Metabolomic screening for diagnostic biomarkers of drug-induced chronic liver injury related cirrhosis / 药学学报

About 15%-20% of drug-induced liver injury (DILI) will progress to chronic manifestation (CH-DILI), which sometimes advances rapidly to liver cirrhosis (LC-DILI) within 0.5-1 year with deteriorative clinical prognosis. Therefore, it is important to find a non-invasive diagnosis for early detection of liver cirrhosis. In this study, the metabolomic profiles revealed significant differences in the metabolites from the plasma of LC-DILI versus CH-DILI. We found 35 differential metabolites through principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Through pathway enrichment analysis, some up-regulated metabolic pathways reflected impaired liver functions such as bile acid, lipid synthesis and decomposition during cirrhosis. Five biomarkers were found to exhibit effective diagnosis value (AUC > 0.6), including phosphatidylcholine, lysoPC (18:1 (9Z)), creatine, taurochenodeoxycholic acid and taurocholic acid. Furthermore, we found that the relative content ratio between phosphatidylcholine and lysoPC (18:1 (9Z)) had a better distinguishing ability (AUC = 0.867). The relative content ratio also had the feature to reduce systematic errors of sample processing and instrument detection, therefore having a greater value for clinical application.

Clinical Analysis of Drug-induced Liver Injury Caused by Polygonum multiflorum and its Preparations / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To analyze hepatotoxicity of Polygonum multiflorum and clinical character- istics of drug-induced liver injury (DILI) caused by Polygonum multiflorum and its preparations.</p><p><b>METHODS</b>A retrospective study was performed in 158 patients treated at 302 Military Hospital between January 2009 and January 2014. All of them had used Polygonum multiflorum and its preparations before the onset of DILI, and their clinical characteristics and prognoses were analyzed.</p><p><b>RESULTS</b>Of the 158 DILI patients who used Polygonum multiflorum or its preparations, 92 (58.2%) combined with Western medicine or Chinese herbal preparations without Polygonum multiflorum; 66 patients (41.8%) used Polygonum mult florum and its preparations alone. In 66 DILI patients induced by Polygonum multiflorum or its preparations alone, 51 cases (77.3%) were induced by Polygonum multiflorum compounds and 22.7% by single Po- lygonum multiflorum; 4 cases (6.1%) were caused by crude Polygonum multiflorum and 62 (93.9%) by processed Polygonum multiflorum and its preparations. Clinical injury patterns were hepatocellular 92.4% (61 cases), cholestatic 1.5% (1 case), and mixed 6.1% (4 cases). Pathological examination was per- formed by liver biopsy in 32 cases (48.15%), manifested as hepatocellular degeneration and necrosis, fibroplasia, Kupffer cells with pigment granule, and a large number of eosinophil infiltration, were ob- served. Four patients were developed into liver failure, 4 into cirrhosis, and 1 died.</p><p><b>CONCLUSION</b>Polygo- num multiflorum and its preparations could induce DILI, but clinical diagnosis of Polygonum multiflorum induced hepatotoxicity should be cautious.</p>

Identification and early diagnosis for traditional Chinese medicine-induced liver injury based on translational toxicology / 中国中药杂志

Recently traditional Chinese medicine (TCM)-induced liver injury has been an unresolved critical issue which impacts TCM clinical safety. The premise and key step to reduce or avoid drug-induced liver injury (DILI) is to identify the drug source of liver injury in early stage. Then the timely withdrawal of drug and treatment can be done. However, the current diagnosis of DILI is primarily governed by exclusive method relying on administering history supplied by patients and experience judgment from doctors, which lacks objective and reliable diagnostic indices. It is obvious that diagnosis of TCM-induced liver injury is especially difficult due to the complicated composition of TCM medication, as well the frequent combination of Chinese and Western drugs in clinic. In this paper, we proposed construction of research pattern and method for objective identification of TCM-related DILI based on translational toxicology, which utilizes clinical specimen to find specific biomarkers and characteristic blood-entering constituents, as well the clinical biochemistry and liver biopsy. With integration of diagnosis marker database, bibliographic database, medical record database and clinical specimen database, an integrative diagnosis database for TCM-related DILI can be established, which would make a transformation of clinical identification pattern for TCM-induced liver injury from subjective and exclusive to objective and index-supporting mode. This would be helpful to improve rational uses of TCM and promote sustainable development of TCM industry.

