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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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Acute liver failure （ALF） is one of the most critical liver diseases in clinical practice and seriously affects the life and health of Chinese people. Due to its high morbidity and mortality rates， unclear pathogenesis， and limited treatment methods， ALF has become a major problem that needs to be solved urgently in the field of liver diseases. In recent years， more and more studies have shown that endoplasmic reticulum stress is a key biological process in the progression of ALF， and the IRE1α/TRAF2/JNK pathway， as a part of endoplasmic reticulum stress signaling， plays a role in amplifying inflammatory response， promoting hepatocyte apoptosis， and inhibiting liver regeneration ability during the progression of diseases. As a traditional treasure of China， traditional Chinese medicine has become a research hotspot in search for effective prevention and treatment drugs for ALF from monomers of Chinese herbs. This article elaborates on the mechanism of action of the IRE1α/TRAF2/JNK pathway in the progression of ALF and summarizes the potential value of several monomers of Chinese herbs in regulating this pathway， such as salidroside， Fructus Broussonetiae， Fructus Psoraleae+Schisandra chinensis， baicalein， genipin， kaempferol， resveratrol， sea buckthorn polysaccharide extract， and luteol， in order to provide a reference for further research and clinical practice of ALF.
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About 1% of the patients with acute hepatitis B can progress to acute liver failure， and 75% of the patients with hepatitis B virus （HBV）-related acute liver failure need to undergo liver transplantation or face death. This article reports a patient with HBV infection-related acute liver failure who achieved clinical cure and HBsAg seroconversion after antiviral therapy and symptomatic/supportive treatment， and dynamic monitoring was performed for immunological markers in peripheral blood.
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ABSTRACT The lymphocyte-depleted classic Hodgkin lymphoma (LDCHL), the rarest subtype of classic Hodgkin lymphoma (CHL), is usually diagnosed at an advanced stage (stage IV) and one that unusually involves the liver, causing a rapidly progressive clinical course. We describe a 40-year-old immunocompromised man presenting with a progressive non-cholestatic jaundice and intermittent fever. The abdominal ultrasonography revealed a nodular liver with coarse echotexture and periportal hypodensities. The thoracic and abdominal contrast-enhanced computed tomography revealed right cervical and paraaortic lymphadenopathy, hepatosplenomegaly, diffuse mural thickening of duodenal and jejunal loops, and bilateral lobulated kidneys. Subsequently, he succumbed to his illness secondary to refractory septic shock. On postmortem examination, he was diagnosed with classic Hodgkin lymphoma (lymphocyte-depleted type) involving paraaortic and mediastinal lymph nodes based on morphology and immunochemistry findings. The lymphomatous process involved the liver (causing multiacinar confluent hepatic necrosis) and spleen, both showing tuberculous foci. This autopsy case depicts an uncommon case of acute liver failure due to infiltration of the liver by LDCHL in an HIV-infected patient. The findings of angiotropism and angioinvasion establish the pathological mechanism of liver failure (hepatocellular necrosis) in such cases.
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Liver failure is a common end-stage liver disease syndrome in clinical practice characterized by massive necrosis of hepatocytes leading to rapid liver failure, and it is currently believed that excessive inflammation and immune response are the core mechanisms of this disease. Endogenous lipid mediators are involved in the regulation of a variety of inflammatory processes, including initiation, maintenance, and regression, and eicosanoids and pro-decomposition lipid mediators, as well as their complex metabolic pathways and transduction signals, play a key role in the regulation of these processes. This article reviews the key role of endogenous lipid mediators in the pathophysiological mechanism of inflammation and immune dysfunction in liver failure and the potential significance and new therapeutic opportunities of lipid immune pathway in liver failure, in order to provide new ideas for the clinical diagnosis and treatment of liver failure.
