Animals ; Intestines ; cytology ; drug effects ; physiology ; Meperidine ; pharmacology ; Mice ; Mice, Inbred Strains ; Muscle, Smooth ; drug effects ; physiology ; Rabbits

Objective:To analyze the effect of nucleos(t)ide analog (NAs) antiviral treatment on the clinical features and prognosis of patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC).Methods:A retrospective analysis was performed on the data of 450 HBV-HCC patients first diagnosed and treated in the Third Hospital of Hebei Medical University from January 2015 to January 2021, including 193 patients in the continuous NAs treatment group and 257 patients in the NAs treatment after hepatocellular carcinoma (HCC) group. The baseline data of the two groups were balanced by propensity score matching. The relapse-free survival rate of HCC was estimated by Kaplan-Meier method, and the risk factors for HCC recurrence were analyzed by Cox proportional risk models. Spearman correlation analysis was used to explore the association between clinical features of HCC and hepatitis B virus (HBV) DNA load in patients receiving continuous NAs treatment.Results:Before matching, the proportions of liver cirrhosis, body mass index≥25.0 kg/m 2, single tumor, maximum tumor diameter ≤5 cm, Child-Pugh grade A, China liver cancer staging Ⅰ in the continuous NAs treatment group were 93.8%(181/193), 45.1%(87/193), 70.5%(136/193), 82.4%(159/193), 74.6%(144/193) and 74.6%(144/193), respectively. All of them were higher than those in the NAs treatment after HCC group (87.5%(225/257), 44.0%(113/257), 61.1%(157/257), 55.3%(142/257), 63.8%(164/257) and 56.0%(144/257), respectively). The proportions of drinking history and portal vein tumor thrombi in the continuous NAs treatment group were 12.4%(24/193) and 3.1%(6/193), respectively, which were lower than 33.9%(87/257) and 10.5%(27/257) in the NAs treatment after HCC group.The differences were all statistically significant ( χ2=4.86, 7.58, 4.27, 36.63, 8.15, 21.05, 27.21 and 8.88, respectively, all P<0.05). After matching, the median relapse-free survival time of the patients in the continuous NAs treatment group and the NAs treatment after HCC group were 388 days and 277 days, respectively. The five-year cumulative relapse-free survival rates were 50.0% and 37.5%, respectively, with statistically significant difference ( χ2=5.30, P=0.021). Multivariate analysis showed that no antiviral therapy before diagnosis of HCC, multiple tumors, maximum tumor diameter ≥5 cm and palliative treatment were independent risk factors for HBV-HCC recurrence (hazard ratio ( HR)=1.509, 1.491, 0.446 and 1.472, respectively, all P<0.05). After matching, the maximum tumor diameter ( r=0.175, P=0.042), incidence of portal vein tumor thrombi ( r=0.210, P=0.014) and recurrence of HBV-HCC ( r=0.178, P=0.038) in the continuous NAs treatment group were positively correlated with HBV DNA load. Conclusions:Early initiation of NAs antiviral treatment can improve the tumor characteristics when the disease progresses to HBV-HCC, and improve the relapse-free survival rate of HBV-HCC patients. No antiviral therapy before diagnosis of HCC, multiple tumors, maximum tumor diameter ≥5 cm and palliative treatment are independent risk factors for HBV-HCC recurrence.

Objective: To explore the risk factors for prognosis in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), and to establish a prognostic model. Methods: A total of 193 patients diagnosed with HBV-ACLF who were admitted to the Department of Infectious Diseases of the Third Hospital of Hebei Medical University were collected from 1st January 2013 to 1st November 2018 as a derivation cohort. Thirty-five patients diagnosed with HBV-ACLF who were admitted to the Fifth Hospital of Shijiazhuang during the period from 1st July 2017 to 1st November 2018 were collected as a validation cohort. The survival condition of all patients at week 12 of admission was observed. The risk factors associated with short-term prognosis were analyzed by using multivariate logistic regression analysis, and a logistic regression equation prediction model was established and verified. The diagnostic performance of the prognostic model was evaluated using the receiver operating characteristic (ROC) curve, and was compared with model for end-stage liver disease (MELD) scoring system, Child-Turcotte-Pugh (CTP) scoring system, sequential organ failure assessment (SOFA) scoring system and chronic liver failure (CLIF)-SOFA scoring system. Results: Multivariate logistic regression analysis showed that age (odds ratio(OR)=2.133, 95% confidence interval(CI)1.033-4.405), total bilirubin (OR=3.371, 95%CI 1.610-7.060), serum creatinine (OR=4.448, 95%CI 1.697-11.661), hepatic encephalopathy (OR=5.313, 95%CI 2.463-11.461), and ascites (OR=2.959, 95%CI 1.410-6.210) were independent risk factors for predicting the short-term prognosis of patients with HBV-ACLF. The newly established logistic regression model (LRM)=-1.726+ 0.757×age+ 1.215×total bilirubin+ 1.049 2×serum creatinine+ 1.670×hepatic encephalopathy (with=1, without=0) + 1.085×ascites (with=1, without=0). The area under the ROC curve of the LRM for predicting the short-term prognosis of patients with HBV-ACLF was 0.82 (95%CI 0.76-0.88). Furthermore, the areas under the ROC curve of the models of MELD, CTP, SOFA, CLIF-SOFA were 0.67 (95%CI 0.60-0.75), 0.73 (95%CI 0.66-0.80), 0.77 (95%CI 0.70-0.83) and 0.72 (95%CI 0.65-0.80), respectively. The ROC-area under curve of the validation cohort was 0.81 (95%CI 0.65-0.97). Conclusions Age, total bilirubin, serum creatinine, hepatic encephalopathy, and ascites are independent risk factors for the prognosis of HBV-ACLF. The prognostic model established based on these factors can accurately predict the patients′ short-term prognosis, which is superior to MELD, CTP, SOFA and CLIF-SOFA.

Objective: To analyze the epidemiological characteristics and the molecular types of human adenovirus (HAdV) from influenza-like illness (ILI) samples with negative influenza virus in Xi'an from January 2013 to December 2015. Methods: Samples from patients with ILI were collected from two national influenza sentinel surveillance hospitals during 2013—2015 in Xi′an. HAdV was detected by real-time PCR, and then the positive samples were inoculated into Hep-2 cells to isolate the viruses. The amplified products were purified and sequenced of hexon gene, and the sequences were compared with the Genebank data and phylogenetic trees were constructed. Results: In 2367 samples, 88 samples were positive for HAdV, the positive rate was 3.72%. There were 7 subtypes detected, and the rates of each subtype are as follows: HAdV-1 was 9.09%, HAdV-2 was 22.73%, HAdV-3 was 23.86%, HAdV-4 was 5.68%, HAdV-5 was 7.95%, HAdV-6 was 3.41% and HAdV-7 was 1.14%. Males had higher infection rate than females, but there was no significant difference. The patients were divided into 6 groups according to age. There were 3 positive samples among those under 1 year of age, 36 positive samples among those 1 to 3 years old, 26 positive samples among those 4 to 6 years old, 16 positive samples in those 7 to 18 years old, 5 positive samples in 19 to 59 years old and 2 positive samples in those older than sixty years of age. HAdV infection was primarily confined to children under 7 years of age. Conclusions HAdV-3 and HAdV-2 were the dominant epidemic strains during 2013—2015 in Xi′an. Children younger than 7 years were the main susceptible population. HAdV infections circulate all year-round and there was no considerable seasonal variation.