Study of clinical characteristics in patients with gp210 antibody-positive primary biliary cholangitis / 中华肝脏病杂志

Objective: To analyze the clinical characteristics and prognostic value of liver function in a large samples of patients with anti-glycoprotein 210 (gp210 antibody) positive primary biliary cholangitis (PBC). Methods: A retrospective study was performed on 931 PBC cases in Beijing You'an Hospital affiliated to Capital Medical University from 2010 to 2019. According to the detection of gp210 antibody, 318 cases were divided into gp210 antibody positive group (positive group) and 613 cases were divided into gp210 antibody negative group (negative group). The differences in demographic, medical history, clinical indicators, B-ultrasound and pathological indicators as well as the histopathological basis were compared between the two groups. SPSS 16.0 software was used for statistical analysis. Measurement data were analyzed by t-test or rank sum test, and enumeration data by χ2 test. Multivariate analysis was used for logistic test, and and survival analysis was used for prognosis. Results: The positive and the negative groups were compared. The ratio of male to female was significantly higher in positive than negative group (1:5.35 vs. 1:9.73, P＜0.05), and the difference was statistically significant. The proportion of hormone use in history of past diagnosed and treated was higher in positive than negative group (12.9% vs. 3.47%, P＜0.05), and the difference was statistically significant. The detection of biochemical indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT) were higher in positive than the negative group (51.1 U/L vs. 41.1 U/L, 62.6 U/L vs. 49.6 U/L, 24.1 μmol/L vs. 17.9 μmol/L, 228.3 U/L vs. 169.6 U/L, 203.9 U/L vs. 147.6 U/L), (P＜0.05), and the differences were statistically significant. Antinuclear antibody (ANA)-positive rate, high titer ratio and immunoglobulin G (IgG) levels were higher in positive than negative group (95.2% vs. 81.6%, 69.7% vs. 48.8%, 17.2 g/L vs. 16.2 g/L), (P＜0.05), and the differences were statistically significant. The incidence of liver failure was higher in positive than negative group (P＜0.05). CK7 and inflammation score were higher in positive group than negative group in liver histopathological observations (0.83±0.53 vs. 0.28±0.47; 1.06±0.39 vs. 0.54±0.65), (P＜0.05), and the differences were statistically significant. Conclusion: The illness condition of patients with gp210 antibody positive PBC is more severe than patients with gp210 antibody negative PBC, and the incidence of liver failure is significantly increased. Cholangiocytes may be the histopathological basis of the clinical characteristics of gp210 antibody positive PBC patients.

Clinical characteristics of drug-induced liver injury in 31 pediatric cases / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics and responsible agents of drug-induced liver injury (DILI) in pediatric patients.</p><p><b>METHODS</b>Thirty-one cases of DILI treated in our hospital's pediatric ward were retrospectively analyzed. The clinical data for each patient were extracted from the patient's medical records, and included reported causes, physical and biochemical features, natural history, blood examination results, and hepatic pathology findings.</p><p><b>RESULTS</b>The 31 pediatric cases of DILI accounted for 1.7% of the 1831 total cases of drug-induced liver injury treated at our hospital between February 2002 to June 2011. The pediatric DILI population was composed of 20 males and 11 females, with an average age of 8.8+/-3.9 years old (range, 0.3-14.0). The liver injury patterns represented among the cases were: hepatocellular (25.8%), cholestasis (25.8%), and mixed hepatocellular-cholestatic (48.4%). Antimicrobials were the most common cause (41.9%) of DILI, followed by the herbal medicine (29.0%) and febrifuge drugs (19.4%). A single drug was implicated in nine cases (29.0%), and two or more drugs were implicated in 22 cases (71%). Most of the children had good prognosis, but those with pre-existing disease had poor prognosis. One child died of hepatic failure, making the death rate 3.23%. The average hospitalization time was 25.2 days, and the patients with hepatocellular injury had shorter hospitalization time than those with mixed injury.</p><p><b>CONCLUSION</b>Drug-induced liver injury in our pediatric population was most often caused by antimicrobials, followed by herbal medicine and febrifuge drugs. Most patients presented with mixed hepatocellular-cholestatic injury. Children with pre-existing diseases or hepatic failure had poor prognosis.</p>

The characteristic of T cells response to HBV-specific antigen proteins in patients with HBV infection / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To analyze the characteristic of T cell response to specific antigen proteins in patients with hepatitis B virus infection.</p><p><b>METHODS</b>76 cases were recruited, including four groups, acute hepatitis B (AHB), active phase of chronic hepatitis B (CHB), inactive HBV carriers (AsC) and past HBV infection. T cell responses stimulated by 3 antigen specific proteins of HBV were detected using enzyme linked immunospot (ELISPOT) assay.</p><p><b>RESULTS</b>(1) There were no significant difference in frequencies to HBsAg, HBcAg and HBeAg in AHB and CHB. The frequencies to HBsAg and HBcAg in AsC were lower than that to HBeAg, and the frequencies to HBsAg in group of past HBV infection were significantly lower than that to HBcAg and HBeAg. (2) The frequencies to HBsAg in AHB and CHB both were higher than in group of past HBV infection. The frequencies to HBcAg of AHB, CHB and AsC were higher than that of group of past HBV infection. (3) There were no significant difference in magnitude to HBsAg, HBcAg and HBeAg in AHB and AsC. In CHB, the magnitude to HBsAg was lower than that to HBcAg. The magnitude of in group of past HBV infection were HBcAg > HBeAg > HBsAg. (4) In four groups, the sequence of the magnitude to HBsAg from high to low was AHB, CHB, group of past HBV infection and AsC. The magnitude to HBcAg in of AsC was lower than other three groups. As to the magnitude to HBeAg, the difference was no significant between any two groups except between AHB and CHB.</p><p><b>CONCLUSIONS</b>The T cell responses in group of AsC to HBeAg were the highest, while the T cell responses to HBcAg were the highest in group of other groups.</p>

