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.

HBsAg loss with Pegylated-interferon alfa-2a in hepatitis B patients with partial response to nucleos(t)-ide analog: new switch study / 中华肝脏病杂志

Objective@#Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.@*Methods@#Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281.@*Results@#At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg < 1 500 IU/mL and week 24 HBsAg < 200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss.@*Conclusion@#Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

Study on changes of blood electrolyte levels and assessment of mortality rate in patients with different degrees of craniocerebral injury / 国际检验医学杂志

Objective To investigate the relationship between electrolyte level change with prognosis in the patients with craniocerebral injury.Methods A total of 360 patients with craniocerebral injury in this hospital during 2012-2015 were selected as the research subjects and divided into the mild craniocerebral injury group (171 cases),moderate craniocerebral injury group(104 cases)and severe craniocerebral injury group(85 cases) according to the Glasgow coma scale.The severe craniocerebral injury group was further divided into the high level blood sodium subgroup(73 cases)and stable level blood sodium subgroup(12 cases)according to the lev-el of blood sodium,meanwhile 70 persons undergoing healthy physical examination were selected as the control group.The plasma electrolyte levels(blood sodium,potassium,chloride)in each group were detected within 5 d after admission.Then the results were statistically analyzed.Results Compared with the control group,the blood sodium,potassium and chloride levels had no statistical difference between the mild and moderate craniocerebral injury groups(P>0.05).The blood sodium and chloride levels in the severe craniocerebral inju-ry group were higher than those in the mild and moderate craniocerebral injury groups,the difference was sta-tistically significant(P<0.01).The blood potassium level had no statistical difference between the mild,mod-erate and severe craniocerebral injury groups with control group(P>0.05).In the severe craniocerebral injury group,there were 58 cases(79.45%)of death in the high level blood sodium subgroup and 4 cases(33.33%) of death in the stable level blood sodium subgroup,the difference was statistically significant(P<0.01).Con-clusion Clinically monitoring the blood sodium level change in the patients with craniocerebral injury,espe-cially severe craniocerebral injury,is conducive to the disease recovery.

Analysis of prognostic factors and construction of a logistic regression model for patients with drug-induced liver failure / 中南大学学报(医学版)

To explore the prognostic factors for patients with drug-induced liver failure (DILF) and construct a logistic regression model (LRM).
 Methods: A retrospective analysis of clinical data was performed in 183 hospitalized patients, who were diagnosed with DILF in Xiangya Hospital, the Second Xiangya Hospital and the Third Xiangya Hospital, Central South University from January 2009 to January 2018. The patients were divided into an improved group (n=67) and an ineffective group (n=116) according to their prognosis. Univariate analysis was performed to screen for possible prognostic factors such as age, Tbil, SCr, PT and complications. According to the results of univariate analysis, the multivariate analysis was performed to determine the independent prognostic factors and construct a LRM. The LRM was compared with the model for end-stage liver disease (MELD), the predictive value of LRM and MELD was evaluated by receiver operating characteristic curve (ROC), the parameters such as area under the ROC (AUC) and total accuracy were compared between the 2 models and verified by another independent sample.
 Results: According to univariate analysis, there was significant differences in age, clinical type, hepatic encephalopathy, hepatorenal syndrome, WBC count, the ratio of aspartic acid transaminase (AST) to glutamine transaminase (ALT) (AST/ALT), Tbil, SCr, PT and alpha-fetoprotein (AFP) between the 2 groups (all P<0.05). Multivariate analysis revealed that: AFP, PT, AST/ALT, hepatic encephalopathy and hepatorenal syndrome were independent prognostic factors for DILF, which could be applied to constructing a LRM. The AUC of LRM and MELD was 0.917 (95% CI 0.876 to 0.959) and 0.709 (95% CI 0.633 to 0.786) respectively, the total accuracy rate of prediction for the LRM and the MELD was 86.7% and 68.3% respectively, there was significant difference in AUC and total accuracy rate between the LRM and the MELD (P<0.05). LRM was superior to MELD.
 Conclusion: AFP, PT, AST/ALT, hepatic encephalopathy and hepatorenal syndrome were independent prognostic factors for DILF; the LRM can well predict the prognosis in the DILF patients, which is superior to the MELD.

