Anormalidades hematológicas en enfermedad hepática, fisiopatología y consideraciones terapéuticas / Hematologic disorders in liver failure: pathophysiology and therapeutic considerations

RESUMEN Las alteraciones en los recuentos celulares sanguíneos representan los hallazgos clínicos más notorios y recurrentes en pacientes que padecen enfermedad hepática, tanto aguda como crónica. Estos cambios constituyen un marcador importante de la disfunción hepática y, a menudo, desempeñan un papel crucial en la evaluación y manejo de estos pacientes. En conjunto con el alargamiento de las pruebas de coagulación, la trombocitopenia es la irregularidad más prevalente en estos individuos. Esta condición, así como las leucopenias, se le atribuye en gran medida al hiperesplenismo, una alteración en la que el bazo retiene y destruye las células sanguíneas, incluidas las plaquetas. Sin embargo, cuando el conteo plaquetario desciende por debajo de 10 x 103/µl, es fundamental considerar otras causas, como factores autoinmunitarios que pueden estar contribuyendo con la trombocitopenia. La anemia, definida como una disminución en el número de glóbulos rojos o en los niveles de hemoglobina, es otra característica constante que acompaña a la enfermedad hepática. Aunque en la mayoría de los casos la anemia es macrocítica, en algunas situaciones puede ser secundaria a eventos hemolíticos, como lo observado en el síndrome de Zieve. Esta diversidad en las manifestaciones de la anemia en pacientes hepáticos subraya la complejidad de las interacciones entre el hígado y los componentes sanguíneos. A pesar de los avances en la comprensión de las causas subyacentes de estas citopenias, las opciones del tratamiento siguen siendo limitadas. Generalmente, las opciones terapéuticas se enfocan en la administración de transfusiones de hemocomponentes para compensar las deficiencias en los recuentos celulares o en el uso de análogos de trombopoyetina (TPO) para estimular temporalmente la producción de las plaquetas en la medula ósea. No obstante, estos tratamientos tienden a abordar los síntomas más que las causas fundamentales de las alteraciones hematológicas en la enfermedad hepática. La persistencia y el empeoramiento de estas alteraciones pueden servir como indicadores tempranos de la progresión de la disfunción hepática. La relación intrincada entre el hígado y la homeostasis hematológica continúa siendo objeto de investigación, la compresión más profunda de estos mecanismos podría abrir potencialmente la puerta hacia enfoques terapéuticos más específicos y efectivos para abordar las citopenias en el contexto de la enfermedad hepática.

ABSTRACT Alterations in blood cell counts are the most prominent and recurrent clinical findings among patients suffering from both acute and chronic liver disease. These changes are an important marker of liver failure and often play a key role in the evaluation and management of these patients. Together with the prolongation of coagulation tests, thrombocytopenia is the most common disorder among these individuals. This condition, as well as leukopenia, is largely attributable to hypersplenism, a disorder in which the spleen retains and destroys blood cells, including platelets. However, when the platelet count drops below 10x103/µl, it is essential to consider other causes, such as autoimmune factors that may be contributing to the development of thrombocytopenia. Anemia, defined as a decrease in red blood cell count or hemoglobin levels, is another common characteristic of liver disease. Although in most cases macrocytic anemia occurs, in some situations it can be secondary to hemolytic events, as observed in Zieve's syndrome. This wide range of manifestations of anemia among liver patients highlights the complex interaction between liver and blood components. Despite advances in understanding the underlying causes of these cytopenias, treatment options remain limited. Therapeutic options generally focus on the transfusion of blood products to compensate for deficiencies in cell counts or on the use of thrombopoietin (TPO) analogues to temporarily stimulate platelet production in the bone marrow. However, these treatments tend to address the symptoms rather than the root causes of hematologic disorders in liver disease. The persistence and worsening of these disorders may serve as early indicators of the progression of liver failure. The complicated relationship between liver and hematological homeostasis remains the subject of research. A deeper understanding of these mechanisms could potentially open the door toward more targeted and effective therapeutic approaches to address cytopenias in the context of liver disease.

