Discontinuation of nucleoside/nucleoside analogues therapy in compensated patients with hepatitis B cirrhosis after HBsAg negative conversion / 中华临床感染病杂志

Objective:To evaluate the safety of discontinuing nucleoside/nucleoside analogue (NAs) therapy in patients with compensated hepatitis B cirrhosis after HBsAg negative conversion.Methods:A total of 3 783 patients with hepatitis B cirrhosis in compensated stage were treated with NAs at Taizhou Hospital, Taizhou Municipal Hospital and Taizhou Enze Hospital from January 2008 to December 2020. The clinical data and laboratory tests results of 85 patients with HBsAg negative conversion were retrospectively analyzed, including 36 cases discontinued the drug, and 49 continued to use drug. Chi-square test and rank-sum test were used for data analysis.Results:During the 24 and 48 months of follow-up, the ALT levels were within the normal range in both groups. There were no significant differences in positive rates of anti-HBs and HBeAg ( χ2=0.75, 0.39 and 0.90, P=0.78 0.84 and 0.34; χ2=0.40, 0.00 and 0.00, P=0.84, 1.00 and 1.00) between two groups. After 48 months of follow-up, 2 cases of primary liver cancer occurred in the discontinuation group and no primary liver cancer occurred in the continuation group ( χ2=0.89, P=0.34). Throughout the follow-up, HBsAg remained negative and HBV DNA load was below the lower limit of detection in both groups. Conclusions:Discontinuation of NAs can be considered after the HBsAg negative conversion in patients with compensated hepatitis B cirrhosis.

Dynamic inflammatory response in a critically ill COVID-19 patient treated with corticosteroids / 浙江大学学报·医学版

OBJECTIVE@#To investigate the effect of corticosteroids therapy on the inflammatory response in a critically ill coronavirus disease 2019 (COVID-19) patient.@*METHODS@#A 55-year old female patient with critical ill COVID-19 was admitted in Taizhou Hospital on January 19, 2020. The patient was treated with methylprednisolone 80 mg on the 2nd day after admission. Thereafter, the dose was adjusted in a timely manner and the therapy lasted for 13 days. The peripheral lymphocyte subsets (CD3T, CD4 T, CD8 T, NK cells, B cells), as well as serum levels of lymphocyte factors (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) were dynamically monitored.@*RESULTS@#On D1 of admission, the numbers of peripheral blood CD3 T, CD4 T, CD8 T, and NK cells were significantly lower than the normal range. With the improvement of the disease, the numbers of CD3 T, CD8 T and CD4 T cells gradually recovered and showed a linear growth trend (linear fitting equation: =18.59+109.4, <0.05). On D2 of admission, the patient's IL-6 and IL-10 levels were significantly higher than normal values, IFN-γ was at a normal high value, and then rapidly decreased; IL-2, IL-4, and TNF-α were all in the normal range. On the D6 and D7, the IL-6 and IL-10 decreased to the normal range for the first time. On the D18, the sputum virus nucleic acid test was negative for the first time, and the fecal virus nucleic acid test was still positive; on the D20 the sputum and fecal virus nucleic acid test were both negative. On D34, the patient recovered and was discharged. At the discharge the muscle strength score of the patient was 44 and the daily life ability evaluation was 90.@*CONCLUSIONS@#In the absence of effective antiviral drugs, early use of appropriate doses of corticosteroids in critically ill patient with COVID-19 can quickly alleviate inflammatory response and improve clinical symptoms, however, it may reduce the number of T cells, and to adjust the dose in time is necessary.

