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BACKGROUND: The increased expression of G3BP1 was positively correlated with the prognosis of liver failure. AIM: To investigate the effect of G3BP1 on the prognosis of acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) after the treatment of artificial liver support system (ALSS). METHODS: A total of 244 patients with ALF and ACLF were enrolled in this study. The levels of G3BP1 on admission and at discharge were detected. The validation set of 514 patients was collected to verify the predicted effect of G3BP1 and the viability of prognosis. RESULTS: This study was shown that lactate dehydrogenase (LDH), alpha-fetoprotein (AFP) and prothrombin time were closely related to the prognosis of patients. After the ALSS treatment, the patient' amount of decreased G3BP1 index in difference of G3BP1 between the value of discharge and admission (difG3BP1) < 0 group had a nearly 10-fold increased risk of progression compared with the amount of increased G3BP1 index. The subgroup analysis showed that the difG3BP1 < 0 group had a higher risk of progression, regardless of model for end-stage liver disease high-risk or low-risk group. At the same time, compared with the inflammatory marks [tumor necrosis factor-α, interleukin (IL)-1ß and IL-18], G3BP1 had higher discrimination and was more stable in the model analysis and validation set. When combined with AFP and LDH, concordance index was respectively 0.84 and 0.8 in training and validation cohorts. CONCLUSION: This study indicated that G3BP1 could predict the prognosis of ALF or ACLF patients treated with ALSS. The combination of G3BP1, AFP and LDH could accurately evaluate the disease condition and predict the clinical endpoint of patients.
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BACKGROUND: Acute-on-chronic liver failure (ACLF) patients exhibit an imbalance in intestinal microbiota, and bile acids (BAs) can affect the composition of intestinal microbiota. Although Artificial liver support system (ALSS) is a treatment for ACLF, the impact of ALSS on intestinal microbiota and serum BA profiles of ACLF patients remains unclear. METHODS: A prospective study was conducted, which included 51 patients diagnosed with ACLF. These patients were stratified into two groups based on the utilization of an ALSS during their treatment period: a standard medical treatment group (SMT group), comprising 19 patients, and an ALSS combined with SMT group (ALSS group), comprising 32 patients. Blood and stool samples were collected from the patients on the day of admission and 14 days after treatment. Additionally, eight healthy controls were recruited, and their stool samples were also collected. The intestinal microbiota was sequenced using the 16S rRNA sequencing technique, while the serum BA profiles were determined using ultra-performance liquid chromatography/mass spectrometry. RESULTS: ACLF patients exhibited imbalances in intestinal microbiota and abnormalities in BA profiles. Compared to SMT alone, the combined ALSS and SMT was more effective in regulating intestinal microbiota imbalance and increasing the concentrations of ursodeoxycholic acid and glycoursodeoxycholic acid. Correlation analysis revealed a significant correlation between intestinal microbiota and Bas. Furthermore, the preliminary correlation heatmap indicated that the Faecalibaculum, Gemmiger, and taurochenodeoxycholic acid were associated with clinical improvement. CONCLUSIONS: Our study identified the compositional characteristics of the intestinal microbiota and serum BA in ACLF patients, emphasizing the impact of ALSS on both intestinal microbiota and serum BA profiles.
