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.

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.

Clinical application value of a predictive model for the efficacy of third-generation cephalosporin in treatment of community-acquired spontaneous bacterial peritonitis / 临床肝胆病杂志

ObjectiveTo investigate the clinical application value of a predictive model for the efficacy of third-generation cephalosporin in the treatment of community-acquired spontaneous bacterial peritonitis （CASBP）. MethodsThis prospective study was conducted among 50 patients with liver cirrhosis and CASBP who were admitted to The Ninth Hospital of Nanchang from January 2021 to June 2022， and the patients were randomly divided into optimized treatment group and traditional treatment group， with 25 patients in each group. The patients in the optimized treatment group received ceftazidime or imipenem for initial treatment based on the above predictive model， and those in the traditional treatment group received ceftazidime for initial treatment， with the subsequent use of antibiotics adjusted based on the efficacy of initial treatment. The two groups were compared in terms of the response rate of initial treatment， cure rate on day 5， and 30-day mortality rate. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsAll patients completed the study. The optimized treatment group had a significantly higher response rate of initial treatment than the traditional treatment group （88.0% vs 60.0%， χ2=5.094， P=0.024）， while there was no significant difference in the cure rate on day 5 between the two groups （80.0% vs 56.6%， χ2=3.309， P=0.069）. As for the patients who received ceftazidime for initial treatment， the optimized treatment group had a significantly higher response rate of initial treatment than the traditional treatment group （88.9% vs 60.0%， χ2=4.341， P=0.037）， while there was no significant difference in the cure rate on day 5 between the two groups （83.3% vs 56.0%， χ2=2.425， P=0.119）. There was no significant difference in 30-day mortality rate between the two groups （8.0% vs 20.0%， χ2=0.664， P=0.415）. For all patients， there was a significant association between response of initial treatment and cure on day 5 （odds ratio ［OR］=9.643， 95% confidence interval ［CI］： 2.292‍ — ‍40.564） and between cure on day 5 and 30-day mortality （OR=0.138， 95%CI： 0.023‍ — ‍0.813）. ConclusionThis predictive model for efficacy helps clinicians to identify the patients who can benefit from third-generation cephalosporin treatment and improve the efficacy of third-generation cephalosporin in the initial empirical treatment of CASBP.

Value of platelet-albumin-bilirubin index combined with AIMS65 score in predicting the short-term prognosis of patients with liver cirrhosis and acute upper gastrointestinal bleeding / 临床肝胆病杂志

ObjectiveTo investigate the value of platelet-albumin-bilirubin index （PALBI） combined with AIMS65 score in predicting rebleeding and death within 6 weeks after admission in patients with liver cirrhosis and acute upper gastrointestinal bleeding （AUGIB）. MethodsA retrospective study was conducted for 238 patients with liver cirrhosis and AUGIB who were hospitalized in The First Affiliated Hospital of Jinzhou Medical University from February 2021 to October 2022， and all patients were followed up for 6 weeks. According to the prognosis， they were divided into death group with 65 patients and survival group with 173 patients， and according to the presence or absence of rebleeding， they were divided into non-rebleeding group with 149 patients and rebleeding group with 89 patients. General data and laboratory markers （including blood routine， liver/renal function， and coagulation）， and PALBI， AIMS65 score， Child-Turcotte-Pugh （CTP） score， and Model for End-stage Liver Disease （MELD） score were calculated on admission. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. A multivariate logistic regression model analysis was used to investigate the risk factors for death or rebleeding within 6 weeks after admission in patients with liver cirrhosis and AUGIB. The receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to investigate the predictive efficacy of each scoring system， and the DeLong test was used for comparison of AUC. ResultsThere were significant differences between the death group and the survival group in hematemesis， past history of varices， albumin （Alb）， total bilirubin （TBil）， international normalized ratio （INR）， creatinine （Cr）， prothrombin time （PT）， systolic blood pressure， PALBI， AIMS65 score， CTP score， and MELD score （all P<0.05）. The multivariate logistic regression analysis showed that hematemesis （odds ratio ［OR］=4.34， 95% confidence interval ［CI］： 1.88‍ ‍—‍ ‍10.05， P<0.001）， past history of varices （OR=3.51， 95%CI： 1.37‍ ‍—‍ ‍8.98， P=0.009）， PALBI （OR=4.49， 95%CI： 1.48‍ ‍—‍ ‍13.64， P=0.008）， and AIMS65 score （OR=3.85， 95%CI： 2.35‍ ‍—‍ ‍6.30， P<0.001） were independent risk factors for death. The ROC curve analysis of each scoring system in predicting survival showed that CTP score， MELD score， PALBI， AIMS65 score， and PALBI combined with AIMS65 score had an AUC of 0.758， 0.798， 0.789， 0.870， and 0.888， respectively， suggesting that PALBI combined with AIMS65 score had a significantly larger AUC than the four scoring systems used alone （all P<0.05）. There were significant differences between the rebleeding group and the non-rebleeding group in hematemesis， history of diabetes， Alb， TBil， INR， Cr， PT， PALBI， AIMS65 score， CTP score， and MELD score （all P<0.05）. The multivariate logistic regression analysis showed that PALBI （OR=2.41， 95%CI： 1.17‍ ‍—‍ ‍4.95， P=0.017） and AIMS65 score （OR=1.58， 95%CI： 1.17‍ ‍—‍ ‍2.15， P=0.003） were independent risk factors for rebleeding. The ROC curve analysis of each scoring system in predicting rebleeding showed that CTP score， MELD score， PALBI， AIMS65 score， and PALBI combined with AIMS65 score had an AUC of 0.680， 0.719， 0.709， 0.711， and 0.741， respectively， suggesting that PALBI combined with AIMS65 score had the largest AUC （all P<0.05）， but with a relatively low specificity. ConclusionPALBI combined with AIMS65 score has a certain value in predicting death within 6 weeks after admission in patients with liver cirrhosis and AUGIB， with a better value than CTP score and MELD score alone. PALBI combined with AIMS65 score has a relatively low value in predicting rebleeding within 6 weeks， with an acceptable accuracy.