Diagnostic value of serum soluble mannose receptor for hepatic fibrosis in patients with chronic hepatitis B / 中华临床感染病杂志

Objective To assess the diagnostic value of serum soluble mannose receptor (sMR) for hepatic fibrosis in patients with chronic hepatitis B (CHB).Methods Fifty patients with CHB undergoing liver biopsy in the Department of Infectious Diseases , Taizhou Hospital of Zhejiang Province from November 2016 to October 2018 were enrolled, including 28 males and 22 females.According to the stage of liver fibrosis, there were 15 cases without fibrosis (S0 group), 12 cases of mild fibrosis (S1-2 group), and 15 cases of moderate-severe fibrosis ( S3-4 group).Twenty healthy subjects (12 males and 8 females) were recruited as controls.Enzyme linked immunosorbent assay (ELISA) was used to detect the serum hyaluronic acid (HA), laminin (LN), procollagen type ⅢN-terminal peptide (PⅢP), collagen type IV (CIV) and sMR in all groups.One-way ANOVA, Spearman correlation analysis and receiver operating characteristic (ROC) curve were used to analyze the data.Results The serum levels of sMR, HA, LN, CIV and PⅢP in S3-4 group were significantly higher than those in S 0 group ( t＝10.20, 4.69, 8.94, 2.35 and 4.34, respectively; all P＜0.05) and S1-2 group (t＝5.77, 4.23, 7.88, 2.71 and 3.43, respectively; all P＜0.05); and serum sMR level in S1-2 group was higher than that in S0 group ( t ＝6.23, P ＜0.05). Spearman rank correlation demonstrated that serum sMR level was positively correlated with the degree of liver fibrosis (r＝0.860, P＜0.01).ROC curve analysis showed that when 228.69 ng／mL was taken as cut-off value of sMR, its specificity and sensitivity for diagnosis of hepatic fibrosis were 93.3%and 88.6%, respectively.The diagnostic efficacy of sMR was significantly better than that of HA , LN, CIV and PⅢP (Z＝3.179, 3.467, 5.241 and 3.567, respectively; all P＜0.05).When 345.80 ng／mL was taken as cut-off value of sMR, the specificity and sensitivity for diagnosis of moderate to severe hepatic fibrosis were 85.7%and 86.7%, respectively; and its diagnostic efficacy was better than that of HA , CIV and PⅢP (Z＝2.253, 2.475 and 2.092, all P ＜0.05).Conclusion Serum sMR level is associated with the progression of liver fibrosis, it may be used as a new serological marker for non-invasive assessment of liver fibrosis.

Curative effect of entecavir combined with glucocorticoid in the treatment of early stage hepatitis B liver failure / 中国医师进修杂志

Objective To observe the curative effect of entecavir combined with glucocorticoid in early stage hepatitis B liver failure. Methods The clinical data of 100 patients with early stage hepatitis B liver failure from February 2012 to February 2017 were retrospectively analyzed. Among them, 50 patients were treated with entecavir combined with glucocorticoid (treatment group), and 50 patients were treated with entecavir (control group). The alanine aminotransferase (ALT), total bilirubin (TBil), total cholesterol (TC), prothrombin activity (PTA), hepatitis B virus (HBV)-DNA, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 levels were compared between 2 groups. Results The ALT, TBil, TC and PTA levels 1, 2, 4 and 8 weeks after treatment in treatment group were significantly lower than those in control group, and there were statistical differences (P<0.05); there was no statistical difference in HBV-DNA between 2 groups (P>0.05). The TNF-α, IL-6 and IL-10 levels 4 weeks after treatment in treatment group were significantly lower than those in control group: (2.5 ± 0.5) μg/L vs. (3.2 ± 0.7) μg/L, (16.8 ± 2.2) μg/L vs. (22.1 ± 2.4) μg/L and (7.3 ± 1.2) μg/L vs. (9.1 ± 1.8) μg/L, and there were statistical differences (P<0.05). Eight weeks after treatment, the effective rate and survival rate in treatment group were significantly higher than those in control group: 80％ (40/50) vs. 54％ (27/50) and 94％ (47/50) vs. 78％ (39/50), and there were statistical differences (P<0.01 or <0.05).In the treatment group, there was no serious adverse reaction during glucocorticoid therapy,and the patients recovered after withdrawal or reduction of glucocorticoid. Conclusions Entecavir combined with glucocorticoid has a significant effect on patients with early stage hepatitis B liver failure. It could improve survival rate, and the adverse effects of glucocorticoid are less.

