Lower level of IL-28A as a predictive index of the artificial liver support system in effective treatment of patients with HBV-ACLF.

BACKGROUND: HBV-related acute-on-chronic liver failure (HBV-ACLF) is the most common type of liver failure with high mortality. Artificial liver support system (ALSS) is an important mean to reduce the mortality of HBV-ACLF but lacking index to assess its effectiveness. The cytokines are closely related to the prognosis of HBV-ACLF patients with ALSS treatment, however, which is not fully understood. METHODS: One hundred forty-two patients with HBV-ACLF and 25 healthy donors were enrolled. The cytokine profile of peripheral blood was determined in the patients before and after ALSS treatment, and their relationship with effectiveness of ALSS treatment in HBV-ACLF was analyzed. RESULTS: Serum IL-28A levels were markedly lower in ALSS-effective patients than those in non-effective patients pre-ALSS treatment. Similarly, serum IL-6 was significantly lower in ALSS-effective patients. Furthermore, for patients with effective treatment, serum IL-28A levels were positively related with IL-6 levels post-ALSS (r = 0.2413, p = 0.0383). The ROC curve analysis showed that serum levels of IL-28A (AUC = 0.6959 when alone or 0.8795 when combined with total bilirubin, platelet count and INR, both p < 0.0001) and IL-6 (AUC = 0.6704, p = 0.0005) were useful indices for separating effective from non-effective ALSS treatment of HBV-ACLF patients. Multivariate logistic regression analysis demonstrated that lower level of IL-28A was independently associated with higher effective rate of ALSS treatments. CONCLUSIONS: Lower level of IL-28A is a predictive biomarker for ALSS in effective treatment of HBV-ACLF patients and IL-28A may be potential target for the treatment of HBV-ACLF.

[Prevention and treatment of infection after artificial liver treatment].

Artificial liver support system is an important method of treating liver failure, but after artificial liver treatment, secondary infections are usually amalgamated. Additionally, infection is a risk factor that aggravates liver failure, leading to an increased mortality and poor prognosis. Therefore, how to prevent and treat occurrence of infection in patients with liver failure is a key factor to improve the efficacy of artificial liver treatment.

Effectiveness and Safety Assessment of Citrate Anticoagulation During Albumin Dialysis in Comparison to Other Methods of Anticoagulation.

Liver failure is a serious and often deadly disease often requiring MARS (Molecular Adsorbent Recirculating System) therapy. Choosing the safe and effective method of anticoagulation during artificial liver support systems seems to be very difficult and extremely important. The aim of this study was to assess effectiveness and safety of regional anticoagulation with citrate in liver failure patients during MARS. We used a single center observational study. We analyzed 158 MARS sessions performed in 65 patients: 105 (66.5%) sessions in 41 patients with heparin anticoagulation, 40 (25.3%) sessions in 19 patients with citrate, and 13 (8%) sessions in only five patients without anticoagulation, that were excluded from part of the analysis. To determine the effectiveness of regional anticoagulation with citrate, probability of filter survival and changes in laboratory parameters were analyzed according to the applied method of anticoagulation. The safety of citrate was determined by Ca/Ca2+ ratio, acid-base balance, bleeding complications, and the need for blood product transfusions. The probability of filter survival in the citrate group was 94% and in the heparin group 82% (P = 0.204). There was no relationship between the method of anticoagulation and effectiveness of MARS therapy in lowering the levels of the analyzed parameters. Only one patient had a Ca/Ca2+ ratio higher than he safety margin. There were no statistically significant changes in pH and lactate level irrespective of anticoagulation; bicarbonate dropped significantly only in the heparin group (P = 0.03). The frequency of bleeding complications and the need for transfusions did not differ significantly between groups. Regional anticoagulation with citrate can be an effective and safe method of anticoagulation during MARS therapy, but requires attentive monitoring and further studies in liver failure patients.

[Changes and perspectives of non-biological artificial liver treatment].

Liver failure is a common clinical syndrome of serious liver diseases with a high mortality rate. Artificial liver support system can significantly reduce the mortality rate of patients with liver failure and is widely used in clinical practice. Due to the shortage of blood resource, the increase in blood-borne diseases, increased demands for liver transplantation, and the change in treatment concepts, single non-biological artificial liver treatment is often unable to satisfy clinical needs, and it is urgent to develop new therapeutic paradigms of non-bioartificial liver. This article reviews the changes and perspectives of non-biological artificial liver in the treatment of liver failure.

