Endoscopic Ruler for varix size measurement:A multicenter pilot study

BACKGROUND We invented Endoscopic Ruler,a new endoscopic device to measure the size of varices in patients with cirrhosis and portal hypertension.AIM To assess the feasibility and safety of Endoscopic Ruler,and evaluate the agreement on identifying large oesophageal varices(OV)between Endoscopic Ruler and the endoscopists,as well as the interobserver agreement on diagnosing large OV using Endoscopic Ruler.METHODS We prospectively and consecutively enrolled patients with cirrhosis from 11 hospitals,all of whom got esophagogastroduodenoscopy(EGD)with Endoscopic Ruler.The primary study outcome was a successful measurement of the size of varices using Endoscopic Ruler.The secondary outcomes included adverse events,operation time,the agreement of identifying large OV between the objective measurement of Endoscopic Ruler and the empirical reading of endoscopists,together with the interobserver agreement on diagnosing large OV by Endoscopic Ruler.RESULTS From November 2020 to April 2022,a total of 120 eligible patients with cirrhosis were recruited and all of them underwent EGD examinations with Endoscopic Ruler successfully without any adverse event.The median operation time of Endoscopic Ruler was 3.00 min[interquartile range(IQR):3.00 min].The kappa value between Endoscopic Ruler and the endoscopists while detecting large OV was 0.52,demonstrating a moderate agreement.The kappa value for diagnosing large OV using Endoscopic Ruler among the six independent observers was 0.77,demonstrating a substantial agreement.CONCLUSION The data demonstrates that Endoscopic Ruler is feasible and safe for measuring the size of varices in patients with cirrhosis and portal hypertension.Endoscopic Ruler is potential to promote the clinical practice of the two-grade classification system of OV.

Daclatasvir plus asunaprevir in treatment-na?ve patients with hepatitis C virus genotype 1b infection

AIM To assess daclatasvir plus asunaprevir(d UAL) in treatment-na?ve patients from China's Mainland, Russia and South Korea with hepatitis C virus(HCV) genotype 1 b infection. METHODS Patients were randomly assigned(3:1) to receive 24 wk of treatment with d UAL(daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period(immediate treatment arm) or following 12 wk of matching placebo(placebodeferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12(SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin(70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in d UAL-treated patients compared with placebo patients during the first 12 wk(doubleblind phase), and during 24 wk of d UAL in both arms combined.RESULTS In total, 207 patients were randomly assigned to immediate(n = 155) or placebo-deferred(n = 52) treatment. Most patients were Asian(86%), female(59%) and aged < 65 years(90%). Among them, 13% had cirrhosis, 32% had IL28 B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/m L. Among patients in the immediate treatment arm, SVR12 was achieved by 92%(95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate(70%). SVR12 was largely unaffected by cirrhosis(89%), age ≥ 65 years(92%), male sex(90%), baseline HCV RNA ≥ 6 million(89%) or IL28 B non-CC genotypes(96%), although SVR12 was higher among patients without(96%) than among those with(53%) baseline NS5 A resistanceassociated polymorphisms(at L31 or Y93 H). during the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving d UAL. during 24 wk of d UAL therapy(combined arms), the most common adverse events(≥ 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were infrequently observed, and all grade 3-4 aminotransferase abnormalities(alanine aminotransferase, n = 9; aspartate transaminase, n = 6) reversed within 8-11 d. Two patients discontinued d UAL treatment; one due to aminotransferase elevations, nausea, and jaundice and the other due to a fatal adverse event unrelated to treatment. There were no treatment-related deaths.CONCLUSION d UAL was well-tolerated during this phase 3 study, and SVR12 with d UAL treatment(92%) exceeded thehistorical SVR rate for peg-interferon plus ribavirin of 70%.

Phase Ⅱb trial of in vivo electroporation mediated dualplasmid hepatitis B virus DNA vaccine in chronic hepatitis B patients under lamivudine therapy

AIM To assess the efficacy and safety of in vivo electroporation(EP)-mediated dual-plasmid hepatitis B virus(HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine(LAM) in patients with chronic hepatitis B. METHODS Two hundred and twenty-five patients were randomized to receive either LAM + vaccine(vaccine group, n = 109) or LAM + placebo(control group, n = 116). LAM treatment lasted 72 wk. Patients received the DNA vaccine or placebo by intramuscular injection mediated by EP at weeks 12(start of treatment with vaccine or placebo, SOT), 16, 24, and 36(end of treatment with vaccine or placebo, EOT). RESULTS In the modified intent-to-treat population, morepatients had a decrease in HBV DNA > 2 log10 IU/m L in the vaccine group at week 12 after EOT compared with the control group. A trend toward a difference in the number of patients with undetectable HBV DNA at week 28 after EOT was obtained. Adverse events were similar. In the dynamic per-protocol set, which excluded adefovir(ADV) add-on cases at each time point instantly after ADV administration due to LAM antiviral failure, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 and 28 after EOT compared with the control group. More patients with undetectable HBV DNA at week 28 after EOT in the vaccine group were also observed. Among patients with a viral load < 1000 copies/mL at week 12, more patients achieved HBeA g seroconversion in the vaccine group than among controls at week 36 after EOT, as well as less virological breakthrough and YMDD mutations. CONCLUSION The primary endpoint was not achieved using the HBV DNA vaccine. The HBV DNA vaccine could only be beneficial in subjects that have achieved initial virological response under LAM chemotherapy.