Clinical and epidemic characteristics of 27 cases with Brucellosis confirmed by bacterial culture / 中国医师杂志

Objective To improve the diagnostic and therapeutic ability of Brucellosis by analyzing the epidemic and clinical characteristics.Methods A retrospective analysis was done on the data of Brucellosis patients treated in our hospital from 2007 to 2016.Results Since the first case was diagnosed in 2012,27 patients [19 male and 8 female,mean age (44.4 ± 16.9) years] were confirmed by clinical manifestations and positive bacterial cultures results.The annual number of cases from 2012 to 2016 was 1,1,6,4 and 15.Among them,10 cases (37.0％) had a history of close contact with goat,7 cases (25.9％)with raw mutton,1 case (3.7％) with raw beef and 1 case (3.7％) with suspicious laboratory contamination while 8 cases (29.6％) had no evident risk factors for Brucellosis.The common clinical manifestation included fever (81.5％),lumbago/joint pain (55.6％),fatigue (33.3％) and hyperhidrosis (22.2％).The white blood cell count was normal among 20 cases (74.1％) while 6 cases (22.2％) with leukopenia.Mild to moderate anemia in 20 cases (74.1％) and decreased platelet number in 4 case (14.8％).The percentage of elevated alanine aminotransferase,aspartate aminotransferase and lactate dehydrogenase was 32.0％,48.0％ and 100％,respectively.Decreased albumin level was found in 23 cases (92.0％).The percentage of elevated erythrocyte sedimentation rate (ESR),C-reactive protein and serum ferritin 75.0％,82.3％ and 77.8％,respectively,while 12 cases (85.7％) with procalcitonin level below 0.5 ng/L.According to follow-up for at least half year,all the cases were cured by active medical management.Conclusions The number of Brucellosis cases is rapidly increasing in our hospital.It's of great significance to know the epidemic and clinical characteristics of Brucellosis.

The clinical value of tumor markers HE 4 ,CA125 ,CA199 ,CA153 and AFP in the early diagnosis of ovarian cancer / 国际检验医学杂志

Objective To investigate the diagnostic value of serum human epididymis protein 4 (HE4) ,carbohydrate antigen 125 (CA125) ,carbohydrate antigen antigen (CA199) ,carbohydrate antigen 153 (CA153) and alpha fetoprotein (AFP) in the early di-agnosis of ovarian cancer .Methods From February 2014 to October 2016 ,117 patients with ovarian cancers who were treated in this hospital were selected ,including 69 cases of ovarian cancer and 48 cases of benign ovarian lesions ,and 70 healthy volunteers were selected as control group .The serum levels of HE4 ,CA125 ,CA199 ,CA153 and AFP were measured in all subjects . Results The positive rates of HE4 ,CA125 ,CA199 ,CA153 and AFP in the ovarian cancer group were 59 .42% ,68 .12% ,33 .33% , 46 .38% and 39 .13% ,respectively ,which were significantly higher than those in the benign ovarian lesion group and the control group (P<0 .05) .The sensitivity of CA125 in the diagnosis of ovarian cancer was 68 .11% ,the specificity was 88 .98% ,the nega-tive predictive value was 78 .33% ,the positive predictive value was 82 .68% ,Youden index was 0 .571 .The diagnostic efficiency was better than that of other tumor markers .Pathological examination revealed 34 cases of serous adenocarcinoma ,18 cases of mucinous adenocarcinoma and 17 cases of endometrioid carcinoma in 69 cases of ovarian cancer .The positive rate of serous adenocarcinoma CA125 was 85 .29% ,significantly higher than mucinous carcinoma and endometrioid carcinoma (χ2 =9 .398 ,P<0 .05) .Conclusion CA125 has a good application value in the early diagnosis of ovarian cancer ,the positive rate is higher in serous adenocarcinoma .