Hepatic Encephalopathy: Pharmacological Therapies Targeting Ammonia.

Hepatic encephalopathy (HE) is a major complication in patients with decompensated cirrhosis, leading to higher readmission rates causing a profound burden of disease and considerable health care costs. Because ammonia is thought to play a crucial role in the pathogenesis of HE, therapies directed at reducing ammonia levels are now being aggressively developed. Ammonia scavengers such as AST-120 (spherical carbon adsorbent), glycerol phenylbutyrate, sodium phenylacetate or sodium benzoate, and ornithine phenylacetate have been used to improve HE symptoms. A new approach, bowel cleansing with polyethylene glycol 3350, appears to be a promising therapy, with a recent study demonstrating a more rapid improvement in overt HE (at 24 hours after treatment) than lactulose. Extracorporeal devices, although now used primarily in research settings, have also been utilized in patients with refractory HE, but are not approved for clinical management.

[A case of chronic hepatitis B with liver failure due to untreated Basedow disease].

A 45-year-old female who complained of high fever and jaundice was admitted to our hospital for severe liver failure. She had a history of treatment for chronic hepatitis B, which had not been observed for a long time. She was diagnosed with liver failure due to severe hyperthyroidism due to untreated Basedow disease and not due to acute exacerbation of chronic hepatitis B. She was successfully treated with artificial liver adjuvant therapy and total thyroidectomy. Hyperthyroidism should, therefore, be considered as one of the possible causes of acute-on-chronic liver failure.

Albumin dialysis with molecular adsorbent recirculating system (MARS) for the treatment of hepatic encephalopathy in liver failure.

Acute, acute-on-chronic and chronic liver diseases are major health issues worldwide, and most cases end with the need for liver transplantation. Up to 90% of the patients die waiting for an organ to be transplanted. Hepatic encephalopathy is a common neuropsychiatric syndrome that usually accompanies liver failure and impacts greatly on the quality of life. The molecular adsorbent recirculating system (MARS) is a recently developed form of artificial liver support that functions on a base of albumin dialysis. It facilitates the dialysis of albumin-bound and water-soluble toxins, allowing the patient to survive and even improving some clinical features of liver failure. The following manuscript reviews the technical features of MARS operation and some of the clinical trials that analyze the efficacy of the system in the therapy of liver diseases.

[Effects of non-bioartificial liver support system on Gc-globulin in patients with liver failure].

OBJECTIVE: To investigate the effects of artificial liver support system(plasma exchange combined with continuous veno - venous hemodiafiltration, PE + CVVHDF) on Gc globulin in patients with liver failure. METHODS: 81 patients with liver failure were divided into 4 groups according to the treatment protocols and indicators such as liver function and clinical symptoms. Totally 29 effective cases and 14 ineffective cases in the ALSS group versus 15 effective cases and 23 ineffective cases in the medical group were included. Finally the changes of Gc globulin were observed in four subgroups before and after treatment. The correlation between Gc globulin and IL-10, IL-4, IL-18, TNFa, endotoxin, NO, sVCAM-1and sICAM-1were analyzed by Pearson correlation analysis. RESULTS: The effectiveness rate was 67.44% in ALSS group and 34.21% in the medical treatment (P less than 0.01). Gc globulin, one of liver cell protection proteins was notably increased following the artificial liver treatment as compared with the increase in the medical treatment (P less than 0.01). The time-response curve of Gc globulin level had a significant upward trend in the effective group as compared to no significant rise in the ineffective group. Moreover, the Gc globulin was negatively correlated with IL-4, IL-18, TNFa, SVCAM-1, SICAM-1 and NO. In contrast, no correlation existed between Gc globulin and IL-10. The treatment with artificial liver can improve the outcome of the patients with liver failure. The level of Gc globulin was correlated with the curative effect and thus may be used as a potential indicator for curative effect forcast in the patients with liver failure.

Heat stroke complicated by liver failure and hyperbilirubinaemia--a case report.

Heat stroke may appear as a result of exposure to high environmental temperature or strenuous exercise. It represents a medical emergency characterized by an elevated core body temperature and multi-organ failure. We have described a case of a 41 year-old female after sun exposure, who was admitted to the hospital with the temperature of 42 degrees C. Because of high plasma bilirubin level the Molecular Adsorbent Recirculating System (MARS) was started. Three sessions of MARS, which lasted for eight hours each, were conducted on 15h, 18th, and 23rd day of hospitalization. The procedure was well tolerated by the patient and resulted in a sustained decline of plasma bilirubin from 33.5 to 14.7 mg/dl. The female was discharged from the hospital in good general condition. The two months follow up showed that the patient felt very well, and the plasma bilirubin was reduced to 2.2 mg/dl.

