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1.
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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2.
Vitamin D levels in Egyptian HCV patients (genotype 4) treated with pegylated interferon.
Mohamed, AA, Sabry, NA, Abbassi, MM, Ibrahim, WA, Ali-Eldin, ZA
Acta gastro-enterologica Belgica. 2013;(1):38-44
Abstract
BACKGROUND/AIM: Vitamin D has been shown to play an important immunomodulatory role. Deficiency of vitamin D has been recently associated to the lack of response to interferon therapy in Hepatitis C virus genotype 1 infected patients. This study aims to evaluate serum level of vitamin D and verify whether circulating vitamin D has any independent role in predicting the rates of HCV virologic response after the administration of pegylated interferon to Egyptian patients infected with genotype 4 HCV. METHODS Fifty patients infected with HCV genotype 4 and not co-infected with neither Hepatitis B virus nor Human Immunodeffiency Virus were recruited for the study. They were treated with ribavirin-pegylated interferon alpha 2a. Viral titer was determined at baseline, at 12 weeks and at end of treatment (48 weeks). Vitamin D levels and a biochemical profile were obtained for the patients at baseline and at end of treatment. Vitamin D control group consisting of 20 healthy patients of similar age and weight to the study group were recruited to obtain vitamin D levels. RESULTS Vitamin D levels in HCV infected patients were significantly lower than in healthy subjects. Responders to ribavirin plus pegylated interferon alpha 2a therapy had significantly higher vitamin D levels than non-responders. CONCLUSION Vitamin D deficiency predicts an unfavorable response to interferon-based treatment of HCV.
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3.
[Comparison of the mechanisms of intralesional steroid, interferon or verapamil injection in the treatment of proliferative scars].
Xu, SJ, Teng, JY, Xie, J, Shen, MQ, Chen, DM
Zhonghua zheng xing wai ke za zhi = Zhonghua zhengxing waike zazhi = Chinese journal of plastic surgery. 2009;(1):37-40
Abstract
OBJECTIVE To investigate the effects of intralesional steroid, interferon alpha-2b or verapamil injection on proliferation, apoptosis and TGF-beta1 expression in keloid and hypertrophic scar in vivo. METHODS 6 patients with keloids and 6 patients with hypertrophic scar were treated with intralesional injection of triamcinolone acetonide (40 mg/ml) or IFN alpha-2b (15 x 10(5) U/ml) or verapamil (2.5 mg/ml). Samples were collected on the 7th day after intralesional injection. Samples of untreated keloid and hypertrophic scar and normal skin were used as control. Expression of PCNA and TGF-beta1 was detected in situ by immunohistochemical staining, and apoptosis was detected in situ by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL). RESULTS 1) Triamcinolone acetonide could prohibit proliferative scars through inhibiting cell proliferation and TGF-beta1 expression, as well as inducing apoptosis. 2) IFN alpha-2b could prohibit proliferative scars through inhibiting cell proliferation and TGF-beta1 expression, but not inducing apoptosis; 3) Verapamil could also prohibit proliferative scars through inhibiting proliferation and TGF-beta1 expression in fibroblasts, as well as inducing apoptosis. While the effect of inducing apoptosis was stronger than that of triamcinolone acetonide, the effect of inhibiting TGF-beta1 expression was weaker than those of triamcinolone acetonide and IFN alpha-2b. CONCLUSIONS Although intraleional injection of steroid, interferon alpha-2b or verapamil were all effective in the treatment of keloid and hypertrophic scar, their mechanisms are not similar.
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4.
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.
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5.
Effect of interferon, ribavirin and ursodeoxycholic acid in patients with hepatitis C infection.
Ljubuncic, P, Konikoff, FM, Blendis, LM, Bomzon, A
Hepato-gastroenterology. 2005;(64):1191-6
Abstract
BACKGROUND/AIMS: Combination therapy of interferon-alpha (IFNalpha) and the oral nucleoside analog, ribavirin is the standard treatment for individuals suffering from hepatitis C virus (HCV) infection. Several studies have shown combination therapy of IFN and antioxidants is therapeutically beneficial in these patients. Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid possessing antioxidant properties. This study evaluated the clinical outcome and extent of oxidative stress in a group of non-responding and disease-relapsed HCV patients treated with IFNalpha, ribavirin and UDCA (triple therapy) for 6 months. METHODOLOGY Twenty patients with chronic HCV disease were treated with triple therapy for six months. During this period, they were monitored for the presence of HCV RNA, standard serum parameters of liver function and the plasma levels of lipid peroxides (LP) and glutathione (GSH) as indices of oxidative stress. The patients were reassessed six months after completion of treatment. RESULTS During the 6-month treatment period, the health status of the patients improved reflected by falls in the serum activities of alanine and aspartate aminotransferases and gamma-glutamyl transpeptidase and an initial lowering of viral (HCV RNA) load. Six months after cessation of treatment, the patients showed biochemical and virological evidence of disease relapse. The elevated plasma LP levels normalized during the treatment period and remained within normal levels 6 months after completion of treatment. Plasma GSH levels fluctuated within the normal range over the 12-month observation period. CONCLUSIONS Treatment of individuals with chronic HCV hepatitis with triple therapy comprising IFNalpha, ribavirin and UDCA improves the health status, as well as lowering the extent of oxidative stress in these individuals. This treatment regimen also resulted in a sustained lowering of plasma lipid peroxide levels in the face of laboratory evidence of disease relapse. This preliminary study is unable to provide an apt explanation for the persistence of normal plasma LP levels in the face of evidence of disease relapse 6 months after completion of treatment. However, we believe these preliminary findings are sufficiently intriguing to warrant further study. Such investigations should include more patients with assessment of the extent of hepatic fibrosis during and after completion of treatment to determine whether this treatment can modify the natural progress of the disease.