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Background: Elevated international normalized ratio of prothrombin time (PT-INR) is one of the key characteristics of acute-on-chronic liver failure (ACLF). Whether the staging of PT-INR has the ability to screen out subgroups of ACLF patients who would be more eligible for artificial liver support system (ALSS) treatment has not been studied in detail. Methods: A previous study enrolled patients receiving ALSS treatment with regional citrate anticoagulation from January 2018 to December 2019. Patients with different PT-INR intervals were retrospectively enrolled: 1.3 ≤ PT-INR < 1.5 (Pre-stage), 1.5 ≤ PT-INR < 2.0 (Early-stage), 2.0 ≤ PT-INR < 2.5 (Mid-stage), and PT-INR ≥ 2.5 (End-stage). The Cox proportional hazards models were used to estimate the association between stages of ACLF or sessions of ALSS treatment and 90 day mortality. Results: A total of 301 ACLF patients were enrolled. The 90 day mortality risk of Early-stage ACLF patients (adjusted hazard ratio (aHR) (95% confidence interval (CI)), 3.20 (1.15-8.89), p = 0.026), Mid-stage ACLF patients (3.68 (1.34-10.12), p = 0.011), and End-stage ACLF patients (12.74 (4.52-35.91), p < 0.001) were higher than that of Pre-stage ACLF patients, respectively. The 90 day mortality risk of Mid-stage ACLF patients was similar to that of Early-stage ACLF patients (1.15 (0.69-1.94), p = 0.591). The sessions of ALSS treatment was an independent protective factor (aHR (95% CI), 0.81 (0.73-0.90), p < 0.001). The 90 day mortality risk in ACLF patients received 3-5 sessions of ALSS treatment was lower than that of patients received 1-2 sessions (aHR (95% CI), 0.34 (0.20-0.60), p < 0.001), whereas the risk in patients received ≥6 sessions of ALSS treatment was similar to that of patients received 3-5 sessions (0.69 (0.43-1.11), p = 0.128). Conclusion: ACLF patients in Pre-, Early-, and Mid-stages might be more eligible for ALSS treatment. Application of 3-5 sessions of ALSS treatment might be reasonable.
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Objective:To assess the predictors of outcomes for different subtypes of liver failure, and the effectiveness of artificial liver support systems in the treatment of liver failure.Methods:The clinical data of 112 patients with hepatitis B virus (HBV)- and non-HBV-related liver failure admitted to the intensive care unit (ICU) of the Fifth People's Hospital of Wuxi were collected from January to December 2020. The relevant etiologies of acute, subacute, acute-on-chronic, subacute-on-chronic, chronic subtype liver failure were analyzed. The efficacies of artificial liver support systems in the treatment of various subtypes of liver failure were also compared. The correlation of various indicators was analyzed by Spearman correlation analysis, the risk factors affecting the prognosis of patients with liver failure were analyzed by multivariate Logistic regression equation, and receiver operator characteristic curve (ROC curve) of subjects was plotted to evaluate the predictive value of each risk factor for the prognosis of patients with liver failure.Results:Among the 112 liver failure patients, 63 were caused by hepatitis B and 49 were caused by non-hepatitis B. The liver failure caused by hepatitis B was 6 times higher than for men than for women, which was higher than that of non-HBV liver failure group (1.33 times). Antithrombin Ⅲ (AT Ⅲ) and total bilirubin (TBil) levels of subacute liver failure were higher than those of pre-liver failure in the HBV liver failure group [AT Ⅲ: (59.33±14.57)% vs. (35.66±20.72)%, TBil (μmol/L): 399.21±112.94 vs. 206.08±126.96, both P < 0.05]. The levels of AT Ⅲ in patients with pre-liver failure and chronic liver failure in the non-HBV liver failure group were significantly higher than those with acute liver failure [(58.33±15.28%), (44.00±19.10)% vs. (31.33±7.57)%, both P < 0.05], patients with acute liver failure had significantly lower level of TBil than pre-liver failure (μmol/L: 107.83±49.73 vs. 286.20±128.92, P < 0.05), the TBil levels in patients with subacute and acute-on-chronic liver failure were also significantly higher than that in pre-liver failure group (μmol/L: 417.27±118.60, 373.00±187.00 vs. 286.20±128.92, both P < 0.05). Patients with subacute liver failure, subacute-on-chronic liver failure and chronic liver failure in the non-HBV failure group were significantly longer than those in acute liver failure (days: 36.00±8.31, 27.52±11.71, 27.72±22.71 vs. 11.00±1.41, all P < 0.05). There was no statistically significant difference in the case fatality rate of using the artificial liver support system between the HBV failure group and the non-HBV failure group (55.6% vs. 50.0%, P < 0.05), the levels of AT Ⅲ in the two groups of surviving patients were significantly higher than that of the dead [HBV liver failure group: (36.20±6.26)% vs. (27.33±8.87)%, non-HBV liver failure group: (41.06±4.16)% vs. (28.71±12.35)%, both P < 0.01]. Correlation analysis showed that there was a clear positive correlation between AT Ⅲ and TBil in the dead patients of HBV liver failure group and the survival and death patients of non-HBV liver failure group ( r values were 0.069, 0.341, 0.064, and