Clinical effect and safety of pegylated interferon-α-2b injection (Y shape, 40 kD) in treatment of HBeAg-positive chronic hepatitis B patients / 中华肝脏病杂志

Objective@#To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control.@*Methods@#This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data.@*Results@#A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events.@*Conclusion@#In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.

Efficacy and safety of pegylated interferon α-2b injection (Y shape, 40 kD) in treatment of patients with genotype 1/6 chronic hepatitis C / 中华肝脏病杂志

Objective@#To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control.@*Methods@#A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed.@*Results@#A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group.@*Conclusion@#In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.

The clinical value of tumor markers HE 4 ,CA125 ,CA199 ,CA153 and AFP in the early diagnosis of ovarian cancer / 国际检验医学杂志

Objective To investigate the diagnostic value of serum human epididymis protein 4 (HE4) ,carbohydrate antigen 125 (CA125) ,carbohydrate antigen antigen (CA199) ,carbohydrate antigen 153 (CA153) and alpha fetoprotein (AFP) in the early di-agnosis of ovarian cancer .Methods From February 2014 to October 2016 ,117 patients with ovarian cancers who were treated in this hospital were selected ,including 69 cases of ovarian cancer and 48 cases of benign ovarian lesions ,and 70 healthy volunteers were selected as control group .The serum levels of HE4 ,CA125 ,CA199 ,CA153 and AFP were measured in all subjects . Results The positive rates of HE4 ,CA125 ,CA199 ,CA153 and AFP in the ovarian cancer group were 59 .42% ,68 .12% ,33 .33% , 46 .38% and 39 .13% ,respectively ,which were significantly higher than those in the benign ovarian lesion group and the control group (P<0 .05) .The sensitivity of CA125 in the diagnosis of ovarian cancer was 68 .11% ,the specificity was 88 .98% ,the nega-tive predictive value was 78 .33% ,the positive predictive value was 82 .68% ,Youden index was 0 .571 .The diagnostic efficiency was better than that of other tumor markers .Pathological examination revealed 34 cases of serous adenocarcinoma ,18 cases of mucinous adenocarcinoma and 17 cases of endometrioid carcinoma in 69 cases of ovarian cancer .The positive rate of serous adenocarcinoma CA125 was 85 .29% ,significantly higher than mucinous carcinoma and endometrioid carcinoma (χ2 =9 .398 ,P<0 .05) .Conclusion CA125 has a good application value in the early diagnosis of ovarian cancer ,the positive rate is higher in serous adenocarcinoma .

Clinical features of patients with primary biliary cirrhosis / 中南大学学报(医学版)

OBJECTIVE@#To determine features of the clinical manifestation in patients with primary biliary cirrhosis (PBC), and to provide a scientific basis for diagnosis of PBC.
@*METHODS@#A total of 102 patients with PBC treated in the Second Xiangya Hospital, Central South University, from January 2013 to January 2015 were retrospectively analyzed. The patients' general condition, clinical manifestations, serum biochemical and immunological parameters were detected.
@*RESULTS@#Of the 102 PBC patients, 91 (89.21%) patients were female. The main symptoms in these patients were fatigue, poor appetite, dry mouth, nausea, vomiting, pruritus, stomachache, and abdominal distension. The major signs were jaundice, splenomegaly, hepatomegaly, edema, and ascites. The main features of serum biochemical parameters in these patients included the increase of alkaline phosphatase and gamma glutamyltranspeptidase (GGT), especially the GGT. The anti-mitochondrial antibodies-M2 (AMA-M2) in 81 and 21 patients was positive and negative, respectively. The differences between the AMA-MA positive and negative groups were not statistically significant (P>0.05). According to clinical manifestation, 102 patients were classified into 2 groups: A non-cirrhosis group (n=56) and a cirrhosis group (n=46). The positive rates in these 2 groups, such as ANA, AMA-M2, anti-gp210, anti-Sp100, anti-Ro52, anti-PML, were 54.35%, 89.13%, 41.30%, 13.04%, 43.38% and 10.87% vs 57.14%, 71.43%, 42.86%, 12.5%, 51.79% and 3.71%, respectively, with no significant difference between them (P>0.05). However, there was significant difference in the positive rate of anti-3E-EPO between the above 2 groups (86.78% vs 58.93%, P<0.05). The positive rates of AMA-M2 and anti-3E-EPO in 30 patients diagnosed by hepatic histopathological examination were higher than those of other antibodies.
@*CONCLUSION@#PBC mainly affects middle-aged women, and its clinical manifestation is various. The autoantibody tests play an important role in diagnosis of PBC. Checking for AMA-A2 and anti-3E-BPO can improve the positive rate of PBC. Liver histopathological examination may provide useful information on disease severity, which can determine the histological stage when the patient's serum autoantibodies are negative.