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6.
Hepatitis B virus-specific T cell response in chronic hepatitis B patients treated with lamivudine and interferon-alpha.
Pontesilli, O, van Nunen, AB, van Riel, D, Carotenuto, P, Niesters, HG, Uytdehaag, FG, De Man, RA, Osterhaus, AD
Liver international : official journal of the International Association for the Study of the Liver. 2004;(4):308-15
Abstract
AIMS: The goal of the present study was to assess the impact combination antiviral therapy has on immune responses in chronic hepatitis B. MATERIALS AND METHODS T cell responses were studied in 16 chronically hepatitis B virus (HBV)-infected patients treated with sequential, partially overlapping, lamivudine-interferon (IFN)-alpha combination therapy. RESULTS HBcAg-specific lymphoproliferative response (LPR) was transiently detected in four of five patients who achieved virus suppression (HBV DNA < 10(4) genome equivalents/ml) at end of dual therapy, and then reverted to pre-treatment viral load after therapy discontinuation. In contrast, no significant HBcAg-specific LPR was detected in 8 patients who did not attain profound HBV suppression, as well as in three patients who experienced no HBV DNA rebound after therapy discontinuation. CONCLUSIONS This pilot study suggests that restored viral replication after pharmacological suppression drives the immune response to HBV in chronically infected patients. Further characterization of the adaptive immunity and its regulatory mechanisms at time of therapy discontinuation appears therefore necessary in controlled trials.
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7.
Liposomal lactoferrin induced significant increase of the interferon-alpha (IFN-alpha) producibility in healthy volunteers.
Ishikado, A, Imanaka, H, Kotani, M, Fujita, A, Mitsuishi, Y, Kanemitsu, T, Tamura, Y, Makino, T
BioFactors (Oxford, England). 2004;(1-4):69-72
Abstract
Interferon-alpha (IFN-alpha) producibility has been widely accepted as one of the important markers to evaluate the immune status. In this study, preliminary clinical tests were carried out to confirm the immunomodulatory activity of liposomal lactoferrin including IFN-alpha producibility and NK activity. In a primary open trial, the liposomal lactoferrin was administered to five healthy males for one week and various immunological indices were evaluated. Furthermore, ten healthy males were administered 319 mg per day of liposomal or non-liposomal lactoferrin for four weeks, and immune status was monitored at 0, 1 and 4 weeks after the intake as well as three weeks after stopping it. In this double-blinded comparative study, the IFN-alpha producibility was significantly increased only in the liposomal lactoferrin group during administration and decreased 3 weeks after stopping it, while the IFN-alpha producibility was unchanged in the non-liposomal lactoferrin group. Although the biological mechanism of IFN-alpha producibility enforced by liposomal lactoferrin has not been wholly understood, it is suggested to be a novel active constituent having preventive and therapeutic effects on inflammatory diseases, cancer and infectious diseases such as chronic hepatitis C.
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8.
[Role of immunomodulatory treatment with Iscador QuS and Intron A of women with CIN1 with concurrent HPV infection].
Jach, R, Basta, A, Szczudrawa, A
Ginekologia polska. 2003;(9):729-35
Abstract
OBJECTIVE The paper presents the role of immunomodulatory treatment with Iscador QuS and Intron A of women with CIN1 and CIN2 with concurrent HPV infection. MATERIAL AND METHODS Clinical material consisted of 96 women aged 18-52 years of life. The women were divided into three groups. Group A (35 women) treated with Iscador QuS administered s.c. twice a week for 3 months, group B (30 women) treated with Intron A, administered twice a week in the cervical injections for 3 months and control group K (31 women) without treatment followed up with cytology and colposcopy. RESULTS In the group A (Iscador QuS) CIN remission was observed in slightly higher percentage (non significant) comparing to the control group. In the group B (Intron A) remission CIN was observed in 24 (80%) cases which was statistically significant comparing to the control and A groups. There were no progression of CIN in the group B and the stationery process was observed statistically more frequent comparing to the control and A groups. There was observed statistically higher percentage of cases without HPV infection in all groups during the experiment. The remission concerned both high and low oncogenic potency viruses. In the highest percentage CIN with concurrent HPV infection remission was observed in the B (Intron A) group. CONCLUSIONS 1/Iscador QuS and specially Intron A increases the CIN1 and CIN2 remission rate. 2/These two agents may also affect the HPV remission.