Analysis of clinical characteristics and death risk factors in patients infected with severe fever with thrombocytopenia syndrome bunyavirus / 中国医师进修杂志

Objective The study the clinical characteristics and death risk factors in patients infected with severe fever with thrombocytopenia syndrome bunyavirus (SFTSV). Methods The clinical data of 56 patients infected with SFTSV from May 2011 to October 2016 were retrospectively analyzed. The clinical characteristics and laboratory examination results were compared between cured patients and death patients. The death risk factors were analyzed by two classification Logistic regression analysis. Results Among the 56 cases, 40 cases were cured and 16 cases were dead, and the time of onset to death was (12 ± 3) d. All patients showed symptoms including fever and weakness. Bone marrow biopsy was performed in 26 cases, and hemophagocytic phenomenon was found in 21 cases. Compared with cured patients, the death patients were older; the rate of underlying diseases was higher; fever time was longer; the incidences of skin and/ or gastrointestinal bleeding, neuropsychiatric symptoms, abnormal troponin and arrhythmias were higher, platelet, CD4+and CD8+were lower; the levels of activated partial thromboplastin time (APTT), creatine kinase (CK), lactate dehydrogenase (LDH), viral load, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were higher, and there were statistical differences (P＜0.01 or ＜0.05). Two classification Logistic regression analysis result showed that viral load ≥ 5 lgTCID50/ml, age ≥ 70 years, platelet ＜ 20 × 109/L, CK ＞ 1 200 U/L, fever time ＞ 8 d, APTT ≥ 120 s, troponin elevation and neuropsychiatric symptoms were the independent risk factors of death in patients infected with SFTSV (P＜0.01 or＜0.05). Conclusions The high viral load, high age, lower platelet, increased CK, prolonged fever time and APTT, elevated troponin and neuropsychiatric symptoms were independent risk factors of death in patients infected with SFTSV. Early identification for the risk factors of death may improve the prognosis.

Analysis on the effect and safety of compound Biejiaruangan tablets combined with entecavir on the treatment of viral hepatitis B cirrhosis / 中国生化药物杂志

Objective To study the effect and safety of compound Biejiaruangan tablets combined with entecavir on the treatment of viral hepatitis B cirrhosis.Methods100 cases with hepatitis B cirrhosis in Zhejiang Taizhou hospital from June 2014 to December 2016 were selected as the research object in this study which were randomly divided into the control group and the experimental group 50 cases in each group.The control group were given entecavir, the experimental group were given compound Biejiaruangan tablets combined with entecavir.The clinical effect and the adverse reaction in the two groups were compared.ResultsThe effective rate was 90.0% in the experimental group, which was significantly higher than 72.0% in the control group(P<0.05).There were 2 patients vomiting in the experimental group, the adverse reaction rate was 4.0%.There were 9 cases of vomiting and headache in the control group, the adverse reaction rate was 18.0%.T,he adverse reaction rate(in the experimental group was significantly lower than that in the control group(P<0.05).ConclusionThe clinical effect of compound Biejiaruangan tablets combined with entecavir on the treatment of viral hepatitis B cirrhosis is better, which can reduce the rate of adverse reactions in a certain extent, is high safety, and worth popularizing.

