Objective To investigate the clinical features of drug-induced liver injury (DILI) and related risk factors. Methods A retrospective analysis was performed for the clinical data of 208 patients who were diagnosed with DILI in The Affiliated Hospital of Southwest Medical University from January 2013 to November 2017, including the type of drugs, clinical data, and laboratory examination results, and among these patients, 80 with DILI caused by antitubercular agents, antitumor drugs, and immune agents were enrolled as observation group. A total of 80 patients who used these three types of drugs and did not develop DILI were enrolled as control group. Related risk factors were analyzed. An analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups. The chi-square test was used for unordered variables of categorical data, the Mann-Whitney U test was used for ranked data, and a logistic regression analysis was used to identify risk factors. Results Of all patients with DILI, 30. 8% had DILI caused by traditional Chinese medicine. There were significant differences in sex, alanine aminotransferase, aspartate aminotransferase (AST) , total bilirubin (TBil) , gamma-glutamyl transpeptidase (GGT) , and total bile acid (TBA) between patients with different types of DILI (χ2= 6. 081, H = 54. 349, 45. 993, 78. 902, 49. 940, and 21. 934, all P < 0. 05) . There were significant differences in AST, TBil, GGT, and TBA between the patients with different prognoses (H = 1. 728, 6. 322, 6. 440, and 2. 353, all P < 0. 05) . Smoking (odds ratio [OR]= 2. 856, P = 0. 026) , diabetes (OR = 2. 726, P = 0. 042) , hyperlipidemia (OR = 3. 390, P = 0. 003) , and body mass index (BMI) ≥28 kg/m2 (OR = 3. 142, P =0. 009) were risk factors for DILI. Conclusion Most DILI cases are caused by traditional Chinese medicine, and hepatocellular type is the most common type of liver injury. Smoking, diabetes, hyperlipidemia, and BMI ≥28 kg/m2 are risk factors for DILI.

Objective To analyze and summarize the clinical data of drug-induced liver injury (DILI) , and to investigate the clinical features and prognosis of DILI. Methods A retrospective analysis was performed for the clinical data of 95 patients with DILI who were admitted to The First Affiliated Hospital of Xi'an Medical University from February 2010 to February 2016, including sex, age, medication history, underlying diseases, clinical manifestation, laboratory and imaging findings, treatment, and prognosis. A logistic regression analysis was used to investigate the influencing factors for prognosis. Results Respiratory system diseases ranked first among the underlying diseases treated by drugs that caused DILI and accounted for 25. 26% (24/95) , and of all patients, 23. 16% (22/95) had tuberculosis. Among the drugs that caused DILI, traditional Chinese medicine ranked first and accounted for 44. 21% (42/95) , followed by antitubercular agents which accounted for 22. 11% (21/95) . DILI often occurred within 15-30 days of medication. Poor appetite was the most common symptom of DILI, and jaundice was the most common positive sign. Elevated alanine aminotransferase was the most common laboratory result of DILI.Acute hepatocellular injury type was the most common type of DILI. Most DILI patients had good prognosis, and patients with response to treatment accounted for 95. 79% (91/95) , including those who were improved or cured. Age (odds ratio [OR]= 0. 054, 95% confidence interval (CI) : 0. 002-0. 076, P = 0. 037) , alkaline phosphatase (OR = 0. 004, 95% CI: 0. 001-0. 006, P = 0. 043) , total bilirubin (OR = 0. 028, 95% CI: 0. 001-0. 039, P = 0. 035) , and direct bilirubin (OR = 0. 008, 95% CI: 0. 001-0. 014, P = 0. 036) were independent risk factors for prognosis. Conclusion DILI does not have specific clinical manifestations and can easily be missed or misdiagnosed. Clinicians should use drugs rationally, monitor the presence of hepatotoxicity, and strengthen the public health education on safe medication.

