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20-Week Study of Clinical Outcomes of Over-the-Counter COVID-19 Prophylaxis and Treatment.
Margolin, L, Luchins, J, Margolin, D, Margolin, M, Lefkowitz, S
Journal of evidence-based integrative medicine. 2021;:2515690X211026193
Abstract
OBJECTIVES AND SETTING.: As the lethal COVID-19 pandemic enters its second year, the need for effective modalities of alleviation remains urgent. This includes modalities that can readily be used by the public to reduce disease spread and severity. Such preventive measures and early-stage treatments may temper the immediacy of demand for advanced anti-COVID measures (drugs, antibodies, vaccines) and help relieve strain also on other health system resources. DESIGN AND PARTICIPANTS.: We present results of a clinical study with a multi-component OTC "core formulation" regimen used in a multiply exposed adult population. Analysis of clinical outcome data from our sample of over 100 subjects - comprised of roughly equal sized regimen-compliant (test) and non-compliant (control) groups meeting equivalent inclusion criteria - demonstrates a strong statistical significance in favor of use of the core formulations. RESULTS.: While both groups were moderate in size, the difference between them in outcomes over the 20-week study period was large and stark: Just under 4% of the compliant test group presented flu-like symptoms, but none of the test group was COVID-positive; whereas 20% of the non-compliant control group presented flu-like symptoms, three-quarters of whom (15% overall of the control group) were COVID-positive. CONCLUSIONS.: Offering a low cost, readily implemented anti-viral approach, the study regimen may serve, at the least, as a stopgap modality and, perhaps, as a useful tool in combatting the pandemic.
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Impact of the introduction of direct-acting anti-viral drugs on hepatocarcinogenesis: a prospective serial follow-up MRI study.
Kumada, T, Toyoda, H, Yasuda, S, Tada, T, Ogawa, S, Takeshima, K, Tanaka, J, Chayama, K, Johnson, PJ
Alimentary pharmacology & therapeutics. 2020;(2):359-370
Abstract
BACKGROUND We conducted a prospective study using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) to determine whether sustained virological response (SVR) by direct-acting anti-viral (DAA) drugs suppresses hepatocarcinogenesis in patients with hepatitis C virus (HCV) infection. AIM: To use serial Gd-EOB-MRI to assess the impact of DAAs on hepatocarcinogenesis. METHODS Between February 2008 and December 2018, 1083 consecutive patients with HCV infection underwent Gd-EOB-MRI. Of these, 719 patients were enrolled, including 210 patients in the 'Non-DAA group', who did not receive DAAs before the introduction of DAAs, and 509 patients in the 'DAA group', who achieved SVR after the introduction of DDAs. Factors associated with hepatocarcinogenesis were analysed by a Cox proportional hazard model. In addition, hepatocarcinogenesis was classified into two types, 'multistep' and 'de novo', on the basis of Gd-EOB-MRI findings. Factors associated with each type were analysed by Fine and Gray proportional hazards models. RESULTS Hepatocarcinogenesis was observed in 67 of 719 (9.3%) patients. Factors associated with hepatocarcinogenesis were male gender, albumin-bilirubin (ALBI) grade 2 or 3, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) ≥5%, the presence of nonhypervascular hypointense nodules (NHHNs) and Non-DAA group. Of 67 patients, multistep hepatocarcinogenesis occurred in 58 patients (86.6%) and de novo hepatocarcinogenesis occurred in nine patients (13.4%). Factors associated with multistep hepatocarcinogenesis were male gender and Non-DAA group. CONCLUSION The eradication of HCV by DAA therapy reduces multistep hepatocarcinogenesis.
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EVALUATION OF ANTIVIRAL THERAPY TREATMENT FOR LIVER CIRRHOSIS CAUSED BY CHRONIC HEPATITIS C AND HEPATITIS C BY 31P-MRS, BASED ON METABOLITE DETECTION.
