Clinical And Histopathological Features Of Drug-Induced Liver Injury And The Role Of Immunocyte

Objective: Drug-induced liver injury refers to the human body exposed to the conventional dose or after high dose,because of the drug itself or its metabolites directly on the liver toxicity,or the human body to a drug or its metabolites produce allergic or metabolic diathesis reaction and lead to liver damage.Its pathogenesis is complex,the role of immune cells in which it is not clear,in recent years,the study found that immune cells is associated with the occurrence of DILI.This study collected a clear diagnosis of 164 cases of patients with DILI,comparative analysis of characteristics of the crowd,mainly induced by drug,clinical manifestation,histopathological features,and by the method of immunohistochemical staining observation of CD68 positive kupffer cells,CD163 positive kupffer cells,CD20 positive B lymphocytes,mum-1 positive plasmacell and CD8 positive T lymphocyte expressed in liver tissue,and proved the role of immune cells in DILI,for the early diagnosis and treatment of the disease and to provide scientific theory basis to prevent chronic.Methods: 164 patients of DILI,which diagnosed by liver biopsy,were enrolled from January 2007 to April 2015 in the department of Traditional and Western Medical Hepatology,Third Hospital of Hebei Medical University,Shijiazhuang,China,15 cases of healthy controls.According to clinical manifestation and ALT/ALP,patients of DILI were divided into three type(108 patients presented with hepatocellular,24 patients with cholestasis,and 32 patients with mixed),immunohistochemical staining method detecting CD68 positive kupffer cells in the liver tissue,positive CD163 kupffer cells,CD20 positive lymphocytes and CD8 positive T lymphocytes and mum-1 positive plasmocyte,results to CD68,and CD163,CD20,CD8,mum-1 integral optical density value.All data was presented as mean±SD.Statistical analysis was performed by one-way analysis of variance(ANOVA)and Student-Newman-Keuls test for evaluating differences between groups using SPSS 16.0.A P-value of less than 0.05 was considered statistically significance.Results:1 The crowd distribution and clinical features: Patients with an average age of 45.99 ± 14.36 years old,which were 42.68%(70/164),50 women 57.9%(95/164).Clinical mainly for nausea,anorexia,and vomiting 54 cases(32.93%),dark urine 48 cases(29.27%),jaundice 41 cases(25.00%),18.90%(31 cases)patients only abnormal liver biochemistry.Clinical classification for hepatocellular injury 108 cases(65.85%),cholestasis injury 24 cases(14.63%),mixed injury 32 cases(19.51%).2 Induce drug types and clinical classification of DILI: the most drugs induced liver injury are multiple pharmacological agents 43 cases(26.2%),followed by Chinese herbal medicine 39 cases(23.8%)and antibiotics 16 cases(16.7%)as the third.3 Hepatic histopathological features: Liver tissue were observed under light microscope and normal characteristics as follows: the liver sections was almost normal;The characteristics of DILI pathology: Water change,ballooning liver cells,liver cells necrosis with lobular or portal tract inflammation,necrosis foci forming occasional,kupffer cell hyperplasia and other mononuclear cells accumulate,often associated with eosinophil infiltration,cholestasis of liver cells and small bile duct.Hepatocellular injury mainly for liver cell and portal vein necrosis and inflammation changes,and necrosis in portal area are relatively mild inflammation;Mixed injury is mainly around the central vein of liver cells deficiency,bridging necrosis formed,with silt bile formation;Cholestasis injury is characterized by hepatocyte ballooning degeneration,cholestasis.4 The expression of CD68,CD163,CD20,CD8 and mum-1 in Liver tissue: Compared to the healthy controls,the protein expression of CD68,and CD163,CD20,CD8,mum-1 DILI set of liver tissue CD68,and CD163,CD20,CD8,mum-1 up-regulated in DILI,including hepatocellular injury CD68,CD163,CD20,CD8,mum-1 expression significantly increased compared with healthy controls,in turn was 335.82 ±27.87 vs 18.36 ±3.63,744.53 ± 52.44 vs 23.29 ±4.61,440.64 ±78.08 vs 7.54 ±3.43,499.567 ± 40.70 vs 9.53 ± 3.43,342.43 ± 70.20 vs 4.93 ±3.15(P<0.001);Cholestasis injury CD68,CD163,CD20,CD8,mum-1 expression significantly increased compared with healthy controls,followed by 302.56± 26.94 vs 18.36±3.63,1070.62 ±59.32 vs 23.29±4.61,292.34 ±26.76 vs 7.54 ±3.43,401.23 ±29.74 vs 9.53 ±3.43,192.34 ± 26.77 vs 4.93 ±3.15(P<0.001);Mixed type CD68,CD163,CD20,CD8,mum-1 expression significantly increased compared with healthy controls,followed by 599.57 ± 40.70 vs 18.36 ±3.63,938.31 ±60.03 vs 23.29 ± 4.61,315.82 ±27.88 vs 7.54 ±3.43,385.24 ±30.53 vs 9.53±3.43,285.24 ± 30.53 vs 4.93 ±3.15(P<0.001);the expression of CD68 in mixed injury was significantly increased compared with hepatocellular injury,cholestasis injury(599.57±40.70 vs 335.82 ±27.87,302.56±26.94,P<0.01);the expression of CD163 in cholestasis injury was significantly increased compared with hepatocellular injury,mixed injury(1070.62±59.32 vs 744.53±52.44 ?938.31±60.03,P<0.01);Liver cell model CD20 cholestasis type and mixed type expression increased(292.34 vs 292.34±26.76,26.76 26.76 mm ±27.88,P < 0.001);the expression of CD8 in hepatocellular injury was significantly increased compared with cholestasis injury,mixed injury(499.567±40.70 vs 401.23±29.74 ? 385.24±30.53,P<0.001);the expression of mum-1 in hepatocellular injury was significantly increased compared with mixed injury,cholestasis injury(342.43±70.20 vs 285.24±30.53?192.34±26.77,P<0.001).Conclusions:1 DILI in patients with women,and older in the majority.2 Combination was among the top of the various types of drugs,followed by Chinese herbal medicine,and the third are antibiotics.3 DILI in patients with immune cells in the liver tissue cells increased significantly,mainly in hepatic sinus and portal area,suggest a variety of immune cells in the pathological process of DILI may play a role.Including CD68,and CD163,CD20,CD8,mum-1 plays an important role in the process of the occurrence of DILI.4 Early detection of DILI,timely stop using the drug,and take effective measures to protect liver is one of the important conditions to improve the prognosis.