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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.
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Acute-on-chronic liver failure has complex conditions， rapid progression， and a high mortality rate， and further studies are still needed to clarify its pathogenesis and etiology. The establishment of animal models for acute-on-chronic liver failure can not only provide a good basis for exploring the pathogenesis of acute-on-chronic liver failure， but also provide an experimental basis for clinical treatment. Through a literature review， this article summarizes the methods commonly used to establish the animal models of acute-on-chronic liver failure， including carbon tetrachloride combined with LPS/GaIN， thioacetamide combined with LPS， serum albumin， and bile duct ligation. This article analyzes the characteristics of various animal models， so as to provide documentary and experimental bases for further exploration of more ideal animal models.
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ObjectiveTo investigate whether menaquinone-4 （MK-4） can exert a protective effect against carbon tetrachloride （CCl4）-induced acute liver injury （ALI） in mice by alleviating ferroptosis. MethodsAfter adaptive feeding， adult male ICR mice， aged 8 weeks， were divided into Control group， MK-4 group， CCl4 model group （6-hour， 12-hour， and 24-hour）， and MK-4+CCl4 group （6-hour， 12-hour， and 24-hour）， with 6 mice in each group. The mice in the Control group were given intraperitoneal injection of an equal dose of corn oil； the mice in the MK-4 group were given intraperitoneal injection of 40 mg/kg MK-4 solution， followed by an equal dose of corn oil after 1 hour； the mice in the MK-4+CCl4 group （6-hour， 12-hour， and 24-hour） were given intraperitoneal injection of 40 mg/kg MK-4 solution， and after 1 hour， the mice in this group and the CCl4 model group （6-hour， 12-hour， and 24-hour） were given intraperitoneal injection of 0.3 mL/kg CCl4 solution， with samples collected at 6， 12， and 24 hours. HE staining was used to observe the pathological changes of mouse liver； Prussian blue staining was used to observe iron accumulation in liver tissue； a biochemical analyzer was used to measure the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）； related kits were used to measure the levels of tissue iron content and the oxidative stress indices malondialdehyde （MDA） and glutathione （GSH） in liver homogenate； RT-PCR was used to measure the expression levels of ferroptosis marker genes （acyl-CoA synthetase long-chain family member 4 ［ACSL4］， prostaglandin-endoperoxide synthase 2 ［PTGS2］， and glutathione peroxidase 4 ［GPX4］） and iron metabolism-related genes （hemojuvelin ［HJV］， transferrin receptor 1 ［TFR1］， and ferroportin ［FPN］）， and Western blot was used to measure the protein expression level of GPX4. 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. ResultsIn the aging study， compared with the Control group， the CCl4 model group （6-hour， 12-hour， and 24-hour） had significant increases in liver weight coefficient and the serum levels of ALT and AST （all P<0.05）， and HE staining also showed that liver injury gradually aggravated over time. Meanwhile， compared with the CCl4 model group （6-hour， 12-hour， and 24-hour）， the MK-4+CCl4 （12-hour） group had significant reductions in liver weight coefficient and the serum levels of ALT and AST （all P<0.05）， with a reduction in the necrotic area of liver tissue， and therefore， 12-hour mouse tissue samples were used for detection in the following study. Compared with the Control group， the CCl4 group had a significant increase in MDA and a significant reduction in GSH （both P<0.05）， and compared with the CCl4 group， the MK-4+CCl4 group had a significant reduction in MDA and a significant increase in GSH （both P<0.05）. Compared with the Control group， the CCl4 group had significant increases in the key ferroptosis indices ASCL4 and PTGS2 and a significant reduction in GPX4 （all P<0.05）； compared with the CCl4 group， the MK-4+CCl4 group had significant reductions in the mRNA expression levels of ASCL4 and PTGS2 and a significant increase in the mRNA expression level of GPX4 （all P<0.05）. Western blotting showed that compared with the Control group， the CCl4 group had a significant reduction in the protein expression level of GPX4 （P<0.05）， and compared with the CCl4 group， the MK-4+CCl4 group had a significant increase in the protein expression level of GPX4 （P<0.05）. Prussian blue staining showed that compared with the Control group， the CCl4 group had a significant increase in iron accumulation； after MK-4 intervention， compared with the CCl4 group， the MK-4+CCl4 group had a significant reduction in iron accumulation. As for the measurement of iron metabolism genes in mouse liver， compared with the Control group， the CCl4 group had a significant increase in iron content， significant reductions in the mRNA expression levels of FPN and HJV， and a significant increase in the mRNA expression level of TFR1 （all P<0.05）； after protection with MK-4， there was a significant reduction in iron content， significant increases in the mRNA expression levels of FPN and HJV， and a significant reduction in the mRNA expression level of TFR1 （all P<0.05）. ConclusionMK-4 intervention in advance can alleviate CCl4-induced ALI in mice， possibly by inhibiting ferroptosis and improving the expression of iron metabolism-related genes in mouse liver.