Laboratory investigation of reactive plasmacytosis in patients with severe fever with throbocytopenia syndrome / 中华传染病杂志

Objective To investigate the immunological characteristics and clinical significance of reactive plasmacytosis in patients with severe fever with throbocytopenia syndrome (SFTS).Methods Bunyavirus-infected patients who were diagnosed with SFTS were collected from March 2015 to October 2015 in Taizhou Hospital.Morphology analysis of bone marrow and peripheral blood (PB) smear, as well as flow cytometry analysis of plasma cell immune phenotype from peripheral blood were conducted.Serum immunoglobulin levels and helper T hymphocytes (Th)1/Th2 cytokine expressions were detected.Mann-Whitney U test was used.Results PB plasma cells from all of the SFTS patients increased in varying degrees, and the phenotype of the plasma cells was CD19+CD38++CD45+CD138+, which indicated normal mature plasma cells.The ratio of PB plasma cells was >0.030 in 10/16 patients, and >0.300 in 2/16 patients.The ratios of PB plasma cells in the patients with severe and critical groups were significantly higher than that in the mild group (0.052 vs 0.016, P0.05).The serum IgG, IgA and IgM levels did not increase in acute stage, with the median of 11.6 g/L, 2.56 g/L and 1.60 g/L (reference value 0.46 to 3.04 g/L), respectively.Conclusion The patients with SFTS show excessive humoral and cellular immunity, and the severity of disease is positively correlated with the ratio of peripheral plasma cells and the levels of cytokines IL-6 and IL-10.

Clinical and histologic improvements in patients with hepatitis B virus-related compensated cirrhosis ;after long-term antiviral treatment / 中华临床感染病杂志

Objective To investigate the effect of long-term antiviral treatment on clinical outcome and liver histology in patients with hepatitis B virus ( HBV)-related compensated cirrhosis .Methods A total of 61 patients with HBV-related compensated cirrhosis receiving antiviral therapy were enrolled from Taizhou Hospital of Zhejiang Province during September 2010 and March 2015, including 26 HBeAg-positive cases and 35 HBeAg-negative cases .Thirty-nine patients were treated with entecavir ( ETV ) and 22 were treated with adefovir dipivoxil ( ADV ) .Biochemical , serological and virological markers were examined every 3 months during treatment, and Child-Turcotte-Pugh (CTP) scores were calculated.All the patients underwent liver biopsy before and 144 weeks after antiviral treatment .Metavir scoring system was used to evaluate the liver histological activity ( A) and fibrosis score ( F) .Wilcoxon rank sum test and paired t-test were used for the evaluation of liver histopathology and liver function before and after treatment , respectively.Results After 144 weeks of antiviral treatment , HBV DNA was reduced and below the lower limit of detection in 58 patients (95.1%), HBeAg disappeared in 14 patients (14/26, 53.8%), and HBeAg seroconversion was observed in 10 patients (10/26, 38.5%); alanine aminotransferase ( ALT), aspartate amino transaminase (AST), total bilirubin (TBil) and CTP score decreased (t=7.489, 8.259, 14.000 and 6.026, all P<0.01), prothrombin time (PT) was shortened (t=9.777, P<0.01), and serum albumin (Alb) increased (t=3.446, P<0.01).Improvements in both liver histologic activity and fibrosis score were observed (Z=5.716 and 6.657, all P<0.01).Liver histological activity decreased from A1 to A0 in 16 cases, from A2 to A0 in 9 cases, from A2 to A1 in 15 cases, from A3 to A0 in 1 case, from A3 to A1 in 5 cases, and from A3 to A2 in 5 cases.Fibrosis score at the baseline was F 4 for all patients, while after treatment, there were 7 patients with F1, 22 with F2, 20 with F3, and F4 remained in rest 12 patients.Conclusion Both clinical and histological improvements can be obtained after long-term antiviral treatment for patients with HBV-related compensated cirrhosis .