Clinical significance of liver function and autoantibodies in patients with acute or chronic drug-induced liver injury / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the clinical significance of liver function and autoantibodies in patients with acute or chronic drug-induced liver injury.</p><p><b>METHODS</b>51 patients with drug-induced liver injury were divided into acute drug induced liver injury group and chronic drug induced liver injury group, liver function and autoantibodies were compared between these two groups.</p><p><b>RESULTS</b>There was no significant difference (P more than 0.05) in alanine aminotransferase [(412.1+/-387.5) U/L and (376.0+/-319.7) U/L], aspartate aminotransferase [(352.5+/-457.9) U/L and (198.8+/-142.7) U/L], total bilirubin [(109.7+/-104.80)micromol/L and(102.4+/-135.7)micromol/L], direct bilirubin [(66.4+/-73.3)micromol/L and (61.2+/-72.1)micromol/L], alkaline phosphatase [(133.4+/-50.1) U/L and (147.4+/-97.3) U/L], gamma-glutamyltransferase [(139.9+/-134.1) U/L and (180.6+/-227.9) U/L], and albumin [(41.3+/-4.9) g/L and (39.8+/-5.3)g/L] between these two groups, however, the level of globulin [(25.1+/-5.3) g/L and (28.6+/-5.1) g/L] was significantly different between these two groups (P less than 0.05). The titers of Anti-nuclear antibody (ANA) and smooth muscle antibody (SMA) were less than or equal to 1:320 in patients with acute drug induced liver injury. The titers of ANA, antimitochondrial antibody (AMA), and SMA were more than or equal to 1:320 in most of the patients with chronic drug induced liver injury.</p><p><b>CONCLUSION</b>Liver function has no value in the diagnosis of acute or chronic drug induced liver injury. High titer autoantibodies are found in patients with chronic drug induced liver injury.</p>

Detection of antigen-epitope-specific cytotoxic T lymphocytes in patients with hepatitis B virus infection by enzyme linked immunospot assay / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the ability of secreting interferon-gamma (IFN-gamma) of the peripheral blood monocular cells (PBMC) stimulated by hepatitis B virus (HBV)-specific cytotoxic T lymphocyte (CTL) epitopes peptides and to analyze the difference of CTL immune response in patients with HBV infection.</p><p><b>METHODS</b>Four HLA-A2-restricted HBV cytotoxic T lymphocyte epitopes [Tp: HBV polymerase 575-583 (FLLSLGIHL), Te1: envelope 28-39 (IPQSLDSWWTSL), Te2: envelope 183-191 (FLLTRILTI) and Tc: core 18-27 (FLPSDFFPSV)] were synthesized. Human leucocyte antigen (HLA)-A2 typing was detected by Flow cytometry. PBMCs which were isolated from patients with chronic hepatitis B(CHB), patients with chronic severe hepatitis B(CSH), subjects with past HBV infection(N1) and healthy blood donors (N2) were stimulated by the four HLA-A2-restricted HBV CTLs epitopes. Enzyme linked immunospot (ELISPOT) assay was used to detect the frequency of secreting IFN-gamma CTL in each group.</p><p><b>RESULTS</b>(1) HLA-A2 typing: 20 of 44 patients with CHB (45.5%) were HLA-A2 positive, 10/18 (55.6%) in CSH and 6/10 (60%) in group N1 were HLA-A2 positive.10 healthy blood donors' HLA-typing was detected in the early study.(2) ELISPOT results: (1) The total responses to the four epitopes in CHB, CSH, N1 and N2 groups were 50% (10/20), 10% (1/10), 83.3% (5/6) and 10% (1/10), respectively. The response in N1 group was significantly higher than that in CSH group (chi(2) = 9.000, P = 0.008) and N2 group (chi(2) = 9.000, P = 0.008). (2) The CTL average magnitude response to Tp epitope, Te1 epitope, Te2 epitope and Tc epitope was also significantly higher in past HBV infection group (77 SFC/10(6) PBMC, 59 SFC/10(6) PBMC, 100 SFC/10(6) PBMC and 57 SFC/10(6) PBMC, respectively) than that of CSH group (10 SFC/10(6) PBMC, 0 SFC/10(6) PBMC, 0 SFC/10(6) PBMC and 20 SFC/10(6) PBMC respectively, all P < 0.01) and N2 group (15 SFC/10(6) PBMC, 0 SFC/10(6) PBMC, 22 SFC/10(6) PBMC and 30 SFC/10(6) PBMC respectively, all P < 0.01).</p><p><b>CONCLUSION</b>This study indicates that the T cell immune response to HBV-specific epitopes might be detected either in patient with chronic HBV infection or with previous HBV infection. This response should be much higher in patients with past HBV infection, even the virus had been cleared for long time. These results demonstrate that HBV-specific CTL might play an important role in the clearance of the virus.</p>