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ObjectiveTo investigate the differences in clinical features and mortality rate between native patients with chronic liver failure （CHF） and migrated patients with CHF after treatment with double plasma molecular adsorption system （DPMAS） in high-altitude areas. MethodsA total of 63 patients with CHF who received DPMAS treatment in the intensive care unit of General Hospital of Tibet Military Command from January 2016 to December 2021 were enrolled， and according to their history of residence in high-altitude areas， they were divided into native group with 29 patients and migrated group with 34 patients. The two groups were compared in terms of baseline data and clinical features before and after DPMAS treatment. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the paired t-test was used for comparison before and after treatment within each group； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups， and the Wilcoxon signed rank sum test was used for comparison before and after treatment within each group； the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison of the risk of death. ResultsCompared with the native group， the migrated group had a significantly higher proportion of Chinese Han patients （χ2=41.729， P<0.001）， and compared with the migrated group， the native group had a significantly longer duration of the most recent continuous residence in high-altitude areas （Z=3.364， P<0.001）. Compared with the native group， the migrated group had significantly higher MELD score and incidence rates of hepatic encephalopathy， hepatorenal syndrome， and gastrointestinal bleeding （Z=2.318， χ2=6.903， 5.154， and 6.262， all P<0.05）. Both groups had significant changes in platelet count （PLT）， hemoglobin count （HGB）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， albumin， total bilirubin （TBil）， direct bilirubin （DBil）， lactate dehydrogenase （LDH）， creatinine （Cr）， and international normalized ratio （INR） after DPMAS treatment （all P<0.05）. Before DPMAS treatment， compared with the native group， the migrated group had significantly higher levels of ALT， AST， TBil， DBil， LDH， Cr， BUN， and INR （all P<0.05） and a significantly lower level of HGB （P<0.05）； after DPMAS treatment， compared with the native group， the migrated group had significantly greater reductions in PLT and HGB （both P<0.05） and still significantly higher levels of ALT， AST， TBil， DBil， LDH， BUN， and INR （all P<0.05）. The 60-day mortality rate of patients after DPMAS treatment was 52.5% （95% confidence interval ［CI］： 41.7 — 63.8） in the native group and 81.3% （95%CI： 77.9 — 85.6） in the migrated group. Compared with the native group （hazard ratio ［HR］=0.47， 95%CI： 0.23 — 0.95）， the migrated group had a significant increase in the risk of death on day 60 （HR=2.14， 95%CI： 1.06 — 4.32， P=0.039）. ConclusionCompared with the native patients with CHF in high-altitude areas， migrated patients have a higher degree of liver impairment， a lower degree of improvement in liver function after DPMAS treatment， and a higher mortality rate. Clinical medical staff need to pay more attention to migrated patients with CHF， so as to improve their survival rates.
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Liver failure （LF）， as a clinical syndrome of severe hepatocyte damage and liver dysfunction， has become a major obstacle to human health due to the triple superposition of high mortality， high morbidity， and high medical resource depletion. It is of great significance to further study the core factors of the disease and supplementary treatment methods to improve the survival rate of patients with LF. The pathogenesis of LF is complex， and mitochondrion is one of the sensitive organelles in hepatocytes and the central link of intracellular energy metabolism. A large number of studies have shown that the structure and function of mitochondria in hepatocytes are changed in LF， and the abnormal structure and function of mitochondria play an important role in the process of LF disease. Among them， multiple factors such as mitochondrial respiratory chain disorder， mitochondrial DNA damage， mitochondrial permeability transition pore opening， mitochondrial quality control imbalance， and mitochondrial oxidative stress are intertwined， forming a complex and unified whole network， which becomes the key node affecting the progression of LF. In recent years， researchers have begun to study drugs that can regulate the function of liver mitochondria to prevent and treat LF. With the deepening of research， traditional Chinese medicine has made breakthroughs in the prevention and treatment of LF. Many studies have confirmed that traditional Chinese medicine can play a role in the prevention and treatment of LF by protecting mitochondrial function， which can be summarized as reducing liver cell damage， inhibiting liver cell death， and promoting liver cell regeneration， so as to effectively compensate for liver function and promote the recovery of liver parenchyma quality and function. This article summarized the structure and function of mitochondria， the relationship between LF and mitochondria， and the research on the intervention of mitochondrial function in the field of traditional Chinese medicine to prevent and treat LF， so as to provide certain ideas and references for the clinical treatment of LF with traditional Chinese medicine.