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.

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.

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.

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.

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.

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.

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.

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.

Clinical study of ICG-R15 combined with three-dimensional image reconstruction technology in preoperative evaluation of liver cancer / 重庆医学

Objective To explore the advantages of indocyanine green clearance rate at 15 min(ICG-R15)combined with three-dimensional image reconstruction technology in preoperativ evaluation of liver cancer,as well as its impact on the efficacy of liver resection surgery.Methods The data of the patients with liver cancer undergoing preoperative three-dimensional image reconstruction evaluation(experimental group,n=65)and traditional CT evaluation(control group,n=70)in the Jining Municipal First People's Hospital from January 2018 to January 2021 were retrospectively analyzed.All patients performed the ICG-R15 test be-fore operation.In the experimental group,45 cases adopted laparotomy and 20 cases adopted laparoscopic sur-gery,which in the control group had 50 cases and 20 cases,respectively.The data of preoperative laboratory tests,intraoperative related indicators and postoperative laboratory tests were collected in the two groups.The influences between the two kinds of evaluation modes on the effects of laparotomy and laparoscopic surgery in liver cancer were compared.Results In laparotomy,compared with the control group,the operation time and postoperative drainage tube extraction time in the experimental group were significantly shortened,the intrao-perative bleeding volume was significantly decreased,the incidence rate of postoperative complications,direct bilirubin and AST levers on 7 d after operation were significantly decreased(P＜0.05);there were no statis-tically significant differences in the intraoperative blood transfusion rate,postoperative hospitalization dura-tion,levels of total bilirubin,ALT and albumin and prothrombin time on 7 d after operation between the two groups(P＞0.05).In laparoscopic surgery,compared with the control group,the postoperative hospitalization duration and postoperative drainage tube extraction time in the experimental group were significantly short-ened,the levels of AST and ALT on 7 d after operation were significantly decreased(P＜0.05);there was no statistically significant difference in the other observation indicators between the two groups(P＞0.05);in the control group,3 cases were converted to laparotomy due to inability to excision during laparoscopic explo-ration.Compared with the control group,the accuracy rate of preoperative evaluation of the number of liver tumors and Couinaud segmentation localization(96.9％vs.85.7％)and preoperative evaluation of liver vas-cular variation(100.0％vs.53.8％)were increased in the experimental group,the percentage of the patients with actual resection range greater than preoperative prediction range was lower(7.7％vs.20.0％),and the differences were statistically significant(P＜0.05).There was no statistically significant difference in the accu-racy of preoperative evaluation of portal vein invasion between the two groups(P＞0.05).Conclusion ICG-R15 combined with three dimensional reconstruction technology in preoperatively assessing liver cancer has more advantages compared with combined traditional CT,moreover which is conducive to reduce intraoperative bleeding,shorten operation time and has the positive effect on the patients'prognosis.

Risk factors for myocardial injury in esophagogastric variceal bleeding patients with cirrhosis / 陆军军医大学学报

