levels > 150 mg/dL. The independent risk factors were low HDL-c, elevated AST/ALT and high TG. Conclusion: The variables associated with a diagnosis of NAFLD were HOMA ≥ 2.5 and age ≥ 28 years. NASH was associated with low HDL-c, high TG and AST/ALT ≤ 1.

Didymin protects against polystyrene nanoplastic-induced hepatic damage in male albino rats by modulation of Nrf-2/Keap-1 pathway

Polystyrene nanoplastics (PS-NPs) are ubiquitous environmental pollutants that can cause oxidative stress in various organs, including the liver. Didymin is a dietary flavanone that displays multiple pharmacological activities. Therefore, the present study evaluated the palliative role of didymin against PS-NPs-induced hepatic damage in rats. Albino rats (n=48) were randomly distributed into 4 groups: control, PS-NPs treated group, PS-NPs + didymin co-administered group, and didymin supplemented group. After 30 days, PS-NPs intoxication lowered the expression of Nrf-2 and anti-oxidant genes [catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GSR), glutathione-S-transferase (GST), and heme oxygenase-1 (HO-1)], whereas the expression of KEAP1 kelch like ECH associated protein 1 (Keap-1) was increased. PS-NPs exposure also reduced the activities of anti-oxidants enzymes (CAT, SOD, GPx, GSR, GST, GSH, and OH-1), while malondialdehyde (MDA) and reactive oxygen species (ROS) levels were increased. The levels of alanine transaminase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were increased in PS-NPs-exposed rats. Moreover, inflammatory indices [interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), nuclear factor-kappa B (NF-κB), and cyclooxygenase-2 (COX-2)] were increased in PS-NPs-exposed rats. Furthermore, PS-NPs intoxication increased the expressions of apoptotic markers including Bax and Caspase-3, as well as reducing Bcl-2 expression. The histopathological analysis showed significant damage in PS-NPs-treated rats. However, didymin supplementation ameliorated all the PS-NPs-induced damage in the liver of rats. Therefore, it was concluded that didymin can act as a remedy against PS-NPs-induced liver toxicity due to its anti-apoptotic, anti-oxidant, and anti-inflammatory activities.

Antioxidant effect of Rosa pimpinellifolia L. fruit extract on cholestatic liver injury: an experimental study

SUMMARY BACKGROUND: Antioxidants have been considered a rational curative strategy to prevent and cure liver diseases involving oxidative stress. An acute obstructive jaundice rat model was established to investigate the in vivo hepatoprotective efficacy of Rosa pimpinellifolia L. METHODS: The experimental jaundice model was performed by binding the main bile duct in 25 male Sprague-Dawley rats. All rats were randomly divided into five groups: first group: laparotomy-sham-only, second group: biliary tract binding (control), and third, fourth, and fifth groups: treatment groups with 250, 500, and 750 mg/kg fruit extracts daily, respectively. RESULTS: Considering dosage, although there was no significant therapeutic effect in the 250 mg/kg of Rosa pimpinellifolia L. group, the best results were found in the 500 mg/kg dose group, while results in the 750 mg/kg dose group showed consistent correlation with proinflammatory response. With regard to biochemical parameters, lipid hydroperoxide level in the rat serum and liver tissue was significantly decreased in all treatment groups. Amadori products, which are one of the early markers of glycol-oxidative stress, showed statistical significance in the treatment. CONCLUSION: It was revealed that the antioxidant effect of Rosa pimpinellifolia L. was more prominent in the early stages of hepatic injury secondary to oxidative stress.

