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Background/Aims@#To investigate the autoantibody against fumarate hydratase (FH), which is a specific liver failure-associated antigen (LFAA) and determine whether it can be used as a biomarker to evaluate the prognosis of acute-on-chronic liver failure (ACLF). @*Methods@#An immunoproteomic approach was applied to screen specific LFAAs related to differential prognosis of ACLF (n=60). Enzyme-linked immunosorbent assay (ELISA) technology was employed for the validation of the frequency and titer of autoantibodies against FH in ACLF patients with different prognoses (n=82). Moreover, we clarified the expression of autoantibodies against FH in patients with chronic hepatitis B (n=60) and hepatitis B virus-related liver cirrhosis (n=60). The dynamic changes in the titers of autoantibodies against FH were analyzed by sample collection at multiple time points during the clinical course of eight ACLF patients with different prognoses. @*Results@#Ultimately, 15 LFAAs were screened and identified by the immunoproteomic approach.Based on ELISA-based verification, anti-FH/Fumarate hydratase protein autoantibody was chosen to verify its expression in ACLF patients. ACLF patients had a much higher anti-FH autoantibody frequency (76.8%) than patients with liver cirrhosis (10%, p=0.000), patients with chronic hepatitis B (6.7%, p=0.022), and normal humans (0%, p=0.000). More importantly, the frequency and titer of anti-FH protein autoantibodies in the serum of ACLF patients with a good prognosis were much higher than that of patients with a poor prognosis (83.9% vs 61.5%, p=0.019; 1.41±0.85 vs 0.94±0.56, p=0.017, respectively). The titer of anti-FH autoantibodies showed dynamic changes in the clinical course of ACLF. @*Conclusions@#The anti-FH autoantibody in serum may be a potential biomarker for predicting the prognosis of ACLF.
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Accurate judgment of conditions and prognosis has important clinical significance in improving survival rate and optimal distribution of liver source in patients with liver failure. This article reviews the current application of prognostic markers for liver failure such as alanine aminotransferase, aspartate aminotransferase, total bilirubin, prothrombin time, prothrombin time activity, and international normalized ratio and summarizes the new markers discovered in recent years, such as inflammatory response-related markers, neutrophil gelatinase-associated lipocalin, immune response-related markers, keratin, intestinal flora, microRNAs, liver failure autoantigen and autoantibody, and hemodynamic disorder. It is pointed out that the prognosis of liver failure is affected by many factors and there is still a lack of more sensitive and effective markers and a standardized prognostic scoring system. The new markers used alone or in combination with traditional markers may help to improve the sensitivity and specificity of prognostic evaluation of liver failure.
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OBJECTIVE:To prepare Polygala fallax rapidly disintegrating oral tablets and investigate its in vitro dissolution. METHODS:The rapidly disintegrating tablets was prepared by direct powder compression method. Using disintegration time as in-dex,the ratio of stuffing bulking agent mannitol to disintegrating agent microcrystalline cellulose,the amount of drug extract,the amount of lubricant magnesium stearate and other influential factors were investigated by single factor test and orthogonal test. The drug dissolution effect of prepared tablet(using senegenin as substance control)was evaluated by in vitro dissolution test(using wa-ter as dissolution medium,paddle method). RESULTS:The optimal formulation was that the amount of drug extract was 15%;the ratio of mannitol to microcrystalline cellulose was 1.5:1;the amount of magnesium stearate was 1.0%. The disintegration time of prepared tablet was(31±4)s;tablet hardness was(3.4±0.2)kg;tablet friability was(0.23±0.07)%(RSD<0.11%,n=3). Ac-cumulative dissolution rate of total saponins was more than 90% within 5 min. The dissolution parameters T50 was equal to 0.84 min and Td was equal to 1.77 min. CONCLUSIONS:Polygala fallax rapidly disintegrating oral tablets will dissolve quickly and dis-integrate rapidly in aqueous solution.