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Objective:To understand the diagnostic value of tuberculosis (TB) pathogenic detection methods (TPDM) in pathological tissue for TB.Methods:A retrospective study was conducted with 190 pathological specimens from different tissues suspected with TB from Third People′s Hospital of Shenzhen during May 2016 and May 2019. Specimens were divided into four groups according to histomorphology: group one, necrotizing granulomatous inflammation (109 cases); group two, non-necrotic granulomatous inflammation (20 cases); group three, non-granulomatous inflammation (45 cases); group four, non-tuberculous lesions (16 cases). The positive rates of each TPDM among specimens from four groups were compared. The positive rates of all TPDM for specimens from group one were compared. Meanwhile, the influence of antituberculosis treatment course on the TPDM was analyzed. Chi-square test or Fisher′s exact test was used for statistical analysis.Results:The positive rates of Ziehl-Neelsen acid-fast staining among the four groups were 17.4%(19/109), 5.0%(1/20), 4.4%(2/45) and 0(0/16), respectively. The positive rates of Mycobacterium tuberculosis (MTB) complex culture were 32.0%(32/100), 4/19, 4.8%(2/42) and 0(0/16), respectively. The positive rates of Mycobacterium tuberculosis/rifampin resistance real-time quantitative nucleic acid amplification detection system (Xpert MTB/RIF) were 74.3%(81/109), 15.0%(3/20), 13.3%(6/45) and 0(0/16), respectively. The positive rates of fluorescent quantitative polymerase chain reaction (FQ-PCR) were 63.0%(58/92), 0(0/15), 2.6%(1/38) and 0(0/10), respectively. The positive rates of simultaneous amplification and testing (SAT) were 32.4%(24/74), 0(0/10), 0(0/15) and 0(0/10), respectively. The differences of each TPDM among four groups were all statistically significant (all P<0.05). The positive rate of Xpert MTB/RIF in group one specimens was significantly higher than those of acid-fast staining, MTB culture and SAT ( χ2=71.016, 37.162 and 35.679, respectively, all P<0.01), while the difference was not statistically significant when compared with FQ-PCR ( χ2=2.517, P=0.112). The positive rate of combined TPDM (85.3%(93/109)) was significantly higher than Xpert MTB/RIF(74.3%(81/109)) ( χ2=4.100, P=0.043). The positive rates of acid-fast staining group 1A (anti-tuberculosis treatment course was less than one month) and group 1B (anti-tuberculosis treatment course was longer than one month) were 14.3%(7/49) and 20.0% (12/60), respectively ( χ2=0.612, P=0.434); those of MTB culture were 48.9% (22/45) and 18.2% (10/55), respectively ( χ2=10.721, P=0.001); those of Xpert MTB/RIF were 69.4%(34/49) and 78.3%(47/60), respectively ( χ2=1.131, P=0.287); those of FQ-PCR were 55.0%(22/40) and 69.2%(36/52), respectively ( χ2=1.965, P=0.161); those of SAT were 43.3%(13/30) and 25.0%(11/44), respectively ( χ2=2.736, P=0.098). Conclusions:The results of TPDM correlate closely with the typical histomorphological features of tuberculosis. Xpert MTB/RIF possesses significantly higher sensitivity than any other single TPDM, and is not attenuated by early anti-tuberculosis treatment. Combined TPDM could significantly improve the sensitivity of TB pathogenic detection, which is suggested to be applied when the tissue specimen is sufficient.
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Objective@#To evaluate the real-world safety and curative effect of ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in non-cirrhotic or compensated cirrhotic patients.@*Methods@#A real-world research method was adopted, and the research was conducted at three medical centers of mainland China. Non- cirrhotic or compensated cirrhotic patients with HCV genotype 1b infection who were initially treated with IFN/PEG-IFN-alpha combined with ribavirin, and ombitasvir combined with dasabuvir for 8 or 12 weeks were taken. Sustained virological response (SVR) and the incidence of adverse events during treatment and follow-up were evaluated after 12 weeks of drug withdrawal at OBV/PTV/r 25/150/100mg once daily and DSV 250mg, twice daily. Median and range were used for description of non-normally distributed data.@*Results@#80 cases of GT1b were included in this study. Of these 88.8% (71/80) were newly diagnosed, 12.5% (10/80) were compensated cirrhotic, 97.5% (78/80) received 12 weeks treatment, and 2.5% (2/80) received 8 weeks treatment. The rate of HCV RNA negative at EOT (end of treatment) was 100% (64/64). A total of 67 patients completed the treatment within 12 weeks, and 43 patients returned to the hospital for further consultations, and SVR12 was 100%(43/43). No patient discontinued the drugs because of an adverse event during treatment.@*Conclusion@#In the real world, Ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in China has 100% rates of EOT and SVR12 with well- tolerability and safety.
