Zinc supplementation prevents the increase of transaminase in chronic hepatitis C patients during combination therapy with pegylated interferon alpha-2b and ribavirin

We investigated the effects of zinc supplementation on clinical observations in chronic hepatitis C patients receiving pegylated interferon (PEG-IFN) alpha-2b plus ribavirin combination therapy. Patients were randomly allocated to receive 150 mg polaprezinc (zinc group, n=11) or no supplement (control group, n=12) daily in addition to PEG-IFN alpha-2b plus ribavirin therapy and 300 mg vitamin E and 600 mg vitamin C supplementation daily for 48 wk. Among the patients who continued treatment, the serum alanine aminotransferase (ALT) level at 12 wk in the zinc group was significantly lower than that in the control group. All patients in the zinc group (9/9) and 67% (8/12) of the control patients at 24 wk, and all patients in the zinc group (7/7) and 60% (6/10) of the control patients at 48 wk showed a decrease in serum ALT levels to within the normal range (7-44 U/L). HCV RNA disappeared in all patients (7/7) in the zinc group and in 8 of 10 control patients at 48 wk. Polaprezinc supplementation decreased plasma thiobarbituric acid reactive substances and prevented the decrease of polyunsaturated fatty acids of erythrocyte membrane phospholipids. No significant differences were observed in the dosage of medicines or other clinical data during the treatment. These observations indicate that polaprezinc supplementation may have induced some antioxidative functions in the liver which resulted in reduced hepatocyte injury during PEG-IFN alpha-2b plus ribavirin therapy.     

Effects of eicosapentaenoic acid supplementation in the treatment of chronic hepatitis C patients

Eicosapentaenoic acid (EPA) has been shown to exert anti-inflammatory actions. To evaluate the effects of EPA on chronic hepatitis C, we administered EPA ethyl ester capsules to patients receiving the combination therapy of interferon alpha-2b and ribavirin. EPA (1,800 mg/d) was supplemented in combination with vitamin E (300 mg/d) and C (600 mg/d) to 5 chronic hepatitis C patients (EPA group). Five patients were administered vitamin E and C but not EPA (control group). Blood samples were obtained before and after 4, 8, 12 and 24 wk of therapy and analyzed for fatty acid compositions of erythrocyte and plasma and serum 8-hydroxy-2'-deoxyguanosine. EPA in erythrocyte membrane rose to 3 fold the basal level in the EPA group, while it decreased significantly in the control group after 24 wk of therapy. Lymphocyte counts in the EPA group increased to 120.8 +/- 25.4% after 4 wk of therapy and maintained the basal level throughout therapy, whereas the counts decreased significantly in controls. The serum alanine aminotransferase level was improved significantly in the EPA group. Changes in lymphocyte counts following 24 wk of therapy correlated with the EPA level in erythrocyte. The serum 8-hydroxy-2'-deoxyguanosine level at 24 wk in the EPA group was significantly lower than that in controls. These observations may suggest the beneficial effect of EPA supplementation in the treatment of chronic hepatitis C patients.     

Experience with combined interferon alpha-2b and ribavirin in the therapy of chronic hepatitis C. Experience with one-year therapy of 100 patients. Multicenter study]

It has been established that the long term interferon therapy in patients with chronic hepatitis C is able to produce sustained remission only in about 20 per cent of the cases. According to the newest data the combined interferon and ribavirin therapy significantly increases the remission of patients in naive, non-responder or relapsed cases. Clinical remission was confirmed by enzyme activity of alaninamino transferase (ALT) and HCV-RNA-PCR tests. In order to get exact data of the remission rate and the symptom free period, a prospective multicenter study has been introduced in Hungary. Ten leading hepatologic units have been involved into the trial. Till now the combined therapy with interferon-alfa-2b (3 MU, three times a week) and ribavirin--(1000-1200 mg daily) for one year has been finished in 100 cases with chronic hepatitis C. The mean value of ALT activity decreased near to the normal level, in 58 patients it was in the normal range. Side effects with mild or moderate grades have been found in 31 cases. The interim report of this multicenter study confirm the efficacy of this combined therapy in chronic hepatitis C.     

聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎的疗效分析

丙型肝炎是由HCV引起的一种主要经血液传播的慢性进展性肝病.HCV感染发病隐匿,缺乏典型的症状和体征,且感染后60％-80％的患者可慢性化,其中约20％的患者在感染20-30年可进展为肝硬化甚至肝细胞癌,目前,聚乙二醇IFN(PegIFNa-2a)联合利巴韦林(RBV)仍是亚太地区HCV感染的标准治疗方案[1].而抗病毒治疗应答受多种因素影响,本文重点研究了PegIFNα-2a联合RBV治疗慢性丙型肝炎(CHC)患者临床与生化和心理指标等相关因素,旨在探讨持续病毒学应答率(SVR)的预后因素,为临床治疗决策提供指.     

Combination therapy for chronic hepatitis C: interferon and ribavirin.

Hepatitis C virus (HCV) infection is one of the commonest causes of liver cirrhosis and hepatocellular carcinoma. This review deals with treatment of chronic HCV infection with a combination of interferon and ribavirin. Recent trials have shown that approximately 40% of patients will clear HCV with combination treatment. This is an important advance in the treatment of this serious viral infection.     

Vitamin E and vitamin C supplementation in patients with chronic obstructive pulmonary disease

The purpose of this study was to determine whether vitamin E or vitamin C supplementation alters the DNA damage of whole blood white blood cells (WBC) in patients with chronic obstructive pulmonary disease (COPD). Thirty-five patients with stable COPD were recruited in this randomized and placebo-controlled study. Patients were randomly assigned to placebo (n = 8), 400 mg/day vitamin E (E400, n = 9), 200 mg/day vitamin E (E200, n = 9), or 250 mg/day vitamin C (C250, n = 9) for 12 weeks. The results showed that vitamin E or C supplementation did not significantly change the mean level of endogenous DNA breakages. Whereas, after 12 weeks of vitamin supplementation, the H2O2-induced DNA breakages were significantly suppressed by 45%, 59%, and 52%, respectively, in E400, E250 and C250 groups (p < 0.05). In addition, neither the level of thiobarbituric acid-reactive substances (TBARS) nor spirometric parameters were significantly changed after 12 weeks of supplementation. In conclusion, vitamin E or C supplementation for 12 weeks may improve the resistance of DNA in whole blood WBC against oxidative challenge, although more research is needed to demonstrate the beneficial effect on slowing the decline of lung function in patients with COPD.     

聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎疗效的影响因素研究

目的 分析聚乙二醇干扰素联合利巴韦林（pegylated interferon plus ribavirin,pegIFN-α/RVB）治疗慢性丙型肝炎（chronic hepatitis C,CHC）疗效的影响因素,以便辅助判断治疗效果及合理变换治疗方案。方法 收集来自江苏省句容市人民医院CHC临床治疗患者的基线资料,采用单因素及多因素Logistic回归进行分析。结果 本研究纳入371例CHC患者,总持续性病毒学应答（sustained virological response,SVR）率为64.7%。多因素Logistic回归分析结果显示,基线病毒载量HCV RNA高（OR=0.95,95%CI：0.91~0.99,P=0.012）、甲胎蛋白（alpha fetoprotein,AFP）水平异常（OR=0.87,95%CI：0.78~0.97,P=0.014）及空腹血糖（blood glucose,GLU）水平异常（OR=0.86,95%CI：0.78~0.95,P=0.004）者更不易获得SVR。结论 pegIFN-α/RVB治疗CHC患者的SVR率较高,基线病毒载量、AFP及GLU均是影响持续病毒学应答的危险因素。     

Combined interferon-alfa-2b and ribavirin therapy in patients with recurrent chronic hepatitis c after liver transplantation

Interferon with ribavirin therapy has been proposed for the treatment of hepatitis C recurring in liver transplants. AIM OF THE STUDY: Was to assess the efficacy of standard combination therapy (interferon plus ribavirin) of chronic hepatitis C in transplanted patients with recurrent severe HCV induced chronic hepatitis. METHODS: 12 patients with HCV-PCR positive reaction (genotype 1b) were treated with the therapy of interferon-alpha-2b (3 MU three times a week) and 800-1000 mg ribavirin daily. Liver biopsy had been done in every patients before and after the treatment. Study endpoints were the end of treatment and the 6 month post-therapy sustained virologic response. RESULTS: At the end of treatment 3 patients were negative for HCV-PCR and all of them had negative reaction after 6 month follow-up period. CONCLUSION: The results are in a good accordance with treatment of patients with chronic hepatitis C without liver transplantation.     