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Acute fulminant hepatic failure is a condition in which a healthy liver deteriorates rapidly following an insult, resulting in the impairment of its synthetic functions. This condition is rare and is associated with high fatality rates. We report the case of a 19-year-old male who was brought to the emergency room in an unconscious state with jaundice and persistent fever for 2–3 weeks after recently commencing intravenous use of morphine. He was found to be hepatitis B surface antigen reactive, and his laboratory tests indicated severe liver dysfunction with elevated levels of serum bilirubin, aspartate transaminase, alanine transaminase, gamma-glutamyl transferase, and International normalized ratio. The patient was diagnosed with fulminant liver failure with coagulopathy and hepatic encephalopathy. The patient’s family was addressed and counseled regarding the urgent need for liver transplantation. However, due to a lack of funds and insurance, supportive treatment was the only option left. Despite all supportive measures, the patient expired within 48 h. This case highlights the importance of various socioeconomic issues involved with liver transplantation, as in a resource-limited setting, urgent transplantation seems nearly impossible. In addition, this case report raises certain ethical issues that need consideration, particularly in an injection drug use scenario. It also highlights the importance of addressing the rising issue of injection drug use among youth, particularly in the regions of Punjab.
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La enfermedad poliquística renal autosómica dominante es considerada la enfermedad renal genética más frecuente y es la cuarta causa de enfermedad renal crónica a nivel mundial. Afecta a cerca de 1 por cada 1000 nacidos vivos. La enfermedad poliquística hepática es la manifestación extrarrenal más frecuente de la enfermedad poliquística renal. La cirrosis hepática constituye un hallazgo tardío en esta enfermedad y su presentación es más común en el anciano, y la descompensación de la enfermedad con insuficiencia hepática como causa de muerte. Presentamos el caso de un paciente masculino de 60 años con antecedentes patológicos personales de la enfermedad poliquística renal con ascitis a tensión, y edemas en ambos miembros inferiores con datos de insuficiencia hepática y evolución desfavorable hasta su fallecimiento. Aunque la presencia de la falla hepática se asocia a un pronóstico precario, la detección precoz puede suponer el inicio de un tratamiento oportuno y apropiado que puede ser beneficioso.
Autosomal dominant polycystic kidney disease is considered the most common genetic kidney disease and the fourth leading cause of chronic kidney disease worldwide. It affects about 1 in 1,000 live births. Polycystic liver disease is the most common extrarenal manifestation of polycystic kidney disease. Liver cirrhosis is a late finding in this disease and its presentation is more common in the elderly. Decompensation of the disease, with liver failure as the cause of death, is rare in polycystic liver disease. We report the case of a 60-year-old male patient with a personal pathological history of polycystic kidney disease with tense ascites and edema in both lower limbs, with evidence of liver failure and unfavorable evolution until his death. Although the presence of liver failure is associated with poor prognosis, its early detection may mean the initiation of timely and appropriate treatment that may be beneficial.
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Acute hepatitis of unknown origin in children has been recently described in the literature, and a case definition has also been proposed for this condition. The exact etiology is unknown and exclusion of infectious, metabolic, autoimmune and toxin mediated injuries is essential. Management for this condition is supportive, but some may require liver transplantation. Infection prevention and control practices are important as the etiology remains unidentified.
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Acetaminophen is a drug widely used in the world and easily accessible due to its antipyretic, analgesics characteristics, among others (1); however, exposure to toxic doses causes organic damage and even death. We present the case of an 18-year-old female patient who ingested 40 grams of acetaminophen and developed severe liver dysfunction, being treated with N-acetylcysteine (NAC) antidotal therapy according to the simplified scheme: Scottish and Newcastle Anti-emetic Pretreatment Paracetamol Poisoning Study Regimen (SNAP), presenting improvement in the clinical course and decrease in liver profiles, coagulation disorder, INR and resolution of the condition.