Portal vein thrombosis in liver cirrhosis： Risk factors and protection strategies / 临床肝胆病杂志

Portal vein thrombosis （PVT） is one of the common complications during the natural course of liver cirrhosis and has an important influence on the progression of liver cirrhosis. This article mainly summarizes the research advances in the risk factors for PVT. There are many risk factors for PVT， and Virchow’s triad， namely venous stasis， hypercoagulability， and vascular endothelial injury and systemic inflammation caused by surgery or trauma， are considered the main reasons for the development and progression of PVT. At present， more prospective studies are still needed to validate the predictive models for the risk of PVT that have certain application prospects in clinical practice. Cirrhotic patients with PVT tend to have a poor prognosis， and complete obstructive PVT is associated with increased mortality after liver transplantation. Recent studies have shown that prophylactic anticoagulant therapy is safe and effective in patients with liver cirrhosis and can thus help with the prevention and treatment of PVT.

Therapeutic effect of transplantation of bone marrow mesenchymal stem cells co-cultured with bone marrow M2 macrophages on a rat model of liver cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the effect of transplantation of bone marrow mesenchymal stem cells （BMSCs） co-cultured with bone marrow-derived M2 macrophages （M2-BMDMs）， named as BMSCM2， on a rat model of liver cirrhosis induced by carbon tetrachloride （CCl4）/2-acetaminofluorene （2-AAF）. MethodsRat BMDMs were isolated and polarized into M2 phenotype， and rat BMSCs were isolated and co-cultured with M2-BMDMs at the third generation to obtain BMSCM2. The rats were given subcutaneous injection of CCl4 for 6 weeks to establish a model of liver cirrhosis， and then they were randomly divided into model group （M group）， BMSC group， and BMSCM2 group， with 6 rats in each group. A normal group （N group） with 6 rats was also established. Since week 7， the model rats were given 2-AAF by gavage in addition to the subcutaneous injection of CCl4. Samples were collected at the end of week 10 to observe liver function， liver histopathology， and hydroxyproline （Hyp） content in liver tissue， as well as changes in the markers for hepatic stellate cells， hepatic progenitor cells， cholangiocytes， and hepatocytes. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the N group， the M group had significant increases in the activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） （P<0.01）； compared with the M group， the BMSC and BMSCM2 groups had significant reductions in ALT and AST （P<0.01）， and the BMSCM2 group had significantly better activities than the BMSC group （P<0.05）. Compared with the N group， the M group had significant increases in Hyp content and the mRNA and protein expression levels of alpha-smooth muscle actin （α-SMA） in the liver （P<0.01）； compared with the M group， the BMSC and BMSCM2 groups had significant reductions in Hyp content and the expression of α-SMA （P<0.05）， and the BMSCM2 group had a significantly lower level of α-SMA than the BMSC group （P<0.01）. Compared with the N group， the M group had significant increases in the mRNA expression levels of the hepatic progenitor cell markers EpCam and Sox9 and the cholangiocyte markers CK7 and CK19 （P<0.01） and significant reductions in the expression levels of the hepatocyte markers HNF-4α and Alb （P<0.01）； compared with the M group， the BMSC and BMSCM2 groups had significant reductions in the mRNA expression levels of EpCam， Sox9， CK7， and CK19 （P<0.05） and significant increases in the mRNA expression levels of HNF-4α and Alb （P<0.05）， and compared with the BMSC group， the BMSCM2 group had significant reductions in the mRNA expression levels of EpCam and CK19 （P<0.05） and significant increase in the expression level of HNF-4α （P<0.05）. ConclusionM2-BMDMs can enhance the therapeutic effect of BMSCs on CCl4/2-AAF-induced liver cirrhosis in rats， which provides new ideas for further improving the therapeutic effect of BMSCs on liver cirrhosis.

