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Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is the template for HBV replication. Currently, there is a lack of therapeutic drugs that directly target cccDNA. Therefore, blocking cccDNA supplements as fast as possible and reducing the existing cccDNA is the key to achieving a complete cure of chronic hepatitis B. Previous studies have suggested that cccDNA had a long half-life, but a recent study showed that it only took a few months to update cycle of cccDNA pool, and its number was much less than previously predicted. In the future, with the advent of new antiviral drugs that can completely inhibit HBV replication, it is expected that the cccDNA pool will be completely cleared due to its supplement complete blockade, so as to achieve virological cure of chronic hepatitis B.
Subject(s)
Humans , Antiviral Agents/therapeutic use , DNA, Circular/genetics , DNA, Viral , Half-Life , Hepatitis B/drug therapy , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Virus ReplicationABSTRACT
Objective:To explore the early predictors for clinical cure by sequential combined interferon therapy in nucleos(t)ide analogues (NAs) experienced patients with chronic hepatitis B(CHB).Methods:CHB patients received NAs treatment≥one year with hepatitis B surface antigen (HBsAg) ≤1 500 IU/mL, hepatitis B e antigen (HBeAg) negative and hepatitis B virus (HBV) DNA <100 IU/mL in the Third Affiliated Hospital of Sun Yat-sen University from June 2016 to September 2019 were included. According to the different treatment regimens, the patients were divided into interferon alone for 48 weeks group (group A), interferon combined with NAs for 12 weeks and continued NAs treatment for 48 weeks group (group B), interferon combined with NAs for 48 weeks group (group C). Basic data such as age and gender of patients were collected. HBsAg, hepatitis B surface antibody (anti-HBs) and alanine aminotransferase (ALT) were monitored at week 4, 8, 12, 24, 36 and 48. The decline of HBsAg from baseline, and the rates of clinical cure at 48 weeks were analyzed. The independent sample t test, chi-square test and rank sum test were used for statistical analysis. Logistic regression analysis was used to achieve the early prediction index of clinical cure at week 48. Results:A total of 1 020 CHB patients were followed up regularly for at least five time points. The rates of clinical cure at week 48 in group A, B and C were 34.6%(157/454), 32.7%(69/211) and 33.5%(119/355), respectively, with no statistical significance ( χ2=0.25, P=0.883). Patients were divided into the cured group (345 cases) and the uncured group (675 cases) according to the clinical outcomes at week 48. The age ((38±13) years old vs (43±12) years old), baseline HBsAg (131.00(359.80) IU/mL vs 437.60(531.50) IU/mL) and the proportion of male patients (81.7%(282/345) vs 89.5%(604/675)) of patients in the cured group were all lower than those of patients in the uncured group. The differences were all statistically significant ( t=6.32, Z=12.67, χ2=11.99, respectively, all P<0.050). There were 212 patients in the cured group who achieved clinical cure within 24 weeks of treatment. The rate of clinical cure at 48 weeks in patients whose HBsAg at week 4 decreased from baseline was higher than that in patients with increased HBsAg (41.6%(149/358) vs 28.2%(108/383)). The difference was statistically significant ( χ2=14.13, P<0.001). The rate of clinical cure at week 48 in patients with HBsAg at week 12 decreased ≤34.03% of baseline was only 6.9%(13/188). Multivariate logistic regression analysis showed that age (odds ratio ( OR)=0.962, 95% confidence interval ( CI) 0.936 to 0.989, P=0.006), HBsAg level at week 24 ( OR=0.950, 95% CI 0.934 to 0.966, P<0.001) and anti-HBs level at week 24 ( OR=1.012, 95% CI 1.005 to 1.019, P=0.001) were early predictors for clinical cure at week 48 of treatment in NAs experienced CHB patients. Conclusions:Clinical cure of NAs experienced CHB patients received sequential combined interferon therapy mostly occurs in the early stage (within 24 weeks). Age, HBsAg level at week 24, and anti-HBs level at week 24 are early predictors for clinical cure of 48-week sequential combined interferon treatment.