Frequency of fibrosis in patients with incidentally detected hepatosteatosis

SUMMARY OBJECTIVE: In this study, we aimed to elucidate fibrosis in patients who visited our outpatient clinic with complaints such as abdominal pain and dyspepsia and who had fatty liver by ultrasound imaging. METHODS: A total of 119 patients who were admitted to the gastroenterology outpatient clinic of our institution with incidentally detected hepatosteatosis on ultrasound imaging were included in the study. Patients with hepatosteatosis were examined for fibrosis with the FibroScan-502-touch (Echosens, Paris, France) elastic tissue ultrasonography device. The effects of these parameters on hepatosteatosis and possible fibrosis degree were investigated. RESULTS: No fibrosis was detected in 75 (63.02%) patients with hepatosteatosis on ultrasound imaging, 20 (10.05%) F1, 22 (18.48%) F2, 1 (0.8%) F3, and 0.1 (0.8%) F4. Accordingly, as the degree of steatosis increases in patients with incidentally detected hepatosteatosis, the degree and frequency of fibrosis increase with statistical significance (p<0.05). A statistically significant difference was found between the alanine transaminase increase and the hepatosteatosis degree (p=0.028). The median value of gamma-glutamyltransferase was 15 U/L in S0, 18.5 U/L in S1, 22 U/L in S2, and 26 U/L in S3 (p<0.047). CONCLUSION: To date, no research exists on fibrosis in patients with incidental hepatosteatosis. The outcomes of this study elaborated that patients with hepatosteatosis in the community could be detected at least at an early stage by following up and diagnosing them with serum markers before they progress to end-stage fibrosis.

Hepatic and skeletal muscle tissue immunometabolism in trained rats / Inmunometabolismo del tejido hepático y muscular esquelético de ratas entrenadas / Imunometabolismo tecidual hepático e muscular esquelético de ratos treinados

ABSTRACT Introduction: Physical exercise can be an alternative for preventing and treating the harmful effects of obesity, mainly inflammatory effects on skeletal muscle and liver tissues. However, no consensus exists regarding this purpose's best physical training model. Objective: Evaluate morphological, metabolic, and inflammatory alterations in rats' skeletal and hepatic muscle tissues caused by aerobic and resistance training. Methods: 24 Wistar rats were divided into sedentary (S), aerobic (AE), and resistance training (R) groups. Blood glucose, total cholesterol, and serum triglycerides were measured periodically. After euthanasia, body mass was measured to calculate the total mass gain during the experiment. High-density lipoprotein (HDL) was measured. Adipose tissue was extracted to calculate its percentage relative to body mass and the liver, soleus, and gastrocnemius muscles for morphological analyses and concentrations of glycogen, lipids, and Tumor Necrosis Factor α (TNF-α). The Kruskall-Wallis test and Dunn's post-test were performed for statistical analysis, adopting p<0.05. Results: Both training models reduced the percentage of adipose tissue, body mass gain, and hepatic TNF-α concentration (p<0.05). AE increased serum HDL, gastrocnemius fiber diameter and reduced the fractal dimension in the soleus (p<0.05). R reduced blood glucose and serum and liver lipids, increased liver and soleus glycogen concentrations, increased gastrocnemius fiber diameter, and decreased TNF-α (p<0.05). Conclusion: Both training models reduced body mass, relative visceral adipose tissue, serum total cholesterol concentration, and liver inflammation. However, resistance training was more effective in promoting metabolic effects in the liver and skeletal muscle and reducing muscle inflammation in rats. Level of Evidence V; Expert Opinion.

RESUMEN Introducción: El ejercicio físico puede ser una alternativa para prevenir y tratar los efectos nocivos de la obesidad, principalmente los efectos inflamatorios sobre los tejidos del músculo esquelético y del hígado. Sin embargo, no existe consenso sobre cuál es el mejor modelo de entrenamiento físico para este fin. Objetivo: Evaluar las alteraciones morfológicas, metabólicas e inflamatorias del entrenamiento aeróbico y de resistencia en sobre los tejidos músculo esqueléticos y hepáticos de ratas. Métodos: 24 ratas Wistar se dividieron en grupos sedentarios (S), aeróbicos (AE) y de entrenamiento de resistencia (R). Se midieron periódicamente glucosa en sangre, colesterol total y triglicéridos. Después de la eutanasia, se midió la masa corporal para calcular la ganancia de masa total durante el experimento. Se midió la lipoproteína de alta densidad (HDL). Se extrajo tejido adiposo para calcular su porcentaje relativo a la masa corporal, así como hígado, músculos sóleo y gastrocnemio para análisis morfológicos y concentraciones de glucógeno, lípidos y Factor de Necrosis Tumoral α (TNF-α). Para el análisis estadístico fueron utilizados Kruskall-Wallis y el post-test de Dunn, adoptando p<0,05. Resultados: Ambos entrenamientos redujeron el porcentaje de tejido adiposo, masa corporal y la concentración de TNF-α hepático (p<0,05). AE aumentó el HDL sérico, el diámetro de la fibra del gastrocnemio y redujo la dimensión fractal en el sóleo (p<0,05). R redujo la glucosa en sangre y los lípidos séricos y hepáticos, aumentó las concentraciones de glucógeno hepático y sóleo, aumentó el diámetro de la fibra del gastrocnemio y disminuyó el TNF-α (p<0,05). Conclusión: Ambos modelos de entrenamiento redujeron la masa corporal, el tejido adiposo visceral relativo, la concentración sérica de colesterol total y la inflamación hepática. El entrenamiento de resistencia demostró ser más eficaz para promover los efectos metabólicos en el hígado y el músculo esquelético, además de reducir la inflamación muscular en ratas. Nivel de Evidencia V; Opinión del Especialista.