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Objective To investigate the predictive factors for acute kidney injury (AKI) in patients with acute liver failure (ALF), and to establish a new predictive model. Methods Clinical data were collected from 253 patients who were diagnosed with ALF in The First Affiliated Hospital of Zhengzhou University from January 2015 to October 2021, and according to the presence or absence of AKI, these patients were divided into non-AKI group with 170 patients and AKI group with 83 patients. Related clinical data and laboratory markers were collected. Non-normally distributed continuous data were expressed as M ( P 25 - P 75 ), and the Mann-Whitney U test was used for comparison between two groups; categorical data were expressed as cases (%), and the chi-square test was used for comparison between two groups. The binary logistic regression analysis was used to investigate the risk factors for AKI in ALF patients, and the receiver operating characteristic (ROC) curve was used to evaluate the performance of the indices obtained in predicting AKI in ALF patients. Results Compared with the non-AKI group, the AKI group had a significantly higher proportion of patients with hypertension, diabetes, hepatic encephalopathy, ascites, and pulmonary infection, significantly higher levels of white blood cell count (WBC), international normalized ratio (INR), C-reactive protein, procalcitonin (PCT), neutrophil-to-lymphocyte ratio, and Model for End-Stage Liver Disease (MELD) score, and significantly lower levels of platelet count, lymphocyte-to-monocyte ratio, and PNI (all P < 0.05). The multivariate logistic regression analysis showed that WBC (odds ratio [ OR ]=1.267, 95% confidence interval [ CI ]: 1.124-1.428, P < 0.001), INR ( OR =1.663, 95% CI : 1.205-2.293, P =0.002), PCT ( OR =1.416, 95% CI : 1.137-1.764, P =0.002), and MELD score ( OR =1.098, 95% CI : 1.029-1.172, P =0.005) were risk factors for the development of AKI in patients with ALF. The ROC curve analysis showed that the combination of WBC+INR+PCT+MELD had the largest area under the ROC curve (AUC) of 0.908 in predicting AKI in ALF patients, while WBC, INR, PCT, and MELD alone had an AUC of 0.776, 0.771, 0.746, and 0.780, respectively, in predicting AKI. Conclusion WBC, INR, PCT, and MELD score are independent influencing factors for AKI in patients with ALF, and the predictive model established based on these four indices has a relatively high predictive value.
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Objective:To summarize the nursing experience of liver transplantation in a patient with acute liver failure, renal injury, shock, hepatic encephalopathy and hyperlactic acidemia caused by K-amine poisoning.Methods:A case of severe K-amine poisoning admitted to the First Affiliated Hospital of Zhejiang University Medical College on June 29, 2022 was treated by multidisciplinary team cooperation. The treatment scheme of blood purification combined with liver transplantation was adopted, individualized nursing measures were implemented, including fluid resuscitation, blood purification, prevention and treatment of complications such as brain edema and infection of hepatic encephalopathy, immunosuppressive treatment after liver transplantation, occupational protection, health education and follow-up management.Results:After careful treatment and nursing, the liver and kidney function of the patient recovered smoothly and was discharged on the 33rd day after liver transplantation.Conclusions:In view of the rapid progress of acute liver failure caused by K-amine poisoning and the involvement of multiple organs, blood purification combined with liver transplantation successfully saved the lives of patients under the cooperation of multidisciplinary teams. Do a good job in disease monitoring and individualized nursing to improve the long-term survival rate of patients.