Efficacy of percutaneous transhepatic variceal embolization alone or in combination with partial splenic embolization in treatment of portal hypertensive hemorrhage in liver cirrhosis： A Meta-analysis / 临床肝胆病杂志

ObjectiveTo investigate the efficacy of percutaneous transhepatic variceal embolization （PTVE） alone or in combination with partial splenic embolization （PSE） in the treatment of portal hypertensive hemorrhage in liver cirrhosis through a meta-analysis. MethodsThis study was conducted according to PRISMA guideline， with a PROSPERO registration number of CRD42023396690. Wanfang Med Online， CNKI， CBM， VIP Databases， PubMed， Embase， the Cochrane Library， and Web of Science databases were searched for articles on PTVE alone or in combination with PSE in the treatment of portal hypertensive hemorrhage in liver cirrhosis published up to December 23， 2022. The articles were selected based on inclusion and exclusion criteria， and related data were extracted. The RevMan 5.4.1 statistical analysis software was used to perform the meta-analysis. ResultsEight articles were finally included， with a total sample size of 592 cases， among which there were 316 cases in the PTVE+PSE group and 276 cases in the PTVE group. The meta-analysis showed that compared with the PTVE group， the PTVE+PSE group had significantly lower postoperative portal vein pressure （standardized mean difference ［SMD］=-1.75， 95% confidence interval ［CI］： -2.33 to -1.16， P<0.05）， postoperative diameter of the portal vein （SMD=-0.87， 95%CI： -1.64 to -0.10， P<0.05）， postoperative rebleeding rate （odds ratio ［OR］=0.17， 95%CI： 0.11 — 0.28， P<0.05）， mortality rate （OR=0.13， 95%CI： 0.04 — 0.37， P<0.05）， and incidence rate of postoperative portal hypertensive gastrointestinal disease （OR=0.17， 95%CI： 0.07 — 0.45， P<0.05］， as well as a significantly higher postoperative platelet level （SMD=0.79， 95%CI： 0.52 — 1.06， P<0.05）， while there were no significant differences between the two groups in the incidence rates of postoperative ascites. ConclusionCompared with PTVE alone， PTVE combined with PSE can effectively reduce the rebleeding rate and mortality rate of portal hypertensive hemorrhage in liver cirrhosis， the incidence rate of portal hypertensive gastrointestinal disease， and portal vein pressure， and it can also shorten the diameter of the portal vein and increase platelet level. Therefore， it is an effective interventional method for the treatment of portal hypertension hemorrhage in liver cirrhosis.

Characteristics of the composition of intestinal flora in cirrhotic patients with malnutrition / 临床肝胆病杂志

