Efficacy of combined therapy in patients with hepatitis B virus-related decompensated cirrhosis

AIM: To investigate the efficacy and safety of combined de novo lamivudine (LAM) and adefovir dipivoxil (ADV) therapy in hepatitis B virus (HBV)-related decompensated liver cirrhosis patients. METHODS: One hundred and forty patients with HBVrelated decompensated cirrhosis were recruited, 70 patients were treated with combined LAM and ADV de novo therapy, and the other 70 patients were treated with LAM alone as controls. The follow-up period was 144 wk. All patients with LAM resistance were shifted to ADV. RESULTS: The percentage of HBV-related decompensated cirrhosis patients with undetectable HBV DNA inde novo combination group was 51.6% (33/64), 84.2% (48/57), and 92.3% (49/53) by weeks 48, 96, and 144, respectively. In monotherapy group, HBV DNA negativity rate was 46.1% (30/65), 56.1% (32/57), and 39.2% (20/51) by weeks 48, 96 and 144, respectively. There was a significant difference between the two groups by weeks 96 and 144 (P = 0.012 and 0.001). The hepatitis B e antigen seroconversion rate was 28.1% (9/32), 40.0% (12/30), and 53.6% (15/28) in the combination group by weeks 48, 96 and 144, respectively, and 24.2% (8/33), 31.0% (9/29), and 37.0% (10/27) by weeks 48, 96 and 144, respectively, in monotherapy group. A total of 68.6% (44/64), 84.2% (48/57), and 92.5% (49/53) patients achieved alanine aminotransferase (ALT) normalization by weeks 48, 96 and 144, respectively in the combination group. In monotherpy group, the ALT normalization rate was 64.6% (42/65) by week 48, 73.7% (42/57) by week 96, and 80.4% (41/51) by week 144. No patients in the combination group exhibited detectable resistance for at least 144 wk. The cumulative resistance rate in monotherapy group at weeks 48, 96, and 144 was 20.0%, 36.8%, and 56.9%. Both combination group and monotherapy group demonstrated an improvement in Child-Turcotte Pugh and Model for End-Stage Liver Disease scores at weeks 48, 96, and 144. All patients tolerated both combination and monotherapy. The ceratinine levels and glomerular filtration rate remained normal in all patients during the follow-up period. CONCLUSION: In HBV-related decompensated liver cirrhosis patients, the combined de novo LAM and ADV therapy is more efficacious and safer compared to LAM alone.

One hundred and ninety-two weeks treatment of entecavir maleate for Chinese chronic hepatitis B predominantly genotyped B or C

BACKGROUND Entecavir(ETV)is a potent and selective nucleotide analog with significant activity against hepatitis B virus(HBV).ETV maleate is a derivative compound of ETV and was reported to have an efficacy and safety profile that is comparable to ETV(Baraclude)when used in Chinese patients with chronic hepatitis B(CHB)in phase III clinical trials(Clinical Trials.gov number,NCT-01926288)at weeks 48,96,and 144.AIM To investigate the antiviral potency and safety of ETV maleate at week 192 in Chinese CHB patients predominantly genotyped B or C.METHODS In this double-blind study,we randomly assigned patients to receive 0.5 mg/d ETV(Group A)or ETV maleate(Group B)(ratio,1:1),each with a placebo tablet for 48 wk.Then,all patients received open-label treatment with 0.5 mg/d ETV maleate starting at week 49.The primary efficacy endpoint was the reduction in HBV DNA levels from baseline.Secondary endpoints included the proportion of patients with undetectable HBV DNA(<20 IU/m L),serologic response,serum alanine aminotransferase(ALT)normalization and development of resistance mutations.RESULTS Two hundred eighteen patients who were hepatitis B e antigen(HBe Ag)positive and 57 who were HBe Ag negative were analyzed and predominantly presented with genotype B(49.82%)or C(48.73%).For the HBe Ag-positive CHB patients,the mean HBV DNA level decrease(6.61 Log10 IU/m L vs 6.69 Log10 IU/m L,P>0.05),viral suppression with HBV DNA<20 IU/m L(83.33%vs 79.17%,P>0.05)and HBe Ag seroconversion(28.77%vs 20.00%,P>0.05)occurred similarly between Groups A and B at week 192.However,there was a significant difference in the proportion of patients with normal ALT levels(91.14%vs 78.38%,P<0.05).For the HBe Ag-negative CHB patients,no significant difference was found between Groups A and B at week 192 in terms of reductions in HBV DNA levels from baseline(6.05 Log10 IU/m L vs 6.03 Log10 IU/m L,P>0.05),percentages of patients who achieved undetectable HBV DNA(100%vs 100%,P>0.05)and rates of ALT normalization(95.65%vs 100.00%,P>0.05).Safety and adverse event profiles were similar between Groups A and B.Two HBe Ag-positive patients in Group A and 5 in Group B developed genotypic resistance to ETV.CONCLUSION Long-term ETV maleate treatment for up to 192 wk is effective and safe in Chinese CHB patients predominantly genotyped as B or C.

