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Artificial Liver Support System Combined with Liver Transplantation in the Treatment of Patients with Acute-on-Chronic Liver Failure

Background The search for a strategy to provide temporary liver support and salvage the patients with acute-on-chronic liver failure (ACLF) remains an important issue. This study was designed to evaluate the experience in artificial liver support system (ALSS) combined with liver transplantation (LT) in the treatment of ACLF. Methodology/Principal Findings One hundred and seventy one patients with HBV related ACLF undergoing LT between January 2001 and December 2009 were included. Of the 171 patients, 115 received 247 sessions of plasma exchange-centered ALSS treatment prior to LT (ALSS-LT group) and the other 56 received emergency LT (LT group). The MELD score were 31±6 and 30±7 in ALSS-LT group and LT group. ALSS treatment resulted in improvement of liver function and better tolerance to LT. The average level of serum total bilirubin before LT was lower than that before the first time of ALSS treatment. The median waiting time for a donor liver was 12 days (2–226 days) from the first run of ALSS treatment to LT. Compared to LT group, the beneficial influences of ALSS on intraoperative blood loss and endotracheal intubation time were also observed in ALSS-LT group. The 1-year and 5-year survival rates in the ALSS-LT group and LT group were 79.2% and 83%, 69.7% and 78.6%. Conclusions/Significance Plasma exchange-centered ALSS is beneficial in salvaging patients with ACLF when a donor liver is not available. The consequential LT is the fundamental treatment modality to rescue these patients and lead to a similar survival rate as those patients receiving emergency transplantation.

Artificial Liver Support System in China: A Review Over the Last 30 Years

Abstract:u2002 Severe viral hepatitis with high mortality is the most common cause of liver failure in China. Treatment of severe viral hepatitis by hemoperfusion was initially adopted in the late 1970s and early 1980s. Following 10u2003years of development in China, a plasma exchange (PE)‐centered artificial liver support system (ALSS), principally dependent on PE technology was developed. Based on the condition and symptoms of each patient, PE was given alone, or combined with hemodialysis, hemofiltration, hemodiafiltration, hemoperfusion, or plasma perfusion. In the late 1990s, training courses for ALSS were developed, and ALSS began to be carried out across China. Guidelines for artificial liver therapy were formulated and published by the Artificial Liver and Liver Failure Group of the Chinese Society of Infection. In recent years, new methods have been attempted, including small pore‐size plasma separators, a molecular adsorbent‐based recirculating system (MARS), and a continuous albumin purification system (CAPS). According to a retrospective analysis published in 2004, ALSS therapy significantly (Pu2003<u20030.001) improved the survival rate of patients with severe hepatitis compared with patients who received only medicines (43.4%, 157/362 vs. 15.4%, 55/358 in chronic patients and 78.9%, 30/38 vs. 11.9%, 5/42 in acute and subacute patients). Furthermore, ALSS has also proved valuable as a bridge to liver transplantation in the treatment of patients with end‐stage severe hepatitis in China. More recently, ALSS has been used in the treatment of drug‐induced liver failure, acute fatty liver during pregnancy, and other difficult‐to‐treat disorders in China.

A Modified MELD Model for Chinese Pre-ACLF and ACLF Patients and It Reveals Poor Prognosis in Pre-ACLF Patients

Background & Aims Acute-on-chronic liver failure (ACLF) is one of the most deadly, prevalent, and costly diseases in Asia. However, no prognostic model has been developed that is based specifically on data gathered from Asian patients with ACLF. The aim of the present study was to quantify the survival time of ACLF among Asians and to develop a prognostic model to estimate the probability of death related to ACLF. Methods We conducted a retrospective observational cohort study to analyze clinical data from 857 patients with ACLF/pre-ACLF who did not undergo liver transplantation. Kaplan–Meier and Cox proportional hazards regression model were used to estimate survival rates and survival affected factors. The area under the receiver operating characteristic curve (auROC) was used to evaluate the performance of the models for predicting early mortality. Results The mortality rates among patients with pre-ACLF at 12 weeks and 24 weeks after diagnosis were 30.5% and 33.2%, respectively. The mortality rates among patients with early-stage ACLF at 12 weeks and 24 weeks after diagnosis were 33.9% and 37.1%, respectively. The difference in survival between pre-ACLF patients and patients in the early stage of ACLF was not statistically significant. The prognostic model identified 5 independent factors significantly associated with survival among patients with ACLF and pre-ACLF: the model for end-stage liver disease (MELD) score; age, hepatic encephalopathy; triglyceride level and platelet count. Conclusion The findings of the present study suggest that the Chinese diagnostic criteria of ACLF might be broadened, thus enabling implementation of a novel model to predict ACLF-related death after comprehensive medical treatment.

Korean red ginseng: a new approach for the treatment of graft-versus-host disease after liver transplantation.