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Copper is an important trace element in the human body, and copper deficiency or overload can lead to a series of body dysfunctions. This review focuses on hepatolenticular degeneration and related diseases of abnormal copper metabolism. Hepatolenticular degeneration has various clinical phenotypes, and related diseases, such as cholestatic liver disease, hereditary ceruloplasmin deficiency, and congenital abnormal glycosylation, may bring confusion to the clinical diagnosis of hepatolenticular degeneration. With reference to the latest research advances and experience in the diagnosis and treatment of hepatolenticular degeneration, this article discusses the pathogenic mechanism and clinical diagnosis of hereditary abnormal copper metabolism from the perspective of liver diseases.
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The clinical phenotype of genetic liver disease is significantly different. Although the incidence of disease is low, because of the wide spectrum of diseases, the overall affected population is not rare. Therefore, clinical concern is a matter of alarm. Additionally, these diseases rarity in clinical practice has covered the recognition, causing increased problem of clinical misdiagnosis. In accordance with the problems encountered in clinical practice of our hospital, we explore the clinical diagnosis of genetic liver disease.
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<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) after failure of nucleoside-analogues (NAs).</p><p><b>METHODS</b>A total of 30 CHB patients who had been previously treated with NAs and had subsequently completed a 48-week course of TDF were retrospectively investigated. Patients' data of HBV DNA level (log10 copies/ml) and rate of undetectable HBV DNA at treatment weeks 0 (baseline), 4, 12, 24, 36 and 48 were collected for evaluation. The lower limit of HBV DNA detection was 100 IU/ml. The serum alanine aminotransferase (ALT) normalization rate, hepatitis B e antigen (HBeAg) seroconversion rate, viral breakthrough (VBT) rate, viral response (VR) rate, and adverse events were determined upon treatment completion. Statistical analyses were carried out using the Student's t-test, the x² test or the Kaplan-Meier method.</p><p><b>RESULTS</b>Over the 48-week treatment period, HBV DNA levels declined significantly from baseline (week 4:(2.11 ± 0.38) log10 IU/ml, t =5.582; week 12:(0.93 ± 0.31) log10 IU/ ml, t =9.303; week 24:(0.75 ± 0.20) log10 IU/ml, t =3.123; week 36:(0.16 ± 0.19) log10 IU/ml, t =10.759; week 48:(0.14 ± 0.25) log10 IU/ml, t =12.202) (all P less than 0.01). However, the rates of HBV DNA reduction and of cumulative reduction were comparable at weeks 24, 36 and 48 (all P more than 0.05). The most robust decline in HBV DNA levels was observed at week 4 ((2.11 ± 0.38) log10 IU/ml) and the highest cumulative HBV DNA reduction was observed at week 24 ((3.79 ± 0.37) log10 IU/ml). The rate of undetectable HBV DNA at week 4 (26.7%) was significantly lower than that at weeks 24 (87.5%, P less than 0.01), 36 (80.0%, P=0.007), and 48 (88.9%, P=0.001). The median time to achieving undetectable HBV DNA was 10.4 weeks (range:3.43-34.0 weeks). At week 48, the rates of VR, HBeAg seroconversion, and VBT were 88.9% ,6.7%, and 0% respectively. During treatment, the levels of creatine kinase were more than two times the upper limit normal in 9.2% of the patients, and were comparable at each time point examined (all P more than 0.05). All patients showed a normal level of serum creatinine throughout the treatment period.</p><p><b>CONCLUSION</b>For CHB patients with non-response to NAs, TDF can suppress HBV DNA replication very quickly and achieve a high rate of ALT normalization with a low rate of adverse events.</p>
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Adult , Female , Humans , Male , Middle Aged , Young Adult , Adenine , Therapeutic Uses , Antiviral Agents , Therapeutic Uses , DNA, Viral , Blood , Hepatitis B e Antigens , Blood , Hepatitis B, Chronic , Drug Therapy , Organophosphonates , Therapeutic Uses , Retrospective Studies , TenofovirABSTRACT