RESUMO Introdução: O exercício físico pode se apresentar como uma alternativa para prevenção e tratamento de efeitos deletérios da obesidade, principalmente efeitos inflamatórios sobre os tecidos muscular esquelético e hepático. No entanto, não há consenso quanto ao melhor modelo de treinamento físico para tal finalidade. Objetivos: Avaliar alterações morfológicas, metabólicas e inflamatórias dos treinamentos aeróbico e resistido sobre os tecidos muscular esquelético e hepático de ratos. Métodos: 24 ratos Wistar foram divididos nos grupos sedentário (S), treinamento aeróbico (AE) e resistido (R). Glicemia, colesterol total e triglicerídeos séricos foram mensurados periodicamente. Após a eutanásia, a massa corporal foi mensurada para calcular o ganho total de massa durante o experimento. A lipoproteína de alta densidade (HDL) foi dosada. O tecido adiposo foi extraído para cálculo de sua porcentagem relativa à massa corporal assim como o fígado e os músculos sóleo e gastrocnêmio para as análises morfológicas e das concentrações de glicogênio, lipídios e Fator de Necrose Tumoral α (TNF-α). Para análise estatística, foram utilizados o teste de Kruskall-Wallis e o pós-teste de Dunn, adotando-se p<0,05. Resultados: Ambos os modelos de treinamento reduziram o percentual de tecido adiposo, ganho de massa corporal e concentração hepática de TNF-α (p<0,05). AE aumentou o HDL sérico, o diâmetro das fibras do gastrocnêmio e reduziu a dimensão fractal no sóleo (p<0,05). R reduziu a glicemia e os lipídios séricos e hepáticos, aumentou a concentração de glicogênio hepático e sóleo, aumentou o diâmetro das fibras gastrocnêmicas e diminuiu o TNF-α (p<0,05). Conclusão: Ambos os modelos de treinamento reduziram a massa corporal, o tecido adiposo visceral relativo, a concentração sérica de colesterol total e a inflamação hepática. No entanto, o treinamento resistido mostrou-se mais eficaz em promover efeitos metabólicos no fígado e no músculo esquelético, além de reduzir a inflamação muscular em ratos. Nível de Evidência V; Opinião do Especialista.

Molecular genetic association of rs8099917 and rs1800795 polymorphisms in the progression of hepatitis Delta virus liver disease

Background: The relationship between viral infections and host factors holds high hopes for identifying the role of Interferon Lambda 3 (IFNL3) and Interleukin 6 (IL-6) polymorphisms in the development of Chronic Liver Disease (CLD) in patients infected with hepatitis Delta virus (HDV) in the Western Brazilian Amazon. Methods: Cross-sectional study conducted with a cohort of 40 chronic HDV patients, 27 with CLD and 13 without evident liver damage. Biological samples from the participants were analyzed using the polymerase chain reaction (PCR) technique, followed by sequencing by the automated Sanger method. Results: The rs8099917 T allele, from the IFNL3 gene, showed a higher frequency in both groups; however, it was not possible to establish an association with HDV infection [OR = 1.42 (0.42 - 4.75; p = 0.556 (95% CI). For IL-6, the rs1800795 G allele was superior to rs1800795 C. Analyzing both distributions in the studied groups, any association with HDV was absent (p > 0.05). Conclusion: The results suggest that the rs8099917 T/G (IFNL3) and rs1800795 G/C (IL-6) polymorphisms are not associated with the evolution of HDV in the studied population.