Correlation of pathology in chronic hepatitis B to viral markers in serum and hepatic tissue / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the relation of the viral markers in serum and those expressed by hepatocytes to pathological lesions of hepatic tissue in patients with chronic hepatitis B.</p><p><b>METHODS</b>The relation of viral markers including HBsAg, HBsAb, HBeAg, HBeAb, HBcAb and HBV DNA in serum of 647 patients with chronic hepatitis B and HBsAg, HBcAg expressed by hepatocytes in 418 of these patients to pathological lesions of hepatic tissue was determined.</p><p><b>RESULTS</b>Viral markers in serum and those expressed by hepatocytes in patients with chronic hepatitis B were closely correlated with pathological lesions of hepatic tissue.</p><p><b>CONCLUSION</b>The degree of inflammation and fibrosis in hepatic tissue is milder in serum HBsAg, HBeAb, HBcAb positive and HBV DNA negative patients but more serious in those with negative hepatocytic expression of HBsAg and HBcAg. HBV DNA is not significantly associated with pathological lesions of hepatic tissue.</p>

Detection of coagulation factor V in patients with severe hepatitis and its clinical significance / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To investigate the prognostic significance and role of coagulation factor V (CFV) levels in clinical diagnostic criteria for severe hepatitis.</p><p><b>METHODS</b>The CFV level and prothrombin activity (PTA) were tested by turbidimetry for 129 times in 58 patients with severe hepatitis. Comparative studies and clinical significance of CFV and PTA were analyzed by SPSS and SDAS softwares.</p><p><b>RESULTS</b>1. The levels of CFV and PTA were 15.3%+/-9.7% and 23.5%+/-10.0%, respectively, at the onset of severe hepatitis. 2. The mortality of severe hepatitis gradually increased with the gradual decrease of CFV or PTA during the most severe stage of the illness (P=0.000). 3. The levels of CFV and PTA decreased continually and rapidly in patients who died but gradually increased in survivors. The decrease or increase of PTA preceded that of CFV on the exacerbation or convalescent stage. 4. Hepatic encephalopathy occurred in 14 cases (24.14%). In 10 cases, it occurred in the terminal stage of the illness, far later than the time of the decrease of CFV. 5. The level of CFV was closely related to PTA (the correlation coefficient was 0.812), the level of CFV was almost consistent with that of PTA.</p><p><b>CONCLUSION</b>1. The level of CFV is an important prognostic indicator in severe hepatitis and is more specific than PTA. 2. Simultaneous determination of CFV and PTA may be helpful in earlier and more accurate diagnosis of severe hepatitis. 3. Possible use of CFV as one of the criteria for liver transplantation in patients with severe hepatitis should be studied.</p>

Correlation of clinical features with pathology in chronic viral hepatitis / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To investigate the correlation of clinical features with pathology in chronic viral hepatitis (CH).</p><p><b>METHODS</b>Analyses of single factor and multiple factors of serum biochemical indices, imaging examination results, symptoms and signs with degree of pathological lesion of hepatic tissue in 973 cases of CH were conducted. Meanwhile, the hepatic functional index (AAPEA index) was used to investigate the role of serum biochemical indices in diagnosis of CH.</p><p><b>RESULTS</b>In these patients with CH,the severity of hepatic lesion was closely correlated to symptoms and signs, biochemical indices such as PTA, ALT, TBIL, ALB, A/G, gamma-globulin (gamma-G) by electrophoresis, AST and cholinesterase (CHE) as well as splenic thickness. AST was superior to ALT in reflecting degree of hepatic inflammatory activity. The total mistaken judgment rate of multiple factor analysis was 28.1%. The correlation coefficient of AAPEA index to degrees of hepatic inflammatory activity, fibrosis and pathological grading was 0.559, 0.545 and 0.529, respectively (P<0.000 1)</p><p><b>CONCLUSIONS</b>The biochemical indices such as PTA, ALT, TBIL, ALB, A/G, gammaG, AST, CHE and the determination of splenic thickness by ultrasonography B could reflect hepatic pathological changes to certain extent. AST was superior to ALT in reflecting degree of hepatic inflammatory activity. Incorrect judgment rate was high in determination of moderate and severe CH by multiple factor analysis. Conformity rate between AAPEA index and pathological diagnosis was better than any of them alone in diagnosing CH.</p>