High sustained virological response to optimized therapy for refractory chronic hepatitis C treatment-na(i)ve patients: a multicenter randomized study / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To perform a prospective,multicenter,open,randomized study to determine a treatment regimen for treatment-naive patients with refractory chronic hepatitis C (RHC) using the predictive value (PV) of early virological response (EVR).</p><p><b>METHODS</b>A total of 438 patients from 18 hospitals were recruited between December 2008 and December 2010 and administered peg-interferon/ribavirin treatment for 12 weeks. Patients who achieved complete EVR (cEVR) were assigned to group A for a 48-week course of treatment, while patients without cEVR were randomly allocated to either group B 1 for a 72-week course of treatment or to group B2 for a 96-week course of treatment. Serum hepatitis C virus RNA levels at baseline,treatment weeks 4, 12 and 24, end of treatment, and post-treatment week 24 were measured and used to evaluate the efficiency of therapy.</p><p><b>RESULTS</b>The overall sustained virological response (SVR) rate was 85.1%. In all, 91.0% of patients achieved cEVR and were assigned to group A, which had an SVR rate of 90.8%. There was no statistically significant difference in the SVR rates of groups B1 and B2 (29.4% vs. 25.0%, P more than 0.05). The positive PV of rapid virological response (RVR), cEVR and delayed virological response (DVR) for SVR was 93.4%, 90.8% and 77.8% respectively, and the negative PV of RVR, EVR and DVR for SVR was 28.0%, 93.3% and 100% respectively. Overall, 66.9% of the patients experienced adverse events (AEs), but only 1.9% of patients experienced sevcre AEs.</p><p><b>CONCLUSION</b>The majority of Chinese RHC treatmentna(i)ve patients (91.0%) can achieve cEVR and a high SVR rate with a low rate of severe AEs using the cEVR guided personal treatment regimen.</p>

Efficacy and related factors of pegylated interferon α-2a plus ribavirin therapy for chronic hepatitis C in non-responders / 中华临床感染病杂志

