Clinical features and prognosis of HBV-related acute-on-chronic liver failure in pregnancy / 临床肝胆病杂志

Objective To investigate the clinical features and prognosis of pregnant women with HBV-related acute-on-chronic liver failure (HBV-ACLF). Methods A retrospective analysis was performed for the clinical data of 26 pregnant women with HBV-ACLF who were admitted to Shanghai Public Health Clinical Center from June 2008 to July 2020, including age, gestational weeks at disease onset, parity, initial symptoms, complications on admission, laboratory markers [white blood cell count, hemoglobin, platelet count, alanine aminotransferase, total bilirubin (TBil), albumin, serum creatinine, Model for End-Stage Liver Disease (MELD) score, HBsAg, and HBV DNA], abdominal ultrasound, mode of delivery, fetus conditions, treatment measures, and prognosis. The t -test was used for comparison of normally distributed continuous data between two groups, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test and the Fisher's exact test were used for comparison of categorical data between two groups. Results Among the 26 patients, 8 died within 28 days after disease onset, and the mortality rate reached 30.8%. There were 22 multiparous patients, accounting for 84.6%, and HBV-ACLF often occurred in the third trimester of pregnancy (20/26, 76.9%), with a mean gestational age of 30.9±5.8 weeks. HBV-ACLF often had atypical clinical manifestations, and initial symptoms included weakness, poor appetite (21/26, 80.8%), and yellow urine (19/26, 73.1%). Compared with the survival group, the death group had significantly higher levels of TBil ( Z =-2.056, P =0.041), prothrombin time ( Z =-2.362, P =0.016), international normalized ratio ( Z =-2.528, P =0.009), and MELD score ( Z =-2.223, P =0.026), a significantly longer time from initial symptom to diagnosis ( Z =-2.468, P =0.021), significantly higher HBV DNA level ( χ 2 =7.571, P =0.021), degree of hepatic encephalopathy ( χ 2 =24.775, P < 0.001), and incidence rate of complications ( χ 2 =5.951, P =0.042), and significantly lower levels of fibrinogen ( Z =-2.667, P =0.006) and prothrombin time activity ( Z =-2.365, P =0.016). Conclusion HBV-ACLF is a serious complication in the third trimester of pregnancy and is often observed in multiparous patients, with an extremely high short-term mortality. It often has atypical clinical manifestations in the early stage, and high MELD score, high viral load, and complications often indicate a poor prognosis.

Clinical features and risk factors of acute hepatitis E with severe jaundice / 临床肝胆病杂志

ObjectiveTo investigate the clinical features of acute hepatitis E (AHE) patients with or without severe jaundice and the risk factors for severe jaundice. MethodsA retrospective analysis was performed for the clinical data of 179 AHE patients who were admitted to Shanghai Public Health Clinical Center Affiliated to Fudan University from January 1, 2018 to March 26, 2020. According to whether total bilirubin (TBil) was ＞171 μmol/L, the patients were divided into AHE-mild jaundice (AHE-M) group and AHE-severe jaundice (AHE-S) group, and the two groups were compared in terms of clinical data and laboratory markers. The t test or the Mann-Whitney U test or the chi-squared test was used for comparison, and a binary logistic regression analysis was used to identify independent risk factors. ResultsOf all 179 patients, 101 (56.42%) were found to have severe jaundice. Compared with the AHE-M group, the AHE-S group had a significantly higher proportion of male patients (80.20% vs 61.54%, χ2=7.612, P=0.006), a significantly longer length of hospital stay ［29 (19-45) days vs 18 (14-22) days, Z=-6.035, P＜0.001］, a significantly higher number of patients with liver failure (23 vs 0, χ2=18.373, P＜0.001), and a significantly poorer prognosis (P＜0.001). Compared with the AHE-M group, the AHE-S group had significantly higher baseline anti-HEV-IgM, alpha-fetoprotein, and liver elasticity (Z=-3.534, -3.588, and -4.496, all P＜0.001), significantly lower baseline CD4 (Z=-2.015, P＜0.05), significantly higher peak values of TBil, direct bilirubin, creatinine, prothrombin time, international normalized ratio, and absolute neutrophil count (Z=-11.016, -10.926, -2.726, -4.787, -4.989, and -6.016, all P＜0.01), a significantly lower peak value of gamma-glutamyl transpeptidase (GGT) (Z=-4.55, P＜0001), and significantly lower valley values of albumin, prealbumin (PA), and absolute lymphocyte count (Z=-4.685, -5.087, and -4.818, all P＜0.001). The logistic regression analysis showed that anti-HEV-IgM (odds ratio ［OR］=1.022, 95% confidence interval ［CI］: 1005-1.039, P=0.012), GGT (OR=0.995, 95%CI: 0.993-0.998, P=0.001), PA (OR=0.991, 95%CI: 0.983-0.999, P=0.02), and neutrophils (OR=1.486, 95%CI: 1.169-1.889, P=0.001) were independent risk factors for severe jaundice in AHE patients. ConclusionThere is a relatively high proportion of male patients among the AHE patients with severe jaundice, with a long length of hospital stay, a large number of patients with liver failure, and poor prognosis. Anti-HEV-IgM, GGT, PA, and neutrophils are independent risk factors for severe jaundice in AHE patients.