BACKGROUNDnGraft-versus-host disease (GVHD) is a rare complication after liver transplantation with an extremely poor prognosis; its occurrence offers great challenges.nnnMETHODSnWe have reported herein one case of acute GVHD after liver transplantation who was treated with a traditional Chinese medicine named Korean Red Ginseng (KRG).nnnRESULTSnThe acute GVHD was successfully cured by KRG.nnnCONCLUSIONSnThe successful salvage of acute GVHD after liver transplantation by KRG may provide a new viable therapeutic option.

Plasma exchange-centered artificial liver support system in hepatitis B virus-related acute-on-chronic liver failure: a nationwide prospective multicenter study in China

BACKGROUNDnPlasma exchange (PE)-centered artificial liver support system reduced the high mortality rate of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). But the data were diverse in different medical centers. The present prospective nationwide study was to evaluate the effects of PE on patients with HBV-ACLF at different stages.nnnMETHODSnFrom December 2009 to December 2011, we evaluated 250 patients at different stages of HBV-ACLF from 10 major medical centers in China. All the laboratory parameters were collected at admission, before and after PE.nnnRESULTSnAmong the 250 patients who underwent 661 rounds of PE, one-month survival rate was 61.6%; 141 (56.4%) showed improvement after PE. Variables such as age (P=0.000), levels of total bilirubin (TB, P=0.000), direct bilirubin (P=0.000), total triglycerides (P=0.000), low-density lipoprotein (P=0.022), Na+ (P=0.014), Cl- (P=0.038), creatinine (Cr, P=0.007), fibrinogen (P=0.000), prothrombin time (PT, P=0.000), white blood cell (P=0.000), platelet (P=0.003) and MELD (P=0.000) were significantly related to prognosis. Multivariate logistic regression analysis showed that age, disease stage, TB, Cr and PT levels were independent risk factors of mortality among HBV-ACLF patients.nnnCONCLUSIONSnPE can improve the clinical outcome of patients with HBV-ACLF. Levels of TB, Cr and PT, age and disease stage help to predict prognosis.

Comparison of Plasma Exchange With Different Membrane Pore Sizes in the Treatment of Severe Viral Hepatitis

Abstract:u2002 Plasma exchange has become an effective mode of blood purification in patients suffering from liver failure. To assist in patient recovery, we compared two plasma separators to identify a plasma separator with suitable pore sizes to remove toxic substances effectively, and retain important plasma components. The study focused on severe viral hepatitis patients. Of 206 rounds of plasma exchange, 137 were completed with the PS‐06 plasma separator (membrane pore sizeu2003=u20030.2u2003µm) and 69 with the EC‐4A plasma separator (membrane pore sizeu2003=u20030.03u2003µm). The efficacy of different plasma separators was compared using survival rate, changes in liver biochemistry, immunoglobulin, and complement parameters. The survival rate of patients treated with PS‐06 was 43.3% (13 of 30 patients). For patients treated with EC‐4A, two patients were bridged to liver transplantation successfully, and 57.9% (11 of 19 patients) survived. In both groups, the levels of total bilirubin, prothrombin time, and bile acid declined significantly. Compared to PS‐06, EC‐4A could retain significantly larger amounts of immunoglobulin and complements. Our study revealed that plasma exchange implementation with membrane pore size 0.03u2003µm could remove adequate bilirubin and bile acid, a class of toxins bound to plasma protein in severe viral hepatitis patients, and reduce the loss of essential plasma macromolecules.

Development of diagnostic criteria and a prognostic score for hepatitis B virus-related acute-on-chronic liver failure

Objective The definition of acute-on-chronic liver failure (ACLF) based on cirrhosis, irrespective of aetiology, remains controversial. This study aimed to clarify the clinicopathological characteristics of patients with hepatitis B virus-related ACLF (HBV-ACLF) in a prospective study and develop new diagnostic criteria and a prognostic score for such patients. Design The clinical data from 1322 hospitalised patients with acute decompensation of cirrhosis or severe liver injury due to chronic hepatitis B (CHB) at 13 liver centres in China were used to develop new diagnostic and prognostic criteria. Results Of the patients assessed using the Chronic Liver Failure Consortium criteria with the exception of cirrhosis, 391 patients with ACLF were identified: 92 with non-cirrhotic HBV-ACLF, 271 with cirrhotic HBV-ACLF and 28 with ACLF with cirrhosis caused by non-HBV aetiologies (non-HBV-ACLF). The short-term (28/90 days) mortality of the patients with HBV-ACLF were significantly higher than those of the patients with non-HBV-ACLF. Total bilirubin (TB) ≥12u2009mg/dL and an international normalised ratio (INR) ≥1.5 was proposed as an additional diagnostic indicator of HBV-ACLF, and 19.3% of patients with an HBV aetiology were additionally diagnosed with ACLF. The new prognostic score (0.741×INR+0.523×HBV-SOFA+0.026×age+0.003×TB) for short-term mortality was superior to five other scores based on both discovery and external validation studies. Conclusions Regardless of the presence of cirrhosis, patients with CHB, TB ≥12u2009mg/dL and INR ≥1.5u2009should be diagnosed with ACLF. The new criteria diagnosed nearly 20% more patients with an HBV aetiology with ACLF, thus increasing their opportunity to receive timely intensive management.