Objective To evaluate the efficacy of pegylated interferon ( PegIFN ) α-2a plus ribavirin ( RBV) therapy for chronic hepatitis C ( CHC) in non-responders, and to investigate the related influencing factors.Methods A prospective, open, multicenter and randomized study was conducted.A total of 81 CHC non-responders were recruited from 10 clinical centers during February 2009 to November 2011.Patients were randomly assigned into two groups:group A (n=37) was given PegIFNα-2a plus RBV treatment for 72 weeks and group B (n=44) was given PegIFNα-2a plus RBV treatment for 96 weeks.Both groups were followed up for 24 weeks after treatment.Virological responses in two groups were observed, and treatment efficacies among patients with different genotypes, and among those with different previous treatment were compared.SAS software was used for statistical analysis.Results Fifty-two patients ( 28 from group A and 24 from group B) completed the study in total.The rates of rapid virological response ( RVR) , complete early virological response ( cEVR ) , end of treatment viral response ( ETVR ) and sustained virological response (SVR) in group A were 25.0% (7/28), 60.7% (17/28), 67.9%(19/28) and 60.7%(17/28), respectively; while those in the group B were 41.7% (10/24), 70.8%(17/24), 70.8%(17/24) and 70.8% (17/24), respectively; and there were no significant differences between two groups (P>0.05).SVR was observed in 82.9%(29/35) of patients with CC genotype of IL-28B, which was higher than that in patients with other genotypes ( 3/13 ) , and the difference was of statistical significance (P0.05).The rates of RVR, cEVR, ETVR and SVR in patients who were previously treated with IFN were 36.4%(12/33), 81.8%(27/33), 81.8%(27/33) and 75.8%(25/33), and the rates of cEVR, ETVR and SVR were higher than those in patients who were previously treated with PegIFN (P0.05).Adverse events occurred in 38 patients (46.9%), but no severe ones were observed. Conclusion The efficacy of PegIFNα-2a plus RBV therapy for CHC in non-responders is satisfactory, which may influenced by IL-28B genotypes and previous treatment.

Fulminant hepatic failure and hepatitis B virus reactivation: case reports and analyses of the pathological mechanism / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the clinical features and mechanisms of hepatitis B virus (HBV) reactivation induced by chemotherapy or immunosuppressive therapy and subsequent fulminant hepatic failure (FHF) in patients with autoimmune diseases.</p><p><b>METHODS</b>Seven cases of FHF related to HBV reactivation were retrospectively assessed. All patients had been confirmed as hepatitis B e antigen (HBeAg) seronegative and had undergone glucocorticoid-based therapy to manage primary diseases, including nephrotic syndrome (2 cases), polycystic kidney disease combined with chronic nephritis (1 case), conditions following kidney transplantation (1 case), lymphadenoma (1 case), idiopathic thrombocytopenic purpura (1 case), and angitis (1 case). Levels of sero-markers of HBV and HBV DNA were recorded. Serum samples from patients were respectively applied to HepG2.2.15 and HepG2 cell lines in order to investigate the effects on cell proliferation (by MTT assay) and apoptosis (by Hoechst 33342 staining assay). Intergroup differences were statistically assessed by the t-test.</p><p><b>RESULTS</b>For all patients, the initial clinical signs of hepatic failure emerged at 4 to 11 months after receipt of the glucocorticoid treatment. At the time of hepatic failure, HBeAg seropositivity was detected in 4 patients, including one patient who also showed seropositivity for the hepatitis B surface antibody (HBsAb). All 7 patients showed high levels of HBV DNA when the hepatitis condition flared. Neither remedial antiviral treatments nor internal medicine comprehensive treatments, including therapeutic plasma exchange, were effective in any of these cases. The duration from clinical signs onset to death ranged from 24 to 47 days. Treatment of HepG2.2.15 and HepG2 cells with serum samples from patients with FHF showed a dosage-effect relationship of the serum concentration on the cellular proliferation inhibition rate, with the serum of patients with FHF having more severe inhibiting effects on the HepG2.2.15 cells than on the HepG2 cells. The HepG2.2.15 cells showed a greater tendency towards apoptosis upon treatment with serum samples from patients with FHF, compared to the HepG2 cells.</p><p><b>CONCLUSION</b>HBV reactivation induced by chemotherapy or immunosuppressive therapy is a problem currently encountered in the management of malignancies or rheumatic autoimmune disease patients. It is critical to verify HBV status prior to initiation of these treatment strategies so that appropriate antiviral prophylaxis may be administered, so as to reduce the risk of HBV reactivation and subsequent repression of cell proliferation and apoptosis that can promote development of FHF and increase a patient's risk of death.</p>

miR-197 Expression in Peripheral Blood Mononuclear Cells from Hepatitis B Virus-Infected Patients