El acetaminofén es un fármaco ampliamente usado en el mundo y de fácil acceso por sus características antipiréticas, analgésicas, entre otras (1); sin embargo la exposición a dosis tóxicas produce daños a nivel orgánico e incluso la muerte. Presentamos el caso de una paciente mujer de 18 años que ingirió 40 gramos de acetaminofén y desarrolló injuria hepática severa, siendo tratada con terapia antidotal de N-acetilcisteína (NAC) según el esquema simplificado: Scottish and Newcastle Anti-Emetic Pretreatment Paracetamol Poisoning Study Regimen (SNAP), presentando mejoría del curso clínico y disminución de los perfiles hepáticos, trastorno de coagulación, INR y resolución del cuadro.
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Objective:To compare the predictive value of parameters extracted from circular region-of-interest (ROI) with whole-liver histogram on gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced T 1 map for postoperative liver failure in patients with liver focal lesions. Methods:The data of patients who underwent Gd-EOB-DTPA-enhanced MRI for focal liver lesions in Zhongshan Hospital, Fudan University from March 2016 to March 2018 were analyzed retrospectively. Forty patients were enrolled, including 30 males and 10 females, aged (56.6±12.1) years. According to the occurrence of postoperative liver failure, forty patients were divided into liver failure group ( n=14) and control group ( n=26). The parameters extracted from circular ROIs and whole liver histogram on T 1 map before Gd-EOB-DTPA enhancement and in hepatobiliary phase (HBP) were compared between the two groups. The receiver operating characteristic (ROC) curve was used to evaluate the value of these parameters in predicting postoperative liver failure. Results:The mean, standard deviation, median and 95% quantile of T 1 HBP in histogram parameters of liver failure group were significantly higher than those of control group (all P<0.05). The three parameters extracted from circular ROIs were not effective in predicting liver failure after hepatectomy (all P>0.05). Among all the liver histogram parameters, the area under the ROC curve of the 95% quantile before T 1 enhancement for predicting postoperative liver failure was 0.702 (95% CI: 0.523-0.881), the standard deviation of T 1 HBP was 0.739 (95% CI: 0.568-0.910), and the 95% quantile of T 1 HBP was 0.721 (95% CI: 0.540-0.903). The predictive efficacy were good (all P<0.05). Among them, the predictive performance of T 1 HBP standard deviation was the best, the area under the ROC curve was 0.739, the sensitivity was 85.7%, the specificity was 57.7%, and the best threshold was 54.8 ms. Conclusions:When Gd-EOB-DTPA enhanced T 1 mapping is used to predict postoperative liver failure in patients with focal liver lesions, the whole-liver histogram analysis is superior to the conventional circular ROI-based statistical method.
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Objective:To investigate the prognostic value of systemic immune-inflammation index (SII) in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF).Methods:The clinical data, including age, gender, complications, laboratory examination results post-admission, SII, model for end-stage liver disease (MELD) score, MELD-Na score, Child-Turcotte Pugh (CTP) score of HBV-ACLF patients treated in Huashan Hospital, Fudan University from January 2016 to August 2021 were retrospectively analyzed. The patients were divided into survival group and death group according to the outcome at 90 days of follow-up.Paired sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis.Pearson correlation was used to analyze the correlation between SII and the prognosis prediction model of HBV-ACLF. The area under the curve (AUC) was used to analyze the clinical efficacies of SII, MELD score, MELD-Na score and CTP score in predicting the prognosis of HBV-ACLF patients, and the optimal cut-off value of SII for predicting the prognosis of HBV-ACLF was calculated. Kaplan-Meier method was used for survival analysis. Results:A total of 140 patients with HBV-ACLF were included. There were 88 patients in the survival group, including 65 males and 23 females, with the age of (47.69±11.96) years. There were 52 cases in the death group, including 40 males and 12 females, with the age of (52.73±12.22) years. The age, aspartate aminotransferase, total bilirubin, serum creatinine, international normalized ratio, neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, SII, MELD score, MELD-Na score, CTP score and the incidence of infection in the death group were all significantly higher than those in the survival group, and albumin, lymphocyte count, platelet count, prognostic nutritional index in the death group were all significantly lower than those in the survival group, and the differences were all statistically significant ( t=-2.39, Z=-2.84, t=-4.81, Z=-2.15, Z=-4.91, Z=-3.47, Z=-3.36, Z=-3.83, Z=-4.69, Z=-4.56, Z=-6.31, χ2=24.96, t=3.06, t=3.03, Z=-7.57 and t=4.12, respectively, all P<0.05). Pearson correlation analysis showed that SII was positively correlated with CTP score ( r=0.272 7, P=0.001), MELD score ( r=0.365 8, P<0.001) and MELD-Na score ( r=0.381 1, P<0.001). The AUC of SII was the largest of 0.80, and 0.76 for MELD score, 0.74 for MELD-Na score and 0.73 for CTP score. The optimal cut-off value of SII was 447.49. Kaplan-Meier analysis showed that the 90 days survival rate of patients with SII≥447.49(38.60%(22/57)) was lower than that of SII<447.49 group (79.52%(66/83)), and the difference between the two groups was significant ( χ2=23.80, P<0.001). Conclusions:SII can be used to assess the severity and prognosis of HBV-ACLF patients. SII ≥447.49 indicates poor prognosis.