Association between intestinal microecology and spontaneous bacterial peritonitis / 临床肝胆病杂志

Spontaneous bacterial peritonitis (SBP) is a common serious complication of end-stage liver disease. Intestinal microecology is closely associated with the development, progression, and prognosis of SBP, and bacterial translocation is the key pathogenesis of SBP. This article summarizes the intestinal microecology in patients with liver cirrhosis and briefly describes the mechanism of action of intestinal flora in the development and progression of SBP, thus providing a theoretical basis for the clinical regulation of intestinal microecology and treatment of SBP.

Efficacy and safety of paritaprevir/ritonavir/ombitasvir combined with dasabuvir in non-cirrhotic Asian adult patients with newly diagnosed and treated chronic HCV genotype 1b infection: a randomized, double-blind, placebo-controlled study - China data / 中华肝脏病杂志

Objective@#To evaluate the safety and efficacy of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily combined with dasabuvir 250mg, twice daily in non-cirrhotic Chinese adult patients with newly diagnosed and treated chronic HCV genotype 1b infection. @*Methods@#A randomized, double-blind, placebo-controlled, multicenter phase 3 clinical trial was conducted in mainland China, Korea, and Taiwan.Safety and efficacy of OBV/PTV/r plus DSV administered for 12 weeks were evaluated in a newly diagnosed and treated (interferon alpha /pegylated interferon alpha) and ribavirin non-cirrhotic adults with chronic HCVgenotype 1b infection. Patients randomly received OBV/PTV/r plus DSV for 12 weeks (Group A), or placebo for 12 weeks (Group B) followed by an open-label phase of OBV/PTV/r plus DSV for 12 weeks. Sustained response (SVR12) rate obtained at 12 weeks and (SVR24) 24 weeks after discontinuation of treatment, and the incidence of adverse events and laboratory abnormalities after double-blind and open-label phase treatment were assessed. @*Results@#A total of 410 cases of Chinese patients were included and randomly assigned to group A and B (with 205 cases in each group) in a 1:1 ratio. The rates of SVR12 and SVR24 were 99% (95% CI: 94.8% - 99.8%) in the newly diagnosed patients in group A (205 patients) and the rates of SVR12 and SVR24 were 100% in treated patients (95% CI: 96.3% - 100%). Different baseline characteristics had no effect on SVR12 and SVR24 rates. Most of the adverse events occurred were mild, asymptomatic, and≥ 3 laboratory abnormalities during treatment were rare, including elevation of alanine aminotransferase (2 cases in double-blind stage A group), aspartate aminotransferase (Double-blind stage A (3 cases) and total bilirubin (1 case in open-label phase B group); however, those mild adverse events could be recovered after drug withdrawal or discontinuation. only1 person discontinued drugs due to adverse events (Group B, open-label phase). @*Conclusion@#The 12 weeks treatment course of OBV/PTV/r combined with DSV produced 99% ~ 100% rates of SVR12 and SVR24 in non-cirrhotic Asian adult patients with newly diagnosed and treated chronic HCV genotype 1b infection, and the tolerance and safety were good.

