Response-guided treatment of cirrhotic chronic hepatitis B patients: Multicenter prospective study

AIM: To observe the effect of response-guided add-on therapy with adefovir(ADV) and lamivudine(LAM) in cirrhotic hepatitis B(CHB) patients.METHODS: A total of 100 patients with CHB and cirrhosis were divided into three arms according to hepatitis B virus(HBV) DNA level after 24 wk LAM monotherapy: Arm A(complete response, HBV DNA ≤ 60 IU/m L, n = 49), Arm B(partial response, HBV DNA: 60-2000 IU/m L, n = 31) and Arm C(inadequate response, HBV DNA > 2000 IU/m L, n = 20). ADV was added to LAM at week 48 in Arms A and B, but at week 24 in Arm C. Virological response, YMDD mutations, biochemical response, and liver function were evaluated.RESULTS: Comparison of the three arms demonstrated that early complete virologic response at week 24was associated with maintained viral suppression(undetectable rate of HBV DNA at week 144 was 95.96%, 66.67% and 35.29%, respectively, P = 0.000) and reduced YMDD mutations(mutation rate at week 144 was 0%, 3.23% and 15%, respectively, P = 0.015) after 144 wk treatment. For patients who failed to achieve complete virological response at week 24, switching to combination therapy further decreased HBV DNA level by 1 log10 IU/m L. All three arms obtained biochemical benefits including decline of alanine aminotransferase and elevation of albumin. In patients who developed HBV DNA breakthrough for YMDD mutations, ADV add-on therapy did not induce further multiple drug resistance to LAM or ADV.CONCLUSION: Optimized response-guided add-on therapy of ADV and LAM maintains long-term suppression of HBV DNA and improves liver function in CHB patients with compensated liver cirrhosis.

Infection within 2 weeks before liver transplantation closely related to prognosis of posttransplant infection:A single-center retrospective observational study in China

Background:Infections still represent the main factors influencing morbidity and mortality following liver transplantation.This study aimed to evaluate the incidence and risk factors for infection and survival after liver transplantation.Methods:We retrospectively examined medical records in 210 liver recipients who underwent liver transplantation between April 2015 and October 2017 in our hospital.Clinical manifestations and results of pathogen detection test were used to define infection.We analyzed the prevalence,risk factors and prognosis of patients with infection.Results:The median follow-up was 214 days;the incidence of infection after liver transplantation was 46.7%(n=98)which included pneumonia(43.4%),biliary tract infection(21.9%),peritonitis(21.4%)and bloodstream infection(7.6%).Among the pathogens in pneumonia,the most frequently isolated was Acinetobacter baumanii(23.5%)and Klebsiella pneumoniae(21.2%).Model for end-stage liver disease(MELD)score(OR=1.083,95%CI:1.045–1.123;P<0.001),biliary complication(OR=4.725,95%CI:1.119–19.947;P=0.035)and duration of drainage tube(OR=1.040,95%CI:1.007–1.074;P=0.017)were independent risk factors for posttransplant infection.All-cause mortality was 11.0%(n=23).The prognostic factors for postoperative infection in liver recipients were prior-transplant infection,especially pneumonia within 2 weeks before transplantation.Kaplan-Meier curves of survival showed that recipients within 2 weeks prior infection had a significantly lower cumulative survival rate compared with those without infection(65.2%vs.90.0%;hazard ratio:4.480;P<0.001).Conclusions:Infection,especially pneumonia within 2 weeks before transplantation,complication with impaired renal function and MELD score after 7 days of transplantation was an independent prognostic factor for postoperative infection in liver transplant recipients.

Histological outcome for chronic hepatitis B patients treated with entecavir vs lamivudine-based therapy