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Abiraterone is commonly used as a targeted drug for the treatment of prostate cancer， which commonly causes adverse drug reactions （ADR）， including abnormal liver function， fatigue， nausea and edema， etc. This study reports a 78-year-old man with a history of hepatitis B and liver cirrhosis after prostate cancer resection who was admitted to the First Affiliated Hospital of Henan University of Chinese Medicine. The patient received abiraterone treatment 1 month before admission and developed gastrointestinal symptoms 3 weeks after the treatment and worsened at 4th week with yellowing of the skin， sclera and urine. Unfortunately， the patient died after 5 weeks of abiraterone treatment （1 week after admission）. Based on test and examination results， the patient was diagnosed with acute-on-chronic liver failure （ACLF）. This paper analyzes the patient’s medical history and the relevant treatment in detail. It is evaluated that ACLF and abiraterone are “probably” related based on Naranjo ADR Probability Scale， suggesting abiraterone may induce severe ADR of liver failure in patients with chronic liver diseases such as cirrhosis. These patients should be monitored dynamically for changes in liver function and treated prophylactically with liver-protective drugs if necessary.
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Objective To investigate the difference in blood lipid parameters between acute-on-chronic pre-liver failure (pre-ACLF) and acute-on-chronic liver failure (ACLF) and the risk factors for disease progression. Methods A retrospective analysis was performed for the related data of 118 patients with ACLF (ACLF group) and 44 patients with pre-ACLF (pre-ACLF group) who were treated in The General Hospital of Western Theater Command from January 2012 to December 2020, including baseline age, albumin, creatinine, routine blood test results, and blood lipids. The independent samples t -test was used for comparison between normally distributed continuous data; and the Mann-Whitney U test was used for comparison between non-normally distributed continuous data; the chi-square test was used for comparison of categorical data between groups. A binary logistic regression analysis was used for multivariate analysis to identify independent predictive factors. The receiver operating characteristic (ROC) curve was used to compare the sensitivity and specificity of related indicators, and Youden index was used to calculate cut-off values. Results Compared with the pre-ACLF group, the ACLF group had significantly lower levels of total cholesterol (TC)[2.02(1.56-2.37) mmol/L vs 3.01(2.57-3.66) mmol/L, Z =5.411, P 0.05). The logistic regression analysis showed that TC (odds ratio [ OR ]=0.003, 95% confidence interval [ CI ]: 0.000-0.068, P < 0.05), LDL ( OR =61.901, 95% CI : 3.354-1142.558, P < 0.05), and WBC ( OR =3.175, 95% CI : 1.097-9.185, P < 0.05) had an independent predictive value, and the ROC analysis showed that the area under the ROC curve of TC was 0.852, the sensitivity of LDL was 0.887, and TC had the best specificity of TC was 0.840. Conclusion There are reductions in blood lipid parameters in the progression from pre-ACLF to ACLF, suggesting that clinicians should pay attention to the changes in lipids in the pre-ACLF stage and adjust the nutritional regimen in a timely manner.