Objective To explore the risk factors for myocardial injury in esophagogastric variceal bleeding(EGVB)patients with liver cirrhosis during hospitalization.Methods A case-control trial was conducted on 235 EGVB patients admitted to our hospital between May 2021 and July 2022.Their basic information,laboratory results and relevant data during hospitalization were collected.According to their myocardial enzyme profiles during hospitalization,they were divided into myocardial injury group(n=46)and non-myocardial injury group(n=189).Univariate regression analysis and clinical correlation analysis were used to preliminarily screen the risk factors for myocardial injury secondary to EGVB caused by liver cirrhosis.Then,multivariate logistic regression analysis was used to further screen the risk factors.A nomogram was constructed based on the selected risk factors and the occurrence of myocardial injury.Receiver operating characteristic(ROC)curve was plotted to analyze the independent predictive value of these factors alone or combined together.Calibration curve analysis and internal verification were utilized to evaluate the predictive performance of the nomogram model.Subgroup verification was performed in the myocardial infarction group.Results Univariate analysis revealed that statistical differences were observed in age,sex,hypertension,renal disease,underlying diseases,vomiting,leukocytosis,increased alanine aminotransferase(ALT)or aspartate aminotransferase(AST),albumin,red blood cell hematocrit(HCT),international normalized ratio(INR),endoscopy within 6 h after admission,and Child-Pugh(CP)class between the myocardial injury group and the non-myocardial injury group(P＜0.01).Multivariate logistic regression analysis showed that age(P=0.014,OR=1.153,95％CI:1.030～1.291),underlying diseases(P=0.005,OR=1.122,95％CI:1.032～2.437),and albumin(P=0.012,OR=0.449,95％CI:0.241～0.837)were independent risk factors for inhospital myocardial injury in EGVB patients with liver cirrhosis.The AUC value of the above indicators combined together for predicting myocardial injury was 0.902.Hosmer-Lemeshow test and calibration curve analysis indicated that the nomogram had good prediction consistency(Chi-square=12.88,P=0.615).Internal verification correctly distinguished 86.4％of verification objects.Subgroup analysis of myocardial injury patients showed that albumin was also an independent risk factor for in-hospital myocardial injury in this population(AUC=0.80).Conclusion Age,underlying diseases,and albumin level are independent risk factors for in-hospital myocardial injury in EGVB patients with liver cirrhosis.Albumin level can be used as an independent risk factor for predicting myocardial infarction.Combination of the above 3 indicators has a high diagnostic value in early identification and prevention of myocardial injury in this patient population.

Value of curvature value of liver surface nodularity based on MRI in liver function evaluation of liver cirrhosis / 实用放射学杂志

Objective To explore the value of curvature value of liver surface nodularity(LSN)based on MRI in evaluating liver function in patients with liver cirrhosis.Methods A retrospective analysis was made on the patients who underwent upper abdomen MR examination at 3.0T.The normal liver function patients and cirrhosis patients were enrolled in the study and then the Child-Pugh score of the patients were calculated.The patients were divided into three groups:normal liver group,compensated cirrhosis group and decompensated cirrhosis group.The water phase imaging of 3D modified Dixon fast field echo(mDixon-FFE)sequence was copied in DICOM format.ITK software was used to manually draw the full-thickness liver edge by two observers.The curvature value of LSN was obtained by using matlab self compiled code for follow up analysis.Kruskal-Wallis H test was used to compare the curvature value between the groups.The receiver operating characteristic(ROC)curve was drawn and the area under the curve(AUC)was obtained.Spearman test was used for the correlation analysis.Results The curvature values of LSN among the normal liver,compensated cirrhosis and decompensated cirrhosis groups gradually increased(P<0.05).Comparing normal liver with compensated cirrhosis,the AUC of diagnosing compensated cirrhosis was 0.84,with the sensitivity of 72.7%and the specificity of 89.3%.Comparing compensated cirrhosis with decompensated cirrhosis,the AUC of diagnosing decompensated cirrhosis was 0.91,with the sensitivity of 80%and the specificity of 90.9%.There was a moderate positive correlation between the curvature value of LSN and liver function score in patients with cirrhosis(r=0.63,P=0.002).Conclusion The curvature value of LSN based on MRI can be used for preliminary evaluation of liver function of liver cirrhosis,with the AUC more than 0.80 and higher sensitivity and specificity.