BACKGROUND/AIMS: This study aimed to investigate the microRNA (miRNA) expression profiles in peripheral blood mononuclear cell (PBMC) of hepatitis B virus (HBV)-infected patients with different clinical manifestations and to analyze the function of miR-197. METHODS: PBMC miRNA expression profiles in 51 healthy controls, 70 chronic asymptomatic carriers, 107 chronic hepatitis B patients, and 76 HBV-related acute on chronic liver failure patients were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). miR-197 mimic and inhibitor were transfected in THP-1 cells. qRT-PCR and ELISA for interleukin (IL)-18 mRNA and protein levels were performed, respectively. RESULTS: The microarray analysis revealed that 17 PBMC miRNA expression profiles (12 miRNAs downregulated and five miRNAs upregulated) differed significantly in HBV-induced liver disease patients presenting with various symptoms. The qRT-PCR results suggested that the PBMC miR-197 levels regularly decreased as the severity of liver disease symptoms became aggravated. IL-18, a key regulator in inflammation and immunity, was inversely correlated with miR-197 levels. Bioinformatic analysis indicated that IL-18 was a target of miR-197. Exogenous expression of miR-197 could significantly repress IL-18 expression at both the mRNA and protein levels in THP-1 cells. CONCLUSIONS: We concluded that multiple PBMC miRNAs had differential expression profiles during HBV infection and that miR-197 may play an important role in the reactivation of liver inflammation by targeting IL-18.

Prognosis and treatment of fulminant Wilson's disease / 中南大学学报(医学版)

OBJECTIVE@#To explore the effective treatment and prognostic factors for fulminant Wilson's disease (FWD).@*METHODS@#We retrospectively analyzed the clinical characteristics, therapeutic Methods and outcomes of 13 FWD patients. We investigated the treatment effect of the joint use of hormones, decoppering, and plasma exchange therapy in patients with FWD, compared the difference in the clinical features, biochemical data and treatment between the survival group and the death group.@*RESULTS@#Thirteen patients with FWD presented with acute hepatic failure and severe jaundice: 7 accompanied with severe hemolytic anemia, 5 with primary peritonitis, 8 with hepatic encephalopathy. Prothrombin activity (PTA) of 5 was below 30% in the 13 patients. Plasma exchange (PE), dimercaptopropansulfonate sodium (DMPS) and short-term methylprednisolone /dexamethasone administration were performed in 7 patients, in which 6 survived and the other 1 who had primary peritonitis with PTA below 30% died. The other 6 patients without above-mentioned treatments all died, in which 4 accompanied with primary peritonitis with PTA all below 30%.@*CONCLUSION@#The level of hepatic failure and the occurrence of infection are the decisive factors for prognosis of patients with FWD. PE with decoppering treatment and corticosteroid administration are effective.

Effect of methylation inhibitor on demethylation pattern of the PD-1 gene in promoter region and PD-1 expression in human T lymphocyte cell line / 中南大学学报(医学版)