P values were 0.723, 1.196 and 0.761, respectively); there was a significant inverse correlation between AT Ⅲ and TBil in the HBV liver failure group ( r = -0.105, P = 0.745). Multivariate Logistic regression analysis showed that AT Ⅲ was an independent risk factor affecting the prognosis of patients with non-HBV liver failure [odd ratio ( OR) = 1.023, 95% confidence interval (95% CI) was -0.001 to 0.001, P = 0.007]. TBil was an independent risk factor affecting prognosis of patients with HBV liver failure ( OR = 1.005, 95% CI was -0.002 to -7.543, P = 0.033). The analysis of ROC curve showed that AT Ⅲ had a predictive value for the prognosis of patients with non-HBV liver failure, the area under the ROC curve (AUC) = 0.747, the 95% CI was 0.592-0.902, P = 0.009. When the optimal truncation value was 39.5%, its sensitivity and specificity were 83.33% and 56.25%, respectively. Conclusions:Artificial liver support system treatment of liver failure was difficult to effectively reduce the mortality of patients with end-stage liver failure. In addition to AT Ⅲ, TBil also could be used as an indicator to assess liver compensatency and predict prognosis in liver failure patients.
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Liver is the most common location for hematogenous spread of solid tumors. Clinically acute hepatic failure ( ALF) secondary to either a solid organ tumor or a hematologic malignancy is rare,but with a poor prognosis and high mortality. The time between the onset of symptoms and ALF was relatively rapid. Malignancy is one of the causes of pediatric acute liver failure (PALF). Common clinical symptoms were jaundice,haemorrhage,and hepatic encephalopathy. It is lack of specific clinical features and difficult to diagnose in early phase. Delayed diagnosis and treatment contribute to poor prognosis. How to combine the treatment of primary tumors and liver protection is critical issue to clinician. The effective therapy for patients with PALF is liver transplantation. In recent years,the development of artificial liver support is to provide a facilitating recovery chance and to prolong the window of opportunity for liver transplantation.
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Objective To conclude nursing experience of full series artificial liver support system in the treatment of acute fatty liver in pregnancy. Methods Development of artificial liver support system according to patient's condition, total continuous renal replacement therapy 7days, double plasma molecular absorb system 3 times, plasma replacement 3 times, molecular adsorbent circulation system 2 times. Results After treatment, the patient was discharged after 20 days in hospital. Conclusions The full range of artificial liver support system can effectively treat the patients with acute fatty liver in pregnancy, it will greatly reduce the mortality of patients with acute fatty liver in pregnancy.
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Objective To observe the efficacy of extracorporeal liver support by using less fresh frozen plasma in the treat‐ment of acute‐on‐chronic liver failure.Methods A total of 45 patients with acute‐on‐chronic liver failure were divided into ob‐servation group[plasma perfusion(PP) with a small amount of plasma+ plasma exchange(PE)] ,control group 1(PE) ,control group 2(PP+PE)in terms of the amount of plasma used on the day of treatment. All the patients received artificial liver treatnts 62 times totally.Results The clinical symptoms were improved in the three groups after treatments.There were significant differences in the decrease of alanine transaminase (ALT) ,aspartate transaminase(AST) and direct bilirubin(DBil)rather than the decrease of total bilirubin(TBil)and blood ammonia among the groups.No significant difference was noted in the liver and kidney function among the three groups. The improvement of the coagulation function was poor in the observation group when compared with the control group 1 and control group 2 and there were significant differences.Conclusion During the short sup‐ply of the plasma ,plasma perfusion combined with small amount of plasma can be considered to be used in artificial liver treat‐ments ,which can effectively decrease the level of TBil ,relieve symptoms and decrease the occurrence of complications.
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Acute liver failure is a pediatric clinical critical disease with complex etiology,rapid progress and medical treatment,contributing to a high fatality rate. Artificial liver support system can remove a variety of toxic substances through mechanical,physicochemical or biological device to replace part of liver function like metabolism,detoxification,or synthesis temporarily to win precious time for liver cell regeneration and further clinical therapy,which has become an important treatment of acute liver failure at present. Considered the limita-tions of different blood purification mode,combined mode of blood purification is mostly applied in clinical ther-apy. This article aims to review the effect of plasma exchange combined with continuous veno-venous hemodial-ysis/filtration for the treatment of children with acute liver failure.
