Risk factors for progression of acute kidney injury in decompensated cirrhosis patients with acute kidney injury / 中华传染病杂志

Objective:To analyze the risk factors for the progression of acute kidney injury (AKI) in decompensated cirrhosis patients with acute kidney injury.Methods:The basic data and laboratory results of decompensated cirrhosis patients with AKI hospitalized in the Department of Infectious Diseases, The First Affiliated Hospital of Naval Medical University from May 2016 to November 2021 were collected. Treatment and intervention were performed according to the International Club of Ascites guidelines. According to the outcome of AKI during hospitalization, patients were divided into the progression group and the non-progression group. Two independent sample rank sum test, two independent sample or approximate t test, chi-square test and binary logistic regression analysis were used for statistical analysis. Results:A total of 263 decompensated cirrhosis AKI patients were enrolled, including 50 in the progressive group and 213 in the non-progressive group. Univariate analysis showed that there were statistically significant differences in baseline total bilirubin, alanine aminotransferase, prothrombin time, serum sodium, white blood cell count, model for end-stage liver disease score, proportion of patients with infection, proportion of patients with upper gastrointestinal hemorrhage, and proportion of patients with primary AKI stage between the two groups ( Z=-6.49, -3.53, t=-3.06, 3.40, -3.55, -8.19 and χ2=14.64, 8.40, 103.98, respectively, all P<0.050). Binary logistic regression analysis showed that primary AKI stage (stage two odds ratio ( OR)=33.176, 95% confidence interval ( CI) 11.294 to 97.458, P<0.001; stage three OR=114.139, 95% CI 25.321 to 514.515, P<0.001), upper gastrointestinal hemorrhage ( OR=3.850, 95% CI 1.238 to 11.971, P=0.020) and total bilirubin ( OR=1.009, 95% CI 1.005 to 1.012, P<0.001) were the risk factors for the progression of AKI in patients with decompensated cirrhosis. Conclusions:Decompensated cirrhosis patients with AKI stage two or three, high baseline total bilirubin value or gastrointestinal hemorrhage have a high risk of AKI progression. It is necessary to strengthen the assessment and take targeted intervention measures at early stage in the clinical practice.

Influence of hepatitis B virus infection on assisted reproductive technology and related prevention measures / 临床肝胆病杂志

Hepatitis B virus (HBV) infection is prevalent in China. With the rapid development of assisted reproductive technology (ART) in recent years, more and more couples with infertility and HBV infection choose ART to promote pregnancy. No conclusion has been reached on the influence of HBV infection on ART procedure and the health status of offspring. This article reviews the influence of HBV infection on ART from the aspects of sperm and oocyte function, laboratory environment, pregnancy outcome, and health of offspring and discusses the prevention measures during ART for people with HBV infection, in order to provide a reference for developing scientific management systems and preventing disease transmission.

Association between hepatitis B virus infection and the incidence risk of chronic pancreatitis / 中华胰腺病杂志

Objective To investigate the correlation of previous hepatitis B virus (HBV) infection with the incidence risk of chronic pancreatitis (CP).Methods This was a case control study.Five hundred and seventy-one patients with CP admitted in the Department of Gastroenterology, Changhai Hospital, Second Military Medical University between January 2015 and October 2016 were enrolled, and 1216 sex and age matched health individuals were also enrolled as the control group.The 5 serum HBV markers(HBsAg,HBsAb, HBeAg, HBeAb and HBcAb) were detected and their correlation with CP incidence was analyzed.Results The positive rate of HBsAg in the CP group and the control group were 3.0% and 3.8%, respectively, and the difference was statistical significant.(OR=0.039, 95% CI 0.02~0.80, P0.05).The positive rate of HBeAb in the CP group and the control group were 24.3% and 10.8%, respectively, and the difference was statistical significant(P<0.00).The positive rate of HBcAb in the CP group and the control group were 50.1% and 16.5%, respectively,and the difference was statistical significant(P<0.000).In the(HBsAb+, HBeAb+, HBcAb+), (HBsAb+, HBcAb+), (HBeAb+, HBcAb+), (HBcAb+) models, the positive rate in CP group was significantly higher than that of the control group(P<0.000).Multivariate regression analysis showed that the positivity of HBsAb and HBeAb were the protection factors for the occurrence of CP(P<0.05),and HBcAb positivity was the independent risk factor for CP (OR=6.931,P<0.000).Conclusions HBsAb and HBeAb poitivity were the protectors for CP, while HBcAb positivity could be considered as an independent risk factor for CP.