Clinical features of sporadic cases with H7N9 avian influenza in Taizhou city of Zhejiang province and characteristics of viral gene / 中华临床感染病杂志

Objective To examine the clinical features of sporadic patients with H7N9 avian influenzain Taizhou city of Zhejiang province and to characterize its viral genes.Methods Fifteen patients with H7N9 influenza infection confirmed by Zhejiang Provincial Centre for Disease Control and Prevention during January 201 4 and January 201 5 were included in the study.The basic diseases,poultry exposure history,clinical manifestation,laboratory examination,imaging features,treatment and outcome and viral gene sequencing were analyzed retrospectively.Results The first clinical symptoms were fever and cough in all patients,acuterespiratory distress syndrome(ARDS)occurred in 1 3 patients,the average time from onset to antiviral therapy was (7 ±2)d.Among 1 5 patients,9 survived and 6 died,including 2 died of multiple organ failure (MOF).The phylogenetic tree showed that there was highly homologous in hemagglutinin (HA)and neuraminidase(NA)genes between human H7N9 virus strains and poultry reference strains.The result of genetic sequencing indicated that human H7N9 virus strains had mutations at 226 (Q226L)sites in HA protein.Conclusions ARDS is likely to occur in patients with H7N9 viral infection,and early antiviral treatment usually leads to a good prognosis.With the occurrence of adaptive mutation in avian influenza virus H7N9,spread from poultry to the human beings may take place.

Clinical analysis of methylprednisolone combined with entecavir in treatment of hepatitis B virus related early stage liver failure / 中国医师进修杂志

Objective To observe the curative effect of methylprednisolone combined with entecavir in treatment of hepatitis B virus (HBV) related early stage liver failure.Methods One hundred and twenty-six patients with HBV related early stage liver failure were divided into treatment group (68 cases) and control group (58 cases) by random digits table method.The patients in 2 groups were given conventional hepatinica treatment and entecavir antiviral treatment,but the patients in treatment group were added methylprednisolone and pantoprazole.The alanine aminotransferase (ALT),total bilirubin (TBil),albumin,prothrombin time (PT),HBV-DNA,tumor necrosis factor (TNF)-α,interleukin (IL)-6 levels were compared between 2 groups,and the adverse reaction of methylprednisolone was observed.Results The ALT,TBil,PT and albumin levels after the first,second,fourth,sixth and eighth week of treatment in treatment group were significantly better than those in control group,and there were statistical differences (P ＜ 0.05).There was no statistical difference in HBV-DNA between 2 groups (P ＞ 0.05).The TNF-α and IL-6 levels after the first and second week of treatment in treatment group were (4.13 ± 1.25) and (1.98 ± 0.67) p g/L,(3.21 ± 0.75)and (1.23 ± 0.29) μ g/L,and in control groups were (5.89 ± 1.78) and (3.67 ± 0.87)μ g/L,(4.12 ± 0.88) and (2.68 ± 0.81) μ g/L.The TNF-α and IL-6 levels in treatment group were significantly lower than those in control group,and there were statistical differences (P ＜ 0.05).The effective rate in treatment group (79.41％,54168) was significantly higher than that in control group (51.72％,30/58),the fatality rate in treatment group (2.94％,2/68) was significantly lower than that in control group (24.14％,14/58),and there were statistical differences (P ＜ 0.05).The adverse reaction of methylprednisolone in treatment group was not found.Conclusion The methylprednisolone combined with entecavir can improve liver function and survival rate in patients with HBV related early stage liver failure,and adverse reaction of methylprednisolone is rare.

The bone marrow morphology characteristics and the clinical significance of six patients with severe fever with thrombocytopenia syndrome / 中华传染病杂志

Objective To investigate the bone marrow morphology characteristics in patients with severe fever with thrombocytopenia syndrome (SFTS)and to evaluate the clinical value of bone marrow morphology examination in the diagnosis of SFTS.Methods The bone marrow morphology and clinical data of six newly diagnosed SFTS patients with positive test of novel bunyavirus infection admitted to Taizhou Hospital from July 2011 to November 2014 were retrospectively analyzed.Results The increased ratio of lymphoid and monocytoid histiocytes (0.02 - 0.23 )and hemophagocytic phenomenon were observed in all of the six patients′ bone marrow smears.Two of the six cases were diagnosed with hemophagocytic lymphohistiocytosis (HLH)according to the clinical diagnosis criteria and the remaining four cases were defined as highly suspected HLH.Conclusions The progression of SFTS disease might be closely related with HLH induced by novel bunyavirus infection.Morphology examination of bone marrow smear is beneficial for the early differential diagnosis of SFTS.