Gu, JS, Sun, RR, Shen, S, Yu, ZJ
Journal of biological regulators and homeostatic agents. 2015;(2):443-50
Abstract
This study discusses the application of magnetic resonance spectrum (MRS) to evaluate the efficacy of antiviral therapy in the treatment of liver cirrhosis caused by chronic hepatitis C and hepatitis C, based on metabolite detection. A total of 54 patients with liver cirrhosis caused by chronic hepatitis C and hepatitis C were selected and divided into treatment group and control group. 31P-MRS imaging was carried out on patients in the two groups both before receiving antiviral treatment and 6 months after treatment to compare the change of metabolite ratio (PE+PC)/(GPE+GPC). It was revealed that no statistically significant difference was found in the comparison of (PC+PE)/(GPC+GPE) ratio in the two groups before treatment, but the difference was found 6 months after treatment; ratio of (PC+PE)/ (GPC+GPE) in the treatment group distinctly decreased 6 months after treatment compared to before treatment, with a statistically significant difference, while the control group had no remarkable change or statistical significance. Moreover, 32 patients were found with sustained virus response to antiviral therapy. Of these, 25 patients possessed a decreased ratio of (PC+PE)/ (GPC+GPE), 4 remained without change and 3 had a slightly increased ratio after antiviral treatment. Of 12 patients with no response, 1 had a decreased ratio of (PC+PE)/ (GPC+GPE), 2 remained without change and 9 had a slightly increased ratio. The differences were all statistically significant in comparison of the two groups. 31P-MRS is thought to be effective for evaluating the efficacy of antiviral therapy through non-invasive detection of liver energy metabolism.
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Significant renoprotective effect of telbivudine during preemptive antiviral therapy in advanced liver cancer patients receiving cisplatin-based chemotherapy: a case-control study.
Lin, CL, Chien, RN, Yeh, C, Hsu, CW, Chang, ML, Chen, YC, Yeh, CT
Scandinavian journal of gastroenterology. 2014;(12):1456-64
Abstract
OBJECTIVE Cisplatin is a known nephrotoxic agent requiring vigorous hydration before use. However, aggressive hydration could be life-threatening. Therefore, in cirrhotic patients with advanced hepatocellular carcinoma (HCC) under cisplatin-based chemotherapy, the risk of nephrotoxicity increased. Because previous studies showed that long-term telbivudine treatment improved renal function in chronic hepatitis B virus (HBV) infected patients, we conducted a case-control study to evaluate the clinical outcome of telbivudine preemptive therapy in HBV-related advanced HCC patients treated by combination chemotherapy comprising 5-fluorouracil, mitoxantrone and cisplatin (FMP). MATERIAL AND METHODS From June 2007 to March 2012, 60 patients with HBV-related advanced HCC, all receiving the same FMP chemotherapy protocol, were enrolled. Of them, 20 did not receive any antiviral therapy, whereas the remaining 40 patients (sex and age matched) received telbivudine preemptive therapy. RESULTS Progressive decrease of aminotransferase levels (p < 0.05) and progressive increase of viral clearance rates (p < 0.001) were found in telbivudine-treated group. No drug resistance developed during the course of treatment. When compared with non-antiviral-treated patients, a significantly higher post-therapeutic estimated glomerular filtration rate (eGFR) was found in the telbivudine-treated group (p < 0.001). In patients with initial eGFR >100 ml/min (n = 34), the median overall survival was significantly longer in the telbivudine-treated group (12.1 vs. 4.9 months; p = 0.042). CONCLUSION Preemptive use of telbivudine significantly prevented eGFR deterioration caused by cisplatin-based chemotherapy in HBV-related advanced HCC. In patients with initially sufficient eGFR level, telbivudine treatment was associated with a longer overall survival.
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Persistence of resistant variants in hepatitis C virus-infected patients treated with the NS5A replication complex inhibitor daclatasvir.
Wang, C, Sun, JH, O'Boyle, DR, Nower, P, Valera, L, Roberts, S, Fridell, RA, Gao, M
Antimicrobial agents and chemotherapy. 2013;(5):2054-65
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Abstract
Daclatasvir (DCV; BMS-790052) is a hepatitis C virus (HCV) NS5A replication complex inhibitor (RCI) with picomolar to low nanomolar potency and broad genotypic coverage in vitro. Viral RNA declines have been observed in the clinic for both alpha interferon-ribavirin (IFN-α-RBV) and IFN-RBV-free regimens that include DCV. Follow-up specimens (up to 6 months) from selected subjects treated with DCV in 14-day monotherapy studies were analyzed for genotype and phenotype. Variants were detected by clonal sequencing in specimens from baseline and were readily detected by population sequencing following viral RNA breakthrough and posttreatment. The major amino acid substitutions generating resistance in vivo were at residues M28, Q30, L31, and Y93 for genotype 1a (GT-1a) and L31 and Y93 for GT-1b, similar to the resistance substitutions observed with the in vitro replicon system. The primary difference in the resistance patterns observed in vitro and in vivo was the increased complexity of linked variant combinations observed in clinical specimens. Changes in the percentage of individual variants were observed during follow-up; however, the overall percentage of variants in the total population persisted up to 6 months. Our results suggest that during the 14-day monotherapy, most wild-type virus was eradicated by DCV. After the end of DCV treatment, viral fitness, rather than DCV resistance, probably determines which viral variants emerge as dominant in populations.