Objective To investigate the expression of programmed death-ligand 1 (PD-L1) on the surface of peripheral blood CD4+and CD8+T cells and its correlation with liver inflammation grade in patients with type 1 autoimmune hepatitis (AIH) . Methods A total of 62 patients with type 1 AIH (43 in the active stage and 19 in the remission stage) who were admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2014 to August 2017 were enrolled, and 20 healthy persons were enrolled as control group. Flow cytometry was used to measure the expression of PD-L1 on the surface of eripheral blood CD4+and CD8+T cells. The t-test or the Mann-Whitney U test was used for the comparison of continuous data between two groups, and a one-way analysis of variance and the least significant difference t-test or the Kruskal-Wallis H test were used for the comparison between multiple groups; the chi-square test was used for comparison of categorical data between groups; Pearson correlation and Spearman rank analysis was performed to investigate correlation.Results Compared with the control group, the type 1 AIH group had significantly higher expression rates of PD-L1 on the surface of peripheral blood CD4+and CD8+T cells (10. 94% ± 4. 52%/9. 93% ± 3. 32% vs 5. 42% ± 2. 64%/4. 86% ± 2. 16%, t = 7. 12 and 6. 41, both P < 0. 05) ; compared with the remission stage group and the control group, the active stage group had significantly higher expression rates of PD-L1 on the surface of peripheral blood CD4+and CD8+T cells (12. 45% ± 5. 61%/11. 13% ± 4. 63% vs 7. 88% ± 3. 85%/7.36% ± 3. 12% and 5. 42% ± 2. 64%/4. 86% ± 2. 16%, F = 15. 76 and 13. 54, both P < 0. 05) , and the remission stage group also had significantly higher expression rates than the control group (both P < 0. 05) . There were gradual increases in the expression rates of PD-L1 on the surface of peripheral blood CD4+and CD8+T cells in the patients with type 1 AIH in G0 group (7. 88% ± 3. 85% and 5. 36% ±3. 12%) , G1-2 group (10. 13% ± 4. 74% and 10. 45% ± 4. 34%) , and G3-4 group (15. 63% ± 5. 98% and 14. 73% ± 5. 12%) (χ2=12. 14 and 10. 32, P < 0. 05) . In the patients in the active stage of type I AIH, the expression rates of PD-L1 on the surface of peripheral blood CD4+and CD8+T cells were positively correlated with total bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and immunoglobulin G (CD4+T cells: r = 0. 687, 0. 736, 0. 702, 0. 647, and 0. 824, all P < 0. 01; CD8+T cells: r = 0. 673, 0. 719, 0. 680, 0. 631, and 0. 817, all P < 0. 01) ; the expression rates of PD-L1 on the surface of peripheral blood CD4+and CD8+T cells were also positively correlated with liver inflammation grade (rs= 0. 768 and 0. 721, both P < 0. 05) . Conclusion In patients with type I AIH, high expression of PD-L1 on peripheral blood T cells is closely associated with liver inflammation grade, suggesting that PD-L1 may be involved in the development and progression of type 1 AIH.

Objective To investigate the clinical features, steroid response, and recurrence of Ig G4-associated sclerosing cholangitis (Ig G4-SC) , and to shorten the time for clinical diagnosis and reduce recurrence rate. Methods A total of 12 patients with Ig G4-SC who were admitted to Peking University First Hospital from December 2011 to March 2017 were enrolled, and they all met the clinical diagnostic criteria for Ig G4-SC in 2012. A retrospective analysis was performed for their clinical data, clinical features, and follow-up data. Results Of all 12 patients, the male/female ratio was 11∶ 1. The mean age of onset was 61. 7 ± 8. 6 years, and the mean time to a confirmed diagnosis was 24. 2 months. Of all 12 patients, 11 (92%) had jaundice, with a mean serum total bilirubin level of 198. 7 ± 57. 7 μmol/L. There were varying degrees of increase in serum alanine aminotransferase level (range 55-453 U/L) . Of all patients, 5 (41. 7%) had acute abdominal pain, with a mean CA19-9 level of 60. 8 ± 12. 5 U/ml. Serum Ig G4 was increased by 1. 5-18. 9 times, with a mean level of 7. 7 ± 2. 0 g/L. Magnetic resonance cholangiopancreatography (MRCP) performed for all patients showed typical manifestations including bile duct wall thickening, lumen stenosis, and intrahepatic and extrahepatic bile duct dilatation; 11 patients (92%) were found to have autoimmune pancreatitis, and 2 (16. 7%) had involvement of more than 3 visceral organs. In two patients who underwent biliary stent implantation before treatment, the biliary stent was removed after 4-6 weeks of steroid treatment. The mean duration of steroid response was 5. 4 months. Among the 8 patients who underwent steroid treatment, 4 (50%, 4/8) experienced recurrence during the reduction of the dose of steroid, among whom 2 experienced recurrence within 8-12 weeks after drug withdrawal. Conclusion Ig G4-SC needs a long time for prognosis, with frequent misdiagnosis and missed diagnosis. Serum Ig G4 level should be measured for elderly male patients with an acute onset of jaundice and bile duct stenosis, bile duct wall thickening, and involvement of the pancreas on MRCP. Steroid treatment should be given as early as possible after diagnosis. Patients may need at least 5-6 months to achieve steroid response. The dose of steroid should be reduced slowly and recurrence and tumorigenesis should be closely monitored.