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Objective:To evaluate the risk factors of clinical cure and biochemical recurrence (BCR) after radical prostatectomy (RP).Methods:The clinical data of 896 patients who underwent RP at Peking University First Hospital from April 2001 to December 2020 were retrospectively analyzed. Average age was (65.90±6.3) years, median preoperative prostate specific antigen (PSA) was 10.75 (0.36-264.20) ng/ml, median prostate volume was 40.0 (12.0-220.9) ml, median PSA density (PSAD) was 0.27 (0.02-3.42) ng/(ml·g). Clinical staging: 432 cases in T 1c stage, 333 cases in T 2a/bstage, 76 cases in T 2c stage, and 55 cases in ≥T 3 stage. Preoperative Gleason score of biopsy: 193 cases in 3+ 3, 315 cases in 3+ 4, 162 cases in 4+ 3, 226 cases in ≥8. The RP surgery was operated by open or laparoscopic or robot-assisted approach. Clinical cure and BCR were used as the end points for analysis. Clinical cure was defined as a decrease in serum PSA level below 0.03 ng/ml 6 weeks after surgery. BCR was defined as the 2 consecutive serum PSA >0.2ng/ml during the follow-up after RP. Multivariate logistic regression was used to analyze the independent risk factors of clinical cure. The Kaplan-Meier method was used to draw the biochemical recurrence-free survival curve, the log-rank method was used for univariate analysis of BCR, and the Cox regression analysis was used for multivariate analysis. Results:All 896 patients were followed-up for 58 (5-241) months, 678 cases (75.7%) achieved clinical cure. Based on univariate analysis and multivariate analysis, among the preoperative indicators, whether the proportion of positive biopsy needles ≥33% ( P=0.007) and preoperative Gleason score of biopsy ( P=0.041) were independent risk factors of clinical cure. A total of 890 cases were included in the analysis of risk factors of BCR, of whom 172 cases (19.3%) had BCR. The 1-, 5-, and 10-year biochemical recurrence-free survival(BFS)rates were 98.1%, 83.1% and 68.4% respectively. The median BFS has not been reached, and the average BFS was 181 months (95% CI 172-189). The results of univariate and multivariate analysis showed that whether achieved clinical cure ( P=0.001) and postoperative pathological staging ( P<0.001) were independent risk factors of BCR. Conclusions:Whether the proportion of positive biopsy needles≥33% and preoperative Gleason score of biopsy were independent risk factors of clinical cure. Postoperative pathological staging and whether achieved clinical cure may be independent risk factors of BCR.
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roduction: The recent prevalence of dermatophytosis in India ranges from 36.6 to 78.4%. Itraconazole is commonly usedsystemic antifungal to treat dermatophytosis.Objective: The objective of the present study was to evaluate the effectiveness and safety of itraconazole given 100 mg twicedaily for the treatment of dermatophytosis.Materials and Methods: The present retrospective questionnaire-based survey was done, wherein dermatologists and generalphysicians were given survey questionnaire. Data analysis up to 4 weeks of treatment with itraconazole was considered forthis study. Efficacy evaluation was considered as percentage of patients achieving clinical cure.Results: A total of 150 doctors completed the survey involving 1100 patients. Out of 1100 patients, 341 patients (31%)responded well to topical therapy alone and were considered as clinically cured as per medical records. In remaining patientswho did not respond well to topical monotherapy, itraconazole was found to be added in 652 patients as 100 mg twice daily for4 weeks. Of these, 456 patients (70%) responded well to therapy in 4 weeks and were considered as clinically cured. Amongthe topical antifungals coprescribed with itraconazole, luliconazole was most commonly prescribed (49%). On comparison ofclinical cure rates in patients who received topical antifungal monotherapy (31%) and itraconazole cotherapy (70%), it was foundthat itraconazole cotherapy was better and the difference between the two therapies was statistically significant (P = 0.001).Conclusion: From the findings of the present analysis, clinical cure rates obtained with itraconazole were more than satisfactory.Although the standard duration of therapy ranges from 1 to 2 weeks, long-term treatment is warranted and that is with topicalantifungals and other supportive measures.