Objective To survey the incidence of hepatocellular carcinoma (HCC) in patients with HBV-related cirrhosis receiving nucleos(t)ide analogues treatment and to assess its risk factors.Methods A total of 141 patients with HBV-related liver cirrhosis receiving nucleos(t) ide therapy from April 2008 to June 2011 were enrolled.The clinical data including virological and biochemical tests were retrospectively analyzed.Univariate and multivariate Cox proportional hazards regression model was used to identify the risk factors of HCC occurrence.Results Patients were followed up for 6.4 to 87.6 months with a median followup time of 32.5 months.During the follow-up period,15 out of 141 patients developed HCC with an average annual incidence rate of 3.8％.HCC incidence was higher in HBeAg positive cirrhosis and in those with family history of liver cancer ( RR =4.524 and 3.858,P ＜ 0.05 ).Conclusions Patients with HBV-related cirrhosis have a high incidence rate of HCC even they recieve nucleos (t) ide analogues treatment.HBeAg positive cirrhosis and family history of liver cancer are independent risk factors for HCC.
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Objective To evaluate the therapeutic efficacy and its related factors of entecavir treatment for patients with acute on chronic hepatitis B liver failure (ACHBLF).Methods One hundred and eight patients with ACHBLF were enrolled and divided into entecavir group (n=53) and control group (n=55).HBV DNA level, liver function and 48-week survival rate were observed, and C ox regression model was established to identify the factors which may affect the efficacy of entecavir treatment.Results Totally 70 patients died in the study and 66 died within 12 weeks.The statistical difference on cumulative survival rate between two groups was observed from the third week on (χ2=5.357, P ＜ 0.05).The 48-weekcumulative survival rate in entecavir group was 47.2% (25/53), while that in the control group was 23.6%(13/55) (χ2=7.432, P ＜ 0.01).In entecavir group, for patients aged ＜ 40 with serum bilirubin level ＜513 μnol/L and international normalized ratio (INR) ＜ 2.5, the fatality rates decreased 74.9%, 75.3%and 76.0%, respectively.Conclusions Entecavir may improve the survival rate of patients with ACHBLF.Age, serum bilirubin level and INR are major factors related to the therapeutic efficacy.
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Objective To investigate the phenotype, frequency of Th17 cells and the association between Th17 cells and viral clearance in patients with H1N1 influenza A. Methods Three groups including 70 confirmed patients with H1N1 influenza A, 30 patients with seasonal influenza as well as 68 healthy subjects as controls were enrolled in this study. The percentages of Th1, Th2, Treg and Th17 lymphocytes in the peripheral blood were determined by intracellular staining and flow cytometry. The levels of interferon-γ (IFN-γ), transforming growth factor-beta (TGF-β),interleukin-6 (IL-6) in plasma and supernatant of the peripheral blood mononuclear cell (PBMC)culture were quantified by enzyme-linked immunosorbent assay (ELISA). Viral load in nasopharyngeal swabs was detected by real time quantitative reverse transcription-polymerase chain reaction (RTPCR). Data were analyzed by one way ANOVA and liner correlation analysis. Results The percentage of Th17 cells in H1N1 influenza A patients was (2. 740±0. 210)%, which the percentage of was significantly decreased compared to healthy subjects (3. 443 ±0. 154)% and seasonal influenza patients (3. 443±0. 277) % (F=4. 242, P＜0. 05); while the percentage of Thl, Th2 and Treg cells were not significantly different among these groups. Moreover, the TGF-β level in plasma of H1N1 influenza A patients was (10±8) ng/mL, which was significantly lower than healthy subjects (43 ±32 ) ng/mL and seasonal influenza patient ( 18 ± 10) ng/mL ( F= 17.72, P＜0.01 ). The TGF-β level in the supernatant of PBMC culture of H1N1 influenza A patients was (782 ± 736) pg/mL, which was significantly lower than healthy subjects (1462±315) pg/mL and seasonal influenza patients (1481 ±348) pg/mL (F=5. 730, P＜0.01). Additionally, the viral clearance period was inversely correlated with the percentage of Th17 cells (r=-0.38, P=0.02). Conclusions The proportion of Th17 cells in patients with H1N1 influenza A is significantly decreased, which is closely correlated with the level of TGF-β. This decrease may results in the delayed viral clearance.