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[Effects of entecavir and Shenxian Yiganling combination therapy on patients with HBeAg-positive chronic hepatitis B for 48 weeks].
Zhang, T, Wang, Y, Sun, KW
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine. 2012;(2):180-2
Abstract
OBJECTIVE To evaluate of the efficacy and safety of entecavir (ETV) combined with Shenxian Yiganling (SY) versus ETV therapy on patients with HBeAg-positive chronic hepatitis B (CHB) for 48 weeks. METHODS One hundred and sixty-four CHB patients were assigned to two groups with the cohort study: the ETV combined with SY treatment group and the ETV control group. The alanine aminotransferase (ALT), the undetectable HBV DNA level, and HBeAg negative conversion rate, and HBeAg serological negative conversion rate were observed before and after treatment. RESULTS At week 48, there was no significant difference in the normalization of ALT levels (70.00% vs 67.61%, P > 0.05) and undetectable HBV DNA levels (72.50% vs 73.24%, P > 0.05) between the two groups. There was significant difference in the HBeAg negative conversion rate (39.44% vs 23.75%) and HBeAg serological negative conversion rate (32.39% vs 15.00%) (both P < 0.05). CONCLUSION ETV combined with SY promoted the HBeAg serological negative conversion rate possibly through the recovery of the immune functions.
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Role of statins in the treatment of chronic hepatitis C virus infection.
Abd-Eldaem, AA, Azmy, MK, Ahmad, YK, Badr, GA, Houssein, MA, El-Dahshan, T
Journal of the Egyptian Society of Parasitology. 2012;(3):535-40
Abstract
This study assessed the clinical outcome of fluvastatin in addition to the standard regimen used now for treatment of chronic HCV in Egypt. A total of 80 patients with chronic hepatitis C virus infection fulfilled clinical, laboratory and histo-pathological criteria were ready for interferon therapy. They were divided into two groups: GI (N = 40) received standard treatment for HCV (Pegylated interferon and Ribavirin) and GII (N = 40) received standard treatment plus Fluvastatin (80 mg/daily). Six months before and after treatment liver function tests and HCV-RNA were evaluated. The results showed that addition of Fluvastatin to the standard HCV treatment (Pegylated interferon and Ribavirin) significantly increased sustained virological response (SVR) from (55%-62.5%; P < 0.01) and significantly decreased viral load in relapse patients (P < 0.001). No significant differences and correlations were found between serum levels of LDL-cholesterol and viral load before and after treatment in both groups.
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[Long-term clevudine therapy in nucleos(t)ide-naïve and lamivudine-experienced patients with hepatitis B virus-related chronic liver diseases].
Lee, HJ, Eun, JR, Lee, CH, Hwang, JS, Suh, JI, Kim, BS, Jang, BK
The Korean journal of hepatology. 2009;(2):179-92
Abstract
BACKGROUNDS/AIMS: Clevudine is an effective antiviral nucleoside analogue, but there are few data regarding its long-term effects, resistance, and safety. The aim of this study was to evaluate the long-term clinical efficacy of clevudine over a 1-year treatment period in nucleos(t)ide-naive and lamivudine-experienced chronic hepatitis B patients. METHODS Nucleos(t)ide-naive (group A, n=196) and lamivudine-experienced (serum hepatitis B virus, HBV DNA >2,000 copies/mL without resistant mutants at the start of clevudine therapy, group B, n=75) patients were included in this study. Basic clinical characteristics including age, sex, the presence of cirrhosis, laboratory data, and hepatitis B surface antigen (HBeAg) positivity were similar between the two groups. Pretreatment serum levels of HBV DNA were 7.4 and 6.6 log(10) copies/mL (P<0.001). The mean treatment duration was 8 months for both groups (range for group A: 3-21 months; range for group B: 3-20 months). Genotypic analysis for resistant mutations in the reverse transcriptase of HBV was performed after viral breakthrough. RESULTS After 1 year of therapy, 75.0% and 51.9% of groups A and B, respectively, had HBV DNA levels of <2,000 copies/mL (P=0.032), and HBeAg seroconversion rates were 16.9% and 16.7%, respectively. The rates of viral breakthrough at 1 year were 10.0% (8/80) and 44.4% (12/27), respectively (P<0.001). Proven sites of mutation of HBV DNA polymerase in naive patients were, for example, L80I, L180M, A181V/T, M204I and V207I. Ten patients complained of prominent fatigue and revealed elevated serum levels of aspartate aminotransferase (AST) and creatine phosphokinase (CPK). Two of these patients presented with severe myopathy from which they recovered completely after quitting clevudine. CONCLUSIONS Clevudine is one of the recommended first-line medicines for the treatment of chronic hepatitis B, but it is not free from resistance, particularly in patients with a history of previous lamivudine treatment, but also in naive patients. Clevudine should be avoided in previously lamivudine-exposed patients. In addition, reelevation of serum AST and CPK levels is not a rare occurrence, and close observation and follow-up tests are essential.