The prognostic value of serum Dnase1L3, CAR combined with MHR in decompensated hepatitis B cirrhosis patients / 中国医师杂志

Objective:To explore the prognostic value of serum deoxyribonuclease 1 like 3 (Dnase1L3), C-reactive protein/albumin ratio (CAR) combined with monocyte to high-density lipoprotein cholesterol ratio (MHR) in decompensated hepatitis B cirrhosis patients.Methods:A prospective selection was conducted on 236 decompensated hepatitis B cirrhosis patients (liver disease group) admitted to the Third Hospital of Qinhuangdao from January 2020 to December 2021, and 185 healthy volunteers (control group) who underwent outpatient physical examinations. The serum levels of Dnase1L3, CAR, MHR, and liver function were detected, and Pearson analysis was conducted to investigate the correlation between Dnase1L3, CAR, MHR, and liver function. Tracking the survival status of patients after 30 days of hospitalization, the risk factors affecting 30 day mortality in decompensated hepatitis B cirrhosis patients were analyzed using a multivariate logistic regression equation. The receiver operating characteristic (ROC) curve analysis was used to assess the value of Dnase1L3, CAR, and MHR in predicting 30 day in-hospital mortality in decompensated hepatitis B cirrhosis patients.Results:The serum levels of Dnase1L3, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBiL), CAR, and MHR in the liver disease group were higher than those in the control group (all P<0.05). The serum levels of Dnase1L3, CAR, and MHR in the liver disease group were positively correlated with AST, ALT, and TBiL (all P<0.05). Among 236 patients, 32 died within 30 days. Model for end-stage liver disease (MELD) scores>18, high Dnase1L3, high CAR, and high MHR were risk factors for 30 day mortality in decompensated hepatitis B cirrhosis patients (all P<0.05). The combined prediction of Dnase1L3, CAR, MHR, and MELD scores for 30 day mortality in decompensated patients with hepatitis B cirrhosis showed an area under the curve of 0.904, which was higher than the predicted values of 0.719, 0.678, 0.763, and 0.742 for individual indicators. Conclusions:The serum Dnase1L3 levels, CAR, and MHR are elevated in patients with decompensated hepatitis B cirrhosis, and are associated with the degree of liver function damage and mortality within 30 days of hospitalization. They have high value in predicting the prognosis of decompensated hepatitis B cirrhosis.

Experience of National TCM Master Wang Qingguo in Treating Liver Cirrhosis with Triplet Herbs / 中国中医药信息杂志

This article summarized the experience of national TCM master Wang Qingguo in treating liver cirrhosis with triplet herbs.Professor Wang believes that the etiology and pathogenesis of liver cirrhosis are always based on the disorders of liver,spleen and kidney function,the dampness and heat retention is an important factor of the disease.When the disease enters the collaterals,blood stasis runs through the development of the disease,qi,blood and water are both pathological products and pathogenic factors.Therefore,supporting the healthy qi and eliminating pathogens,and treating both manifestation and root cause of disease are important treatment principles for liver cirrhosis.Professor Wang takes the whole as the main principle and selects triplet herbs that are suitable for the pathogenesis at different stages of disease development.He emphasizes the three methods of soothing the liver and promoting dampness,removing blood stasis and diuresis,and supporting the healthy qi and eliminating pathogens.He flexibly applies the treatment,and the clinical efficacy is remarkable.

TCM constitution distribution and clinical features of patients with hepatitis B cirrhosis and dysplastic nodules / 临床肝胆病杂志

