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Meta-analysis of arbidol versus lopinavir/ritonavir in the treatment of coronavirus disease 2019.
Yu, M, Wang, DC, Li, S, Lei, YH, Wei, J, Huang, LY
Journal of medical virology. 2022;(4):1513-1522
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Abstract
OBJECTIVES To systematically evaluate the efficacy and safety of arbidol and lopinavir/ritonavir (LPV/r) in the treatment of coronavirus disease 2019 (COVID-19) using a meta-analysis method. METHODS The China Knowledge Network, VIP database, WanFang database PubMed database, Embase database, and Cochrane Library were searched for a collection of comparative studies on arbidol and lopinavir/ritonavir in the treatment of COVID-19. Meta-analysis was used to evaluate the efficacy and safety of Arbidol and lopinavir/ritonavir in the treatment of COVID-19. RESULTS The results of the systematic review indicated that Arbidol had a higher positive-to-negative conversion rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid on Day 7 (p = 0.03), a higher positive-to-negative conversion rate of SARS-CoV-2 nucleic acid on Day 14 (p = 0.006), a higher improvement rate of chest computed tomography on Day 14 (p = 0.02), a lower incidence of adverse reactions (p = 0.002) and lower rate of mortality (p = 0.007). There was no difference in the rate of cough disappearance on Day 14 (p = 0.24) or the rate of severe/critical illness (p = 0.07) between the two groups. CONCLUSIONS Arbidol may be superior to lopinavir/ritonavir in the treatment of COVID-19. However, due to the small number of included studies and the number of patients, high-quality multicenter large-sample randomized double-blind controlled trials are still needed for verification.
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Evaluation of Pharmacokinetic Drug Interactions of the Direct-Acting Antiviral Agents Elbasvir and Grazoprevir with Pitavastatin, Rosuvastatin, Pravastatin, and Atorvastatin in Healthy Adults.
Caro, L, Prueksaritanont, T, Fandozzi, CM, Feng, HP, Guo, Z, Wolford, D, Panebianco, D, Fraser, IP, Levine, V, Swearingen, D, et al
Clinical drug investigation. 2021;(2):133-147
Abstract
BACKGROUND Many people infected with hepatitis C virus have comorbidities, including hypercholesterolemia, that are treated with statins. In this study, we evaluated the drug-drug interaction potential of the hepatitis C virus inhibitors elbasvir (EBR) and grazoprevir (GZR) with statins. Pitavastatin, rosuvastatin, pravastatin, and atorvastatin are substrates of organic anion-transporting polypeptide 1B, whereas rosuvastatin and atorvastatin are also breast cancer resistance protein substrates. METHODS Three open-label, phase I clinical trials in healthy adults were conducted with multiple daily doses of oral GZR or EBR/GZR and single oral doses of statins. Trial 1: GZR 200 mg plus pitavastatin 10 mg. Trial 2: Part 1, GZR 200 mg plus rosuvastatin 10 mg, then EBR 50 mg/GZR 200 mg plus rosuvastatin 10 mg; Part 2, EBR 50 mg/GZR 200 mg plus pravastatin 40 mg. Trial 3: EBR 50 mg/GZR 200 mg plus atorvastatin 10 mg. RESULTS Neither GZR nor EBR pharmacokinetics were meaningfully affected by statins. Coadministration of EBR/GZR did not result in clinically relevant changes in the exposure of pitavastatin or pravastatin. However, EBR/GZR increased exposure to rosuvastatin (126%) and atorvastatin (94%). Coadministration of statins plus GZR or EBR/GZR was generally well tolerated. CONCLUSIONS Although statins do not appreciably affect EBR or GZR pharmacokinetics, EBR/GZR can impact the pharmacokinetics of certain statins, likely via inhibition of breast cancer resistance protein but not organic anion-transporting polypeptide 1B. Coadministration of EBR/GZR with pitavastatin or pravastatin does not require adjustment of either dose of statin, whereas the dose of rosuvastatin and atorvastatin should be decreased when coadministered with EBR/GZR.
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Switching Lamivudine with Adefovir Dipivoxil Combination Therapy to Entecavir Monotherapy Provides Better Viral Suppression and Kidney Safety.