Expression and role of interleukin 35-producing B cells and interleukin 35 from peripheral blood of patients with chronic hepatitis B / 中华传染病杂志

Objective To explore the level of interleukin 35-producing B cells (i35-Breg) as well as its effect factors,interleukin-35 (IL-35),in peripheral blood of patients with chronic hepatitis B (CHB),and their relationship with hepatitis B virus (HBV) DNA and liver inflammatory degree.Methods A total of 35 treatment-naive CHB patients,17 interferon (IFN)-treated HBeAg-positive CHB patients and 15 healthy controls (HC) were enrolled.The levels of i35-Breg and IL-35 in peripheral blood were tested by flow cytometry and enzyme-linked immunosorption assay (ELISA).Kruskal-Wallis test,Wilcox rank sum test and two variables correlation analysis were used for statistical analysis.Results The percentage of i35-Breg cells as well as IL-35 level in peripheral blood of naive CHB patients were 3.05％ (0.89％,4.97％) and 2.81 μg/L (0.30 μg/L,12.33 μg/L),respectively,which were both significantly higher than those in HC group,which were 0.17％ (0.13％,0.45％) and 0.17 μg/L(0,1.93 μg/L),respectively.The difference were statistical significant (Z=-3.309 and-2.419,respectively,P=0.001 and 0.016,respectively).The peripheral level of i35-Breg was negatively correlated with the viral load in treatment-naive CHB patients (r=-0.529,P=0.008),while there was no correlation between the peripheral level of IL-35 and the viral load in treatment-naive CHB patients (r=0.11,P=0.54).The levels of i35-Breg and IL-35 in HBeAg positive CHB patients were 3.16％ (1.34％,5.62％) and 4.58μg/L (0.79μg/L,22.37 μg/L),respectively,which were both higher than those in HC group.The difference was statistically significant (F=3.39 and 3.37,respectively,both P＜0.01).Compared to HC group,the IL-35 levels in peripheral blood of CHB patients with ALT and AST levels less than 300 U/L were 3.03 μg/L (0.74 μg/L,22.37 μg/L) and 3.25 μg/L (0.83 μg/L,22.35 μg/L),respectively,with statistically significant difference (F=2.868 and 3.114,respectively,both P＜0.01).Compared to HC group,the peripheral level of i35-Breg in treatment-naive CHB patients with ALT levels less than 300 U/L was 3.14％ (1.03％,4.65％),with statistically significant difference (F=3.219,P=0.004).The IL-35 level showed a decreased trend in CHB who received IFN therapy,but there was no statistically significant difference (x2 =1.45,P =0.48).Furthermore,the baseline IL-35 level in patients who developed sustained viral response (SVR) was 0 (0,13.33 g/L),which was lower than that in patients who developed partial or primary no response 0.61 μg/L (0,24.72 μg/L).However,there was no statistical difference (F=0.75,P =0.68).Conclusions i35-Breg as well as its effect factor,IL-35,are involved in the progression of chronic HBV infection.The percentage of i35-Breg cells as well as IL-35 level in peripheral blood of treatment-naive CHB patients are increased.The peripheral level of i35-Breg is negatively correlated with the viral load,while there is no correlation between the peripheral level of IL-35 and the viral load.The percentage of i35-Breg cells as well as IL-35 level in CHB patients with low inflammatory degree are increased.

Cholestasis morbidity rate in first-hospitalized patients with chronic liver disease in Shanghai / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the epidemiological status of cholestasis in first-hospitalized patients with chronic liver disease in Shanghai, and to provide a scientific basis for developing prevention and treatment measures.</p><p><b>METHODS</b>From April 2005 to September 2014, 5,146 first-hospitalized patients in Shanghai with a diagnosis of chronic liver disease were enrolled in this study. Clinical data of the 4,660 patients who fit the study criteria for participation were collected for retrospective analysis.Diagnosis of cholestasis was made according to serum alkaline phosphatase (ALP) levels higher than 1.5 times the upper limit normal (ULN) and gamma-glutamyltransferase (GGT) levels higher than 3 times the ULN. The incidence rate of cholestasis was assessed for relation to age, sex, etiology, and type of liver disease, and statistically compared to the general clinical data and specific biochemical indicators with potential sex-related differences. T-test and chi-square test were performed for the statistical analyses.</p><p><b>RESULTS</b>Of the 4,660 study participants, 10.26% had cholestasis; the prevalence of cholestasis increased with increasing age in male patients. The distribution of the cholestasis incidence according to the type of chronic liver disease was: 75.00%, primary sclerosing cholangitis; 42.86%, primary biliary cirrhosis; 35.97%, hepatic tumor; 30.77%, autoimmune hepatitis; 28.31%, drug-induced liver disease; 16.46%, alcoholic hepatitis; 13.98%, cryptogenic cirrhosis; 12.99%, schistosomal cirrhosis; 7.53%, alcoholic cirrhosis; 7.32%, mixed cirrhosis; 5.94%, viral liver cirrhosis; 2.70%, nonalcoholic fatty liver disease. There was no significant difference in the prevalence of cholestasis between the two sexes. In the patients with cholestasis, the levels of GGT and total bilirubin were significantly different between the two sexes.</p><p><b>CONCLUSION</b>The incidence rate of cholestasis in first-hospitalized patients with chronic liver disease was 10.26%, and the rate increased with increased age. Patients with primary sclerosing cholangitis or primary biliary cirrhosis had higher incidence rates of cholestasis. Incidence rates of cholestasis of the various chronic liver diseases were not related to sex.</p>

