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.     

Anti-IL-6 receptor monoclonal antibody as a new treatment of endometriosis

Immunologic Research - Many pro-inflammatory cytokines especially tumor necrotic factor alpha (TNFα), interleukin (IL)-1β, and IL-6 have crucial role in the pathogenesis of endometriosis....     

Impact of cigarette smoking on response to interferon therapy in chronic hepatitis C Egyptian patients

AIM: Smoking may affect adversely the response rate to interferon-α. Our objective was to verify this issue among chronic hepatitis C patients. METHODS: Over the year 1998, 138 chronic hepatitis C male Egyptian patients presenting to Cairo Liver Center, were divided on the basis of smoking habit into: group I which comprised 38 smoker patients (>30 cigarettes/d) and group II which included 84 non-smoker patients. Irregular and mild smokers (16 patients) were excluded. Non eligible patients for interferon-~ therapy were excluded from the study and comprised 3/38 (normal ALT) in group I and 22/84 in group II (normal ALT, advanced cirrhosis and thrombocytopenia). Group I was randomly allocated into 2 sub-groups: group Ia comprised 18 patients who were subjected to therapeutic phlebotomy while sub-group Ib consisted of 17 patients who had no phlebotomy. In sub-group Ia, 3 patients with normal ALT after repeated phlebotomies were excluded from the study. Interferon-α2b 3 MU/TIW was given for 6 mo to 15 patients in group Ia, 17 patients in group Ib and 62 patients in group II. Biochemical, virological end-of- treatment and sustained responses were evaluated.RESULTS: At the end of interferon-α treatment, ALT was normalized in 3/15 patients (20%) in group Ia and 2/17 patients (11.8%) in group Ib compared to17/62 patients (27.4%) in group II (P=0.1). Whereas 2/15 patients (13.3%) in group Ia. and 2/17 patients (11.8%) in group Ib lost viraemia compared to 13/62 patients (26%) in group II(P=0.3). Six months later, ALT was persistently normal in 2/15 patients (13.3%) in group la and 1/17 patients (5.9%) in group Ib compared to 9/62 patients (14.5%) in group Ⅱ (P= 0.47). Viraemia was eliminated in 1/15 patients (6.7%) in group Ia and 1/17 patients (5.9%) in group Ib compared to 7/62 patients (11.3%) in group Ⅱ, but the results did not mount to statistical significance (P = 0.4). CONCLUSION: Smokers suffering from chronic hepatitis C tend to have a lower response rate to interferon-α compared to non-smokers. Therapeutic phlebotomy improves the response rate to interferon-α therapy among this group.     

Response of hepatitis C genotype-4 naïve patients to 24 weeks of Peg-interferon-alpha2b/ribavirin or induction-dose interferon-alpha2b/ribavirin/amantadine: a non-randomized controlled study

BACKGROUND AND AIM: Currently, pegylated interferon is the most effective therapy for hepatitis C but its cost is out of reach of most patients in the developing countries. The aim of this study was to assess the response rate of genotype-4 patients to 24 wks of peg-interferon-alpha2b (Peg-IFN-alpha2b) and ribavirin (RBV) or interferon-alpha2b (IFN-alpha2b) with RBV and amantadine (AMD) as an alternative option. METHODS: In a controlled study, 180 biopsy-proven na?ve chronic hepatitis C patients were allocated into three groups based on their financial affordability to any of the study regimens. Group I (control) comprised 40 patients who received Peg-IFN-alpha2b in a flat dose of 100 mug/wk (the dose available in Egypt) plus RBV 1,000-1,200 mg per day based on body weight for 48 wks. Group II comprised 70 patients who received the same regimen for 24 wks. Group III comprised 70 patients who received induction-dose triple therapy (IDTT) in the form of IFN-alpha2b 3 MU once daily for the first 4 wks then reduced to TIW for 20 wks plus RBV 1,000-1,200 mg per day based on body weight and AMD 100 mg twice daily for 24 wks. Six patients from group I, eight patients from group II, and four from group III discontinued the study either due to financial limitations and/or intolerable adverse effects of the drugs. RESULTS: Intention-to-treat analysis revealed that sustained virological response (SVR) achieved in 22 (55.0%), 34 (48.6%), and 20 (28.6%) in groups I, II, and III, respectively. Adherence-to-treatment analysis (80/80/80) revealed that SVR achieved in 22 (64.7%), 34 (54.8%), and 20 (30.3%) in groups I, II, and III, respectively. In absence of eradication of hepatitis-C-virus-RNA at week 12, there was virtually no chance of achieving SVR. These data collectively may indicate that genotype 4 is "not difficult to treat" as previously reported. CONCLUSION: Response of genotype-4 patients to 24 wks of Peg-IFN-alpha2b/RBV did not significantly differ from 48 wks, but was significantly higher than IDTT. Although SVR achieved by IDTT is less than Peg-IFN-alpha, yet it might provide a second option when the latter is not affordable. Early virological response should be used as a predictor to SVR to avoid unnecessary expenses in nonresponders patients.     

