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 To investigate the importance of a nomogram model based on biomarkers and CT signs in the prediction of the invasive risk of ground glass nodules. Methods A total of 322 patients with ground glass nodule, including 240 and 82 patients in the model and verification groups, respectively, were retrospectively analyzed. Independent risk factors for the invasive risk of ground glass nodules were screened out after using single and multiple Logistic analysis. R software was used to construct the nomogram model, and clinical decision curve analysis (DCA), receiver operating curve (ROC), and calibration curve were used for internal and external verification of the model. Results In this study, the independent risk factors for the invasive risk of ground glass nodules included systemic immune-inflammation index (SII), CYFRA21-1, edge, vascular cluster sign, and nodular consolidation tumor ratio (CTR). The area under the ROC curve of the constructed nomogram model had a value of 0.946, and that of the external validation group reached 0.932, which suggests the good capability of the model in predicting the invasive risk of ground glass nodules. The model was internally verified through drawing of calibration curves of Bootstrap 1000 automatic sampling. The results showed that the consistency index between the model and actual curves reached 0.955, with a small absolute error and good fit. The DCA curve revealed a good clinical practicability. In addition, nodule margin, vascular cluster sign, and CTR were correlated with the grade of pathological subtype of invasive adenocarcinoma. Conclusion A nomogram model based on biomarkers and CT signs has good value and clinical practicability in the prediction of the invasive risk of ground glass nodules.

Objective:To optimize indirect immunofluorescence on salt-split skin (IIF-SSS), and to evaluate its performance in detection of bullous pemphigoid (BP) antibodies.Methods:Normal human foreskin and non-foreskin skin tissues were used to prepare salt-split substrates under 3 different experimental conditions: traditional group rotated at 4 ℃ for 48 - 72 hours, low-temperature immersion group soaked at 4 ℃ for 48 - 72 hours, room-temperature immersion group soaked at 25 ℃ (range: 23 - 27 ℃) for 24 hours. Serum samples were obtained from 20 patients with bullous pemphigoid (BP) in Hospital of Dermatology, Chinese Academy of Medical Sciences between August 2019 and August 2020, and subjected to IIF on the intact skin or salt-split substrates by using a multiple dilution method. Paired-sample t test was used for comparisons of means between two paired samples. Results:No dermal-epidermal separation was observed in the substrates prepared in the low-temperature immersion group at 48 - 72 hours, while dermal-epidermal separation occurred in the lower lamina lucida of the foreskin and non-foreskin substrates in the room-temperature immersion group and the traditional group. For the 20 patients with BP, the reciprocal end-point titers ( M[ Q1, Q3]) detected with the salt-split non-foreskin skin and salt-split foreskin in the room-temperature immersion group, and with the salt-split non-foreskin skin in the traditional group were 5 120 (2 560, 17 920), 1 280 (640, 2 560), 1 280 (640, 2 560), respectively. Moreover, 19 (95%) patients with BP showed that the reciprocal end-point titers detected with the substrates in the room-temperature immersion group were 1 - 5 times those in the traditional group ( t = 8.04, P<0.001), suggesting that the performance of salt-split skin in the room-temperature immersion group was superior to that in the traditional group in the detection of BP antibodies; however, there was no significant difference in the reciprocal end-point titers of BP antibodies between the salt-split foreskin in the room-temperature immersion group and salt-split non-foreskin skin in the traditional group ( t<0.001, P>0.05). The reciprocal end-point titers in 20 BP sera detected by conventional IIF on the intact non-foreskin skin and foreskin were 320 (160, 640) and 480 (160, 1 120), respectively; the reciprocal end-point titers detected by IIF on the salt-split foreskin and non-foreskin skin in the room-temperature immersion group, as well as on the salt-split non-foreskin skin in the traditional group, were all consistent with or 1 - 7 times higher than those detected by conventional IIF ( t = 6.47, 14.83, 5.26, respectively, all P<0.001) . Conclusion:The soaking method at room temperature 25 ℃ (23 - 27 ℃) for preparing salt-split substrates has advantages of short duration and simple procedure, and the sensitivity of IIF-SSS using the substrates prepared by this method is equal or superior to the traditional salt-split method for detecting BP antibodies.