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BACKGROUND:It is reported that bone marrow mesenchymal stem cell(BMSC)transplantation might be a promising treatment for liver fibrosis.But the mechanism is still unclear.OBJECTIVE:To observe the hepatic stellate cells apoptosis induced by BMSC transplantation,and to study the mechanism of BMSC in treating hepatic fibrosis in vivo.METHODS:CCl_4 subcutaneous injection was performed to induce rat liver fibrosis.After 8 weeks of CCU injection,20 rats which underwent successful model establishment were randomly divided into experimental group and control group,10 in each group.The experimental group received MSC transplantation via tail vein injection,and the control group were given DMEM instead.The rats were killed and the livers were harvested at three time point,the day of MSC transplantation,3 days after transplantation,and 7 days after transplantation.The hydroxyproline content was detected by HE and Masson staining,and the expression changes of α-smooth muscle actin(α-SMA)proteins were determined using immunohistochemistry.The apoptosis of hepatic stellate cells were determined by α-SMA and TUNEL(terminal dUTP nick-end labeling)dual-staining.RESULTS AND CONCLUSION:After 8 weeks of CCU injection,the hydroxyproline content increased and histology indicated progress of liver fibrosis.At 7 days after MSC transplantation,the hydroxyproline in the liver was decreased,and the liver fibrosis was alleviated in the experimental group but aggravated in the control group.Immunohistochemistry indicated that α-SMA positive cells were increased at 8 weeks after CCU injection.At day 7 after transplantation,α-SMA positive cells in the experimental group were significantly less than control group(P ＜ 0.05).At 3 days after transplantation,the hepatic stellate cells apoptosis in the experimental group was significantly aggravated compared with control group(P ＜ 0.05).This suggested that MSC transplant was an effective treatment for liver fibrosis.MSC inducing hepatic stellate cells apoptosis may be one of the mechanisms.
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Objective To investigate the revaccination efficacy of different dosages of hepatitis B vaccine among adult non-and hyporesponders so as to improve the protection rate of hepatitis B vaccination.Methods The healthy adults who were immunized with hepatitis B vaccine at least one standard scheme in two years and negative for hepatitis B markers were enrolled in this randomized and open-label study.The hepatitis B vaccine was injected intramuscularly in the deltoid muscle on an upper arm according to routine schedule (month 0,1,6).The adults were randomly given four different dosages:73 in group A were given hepatitis B vaccine 10 μg (made in China) each time;69 in group B were given hepatitis B vaccine (made in China) 20 μg each time;70 in group C were given gene recombinant yeast hepatitis B vaccine (Engerix) 20 μg each time and 48 in group D were given gene recombinant yeast hepatitis B vaccine 40 μg each time.The serum anti-HBs was tested before and 1,2,8,12 months after the first injection.The comparison of means was done by one-factor analysis of variance and the comparison of rates was done by chi square test.Results The anti-HBs positive rates were the highest at months 8 of re-immunization in group B,C and D,which were 68.1%,70.0% and 77.1%,respectively,and were all higher than that in group A (53.4%)(χ2=21.465,P＜0.01).The anti-HBs positive rate increased in group B,C and D with increasing immunized times and over time,but there was no significant difference;it went down at 12 months after re-immunization.The anti-HBs positive rates at 1,2,8 and 12 months after re-immunization in group A were 8.2%,19.2%,53.4% and 43.8%,respectively and differences were significant (χ2=53.07,P＜0.01).The anti-HBs levels in group B,C and D were all higher than that of group A(F=7.551,P＜0.05) at month 12 of re-immunization.There were no significant differences of anti-HBs levels at different re-immunization time points in group B,C and D.Conclusion Revaecination of hepatitis B vaccine can induce immune responses and increasing dosages can improve the immune efficacy in non- and hyporesponders.