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Objective:To explore the application of list nursing management combined with different artificial liver treatment modes in patients with liver failure.Methods:Fifty-three patients with liver failure hospitalized in Bethune Hospital of Shanxi Province from July 2020 to July 2021 were selected as the control group, 63 patients with liver failure hospitalized in Bethune Hospital of Shanxi Province from July 2021 to July 2022 were selected as the intervention group. According to the different treatment modes of artificial liver for patients, plasma exchange (PE), double plasma molecular adsorption system (DPMAS) and PE + DPMAS treatment were set up in the two groups. The control group received routine nursing care, while the intervention group received checklist nursing care in addition. The changes of albumin (ALB) and prothrombin time (PT) indexes before and after the different treatment modes were compared, together with the occurrence of complications between the two groups after the intervention.Results:The baseline data between the two groups was balanced, the difference had no statistical significant ( P>0.05). After the therapy, the level of ALB of patients who had accepted DPMAS and PE + DPMAS in the intervention group were 25.3(24.0, 27.9) and 23.2(22.4, 26.3) g/L, which were lower than the 28.2(26.3, 29.7) and 29.4(27.2, 30.0) g/L in the control group, the differences were significant ( Z = 2.47, 3.55, both P<0.05). After the therapy, the level of PT of patients in the intervention group under all three treatment modes were 15.8(14.8, 16.8), 22.7(19.2, 26.2) and 6.0(14.6, 20.0) s, which were lower than the 17.4(15.9, 20.9), 26.3(21.4, 36.4) and 21.2(16.9, 23.4) s in the control group, the differences were significant ( Z = 2.10, 2.07, 2.21, all P<0.05). In the intervention group, there were 6 cases of hypotension, anaphylaxis, bleeding, coagulation and infection under the DPMAS treatment mode, which was significant lower than the 11 cases in the control group ( χ2 = 4.97, P<0.05). There were 4 cases in the intervention group with the PE + DPMAS treatment mode occurred complications in above, which were significant lower than the 11 cases in the control group ( χ2 = 6.87, P<0.01). Conclusions:Artificial liver treatment can improve patients′ liver function and coagulation, and list nursing management may help to improve the effect of artificial liver treatment. It can improve nurses′ awareness of risk prejudgement, reduce various risks in the treatment process, reduce the incidence of adverse reactions, and enhance health care and patient satisfaction.
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Objective:To explore the impact of serum carbamoyl phosphate synthase 1 (CPS1) level on prognosis of patients with hepatitis E-related acute liver failure (HEV-ALF).Methods:This retrospective analysis included 100 HEV-ALF patients, 100 patients with acute hepatitis E (AHE) and 100 healthy controls who admitted or underwent health checkup from December 2018 to June 2019 in six hospitals, including the First Affiliated Hospital, Zhejiang University School of Medicine. HEV-ALF patients were divided into non-survial ( n=21) and survival ( n=79) subgroups according to results of 30-day follow-up results. HEV-ALF patients were also divided into the high ( n=50) and low ( n=50) serum CPS1 level groups. HEV-ALF patients were further divided into the improvement ( n=55), fluctuation ( n=32) and deterioration ( n=13) subgroups. The general clinical data from all participants were collected. Serum CPS1 levels were detected by enzyme linked immunosorbent assay. The survival time in the high and low serum CPS1 level groups were presented in the Kaplan-Meier curve. The correlation between serum CPS1 level and HEV-ALF related conventional parameters was also analyzed by linear regression. The efficacy of serum CPS1 level on predicting the 30-day mortality of HEV-ALF patients was estimated by the receiver operating characteristic curve and area under curve (AUC). Results:Serum CPS1 level was significantly higher in HEV-ALF patients than in AHE patients [958.59 (665.52, 1 105.83) pg/ml vs 549.38 (495.02, 649.08) pg/ml, P<0.001], and serum CPS1 level was significantly higher in AHE patients than in healthy controls [549.38 (495.02, 649.08) pg/ml vs 469.89 (373.32, 564.53) pg/ml, P<0.001]. The level of serum CPS1 was significantly lower in the HEV-ALF survival group than in the HEV-ALF non-survival group [922.6 (652.7, 1, 042.3) pg/ml vs 1 252.8 (933.3, 1 555.8) pg/ml, P<0.001]. In addition, the survival time was shorter in the high serum CPS1 level group than in the low serum CPS1 level group [24.59 (22.11, 27.06) d vs 28.16 (26.25, 30.07) d, P=0.045]. Serum CPS1 levels were increased in the fluctuation and deterioration groups [Fluctuation: 1 328.3 (1 184.3, 1 964.0) pg/ml vs 1 245.7 (1 102.0, 1 937.6) pg/ml, P<0.01; Deterioration: 1 483.6 (1 275.9, 1 656.8) pg/ml vs 1 332.2 (1 197.4, 1 509.8) pg/ml, P<0.01], while decreased in the improvement group [810.3 (599.7, 904.5) pg/ml vs 922.6 (679.5, 1 039.6) pg/ml, P<0.01] over time. Besides, a linear positive correlation was found between serum CPS1 level and alanine aminotransferase (ALT) and total bilirubin (TBIL) (ALT: r=0.339, P<0.001; TBIL: r=0.304, P=0.002). The AUC of serum CPS1 level to predict the 30-day mortality of HEV-ALF patients was 0.803 (95% CI 0.666-0.941), the sensitivity and specificity were 66.67% and 97.47%, respectively. Conclusion:Serum CPS1 level was significantly increased in HEV-ALF patients, and closely related to the prognosis of patients with HEV-ALF.