Optimized strategy peginterferon-α-2a therapy for hepatits B e antigen positive chronic hepatitis B patients with suboptimal response at 24 weeks / 中华传染病杂志

Objective To investigate the efficacy and safety of different optimal therapy strategies for hepatits B e antigen (HBeAg) positive chronic hepatitis B (CHB) patients with suboptimal response to peginterferon-α-2a (peg-IFN-α-2a) at 24 weeks.Methods This open-label,single-center and prospective clinical observational study was conducted in Department of Infectious Diseases at Shanghai Changhai Hospital between January 2009 and December 2011.The cases of HBeAg-positive CHB with suboptimal response to peg-IFN-α-2a at week 24 were enrolled.Based on virological markers and patient preference,patients were treated with either peg-IFN-α-2a add-on adefovir dipivoxil (ADV) or switch-to telbivudine (LdT).Hepatitis B virus (HBV) virological and serological data were collected at week 12,24 and 48 after the initiation of optimal therapy.Adverse reactions were also monitored.Therapeutic efficacy was compared between two groups of patients before and after treatment by x2 test.Kruskall Wallis test and Mann-Whitney test were used for analysis of continuous variables.Results Among 193 HBeAg positive CHB patients treated with interferon,67 had suboptimal response and were enrolled.Forty five cases received peg IFN-α-2a add-on ADV treatment and 22 cases received switch-to LdT treatment.After 48 weeks of optimized therapy,the total tBeAg seroconversion rate was 25.3 ％.The rates of HBeAg loss,HBV DNA negative and alanine aminotransferase normalization were 26.8％,73.1％ and 83.5％,respectively.The peg-IFN-α-2a switch-to LdT strategy had better HBV DNA inhibition efficiency compared with the peg-IFN-α-2a add-on ADV strategy at week 12,24 and 48 (P=0.00,0.00 and 0.01,respectively).However,there was no significant difference of HBV DNA negative rate between two groups at week 48 (x2 =0.01,P=0.89).The obviously intolerable adverse reaction was not reported in two optimized strategy groups.Conclusions The 48-week optimized treatment for HBeAg positive CHB with suboptimal response to peg-IFN-α-2a at week 24 could achieve a higher HBeAg seroconversion rate.The switch-to LdT strategy may have better HBV DNA inhibition efficiency.Both strategies show satisfactory safety and tolerance.

Effects of T helper type 17 cells and T regulatory cells imbalance in patients with chronic hepatitis B virus infection / 中华传染病杂志

ObjectiveTo investigate the effects of the imbalance between regulatory T cells (Treg) and T helper 17 cells (Th17) in patients with chronic hepatitis B virus (HBV) infection.MethodsThe serum concentration of Treg/Th17 differentiation-related cytokines in 34 patients with chronic hepatitis B (CHB),20 patients with HBV related acute on chronic liver failure (ACHBLF),and 20 healthy controls (NC) were measured by enzyme-linked immunosorbent assay (ELISA) and proportion of peripheral Th17 and Treg cells were analyzed by flow cytometry.Numeration data was analyzed by Fisher's exact propability method and measurement data was tested by one-factor analysis of variance or Turkey multiple comparison.Results The levels of Th17 differentiation-related cytokines,II-1β (3.97±2.85) pg/mL,IL-6 (12.75±-8.87) pg/mL,and IL-21 (360.0±335.7) pg/ mL in patients with ACHBLF were significantly increased than those in NC,which were (1.87 ±0.94) pg/mL(q=4.559,P＜0.01),(5.28±0.72) pg/mL(q=7.309,P＜0.01) and (46.68±20.17) pg/mL(q=6.946,P＜0.01 ),respectively.The proportion of Th17 increased markedly in patients with ACHBLF than that in NC(q=3.972,P＜0.05).However,compared to NC and patients with ACHBLF,the Treg differentiation-related cytokine,TGF-β,in patients with CHB,increased significantly (q=4.536 and 5.323,respectively; both P＜0.01).And the population of Treg also increased markedly in CHB patients.The level of IL-17A which was the characteristic effector cytokine of Th17 was the highest in patients with ACHBLF.The peripheral Th17 cell proportion was positively correlated with the level of serum total bilirubin in patients with ACHBLF (γ=0.74,P＜0.01).Conclusions Th17 and Treg imbalance including cytokine profiles and cell numbers exists in patients with chronic HBV infection.The Th17 are active in patients with ACHBLF and Treg are active in patients with CHB.