Objective To investigate the association between acute ischemic cerebral infarction (AICI) and nonalcoholic fatty liver disease (NAFLD) in Uygur patients in Urumqi, China and possible risk factors. Methods A retrospective analysis was performed for the clinical data of 294 Uygur patients with AICI who were admitted to The Second Affiliated Hospital of Xinjiang Medical University from September2011 to July 2017, and according to the diagnosis based on abdominal ultrasound, these patients were divided into case group with 110 patients (AICI complicated by NAFLD) and control group with 184 patients (without NAFLD) . The two groups were observed in terms of general information, biochemical parameters, and intima-media thickness (IMT) of the common carotid artery. The AICI patients were divided into ≤30 years group, 31-45 years group, 46-60 years group, 61-75 years group, and ≥60 years group according to age, and the incidence rate of NAFLD was compared between these groups. The t-test was used for comparison of continuous data between groups, the chi-square test was used for comparison of categorical data between groups, and a multivariate logistic regression analysis was performed.Results Compared with the control group, the case group had significantly higher age, body mass index, waist-hip ratio, Hb A1 c, fasting blood glucose, uric acid, alanine aminotransferase (ALT) , gamma-glutamyl transpeptidase, triglyceride (TG) , total cholesterol, and low-density lipoprotein cholesterol (LDL-C) and a significantly lower aspartate aminotransferase level (t = 9. 814, 5. 569, 8. 139, 3. 592, 3. 514, 15. 703, 15. 113, 8. 092, 10. 834, 7. 719, 11. 481, and 7. 561, all P < 0. 05) . The case group had a significantly higher proportion of the patients with a smoking history than the control group (χ2= 14. 060, P < 0. 05) . The logistic regression analysis showed that the increases in age (odds ratio [OR]= 1. 301, 95% confidence interval [CI]: 1. 065-1. 589, P < 0. 05) and serum levels of ALT (OR =1. 383, 95% CI: 1. 059-1. 805, P < 0. 05) , TG (OR = 1. 335, 95% CI: 1. 091-1. 634, P < 0. 05) , and LDL-C (OR = 1. 358, 95%CI: 1. 125-1. 639, P < 0. 05) and a smoking history (OR = 1. 423, 95% CI: 1. 105-1. 833, P < 0. 05) were closely associated with NAFLD in AICI patients. The incidence rate of NAFLD in AICI patients increased with age, and there was a significant difference between different age groups (χ2= 13. 558, P = 0. 009) ; the 61-75 years group and the > 76 years group had an incidence rate of NAFLD of44. 09% and 51. 35%, respectively, which were significantly higher than that in the other three groups (P < 0. 05) . Conclusion Increases in age and serum levels of ALT, TG, and LDL-C and a smoking history are independent risk factors for NAFLD in patients with AICI, and AICI patients aged over 60 years have a high incidence rate of NAFLD.