study on clinical value of the detection about serum and Unconjugated Bilirubin in diagnosis of neonatal jaundice

In this paper, the clinical value of the detection about serum and unconjugated bilirubin [UCB] in neonatal jaundice was studied to found an effective and rapid method for diagnose of neonatal jaundice. ALB [Serum Albumin], total serum bilirubin [TSB] and UCB were detected by ELISA method among the 100 cases with neonatal jaundice selected for the study. The values of ALB, UCB and TSB in moderate jaundice patients were [42.83 +/- 3.87] g/L, [287.35 +/- 44.38] microm/L, [304.16 +/- 43.40] microm/L, respectively; as for the severe jaundice patients, the values were [38.41 +/- 4.82] g/L, [354.38 +/- 48.75] microm/L, [375.20 +/- 47.51] microm/L. The results showed significant differences with the p< 0.05 between moderate and severe jaundice patients. The level of ALB, UCB, TSB in hemolytic jaundice, obstructive jaundice and jaundice caused by other infections also had significant differences, and the difference was statistically significant [p<0.05]. The detection of ALB and UCB provides a useful method for the diagnosis and assessment of neonatal jaundice

Drug resistance profile and serotype of streptococcus of pneumoniae infected pediatric patients

To investigate the surviliance of drug resistance and serotype monitoring of steptococcus pneumoniae in hospitalized children. the pathogenic bacteria isolation and identification methods were employed to do the bacteria isolation identification and drug sensitive test on the specimens from Women and Infants Hospital of Zhengzhou. From the specimens, there were 134 detected strains of Streptococcus pneumoniae, and the drug resistance to erythromycin and clindamycin were respectively 97.7% and 89.9%, and the drug resistance to tetracycline, azithromycin and paediatric compound sulfamethoxazole were respectively 86. 3%, 58. 3%, 51. 2%. The vancomycin resistant Streptococcus pneumoniae were often not found. the Streptococcus pneumoniae in children were generally with drug resistant in Zhengzhou area. It shall strengthen drug resistance surviliance, and reasonably choose antibacterial agents

TACE treatment for patients with inoperable hepatocellular carcinoma and hepatic failure history:initial experience in seven cases / 介入放射学杂志

Objective To discuss the safety and efficacy of transcatheter arterial chemoembolization (TACE) in treating patients with inoperable hepatocellular carcinoma (HCC) who has a history of hepatic failure. Methods A total of 7 HCC patients who had a history of hepatic failure (study group) were enrolled in this study. TACE was carried out in all these 7 patients. Other 51 patients who had no liver failure history were used as the control group. All the patients were followed up for at least six months. The postoperative adverse events, changes of liver function and the prognosis were recorded, and the results were compared between the two groups. Results In the study group, neither treatment-related death nor severe adverse events occurred. No significant difference in the occurrence of mild adverse events existed between the two groups. After TACE the liver functions, including alanine aminotransferase, total bilirubin, prolonged prothrombin time, albumin, etc. in the study group were significantly worse than those in the control group,groups. Conclusion For patients with inoperable hepatocellular carcinoma who has a history of hepatic failure, TACE is a safe and effective treatment.

Study of peripheral blood monocytes in patients with hepatitis B virus-related acute-on-chronic liver failure under immune dysfunction state / 中华消化杂志

Objective To study apoptosis and antigen presentation changes of monocytes in HBV-related acute-on-chronic liver failure (ACLF) patients under immune dysfunction state.Methods Peripheral blood samples of 26 HBV-related ACLF patients (ACLF group),20 active chronic hepatitis B patients (CHB group) and 18 healthy individuals (control group) were collected.The changes of apoptosis and proliferation (Ki67) in monocytes and the expression of surface markers including human leukocyte antigen (HLA)-DR and B7 molecules (CD86) of monocytes were analyzed by flow cytometry. Results The percentage of Annexin V expressed monocytes of ACLF group (64％) was significantly higher than that of CHB group (28％) and control group (20％),and the difference was statistically significant (x2 value was 11.75 and 27.23 ; both P＜0.01),which indicated that monocytes apoptosis increased.The Ki67 expression in monocytes of ACLF group was lower than that of CHB group and control group,and the difference was statistically significant (x2 value was 4.71 and 4.83; both P＜ 0.05),which indicated that activated monocytes reduced. The mean fluorescence intensity (MFI) of HLA-DR and CD86 of monocytes in ACLF group was 22.85 and 11.63,which was significantly lower than that of CHB group and control group,indicating the antigen presentation ability of monocytes injured. The percentage of Annexin Ⅴ positive monocytes in survivals (62 ％ ) was significantly higher than that of dead patients (46 ％ ) in ACLF group.Conclusion In HBV-related ACLF patients under immune dysfunction state,the apoptosis of peripheral blood monocytes increased,and the quantity of activated cells reduced,resulting in the decline of the antigen presentation ability of monocytes.