Lian, JS, Zhang, XL, Lu, YF, Chen, JY, Zhang, YM, Jia, HY, Zhang, Z, Yang, YD
International journal of medical sciences. 2019;(1):17-22
Abstract
Introduction: Most chronic hepatitis B (CHB) patients in China are primitively treated with a combination of lamivudine (LAM) and adefovir dipivoxil (ADV). Although antiviral resistance can be avoided with this combination therapy, using it can have harmful side effects related to ADV, specifically kidney and bone injury. This study was designed to compare viral suppression and kidney safety when switching LAM and ADV combination therapy de novo to entecavir (ETV) monotherapy in patients with CHB and compensated hepatic cirrhosis. Materials and methods: In total, 360 CHB and compensated liver cirrhosis patients who received treatment of LAM and ADV combination therapy for more than 1 year were included in this study. One hundred and eighty patients continued combination therapy to serve as a control group and the other 180 patients were switched to ETV monotherapy to serve as the experimental group. The total course of therapy was 3 years. Laboratory studies were done every 3 months to measure liver and kidney function. Studies included glomerular filtration rate (eGFR), HBV-DNA, urine β2-microglobulin (β2-M) and retinol binding protein (RBP). Results: In the experimental group, an HBV-DNA level below 20 IU/ml was found in 77.65%, 85.88%, and 94.77% in years 1, 2, and 3, respectively. In the control group, HBV-DNA levels were below 20 IU/ml in 69.66%, 75.42%, and 85.80% in years 1, 2, and 3, respectively. Low HBV-DNA levels in the experimental group were significantly less common than in the control group on the second and third year; P values were 0.009 and 0.006 for years 2 and 3, respectively. The cumulative genetic mutation rate was 3.49% in the experimental group and 8.88% in the control group (P=0.044). Decreases in eGFR more than 30% from baseline were found in 0%, 0.56%, and 1.74% of patients in the experimental group and 4.49%, 9.14% and 14.79% in patients in the control group in the first, second, and third year, respectively. Serum creatinine more than 50 μmol/L above baseline was found in 0%, 0% and 1.74% of patients in the experimental group and 1.12%, 4.00% and 5.32% of patients in the control group in years 1, 2, and 3, respectively. The urine β2-M and RBP levels were abnormal more often in the experimental group than in the control group. Conclusion: Switching to ETV monotherapy can decrease HBV-DNA levels, reduce the genetic mutation rate, and prevent renal damage caused by LAM and ADV combination therapy in patients with CHB and compensated liver cirrhosis. Patients receiving LAM and ADV combination therapy de novo should be switched to ETV monotherapy immediately.
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Comparative efficacy of tenofovir and entecavir in nucleos(t)ide analogue-naive chronic hepatitis B: A systematic review and meta-analysis.
Chen, MB, Wang, H, Zheng, QH, Zheng, XW, Fan, JN, Ding, YL, Niu, JL
PloS one. 2019;(11):e0224773
Abstract
OBJECTIVE To compare the efficacy of tenofovir and entecavir in nucleos(t)ide analogue-naive chronic hepatitis B. METHODS The Web of Science, PubMed, Cochrane Library, EMBASE, Clinical Trials and China National Knowledge Infrastructure(CNKI) databases were electronically searched to collect randomized controlled trials (RCTs) regarding the comparison between tenofovir and entecavir in nucleos(t)ide analogue-naive chronic hepatitis B (CHB) since the date of database inception to July 2019. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. RevMan 5.3 software was used for the meta-analysis. RESULTS Early on, tenofovir had a greater ability to inhibit the hepatitis B virus, I2 = 0% [RR = 1.08, 95% CI (1.03, 1.13), P<0.01] (96 weeks). Entecavir can normalize the ALT levels earlier, I2 = 0% [RR = 0.87, 95% CI (0.77, 0.98), P = 0.02] (48 weeks). However, there was no statistically significant difference between TDF and ETV at 144 weeks. Tenofovir was as effective as entecavir in terms of HBeAg clearance and HBeAg seroconversion, I2 = 0% [RR = 1.05, 95% CI (0.68, 1.62), P = 0.82]; I2 = 69% [RR = 0.93, 95% CI (0.54, 1.61), P = 0.80]. The difference in the incidence of elevated creatine kinase levels was not statistically significant I2 = 0% [RR = 0.66, 95% CI (0.27, 1.60), P = 0.35]. CONCLUSIONS Tenofovir and entecavir were equally effective in the treatment of patients with nucleos(t)ide analogue-naive chronic hepatitis B. In addition, TDF has an advantage in the incidence of hepatocellular carcinoma. Additional RCTs and a large-sample prospective cohort study should be performed.