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ABSTRACT BACKGROUND: Liver transplantation (LT) is the only treatment that can provide long-term survival for patients with acute-on-chronic liver failure (ACLF). Although several studies identify prognostic factors for patients in ACLF who do not undergo LT, there is scarce literature about prognostic factors after LT in this population. AIM: Evaluate outcomes of ACLF patients undergoing LT, studying prognostic factors related to 1-year and 90 days post-LT. METHODS: Patients with ACLF undergoing LT between January 2005 and April 2021 were included. Variables such as chronic liver failure consortium (CLIF-C) ACLF values and ACLF grades were compared with the outcomes. RESULTS: The ACLF survival of patients (n=25) post-LT at 90 days, 1, 3, 5 and 7 years, was 80, 76, 59.5, 54.1 and 54.1% versus 86.3, 79.4, 72.6, 66.5 and 61.2% for patients undergoing LT for other indications (n=344), (p=0.525). There was no statistical difference for mortality at 01 year and 90 days among patients with the three ACLF grades (ACLF-1 vs. ACLF-2 vs. ACLF-3) undergoing LT, as well as when compared to non-ACLF patients. CLIF-C ACLF score was not related to death outcomes. None of the other studied variables proved to be independent predictors of mortality at 90 days, 1 year, or overall. CONCLUSIONS: LT conferred long-term survival to most transplant patients. None of the studied variables proved to be a prognostic factor associated with post-LT survival outcomes for patients with ACLF. Additional studies are recommended to clarify the prognostic factors of post-LT survival in patients with ACLF.
RESUMO RACIONAL: O transplante hepático (TH) é o único tratamento a proporcionar sobrevida a longo prazo para pacientes com "acute-on-chronic liver failure" (ACLF). Vários estudos identificaram fatores prognósticos para pacientes em ACLF que não realizam TH, porém há poucos dados na literatura sobre fatores prognósticos nessa população transplantada. OBJETIVOS: Avaliar desfechos de pacientes ACLF submetidos a TH, e seus preditores de mortalidade. MÉTODOS: Foram avaliados pacientes em ACLF submetidos a TH entre janeiro de 2005 e abril de 2021. Variáveis como valores CLIF-C ACLF e pontuação no ACLF foram comparadas com os desfechos. RESULTADOS: A sobrevida de ACLF pós TH de pacientes (n=25) em 90 dias, 1, 3, 5 e 7 anos, foi de 80, 76, 59,5, 54,1 e 54,1% versus 86,3, 79,4, 72,6, 66,5 e 61,2% para pacientes submetidos a TH por outras indicações (n=344), (p=0,525). Não houve diferença estatística para mortalidade em 01 ano e 90 dias entre pacientes com os três graus de ACLF (ACLF-1 vs. ACLF-2 vs. ACLF-3), bem como quando comparados a pacientes não ACLF. O escore "chronic liver failure consortium" (CLIF-C) ACLF não se correlacionou com desfechos de óbito. Nenhuma das outras variáveis estudadas mostrou-se preditora independente de mortalidade em 90 dias, após um ano ou global. CONCLUSÕES: TH conferiu sobrevida em longo prazo à maioria dos pacientes transplantados, semelhante aos pacientes submetidos à TH por outras indicações. Nenhuma das variáveis estudadas mostrou-se fator prognóstico associado a desfechos de sobrevida pós-TH para pacientes com ACLF. Estudos adicionais são necessários para estabelecer fatores prognósticos pós-TH em pacientes com ACLF.