Therapeutic effects of human umbilical cord mesenchymal stem cell transplantation on acute liver failure in rats / 中华传染病杂志

Objective To study the therapeutic effects of human umbilical cord mesenchymal stem cells (hUCMSCs) on acute liver failure ( ALF) induced by D-galactosamine (D-gal) and lipopolysaccharide (LPS) in rats. Methods The ALF model was obtained through intraperitoneal injection of D-gal(300 mg/kg)and LPS (20μg/kg)in Wister rats. The hUCMSCs were transplanted after intoxication. All rats were divided into four groups, and each group received either hUCMSCs or 0.9% NaCl solution through intraperitoneal or tail-intravenous injection. To evaluate the liver function of each group, the levels of alanine aminotransferase (ALT), total bilirubin (TBil) and serum albumin (Alb) were measured on the day of hUCMSCs transplantation and the following 1, 2, 3, 5 and 7 days. All rats were then sacrificed to examine the liver histology at day 7. Analyses were done by using Fisher's exact test, unpaired t test and Mann-Whitney U test. Results There were no significant differences of survival rates among four groups (Fisher's exact test, both P = 1. 00). The levels of ALT, TBil and Alb in group receiving hUCMSCs intraperitoneally were (804. 9 ± 88. 0) U/L,(17. 4±2. 7) μmol/L and (20. 9±0. 8) g/L, respectively after 2 days of injection, whereas in the corresponding control group, those were (1294. 3± 171. 4) U/L, (32. 3±5. 5) μmol/L and (16. 1±0. 9) g/L, respectively, which indicated that hUCMSCs transplantation significantly improved the liver function (t = 2. 640, P =0.020;t=2.529, P = 0. 025;t= - 3. 833, P = 0. 002). Both of hUCMSCs-transplanted groups showed no significant differences. Liver histological data showed that transplantation of hUSMSCs through either intraperitoneal or tail-intravenous injection alleviated liver damage (U=4. 500, P = 0. 005;U=4. 500, P = 0. 008) and the mitotic index also increased in hUCMSCs-transplanted groups (U=4. 000, P = 0. 005; U=5. 500, P = 0. 013). Conclusions The levels of ALT, TBil and Alb can rapidly normalize in ALF rats after injected with hUCMSCs either intraperitoneally or tail-intravenously. hUCMSCs application raises the mitotic index, enhances hepatocellular regeneration and improves histological status.

The study on the immune suppression with severity of HBV-related acute-on-chronic liver failure patients / 中华消化杂志