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Universal prophylaxis or preemptive strategy for cytomegalovirus disease after liver transplantation: a systematic review and meta-analysis.
Mumtaz, K, Faisal, N, Husain, S, Morillo, A, Renner, EL, Shah, PS
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2015;(2):472-81
Abstract
We systematically reviewed and meta-analyze the efficacy of universal prophylaxis (UP) and preemptive (PE) strategies (using ganciclovir or valganciclovir) in preventing cytomegalovirus (CMV) disease (CMD) among liver transplant recipients (LTRs). We performed an electronic search of MEDLINE, EMBASE and the Cochrane Database till December 2013. Studies that assessed UP or PE for preventing CMD in LTRs were included. The risk of bias was assessed using the Newcastle-Ottawa scale. The primary outcome was CMD, secondary outcomes being acute cellular rejection (ACR), graft loss (GL) and mortality. Due to the heterogeneity of comparative studies, an indirect comparison was performed. Pooled incidence rates with 95% confidence interval (CI) are calculated for each outcome using a random-effects model. Thirty-two studies involving 2456 LTRs were included. The majority of the studies were of low risk of bias. Irrespective of donor/recipient CMV sero-status, CMD was 10% with UP (95% CI: 6-14; I(2) = 87%; 16 studies, n = 1581) and 7% with PE (95% CI: 3-10; I(2) = 84%; 16 studies, n = 875) (mean difference 2.6; 95% CI: -3.25 to 8.45, p = 0.34). Likewise, ACR and mortality were similar with the two strategies. However, GL was significantly lower in the UP group, regardless of donor/recipient sero-status. In indirect comparison, the incidence of CMD, ACR and mortality in LTRs were similar with two strategies. Trials comparing the two strategies directly are needed.
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Randomized study comparing vitamin D3 and 1α-Hydroxyvitamin D3 in combination with pegylated interferon/ribavirin therapy for chronic hepatitis C.
Omori-Mizuno, Y, Nakayama, N, Inao, M, Funyu, J, Asabe, S, Tomita, K, Nishikawa, K, Hosoda, Y, Tanaka, M, Hashimoto, Y, et al
Journal of gastroenterology and hepatology. 2015;(9):1384-90
Abstract
BACKGROUND AND AIM An intention-to-treat prospective randomized study was carried out to compare the potentiation of antiviral efficacies between cholecalciferol, non-activated vitamin D3 supplement, and alfacalcidol, activated 1α-Hydroxyvitamin D3 [1α (OH)-vitamin D3]. METHODS Chronic hepatitis patients with genotype 1b hepatitis C virus (HCV) infection showing serum HCV-RNA levels greater than 5 Log IU/mL received oral administration of cholecalciferol (2000 IU/day) or alfacalcidol (0.5 μg/day) for 4 weeks, and then they were given pegylated interferon (Peg-IFN)-α2a plus ribavirin therapy in combination with either vitamin D3 for 48 or 72 weeks according to the response-guided manner. RESULTS A total of 36 patients were evaluated. Serum 25-hydroxyvitamin D3 [25(OH)-D3] levels were increased only in patients in the cholecalciferol group during the lead-in vitamin D administration, and the levels at 4 weeks were higher in these patients than in those in the alfacalcidol group (P < 0.001), while serum 1α,25-dihydroxyvitamin D3 [1α,25(OH)2 -D3] levels were not different between both groups. Rapid virological response was obtained in six (33%) patients in the cholecalciferol group; the ratio was higher than that in the alfacalcidol group (one patient; 6%, P < 0.05). Serum HCV-RNA level decline at 4 weeks of combined Peg-IFN-α2a plus ribavirin therapy compared with the baseline levels were greater in the cholecalciferol group (4.6 Log IU/mL) than in the alfacalcidol group (3.5 Log IU/mL) (P < 0.05), when four patients showing null response to the therapy was excluded. However, both complete early virological response and sustained viral response rates were not different between both groups. CONCLUSION Cholecalciferol produced superior potentiation of the antiviral activity than alfacalcidol only during the initial periods of combined Peg-IFN-α2a plus ribavirin therapy through upregulation of serum 25(OH)-D3 levels.