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Objective@#To study the changes in the functional connections of the central executive network in patients with depression after clinical cure.@*Methods@#Seventeen depression patients who met the clinical cure standard (patient group) and twenty-two healthy controls (control group) were selected.The baseline rs-fMRI data were collected from the healthy control group and the patient group respectively, and the rs-fMRI data in the patient group were collected again after 6 months.Compared the changes of central executive network function connection between the two groups.@*Results@#At baseline, there was a high functional connection in the left inferior parietal lobule(MNI: x, y, z=-39, -69, 33)and right insula(MNI: x, y, z=15, -45, 30) in the patient group compared with the control group.Compared with the baseline, there were high functional connections in part of the left inferior parietal lobe (MNI: x, y, z=-60, -48, 21) and the right dorsolateral prefrontal lobe (MNI: x, y, z=24, 18, 60), and low functional connections in part of the left inferior parietal lobe (MNI: x, y, z=-51, -69, 18) in patient group 6 months after clinical cure.Compared with the control group, there was a high functional connection in the right dorsolateral prefrontal lobe (MNI: x, y, z=45, 51, -6) and the right inferior parietal lobe (MNI: x, y, z=42, -48, 27) in patient group 6 months after clinical cure.@*Conclusion@#The functional connection of central executive network of depression patients has not been restored, and the related abnormality is not stable in six months after reaching the clinical cure standard.
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Chronic hepatitis B virus (HBV) infection remains a major world public health problem. Current guidelines for the prevention and treatment of chronic hepatitis B (CHB) have suggested clinical cure (also known as functional cure) as the ideal therapeutic goal, which is associated with decreased risk of cirrhosis and hepatocellular carcinoma. Clinical cure is defined as sustained, undetectable serum HBsAg, HBeAg and HBV DNA with or without seroconversion to anti-HBs, but with the persistence of residual cccDNA, accompanied by resolution of liver injury after the completion of a finite course of treatment. Accumulating data from a series of randomized controlled trials as well as clinical practice have confirmed certain clinical benefit of optimal sequential/ combination strategies of direct acting antiviral drugs (DAA) [such as nucleoside analogues (NA)] or immunomodulators (such as pegylated interferon alpha (Peg-IFN)] for appropriately selected CHB patients. This consensus provides an updated and comprehensive analysis of the data supporting the use of combination therapies and summarizes the roadmap towards clinical cure of CHB to guide decision-making in clinical practice.
ABSTRACT
Chronic hepatitis B virus (HBV) infection remains a major world public health problem. Current guidelines for the prevention and treatment of chronic hepatitis B (CHB) have suggested clinical cure (also known as functional cure) as the ideal therapeutic goal, which is associated with decreased risk of cirrhosis and hepatocellular carcinoma. Clinical cure is defined as sustained, undetectable serum HBsAg, HBeAg and HBV DNA with or without seroconversion to anti-HBs, but with the persistence of residual cccDNA, accompanied by resolution of liver injury after the completion of a finite course of treatment. Accumulating data from a series of randomized controlled trials as well as clinical practice have confirmed certain clinical benefit of optimal sequential/ combination strategies of direct acting antiviral drugs (DAA) [such as nucleoside analogues (NA)] or immunomodulators (such as pegylated interferon alpha (Peg-IFN)] for appropriately selected CHB patients. This consensus provides an updated and comprehensive analysis of the data supporting the use of combination therapies and summarizes the roadmap towards clinical cure of CHB to guide decision-making in clinical practice.