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Acute-on-chronic liver failure (ACLF) is a clinical syndrome with the manifestations of liver failure such as acute deepening of jaundice and coagulation disorder due to various predisposing factors, characterized by multiple organ failure and high mortality rate within a short period of time. In terms of traditional Chinese medicine, ACLF belongs to the categories of "acute jaundice", "scourge jaundice", and "liver failure", and now there is still a lack of specific medical treatment methods in clinical practice. With the orientation of "key clinical problems of traditional Chinese and Western medicine" in the guidelines, the working group constructed the clinical problems associated with ACLF based on the principles of Participants, Interventions, Comparisons, and Outcomes and followed the principles of evidence-based medicine. Through systematic review and objective evaluation of the clinical evidence concerning the efficacy of integrated traditional Chinese and Western medicine therapy for ACLF in the past 10 years, the guidelines were developed with reference to the latest diagnosis and treatment guidelines and expert consensus in China and globally and the comments from multidisciplinary experts, in order to provide guidance and reference for the diagnosis and treatment of ACLF among clinicians and further improve the diagnosis and treatment level of ACLF in China.
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Objective To investigate the association between platelet count (PLT) and the prognosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), to establish a new PLT-related scoring model, and to assess its value in predicting the short-term prognosis of HBV-ACLF. Methods A retrospective cohort study was conducted among the patients with HBV-ACLF who were hospitalized and treated in Department of Gastroenterology, The General Hospital of Western Theater Command, from January 2018 to January 2022. Clinical data within 24 hours after admission were collected from all patients, and according to the survival after 180 days of follow-up, the patients were divided into survival group and death group. The independent-samples t test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The Pearson correlation coefficient was used to investigate the correlation between different indicators, and the logistic regression model was used to analyze the influencing factors for prognosis. The receiver operating characteristic (ROC) curve was used to assess the predictive value of the prognostic model, and the Kaplan-Meier curve analysis was used to investigate the survival condition of the high AIP group and the low AIP group. Results A total of 236 patients were enrolled, with a 180-day survival rate of 75.85% (179/236). Compared with the survival group, the death group had significantly higher age (53.98±10.45 vs 47.44±12.46, P =0.001), international normalized ratio (INR) [1.78 (1.46-2.04) vs 1.47 (1.23-1.68), P < 0.001], total bilirubin [275.60 (165.00-451.45) vs 230.60 (154.90-323.70), P =0.035], Model for End-Stage Liver Disease (MELD) score [21.47 (18.14-24.76) vs 18.67 (15.70-21.62), P < 0.001], and albumin-bilirubin (ALBI) score [-1.06 (-1.64~-0.86) vs-1.32 (-1.73~-1.01), P =0.034], as well as significantly lower PLT [80.00 (50.00~124.50) vs 115.00 (82.00~143.00), P =0.001] and platelet-to-white blood cell ratio (PWR) [13.40 (9.54~20.70) vs 18.49 (13.95~24.74), P =0.001]. The Pearson correlation analysis showed that PLT was negatively correlated with liver cirrhosis and INR ( r =-0.332 and -0.194, P < 0.001 and P =0.003). The multivariate logistic regression analysis showed that age (odds ratio [ OR ]=1.045, 95% confidence interval [ CI ]: 1.015-1.076), PLT ( OR =0.990, 95% CI : 0.983-0.998), and INR ( OR =2.591, 95% CI : 1.363-4.925) were independent risk factors for the 180-day prognosis of HBV-ACLF patients. The new predictive model was established as follows: AIP=0.006×age+0.187×INR-0.001×PLT. The AIP scoring model had an area under the ROC curve (AUC) of 0.718 in predicting the 180-day prognosis of HBV-ACLF patients, with a sensitivity of 81.1% and a specificity of 54.1%, while PLT, PWR, LPACLF score, MELD score, and ALBI score had an AUC of 0.673, 0.659, 0.588, 0.647, and 0.578, respectively. The AIP scoring model had an optimal cut-off value of 0.48. The Kaplan-Meier survival analysis showed that the high AIP group had a significantly lower survival rate than the low AIP group ( P < 0.001). Conclusion The PLT-related scoring model has a better value than other models in predicting the prognosis of HBV-ACLF, and HBV-ACLF patients with a relatively high PLT level tend to have a high overall survival rate.
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At present, hepatectomy has become the preferred treatment modality for most benign and malignant hepatobiliary diseases. Liver failure is a common complication after hepatectomy, and for malignant diseases, how to remove the lesion to the maximum extent and reduce the incidence rate of liver failure after hepatectomy is the key problem at present. Accurate and adequate preoperative evaluation of liver reserve function can provide a basis for judging the progression, therapeutic outcome, and prognosis of liver diseases. There are currently various methods for evaluating liver reserve function and surgical feasibility, each with its own advantages and disadvantages, and there is still a lack of a single comprehensive evaluation method. This article reviews the characteristics of commonly used evaluation methods and related research advances.