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Comparison of the forty-eight week efficacy between telbivudine and entecavir in HBeAg-positive Asian patients with chronic hepatitis B: A meta-analysis.
Wang, N, Hu, HD, Sun, H, Feng, Q, Hu, P, Liu, Q, Ren, H
The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology. 2013;(3):230-40
Abstract
BACKGROUND/AIMS: Telbivudine and entecavir are two pharmacologic agents recommended and also widely used for the treatment of chronic hepatitis B in most Asian countries. There are few conclusive results when comparing the efficacy of these two drugs for the treatment of chronic hepatitis B. The aim of this study is to evaluate, by means of meta-analysis, the short-term efficacy between the two drugs in nucleos(t)ide-naïve Asian HBeAg-positive chronic hepatitis B patients. MATERIALS AND METHODS We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, the Wanfang Database and CNKI (National Knowledge Infrastructure). Twelve eligible trials (1011 patients in total) were included into this study, and they were evaluated for quality and heterogeneity. RESULTS Meta-analysis date showed the rate of HBeAg clearance and rate of HBeAg seroconversion in the telbivudine group was higher than the entecavir group, respectively. There was no statistically significant difference however between the two groups in the rate of alanine aminotransferase normalization, or the rate of HBV DNA suppression. Although creatine kinase elevations occurred more frequently in the telbivudine group than when compared to the entecavir group, there was no statistically significant difference between the two groups in the short-term treatment duration. CONCLUSIONS For the short-term treatment of HBeAg-positive nucleos(t)ide-naïve Asian patients with chronic hepatitis B, telbivudine is as potent as entecavir in normalizing alanine aminotransferase and suppressing HBV DNA, and telbivudine is superior to entecavir in clearing HBeAg and developing anti-HBe. Careful monitoring is needed to avoid adverse events, as well as drug resistance during antiviral therapy with telbivudine.
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Lamivudine versus telbivudine in the treatment of chronic hepatitis B: a systematic review and meta-analysis.
Jiang, H, Wang, J, Zhao, W
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 2013;(1):11-8
Abstract
The purpose of this study was to evaluate the efficacy of lamivudine (LAM) versus telbivudine (LdT) in the treatment of chronic hepatitis B (CHB). Randomized controlled studies (RCTs) involving the use of LAM versus LdT in CHB patients were included in the study. Data were obtained from the Cochrane-controlled trials register, EMBASE and MEDLINE databases (1/1990 to 12/2011). Two reviewers performed quality assessment and extracted data independently. Eight RCTs were included in the main analysis. Eight eligible trials were included in the analysis. At the end of one-year treatment, LdT was better than LAM at the virological response (RR = 1.43, 95 % CI = 1.12-1.84, P = 0.005), while less than LAM at the viral breakthrough (RR = 0.34,95 % CI = 0.25-0.48, P < 0.00001), viral resistance (RR = 0.41,95 % CI = 0.28-0.58, P < 0.00001), but there was no statistically significant difference in the biochemical response (RR = 1.13,95 % CI = 0.99-1.29, P = 0.06), HBeAg seroconversion (RR = 1.13,95 % CI = 0.92-1.39, P = 0.25), therapeutic response (RR = 1.22,95 % CI = 1.00-1.50, P = 0.05) and adverse events (RR = 1.07,95 % CI = 1.00-1.14, P = 0.05). The creatine kinase (CK) elevation occurred more frequently in the LdT group than in LAM group (RR = 2.43,95 % CI = 1.57-3.75, P < 0.0001). When treatment prolonged to 2 years, LdT was better than LAM at the HBeAg seroconversion (RR = 1.29,95 % CI = 1.12-1.50, P = 0.0007) and therapeutic response (RR = 1.34,95 % CI = 1.21-1.49, P < 0.00001). LdT was more effective in inhibiting HBV replication and promoting HBeAg seroconversion than LAM for CHB patients, whereby adverse effects such as CK elevation must be paid attention to.