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Antiviral therapy in neonatal cholestatic cytomegalovirus hepatitis.
Ozkan, TB, Mistik, R, Dikici, B, Nazlioglu, HO
BMC gastroenterology. 2007;:9
Abstract
BACKGROUND Neonatal hepatitis refers to a heterogeneous group of disorders, caused by many factors including cytomegalovirus infection, revealing similar morphologic changes in the liver of an infant less than 3 months of age. Approximately 40% of cholestasis in infants is due to neonatal hepatitis. It may cause latent or acute cholestatic or chronic hepatitis, including cirrhosis in immunocompetant infant. METHODS Twelve infants diagnosed with neonatal cytomegalovirus hepatitis in the last one year were included in the study. Group 1 consisted of seven babies treated with ganciclovir for 21 days. Group 2 included five cases who did not receive antiviral treatment. Physical examination, biochemical, serologic and virologic tests were done for both groups at the time of diagnosis and in the third month. RESULTS Initial levels of total bilirubin, aminotransferases, gamma glutamyl transpeptidase, and alkaline phosphatase revealed a significant decrease after the treatment in Group 1 (p < 0.05) when compared with Group 2. This study revealed that ganciclovir treatment is a safe and effective in cases with cholestatic hepatitis. Similarly, all the patients in the treatment group had evidence of improvement serologically and virologically, while the comparison group did not reveal any significant change(p < 0.01). CONCLUSION The clinical spectrum of perinatal infection varies from an asymptomatic infection or a mild disease to a severe systemic involvement, including central nervous system. The treatment in the early period of infection improved serologic markers and cholestatic parameters significantly. Further studies will lead us to clarify the efficacy of ganciclovir treatment in the early period of cytomegalovirus hepatitis, and the preventive role of anti-viral therapy on progressive liver disease due to cholestasis and hepatitis in neonatal cytomegalovirus infection.
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Bone mineral density and cytokine levels during interferon therapy in children with chronic hepatitis B: does interferon therapy prevent from osteoporosis?
Gur, A, Dikici, B, Nas, K, Bosnak, M, Haspolat, K, Sarac, AJ
BMC gastroenterology. 2005;:30
Abstract
BACKGROUND Our aim was to determinate bone mineral density (BMD), levels of biochemical markers and cytokines in children with chronic hepatitis B treated with interferon (IFN)-alpha and to investigate effect of IFN-alpha therapy on these variables. To the best of our knowledge, this is first study carried out about BMD and cytokine levels in pediatric patients with chronic hepatitis B treated with IFN-alpha. METHODS BMD, levels of parathyroid hormone (PTH), osteocalcin, C-terminal cross-linking telopeptide of type I collagen (CTX), calcium, alkaline phosphates (ALP), cytokines as TNF-alpha, interleukin (IL)-1beta, IL-2r, IL-6, and IL-8 were studied in 54 children with chronic hepatitis B (4-15 years old) treated with interferon alone (n = 19) or in combination with lamivudine (n = 35) for six months and as controls in 50 age-matched healthy children. RESULTS There was no significant difference in respect to serum IL-1beta, TNF-alpha and osteocalcin levels while serum IL-2r (p = 0.002), IL-6 (p = 0.001), IL-8 (p = 0.013), PTH (p = 0.029), and CTX (p = 0.021) levels were higher in children with chronic hepatitis B than in healthy controls. BMD of femur neck (p = 0.012) and trochanter (p = 0.046) in patients were higher than in healthy controls. There was a statistically significant correlation between serum IL-1beta and osteocalcin (r = -0.355, p < 0.01); between serum IL-8 and CTX levels (r = 0.372, p = 0.01), and ALP (r = 0.361, p = 0.01); between serum ALP and femur neck BMD (r = 0.303, p = 0.05), and trochanter BMD (r = 0.365, p = 0.01); between spine BMD and IL-2R (r = -0.330, p < 0.05). CONCLUSION In conclusion, our study suggest that BMD of femur, serum IL-2r, IL-6, IL-8, PTH, and CTX levels were higher in children with chronic hepatitis B treated with IFN-alpha alone or combination with lamivudine than in healthy children. High femur BMD measurements found in patients may suggest that IFN-alpha therapy in children with chronic hepatitis B could contribute indirectly to prevent from hip osteoporosis. Additionally, further investigations on effects of IFN-alpha for bone structure in children should be performed in the future.