Expression of recombinant protein VP1and its application in developing enzyme-linked immunoassay for Echovirus 30 / 中华临床感染病杂志

Objective To express VP1recombinant protein of Echovirus 30 (ECHO30) in E.coli BL21(DE3) and to develop an enzyme-linked immunoassay (EIA) based on the recombinant antigen for detecting antibodies to ECHO30.Methods The target VP1gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR).The PCR products of the gene were inserted into pET44a vector,and then expressed in E.coli BL21( DE3 ).The purified recombinant protein was used for the development of EIA.Results The molecular weight of the recombinant protein was 95 000,and the antigenicity of which was identified by Western blot and EIA.Conclusion The recombinant protein VP1has been successfully expressed and purified,which can be used as diagnostic antigen.

Diagnosis and treatment of hepatic veno-occlusive disease induced by sedum aizoon in HBsAg positive patients / 中华临床感染病杂志

Objective To review the diagnosis and treatment of hepatic veno-occlusive disease(HVOD)induced by sedum aizoon in HBsAg positive patients. Methods Clinical data of 35 HBsAg positive cases who took sedum aizoon decoction and developed HVOD were collected, the clinical manifestation, imaging examination, histological examination of liver puncture biopsy, and the outcomes of patients were reviewed. Results Hepatomegaly, liver dysfunction, abdominal effusion and map-like density changes in liver CT scan were observed in 35 patients. Liver biopsy wag performed in 17 patients. In histopathological examination, the swelling and point-like necrosis of liver cells, expansion and congestion of sinus, endothelial swelling, wall thickening, incomplete lumen occlusion of small liver vascular were observed. Map-like density changes in liver CT scan were found in all 17 patients who were diagnosed by histological examination. Fifteen patients presented small amount of ascites within 4 weeks of onset, 13 of whom recovered or improved after treated with low-molecular weight heparin and albumin; while among the remaining 20 patients. only half of them were benefited from the same treatments. Conclusion HVOD can be diagnosed by liver CT scan instead of histological examination; treatment of patients in early stage may improve the outcome.

Expression of Toll-like receptors in peripheral blood mononuclear cells and serum inflammatory cytokine in patients with liver failure / 中华临床感染病杂志

Objective To investigate the expression of Toll-like receptor 2 and 4 (TLR2 and TLR4) in peripheral blood mononuclear cells (PBMCs) and the serum inflammatory cytokine levels in patients with liver failure. Methods The expressions of TLR2 mRNA and TLR4 mRNA in PBMCs were detected by RT-PCR in 20 healthy controls, 20 chronic hepatitis B (CHB) patients, 18 liver failure patients in early stage and 14 in intermediate-end stage. The serum contents of endotoxin, TNF-α and IL-6 were detected by ELISA. Results Compared with the healthy controls, the expression of TLR2 mRNA and TLR4 mRNA, and the contents of endotoxin, TNF-α and IL-6 increased in CHB patients and liver failure patients ( both early stage and intermediate-end stage) ( F = 32.997, 37.476, 23. 951,57. 265 and 38. 403, P < 0.01 ). TLR2 mRNA expression in liver failure patients in intermediate-end stage was higher than that in the early stage, but that for TLR4 mRNA was lower than that in early stage. The expressions of TLR2 mRNA and TLR4 mRNA in PBMCs were significantly correlated with the contents of TNF-α and IL-6 ( r = 0. 917 and 0. 788, P < 0. 01 ). Conclusion The inflammation reaction mediated by TLR2 and TLR4 might participate in the pathogenesis of liver failure.