Transmission risk of patients with COVID-19 meeting discharge criteria should be interpreted with caution

目前全球新型冠状病毒流行形势仍严峻且持续恶化。评估符合出院标准的2019冠状病毒病(COVID-19)患者的传染性对于疾病控制至关重要。本研究报告两例核酸检测结果与临床表现及影像学表现不相符的患者,以此来呼吁临床工作者谨慎考虑符合出院标准的COVID-19患者的传染性。

Interferon-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients: a preliminary matched case-control study

Background:Currently,there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Because of its broad antiviral activity,interferon(IFN)should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019(COVID-19),especially while COVID-19-specific therapies are still under development.Methods:Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital,School of Medicine,Zhejiang University in Hangzhou,China,from January 19 to February 19,2020 were enrolled in a retrospective study.The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2 b inhalation treatment after admission.Propensity-score matching was used to balance the confounding factors.Results:A total of 104 confirmed COVID-19 patients,68 in the IFN group and 36 in the control group,were enrolled.Less hypertension(27.9%vs.55.6%,P=0.006),dyspnea(8.8%vs.25.0%,P=0.025),or diarrhea(4.4%vs.19.4%,P=0.030)was observed in the IFN group.Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group.Glucocorticoid dosage was lower in the IFN group(median,40 vs.80 mg/d,P=0.025).Compared to the control group,fewer patients in the IFN group were ventilated(13.2%vs.33.3%,P=0.015)and admitted to intensive care unit(ICU)(16.2%vs.44.4%,P=0.002).There were also fewer critical patients in the IFN group(7.4%vs.25.0%,P=0.017)upon admission.Although complications during admission process were comparable between groups,the discharge rate(85.3%vs.66.7%,P=0.027)was higher and the hospitalization time(16 vs.21 d,P=0.015)was shorter in the IFN group.When other confounding factors were not considered,virus shedding time(10 vs.13 d,P=0.014)was also shorter in the IFN group.However,when the influence of other factors was eliminated using propensity score matching,virus shedding time was not significantly shorter than that of the control group(12 vs.15 d,P=0.206).Conclusions:IFN-α2 b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.

Comparison of epidemiological and clinical characteristics of COVID-19 patients with and without Wuhan exposure history in Zhejiang Province,China

Background:A novel coronavirus called severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),first identified in Wuhan,China,has been rapidly spreading around the world.This study investigates the epidemiological and clinical characteristics of coronavirus disease 2019(COVID-19)patients in Zhejiang Province who did or did not have a history of Wuhan exposure.Methods:We collected data from medical records of confirmed COVID-19 patients in Zhejiang Province from Jan.17 to Feb.7,2020 and analyzed epidemiological,clinical,and treatment data of those with and without recorded recent exposure in Wuhan.Results:Patients in the control group were older than those in the exposure group((48.19±16.13)years vs.(43.47±13.12)years,P<0.001),and more were over 65 years old(15.95%control vs.5.60%exposure,P<0.001).The rate of clustered onset was also significantly higher in the control group than in the exposure group(31.39%vs.18.66%,P<0.001).The symptom of a sore throat in patients in the exposure group was significantly higher than that in the control group(17.30%vs.10.89%,P=0.01);however,headache in the exposure group was significantly lower than that in the control group(6.87%vs.12.15%,P=0.015).More patients in the exposure group had a significantly lower level of lactate dehydrogenase(LDH)and aspartate aminotransferase(AST)than those in the control group.There was no significant difference in any degree of COVID-19 including mild,severe,and critical between the two groups.Conclusions:From the perspective of epidemiological and clinical characteristics,there was no significant difference between COVID-19 patients with and without Wuhan exposure history.

