scholarly journals Short-term and long-term safety and efficacy of tenofovir alafenamide, tenofovir disoproxil fumarate and entecavir treatment of acute-on-chronic liver failure associated with hepatitis B

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Juan Li ◽  
Chunhua Hu ◽  
Yi Chen ◽  
Rou Zhang ◽  
Shan Fu ◽  
...  

Abstract Background & Aims There is limited evidence on the efficacy and safety of nucleos(t) ide analogues (NAs) in the treatment of HBV-ACLF. Our objective was to evaluate the outcomes among TAF, TDF and ETV, three first-line antivirals against chronic hepatitis B, in patients with HBV-ACLF. Methods Patients with HBV-related ACLF were recruited and received daily TAF (25 mg/d), TDF (300 mg/d) and ETV (0.5 mg/d). They were prospectively followed-up. The primary endpoint was overall survival at week 12 and week 48, the secondary endpoints were virological response and biochemical response. Results Forty gender and age matched eligible subjects were recruited and divided into three groups: TAF group, TDF group and ETV group. By week 48, 8 (80%) patients in TAF group, 6 (60%) patients in TDF group and 17 (85%) patients in ETV group survived without liver transplantation (P = 0.251). After 4 weeks of NAs treatment, all three groups showed paralleling reduction of HBV DNA levels. All three groups presented similar biochemical responses at week 4, patients treated with TAF showed a priority in total bilirubin reduction, albumin and cholesterol maintenance. Additionally, although there was no significant difference in changes of serum urea, serum creatinine, serum cystatin C and estimated GFR among the three groups by treatment week 4, TDF showed unfavorable renal safety even in short -term treatment. The treatment using NAs was well-tolerated and there was no serious drug-related adverse event reported. Conclusions TAF, TDF and ETV are of similar efficacy and safety in short-term and long-term treatment of HBV-ACLF. Trial registration This study is ongoing and is registered with ClinicalTrials.gov, NCT03640728 (05/02/2019).

2021 ◽  
Author(s):  
Juan Li ◽  
Chunhua Hu ◽  
Yi Chen ◽  
Rou Zhang ◽  
Shan Fu ◽  
...  

Abstract Background & Aims: There is limited evidence on the efficacy and safety of nucleos(t)ide analogues (NAs) in the treatment of HBV-ACLF. Our objective was to evaluate the outcomes among TAF, TDF and ETV, three first-line antivirals against chronic hepatitis B, in patients with HBV-ACLF. Methods: Patients with HBV-related ACLF were recruited and received daily TAF (25mg/d), TDF (300 mg/d) and ETV (0.5 mg/d). They were prospectively followed-up. The primary endpoint was overall survival at week 12 and week 48, the secondary endpoints were virological response and biochemical response. Results: Forty gender and age matched eligible subjects were recruited and divided into three groups: TAF group, TDF group and ETV group. By week 48, 8 (80%) patients in TAF group, 6 (60%) patients in TDF group and 17 (85%) patients in ETV group survived without liver transplantation (P = 0.251). After 4 weeks of NAs treatment, all three groups showed paralleling reduction of HBV DNA levels. All three groups presented similar biochemical responses at week 4, patients treated with TAF showed a priority in total bilirubin reduction, albumin and cholesterol maintenance. Additionally, although there was no significant difference in changes of serum urea, serum creatinine, serum cystatin C and estimated GFR among the three groups by treatment week 4, TDF showed unfavorable renal safety even in short term treatment. The treatment using NAs was well-tolerated and there was no serious drug-related adverse event reported. Conclusions: TAF, TDF and ETV are of similar efficacy and safety in short-term and long-term treatment of HBV-ACLF. This study is ongoing and is registered with ClinicalTrials.gov, NCT03640728 (05/02/2019).


2017 ◽  
Vol 64 (1) ◽  
pp. 22-25
Author(s):  
P. Potucek ◽  
M. Radik ◽  
G. Doka ◽  
E. Kralova ◽  
P. Krenek ◽  
...  

AbstractBlood pressure (BP) rhythm is exhibited in a circadian pattern regulated by complex system of endogenous factors. Administration of pharmacological treatment at the right time can influence the efficacy of treatment; but while kidneys play significant role in BP regulation, little is known about their role in chronopharmacotherapy. This study aimed to compare differences between morning and evening dosing with valsartan and amlodipine combination in both short-term and long-term settings and to elucidate the role of kidneys in chronopharmacology. Spontaneously hypertensive rats aged between 8 and 10 weeks were daily treated with 10mg/kg of valsartan and 4 mg/kg of amlodipine, either in the morning or in the evening with treatment duration of 1 and 6 weeks. After short-term treatment, only morning treatment group demonstrated significantly better outcomes in terms of BP control when compared to placebo. After long-term treatment, both treatment groups gained superior results in BP control against placebo; however, no significant difference was seen between morning and evening treatment. Interestingly, clock gene expression in kidney has been significantly modulated only in the evening-treated groups, with treatment intensifying the reduced Bmal1 levels, while Per2 expression was less altered. However, no direct relation with the outcomes of the therapy has been observed, suggesting that pharmacotherapy may serve as an independent modulator of peripheral circadian clock in the kidney.


