The use of vitamin E in preventing taxane-induced peripheral neuropathy.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of chemotherapy. Several trials have evaluated the protective effect of vitamin E in preventing CIPN with controversial results. This study aims to outline the role of vitamin E in preventing CIPN. METHODS: A prospective phase II, open-label randomized controlled study was conducted in patients receiving taxane-based chemotherapy in Ain Shams University Hospitals, using vitamin E at a dose of 400 mg twice daily. The primary endpoint was the incidence of grade ≥ 2 sensory neuropathy according to CTCAE v 5.0 in each treatment arm. Secondary endpoints include time to onset and the duration of grade ≥ 2 sensory neuropathy. RESULTS: A total of 140 patients were randomized between the control and vitamin E arms. There was no difference in the incidence of grade ≥ 2 sensory neuropathy between the two arms (25.7% in each arm; P = 1.0), as well as the time to onset of neuropathy (P = 0.24). However, there was a statistically significant difference between the 2 arms as regards the duration of neuropathy. The median duration was 12.5 vs. 5 weeks in the control and vitamin E arms respectively (P = 0.01). CONCLUSION: Our study did not demonstrate a protective role of vitamin E in decreasing the incidence of CIPN in patients receiving taxane-based chemotherapy. However, the recovery from CIPN was much better as compared to the control arm, which may indicate a role for vitamin E in decreasing the duration and severity of CIPN.

Protein kinase expression as a predictive factor for interferon response in chronic hepatitis C patients.

Egypt has the highest prevalence of hepatitis C virus (HCV) worldwide. Currently, combined pegylated interferon and ribavirin therapy are the standard treatment. The biological activity of interferon (IFN) is mediated by the induction of intracellular antiviral proteins, such as 2'-5' oligoadenylate synthetase, and dsRNA-activated protein kinase. IFN-inducible double-stranded RNA-activated protein kinase (PKR) is thought to play a key antiviral role against HCV. Some studies observed that PKR expression was higher in sustained viral responders compared with the non-responders. The PKR is considered as antiviral toward HCV and responsible for IFN's effect against HCV while others have showed that, there were kinetic results indicate that HCV infection is not altered by reduced levels of PKR, indicating that HCV is resistant to the translational inhibitory effects of the phosphorylated forms of PKR. This study was conducted on 50 consecutive patients with chronic HCV infection (CHC) and 20 healthy controls. All the patients were subjected to clinical and laboratory assessment, abdominal ultrasound, and liver biopsy. Determination of PKR gene quantity by using a real time PCR was done at the baseline and at the end of treatment for all patients and controls. Pre-treatment levels of protein kinase gene were significantly higher in responders in comparison with non-responders (P < 0.001). It was found that 97.06% of patients who were responding to treatment had the expression of protein kinase gene greater than 2(6) cycle threshold.

A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis.

PURPOSE: Milk thistle or its purified extract, silymarin (Silybum marianum), is widely used in treating acute or chronic hepatitis. Although silymarin is hepatoprotective in animal experiments and some human hepatotoxic exposures, its efficacy in ameliorating the symptoms of acute clinical hepatitis remains inconclusive. In this study, our purpose was to determine whether silymarin improves symptoms, signs and laboratory test results in patients with acute clinical hepatitis, regardless of etiology. METHODS: This is a randomized, placebo-controlled trial in which participants, treating physicians and data management staff were blinded to treatment group. The study was conducted at two fever hospitals in Tanta and Banha, Egypt where patients with symptoms compatible with acute clinical hepatitis and serum alanine aminotransferase (ALT) levels >2.5 times the upper limit of normal were enrolled. The intervention consisted of three times daily ingestion of either a standard recommended dose of 140 mg of silymarin (Legalon, MADAUS GmbH, Cologne, Germany), or a vitamin placebo for four weeks with an additional four-week follow-up. The primary outcomes were symptoms and signs of acute hepatitis and results of liver function tests on days 2, 4 and 7 and weeks 2, 4, and 8. Side-effects and adverse events were ascertained by self-report. RESULTS: From July 2003 through October 2005, 105 eligible patients were enrolled after providing informed consent. No adverse events were noted and both silymarin and placebo were well tolerated. Patients randomized to the silymarin group had quicker resolution of symptoms related to biliary retention: dark urine (p=0.013), jaundice (p=0.02) and scleral icterus (p=0.043). There was a reduction in indirect bilirubin among those assigned to silymarin (p=0.012), but other variables including direct bilirubin, ALT and aspartate aminotransferase (AST) were not significantly reduced. CONCLUSIONS: Patients receiving silymarin had earlier improvement in subjective and clinical markers of biliary excretion. Despite a modest sample size and multiple etiologies for acute clinical hepatitis, our results suggest that standard recommended doses of silymarin are safe and may be potentially effective in improving symptoms of acute clinical hepatitis despite lack of a detectable effect on biomarkers of the underlying hepatocellular inflammatory process.