OBJECTIVE@#To observe the demethylation effect of demethylation inhibitor 5-azacytidine (5-Zac) on programmed death receptor 1 (PD-1) in Molt-4 cells (T lymphocyte cell line) and to investigate the relationship between DNA demethylation and expression of PD-1.@*METHODS@#Molt-4 cells were cultured in the medium containing different concentrations of 5-Zac(0, 5, 10 μmol/L) for 72 h. According to the concentrations of 5-Zac, the Molt-4 cells were divided into a 0 μmol/L 5-Zac group, a 5 μmol/L 5-Zac group, and a 10 μmol/L 5-Zac group. The expression of PD-1 in Molt-4 cells was detected by flow cytometry and the apoptosis rate was calculated. The mRNA transcription level of PD-1 was detected by real-time polymerase chain reaction; Molt-4 cell DNA in all groups were treated by sodium bisulfite. The PD-1 promoter fragment was amplified by PCR, the amplification fragments were transformed into E. coli., the positive clones were selected for equencing, and the methylation status of the fragments of PD-1 promoter was examined. RESULTS Seventy-two hours after the 5-Zac treatment, the expression rate of PD-1 in the Molt-4 cells in the 0 μmol/L 5-Zac group, the 5 μmol/L 5-Zac group, and the 10 μmol/L 5-Zac group was (1.13 ± 0.01)%, (18.96 ± 1.87)%, and (63.09 ± 6.25)% respectively, in a low concentration-dependent way. The PD-1 mRNA expression level was increased significantly with the 5-Zac treatment. Cells apoptosis showed that:compared with the 0 μmol/L 5-Zac group, the apoptosid rate in the 5 μmol/L 5-Zac group and 10 μmol/L 5-Zac group was signficantly increased, which was (1.9 ± 0.06)%, (8.89 ± 1.36)%, and (24.50 ± 3.68)% in the 0 μmol/L 5-Zac group, the 5 μmol/L 5-Zac group, and the 10 μmol/L 5-Zac mol/L group respectively. The bisulfite genomic sequencing showed that the demethylation probability of CpG points on -601 bp and -553 bp was significantly increased in the 5-Zac treated cells compared with those untreated.@*CONCLUSION@#5-Zac can result in the increase of PD-1 expression in the human lymphoid cell series Molt-4 in vitro, and the apoptosis rate increases, which is related to PD-1 gene promoter demethylation.

5-azacytidine induces PD-1 gene promoter demethylation and PD-1 protein expression in human lymphoid cell series Molt-4 cells / 中华微生物学和免疫学杂志

Objective To investigate the demethylation and changes in gene expression of programmed death receptor-1 ( PD-1) caused by methylation inhibitor 5- azacytidine (5-Zac) in lymphocyte series Molt-4 cells and its mechanism. Methods Molt-4 cells were cultured in different concentrations of 5-Zac(0, 5, 10 Umol/L)for 72 h, ratio of cell expressing PD-1 and apoptosis rate were detected by FCM, transcription of PD-1 gene mRNA was detected by RT-PCR. Molt-4 cell DNA of all groups were disposed by sodium bisulfite, PD-1 gene promoter fragment binded with transcription factor Brn-2 was amplified by PCR,these amplification fragments were transformed into E. coli. Positive clones were selected by sequencing,methylation status of the fragments binded with transcription factor Brn-2 was examined. Results S-Zac could increase the PD-1 expression of Molt-4 cells. PD-1 expression rate in 0 μmol/L 5-Zac( 1. 13%±0.01% ) treated cells was found more lower than that in both 5 μmol/L and 10 μmol/L 5-Zac treated cells (18. 96% ±1. 87% , 63. 09% ± 6. 25% , P < 0. 05 ) , and they showed concentration-dependent (P <0.01). Cells apoptosis rate and PD-1 mRNA expression were also observed increased significantly with 5-Zac treating. Demethylation probability of CG points showed significant difference between transcription factor Brn-2 binding site and other four locations (P < 0.05 ). Conclusion 5 -Zac inhibits cell grouth in human lymphoid cell series Molt-4 by inducing PD-1 gene expression and promoter demethylation. PD-1 gene promoter binding transcription factor Brn-2 fragment CG point demethylation may be one of the important mechanisms in 5-Zac treated Molt-4 cells.