外周血单核细胞IFN-α和IL-18表达与慢性丙肝患者干扰素应答的关系

目的检测慢性丙肝(CHC)患者外周血单核细胞(PBMC)α干扰素(IFN-α)及白细胞介素18(IL-18)mRNA的表达,探讨慢性丙肝患者细胞免疫功能与干扰素应答的关系。方法聚肌胞(PolyIC)体外刺激正常对照组和慢性丙型肝炎病毒(HCV)感染组患者PBMC,取培养上清利用病毒保护试验测定IFN-α2b治疗前后病人PBMC表达的干扰素抗病毒生物学活性。同时用脂多糖(LPS)体外刺激不同组PBMC,RT-PCR检测PBMC IL-18 mRNA水平的变化。结果治疗前干扰素治疗应答组患者(n=12)和无应答组患者(n=26)PBMC分泌的干扰素抗病毒生物学活性显著低于正常对照组(n=20)(均P<0.01)。应答组患者PB-MC分泌的干扰素活性随治疗时间延长而增加,1个月已显著高于无应答组患者(P<0.01);无应答组患者PBMC分泌的干扰素活性始终处于低下水平。治疗前,应答组患者和无应答组患者PBMC IL-18 mRNA水平也显著低于正常对照组(均P<0.01);治疗后,应答组患者IL-18 mRNA水平随治疗时间延长而升高,1个月时显著高于无应答组患者(P<0.01),无应答组患者IL-18 mRNA水平始终较低。PBMC IFN-α活性和IL-18 mRNA水平有良好的正相关性(r=0.873,P<0.01)。结论慢性HCV感染无应答组的细胞免疫功能受损,不能正常表达IFN-α和IL-18,而应答组经干扰素治疗后表达能力逐渐恢复。慢性丙肝患者PBMC IFN-α活性和IL-18 mRNA水平检测可以作为干扰素治疗预后的判断指标。     

Vitamin E supplementation and oxidative status of peripheral blood mononuclear cells and lymphocyte subsets in hemodialysis patients.

Increased oxidative damage to cell membrane constituents causes profound changes in the membrane cytoarchitecture and modifications of the membrane physiological properties, e.g., the ability to respond to hormonal stimuli. In uremic patients receiving intermittent hemodialysis, a metabolic block of the phosphate pentose shunt has been described. This leads to insufficient detoxication of the hydroxyl radicals formed within the cells and therefore to increased oxidative damage to the polyunsaturated fatty acid constituents of the cell membranes. Vitamin E is known to reduce this oxidative damage and its harmful effects. We studied vitamin E (alpha-tocopherol acetate) administration in 10 chronically uremic patients receiving intermittent hemodialysis for positive effects on cell membrane-receptor response. The patients were studied before and after treatment for the extent of oxidative damage in peripheral mononuclear cells and for response to monoclonal antibodies to specific markers of T-lymphocyte subsets. After vitamin E treatment, oxidative damage decreased, and the membranes of peripheral mononuclear cells contained greater amounts of some unsaturated fatty acids. This is in agreement with a modification of the membrane phenotype markers of T-lymphocyte subsets and seems to confirm in vivo that changes in membrane structure first induced by increased oxidative damage due to the blockage of the phosphate pentose shunt can be reduced by the antioxidant action of vitamin E, which significantly influences the expression of membrane determinants.     

Effect of interferon therapy on carbohydrate metabolism in chronic hepatitis C patients]

Reversible impact of alpha-interferon on carbohydrate (CH) metabolism was observed in patients with hepatitis C treated with interferon between 1993 and 1997. Of the 32 patients 3 individuals had known to have diabetes mellitus before the treatment and 1 had impaired glucose tolerance (IGT). 28 patients proved to have normal CH metabolism before the interferon treatment. To each patients was interferon alpha was administrated in a dose 3 MU TIW. During the 6 months interferon therapy of the 3 patients treated with oral antidiabetic drug one's diabetes mellitus did not deteriorated, but 2 patients required insulin therapy. In the patient with known IGT a manifested diabetes mellitus has gradually developed. Out of the 28 patients with normal CH metabolism in 9 cases developed IGT, 19 patient's CH metabolism did not change significantly. All of the changes induced by interferon proved to be reversible.     