Objective To explore the association of immune suppression with the severity of HBV-related acute-on-chronic liver failure(ACLF) patients.Methods From August 2009 to April 2010 in Shanghai Public Health Clinical Center, the peripheral blood samples and clinical data of 27 HBV-related ACLF patients (ACLF group), 28 patients wit h chronic active hepatitis B (CHB group)and 8 healthy individuals (Control group) were collected.APACHE Ⅲ score and the grade of hepatic encephalopathy were as quantitative index to evaluate the severity degree of the disease.The absolute counts of the subsets of T lymphocytes and human leukocyte antigen (HLA)-DR expression on the surface of monocyte in patients' peripheral blood were examined by flow cytometry, the proinflammatory cytokines and anti-inflammatory cytokines(IFN-γ, TNF-α, IL-2, IL-4, IL-10) in patients' plasma were detected by cytometric bead array (CBA) kit.The data was analyzed with SPSS 16.0 software.Results Compared with CHB group and control group, the level of anti-inflammatory eytokire IL-10 markedly increased ir HBV-related ACLF patients (Z= -4.279 ,U= 124, P＜0.01;Z= - 3.871, U= 9.5, P= 0.0001 ), however the level of pro-inflammatory cytokines IFN-γ、 TFN-α、IL-2 、 IL-4 in plasma were at low limit of detectable value.Meanwhile the expression quantity of HLA-DR on the peripheral blood monocytes significantly down-regulated (Z= -4.714, U= 98, P＜0.01;7= - 4.086, U = 4, P＜ 0.01), and there was negative correlation between HLA-DR expression quantity and APACHE Ⅲ score (R2 =0.2667, P=0.0167).In addition, the absolute counts of CD4+T lymphocytes in adaptive immune cells significantly decreased (Z= -4.411, U= 116, P＜0.01; Z=-3.575, U= 17, P= 0.0004).Conclusions The immune system of HBV-related ACLF patients displays immune dysfunction like monocyte function inhibition; CD4+ T lymphocytes depletion and high level of anti-inflammatory eytokines, the persistent down-regulation of the HLA-DR expression on monocyte is an indicator for the severity of disease.

Study of phenotypes and functions of dendritic cells derived from the peripheral blood mononuclear cells of patients with chronic severe hepatitis B / 中华传染病杂志

Objective To understand the immune regulatory function of monocyte-derived dendritic cells (MoDC) in patients with chronic severe hepatitis B (CSHB) and its roles in the severe illness progression of chronic hepatitis B (CHB) by detecting surface phenotype of MoDC and expression level of cytokines in MoDC after polyl : C treatment. Methods The peripheral blood mononuclear cells (PBMC) were isolated by Ficoll density gradient separation from 37 patients with CSHB, 20 patients with CHB, and 20 healthy controls (NC). Purified PBMC were acquired using immunomagnetic anti-CD14-beads. Then PBMC were induced to immature dendritic cell (iDC) in vitro. PolyI : C was added to induce DC maturation. The mean fluorescence intensity (MFI) of the phenotype marker molecules including HLA-DR, CD83, CD86 and CD80 on surface of iDC and mature DC (mDC) were detected by flow cytometry. The supernatants of MoDC culture were collected at 12,24 and 48 h after polyI : C treatment, respectively and the release levels of interleukin (IL)-12, IL-6and tumor necrosis factor (TNF)-α were determined by enzyme linked immunosorbent assay (ELISA). Comparisons among groups were done by single factor analysis of variance and homogeneity of variance was tested. Results There were no significant differences of phenotype marker molecules on cell surface of iDC, including HLA-DR, CD83, CD86 and CD80 in CSHB, CHB and NC groups.However, the expressions of HLA-DR, CD83, CD86 and CD80 on cell surface of mDC in CSHB group were lower than those in CHB and NC groups (F=59.73, 13.95, 34.80 and 73.02, respectively; all P＜0. 05). The secretions of IL-12 at three time points of 12 h, 24 h and 48 h after polyI : C treatment in group NC were higher than those in CHB and CSHB groups (F= 151.34, 126.65 and 72.76, respectively; P＜0.05), and peaked at 24 h which were (48.2±7.6), (56.7±11.8) and (97.8±16.2) ng/L, respectively. The secretions of IL-6 at the above three time points were CSHB＞CHB＞NC (F=92.50, 86.89 and 64.57, respectively; all P＜0. 05) and peaked at 12 h which were (1698.3±340.4), (965.8±231.7), (697.8±213.6) ng/L, respectively. The secretions of TNF-αat the above three time points were CSHB＞CHB＞NC (F=58.66, 122.36 and 44.73, respectively;all P＜0. 05) and were (19 672. 7±4214. 7), (9946. 1 ± 2586 5), (6659. 2±955. 8) ng/L,respectively at 24 h after treatment. Conclusions MoDCs of CSHB patients show mature defection and abnormal cytokine secretion. The expression level of IL-12 which mediates cellular immune is low.Meanwhile, the productions of IL-6 and TNF-α which mediate inflammatory response are up-regulated. This may be one of the major factors which lead to exacerbation of liver inflammation and ultimately development of severe hepatitis.