High expression of type I inositol 1,4,5-trisphosphate receptor in the kidney of rats with hepatorenal syndrome

AIM To detect the expression of typeⅠ inositol 1,4,5-trisphosphate receptor(IP3 RI) in the kidney of rats with hepatorenal syndrome(HRS).METHODS One hundred and twenty-five Sprague-Dawley rats were randomly divided into four groups to receive an intravenous injection of D-galactosamine(D-Gal N) plus lipopolysaccharide(LPS; group G/L, n = 50), D-Gal N alone(group G, n = 25), LPS alone(group L, n = 25), and normal saline(group NS, n = 25), respectively.At 3, 6, 9, 12, and 24 h after injection, blood, liver, and kidney samples were collected. Hematoxylineosin staining of liver tissue was performed to assess hepatocyte necrosis. Electron microscopy was used to observe ultrastructural changes in the kidney. Western blot analysis and real-time PCR were performed to detect the expression of IP3 RI protein and m RNA in the kidney, respectively.RESULTS Hepatocyte necrosis was aggravated gradually, which was most significant at 12 h after treatment with D-galactosamine/lipopolysaccharide, and was characterized by massive hepatocyte necrosis. At the same time, serum levels of biochemical indicators including liver and kidney function indexes were all significantly changed. The structure of the renal glomerulus and tubules was normal at all time points. Western blot analysis indicated that IP3 RI protein expression began to rise at 3 h(P < 0.05) and peaked at 12 h(P < 0.01). Real-time PCR demonstrated that IP3 RI m RNA expression began to rise at 3 h(P < 0.05) and peaked at 9 h(P < 0.01).CONCLUSION IP3 RI protein expression is increased in the kidney of HRS rats, and may be regulated at the transcriptional level.

Epidemiological and clinical characteristics of fifty-six cases of COVID-19 in Liaoning Province, China

BACKGROUND Pneumonia of uncertain cause has been reported in Wuhan,China since the beginning of early December 2019.In early January 2020,a novel strain ofβ-coronavirus was identified by the Chinese Center for Disease Control and Prevention from the pharyngeal swab specimens of patients,which was recently named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).There is evidence of human-to-human transmission and familial cluster outbreak of SARSCoV-2 infection.The World Health Organization(WHO)recently declared the SARS-CoV-2 epidemic a global health emergency.As of February 17,2020,71329 laboratory-confirmed cases(in 25 countries,including the United States and Germany)have been reported globally.Other than its rapid transmission,the epidemiological and clinical characteristics of coronavirus disease 2019(COVID-19)remain unclear.In December 2019,coronavirus disease(named COVID-19 by the WHO)associated with the SARS-CoV-2 emerged in Wuhan,China and spread quickly across the country.AIM To analyze the epidemiological and clinical characteristics of confirmed cases of this disease in Liaoning province,a Chinese region about 1800 km north of Wuhan.METHODS The clinical data of 56 laboratory-confirmed COVID-19 cases due to 2019-nCoV infection were analyzed.The cases originated from eight cities in Liaoning province.RESULTS The median age of the patients was 45 years,and 57.1%of them were male.No patient had been in direct contact with wild animals.Among them,23 patients(41.1%)had resided in or traveled to Wuhan,27 cases(48.2%)had been in contact with confirmed COVID-19 patients,5 cases(8.9%)had been in contact with confirmed patients with a contact history to COVID-19 patients,and 1 case(1.8%)had no apparent history of exposure.Fever(75.0%)and cough(60.7%)were the most common symptoms.The typical manifestations in lung computed tomography(CT)included ground-glass opacity and patchy shadows,with 67.8%of them being bilateral.Among the patients in the cohort,78.6%showed reduction in their lymphocyte counts,57.1%showed increases in their C-reactive protein levels,and 50.0%showed decreases in their blood albumin levels.Eleven patients(19.6%)were admitted to intensive care unit,2 patients(3.5%)progressed to acute respiratory distress syndrome,4 patients(7.1%)were equipped with non-invasive mechanical ventilation,and 1 patient(1.8)received extracorporeal membrane oxygenation support.There were 5 mild cases(5/56,8.9%),40 moderate cases(40/56,71.4%),10 severe cases(10/56,17.9%),and 1 critical case(1/56,1.8%).No deaths were reported.CONCLUSION SARS-CoV-2 can be transmitted among humans.Most COVID-19 patients show symptoms of fever,cough,lymphocyte reduction,and typical lung CT manifestations.Most are moderate cases.The seriousness of the disease(as indicated by blood oxygen saturation,respiratory rate,oxygenation index,blood lymphocyte count,and lesions shown in lung CT)is related to history of living in or traveling to Wuhan,underlying diseases,admittance to intensive care unit,and mechanical ventilation.