[The efficacy of artificial liver support system treatment on hepatic failure in China: a meta-analysis].

OBJECTIVE: Conducting a meta-analysis to evaluate the efficacy of artificial liver support system (ALSS) in the treatment of hepatic failure in China. METHODS: Clinical trials comparing ALSS vs. routine medical treatment of hepatic failure in China were identified from computer-based literature. The pooled odds ratio and 95% confidence interval (CI) of prognostic indicators, such as survival rate and clinical improvement rate at discharge, were used to measure the magnitude of the efficacy. RESULTS: Ten trials including 1030 patients were identified. The odds ratio (95% CI) of survivorship or improvement of ALSS over routine medical treatment in early, intermediate and advanced stages of hepatic failure were 3.72 (2.03-6.83), 2.79 (2.88-4.14) and 1.85 (0.96-3.56) respectively. CONCLUSION: ALSS treatment is more effective in early and intermediate stages of hepatic failure than routine medical treatment, but not in its advanced stage.

Treatment of severe liver failure with a bioartificial liver.

Orthotopic liver transplantation (OLT) is the definitive therapy for severe liver failure. However, many patients die before an organ becomes available, mostly from cerebral edema. To provide temporary liver support, we developed a bioartificial liver (BAL) based on porcine hepatocytes and a charcoal column. Fifty-four consecutive BAL treatments were carried out in three groups of patients: Group I (n = 15) patients presented with FHF were listed for emergent OLT, Group II (n = 3) patients with primary non-function (PNF) of their liver grafts required urgent re-transplantation and Group III (n = 10) patients with acute exacerbation of chronic liver disease were not candidates for OLT. Patients were managed in a critical care unit receiving maximal standard support. Each BAL treatment was conducted for 6 hours. In Group I, all patients showed significant neurologic improvement, intracranial pressure (ICP) decreased and cerebral perfusion pressure (CPP) increased; other significant improvements, included lowered plasma ammonia and liver enzymes and increased glucose. One patient recovered spontaneously without OLT, all other patients were "bridged" to OLT, and recovered. Group II: PNF patients showed similar benefits. Group III: Chronic liver patients demonstrated transient beneficial effects after BAL treatment(s), however, most (n = 8) eventually succumbed to sepsis and multiple organ failure as they were not candidates for OLT; two patients, recovered, later were successfully transplanted and survived. Our clinical experience demonstrates that the BAL can serve as a bridge to OLT in patients with acute liver failure.

Treatment of hepatic failure with artificial liver support system.

OBJECTIVE: To assess the effectiveness of artificial liver support system (ALSS) treatment in patients with hepatic failure. METHODS: 235 cases of hepatic failure were treated with ALSS in our hospital. All data were analyzed by SPSS. The effectiveness of ALSS treatment was compared according to different stages (i.e., early, middle and end stages). RESULTS: 108 patients survived after therapy of ALSS. After each ALSS treatment, the liver function of these patients was greatly improved, the serum endotoxin and HBV-DNA concentrations were significantly decreased, and the serum concentration of aromatic amino acids (AAA) such as methionine decreased while the ratio of branched chain amino acids and aromatic amino acids (BCAA/AAA ratio) increased; patients treated with ALSS in the early or middle stages of disease had much higher survival rates than patients in the end stage of disease. CONCLUSION: ALSS is a reliable therapy for advanced liver diseases and treatment at early or middle stages is appropriate.

Artificial liver support molecular adsorbents recirculating system therapy as a bridge to re-transplantation in two cases of long anhepatic duration.

BACKGROUND: Molecular adsorbents recirculating system (MARS) liver support therapy is the development of albumin dialysis. This study was to assess the successful application of MARS artificial liver support therapy as a bridge to re-transplantation in two cases of long anhepatic duration. METHODS: MARS therapy was given after failure plasma-exchange (PE) treatment, which resulted in circulatory derangement and acute renal dysfunction in a 36-year-old male patient. Finally his uncontrolled anhepatic condition led to a successful re-transplantation. In another 48-year-old man who was diagnosed as having primary nonfunction (PNF) during the liver transplantation, 10-hour MARS treatment contributed to smooth bridging of his anhepatic phase. RESULTS: The two anhepatic patients were bridged for 26 and 17 hours respectively to re-transplantation with MARS therapy. CONCLUSION: Our experience proves that MARS artificial liver can be an effective support for long time bridging PNF until re-transplantation is available.