High viral load is the risk factor of delayed recovery in patients with acute hepatitis B infection / 中华传染病杂志

Objective To identify the relationship between viral factors and disease progression in patients with acute hepatitis B virus (HBV) infection. Methods Ninety-seven adult patients with acute HBV infection in Shanghai Changhai Hospital were enrolled in this study and followed up for 24 weeks. Epidemiological, biochemical and virological parameters of all patients were collected. HBV S region from sera of 54 patients with acute HBV infection were genotyped using direct nucleotide sequencing. Differences of means between groups were compared by t-test, and frequency between groups was compared by X test. Results The clinical manifestations of all patients were mild and the 83 patients spontaneously developed HBeAg and HBsAg seroconversion. However, 14 patients had a tendency of chronicity, with HBV DNA level higher than patients without chronicity tendency [(6. 17 ±1. 04) 1g copy/mL vs (3. 86±1. 85)1g copy/mL;t = 5. 95, P<0. 01]. Among the 14 patients, 6 obtained HBsAg seroconversion after antiviral therapy and the other 8 developed to be sustained HBV carrier who had not received antiviral therapy. The main genotypes of acute HBV infection were genotypes B and C. There were no statistically significant differences of epidemiological factors and biochemical results between patients with the two genotypes of HBV infection. High viral load at baseline was the risk factor of chronicity tendency. Conclusions The main genotypes of acute HBVinfection in Changhai Hospital in the year from 2003 to 2007 are genotypes B and C. There is no significant relationship between genotype and clinical outcome. While high viral load at baseline is significantly associated with chronicity tendency. Proper antiviral therapy can decrease sustained HBV infection rate.

Comparison of genotype distribution of patients with acute hepatitis B infection or chronic hepatitis B infection in Shanghai / 中华传染病杂志

Objective To investigate the distribution of genotypes in chronic HBV infection (CHB) and acute HBV infection (AHB) patients in Shanghai. Methods Sixty-two patients with AHB and 73 patients with CHB admitted to ('hanghai Hospital of Shanghai between 2003 and 2007 were studied. Viral genotypes of all the patients were determined by direct gene sequencing.Meanwhile, epidemiological, clinical and biochemical parameters of all patients were collected. Mean values of different groups were compared by t test while frequency was compared by chi square test. Results The major prevalent genotypes in both AHB and CHB patients were genotype B and C (48.4% vs 51.6% in AHB patients and 26.0% vs 74.0% in CHB patients). The proportion of genotype B was higher in AHB patients compared to CHB patients (P= 0.02). Epidemiological factors and clinical outcomes were not statistically different among patients with different viral genotypes. The proportion of genotype C was much higher in CHB patients compared to AHB patients (P=0.006). The main transmission route of AHB was heterosexual interaction which was 18 out of 62 (29.0%), but in CHB patients, it was prenatal transmission which was 38 out of 73 (52.1%). Conclusions In shanghai, the main HBV genotypes in both AHB and CHB patients are genotype B and C. The proportion of genotype B is relatively high in AHB patients while proportion of genotype C is more common in CHB patients. There is no significant relationship between genotypes and the clinical outcomes of AI-IB patients.

Levofloxacin distribution in serum and ascites in patients with cirrhosis and evaluation of its efficacy in treatment of spontaneous bacterial peritonitis / 第二军医大学学报

Objective: To study the distribution of levofloxacin in the serum and ascites in patients with cirrhosis and to evaluate its efficacy in treatment of patients with spontaneous bacterial peritonitis(SBP). Methods:（1）Concentration of levofloxacin in the serum and ascites was detected with HPLC in 7 patients with cirrhosis at different time (in the serum: 0.5, 1, 1.5, 2 and 12 h;in the ascites:2, 4, 6 and 12 h). （2）The effects of levofloxacin were observed in treatment of 30 patients with SBP. Results:（1） Levofloxacin was determined in serum and ascites of patients with cirrhosis, whose concentration depended on the duration after oral administration. In serum: tmax was 1.5 h and cmax was (3.913±1.388) μg/ml. In ascites: tmax was 6.0 h and cmax was (2.520±1.213) μg/ml. The levels decreased gradually after reaching peak concentration, then stabilized from 12 h.（2）The symptoms and signs were significantly improved in patients with SBP treated with the levofloxacin. Conclusion: After the oral administration, levofloxacin can both distribute in serum and ascites, and it is efficient in the treatment of the patients with SBP.