Objective:To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF).Methods:Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients.Results:Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs( P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion:HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.

Objective To evaluate the value of indirect immunofluorescence (IIF) on three different substrates including normal human skin (NS),monkey esophagus (ME) and salt-split human skin (SS) in the diagnosis of autoimmune subepidermal bullous diseases.Methods A total of 56 patients with autoimmune subepidermal bullous diseases,including 47 with bullous pemphigoid (BP),6 with epidermolysis bullosa acquisita (EBA),2 with linear IgA bullous dermatosis,and 1 with anti-P200 pemphigoid,were diagnosed in and enrolled from Department of Dermatology,Institute of Dermatology,Chinese Academy of Medical Sciences between January 2015 and December 2016.Seventy patients with pemphigus,15 patients with chronic eczema and 15 healthy adults served as controls.Blood samples collected from these patients and controls were subjected to IIF on three different substrates including NS,ME and SS,and the fluorescence deposition was observed.The sensitivities and specificities of IIF in the diagnosis of different subepidermal bullous diseases were compared.Statistical analysis was carried out with SPSS 13.0 software by using chi-square test for the comparison of enumeration data.Results IIF on NS or ME in the serum of patients with BP showed linear deposition of fluorescent material along the basement membrane zone.IIF on SS showed linear deposition of fluorescent material in the epidermis in the patients with BP,but in the dermis in the patients with EBA and anti-P200 pemphigoid.The sensitivities of IIF on NS,ME or SS in the diagnosis of subepidermal bullous diseases were 73.2％,60.7％ and 94.6％ respectively,and the specificities were 98.0％,100％ and 97.1％ respectively.There were significant differences among the sensitivities (x2 =18.2,P ＜ 0.05),but no significant difference was observed among the specificities (P ＞ 0.05).The diagnostic sensitivity of IIF on SS was significantly higher than that of IIF on NS or ME(x2 =8.0,16.7,both P ＜ 0.05).Conclusion In the diagnosis of autoimmune subepidermal bullous diseases,IIF on SS is superior to IIF on ME or NS.

Objective To evaluate the prevalence and risk factors of metabolic syndrome among hepatitis C patients in Chinese Han population .Methods This was a multicenter ,cross-sectional study . A total of 997 Chinese Han patients with hepatitis C virus (HCV) infection were enrolled .Demographic data ,anthropometric data and clinical parameters related to metabolic syndrome were collected .Statistical analysis was performed by t-test (normal distribution) or Mann-Whitney U two-sample test (non-normal distribution) and χ test .Binary logistic regression analyses were used to determine the parameters significantly related to metabolic syndrome .Results Among the 997 patients ,170 (17 .1%) patients were diagnosed with metabolic syndrome .Binary logistic regression showed that genotype 2 (OR＝1 .594 ;95% CI :1 .045－2 .431 , P＝ 0 .030) ,older age (OR＝ 1 .040 ;95% CI :1 .022 －1 .058 , P＜ 0 .01) , overweight (OR＝3 .876 ;95% CI :2 .593－5 .792 ,P＜0 .01) ,fatty liver history (OR＝2 .106 ;95% CI : 1 .384－3 .204 ,P＝0 .001) ,homeostasis model assessment insulin (HOMA-IR) (OR＝1 .263 ;95% CI :1 .118－1 .427 , P＜0 .01) ,fasting insulin (OR＝0 .949 ;95% CI :0 .915 －0 .985 , P＝0 .006) ,lower serum albumin level (OR＝0 .957 ;95% CI :0 .915 －1 .000 , P＝0 .049) and higher γ-GT level (OR＝1 .004 ;95% CI :1 .000 －1 .008 , P＝ 0 .0041 ) were all significantly associated with the presence of metabolic syndrome .Conclusions Hepatitis C patients with genotype 2 ,older age ,overweight ,fatty liver history ,higher HOMA-IR ,lower fasting insulin level ,lower serum albumin level or higher γ-GT level should be screened for metabolic syndrome .