[Treatment of severe hepatitis with artificial liver support system and liver transplantation].

OBJECTIVE: To observe and investigate the efficacy of the hybrid artificial liver support system plus liver transplantation in the treatments of patients with severe viral hepatitis. METHODS: Eight severe viral hepatitis patients with metaphase and advanced stage liver failure received the artificial liver support using a self-command extracorporeal hybrid artificial liver support system and orthotopic liver transplantation after the artificial support for 3-14 days. RESULTS: The liver failure of the 8 patients was controlled by the hybrid artificial liver support effectively. All patients were successfully bridged to orthotopic liver transplantation. Four out of the eight patients survived after transplantation. Four patients died of pulmonary infection or hepatorenal syndrome. CONCLUSIONS: Artificial liver support system combined with liver transplantation can be regarded as an efficient measure for the treatment of metaphase and advanced stage patients of severe viral hepatitis.

[Study of severe hepatitis treated with a hybrid artificial liver support system].

OBJECTIVES: To evaluate the efficacy of a hybrid artificial liver support system in the treatment of chronic severe hepatitis. METHODS: The hybrid artificial liver support system (HALSS) consisted of a bioreactor containing more than 5 x 10(9) porcine hepatocytes and plasma exchange device. 15 patients with chronic severe viral hepatitis were treated with the hybrid system. RESULTS: All the patients experienced a reduction in symptoms, such as fatigue, abdominal distention or ascites. After each treatment serum total bilirubin decreased markedly (from 493.5 micromol/L+-139.8 micromol/L to 250.9 micromol/L+-91.3 micromol/L, t=8.695, P<0.001), while prothrombin activity increased (from 24.5%+-8.4% to 30.6%+-6.3%, t=3.325, P<0.01). There were 11 patients whose progress of hepatocytes necrosis stopped after HALSS treatment, and finally they recovered completely. Four patients died of their worsen conditions. No serious adverse events were noted in the 15 patients. CONCLUSION: HALSS is a reliable hepatic support device for chronic severe hepatitis.

[Effects evaluation of middle mode artificial liver in treatment of severe hepatitis].

OBJECTIVE: To evaluate the clinical efficacy and safety of middle mode artificial liver-plasma pheresis in treatment of severe hepatitis. METHODS: Seventeen patients with severe hepatitis were treated with plasma pheresis. The results of liver function, renal function, blood routine, prothrombin time (PT), prothrombin time activity (PTa) before and after the treatment were analyzed. All patients were observed closely. RESULTS: Symptoms of patients treated with plasma pheresis were improved, and the total effective rate reached 58.8 percent, but the survival rate was only 11.8 percent. Compared with those before the therapy, there were significant differences in aminotransferase, total bilirubin, direct bilirubin, PT, PTa and total protein level after treatment (P<0.05 or P<0.01). The side-effects were mild. CONCLUSION: Middle artificial liver is effective in the treatment of severe hepatitis.

[Therapeutic application of molecular adsorbent recirculation system in the treatment of multiple organ dysfunction syndrome patients].

OBJECTIVE: To assess the effectiveness of molecular adsorbent recirculation system (MARS) to remove nitric oxide(NO) and cytokines in multiple organ dysfunction syndrome(MODS) in patients with severe liver failure. METHODS: Single MARS treatment were performed for 198 times with duration ranging from 6 to 24 hours on 61 MODS patients (42M/19F). The efficacy was evaluated by sequential organ failure assessment, biochemical parameters and the levels of pro-inflammatory cytokines. RESULTS: The MARS therapy resulted in a significant removal of NO and certain cytokines such as tumor necrosis factor-alpha(TNF-alpha), interleukin-2(IL-2), IL-6, IL-8, and lipopolysaccharide-binding protein(LBP), together with marked reduction of other non-water soluble albumin bound toxins and water soluble toxins. These were associated with an improvement of the patients' clinical conditions, including deranged hemodynamics, respiratory function, cardiovascular and renal functions, hepatic encephalopathy, thus resulting in a marked decrease of sequential organ failure assessment(SOFA) score and improved outcome. Twenty-five patients were able to be discharged from the hospital, and successful liver transplantation could be performed in 6 patients. The overall survival rate of 61 patients was 41.0%. CONCLUSION: MARS could be used for the treatment of MODS patients associated with elevated levels of NO and cytokines with satisfactory results.