Vitamin C supplementation decreases oxidative DNA damage in mononuclear blood cells of smokers

Summary. Background: Antioxidants, in particular vitamin C, have been suggested to decrease oxidative DNA damage. Such effects have been shown in mononuclear blood cells in the first few hours after ingestion, whereas studies of longer-term effects in well-nourished humans have been mainly negative. Aim: To investigate the antioxidant effect of vitamin C in terms of oxidative DNA damage measured by the comet assay and DNA repair measured by expression of OGG1 mRNA in blood cells of male smokers given 2 × 250 mg vitamin C daily as plain or slow release tablets combined with plain release vitamin E 2 × 91mg, or placebo for 4 wk. Results: This study showed a difference in DNA protective effects between a slow release and a plain release vitamin C formulation. Ingestion of slow release vitamin C formulation was associated with fewer endonuclease III and formamidopyrimidine DNA glycosylase sensitive sites measured by the comet assay in mononuclear blood cells obtained 4 h and 8 h after a single tablet and 4 wk after two tablets a day. Ingestion of the vitamin formulation with plain release only indicated a damage-reducing effect 4 h after intake of a single tablet, and the effect was more apparent on endonuclease III than formamidopyrimidine DNA glycosylase sites. Overall the slow release tablets of vitamin C formulation had a more pronounced and a sustained protective effect on base damage compared with the plain release tablets. Plasma vitamin E was unaltered in the first 12 h after ingestion of a single tablet, suggesting that the antioxidant effect was mediated by vitamin C. Differences in plasma vitamin C levels at steady state could not explain the difference between the two vitamin C formulations, whereas wider amplitudes of plasma vitamin C were seen after ingestion of plain release formulation compared to slow release formulation. Assessment of OGG1 mRNA levels by RT-PCR did not indicate increased expression of this DNA repair gene after 4 wk of vitamin supplementation. Conclusion: This study suggests that long-term vitamin C supplementation at high dose, i. e. 500 mg together with vitamin E in moderate dose, 182mg, decreases the steady-state level of oxidative DNA damage in mononuclear blood cells of smokers.     

Current trends and first clinical studies of therapy for chronic hepatitis C in children using pegylated interferon alpha and ribavirin

Our aim was to evaluate the recent clinical data concerning the course of chronic hepatitis C in children and the rationale indications for therapy. There is no doubt that in adult group the pegylated interferon is better than standard interferon and results in higher response rate in combination with ribavirin. Actually complicating the issues surrounding hepatitis C in children is the lack of information on the efficacy and safety of this therapy in pediatric age group. The first preliminary data of our clinical study concerning the therapy with pegylated interferon alpha 2b and ribavirin in 10 children with chronic hepatitis C (genotype 1) suggest a good tolerance of this drug and the end of treatment virologic response in 8 children (80%).     

Controlled trial with interferon alfa 2-b in chronic hepatitis C patients

Thirty-eight chronic hepatitis C (CHC) Egyptian patients with persistently elevated serum alanine aminotransferase (ALT) for 6 months were randomly allocated into 2 groups: Group I (19 patients) received 3 million units (MU) of interferon alpha - 2b (Intron-A) subcutaneously thrice weekly for 6 months. In group I, complete response (normalization of ALT by the end of treatment) was achieved in 8 patients (42.1%), partial response (decrease of ALT by at least 50% of the pretreatment values) in 7 patients (36.8%) and no response in 4 (21.1%). Sustained response for 6 months after the end of therapy was attained in 4 of the 8 (50%) complete responders. Thus attaining an overall sustained response in 4 of the 19 patients (21.1%). In group II, spontaneous normalization of ALT was established in 1 patient (5.3%). Repeat liver biopsies in 16 patients of the interferon group, revealed moderate improvement in the degree of lobular inflammation, hepatocyte necrosis and portal inflammation. We conclude from this study that treatment of CHC with 3 MU of IFN-alfa 2b thrice weekly for 6 months is associated with a low response rate (21.1%). To improve the results, escalation of the IFN dose and/or prolongation of the treatment period should be considered.