Objective To establish a noninvasive diagnosis equation for nonalcoholic fatty liver disease (NAFLD) using related clinical and laboratory markers, and to investigate the value of this equation in the prediction and diagnosis of NAFLD. Methods A total of 127 patients who were diagnosed with NAFLD in The First Affiliated Hospital of Xi' an Medical University from November 2016 to November 2017 were enrolled, and 30 healthy individuals were enrolled as healthy controls. Related data were recorded, including sex, age, body mass index (BMI) , medical history, alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , gamma-glutamyl transpeptidase (GGT) , blood urea nitrogen (BUN) , uric acid (UA) , serum creatinine (SCr) , total cholesterol (TC) , triglyceride (TG) , high-density lipoprotein (HDL) , low-density lipoprotein (LDL) , Hb Alc, free fatty acid (FFA) , fasting blood glucose (FPG) , fasting insulin (FINS) , platelet count (PLT) , and results of ultrasound examination and Fibro Scan examination. The t-test was used for comparison of continuous data between groups; the Pearson correlation analysis was performed to investigate correlation; the multiple linear regression equation model was used to establish the regression equation; the receiver operating characteristic (ROC) curve was plotted to calculate the sensitivity and specificity of this regression equation. Results The indices related to fatty liver included BMI (r = 0. 308, P = 0. 005) , ALT (r = 0. 379, P < 0. 001) , AST (r = 0. 318, P = 0. 004) , GGT (r = 0. 293, P = 0. 009) , UA (r = 0. 244, P = 0. 033) , and FFA (r = 0. 249, P =0. 030) . A multiple regression analysis was performed for controlled attenuation parameter (CAP) on Fibro Scan; the regression model of CAP had statistical significance (F = 11. 113, P < 0. 001) , and its adjusted determination coefficient R2 was 0. 274, suggesting that the variation caused by regression accounted for 27. 4% of all variations; ALT had the greatest influence on CAP (β = 0. 358, P = 0. 001) , followed by BMI (β = 0. 258, P = 0. 012) . The regression equation established was CAP = 113. 163 + 0. 252 × ALT + 6. 316 × BMI. This diagnostic equation had an area under the ROC curve of 0. 927, a sensitivity of 87. 68%, and a specificity of 90. 00%, at the cut-off value of277. 67 (P < 0. 001) , suggesting that it had high diagnostic efficiency. Conclusion Compared with current diagnosis equations, the equation established in this study has a larger area under the ROC curve and higher specificity and sensitivity. It also has a simple calculation method and strong practicability and operability and helps to screen out early NAFLD and improve the awareness of self-intervention, which can further reduce the harm and delay the progression of NAFLD in the world.

Objective To investigate the influence of bisphenol A (BPA) , an environmental endocrine disruptor, on inflammatory response in rats with nonalcoholic fatty liver disease (NAFLD) , as well as its adverse effect on intestinal mucosal barrier. Methods A total of 18 mature male rats were randomly divided into normal group, NAFLD group, and NAFLD + BPA group, with 6 rats in each group. liver pathological changes were observed under a light microscope; ELISA was used to measure the serum levels of tumor necrosis factor-α (TNF-α) , interleukin-1β (IL-1β) , interleukin-6 (IL-6) , and interleukin-8 (IL-8) ; the terminal colorimetric analysis with Limulus amebocyte lysate was used to measure the level of endotoxin; an immunofluorescence assay was used to measure the expression of occluding protein in the intestinal mucosa; real-time PCR was used to measure the mRNA expression of ZO-1 in the intestinal mucosa. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the SNK-q test was used for further comparison between two groups. Results Liver pathological examination showed that the rat model of NAFLD was established successfully. After the 8-week treatment with 100 nmol/L BPA, compared with the normal group and the NAFLD group, the NAFLD + BPA group had significant increases in the expression of TNF-α (127. 65 ± 22. 4 pg/ml vs 64. 87 ± 10. 83 pg/ml and 92. 34 ± 10. 68 pg/ml, P < 0. 05) , IL-6 (199. 34 ± 17. 46 pg/ml vs 91. 27 ± 9. 82 pg/ml and 181. 93 ± 20. 11 pg/ml, P < 0. 05) , and IL-8 (258. 79 ± 12. 82 pg/ml vs 123. 76 ±19. 68 pg/ml and 201. 64 ± 22. 34 pg/ml, P < 0. 05) and the level of endotoxin (0. 88 ± 0. 26 EU/ml vs 0. 27 ± 0. 09 EU/ml and 0. 63 ±0. 15 EU/ml, P < 0. 05) . The NAFLD group and the NAFLD + BPA group had a significantly higher level of IL-1β than the normal group (186. 31 ± 20. 06 pg/ml and 208. 78 ± 13. 77 pg/ml vs 112. 84 ± 23. 12 pg/ml, both P < 0. 05) , but there was no significant difference between these two groups. Compared with the normal group, the NAFLD group and the NAFLD + BPA group had significant reductions in the expression of occluding protein and the mRNA expression of ZO-1 in the intestinal mucosa, and the NAFLD + BPA group had a significantly greater reduction in the mRNA expression of ZO-1 than the control group and the NAFLD group (33. 25 ± 11. 04 vs 68. 03 ± 11. 73/45. 24 ±6. 98, P < 0. 05) . Conclusion In the background of NAFLD, long-time exposure to low-dose BPA can increase the release of some inflammatory factors, promote endotoxemia, and thus damage intestinal mucosal barrier.

Objective To investigate the antioxidant effect of berberine in a rat model of nonalcoholic steatohepatitis (NASH) and an in vitro model of oxidative stress induced by H2 O2. Methods High-fat diet was used to establish a rat model of NASH. After three weeks of treatment with berberine 18 mg/kg/d by gavage, HE staining was used to observe liver pathological changes, and the activities of glutathione (GSH) and superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in liver tissue were measured. An in vitro model of oxidative stress induced by reactive oxygen species (ROS) due to H2 O2 was established; flow cytometry was used to measure the level of ROS, and the activities of SOD, GSH, lactate dehydrogenase (LDH) , and chloramphenicol acetyltransferase (CAT) in hepatocytes were measured. A one-way analysis of variance was used for comparison of continuous data between groups, and the Bonferroni test was used for further comparison between two groups; the t-test was used for comparison of continuous data between two groups. Results NASH rats had significant improvements in the extent of infiltration of inflammatory cells, focal necrosis, and ballooning degeneration of hepatocytes after berberine treatment. Compared with the NASH model group, the berberine group had significant increases in the activities of GSH (29. 8 ±2. 4 U/mg vs 19. 9 ± 1. 3 U/mg, P < 0. 001) and SOD (26. 6 ± 1. 9 μg/mg vs 19. 7 ± 1. 4 μg/mg, P < 0. 001) and a significant reduction in the level of MDA (19. 8 ± 1. 5 nmol/mg vs 24. 0 ± 2. 0 nmol/mg, P < 0. 001) . In the in vitro model of oxidative stress induced by H2 O2, the H2 O2 group had a significant increase in the level of ROS compared with the berberine + H2 O2 group (69. 8% ± 1. 9% vs 50. 4% ±6. 5%, t = 24. 42, P = 0. 008) . Compared with the H2 O2 group, the berberine + H2 O2 group had significant increases in the activities of SOD (25. 5 ± 1. 3 μg/mg vs 18. 8 ± 1. 0 μg/mg, P < 0. 001) and GSH (27. 1 ± 0. 6 U/mg vs 16. 79 ± 3. 8 U/mg, P < 0. 001) in hepatocytes; there was no significant difference in the level of LDH between the berberine + H2 O2 group and the H2 O2 group (P = 0. 103) , and there was no significant difference in the activity of CAT across all groups (F = 3. 76, P = 0. 060) . Conclusion Both in vivo and in vitro models show that berberine has a good antioxidant effect, possibly by increasing the activities of antioxidant enzymes.