An-Luo-Hua-Xian Pill Improves the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated with Entecavir

Background and Aims:Chronic hepatitis B(CHB)can cause liver fibrosis and lead to cirrhosis and cancer.As the effectiveness of antiviral therapy to reverse liver fibrosis is limited,We aimed to evaluate the effect of An-Luo-Hua-Xian pill(ALHX)on fibrosis regression in CHB patients treated with entecavir(ETV).Methods:Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX(ETV+ALHX)between October 1,2013 and December 31,2020.Demographic,laboratory,and liver histology data before and after 78 weeks of treatment were collected.The Ishak fibrosis score(F)was used and fibrosis regression required a decrease in F of≥1 after treatment.Results:A total of 780 patients were enrolled,and 394 with a second liver biopsy after treatment were included in the per-protocol population,132 in ETV group and 262 in ETV+ALHX group.After 78 weeks of treatment,the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients:124/211(58.8%)vs.45/98(45.9%),p=0.035.The percentage of patients with a decreased liver stiffness measurement(LSM)was higher in the ETV+ALHX group:156/211(73.9%)vs.62/98(63.%),p=0.056.Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression[odds ratio(OR)=1.94,p=0.018],and a family history of hepatocellular carcinoma was on the contrary.(OR=0.41,p=0.031).Conclusions:ETV combined with ALHX increased liver fibrosis regression in CHB patients.

3-year Treatment of Tenofovir Alafenamide vs.Tenofovir Disoproxil Fumarate for Chronic HBV Infection in China

Background and Aims:Tenofovir alafenamide(TAF)has similar efficacy to tenofovir disoproxil fumarate(TDF)but with improved renal and bone safety in chronic hepatitis B patients studied outside of China.We report 3-year results from two phase 3 studies with TAF in China(Clinicaltrials.gov:NCT02836249 and NCT02836236).Methods:Chinese hepatitis B e antigen(HBeAg)-positive and-negative chronic hepatitis B patients with viremia and elevated alanine aminotransferase were randomized 2:1 to TAF or TDF treatment groups and treated in a double-blind fashion for 144 weeks(3 years).Efficacy responses were assessed by individual study while safety was assessed by a pooled analysis.Results:Of the 334 patients(180 HBeAg-positive and 154 HBeAg-negative)randomized and treated,baseline characteristics were similar between groups.The overall mean age was 38 years and 73%were male.The mean HBV DNA was 6.4 log10 IU/mL.The median alanine aminotransferase was 88 U/L,and 37%had a history of antiviral use.At week 144,the proportion with HBV DNA<29 IU/mL was similar among the two groups,with TAF at 83%vs.TDF at 79%,and TAF at 93%vs.TDF at 92%for the HBeAg-positive and-negative patients,respectively.In each study,higher proportions of TAF than TDF patients showed normalized alanine aminotransferase(via the American Association for the Study of Liver Diseases and the China criteria)and showed loss of HBsAg;meanwhile,the HBeAg seroconversion rates were similar.Treatment was well-tolerated among the TAF patients,who showed a smaller median decline in creatinine clearance(−0.4 vs.−3.2 mL/min;p=0.014)and less percentage change in bone mineral density vs.TDF at hip(−0.95%vs.−1.93%)and spine(+0.35%vs.−1.40%).Conclusions:In chronic hepatitis B patients from China,TAF treatment provided efficacy similar to TDF but with better renal and bone safety at 3 years.

Noncontrast-enhanced MRI-based Noninvasive Score for Portal Hypertension(CHESS1802):An International Multicenter Study

Background and Aims:This study aimed to determine the performance of the non-invasive score using noncontrastenhanced MRI(CHESS-DIS score)for detecting portal hy-pertension in cirrhosis.Methods:In this international multicenter,diagnostic study(ClinicalTrials.gov,NCT03766880),patients with cirrhosis who had hepatic venous pressure gradient(HVPG)measurement and noncontrast-enhanced MRI were prospectively recruited from four university hospitals in China(n=4)and Turkey(n=1)between December 2018 and April 2019.A cohort of patients was retrospectively recruited from a university hospital in Italy between March 2015 and November 2017.After segmentation of the liver on fat-suppressed T1-weighted MRI maps,CHESS-DIS score was calculated automatically by an in-house developed code based on the quantification of liver surface nodularity.Results:A total of 149 patients were included,of which 124 were from four Chinese hospitals(training cohort)and 25 were from two international hospitals(validation cohort).A positive correlation between CHESS-DIS score and HVPG was found with the correlation coefficients of 0.36(p<0.0001)and 0.55(p<0.01)for the training and validation cohorts,respectively.The area under the receiver operating characteristic curve of CHESS-DIS score in detection of clinically significant portal hypertension(CSPH)was 0.81 and 0.9 in the training and validation cohorts,respectively.The intra-class correlation coefficients for assessing the inter-and intra-observer agreement were 0.846 and 0.841,respectively.Conclusions:A non-invasive score using noncontrast-enhanced MRI was developed and proved to be significantly correlated with invasive HVPG.Besides,this score could be used to detect CSPH in patients with cirrhosis.