CNS Spectrums ◽  
1998 ◽  
Vol 3 (9) ◽  
pp. 64-71 ◽  
Author(s):  
Gary A. Christenson ◽  
Scott J. Crow ◽  
James E. Mitchell ◽  
Thomas B. Mackenzie ◽  
Ross D. Crosby ◽  
...  

AbstractThis short-term, open-label study investigates short- and long-term effects of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine for the treatment of trichotillomania (TTM). Additionally, this study aimed to test the hypothesis that the presence of hair pulling compulsiveness is predictive of SSRI response. Nineteen subjects meeting the Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised, (DSM-III-R) criteria for TTM were treated with fluvoxamine at doses up to 300 mg/day. Random regression analysis of change across time for patients who completed the study (n=14) and those who dropped out (n=5) revealed statistically significant improvements in Physician Rating Scale, hair-pulling episodes, Trichotillomania Impairment Scale, and Trichotillomania Symptom Severity Scale, but not in estimated amount of hair pulled. In addition, the percentage of patients' focused or compulsive hair-pulling symptoms was predictive of treatment response. Unfortunately, all three subjects who entered long-term treatment displayed substantial movement back toward baseline by the end of 6 months. We concluded that fluvoxamine produces moderate reductions in symptoms during the short-term treatment of TTM and that the presence of focused or compulsive hair pulling may be predictive of treatment response. However, responses may be short lived when treatment is extended.


2020 ◽  
Vol 15 (2) ◽  
pp. 110-124
Author(s):  
Joy E. Ikekpeazu ◽  
Oliver C. Orji ◽  
Ikenna K. Uchendu ◽  
Lawrence U.S. Ezeanyika

Background and Objective: There may be a possible link between the use of HAART and oxidative stress-related mitochondrial dysfunction in HIV patients. We evaluated the mitochondrial and oxidative impacts of short and long-term administration of HAART on HIV patients attending the Enugu State University Teaching (ESUT) Hospital, Enugu, Nigeria following short and long-term therapy. Methods: 96 patients categorized into four groups of 24 individuals were recruited for the study. Group 1 comprised of age-matched, apparently healthy, sero-negative individuals (the No HIV group); group 2 consisted of HIV sero-positive individuals who had not started any form of treatment (the Treatment naïve group). Individuals in group 3 were known HIV patients on HAART for less than one year (Short-term treatment group), while group 4 comprised of HIV patients on HAART for more than one year (Long-term treatment group). All patients were aged between 18 to 60 years and attended the HIV clinic at the time of the study. Determination of total antioxidant status (TAS in nmol/l), malondialdehyde (MDA in mmol/l), CD4+ count in cells/μl, and genomic studies were all done using standard operative procedures. Results: We found that the long-term treatment group had significantly raised the levels of MDA, as well as significantly diminished TAS compared to the Short-term treatment and No HIV groups (P<0.05). In addition, there was significantly elevated variation in the copy number of mitochondrial genes (mtDNA: D-loop, ATPase 8, TRNALEU uur) in the long-term treatment group. Interpretation and Conclusion: Long-term treatment with HAART increases oxidative stress and causes mitochondrial alterations in HIV patients.


1992 ◽  
Vol 117 (3) ◽  
pp. 384-388 ◽  
Author(s):  
Tomio Johjima ◽  
Joyce G. Latimer ◽  
Hiroshi Wakita

Pot-grown seedlings of seven lines [`Red Cherry' (RC), `Moneymaker' (MM), `Dantobi-yohzu' (DY), `Furikoma' (FK), RC × FK, MM × DY, and MM × FK] of tomato (Lycopersicon esculentum Mill.) were brushed with a suspended steel bar for 1.5 minutes twice daily for 18 days (short-term treatment) before being transplanted to beds in a plastic greenhouse. Brushing was continued on a selected group of plants for an additional 10 days (long-term treatment). Short-term brushing slightly reduced the number of leaves, but markedly reduced leaf size and stem elongation of all lines. Dry weights of lamina, petioles, and stems of brushed plants of each cultivar except FK were less than those of the respective controls. However, the ratios of root: shoot dry weight of brushed plants were unchanged or higher than those of the respective controls. Short-term brushing did not increase the total number or weight of tomato fruits harvested over 1 month and did not improve fruit quality, size, or color. Long-term brushing reduced the total yield (number and weight) of fruits of RC and total fruit weight of DY. With respect to sensitivity to mechanical stress, cultivars with taller growth habits were more responsive to brushing than were those with shorter growth habits. These characteristic responses to mechanical stress also were exhibited by the hybrid lines.