Evaluation of risk factors for intrafamilial transmission of HCV infection in Egypt

The objectives of this study were to define the prevalence of intrafamilial transmission of HCV and evaluate the risk factors in this setting. A cross-sectional, family-based seroepidemiological study was performed in Cairo Liver Center and Oncology Diagnostic Unit, Ain Shams University. A total of 102 index patients (72 males and 30 females) with type C chronic liver disease and their 305 family contacts were studied. Only 265 family contacts were eligible for the study as they showed no previous history of exposure to risk factors. Overall, 15 family contacts (5.7%) were positive for anti-HCV, indicating a lower anti-HCV prevalence among family contacts than the general population in Egypt. Spouses were at higher risk of infection (16.7%) than family members (2.6%). Among the repeatedly positive samples for anti-HCV, only 3 samples were HCV-RNA positive (1.1%), all were spouses. Logistic regression analysis revealed that spouses reporting promiscuous sexual relations were at higher risk than those with normal sexual relations. Contacts sharing personal objects were also at higher risk to develop HCV infection. Index cases reporting previous blood transfusion (18.6%), i.v. antibilharzial therapy (33.3%), multiple sex partners (1.0%) or advanced liver diseases were more infective to their family contacts. The contacts of index cases had increasing risk of HCV infection with increase in age and duration of contact. The prevalence rate of intrafamilial spread of HCV infection is low compared to the rate among general population, emphasizing its limited role in transmitting HCV infection. Long duration of sexual contact and promiscuous sexual activities were major risk factors in this setting.     

Murine neutralizing antibody response and toxicity to synthetic peptides derived from E1 and E2 proteins of hepatitis C virus

Introduction

The highest estimated prevalence of HCV infection has been reported in Egypt, nearly 12% mostly type 4. Currently, a commercial vaccine to protect this high risk population as well as global HCV infected patients is not available.

Objectives

In the present study, we aim at: (1) examining the viral binding capacities of purified monospecific polyclonal murine antibodies raised against genetically conserved viral protein sequences, i.e. synthetic peptides derived from those sequences located within envelope proteins and (2) assessment of immunogenic properties and safety parameters of those peptides individually and in a vaccine format in mice.

Methods

Purified IgG Abs from immunized mice were used in immunocapture RT-PCR experiments to test viral neutralization by Abs raised against each of 4 peptides termed p35 (E1), p36 (E2), p37 (E2) and p38 (E2). Swiss mice were immunized with each of the 3 peptides (p35, p37 and p38) which generated neutralizing antibodies in immunocapture experiments. Antibody responses to corresponding peptides were determined using different routes of administration, different adjuvants, different doses and at different time points post-injection. To explore the dose range for future pharmacological studies, three doses namely 50 ng, 10 μg and 50 μg/25 gm mouse body weight were tested for biochemical and histopathological changes in several organs.

Results

Murine Abs against p35, p37 and p38 but not p36 showed HCV neutralization in immunocapture experiments. Subcutaneous injection of peptides elicited higher responses than i.m. and i.p. Immunization with Multiple Antigenic Peptide (MAP) form or coupled to Al PO4 elicited the highest Ab responses. Peptide doses of 50 ng/25 gm body weight or less were effective and safe, however dose assessment still requires further study. Histopathological changes were observed in animals that received doses ∼1000 times higher than the potential therapeutic dose.

Conclusion

Exploration of humoral immunogenicity, neutralization capacity and safety suggested that the peptides presented herein are candidate vaccine components for further preclinical assessment.     

Effect of surveillance for hepatocellular carcinoma on tumor staging and treatment decisions in Egyptian patients

Purpose  

Egyptian hepatocellular carcinoma (HCC) patients present at advanced stages. We aimed to study the influence of surveillance versus non-surveillance on HCC staging and the potential therapeutic options.     

Ethnic differences in polymorphisms of tumor necrosis factor-alpha, interleukin-10, and transforming growth factor-beta1 genes in patients with chronic hepatitis C virus infection

Ethnic differences in the outcome of hepatitis C have been described. Our aim was to investigate ethnic differences in the distribution of genotypes associated with polymorphisms of the tumor necrosis factor-alpha promoter, interleukin-10 promoter, and transforming growth factor-beta1 leader sequence in patients with hepatitis C. Genomic DNA was obtained from 71 Egyptians and 67 Caucasians (hepatitis C and control patients). Amplification of appropriate gene segments was followed by direct sequencing. Infrequently occurring polymorphisms were identified at positions -244 and -77 of the tumor necrosis factor-alpha promoter and at positions -851 and -657 of the interleukin-10 promoter. The G/A genotype associated with tumor necrosis factor-alpha promoter positions -376 and -244 was more frequent in Egyptians (P =0.001 and P =0.004, respectively). The -244 G/A genotype occurred only in healthy Egyptians (P =0.024). Thus, ethnic differences in the distribution of genotypes of the tumor necrosis factor-alpha promoter exist, which may have clinical implications on the outcome of hepatitis C.     

Curse of schistosomiasis on Egyptian liver

Schistosomiasis is a chronic parasitic disease caused by atrematode blood fluke of the genus schistosoma that belongsto the schistosomatidae family. The ancient Egyptianscontracted the disease more than 4 000 years ago. It wasrecognized through haematuria, the main sign of urinarybilharziasis was recorded in the Kahun papyrus 1900 B.C.“ a-a-a-“ disease.