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Liver transplantation is the only effective therapy to reduce the high mortality associated with acute liver failure and acute on chronic liver failure (ACLF). Single-pass albumin dialysis (SPAD) is an extracorporeal supportive therapy used as a bridge to liver transplantation or regeneration. We report a 44-year-old man with alcoholic cirrhosis admitted for critical COVID-19 pneumonia that evolves with ACLF. SPAD technique was performed completing six sessions, with a reduction of bilirubin and ammonia levels. He evolved with severe respiratory failure and refractory septic shock, dying. SPAD is a safe and efficient technique aimed to eliminate liver toxins, preventing multiorgan damage interrupting the process known as the "autointoxication hypothesis". It is easy to implement in any critical patient unit and has lower costs than other extracorporeal liver support therapies.
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Humanos , Masculino , Adulto , Transplante de Fígado , Insuficiência Hepática Crônica Agudizada/etiologia , Insuficiência Hepática Crônica Agudizada/terapia , COVID-19/complicações , Diálise Renal/métodos , Albuminas/uso terapêuticoRESUMO
Drug induced liver injury (DILI) can be can be triggered by many medications including antituberculosis drugs. We present the case of a 37-year-old woman with a smear- positive pulmonary tuberculosis who started treatment with first-line antituberculosis drugs and 4 weeks later presented jaundice, somnolence and a morbilliform generalized rash with progressive neurologic deterioration which had a fatal outcome. Antituberculosis drugs can cause DILI in 2 to 28% of patients and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) in 1.2%. Acute liver failure (ALF) can occur in 35% of patients with DILI with an overall mortality of 9.7%. If the ALF is unresponsive to medical treatment, liver transplantation has shown promising results and can avoid progression of complications. DILI can be a serious medical condition in patients receiving antituberculosis drugs. If ALF develops and is unresponsive to medical treatment, liver transplantation should be considered as the treatment of choice.
La injuria hepática inducida por fármacos (IHIF) puede ser desencadenado por varios medicamentos incluyendo fármacos anti tuberculosos. Presentamos el caso de una paciente mujer de 37 años con un frotis positivo para tuberculosis pulmonar quien inició tratamiento de primera línea y 4 semanas después, presentó ictericia, somnolencia y un exantema generalizado de tipo morbiliforme con deterioro neurológico progresivo y un desenlace fatal. Los fármacos anti tuberculosos pueden producir injuria inducida por fármacos en 2 a 28% de pacientes y síndrome de DRESS (reacción de sensibilidad a medicamentos con eosinofilia y síntomas sistémicos) en 1,2%. La falla hepática aguda (FHA) en pacientes con injuria hepática inducida por fármacos, puede presentarse en un 35% con una mortalidad del 9,7%. Si la FHA no responde a tratamiento médico, el trasplante hepático ha mostrado resultados positivos y evita la progresión de complicaciones. La IHIF puede ser una condición médica grave en pacientes que reciben medicamentos antituberculosos. Si se desencadena una FHA y no responde a tratamiento médico, debe considerarse con urgencia la posibilidad de trasplante hepático.