AIM: To compare the histological outcome of chronic hepatitis B(CHB) patients treated with entecavir(ETV) or lamivudine(LAM)-based therapy.METHODS: We conducted a retrospective analysis of data from 42 CHB patients with advanced fibrosis(baseline Ishak score ≥ 2) or cirrhosis who were treated with ETV or LAM-based therapy in Beilun People's Hospital, Ningbo between January 2005 and May 2012. The patients enrolled were more than 16 years of age and underwent a minimum of 12 mo of antiviral therapy. We collected data on the baselinecharacteristics of each patient and obtained paired liver biopsies pre- and post-treatment. The Knodell scoring system and Ishak fibrosis scores were used to evaluate each example. An improvement or worsening of necroinflammation was defined as ≥ 2-point change in the Knodell inflammatory score. The progression or regression of fibrosis was defined as ≥ 1-point change in the Ishak fibrosis score. The continuous variables were compared using t-test or Mann-Whitney test, and the binary variables were compared using χ2 test or Fisher's exact test. The results of paired liver biopsies were compared with a Wilcoxon signed rank test.RESULTS: Nineteen patients were treated with ETV and 23 patients were treated with LAM therapy for a mean duration of 39 and 42 mo, respectively. After long-term antiviral treatment, 94.74%(18/19) of the patients in the ETV arm and 95.65%(22/23) in the LAM arm achieved an HBV DNA level less than 1000 IU/m L. The majority of the patients(94.74% in the ETV arm and 73.91% in the LAM arm) had normalized ALT levels. The median Knodell necroinflammatory score decreased from 11 to 0 in the patients receiving ETV, and the median Knodell score decreased from 9 to 3 in the patients receiving LAM(P = 0.0002 and < 0.0001, respectively). The median Ishak fibrosis score showed a 1-point reduction in ETV-treated patients and a 2-point reduction in LAM-treated patients(P = 0.0019 and 0.0205, respectively). The patients receiving ETV showed a more significant improvement in necroinflammation than the LAM-treated patients(P = 0.0003). However, there was no significant difference in fibrotic improvement between the two arms. Furthermore, two patients in each arm achieved a fibrosis score of 0 post-treatment, which indicates a full reversion of fibrosis after antiviral therapy.CONCLUSION: CHB patients with advanced fibrosis or cirrhosis benefit from antiviral treatment. ETV is superior to LAM therapy in improving necroinflammatory but not fibrotic outcome.

Tenofovir disoproxil fumarate in Chinese chronic hepatitis B patients:Results of a multicenter,double-blind,double-dummy,clinical trial at 96 weeks

BACKGROUND Tenofovir disoproxil fumarate(TDF)is a prodrug of a nucleotide analogue.As an antiviral drug,TDF has been proposed in the first-line treatment of chronic hepatitis B(CHB).Qingzhong,a brand name of TDF,commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd.,and Viread,another brand name of TDF,commercialized by GlaxoSmithKline,have both been approved by the State Food and Drug Administration,China.AIM To investigate the efficacy and safety of the two TDF agents in the treatment of Chinese CHB patients.METHODS This trial was registered at ClinicalTrials.gov with the identifier number of NCT02287857.A total of 330 Chinese CHB patients,among which 232 were hepatitis B e antigen(HBeAg)-positive,were included in this 5-year-long,multicenter,double-blinded,double-dummy,randomized-controlled,noninferiority phase III trial.The participants were initially randomized into two groups:Group A(n=161),in which the participants received 300 mg Qingzhong once a day for 48 wk;and Group B,in which the participants received 300 mg Viread once a day for 48 wk.Starting from week 49,all the participants in Groups A and B received 300 mg Qingzhong once a day until the 96th week.In this study,the primary endpoint was the decrease in plasma level of hepatitis B virus(HBV)DNA at the 96th week,while the secondary endpoints were suppression of HBV replication,alanine aminotransferase(ALT)normalization,HBeAg loss,and HBeAg seroconversion rates.RESULTS For the participants with HBeAg-positive CHB,the decrease in mean HBV DNA level relative to the baseline value was comparable between Groups A and B(5.77 vs 5.73 log10 IU/mL,P>0.05)at the 96th week.In addition,similar percentages of HBeAg-positive participants in the two groups exhibited undetectable levels of HBV DNA,HBeAg loss,and HBeAg seroconversion(71.05%vs 77.97%,31.00%vs 27.27%,and 20.22%vs 15.79%,respectively,in Group A vs Group B;P>0.05).For the participants with HBeAg-negative CHB,the decrease in mean HBV DNA level relative to the baseline value was also comparable between Groups A and B(4.46 vs 4.70 log10 IU/mL,P>0.05)at the 96th week.In addition,similar percentages of HBeAg-negative participants in the two groups exhibited undetectable levels of HBV DNA(87.23%vs 94.12%in Group A vs Group B,respectively;P>0.05).Finally,similar percentages of CHB patients(HBeAg-positive or HBeAg-negative)in the two groups exhibited normalization of ALT(80.14%vs 84.57%in Group A vs Group B,respectively;P>0.05),and similar incidences of adverse events were observed(106 vs 104 in Group A vs Group B,respectively;P>0.05).CONCLUSION Both Qingzhong and Viread are effective and safe in the treatment of Chinese CHB patients according to the results of our clinical trial.