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Liver transplantation is the best treatment for end-stage liver disease.Because of the severe shortage of donor sources,most of the patients died while waiting for liver grafts.Artificial liver support system can improve the liver function in a short time,and help patients to pass the waiting periods.Artificial liver support system takes place of composition,detoxification and metabolism function of liver,stabilizes the physiological and biochemical index of liver,relieves the burden of liver and helps patients to prepare for the liver transplantation.With the wide application of artificial liver support system,new types of the artificial liver support systems gradually conquered the defects of the old types,but they still have their own defects.This review concludes the merits and demerits of artificial liver systems,its clinical application and the problems so as to help the treatment of end-stage liver disease.
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Objective To investigate the optimal therapy for patients with acute-on-chronic liver failure induced by hepatitis B.Methods A total of 302 patients with acute-on-chronic liver failure induced by hepatitis B in the Affiliated Infectious Diseases Hospital of Fujian Medical University were enrolled during January 2008 to January 2010.Patients were divided into group A ( medical treatment,n =57 ),group B (medical + antiviral treatment,n =80),group C ( medical + antiviral + artificial liver support system (ALSS),n =124) and group D (medical + antiviral + ALSS + traditional Chinese medicine treatment,n =41 ).Liver and renal function,prothrombin activity (PTA) and HBV DNA load were observed at the baseline,week 1,4,8,12 and the end of the treatment.All groups were followed up for 48 weeks to observe the survival rates.Kruskal-Willis H test was used to compare the efficacies in four groups,and Cox proportional hazards regression model was used for survival analysis. Results There was no difference among four groups in curative effects at week 4 ( H =3.213,P =0.360 ),but there was significant difference at week 12 (H =8.722,P =0.033).The one-year mortality rates for groups A,B,C,D were 36.84％ (21/57),32.50％ (26/80),26.61％ (33/124) and 24.39％ ( 10/41 ),respectively.The death risks of group C and D were 0.566 and 0.396 times of that in group B ( P =0.036 and 0.016).Conclusion Nucleoside analogue and ALSS plus medical treatment can effectively increase the survival rates of the patients with acute-on-chronic liver failure induced by hepatitis B.
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Despite a combination of all available treatment, the mortality of liver failure is very high,especially in children patients. Artificial liver support methods have been tested for over 50 years. Standard techniques of blood purification like hemodialysis, adsorption, hemo or plasma filtration as well as bioreactorbased approaches using liver cells or tissues have been used. It' s believed that the damaged liver has the ability to return to normal. Artificial liver support systems are expected to be useful for temporary support of liver function. If the liver does not regenerate to normal functions, an artificial liver support system may be useful as a bridge to liver transplantation. In conclusion, artificial liver support method appears to be a reliable therapy for advanced liver diseases and has significantly decreased the mortality of liver failure. Artificial liver support system has been used in children patients as well, but it still needs more researches.
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Multiple organ dysfunction(MODS) can be seen in critically ill children.Modality of extracorporeal life support (ECLS) is the use of mechanical devices to support life when the native organ failure occurs.Extracorporeal devices can effectively support heart,lung,liver,and kidney function of the sick children with MODS.Unlike the adult experience,ECLS is an effective therapy in children with MODS,because the underlying disease possibly is reversible.This article focuses on the different modalities of ECLS which involve extracorporeal membrane oxygenation,continuous renal replacement therapy,artificial liver support system,hemoperfusion and plasma exchange.