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Objective:To investigate the clinical characteristics and risk factors for the progression of acute-on-chronic liver failure(ACLF)associated with hepatitis B in elderly patients.Methods:A total of 168 elderly patients with hepatitis B-related acute-on-chronic liver failure(HBV-ACLF)at Tianjin Third Central Hospital who met the diagnostic criteria of the Asian Pacific Association for the Study of the Liver(APASL)-ACLF were enrolled, 176 non-elderly HBV-ACLF patients served as the control group during the same period, and their baseline and progression data were recorded.At the same time, the elderly group was divided into the progressive subgroup and the non-progressive subgroup based on the diagnostic criteria of the European Society for the Study of the Liver(EASL)-ACLF, and their baseline and progression data were recorded.Independent risk factors for HBV-ACLF progression in the elderly were analyzed using multivariate Cox proportional risk model regression.Results:Compared with non-elderly patients with HBV-ACLF, elderly patients were more likely to progress to meet the EASL-ACLF diagnostic criteria and have higher mortality.Multivariate Cox proportional risk model regression analysis showed that baseline arterial lactic acid levels( HR=1.77, 95% CI: 1.36-2.30, P<0.01), secondary nosocomial infections( HR=13.90, 95% CI: 3.73-51.87, P<0.01), rates of change in maximum total bilirubin( HR=1.08, 95% CI: 1.01-1.15, P=0.04), rates of change in maximum MELD( HR=4.06, 95% CI: 1.53-10.77, P=0.01)and rates of change in maximum CLIF-SOFA( HR=12.74, 95% CI: 2.46-66.08, P<0.01)were independent risk factors for progression of HBV-ACLF in elderly patients. Conclusions:Compared with non-elderly patients, elderly patients with HBV-ACLF have more advanced disease and higher mortality.Therefore, risk factors should be identified as soon as possible and treatment plans should be formulated as soon as possible to further reduce the mortality.
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Objective To investigate the protective effect of adult human liver-derived stem cell exosomes (HLSC-exo) intravenously injected at different time points against acute liver injury induced by concanavalin A (ConA) in mice. Methods HLSC-exo was extracted by differential centrifugation. Western blot was used to measure the expression of the marker proteins CD9 and CD63, and nanoparticle tracking analysis was used to investigate particle size distribution. A total of 56 male C57BL/6 mice were randomly divided into blank control group, ConA model group, and HLSC-exo treatment group. The ConA model group and the HLSC-exo treatment group were further divided into 3-, 6-, and 12-hour subgroups according to the interval between phosphate buffer or HLSC-exo injection and ConA injection. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) were measured, and the gross morphology and histopathology of the liver were compared between groups. 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. Results HLSC-exo was a membranous vesicle with a diameter of 90-110 nm, with a clear saucer-like structure under an electron microscope and marked expression of its specific marker proteins CD9 and CD63. In the blank control group, the levels of ALT and AST were 31.81±6.74 U/L and 69.75±8.30 U/L, respectively. Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had significant increases in the levels of ALT and AST (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had significant reductions in the levels of ALT and AST (225.58±115.59 U/L vs 1989.32±347.67 U/L, 1174.71±203.30 U/L vs 2208.33±349.96 U/L, 303.53±126.68 U/L vs 2534.27±644.72 U/L, 1340.70±262.56 U/L vs 2437.13±288.13 U/L, all P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had significantly greater reductions ( P < 0.001). In the blank group, the levels of IL-10 and TNF-α were 313.51±10.97 pg/ml and 476.05±7.31 pg/ml, respectively. Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had a significant reduction in the level of IL-10 (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had a significant increase in the level of IL-10(331.61±10.46 pg/ml vs 266.20±8.15 pg/ml, 288.13±10.74 pg/ml vs 264.41±9.12 pg/ml, both P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had a significantly greater increase ( P < 0.001). Compared with the blank control group, the 3-, 6-, and 12-hour ConA model groups had a significant increase in the level of TNF-α (all P < 0.001); compared with the 3-and 6-hour ConA model groups, the 3-and 6-hour HLSC-exo treatment groups had a significant reduction in the level of TNF-α (478.26±12.99 pg/ml vs 551.31±17.70 pg/ml, 515.58±7.18 pg/ml vs 556.21±11.15 pg/ml, both P < 0.001); compared with the 6-hour HLSC-exo treatment group, the 3-hour HLSC-exo treatment group had a significantly greater reduction ( P < 0.001). Compared with the 3-and 6-hour ConA model groups in terms of the gross morphology and histopathology of the liver, the 3-and 6-hour HLSC-exo treatment groups had a significant reduction in the degree of hepatocyte necrosis, and the 3-hour HLSC-exo treatment group had a basically complete lobular structure, with sporadic spotty necrosis; the 12-hour HLSC-exo treatment group had no significant improvement in hepatocyte necrosis compared with the 12-hour ConA model group. Conclusion Intravenous injection of adult HLSC-exo can alleviate acute liver injury induced by ConA in mice, and injection at 3 hours in advance has the most significant protective effect. Regulation of cytokines is one of the important mechanisms for HLSC-exo to alleviate liver injury.