ObjectiveTo investigate the characteristics of the composition of intestinal flora and the serum level of endotoxin in cirrhotic patients with malnutrition， and to provide new diagnosis and treatment ideas for improving the nutritional status of patients with liver cirrhosis. MethodsA total of 58 patients with liver cirrhosis who were hospitalized in Department of Gastroenterology， People’s Hospital of Zhengzhou， from March 2021 to November 2022 were enrolled as experimental group （LC group）， and according to the Royal Free Hospital-Nutritional Prioritizing Tool， they were divided into low malnutrition risk group （LC-A group with 28 patients） and moderate/high malnutrition risk group （LC-B group with 30 patients）； 25 individuals who underwent physical examination during the same period of time were enrolled as control group （HC group）. Peripheral blood and feces samples were collected from all subjects. The limulus amebocyte lysate gel method was used to measure the concentration of endotoxin in peripheral blood， and high-throughput sequencing and bioinformatics analysis were used to investigate the characteristics of intestinal flora. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test were used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups. The chi-square test was used for comparison of categorical data between groups. The Spearman test was used for correlation analysis. ResultsThere were significant differences between the three groups in the levels of alanine aminotransferase （H=7.054， P<0.05）， gamma-glutamyl transpeptidase （H=9.644， P<0.05）， albumin （Alb） （F=32.768， P<0.05）， total bilirubin （TBil） （H=20.980， P<0.05）， and serum endotoxin （F=108.672， P<0.05）. There was a significant difference in Chao1 index between the three groups （F=5.110， P=0.008） and between the HC group and the LC-B group （P<0.05）. Compared with the HC group， the LC-A group and the LC-B group had significant reductions in Chao1 index and Shannon index， and there was a significant difference in Chao1 index between the HC group and the LC-B group （P<0.05）. At the phylum level， the intestinal flora in each group was mainly composed of Bacteroidota， Firmicutes， Proteobacteria， and Actinobacteriota， accounting for more than 95% of all phyla， and there was a significant difference in the relative abundance of Firmicutes between the HC group and the LC-B group （P<0.05）. Serum endotoxin was significantly negatively correlated with Ruminococcaceae （r=-0.420， P=0.007）， and spirochete was significantly positively correlated with TBil （r=0.419， P=0.007） and was significantly negatively correlated with Alb （r=-0.492， P=0.001）. ConclusionThere are unique changes in intestinal flora in cirrhotic patients with malnutrition， and differentially expressed flora are associated with endotoxemia. Improving intestinal microecology in liver cirrhosis may help to improve nutritional status.

An excerpt of Asia-Pacific Association for the Study of the Liver guidelines on management of ascites in liver disease （2023） / 临床肝胆病杂志

Asia-Pacific Association for the Study of the Liver published the guidelines on management of ascites in liver disease in May 2023， which introduces the diagnosis， differential diagnosis， and treatment of ascites， hyponatremia， hepatic hydrothorax， and hepatorenal syndrome in patients with liver cirrhosis and acute-on-chronic liver failure. This article summarizes the main recommendations in the guidelines， so as to provide a reference for the treatment of ascites in patients with liver diseases in China.

An excerpt of AASLD practice guidance on risk stratification and management of portal hypertension and varices in cirrhosis （2023） / 临床肝胆病杂志

This Practice Guidance intends to coalesce best practice recommendations for the identification of portal hypertension （PH）， for prevention of initial hepatic decompensation， for the management of acute variceal hemorrhage （AVH）， and for reduction of the risk of recurrent variceal hemorrhage in chronic liver disease. The most significant changes in the current Guidance relate to recognition of the concept of compensated advanced chronic liver disease， codification of methodology to use noninvasive assessments to identify clinically significant PH （CSPH）， and endorsement of a change in paradigm with the recommendation of early utilization of nonselective beta-blocker therapy when CSPH is identified. The updated guidance further explores potential future pharmacotherapy options for PH， clarifies the role of preemptive transjugular intrahepatic portosystemic shunt in AVH， discusses more recent data related to the management of cardiofundal varices， and addresses new topics such as portal hypertensive gastropathy and endoscopy prior to transesophageal echocardiography and antineoplastic therapy.