Evaluation of Endotoxin in Culture Medium for Human in vitro Fertilization

Objective To determine whether the presence of bacterial endotoxin in the commercial culture media utilized for human in vitro fertilization (IVF), and evaluate the difference in detecting endotoxin in culture medium between the human sperm motility assay and the 2-cell mouse embryo assay. Methods Thirty-six batches of culture media commonly used in IVF laboratories from 3 manufacturers were determined for the presence of endotoxin before using the medium for the assisted reproductive programs (group A). After being used, 25 specimens among above media were also tested (group B). The chromogenic limulus amoebocyte lysate (LAL) test was used for quantification the content of endotoxin. In addition, the human sperm motility assay was compared with the 2-cell mouse embryo assay to evaluate the difference in detecting endotoxin in culture medium. Results Endotoxin was not detected in group A. However, 2 samples were positive in group B. Sperm did not show significant change in motility in group A during 24 h of incubation when compared with the control (P>0.05). However, in group A the 2-cell embryo development to blastocyst was suppressed in 3 batches of media. Conclusions Regular screening of each batch of culture medium should be performed if possible although there was no evidence of endotoxin contamination in commercially prepared pre-tested media. Culture environment should be stringently controlled in case the medium is polluted. The sensitivity of the sperm motility assay was lower than that of the mouse embryo assay for detecting low levels of endotoxin or toxic compounds in the medium.

Expression and significance of NF-κB, TGF-β1 and other biochemical indicators in patients with polycystic ovary syndrome

Objective: To explore the expression and significance of serum NF-κB, TGF-β1, VEGF, sFlt-1, leptin, adiponectin, LH, FSH and PRL in patients with polycystic ovary syndrome by comparing serum levels of the various biochemical indicators among the cases. Methods:A total of 30 patients with polycystic ovary syndrome in our hospital from May 2016 to June 2017 were selected as the observation group. At the same time, 30 patients who were treated for other causes of infertility or tubal ovarian cysts were selected as control group. ELISA method was used to detect the serum levels of NF-κB, TGF-β1, VEGF, sFlt-1. Radioimmunoassay was used to detect the serum levels of leptin and adiponectin. Chemiluminescence immunoassay was used to detect the serum levels of LH, FSH and PRL. Results: The serum NF-κB, TGF-β1, VEGF, leptin, LH levels of observation group were significantly higher than control group. The serum sFlt-1, adiponectin, FSH and PRL levels of observation group were significantly lower than control group. The differences were statistically significant. Conclusion: NF-κB, TGF-β1, VEGF, sFlt-1, leptin, adiponectin, LH, FSH and PRL may play a role in pathogenesis of PCOS.

Neutralizing antibodies against SARS-CoV-2 virus after vaccination in patients with neurofibromatosis type 1

Dear Editor,The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has triggered a COVID-19 pandemic that has caused high morbidity and mortality worldwide.1 COVID-19 vaccines are urgently needed to protect all susceptible populations from SARS-CoV-2 infection.Neurofibromatosis type 1(NF1)is a hereditary dominant disease that affects approximately one in every 3000 newborns.

Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients

Background:A patient’s infectivity is determined by the presence of the virus in different body fluids,secretions,and excreta.The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease(COVID-19)remain unclear.This study analyzed the clearance time and factors influencing 2019 novel coronavirus(2019-nCoV)RNA in different samples from patients with COVID-19,providing further evidence to improve the management of patients during convalescence.Methods:The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20,2020 to February 10,2020 were collected retrospectively.The reverse transcription polymerase chain reaction(RT-PCR)results for patients’oropharyngeal swab,stool,urine,and serum samples were collected and analyzed.Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive(minimum 24 h sampling interval)negative RT-PCR results for viral RNA from oropharyngeal swabs.The effects of cluster of differentiation 4(CD4)+T lymphocytes,inflammatory indicators,and glucocorticoid treatment on viral nucleic acid clearance were analyzed.Results:In the 292 confirmed cases,66 patients recovered after treatment and were included in our study.In total,28(42.4%)women and 38 men(57.6%)with a median age of 44.0(34.0-62.0)years were analyzed.After in-hospital treatment,patients’inflammatory indicators decreased with improved clinical condition.The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5(6.0-11.0)days.By February 10,2020,11 convalescent patients(16.7%)still tested positive for viral RNA from stool specimens and the other 55 patients’stool specimens were negative for 2019-nCoV following a median duration of 11.0(9.0-16.0)days after symptom onset.Among these 55 patients,43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs,with a median delay of 2.0(1.0-4.0)days.Results for only four(6.9%)urine samples were positive for viral nucleic acid out of 58 cases;viral RNA was still present in three patients’urine specimens after throat swabs were negative.Using a multiple linear regression model(F=2.669,P=0.044,and adjusted R2=0.122),the analysis showed that the CD4+T lymphocyte count may help predict the duration of viral RNA detection in patients’stools(t=-2.699,P=0.010).The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group(15 days vs.8.0 days,respectively;t=2.550,P=0.013)and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group(20 days vs.11 days,respectively;t=4.631,P<0.001).There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results(P>0.05).Conclusions:In brief,as the clearance of viral RNA in patients’stools was delayed compared to that in oropharyngeal swabs,it is important to identify viral RNA in feces during convalescence.Because of the delayed clearance of viral RNA in the glucocorticoid treatment group,glucocorticoids are not recommended in the treatment of COVID-19,especially for mild disease.The duration of RNA detection may relate to host cell immunity.