Symptomatic acute hepatitis C in Egypt: diagnosis, spontaneous viral clearance, and delayed treatment with 12 weeks of pegylated interferon alfa-2a.

BACKGROUND AND OBJECTIVES: The aim of this study was to estimate the proportion of spontaneous viral clearance (SVC) after symptomatic acute hepatitis C and to evaluate the efficacy of 12 weeks of pegylated interferon alfa-2a in patients who did not clear the virus spontaneously. METHODS: Patients with symptomatic acute hepatitis C were recruited from two "fever hospitals" in Cairo, Egypt. Patients still viremic three months after the onset of symptoms were considered for treatment with 12 weeks of pegylated interferon alfa-2a (180 microg/week). RESULTS: Between May 2002 and February 2006, 2243 adult patients with acute hepatitis were enrolled in the study. The SVC rate among 117 patients with acute hepatitis C was 33.8% (95%CI [25.9%-43.2%]) at three months and 41.5% (95%CI [33.0%-51.2%]) at six months. The sustained virological response (SVR) rate among the 17 patients who started treatment 4-6 months after onset of symptoms was 15/17 = 88.2% (95%CI [63.6%-98.5%]). CONCLUSION: Spontaneous viral clearance was high (41.5% six months after the onset of symptoms) in this population with symptomatic acute hepatitis C. Allowing time for spontaneous clearance should be considered before treatment is initiated for symptomatic acute hepatitis C.

HCV-related morbidity in a rural community of Egypt.

The origin of the hepatitis C virus (HCV) epidemic in Egypt has been attributed to intravenous schistosomiasis treatment in rural areas in the 1960s to 70s. The objective of this study was to estimate the HCV-related morbidity in a rural area where mass schistosomiasis treatment campaigns took place 20-40 years before. The study sample included 2,425 village residents aged 18-65 years recruited through home-based visits. Overall, HCV antibody prevalence was 448/2,425 = 18.5% (95% CI = 16.9-20.1%), reaching 45% in males over 40 years, and 30% in females over 50 years. Of those with HCV antibodies, 284/448 (63.4%, 95% CI = 58.7-67.9%) had chronic HCV infection, among which 107/266 (40.2%, 95% CI = 34.3-46.4%) had elevated alanine aminotransferase (ALT). As part of pre-treatment screening, 26 consenting patients had a liver biopsy: 13 (50.0%) had a treatment indication. Thus, of all patients with HCV antibodies, 13 (2.9%) were eligible for treatment and willing to be treated. The relatively low level of morbidity observed in this study is discussed in view of co-factors of HCV infection progression, such as young age at infection, absence of alcohol intake, the prevalence of Schistosoma mansoni infection, and the prevalence of chronic hepatitis B.

Effect of interferon-alpha on experimental Schistosoma mansoni infection in mice.

