Li’s Artificial Liver In The Treatment Of Chronic Acute-on-Chronic Liver Failure (HBV)

Background:Hepatitis B virus (HBV) has a high prevalence rate worldwide, with>2billion people being infected and approximately400million individuals with chronic HBV infection. In China, acute exacerbation of chronic hepatitis B is the most common cause of liver failure, in contrast to that in Western countries where drugs, alcohol, and hepatitis C are more common. Generally, in compensated liver disease, the normal synthesis, detoxification, excretion, and biotransformation functions of the liver are affected. When exacerbation of liver failure occurs, new hepatocyte necrosis develops in addition to the original pathologic damage; this necrosis is usually characterized by coagulopathy, jaundice, hepatic encephalopathy (HE), and ascites.Despite recent progress in antiviral therapy, liver failure remains a therapeutic challenge with a high mortality rate. Liver transplantation, the only effective treatment, is hampered by a shortage of organs and the high frequency of concomitant conditions that contraindicate the procedure.Li’s Artificial liver, which originated from concept of liver cell regeneration, is an effective alternative treatment for liver failure that temporarily eliminates toxic substances and replaces the failed liver with an environment for the regeneration of hepatocytes or an environment that enables waiting for liver transplantation. Many types of extracorporeal blood purification systems, including plasma exchange (PE), continuous hemodiafiltration, and molecular adsorbent recirculating system (MARS), have been used in the treatment of liver failure. In China, with the progress and promotion of artificial liver technology, PE has been used as the main technique for approximately20years, in patients suffering from liver failure. In liver failure, a wide range of potentially toxic substances, including bilirubin, bile acid, short chain fatty acids, aromatic amino acids, cytokines, and ammonia, accumulate in the systemic circulation and are involved in multi-organ complications. Most of these toxins are protein-bound, especially to albumin. The most direct method to remove toxic substances is by plasma exchange (PE), where the toxic plasma is replaced with fresh normal plasma. PE also involves removal of stimulatory factors released due to liver injury that are responsible for increase complications. Many studies have shown that PE reduces mortality, but no multicenter large study with a large sample size has been performed. Therefore, we performed a prospective multicenter study at the first affiliated hospital of Medical College, Zhejiang University with10hospitals involved in China, for determining the efficiency of PE on different stages of HBV-ACLF in order to establish a baseline for similar future studies. Through the observation of clinical data, we draw the corresponding conclusion. And then on these basis, for evaluating the effect of artificial liver in liver failure in the treatment of severe hepatitis, we design the random controlled strategy and scheme of different clinical stages with different Li’s artificial liver. We found a phenomenon in the study of clinical application, however,for finding out mechanism and pathogenesis of Li’s artificial live application in acute on chronic liver failure, we need to establish a clinical blood sample,tissue specimen database, to provide the platform for a unified national follow-up laboratory detection and mechanism research. In this demand, the sample management software was designed to provide digital support for subsequent laboratory pathogenesis and mechanism research work.Methods:From December2009to2011, we evaluated250patients at different stages of HBV-ACLF from10hospitals in China. The follow-up continued until the end of the study (30Jan2012). The maximum follow-up period for enrolled patients was1months after diagnosis of HBV-ACLF. In order to determine therapeutic efficacy and risk factors for short-term prognosis, laboratory parameters were collected at admission and before and after PE. On the basis of observation in the clinical data of the patients with acute-on-chronic liver failure, we designed large sample randomized controlled research strategy about how to effectively applicate different Li’s artificial liver according to the different stages and clinical sample management system. As strictly in accordance with the scheme of clinical research and sample management, it will provide the evidence for more accurate evaluation of Li’s artificial liver.Results:Among the250patients who underwent661rounds of PE,141(56.4%) showed improvement after PE. Variables such as age (p=0.000) and levels of total bilirubin (TB, p=0.000), direct bilirubin (DB,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), and platelet (p=0.003) were significantly related to prognosis of patients with HBV-ACLF after PE. Multivariate logistic regression analysis showed that age, disease stage, TB levels, PT, and Cr levels were independent risk factors for prognosis among HBV-ACLF patients. According to clinical observations, we designed scheme of different Li’s artificial liver support system in the treatment of different stages of acute on chronic liver failure. According to the plan we formulated the specimen management strategy, designed the remote sample management system, and got the software copyright. Now it has been applied into the management of sample from research.Conclusions:Li’s artificial liver helped to reduce the mortality of HBV-ACLF, especially in early-stage ACLF. The levels of TBil and Cr and PT were independent prognostic factors of PE treatment for HBV-ACLF. Further, when the stage of ACLF that reflects the number and severity of complications, is considered, it is an additional independent factor for prognosis. So for the patients of the later phase, liver transplantation must be taken into consideration. On the basis of clinical observation, program for design of randomized controlled study of Li’s artificial liver will be much more thoughtful. With the support of digital management we can provide more reliable and scientific evidence of mechanism of Li’s artificial liver from blood sample from research, which will finally effectively guide the clinical treatment.