Effect of Fuzheng Huayu prescription on hepatocyte extinction and regeneration in a mouse model of liver cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the effect of Fuzheng Huayu prescription on hepatocyte extinction and regeneration in fibrotic liver and its mechanism of action in promoting hepatocyte regeneration. MethodsMice were given intraperitoneal injection of CCl4 for 6 weeks to establish a model of liver cirrhosis， and there were 10 mice in the model group， 10 in the sorafenib group， 10 in the Fuzheng Huayu prescription group， and 9 in the normal control group. Since week 4 of modeling， the mice in the Fuzheng Huayu prescription group and the sorafenib group were given the corresponding drug by gavage at a dose of 4.8 g/kg and 4 mg/kg， respectively， for three consecutive weeks， and those in the normal group and the model group were given an equal volume of sodium carboxymethyl cellulose. Serum liver function parameters were measured； the METAVIR scoring system was used to evaluate liver inflammation and fibrosis stage； Sirius Red staining and hydroxyproline （Hyp） content in liver tissue were used to evaluate collagen deposition； immunohistochemistry was used to measure the protein expression levels of type IV collagen， CD31， CD32b， Ki67， CyclinD1， glutamine synthetase， Wnt2， and HGF， and Western blot was used to measure the expression levels of Wnt2， LRP6， β-catenin， p-β-catenin， and CyclinD1 in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， the Fuzheng Huayu prescription group and the sorafenib group showed the following changes： significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of Hyp in liver tissue （all P<0.01）； a significant reduction in METAVIR score； significant reductions in the expression levels of type Ⅳ collagen and CD31 （all P<0.05） and a significant increase in the expression level of CD32b （P<0.01）； significant reductions in the number of parenchymal extinction lesions and significant increases in the expression levels of Ki67 and CyclinD1 in liver tissue （all P<0.01）； significant increases in the protein expression levels of Wnt2， LRP6， β-catenin， and CyclinD1 and a significant reduction in the protein expression level of p-β-catenin （all P<0.05）； significant increases in the number of cells stained positive for both CD32b and Wnt2. ConclusionFuzheng Huayu prescription can inhibit hepatic sinusoidal capillarization， improve the Wnt2 exocrine function of liver sinusoidal endothelial cells， activate the Wnt/β-catenin signaling pathway associated with hepatocyte regeneration， and finally reverse liver cirrhosis.

The preliminary therapeutic effect of endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips in treatment of cirrhotic patients with gastric varices and gastric-renal shunt / 临床肝胆病杂志

ObjectiveTo investigate the safety and efficacy of endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips in the treatment of cirrhotic patients with gastric varices and gastric-renal shunt （GRS）. MethodsThe patients who attended Beijing Ditan Hospital， Capital Medical University， due to liver cirrhosis and gastric varices from February to June 2023 were enrolled， and all patients were confirmed to have GRS and received endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips. The primary evaluation index was alleviation or disappearance of varicose veins after surgery， and the secondary evaluation indices were surgical completion and complications. ResultsA total of 11 patients were enrolled in this study， among whom there were 7 male patients and 4 female patients， with a median age of 55 years. Of all patients， 1 had Child class A liver function， 7 had Child class B liver function， and 3 had Child class C liver function. The maximum （median） diameter of the shunt was 8 mm， and the minimum （median） diameter of the shunt was 4 mm. The median blood flow velocity of the target vessel was 11 cm/s before treatment and 5 cm/s after occlusion with metal clips. The median amount of tissue adhesive injected was 2 mL， and the amount of lauromacrogol used was 1 mL. Disappearance of blood flow signals was observed in all patients after surgery （100%）， and the success rate of surgery was 100%. No patient experienced rebleeding after follow-up for 6 weeks. Gastroscopy at 1 month after surgery showed that gastric varices were eradicated or almost disappeared in 9 patients and were alleviated in 2 patients. ConclusionEndoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips is a feasible， safe， and effective treatment method for cirrhotic patients with gastric varices and GRS.

Changing trend of the disease burden of liver cirrhosis in China from 1990 to 2019 / 临床肝胆病杂志

ObjectiveTo investigate the prevalence of liver cirrhosis and the changing trend of the disease burden of liver cirrhosis in the Chinese population from 1990 to 2019， and to provide a data reference for formulating the prevention and treatment strategies for liver cirrhosis in China. MethodsThe Global Burden of Disease Study 2019 was used to collect the data on the incidence rate， mortality rate， disability-adjusted life years （DALY）， years of life lost （YLL）， and years lived with disability （YLD） of liver cirrhosis. The Joinpoint regression model was used to analyze the changing trend of disease burden； the age-period-cohort （APC） model was used to evaluate age， period， and cohort effects； R software BAPC package was used to predict future changes in disease burden. ResultsFrom 1990 to 2019 in China， there were increases in the numbers of liver cirrhosis cases and prevalent cases in the general population， as well as in the male and female populations， while there was a reduction in the number of deaths. From 1990 to 2019， the standardized incidence rate， standardized prevalence rate， and standardized mortality rate of liver cirrhosis in the Chinese population showed a downward trend， with a mean annual reduction of 0.62% （95% confidence interval ［CI］： -0.74% to -0.50%， t=9.99， P<0.001）， 0.44% （95%CI： -0.53% to -0.35%， t=13.18， P<0.001）， and 3.02% （95%CI： -3.12% to -2.93%， t=7.58， P<0.001）， respectively. From 1990 to 2019， the standardized DALY， YLL， and YLD rates of liver cirrhosis in the Chinese population also showed a downward trend， with a mean annual reduction of 3.27% （95%CI： -3.37% to -3.18%， t=6.22， P<0.001）， 3.32% （95%CI： -3.42% to -3.22%， t=9.31， P<0.001）， and 1.42% （95%CI： -1.49% to -1.34%， t=4.93， P<0.001）， respectively. From 1990 to 2019， the incidence rate of liver cirrhosis in the Chinese population first increased and then decreased with age， while the mortality rate showed an increasing trend， and the risks of disease onset and death showed a decreasing trend with time and birth cohort. The predictive model showed that the standardized incidence rate， prevalence rate， mortality rate， and DALY rate of liver cirrhosis in China will show a decreasing trend from 2020 to 2030. Alcohol was the most important risk factor for both male and female populations， followed by medication. ConclusionThe disease burden of liver cirrhosis in China shows a decreasing trend from 1990 to 2019， with sex and age differences， especially in the middle-aged male population. Effective measures should be taken for intervention.