ObjectiveTo investigate the characteristics of TCM constitution distribution in hepatitis B cirrhosis patients with dysplastic nodules （DN）， and to provide a basis for the prevention and treatment of precancerous lesions of liver cancer. MethodsThis study was conducted among 113 hepatitis B cirrhosis patients with DN， 105 hepatitis B cirrhosis patients with regenerative nodules （RN）， and 70 hepatitis B cirrhosis patients with small hepatocellular carcinoma （sHCC） who were hospitalized in Guangdong Provincial Hospital of Traditional Chinese Medicine from May 2015 to March 2023. Related data were collected， including age， sex， liver function Child-Pugh class， TCM constitution type， and laboratory markers. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups； the chi-square test was used for comparison of categorical data between groups， and the Bonferroni correction method was used for further comparison between two groups. ResultsThe main TCM constitution types of hepatitis B cirrhosis patients with DN were Qi-deficiency constitution （27 patients， 23.89%）， blood-stasis constitution （26 patients， 23.01%）， and phlegm-dampness constitution （23 patients， 20.35%）. There were significant differences between the three groups in the proportion of patients with phlegm-dampness constitution or damp-heat constitution （χ2=6.822 and 6.383， both P<0.05）； the hepatitis B cirrhosis patients with RN had the highest proportion of patients with phlegm-dampness constitution （30.48%）， followed by those with DN （20.35%） and those with sHCC （14.29%）， while the hepatitis B cirrhosis patients with sHCC had the highest proportion of patients with damp-heat constitution （27.14%）， followed by those with DN （16.81%） and those with RN （12.38%）. There were significant differences between the hepatitis B cirrhosis DN patients with different TCM constitution types in sex， age， Child-Pugh class， prealbumin， albumin （Alb）， aspartate aminotransferase， total bilirubin （TBil）， total bile acid， and alpha-fetoprotein （all P<0.05）. Compared with the male hepatitis B cirrhosis DN patients， female patients showed a significantly higher proportion of patients with Qi-deficiency constitution （χ2=4.895， P=0.027）. Among the patients with Qi-deficiency constitution， the patients with Child-Pugh class A liver function accounted for a significantly lower proportion than those with Child-Pugh class B liver function （χ2=6.380， P=0.012）， while among the patients with phlegm-dampness constitution， the patients with Child-Pugh class A liver function accounted for a significantly higher proportion than those with Child-Pugh class B liver function （χ2=8.515， P=0.004）. The patients with phlegm-dampness constitution had significantly higher levels of prealbumin and Alb than those with the other four constitutions （all P<0.05）， as well as significantly lower levels of TBil and total bile acid than those with damp-heat constitution （P<0.05）； the patients with Yin-deficiency constitution had a significantly lower level of Alb than those with qi-deficiency constitution， blood-stasis constitution， or phlegm-dampness constitution （all P<0.05）； the patients with Yin-deficiency constitution had a significantly lower proportion of patients with abnormal alpha-fetoprotein than those with non-Yin-deficiency constitutions （χ2=4.448， P=0.035）. ConclusionHepatitis B cirrhosis patients with DN mainly have the TCM constitution types of Qi deficiency， blood stasis， and phlegm dampness. The patients with phlegm-dampness constitution seem to have a low probability of carcinogenesis， while those with damp-heat constitution and Yin-deficiency constitution have a relatively high risk of carcinogenesis.

Professor ZHOU Zhongying's Experience in Differentiating and Treating Hepatitis and Liver Cirrhosis from Deficiency and Excess / 中医杂志

This paper summarized Professor ZHOU Zhongying's experience in differentiating and treating hepatitis and liver cirrhosis from deficiency and excess. It is considered that the pathogenesis of hepatitis and liver cirrhosis belongs to deficiency in root and excess in branch， with depletion of liver， spleen and kidney as the root， and constraint and bind of damp-heat and stasis toxin as the branch. Moreover， mutual cause and promotion between deficiency and excess leads to the disease. For general principle of treatment， it is recommended to clear and transform pathogenic excess， supplement deficiency and rectify the healthy qi. In the early stage of hepatitis and cirrhosis， excess pathogen hyperactivity is the main manifestation， which can be treated by clearing and transforming damp-heat and stasis toxin， supplemented by regulating spleen and stomach， with modified Yinchenhao Decoction （茵陈蒿汤） and Biejiajian Pill （鳖甲煎丸）. In the middle and late stages， cases with deficiency-excess complex were more common， which should be treated by clearing damp-heat and stasis toxin， regulating and supplementing liver-spleen-kidney， using medicinals with the function of clearing heat and dispelling damp， dissolving stasis and resolving toxins to treat the branch. Moreover， Liujunzi Decoction （六君子汤）， Yiguan Decoction （一贯煎）plus Erzhi Pill （二至丸） and Buzhong Yiqi Decoction （补中益气汤） modifications are suggested respectively in correspondence to the different kinds of root deficiency including irregular liver and spleen， liver and kidney yin deficiency， and liver-spleen-kidney deficiency.