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The role of the high mobility group box 1 (HMGB-1) in acute hepatic failure and the ef- fect of artificial liver support system treatment on HMGB-1 level were investigated. Pig models of acute hepatic failure were induced by D-galactosamine and randomly divided into two groups with or without artificial liver support system treatment. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were detected by the enzyme linked immunosorbent assay (ELISA), the expression of HMGB-1 by Western blot, and serum levels of HMGB-1, liver function and hepatic pathology were observed after artificial liver support system treatment. The levels of TNF-α and IL-1β were increased and reached the peak at 24th h in the acute hepatic failure group, then quickly decreased. The serum level of HMGB-1 was increased at 24th h in the acute hepatic failure group and reached the peak at 48th h, then kept a stable high level. Significant liver injury appeared at 24th h and was continuously getting worse in the pig models of acute hepatic failure. In contrast, the liver injury was significantly alleviated and serum level of HMGB-1 was significantly decreased in the group treated with artificial liver support system (P＜0.05). It was suggested that HMGB-1 may participate in the inflammatory response and liver injury in the late stage of the acute liver failure. Artificial liver support system treatment can reduce serum HMGB-1 level and relieve liver pathological damage.
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Objective:To establish a new fluorescence-based quantitative PCR assay for detecting hepatitis B virus covalently closed circular DNA(HBV cccDNA).To explore the effect of artificial liver support system(ALSS)on total HBV DNA and HBV cccDNA in sera of patients with fulminant hepatitis B.Methods:The serum specimens from 50 patients of fulminant hepatitis B prior to and after treatment with ALSS were collected.Then HBV cccDNA was quantitatively detected by fluorescent PCR with specific primer set and Taqman probe.And the results were analyzed by SAS8.0 statistics software.Results:We successfully established a new fluorescence-based quantitative PCR method for HBV cccDNA.HBV cccDNA was detectable in sera of the patients with fulminant hepatitis B.The level of total HBV DNA and HBV cccDNA decreased significantly following plasma exchange in ALSS.The levels of total HBV DNA and HBV cccDNA had positive correlation with degree of PT,ALT,andAST.Total HBV DNA also had positive correlation with HBV cccDNA.Conclusion:The level of total HBV DNA and HBV cccDNA has positive correlation with degree of PT,ALT,and AST,which might be indication of hepatocyte damage.The finding that significant decrease in total HBV DNA and HBV cccDNA after plasma exchange in ALSS may provide a clue of further research about the fulminant hepatitis B treated with ALSS.
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Objective To evaluate the application of artificial liver support system (ALSS) in severe hepatitis patients before liver transplantation. Methods Double lumen catheters were inserted into the femoralvein to construct the blood conduit in patients receiving ALSS. The blood purification apparatus was applied for plasma replacement and blood perfusion with PIS separator and HA hemoperfusion apparatus. The plasma replacement capacity was 3000ml-4000ml (average 3200 ml) with albumin 20g. The average dosages of both heparin and protamine were 25 mg. The separation speed was 26 ml/min. The replacement blood flow was 100-150 ml/min, and the average treatment time was 120 min. Results The liver function markers, including TB, DB, ALT, AST and NH 3, were improved in patients with ALSS. Conclusion ALSS could correct the imbalance of homeostasis of the patients, eliminate the toxic substances effectively and provide valuable support for liver transplantation.
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Objective:To observe the therapeutic effects of plasma exchange in severe hepatitis. Methods:53 cases served as treatment group and 49 cases as control group. Both groups were similar in basic medical treatment, and an additional treatment of plasma exchange was carried in the treatment group. 186 times of plasmas exchange were performed in the treatment group, to observe and compare the changes in patients of the 2 groups in symptoms、liver functions and survival rates. Results:The clinical symptoms of patients in the treatment group were obviously improved, the liver functions were also obviously improved in the treatment group as compared with the control group, and the survival rate of treatment group was higher than that of control group(73.58% vs 46.94%, P
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Objective To explore the therapeutic effects an d the appropriate treating time of the artificial liver support system through obs ervation and analysis of the changes of the liver function indexes before and af ter the treatment of the artificial liver support system. Methods The changes of BIL-T, BIL-D, ALT, AST, ALP, TBA, ALB, GLB, A/G of the liver fu nction indexes in a total of 38 cases with serious hepatitis treated by artifici al liver support system were observed. Besides, the dynamic changes of the BIL- T, ALT of one case of middle stage and late stage serious type hepatitis respect ively before and after the artificial liver treatment several times were observe d. Results The BIL-T, BIL-D, ALT, AST, ALP of the liver func tion indexes after the artificial liver support system treatment showed remarkab le decline, significant differences existed before and after the treatment (P