Bacterial coinfection is associated with severity of avian influenza A (H7N9), and procalcitonin is a useful marker for early diagnosis

Patients contracting avian influenza A (H7N9) often develop severe disease. However, information on the contribution of bacterial coinfection to the severity of H7N9 is limited. We retrospectively studied 83 patients with confirmed H7N9 infection from April 2013 to February 2014. The severity of patients with bacterial coinfection and markers for early diagnosis of bacterial coinfection in H7N9 were analyzed. We found Staphylococcus aureus was the most prevalent pathogen. Higher Acute Physiology and Chronic Health Evaluation II score, shock, renal replacement treatment, mechanical ventilation, and extracorporeal membrane oxygenation treatment were more frequently observed in patients with bacterial coinfection. Procalcitonin is more sensitive than C-reactive protein in determining bacterial coinfection in H7N9 patients. In conclusion, H7N9 infection patients with bacterial coinfection had a more severe condition. Elevated procalcitonin is an accurate marker for diagnosing bacterial coinfection in H7N9 patients, thus enabling earlier antibiotic therapy.

A single-center experience of non-bioartificial liver support systems among Chinese patients with liver failure

Introduction Liver failure is one of the most deadly, prevalent, and costly diseases worldwide. Non-bioartificial liver support systems (NBALs) have been shown to be effective in improving the clinical symptoms and laboratory parameters of patients with liver failure. The main aim of this large case series analysis was to investigate the status of NBALs and their effectiveness in improving survival in liver-failure patients. Methods In this retrospective study, 460 patients with liver failure who received NBAL treatment in addition to conventional medications were compared with 422 patients who were treated with conventional medications alone. Kaplan-Meier and life table analyses were used to estimate survival rates. Results Clinical outcomes were improved after NBAL treatment. The 30-day survival rates of subacute liver failure (SALF) patients were 63% among those who received NBALs and 21% among those who did not receive NBALs (p<0.01). Similarly, the 30-day survival rate of acute-on-chronic liver failure (ACLF) patients who received NBALs was 47%, significantly higher than that of the non-NBAL patients (p<0.05). The survival rates of ACLF patients with low Model for End-Stage Liver Disease (MELD) scores (MELD≤20) were 64% and 40% among whom received NBALs and those who did not, respectively (p<0.01). Conclusions NBAL treatment is helpful to improve the survival of patients with ALF, SALF or ACLF. ACLF patients with lower MELD scores showed improved outcomes relative to those with higher MELD scores.

Response-guided treatment of cirrhotic chronic hepatitis B patients: multicenter prospective study.

AIMnTo observe the effect of response-guided add-on therapy with adefovir (ADV) and lamivudine (LAM) in cirrhotic hepatitis B (CHB) patients.nnnMETHODSnA total of 100 patients with CHB and cirrhosis were divided into three arms according to hepatitis B virus (HBV) DNA level after 24 wk LAM monotherapy: Arm A (complete response, HBV DNA ≤ 60 IU/mL, n = 49), Arm B (partial response, HBV DNA: 60-2000 IU/mL, n = 31) and Arm C (inadequate response, HBV DNA > 2000 IU/mL, n = 20). ADV was added to LAM at week 48 in Arms A and B, but at week 24 in Arm C. Virological response, YMDD mutations, biochemical response, and liver function were evaluated.nnnRESULTSnComparison of the three arms demonstrated that early complete virologic response at week 24 was associated with maintained viral suppression (undetectable rate of HBV DNA at week 144 was 95.96%, 66.67% and 35.29%, respectively, P = 0.000) and reduced YMDD mutations (mutation rate at week 144 was 0%, 3.23% and 15%, respectively, P = 0.015) after 144 wk treatment. For patients who failed to achieve complete virological response at week 24, switching to combination therapy further decreased HBV DNA level by 1 log10 IU/mL. All three arms obtained biochemical benefits including decline of alanine aminotransferase and elevation of albumin. In patients who developed HBV DNA breakthrough for YMDD mutations, ADV add-on therapy did not induce further multiple drug resistance to LAM or ADV.nnnCONCLUSIONnOptimized response-guided add-on therapy of ADV and LAM maintains long-term suppression of HBV DNA and improves liver function in CHB patients with compensated liver cirrhosis.