Staged Differentiation and Treatment of Liver Cirrhosis with Newly Modified Chaihu Biejia Decoction （柴胡鳖甲汤） / 中医杂志

Based on Chaihu Biejia Decoction （柴胡鳖甲汤， CBD） created by Professor LIU Duzhou， a newly modified CBD has been formulated. The differentiation and treatment of liver cirrhosis can be divided into three stages， that is， the early stage when liver cirrhosis is about to be， the middle stage when liver cirrhosis is formulated after long accumulations， and the late stage when liver cirrhosis has been transformed. Following the pathogenesis， it is recommended to differentiate the abnormal exuberance of zang-fu （脏腑） organs， qi or blood， deficiency or excess， cold or heat in three stages， and newly modified CBD is taken as the basic formula for further modifications. In early stage of liver cirrhosis， the treatment is mainly to invigorate blood and dissolve stasis， clear dampness and heat， and modifications should be made in accordance with the different causes flexibly. The treatment for the middle stage is to soften hardness and dissipate masses， dissolve stasis and clear heat， while fortifying the spleen and supplementing kidneys is accompanied. In the later stage when the healthy qi declines， and the disease is severe and evil prevails， the treatment is to reinforce healthy qi and supplement deficiency， take mild purgation and dispersion， and medicinals to promote urination， stanch bleeding， direct the turbid downward， or open the orifices can be added in accordance with the syndromes so as to treat the branch.

Diagnostic value of detachable string magnetically controlled capsule endoscopy in patients with liver cirrhosis / 西安交通大学学报(医学版)

【Objective】 To investigate the diagnostic value of detachable string magnetically controlled capsule endoscopy (ds-MCE) in patients with liver cirrhosis. 【Methods】 Patients with liver cirrhosis were screened for esophagogastroduodenoscopy (EGD) and ds-MCE examination to assess the accuracy of ds-MCE in identifying gastroesophageal varices, high-risk esophageal varices and portal hypertensive gastropathy using EGD as the gold standard, and evaluate the detection of portal hypertensive enteropathy and the comfort level of patients. 【Results】 From May 2021 to July 2022, a total of 53 patients with liver cirrhosis were successfully enrolled. With EGD as the gold standard, ds-MCE detected esophageal varices with 95.45% for sensitivity, 100% for specificity and adjusted positive predictive value (PPV), 95.65% for adjusted negative predictive value (NPV), and 0.877 for Kappa value (P<0.001). For detection of gastric varices, ds-MCE had sensitivity, specificity, adjusted PPV, and adjusted NPV of 93.94%, 90%, 90.38% and 93.69%, and Kappa value of 0.839 (P<0.001). For detection of portal hypertension gastropathy, ds-MCE had sensitivity, specificity, adjusted PPV and adjusted NPV of 80%, 90.70%, 89.59% and 81.93%, and Kappa value of 0.657(P<0.001). In differentiating high-risk esophageal varices, the sensitivity, specificity, adjusted PPV, and adjusted NPV were 76%, 100%, 100% and 77.43%, respectively; Kappa value was 0.770 (P<0.001). Of the patients with liver cirrhosis, 26.0% (13/50) were diagnosed with portal hypertensive enteropathy. The main mucosal changes were edema, erythema, and vascular dysplasia. The ds-MCE comfort score of 3(2, 4) was higher than that of the traditional EGD 1(0, 3) (P<0.000 1). 【Conclusion】 Compared with EGD, ds-MCE is an accurate, safe, feasible and comfortable method for detecting esophagogastric varices and portal hypertensive gastropathy in patients with liver cirrhosis. It is a potential alternative to EGD screening surveillance of gastroesophageal varices in patients with liver cirrhosis.