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Objective To investigate the value of Charlson comorbidity index (CCI) in predicting the short- and long-term risks of death in patients with acute-on-chronic liver failure (ACLF). Methods A total of 317 patients with ACLF who attended The First Hospital of Lanzhou University from December 1, 2016 to December 1, 2021 were enrolled, and according to their prognosis, they were divided into death group with 169 patients and survival group with 148 patients. The two groups were analyzed in terms of clinical data and follow-up data. The group 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. The univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate the influencing factors for the prognosis of ACLF patients. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for comparison of survival time between patients with different CCI scores. The receiver operating characteristic (ROC) curve was used to evaluate the performance of CCI and other indices in assessing the prognosis of ACLF patients. Results Among the 317 patients, there were 225 (71.0%) male patients. There were significant differences between the death group and the survival group in age, hemoglobin, white blood cell count, total bilirubin, albumin, Model for End-Stage Liver Disease (MELD) score, prothrombin time activity, CCI, age-adjusted Charlson co-morbidity index (ACCI), and follow-up time (all P < 0.05). The multivariate Cox regression analysis showed that the CCI (hazard ratio [ HR ]=1.351, 95% confidence interval [ CI ]: 1.112-1.641, P =0.002), ACCI ( HR =1.200, 95% CI : 1.011-1.423, P =0.037), and MELD score ( HR =1.076, 95% CI : 1.054-1.099, P < 0.001) were independent risk factors for the prognosis of ACLF patients. Based on CCI score, the patients were divided into CCI ≤4 group with 167 patients, CCI=5 group with 64 patients, and CCI ≥6 group with 86 patients, with a 3-year mortality rate of 26.5%, 83.2%, and 96.9%, respectively, and there was a significant difference in survival time between any two groups after 3 years of follow-up and at the time of follow-up till September 2022 (all P < 0.001). CCI, ACCI, and MELD scores had an area under the ROC curve of 0.845, 0.811, and 0.790, respectively, in predicting the prognosis of ACLF patients. Conclusion As commonly used comorbidity assessment indices, CCI and ACCI scores have certain value in evaluating the short- and long-term prognosis of ACLF patients.
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Objective To investigate the value of a risk assessment model in predicting venous thromboembolism (VTE) in patients with liver failure after artificial liver support therapy. Methods A retrospective analysis was performed for the clinical data of 124 patients with liver failure who received artificial liver support therapy in Affiliated Drum Tower Hospital of Nanjing University Medical School from March 2019 to December 2021, among whom there were 41 patients with VTE (observation group) and 143 patients without VTE (control group). Related clinical data were compared between the two groups, and the Caprini risk assessment model was used for scoring and risk classification of the patients in both groups. The t -test was used for comparison of continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups; the Mann-Whitney U rank sum test was used for comparison of ranked data between two groups. The logistic regression analysis was used to investigate the independent risk factors for VTE in patients with liver failure after artificial liver support therapy. The receiver operating characteristic (ROC) curve was used to investigate the value of Caprini score and the multivariate predictive model used alone or in combination in predicting VTE. Results The observation group had a significantly higher Caprini score than the control group (4.39±1.10 vs 3.12±1.04, t =6.805, P < 0.001). There was a significant difference between the two groups in risk classification based on Caprini scale ( P < 0.05), and the patients with high risk or extremely high risk accounted for a higher proportion among the patients with VTE. The univariate analysis showed that there were significant differences between the two groups in age ( t =6.400, P < 0.001), catheterization method ( χ 2 =14.413, P < 0.001), number of times of artificial liver support therapy ( Z =-4.720, P < 0.001), activity ( Z =-6.282, P < 0.001), infection ( χ 2 =33.071, P < 0.001), D-dimer ( t =8.746, P < 0.001), 28-day mortality rate ( χ 2 =5.524, P =0.022). The multivariate analysis showed that number of times of artificial liver support therapy (X 1 ) (odds ratio [ OR ]=0.251, 95% confidence interval [ CI ]: 0.111-0.566, P =0.001), activity (X 2 ) ( OR =0.122, 95% CI : 0.056-0.264, P < 0.001), D-dimer (X 3 ) ( OR =2.921, 95% CI : 1.114-7.662, P =0.029) were independent risk factors for VTE in patients with liver failure after artificial liver support therapy. The equation for individual predicted probability was P =1/[1+e -(7.425-1.384X 1 -2.103X 2 +1.072X 3 ) ]. The ROC curve analysis showed that Caprini score had an area under the ROC curve of 0.802 (95% CI : 0.721-0.882, P < 0.001), and the multivariate model had an area under the ROC curve of 0.768 (95% CI : 0.685-0.851, P < 0.001), while the combination of Caprini score and the multivariate model had an area under the ROC curve of 0.957 (95% CI : 0.930-0.984, P < 0.001). Conclusion The Caprini risk assessment model has a high predictive efficiency for the risk of VTE in patients with liver failure after artificial liver support therapy, and its combination with the multivariate predictive model can significantly improve the prediction of VTE.