Therapeutic effect and safety evaluation on 6-year highly active antiretroviral therapy for Chinese HIV-1 infected patients / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the long-term efficacy and safety of nevirapine (NVP)-based regimens for HIV-infected Chinese patients in routine clinical practice.@*METHODS@#From October 2002 to May 2004, 57 HIV-1-infected patients commenced highly active antiretroviral therapy (HAART), and were followed to December 2008. They originally received 2 nucleoside reverse transcriptase inhibitors (NRTIs) and nevirapine. HIV RNA levels, T lymphocyte subsets and safety were assessed. Blood routine test and main laboratory parameter changes were traced. If apparent side effects or virological failure appeared we would, if necessary, terminate the therapy or change the regimen.@*RESULTS@#Of the 57 subjects, 34 were followed-up for more than 4 years. After 5-6 years, 63.3% of the subjects (19/30) had HIV RNA levels<50 copies/microL, and the median increase in CD4(+) cell count from the baseline was 329 cells/microL. The mean decrease in CD8(+) cell count was 128 cells/microL. At the same time, the CD4(+) CD45RA+CD62L cell count and CD4(+)CD45RO(+) cell gradually increased, and the counts of CD8(+)CD38(+) cell declined gradually. These changes are apparent 2 years after HAART. The increase rate slowed down after 2 years. But they did not recover completely as well as healthy people at year 6. About 56% (32/57) of HIV-infected patients developed various drug-related side effects. The most common was gastrointestinal side effect, followed nervous disorder, baldness, and rashes, mostly happened in 6 months. Gamma-GT increased occurred in 29.8% of patients (17/57), and serum cholesterol and triglyceride elevated in 26.3% of the patients (15/57). Six patients developed lipodystrophy, mainly in female patients, and 25 patients showed abnormal blood picture and liver function, renal function changes and amylase elevation. Grade 3-4 adverse events occurred in 3 cases (2 peripheral neuropathy, and 1 suspected lactic acidosis). One subject experienced grade 3 rashes.@*CONCLUSION@#Antiretroviral therapy with NVP-based regimens is safe and effective by suppressing HIV viremia and producing continued CD4 cell increases in subjects with HIV or AIDS for 6 years.

The establishment of a cell strain expressing HIV Vpr and the study on Vpr induced apoptosis / 中华微生物学和免疫学杂志

Objective To establish cell strain expressing the genes of HIV vpr and mutant HIV vpr-FS, and to explore cell apoptosis ability by HIV Vpr and Vpr-FS. Methods The recombinant plasmids were constructed by cloning HIV vpr and HIV vpr-FS genes into the eukaryotic expression vector pcDNA3.1respectively. To determine the primary structures of HIV vpr and HIV vpr-FS, plasmids were cleaved by restriction enzymes. After the plasmids were transfected into HeLa cells by liposome, the HeLa cells were selected with G418 selective medium, mRNA expression of HIV vpr or HIV vpr-FS of transfected cells was detected by RT-PCR, and Vpr and Vpr-FS protein expression were detected by Western blot assay respectively. The DNA content and the percentage of apoptosis in HeLa HIV vpr cell, HeLa HIV vpr-FS cell and HeLa pcDNA3.1 cell were monitored by flow cytometry and the DNA fragmentation was analyzed by agarose gel electrophoresis. Results BamH Ⅰ and Hind Ⅲ cleavaged products of pcDNA3.1-vpr and pcDNA3.1-vpr-Fincluded 342 bp length fragments suggesting that the length of DNA sequence containing HIV vpr (HIV vpr-FS) within pcDNA3.1 was the same as theoretical length. The HeLa cells transfected by pcDNA3.1-vpr or pcDNA3, l-vpr-FS and selected with G418 could express HIV vpr or HIV vpr-FS by RT-PCR, and express HIV Vpr or HIV Vpr-FS protein by Western blot. The results of flow cytometry and DNA fragmentation showed that there was significant different in the number of apoptotic cells between HeLa HIV vpr cell and HeLa HIV vpr-FS cell, but the difference between HeLa HIV vpr-FS cell and control group was not obvious. Conclusion Recombinant plasmids pcDNA3.1-vpr and pcDNA3. 1-vpr-FS were constructed successfully, and the cell strain expressing HIV Vpr and HIV Vpr-FS proteins was established. The HIV Vpr could induce host cell apoptosis, while the mutant of Vpr did not or weakened this ability. This study provides foundation for further study on HIV vpr gene.