An excerpt of American Association for the Study of Liver Diseases practice guidance on acute-on-chronic liver failure and the management of critically ill patients with cirrhosis in 2023 / 临床肝胆病杂志

The expert panel of American Association for the Study of Liver Diseases published Practice guidance on acute-on-chronic liver failure and the management of critically ill patients with cirrhosis on November 9， 2023 in Hepatology. This practice guidance elaborates on the definition of acute-on-chronic liver failure， prediction models， and the management of liver cirrhosis comorbid with acute-on-chronic liver failure and organ failure in critically ill patients， and this article gives an excerpt of the key points in the practice guidance.

Survival rate and quality of life in patients with liver cirrhosis complicated with bacterial infection / 公共卫生与预防医学

Objective To analyze the short-term survival and prognostic quality of life of patients with liver cirrhosis complicated by bacterial infection. Methods This study collected and analyzed 300 patients with liver cirrhosis complicated with infection who were hospitalized in the First Affiliated Hospital of Hebei North University, and followed up to discuss their survival and quality of life. Results In this study, the top two causes of infection were spontaneous bacterial peritonitis (60.67% of patients) and pneumonia (50.67% of patients). The second causes were urinary tract infections (15.33%), gastrointestinal infections (12.33%), and other causes. There was no statistically significant difference between male and female patients (P>0.05). In addition, the proportion of hospital infections was 71.00%, and there was no statistically significant difference between male and female patients (P>0.05). A total of 353 strains of pathogenic bacteria were isolated in this study (73.37% of patients with hospital infections). The distribution analysis of pathogenic bacteria showed that the highest proportion of ECO was 35.98%, followed by Klebsiella pneumoniae (18.98%). The distribution trend of 259 strains of pathogenic bacteria among hospital patients was consistent with that of all strains, and the difference was not statistically significant (P>0.05). Gram negative bacteria accounted for 79.60% (281/353) of all detected strains, of which Escherichia coli was mostly detected in patients with spontaneous bacterial peritonitis, Klebsiella Pneumoniae (KPN) and Pseudomonas aeruginosa (PAE) were mostly detected in patients with pneumonia, and Enterococcus (ENF) was mostly detected in patients with urinary tract infection; Among gram-negative bacteria, Staphylococcus epidermidis (SEP) and Staphylococcus aureus (SAU) are mostly found in patients with other infectious causes (blood flow infection, etc.) , and Streptococcus (STR) accounts for a high proportion in patients with Spontaneous bacterial peritonitis. In this study, 9 cases of death prognosis were detected during follow-up, and there was no statistically significant difference in the detection of death prognosis between different bacterial strains in both genders, as well as the difference in detection of death prognosis between hospital infections and out of hospital infections in both genders (P>0.05). There was no statistically significant difference in the detection of death prognosis between males and females due to different causes of infection, P>0.05. The quality of life scores of 291 surviving patients were compared between baseline and follow-up, indicating an increase in follow-up scores, especially in the dimensions of physiological function and physical pain. There was no statistically significant difference between different bacterial strains, infection causes, and hospital/non hospital infections (P>0.05) . Conclusion Spontaneous bacterial peritonitis and pneumonia are the main causes of infection that deserve special attention, and the main pathogens of infection are Gram negative bacteria. Targeted treatment and rehabilitation should be provided for patients with liver cirrhosis complicated by infection. At the same time, the proportion of hospital infections is relatively high, and attention should be paid to, prevention and control measures should be implemented as well.