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Although pediatric acute liver failure (PALF) is rare in clinical practice, it seriously threatens the life and health of children due to acute onset and rapid progression. PALF has various etiologies, and at present, it is still unable to identify the etiology in a relatively large proportion of children. The clinical manifestations of PALF are also different from those of adults, and it is difficult to judge early hepatic encephalopathy in infants and young children. It is very important to maintain the stability of internal environment, provide etiological treatment, and avoid drug abuse and the abuse of blood products. Blood purification can be performed for patients with related indications to win more time for autogenous liver function recovery and liver transplantation, and the precise diagnosis and treatment of PALF should be taken seriously in clinical practice.
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Neonatal acute liver failure is a rare and life-threatening disease in the neonatal period with complete or substantial loss of liver function, and liver cirrhosis can be identified after birth, with a high mortality rate. The main etiologies of this disease include autoimmune liver diseases during pregnancy, viral infection, blood diseases, metabolic diseases, ischemic injury, and other rare causes. At present, etiological treatment is the main treatment method, and liver transplantation is still an important option for patients with unknown etiology or no response to established treatments. Currently there are few studies on neonatal acute liver failure, so prospective studies are needed to investigate the influencing factors for treatment and prognosis.
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Acute liver failure (ALF) in infants and children is a severe life-threatening disease caused by multiple etiologies. Recurrent acute liver failure (RALF) is defined as the occurrence of acute liver injury two or more times, with at least one episode meeting the diagnostic criteria for ALF. Biochemical parameters usually return to normal between acute liver injury episodes in children with RALF. Clinical etiologies of RALF include infections, immunologic disorders, drug, and toxin, as well as hereditary or metabolic disorders, and some episodes of RALF caused by hereditary liver disorders are always associated with fever. This article discusses the diagnosis and treatment of fever-related RALF caused by genetic defects of NBAS, SCYL1, and RINT1.
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Acute liver failure (ALF) is a rare and extremely severe clinical form of Wilson's disease (WD), characterized by progressive aggravation of jaundice and significant coagulation disorder with acute intravascular hemolysis. There is a high risk of severe complications such as hepatic encephalopathy and acute renal failure, and the disease progresses rapidly after onset and has a high mortality rate. At present, it is difficult to diagnose WD presenting as ALF in the early stage due to a lack of unified indicators for rapid diagnosis. Liver transplantation was considered the only effective treatment method for this disease in the past; however, recent studies have shown that medical treatment without liver transplantation can achieve autologous liver relief and recovery in some patients with WD-ALF.
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Acute liver failure (ALF) in children has complex etiologies, among which inherited metabolic diseases account for a high proportion, especially in infants and young children. Inherited metabolic diseases are a group of congenital diseases with destruction of cell physiological function caused by metabolism-related gene mutations, with various types and diverse clinical manifestations. ALF is one of the serious complications caused by such diseases and is easily neglected due to a lack of specific manifestations. ALF caused by such etiologies should be identified as early as possible to reverse the progression of ALF and improve the prognosis of patients. This article summarizes the common inherited metabolic diseases that can cause ALF in children, in order to improve the awareness of such etiology among physicians.
RESUMO
Pediatric acute liver failure (PALF) is a rare syndrome with high mortality, and at present, liver transplantation is still the only effective treatment method for PALF. In recent years, the technology of liver transplantation in children has become more and more mature and has significantly improved the prognosis of PALF patients in China. However, there are still many problems in liver transplantation for PALF patients. Comprehensive discussion of objective problems before, during, and after liver transplantation may further improve the overall prognosis of PALF patients.