To investigate the immunomodulatory effect of the Th1 mediated cytokine IFN-alpha on schistosomiasis, this cytokine was weekly injected into mice experimentally infected with S. mansoni, beginning from day 0 (group II), week 3 (group III), week 6 (group IV) and week 10 (group V) post-infection. TGF-beta1 serum levels were estimated on a weekly basis and beginning one week after initiation of IFN-alpha therapy, while all animals were sacrified on week 14 to be used for egg counts in liver and small intestine, oogram study for determination of the maturity of deposited eggs, and histopathological examination of stained liver sections. IFN-alpha treated groups were characterized by a more intense oviposition in the intestine (liver/intestine ratio less than 1), with higher egg numbers the earlier IFN-alpha was administered. Oograms of the intestine indicated the level of immature eggs to be statistically significantly higher in group II, III and IV than in the control group I (p < 0.05). In IFN-alpha medicated mice, the mean numbers and diameters of hepatic granulomas were less than in GI, in addition to a lower representation of fibrocellular and fibrous granulomas among them (all parameters p < 0.05), especially in Gs IV & V. The inflammatory cell population in the form of eosinophils, histiocytes and giant cells was more pronounced in Gs III, IV & V. TGF-beta1 serum levels showed a progressive rise, however more pronounced in the untreated control. A statistically positive significant was established between TGF-beta1 levels and number, size and percentage of fibrotic hepatic granulomas in all groups.

Early post-treatment immunoglobulin profile in human schistosomiasis.

In a trial at determining the most relevant immunoglobulin isotype that could reflect success of praziquantel treatment, an ELISA using soluble egg antigen (SEA) was applied on sera of Egyptian patients suffering from active intestinal schistosemiasis without hepatic complications, determining the levels of IgE, IgA, IgM, IgG1, IgG2, IgG3 and IgG4 raised against the SEA, both, pre- and early post-treatment. The positive results obtained to all anti-SEA immunoglobulin isotypes before treatment support the usefulness of this technique in the diagnosis of schistosomiasis. Except for IgG3 subclass, a statistically significant correlation was found between egg output-reflecting intensity of infection- and the different immunoglobulin levels, especially anti-SEA IgG4. When repeating the assay 5-6 months after treatment, the immunoglobulin levels showed either a rise (in case of IgE) or a drop (in case of IgA, IgM & IgG1-4), all of statistical significance, yet, IgG1-4 were still positive. So, ELISA could not give a definite indication of cure after anti-bilharzial treatment. IgE, IgG2 and IgG4 were revealed to be the most significant immunoglobulin isotypes at the post-treatment level, both statistically and due to their implications on resistance/ susceptibility to re-infection and also due to the correlation of IgG4 with the tendency to develop periportal fibrosis. Conclusively, although not having defined a particular Ig isotype as marker for cure, yet it exposed the urge for early post-treatment determination of IgE and IgG4 isotypes, which could serve as markers for picking up high risk patients susceptible to reinfection or liable to develop bilharzial periportal fibrosis, and who might benefit from a second course of specific treatment.

Cerebrospinal echinococcosis: serodiagnosis using different hydatid cyst fluid antigens.

Cerebrospinal hydatid disease diagnosis may impose some problems, as ultrasonography is not applicable and serology may not detect the low antibody titre often associated with intracranial or orbital cystic echinococcosis. Serological tests were performed on 14 cases with intracranial or spinal cystic lesions, out of which 9 were cases of hydatidosis, in addition to 26 cases with other parasitic diseases as detected by stool examination. The sensitivity of all tests and antigens used did not exceed 6 out of the 9 positive cases, and achieved by the Eg1 and Eg2 when applied in the ELISA. The specificity of this technique using the two antigens was 92.3%& 76.9%, respectively. Semi-purified Em1 and purified 44 KDa used in the ELISA, crude Eg1 used for the CIEP and the crude commercial antigen of the IHAT, all gave lower sensitivities than the former two antigens, yet their specificities amounted to 100%. In conclusion, for diagnosis of cerebrospinal hydatidosis the home-prepared Eg1 antigen is recommended in the ELISA system, as it is relatively easily prepared from available resources to be supplemented with radio-imaging techniques especially Magnetic Resonance Imaging and/or MR spectroscopy, the latter being very helpful in clearly differentiating various types of intracranial cysts.