Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective:Hepatic fibrosis is a common pathological basis for many chronic liver diseases and can progress to cirrhosis,a leading cause of mortality in liver diseases.Early identification and reversal of hepatic fibrosis are key in the treatment of chronic liver disease.This study aims to compare the expression levels of serum core fucosylated low molecular weight kininogen(LMWK-Fc)and alpha-galactosylated(α-Gal)antibodies in patients with hepatic fibrosis at different stages,and to evaluate their diagnostic efficacy for hepatic fibrosis. Methods:A retrospective analysis was conducted on 275 patients with chronic liver disease who visited the Department of Infectious Diseases at the Second Xiangya Hospital of Central South University between June 2022 and March 2023.Among these,115 patients underwent liver biopsy.Based on the extent of collagen deposition and its impact on liver structure and microcirculation,patients were staged from 0 to 4:S0(no significant collagen deposition in liver tissues;liver structure and microcirculation are normal),S1(mild collagen deposition in liver tissues,with partial disruption of lobule structure,but microcirculation remains largely normal),S2(moderate collagen deposition in liver tissues,with partial disruption of lobule structure and microcirculation),S3(extensive collagen deposition in liver tissues,with substantial disruption of lobule structure and microcirculation),and S4(development of cirrhosis,with heavy collagen deposition,complete disruption of lobule structure,and severe impairment of microcirculation).Patients were grouped as no fibrosis(S0),fibrosis(S1-S2),and significant fibrosis(S3-S4).For the 160 patients without liver biopsy,they were categorized based on liver stiffness measurement(LSM)value:no fibrosis(F0:LSM＜7.3 kPa),fibrosis(F1-F2:LSM 7.3-12.4 kPa),and significant fibrosis(F3-F4:LSM＞12.4 kPa).Demographic data(age,gender)and laboratory indicators(alanine transaminase,aspartate transaminase,gamma-glutamyl transferase,alkaline phosphatase,alpha-fetoprotein,platelet count)were collected to calculate the fibrosis-4 index(FIB-4)and aspartate aminotransferase-to-platelet ratio index(APRI).Serum LMWK-Fc and α-Gal antibodies were measured and compared across the groups,and their correlation with fibrosis severity was analyzed.The receiver operating characteristic(ROC)curve was used to assess the predictive value of serum LMWK-Fc and α-Gal antibody levels for hepatic fibrosis. Results:Among the 160 patients without complete liver biopsy,serum α-Gal antibody and LMWK-Fc levels increased progressively from the no fibrosis group to the significant fibrosis group,with statistically significant differences(P＜0.05).Among the 115 patients with liver biopsy,serum LMWK-Fc levels were significantly higher in the fibrosis group and the significant fibrosis groups compared with the no fibrosis group,and α-Gal antibody levels were significantly higher in the significant fibrosis group compared with the no fibrosis group and the fibrosis group(P＜0.001,P=0.032,respectively).Univariate and multivariate linear regression analyses showed that hepatic fibrosis was correlated with gender and LMWK-Fc levels(both P＜0.05),but not with age,α-Gal antibody levels,FIB-4,or APRI(all P＞0.05). Conclusion:The expression levels of serum LMWK-Fc and α-Gal antibodies vary across different stages of hepatic fibrosis,suggesting a potential association with fibrosis progression.LMWK-Fc levels have a certain predictive value for the diagnosis of hepatic fibrosis.

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.

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.

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.

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.
China ; Humans ; Liver Failure ; chemically induced ; diagnosis ; Logistic Models ; Predictive Value of Tests ; Prognosis ; ROC Curve ; Retrospective Studies ; Severity of Illness Index

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 .

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.

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.