Clinical characteristics of different subtypes and risk factors for the severity of illness in patients with COVID-19 in Zhejiang, China

Background The outbreak of coronavirus disease 2019(COVID-19)is now becoming an enormous threat to public health.The clinical spectrum of COVID-19 is extensive,of which critical cases are with rapid disease progression and high mortality.The aim of our study is to summarize the characteristics of different subtypes and explore risk factors of illness severity for early identification and prompt treatment.Methods In this retrospective study,we collected data of patients confirmed COVID-19 in Zhejiang Province from 17 January to 12 February 2020.According to the definition of clinical classification,we divided confirmed cases into four types,and summarize epidemiological and clinical characteristics,laboratory and radiograph findings,treatments,and outcomes,respectively.Moreover,we used univariate and multivariate ordinal logistic regression models to explore risk factors for the severity of illness in patients with COVID-19.Results A total of 788 patients were enrolled in our study,of whom 52 cases(6.6%)were mild type,658 cases(83.5%)were common type,61 cases(7.2%)were severe type,and 17 cases(2.2%)were critical type.Multivariate ordinal logistic regression demonstrated increasing odds of the severity of illness in patients with COVID-19 associated with male(odds ratio[OR]=1.7,95%confidence interval[CI]:1.2–2.6 P=0.008),fever(OR=3.6,95%CI:2.1–6.3,P<0.001),cough(OR=1.7,95%CI:1.0–2.9,P=0.041),hemoptysis(OR=3.4,95%CI:1.1–10.3,P=0.032),gastrointestinal symptoms(OR=1.9,95%CI:1.0–3.5,P=0.047),hypertension(OR=2.6,95%CI:1.2–5.6,P=0.013).With the increase of age-grading,risk for the severity of illness was gradually higher(≤18 years[OR=1.0],19–40 years[OR=12.7,95%CI:4.5–36.0,P<0.001],41–65 years[OR=14.8,95%CI:5.2–42.1,P<0.001],≥66 years[OR=56.5,95%CI:17.1–186.5,P<0.001]).Conclusions Clinicians should pay close attention to these features in patients with COVID-19 including older age,male,fever,cough,hemoptysis,gastrointestinal symptoms and hypertension to identify the severity of illness as early as possible.

Safety of protease inhibitors and Arbidol for SARS-CoV-2 pneumonia in Zhejiang Province,China

目的:评价蛋白酶抑制剂联合阿比多尔的抗病毒方案在严重急性呼吸综合征冠状病毒2(SARS-CoV-2)肺炎患者中应用的安全性.创新点:首次评价了蛋白酶抑制剂联合阿比多尔的抗病毒方案在SARS-CoV-2肺炎患者中安全性良好.方法:回顾性分析了52例SARS-CoV-2肺炎患者的临床资料,分析患者入院时以及抗病毒治疗期间症状、肝功能及血脂水平等的变化.结论:该方案最常见的不良反应为消化道症状和血脂代谢异常,血清甘油三酯、总胆固醇和低密度脂蛋白胆固醇水平均较治疗前显著升高;与洛匹那韦/利托那韦相比,达芦那韦/考比司他对血脂代谢的负面影响较小;建议对使用蛋白酶抑制剂联合阿比多尔抗病毒方案的患者密切监测和随访血脂水平变化.

Erratum to:Transmission risk of patients with COVID-19 meeting discharge criteria should be interpreted with caution

The original version of this article unfortunately contained a mistake.For Fig.la in p.409,the citation of a reference,as well as the permission to reprint this picture,was missing.The correct version and the corresponding reference are given below:(a)Chest computed tomography(CT)image of Patient 1 on admission presents multiple ground-glass opacities distributed in the periphery of inferior lobe of both lungs.Reprinted from Zhang et al.(2020),with kind permission from Springer Nature.