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Body is equipped with organic cation transporters (OCTs). These OCTs mediate drug transport and are also involved in some disease process. We aimed to investigate whether liver failure alters intestinal, hepatic and renal Oct expressions using bile duct ligation (BDL) rats. Pharmacokinetic analysis demonstrates that BDL decreases plasma metformin exposure, associated with decreased intestinal absorption and increased urinary excretion. Western blot shows that BDL significantly downregulates intestinal Oct2 and hepatic Oct1 but upregulates renal and hepatic Oct2. In vitro cell experiments show that chenodeoxycholic acid (CDCA), bilirubin and farnesoid X receptor (FXR) agonist GW4064 increase OCT2/Oct2 but decrease OCT1/Oct1, which are remarkably attenuated by glycine-β-muricholic acid and silencing FXR. Significantly lowered intestinal CDCA and increased plasma bilirubin levels contribute to different Octs regulation by BDL, which are confirmed using CDCA-treated and bilirubin-treated rats. A disease-based physiologically based pharmacokinetic model characterizing intestinal, hepatic and renal Octs was successfully developed to predict metformin pharmacokinetics in rats. In conclusion, BDL remarkably downregulates expressions of intestinal Oct2 and hepatic Oct1 protein while upregulates expressions of renal and hepatic Oct2 protein in rats, finally, decreasing plasma exposure and impairing hypoglycemic effects of metformin. BDL differently regulates Oct expressions via Fxr activation by CDCA and bilirubin.
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Objective To investigate the expression of myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg), IL-17-producing CD4 + T cells (Th17), and CD8 + T cells (Tc17) in hepatitis B virus-related acute-on-chronic pre-liver failure (pre-ACHBLF), and to provide ideas for the early treatment of acute-on-chronic hepatitis B liver failure (ACHBLF). Methods A total of patients with pre-ACHBLF and 15 patients with ACHBLF who were hospitalized in Shijiazhuang Fifth Hospital, from August 2018 to May 2019 were enrolled as subjects, and 15 patients with chronic hepatitis B (CHB) and 15 healthy controls (HC) who underwent physical examination were enrolled as controls. Flow cytometry was used to measure the expression levels of MDSC and Th17, Treg, and Tc17 cells in peripheral blood; a blood analyzer was used to measure routine blood parameters and calculate neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index(SIRS) to evaluate the degree of inflammation, and the correlation between the expression of immune cells and the degree of inflammation was analyzed. An analysis of variance for independent samples 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, and the Nemenyi test was used for further comparison between two groups. A Pearson linear correlation analysis or Spearman's rank correlation analysis was used to investigate the correlation between variables. Results Compared with the CHB group, the ACHBLF and pre-ACHBLF groups had significant increases in the expression levels of Th17, Treg, and Tc17 cells, and the pre-ACHBLF group also had a significant increase in the expression level of MDSC (all P < 0.05). The correlation analysis showed that in pre-ACHBLF patients, MDSC were positively correlated with leukocyte count, neutrophil count, NLR, MLR, and SII ( r =0.775, 0.727, 0.571, 0.786, and 0.846, all P < 0.05), and Treg cells were only positively correlated with leukocyte count ( r =0.618, P =0.043); Th17/Treg ratio and Tc17 cells were negatively correlated with the number of lymphocytes ( r =-0.790 and -0.795, both P < 0.05). Conclusion Cellular immune dysfunction is observed in patients with pre-ACHBLF, and the expression of MDSC is closely associated with the degree of inflammation and should be taken seriously in the early stage.