Subject(s)
Humans , Antiviral Agents , Therapeutic Uses , Consensus , DNA, Viral , Blood , Hepatitis B Surface Antigens , Blood , Hepatitis B e Antigens , Blood , Hepatitis B virus , Hepatitis B, Chronic , Therapeutics , Practice Guidelines as Topic , Randomized Controlled Trials as TopicABSTRACT
709 clinical mastitis cases were analyzed and treated with antimicrobial combination cephalexin-neomycin and the anti-inflammatory prednisolone. A sample of milk was collected to perform a microbiological culture before starting the treatment and 14 days later. Somatic cell count (SCC) was obtained from samples collected on the day of the clinical case (D0), 14 days after (D14) and 28 days after (D28). Of the total, 435 (61.4%) at the D0 exhibited growth of microorganisms. Of the isolated agents, 365 (84%) were Gram-positive, and 66 (16%) were Gram-negative. A clinical cure was achieved in 63% of cases. Bacteriological cure occurred in 75% of cases. Only at D28 after the clinical case a significant SCC reduction was verified. The logistic regression for clinical cure showed significant effects for days in milk and parity (P< 0.05). For bacteriological cure, there were significant effects of Log (SCC) D0; clinical cure and quarter affected (P< 0.05). In the principal component analysis, the Temperature-Humidity Index was associated with reduced clinical cure of clinical mastitis cases.(AU)
Setecentos e nove casos clínicos de mastite foram analisados e tratados com combinação antimicrobiana à base de cefalexina-neomicina e o anti-inflamatório prednisolona. Uma amostra de leite foi coletada para realização de cultura microbiológica antes do início do tratamento e 14 dias depois. A contagem de células somáticas (SCC) foi obtida de amostras coletadas no dia do caso clínico (D0), 14 dias após (D14) e 28 dias após (D28). Do total, 435 (61,4%) no D0 apresentaram crescimento de microrganismos, enquanto em 274 (38,6%) não houve crescimento. Dos agentes isolados, 365 (84%) eram Gram-positivos e 66 (16%) eram Gram-negativos. A cura clínica foi alcançada em 63% dos casos. A cura bacteriológica ocorreu em 75% dos casos. Apenas no D28 verificou-se uma redução significativa na SCC. A regressão logística para a cura clínica mostrou efeitos significativos para dias em lactação e paridade (P<0,05). Para a cura bacteriológica, houve efeitos significativos de Log (SCC) D0; cura clínica e quarto afetado (P<0,05). Na análise do componente principal, o índice de temperatura-umidade foi associado com a redução da cura clínica dos casos clínicos da mastite.(AU)
Subject(s)
Animals , Female , Cattle , Cattle/abnormalities , Hybrid Cells , Mastitis, Bovine/microbiologyABSTRACT
Chronic hepatitis B (CHB) is still a global public health problem, resulting in the high risk of decompensated cirrhosis and hepatocellular carcinoma.At present, there are no single available medications that can induce both potent HBV DNA suppression, and high rates of HBeAg and HBsAg clearance.Therefore, there is great interest in developing combination therapies for patients with chronic HBV infection, which can achieve sustained viral suppression and HBsAg negative inversion after a finite course of treatment leading to clinical cure.This article reviews the current status and advances of combination therapy for CHB.
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BACKGROUND: The primary objective of this meta-analysis is aimed at determining whether β-lactams prolonged infusion in patients with nosocomial pneumonia (NP) results in higher cure rate and improved mortality compared to intermittent infusion. MATERIALS AND METHODS: Relevant studies were identified from searches of MEDLINE, EMBASE, and CENTRAL from inception to September 1st, 2015. All published articles which evaluated the outcome of extended/continuous infusion of antimicrobial therapy versus intermittent infusion therapy in the treatment of NP were reviewed. RESULTS: A total of ten studies were included in the analysis involving 1,051 cases of NP. Prolonged infusion of β-lactams was associated with higher clinical cure rate (OR 2.45, 95% CI, 1.12, 5.37) compared to intermittent infusion. However, there was no significant difference in mortality (OR 0.85, 95% CI 0.63-1.15) between the two groups. Subgroup analysis for β-lactam subclasses and for severity of illness showed comparable outcomes. CONCLUSION: The limited data available suggest that reduced clinical failure rates when using prolonged infusions of β-lactam antibiotics in critically ill patients with NP. More detailed studies are needed to determine the impact of such strategy on mortality in this patient population.