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9.
Effect of alpha 2b interferon on inducement of mIL-2R and treatment of HCV in PBMC from patients with chronic viral hepatitis C.
Wang, J, Xiang, GJ, Liu, BX
World journal of gastroenterology. 2003;(4):751-4
Abstract
AIM: To study the level of membrane interleukin-2 receptor (mIL-2R) on surface of peripheral blood mononuclear cells (PBMC) and the therapeutic efficacy of alpha 2b interferon on the treatment of HCV-RNA in PBMC of patients with chronic hepatitis C and to compare the negative rates of HCV-RNA in PBMC, HCV-RNA and anti-HCV in serum. METHODS Before and after treatment of alpha 2b interferon, the level of mIL-2R of patients with chronic hepatitis C was detected by biotin-streptavidin (BSA). The therapeutic group (26 cases) was treated with alpha 2b interferon (3 MU/d) and control therapeutic group (22 cases) was treated with routine drugs (VitC, aspartic acid). The total course of treatment with alpha 2b interferon and routine drug was six months and per course of the treatment was three months. The levels of HCV-RNA in PBMC, HCV-RNA and anti-HCV in serum were detected before and after a course of the treatment. RESULTS Before and after treatment of alpha 2b interferon and routine drugs, the levels of mIL-2R in silence stage were (3.44+/-0.77) % and (2.95+/-0.72) %, the levels of mIL-2R in inducement stage were (33.62+/-3.95) % and (30.04+/-3.73) %. There was a significant difference between two groups (P<0.01-P<0.05). After treatment of alpha 2b interferon with 3 MU/d for two courses of the treatment, the total negative rates of HCV-RNA in the PBMC and HCV-RNA, anti-HCV in serum were 42.31 % (11/26), 57.69 % (15/26), 65.38 %(17/26) respectively. After the treatment of routine drug, the negative rates of HCV-RNA in PBMC and HCV-RNA, anti-HCV in serum were 13.64 % (3/22), 22.73 % (5/22), 27.27 % (6/22) respectively. There was high significant difference in the group treated with alpha 2b interferon and the group treated with routine drugs (P<0.01-P<0.05). CONCLUSION The mIL-2R can be induced by alpha 2b interferon during the treatment. The alpha 2b interferon has a definite effect on the treatment of HCV-RNA in PBMC. The curative effect of alpha 2b interferon is better than that of the routine drugs.
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10.
Hepatic iron concentration does not influence response to therapy with interferon plus ribavirin in chronic HCV infection.
Pianko, S, McHutchison, JG, Gordon, SC, Heaton, S, Goodman, ZD, Patel, K, Cortese, CM, Brunt, EM, Bacon, BR, Blatt, LM
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research. 2002;(4):483-9
Abstract
In patients with chronic hepatitis C, prior studies have suggested that increased hepatic iron concentration (HIC) is predictive of a poor response to interferon (IFN) monotherapy. The aim of this study was to assess the importance of HIC on the virologic response to therapy with IFN alone or when combined with ribavirin. Records of 91 patients were reviewed for inclusion in this study. Fifty-one received IFN alone, and 40 received IFN plus ribavirin. HIC and serum iron studies, alanine aminotransferase (ALT) values, hepatitis C virus (HCV) genotype, and HCV RNA were determined prior to therapy. Sustained response was defined as the absence of HCV RNA 6 months after the end of therapy. In the IFN monotherapy group, mean HIC was higher for nonresponders (803 + 89 microg/g, range 130-2808 microg/g) compared with sustained responders (241 + 54 micro g/g, range 187-295 microg/g) (p < 0.01). In contrast, in the combination therapy group, the mean HIC was similar for both groups (533 + 86 microg/g, range 79-1338 microg/g in the nonresponders, and 662 + 95 microg/g, range 94-2031 microg/g, in the sustained responders). No difference between transferrin saturation and serum ferritin level was observed in sustained responder or nonresponder patients treated with IFN plus ribavirin. IFN monotherapy nonresponder patients tended to have a higher HIC. With IFN plus ribavirin, the sustained virologic response rate was not affected by the HIC.