2009 ◽  
Vol 1 (3) ◽  
pp. 238 ◽  
Author(s):  
Joanne Barnes

SUMMARY MESSAGE: There is evidence that Devil’s Claw can be an effective short-term treatment for acute exacerbations of low back pain and, to a lesser extent, in rheumatic and osteoarthritic conditions. Acute adverse effects reported in clinical trials were mild diarrhoea and flatulence. Long-term adverse effects have not been studied. As with all herbal medicines, Devil’s Claw products differ in their pharmaceutical quality, and the implications of this for efficacy and safety should be considered.


Impact ◽  
2021 ◽  
Vol 2021 (5) ◽  
pp. 51-53
Author(s):  
Yuya Yoshida

Autoimmune diseases occur when the body begins to attack normal cells instead of fighting off diseases and infections. There are ways of treating autoimmune diseases, but these provide only short-term relief, and there is no cure. Therefore, relapse tends to be an inevitable part of autoimmune diseases. Dr Yuya Yoshida is a specialist in immunology based in the Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Japan, who is investigating the possibility of inducing immune tolerance and, in doing so, eliminating the need for long-term treatment. He and his team are working to devise a treatment strategy that enables complete short-term treatment and can then maintain long-term remission without the need for drug treatment. The ultimate goal for the team is a breakthrough in the treatment of autoimmune diseases, which would have far-reaching benefits for patients and the field of medicine. A key focus for Yoshida and his team is how an immunomodulating medication called fingolimod (FTY720) could be used to induce immune tolerance and, in doing so, stop the cycle of remission and relapse. There is potential for FTY720 to be used to develop new treatments and eliminate the need for patients to rely on long-term treatment. In particular, the researchers are focusing on multiple sclerosis and rheumatoid arthritis. One investigation involves the use of animal models to explore the construction of effective induction of immune tolerance to rheumatoid arthritis using FTY720.


2019 ◽  
Vol 21 (7) ◽  
pp. 890-900 ◽  
Author(s):  
Jubayer A Hossain ◽  
Md A Latif ◽  
Lars A R Ystaas ◽  
Sandra Ninzima ◽  
Kristoffer Riecken ◽  
...  

Abstract Background Suicide gene therapy for malignant gliomas has shown encouraging results in the latest clinical trials. However, prodrug application was most often restricted to short-term treatment (14 days), especially when replication-defective vectors were used. We previously showed that a substantial fraction of herpes simplex virus thymidine kinase (HSV-TK) transduced tumor cells survive ganciclovir (GCV) treatment in an orthotopic glioblastoma (GBM) xenograft model. Here we analyzed whether these TK+ tumor cells are still sensitive to prodrug treatment and whether prolonged prodrug treatment can enhance treatment efficacy. Methods Glioma cells positive for TK and green fluorescent protein (GFP) were sorted from xenograft tumors recurring after suicide gene therapy, and their sensitivity to GCV was tested in vitro. GBM xenografts were treated with HSV-TK/GCV, HSV-TK/valganciclovir (valGCV), or HSV-TK/valGCV + erlotinib. Tumor growth was analyzed by MRI, and survival as well as morphological and molecular changes were assessed. Results TK-GFP+ tumor cells from recurrent xenograft tumors retained sensitivity to GCV in vitro. Importantly, a prolonged period (3 mo) of prodrug administration with valganciclovir (valGCV) resulted in a significant survival advantage compared with short-term (3 wk) application of GCV. Recurrent tumors from the treatment groups were more invasive and less angiogenic compared with primary tumors and showed significant upregulation of epidermal growth factor receptor (EGFR) expression. However, double treatment with the EGFR inhibitor erlotinib did not increase therapeutic efficacy. Conclusion Long-term treatment with valGCV should be considered as a replacement for short-term treatment with GCV in clinical trials of HSV-TK mediated suicide gene therapy.


2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Yuanchun Yue ◽  
Xiaoxi Xu ◽  
Baoyu Yang ◽  
Jing Lu ◽  
Shuwen Zhang ◽  
...  

The gut microbiota plays an important role in intestinal health. Probiotics such as Lactobacillus are known to regulate gut microbes and prevent diseases. However, most of them are unable to colonize their stability in hosts’ intestinal tracts. In this study, we investigated the ability of Lactobacillus casei SY13 (SY13) to colonize the intestinal tract of BALB/c mice, after its oral administration for a short-term (once for a day) and long-term (once daily for 27 days) duration. Furthermore, we also evaluated the influence of its administration on the gut microbial structure and diversity in mice. Male BALB/c mice were gavaged with 108 colony-forming units (CFU) of SY13, and TaqMan-MGB probe and Illumina MiSeq sequencing were performed to assess the colonization ability and bacterial community structure in the cecum contents. The results showed that long-term treatment with SY13 enhanced its ability to form a colony in the intestine tract in contrast to the short-term treatment group, whose colony was retained for only 3 days. Oral administration of SY13 also significantly enhanced the gut microbial diversity. Short-term treatment with SY13 (SSY13) elevated Firmicutes and diminished Bacteroidetes phyla compared with long-term treatment (LSY13) and controls. The findings laid the foundation for the study of probiotic colonization ability and improvement of microbiota for the prevention of gut diseases.


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