De novo combined lamivudine and adefovir dipivoxil therapy vs entecavir monotherapy for hepatitis B virus-related decompensated cirrhosis

AIM:To compare efficacy of combined lamivudine(LAM)and adefovir dipivoxil(ADV)therapy with that of entecavir(ETV)monotherapy for hepatitis B virus(HBV)-related decompensated liver cirrhosis.METHODS:A total of 120 na ve patients with HBVrelated decompensated cirrhosis participated in this study.Sixty patients were treated with combined LAM and ADV therapy(LAM+ADV group),while the other60 were treated with ETV monotherapy(ETV group)for two years.Tests for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time(PT),and ultrasonography or computed tomography scan of the liver were performed every1 to 3 mo.Repeated measure ANOVA and theχ2test were performed to compare the efficacy,side effects,and the cumulative survival rates at 48 and 96 wk.RESULTS:Forty-five patients in each group were observed for 96 wk.No significant differences in HBV DNA negative rates and alanine aminotransferase(ALT)normalization rates at weeks 48(χ2=2.12 and 2.88)and96(χ2=3.21 and 3.24)between the two groups were observed.Hepatitis B e antigen seroconversion rate in the LAM+ADV group at week 96 was significantly higher in the ETV group(43.5%vs 36.4%,χ2=4.09,P<0.05).Viral breakthrough occurred in 2 cases(4.4%)by week 48 and in 3 cases(6.7%)by week 96 in the LAM+ADV group,and no viral mutation was detected.In the ETV group,viral breakthrough occurred in 1 case(2.2%)at the end of week 96.An increase in albumin(F=18.9 and 17.3),decrease in total bilirubin and in ALT(F=16.5,17.1 and 23.7,24.8),reduced PT(F=22.7 and 24.5),and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores(F=18.5,17.8,and 24.2,23.8)were observed in both groups.The cumulative rates of mortality and liver transplantation were 16.7%(10/60)and 18.3%(11/60)in the LAM+ADV and ETV groups,respectively.CONCLUSION:Both LAM+ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,and decrease mortality.

Early kidney injury during long-term adefovir dipivoxil therapy for chronic hepatitis B

AIM: To evaluate urine β2-microglobulin(β2-M), retinol-binding protein(RBP) excretion, and renal impairment with adefovir dipivoxil(ADV) for chronic hepatitis B. METHODS: We enrolled 165 patients with chronic hepatitis B infection who were treated with ADV monotherapy(n = 90) or ADV plus lamivudine combination therapy(n = 75). An additional 165 chronic hepatitis B patients treated with entecavir were recruited as controls. We detected serum creatinine, urine β2-M, and RBP levels, and estimated the glomerular filtration rate(e GFR) at the initiation of antiviral therapy and every 6 mo for a period of five years. RESULTS: Urine β2-M abnormalities were observed in patients during the first(n = 3), second(n = 7), third(n = 11), fourth(n = 16), and fifth(n = 21) year of ADV treatment. Urinary RBP abnormalities were observed in patients during the first(n = 2), second(n = 8), third(n = 12), fourth(n = 15), and fifth(n = 22) year of ADV treatment. e GFR decreased 20%-30% from baseline in 20 patients, 30%-50% in 12 patients, and > 50% in 3 patients during the five years of treatment. Further analysis indicated that decreases in e GFR of ≥ 30% relative to the baseline level correlated significantly with urine RBP and β2-M abnormalities. In contrast, both serum creatinine and e GFR remained stable in patients treated with entecavir, and only one of these patients developed a urine β2-M abnormality, and two developed urine RBP abnormalities during the five years of treatment. CONCLUSION: Urine RBP and β2-M are biomarkers of renal injury during long-term ADV treatment for chronic hepatitis B, and indicate when treatment should be switched to entecavir.

A serum metabolomic analysis for diagnosis and biomarker discovery of primary biliary cirrhosis and autoimmune hepatitis

Because of the diversity of the dinical and laboratory manifestations, the diagnosis of autoimmune liver disease （AILD） remains a challenge in clinical practice. The value of metabolomics has been studied in the diagnosis of many diseases. The present study aimed to determine whether the metabolic profiles, based on ultraperformance liquid chromatography-mass spectrometry （UPLC-MS）, differed between autoimmune hepatitis （AIH） and primary biliary cir- rhosis （PBC）, to identify specific metabolomic markers, and to establish a model for the diagnosis of AIH and PBC. METHODS： Serum samples were collected from 20 patients with PBC, 19 patients with AIH, and 25 healthy individuals. UPLC-MS data of the samples were analyzed using principal component analysis, partial least squares discrimination analysis and or- thogonal partial least squares discrimination analysis. RESULTS： The partial least squares discrimination analysis model （R2y=0.991, Q2=0.943） was established between the AIH and PBC groups and exhibited both sensitivity and speci- ficity of 100%. Five groups of biomarkers were identified, in- eluding bile acids, free fatty acids, phosphatidylcholines, lyso- lecithins and sphingomyelin. Bile acids significantly increased in the AIH and PBC groups compared with the healthy con- trol group. The other biomarkers decreased in the AIH andPBC groups compared with those in the healthy control group. In addition, the biomarkers were downregulated in the AIH group compared with the PBC group. CONCLUSIONS： The biomarkers identified revealed the pathophysiological changes in AILD and helped to discrimi- nate between AIH and PBC. The predictability of this method suggests its potential application in the diagnosis of AILD.

Hepatitis B surface antigen levels during natural history of chronic hepatitis B: A Chinese perspective study

AIM: To determine the baseline hepatitis B surface antigen (HBsAg) levels during the different phases of chronic hepatitis B (CHB) patients in China.

Efficacy and Safety of Tenofovir Disoproxil Treatment for Chronic Hepatitis B Patients with Genotypic Resistance to Other Nucleoside Analogues： A Prospective Study

Background： Tenofovir disoproxil （TDF） is a promising salvage therapy for patients with chronic hepatitis B （CHB） who failed regimens of other nucleoside analogues （NAs）. In this study, we aimed to investigate the clinical efficacy and safety ofTDF monotherapy in Chinese CHB patients with genotypic resistance. Methods： A total of 33 CHB patients who had tailed treatment with other NAs and had genotypic resistance were switched to TDF monotherapy for 48 weeks. Patients＇ demographic data （age, sex, history of hepatitis B virus [HBV] therapy）, laboratory testing results （hepatitis B e antigen [HBeAg] status, HBV DNA levels, alanine aminotransferase [ALT] levels, serum creatinine, urinary protein, genotypic assay）, clinical symptoms, and liver color ultrasound examinations were collected for evaluation at day 0 （baseline） and the 12th, 24th, 36th, and 48th weeks after initiating treatment. Statistical analyses were carried out using rank sum test or rank correlation. Results： With regard to efficacy, the study found that all patients who switched to TDF monotherapy had undetectable HBV DNA levels after 48 weeks. In addition, patients with lower baseline HBV DNA levels realized earlier virological undetectability （r = 0.39, P = 0.030）. AET levels were normal in 30 of 33 patients （91%）. HBeAg negative conversion occurred in 7 of 25 patients （28%）, among whom HBeAg seroconversion （12%） and H BeAg seroclearance （16%） occurred. The time of complete virological response was significantly affected by the number of resistance loci （r = 0.36, P = 0.040）. Concerning safety, the study found that no adverse events were observed during the 48 weeks. Conclusion： TDF monotherapy is an effective and safe salvage treatment for CHB patients who are resistant to other NAs.

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.