Objective To investigate the clinical manifestations, treatment, and prognosis of sinusoidal obstruction syndrome induced by pyrrolidine alkaloids in China. Methods Related databases were searched, and 107 articles on sinusoidal obstruction syndrome published from January 1980 to April 2017 in China were included, with 407 patients in total. Related data of this disease were analyzed, including sex, age, regional distribution, clinical manifestations, imaging and pathological findings, and prognosis. Results The male/female ratio of 407 patients was 1: 1. 22, and the age of onset ranged from 13 months to 81 years. Major clinical manifestations included abdominal distension, abdominal pain, ascites, and hepatomegaly. The most typical abdominal CT findings were hepatomegaly and a map-like or patchy change after enhancement. Pathological examination showed sinusoidal expansion and congestion and varying degrees of stenosis of small hepatic veins. Of all 407 patients, 302 had response and 90 died, resulting in a mortality rate of 22. 1%. Conclusion In China, the male population has a higher incidence rate of sinusoidal obstruction syndrome than the female population, and sinusoidal obstruction syndrome can occur at any age. Major clinical manifestations include abdominal distension, abdominal pain, ascites, and hepatomegaly, which can be used to make a definite diagnosis in combination with typical liver CT manifestations. Pathological findings by liver biopsy are the gold standard for diagnosis. Symptomatic treatment is the major treatment modality, and some patients may have poor prognosis.

Objective To investigate the risk factors for early complications after liver transplantation and to improve the prognosis. Methods The clinical data of 147 patients who underwent orthotopic liver transplantation in the Hepatic Transplantation Center of The First Hospital of Jilin University from September 2011 to April 2017 were retrospectively analyzed. According to the presence or absence of early complications after surgery, these patients were divided into non-complication group (n = 11) and complication group (n = 136) . The possible factors associated with early complications after surgery were collected, including donor factors (age and whether the blood type of the donor matches that of the recipient) , recipient factors (sex, age, primary disease, Model for End-Stage Liver Disease [MELD]score, aspartate aminotransferase [AST], alanine aminotransferase[ALT], albumin [Alb], platelet [PLT], hemoglobin [Hb], fibrinogen, total bilirubin, creatinine, PLT/Alb ratio [PAR], and neutrophil/lymphocyte ratio [NLR]) , intraoperative factors (cold ischemia time, warm ischemia time, intraoperative blood loss, and duration of anhepatic phase) , and postoperative factors (AST and ALT immediately and 12, 24, 48, and 72 hours after operation) . The clinical data were analyzed to investigate the association between these factors and early complications.The t test was used for comparison of normally distributed continuous data; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data. The chi-square test was used for comparison of categorical data. Backward logistic regression was used for multivariate analysis. Results MELD score (t =-3. 86, P = 0. 002) , Alb (t = 2. 19, P = 0. 049) , PLT (Z = 467. 00, P = 0. 039) , PAR (Z = 500. 00, P = 0. 068) , fibrinogen (t = 1. 80, P = 0. 096) , TBil (Z =-1. 98, P = 0. 047) , preoperative AST (Z = 417. 00, P =0. 015) , and preoperative ALT (Z = 501. 50, P = 0. 070) were associated with postoperative complications. PAR and preoperative AST were independent risk factors for early complications (odds ratio [OR]= 3. 84, 95% confidence interval [CI]: 1. 03-14. 34, P < 0. 05; OR =0. 25, 95% CI: 0. 07-0. 94, P < 0. 05) . The 147 patients were divided into high-PAR group (PAR ≥3 × 109/g; n = 55) and low-PAR group (PAR < 3 × 109/g; n = 92) ; PAR was associated with postoperative vascular and biliary complications (χ2= 2. 87, P = 0. 090;χ2= 3. 54, P = 0. 060) . The 147 patients were divided into normal preoperative AST group (AST < 40 U/L; n = 93) and abnormal preoperative AST group (AST ≥40 U/L; n = 54) ; preoperative AST level was associated with postoperative pleural effusion (χ2= 3. 03, P =0. 082) . Conclusion Fibrinogen, PLT, Alb, TBil, PAR, MELD score, and preoperative AST and ALT are associated with the development of early complications after liver transplantation, and PAR and preoperative AST are independent risk factors for early complications.To improve the prognosis and postoperative survival, these factors, particularly PAR, should be fully assessed for the liver transplantation recipient before operation, and specific interventions should be provided accordingly.