Objective: To evaluate the efficacy and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily and dasabuvir (DSV) 250 mg twice daily combined with ribavirin in adult patients of Mainland China with chronic HCV genotype 1b infection and compensated cirrhosis. Methods: An open-label, multicenter, phase 3 clinical trial study was conducted in mainland China, Taiwan, and South Korea. Adult patients with compensated cirrhosis (Metavir score =F4) who were newly diagnosed and treated for hepatitis C virus genotype 1b infection with ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin for 12 weeks were included. Assessed SVR rate of patients obtained at 12 and 24 weeks after drug withdrawal. Efficacy and safety were evaluated in patients who received at least one time study drugs. Results: A total of 63 patients from mainland China were enrolled, 62 of whom (98.4%) had a baseline Child-Pugh score of 5 points. The overall rate of SVR12 and SVR24 in patients was 100% (95% CI: 94.3% to 100.0%). Most of the adverse events that occurred were mild. The incidence of common (≥10%) adverse events and laboratory abnormalities included elevated total bilirubin (36.5%), weakness (19.0%), elevated unconjugated bilirubin (19.0%) and conjugated bilirubin (17.5%), and anemia (14.3%). Three cases (4.8%) of patients experienced Grade ≥ 3 adverse events that were considered by the investigators to be unrelated to the study drug. None patients had adverse events leading to premature drug withdrawal. Conclusion Mainland Chinese patients with chronic HCV genotype 1b infection and compensated cirrhosis who were treated with OBV/PTV/r plus DSV combined with RBV for 12 weeks achieved 100 % SVR at 12 and 24 weeks after drug withdrawal. Tolerability and safety were good, and majority of adverse events were mild.

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 evaluate the two-dimensional shear wave elastography(2D SWE)in predicting the prognosis of the patients with acute-on-chronic hepatitis B liver failure(ACLF-HBV).[Methods]312 patients diagnosed with ACLF-HBV at the De-partment of Infectious Diseases in the Third Affiliated Hospital of Sun Yat-sen University from October 1st 2013 to December 31th 2015 were recruited. The baseline data of all patients,including 2D SWE,laboratory data,ultrasonographic data,Model for End-stage Liver Disease score(MELD),Child-Turcotte-Pugh score(CTP),and King′s College Hospital score(KCH),were collected when enrolled. All patients were followed up for at least 90 days and their clinical outcomes(recovering or worsening)were recorded. 2D SWE values of all patients were dynamically collected every 2~4 weeks during the follow-up until death,liver transplantation, or discharging from hospital.[Results]The worsening patients showed higher 2D SWE values than the recovering ones[(44.0 ± 7.5) kPa vs(36.8 ± 10.3)kPa,t=-6.5,P=0.000],2D SWE value less than 39.2 kPa could be a prediction of the patient′s recovery in 90 days.The predictive value of 2D SWE(AUROC=0.73)was higher than that of KCH(AUROC:0.65,z=2.1,P=0.033). Among all the dynamically measured patients,2D SWE rose from(42.1 ± 8.0)kPa to(47.5 ± 9.3)kPa in the worsening group during the 90-day follow-up,while nearly stable in the recovery group.[Conclusion]Noninvasive liver stiffness measurement by 2D SWE is a use-ful method in evaluating the prognosis of ACLF-HBV patients. Taking a cutoff of 39.2 kPa,patients with higher 2D SWE values could have worse clinical outcomes ,otherwise better. It seems that dynamically measuring 2D SWE values could also be helpful ,but more research in the future should be needed.