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Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B.
Heathcote, EJ, Marcellin, P, Buti, M, Gane, E, De Man, RA, Krastev, Z, Germanidis, G, Lee, SS, Flisiak, R, Kaita, K, et al
Gastroenterology. 2011;(1):132-43
Abstract
BACKGROUND & AIMS Tenofovir disoproxil fumarate (TDF), a nucleotide analogue and potent inhibitor of hepatitis B virus (HBV) polymerase, showed superior efficacy to adefovir dipivoxil in treatment of chronic hepatitis B through 48 weeks. We evaluated long-term efficacy and safety of TDF monotherapy in patients with chronic hepatitis B who were positive or negative for hepatitis B e antigen (HBeAg(+) or HBeAg(-)). METHODS After 48 weeks of double-blind comparison of TDF to adefovir dipivoxil, patients who underwent liver biopsy were eligible to continue the study on open-label TDF for 7 additional years; data presented were collected up to 3 years (week 144) from 85% of participants. Primary efficacy end points at week 144 included levels of HBV DNA and alanine aminotransferase, development of resistance mutations, and presence of HBeAg or hepatitis B surface antigen (HBsAg). RESULTS At week 144, 87% of HBeAg(-) and 72% of HBeAg(+) patients treated with TDF had levels of HBV DNA <400 copies/mL. Among patients who had previously received adefovir dipivoxil and then received TDF, 88% of the HBeAg(-) and 71% of the HBeAg(+) patients had levels of HBV DNA <400 copies/mL; overall, 81% and 74%, respectively, maintained normalized levels of alanine aminotransferase and 34% had lost HBeAg. Amino acid substitutions in HBV DNA polymerase that are associated with resistance to tenofovir were not detected in any patient. Cumulatively, 8% of HBeAg(+) patients lost HBsAg. TDF maintained a favorable safety profile for up to 3 years. CONCLUSIONS TDF was safe and effective in the long-term management of HBeAg(+) and HBeAg(-) patients with chronic hepatitis B.
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A new topical treatment protocol for oral hairy leukoplakia.
Moura, MD, Haddad, JP, Senna, MI, Ferreira e Ferreira, E, Mesquita, RA
Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. 2010;(5):611-7
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Abstract
OBJECTIVE The aim of this study was to present a new topical treatment protocol for oral hairy leukoplakia (OHL), consisting of a 25% podophyllin resin with a 1% penciclovir cream (PP), and to compare this topical treatment protocol's efficacy with that of 2 other topical treatment protocols: a 25% podophyllin resin (P) and a 25% podophyllin resin with a 5% acyclovir cream (PA). STUDY DESIGN Forty-two human immunodeficiency virus-positive patients with 69 OHL lesions were randomly treated using P, PA, or PP (14 patients in each topical treatment protocol). Clinical healing was determined when the white plaque could no longer be seen in the primary location of the lesion. Topical treatment performance was evaluated by clinical healing within each week of topical treatment protocol as well as by the recurrence of the lesion. Statistical survival analysis was performed using a Cox proportional hazards model. RESULTS Approximately 55% of the patients presented with clinical healing of OHL within 7-8 weeks of each topical treatment protocol. After the sixth week, the PA treatment protocol presented a faster clinical healing rate of OHL. Recurrence was observed in 3 and 7 OHL lesions treated with P and PP treatment protocols, respectively. CONCLUSIONS The PP treatment protocol proved to be effective; however, the PA treatment protocol was more effective in the clinical healing rate for OHL than P and PP after the sixth week of treatment, and no recurrent OHL was observed in the PA treatment group.