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Objective To investigate the balance of Th1/Th2 cytokines and its relationship with prognosis of severe chronic hepatitis B ( CHB ). Methods Peripheral blood samples were collected from 112 severe CHB patients, 30 CHB patients and 30 healthy controls. IL-4, IFN-γ levels and HBV DNA loads were measured by ELISA and fluorescent PCR, respectively. The levels of cytokines in different stages, and their correlations with HBV DNA loads and short-term prognosis were analyzed. Results Higher levels of IL-4, IFN-γ and Th1/Th2 ratios in peripheral blood were detected in patients with severe CHB than those with CHB and the healthy controls (Z = 8.968, 10. 004 and 26. 067, P =0. 009, 0. 007 and 0. 000). IL4 levels in patients with end-stage server CHB were markedly higher than those in other stages ( Z = 3. 672 and 3. 158, P= 0.000 and 0.002), while their Thl/Th2 ratios were lower (Z=3. 161 and 2. 166, P=0.002 and 0. 030). No significant differences on levels of IL-4, IFN-γ and Th1/Th2 ratios were observed in severe CHB patients with different HBV DNA levels (Z =4.431, 2.626 and 0. 140, P =0.219, 0.403 and 0. 987). Elevated IL-4 was closely correlated with the high case-fatality rate within 12 weeks. Conclusions The balance between Th1 and Th2 cytokines is- disturbed in patients with severe CHB. Thl/Th2 ratio decreases with the aggravation of diseases, which may indicate unfavorable short-term prognosis.
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Objective To investigate the therapeutic effects of recombinant yeast hepatitis B virus(HBV)vaccine combined with interferon(IFN)α-1b and determine the rational dosage of HBV vaccine for the further clinical study with larger sample.Methods Two hundreds and sixteen patients with chronic hepatitis B(CHB)were enrolled in this randomized,multi-center,double-blinded and placebo-controlled clinical trial.All the subjects were not treated with antiviral drugs within 6 months and randomly divided into 90μg,60μg and placebo groups with a ratio of 1:1:1.All the patients were intramuscularly administrated with 90μg or 60μg recombinant HBV vaccine or placebo at week 0,2,6,10,14,18,22,respectively.Meanwhile,they were also treated with IFNα-1b 50μg,3 times a wcek for 24 weeks.All patients were followed up for 24 weeks after withdrawal of anti-HBV therapy.Serum HBV DNA level,HBeAg titer and liver function were monitored frequently.Interferon-γ secreting lymphoeytes were detected by Enzyme-linked immunospot(ELISPOT)in part of the patients.Results The serum HBV DNA levels were(6.03±1.79),(5.52±1.82)and(6.29±1.70)log10 copy/mL at week 24 of treatment in high dose,low dose and placebo groups,respectively (P=0.458).And the serum HBV DNA levels were(5.92±1.98),(5.49±1.99)and(6.16±1.76)log10 copy/mL at weck 24 after withdrawal of treatment,respectively(P=0.720).The rates of patients whose HBV DNA＜1×105 copy/mL in these three groups were 30.4%,39.4% and 20.8% at week 24 of treatment,respectively and there was significant difference between high dose group and low dose group(P=0.015).The rate of patients whose HBV DNA＜1×105 copy/mL at week 24 after withdrawal was highest in low dose group,but no significant differences before and after treatment in these three groups(P=0.257).The HBV DNA negative rates were 17.4%,25.4% and 6.9% in these three groups,respectively,which were significantly different(P=0.012).At week 24 of treatment and week 24 after withdrawal of treatment,the alanine aminotransferase normalization rate,HBeAg seroconversion rate were highest in low dose group,but no significant differences in these three groups.ELISPOT positive rates at week 24 of treatment and week 24 after withdrawal of treatment in high close and low dose groups were higher than that in placebo group(P＜0.05).The incidence of adverse events was similar and there was no drug related severe adverse events in each group.Conclusion Recombinant HBV vaccine maybe contribute to anti-HBV therapy and 60μg of dosage seems to be rational.
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0.05).The death rate of cases with pneumonia combined with ascites was higher than that of cases with ascites only(?2=4.894,P=0.027) and cases without ascites and infections(?2=9.260,P=0.002).Unfavorable prognosis was found in cases with Enterococcus faecium isolated before OLT.CONCLUSIONS Severe lung infection before OLT is one of the main reasons of death.It is important to grasp characteristics of infection,evaluate risk fully,control infections and screen cases strictly before OLT to improve survival rate.