The role of prophylactic antibiotics in hepatitis B virus-related acute-on-chronic liver failure patients at risk of bacterial infection: a retrospective study

Background:Acute-on-chronic liver failure(ACLF)is characterized by an excessive systemic inflammatory response and organ failure and has high mortality.Bacterial infections(Bis)worsen the clinical course of ACLF and carry a poor prognosis in ACLF patients.The efficacy of third-generation cephalosporins has been challenged in recent years.The aim of this study was to characterize the difference between ACLF patients with and without Bis and to provide a reference for medical intervention.

Incidence and Potential Causes affecting Monozygotic Twin Formation Following in vitro Fertilization and Embryo Transfer

Objectives To study the incidence and potential causes of monozygotic twins after in vitro fertilization and embryo transfer(IVF-ET).Methods A retrospective study was performed on women carrying monozygotic twins(MZTs) after conventional IVF-ET treatment at the Third Affiliated Hospital of Guangzhou Medical College in China from January 2003 to May 2009.The incidence and the miscarriage rate for MZTs following IVF-ET were examined in relation to maternal age,duration of infertility,type and dose of hormone treatment,conventional IVF-ET cycles versus intracytoplasmic sperm injection(ICSI) cycles,the use of fresh or frozen-thawed embryos,and day(post-fertilization) of embryo transfer.Results Sixteen MZT pregnancies occurred in 2 161 patients(incidence of 0.74%),of which 5 miscarried(31.25%).No significant difference was found between MZT and non-MZT groups in terms of maternal age,duration of infertility,duration of gonadotropin(Gn) administration,dosage of Gn,number of oocytes retrieved,number of oocytes fertilized,or number of embryos transferred(P>0.05).The incidence of MZT was not statistically different between conventional IVF-ET cycles and ICSI cycles,between fresh embryos transfer cycles and frozen-thawed embryo cycles,or between different transfer days(P>0.05).Conclusion The incidence of MZTs following IVF-ET treatment greatly exceeds that observed following spontaneous conception.Intracytoplasmic sperm injection,frozenthawed procedures,and embryo transfer on different days were not correlated with an increased incidence of MZT pregnancies.

Impact of Blood Clot in Oocyte-Corona-Cumulus Complex during in vitro Fertilization and Embryo Transfer

Objective To study the impact of blood clots in the oocyte-corona-cumulus complexes (OCCC) during in vitro fertilization and embryo transfer (IVF-ET). Methods The OCCCs were harvested from the patients undergoing long protocol ovarian hyperstimulation. The OCCCs with blood clots removed or not, were randomly grouped into A or B. The OCCCs without blood clots were group C (the control). Results The patient's age, infertility duration, the average GN consumption, the average days of superovulation and an average number of harvested oocytes showed no significant difference in the 3 groups. The fertilization rate and 2PN rate in group A were the highest, which were 85.4% and 71.1%, respectively, followed by group C, which were 77.5% and 64.9%, respectively. The lowest fertilization rate and 2PN rate were in group B, 75.8% and 62.2%, respectively. Those in group A were significantly higher than those in groups B and C (P<0.01), while there was no significant difference between group B and group C . The implantation rates and pregnancy rates showed no significant difference in the 3 groups after transplantation, even if group A got the highest rate among the 3 groups. Conclusion Removing the blood clots in OCCC can improve the outcome of IVF-ET without increasing the cost and complexity of the operation.