Increased recurrence rates of hepatocellular carcinoma after DAA therapy in a hepatitis C‐infected Egyptian cohort: A comparative analysis

In Egypt, hepatocellular carcinoma (HCC) is the most common form of cancer and direct‐acting antivirals (DAA) are administered on a large scale to patients with chronic HCV infection to reduce the risk. In this unique setting, we aimed to determine the association of DAA exposure with early‐phase HCC recurrence in patients with a history of HCV‐related liver cancer. This was a prospective cohort study of an HCV‐infected population from one Egyptian specialized HCC management centre starting from the time of successful HCC intervention. The incidence rates of HCC recurrence between DAA‐exposed and nonexposed patients were compared, starting from date of HCC complete radiological response and censoring after 2 years. DAA exposure was treated as time varying. Two Poisson regressions models were used to control for potential differences in the exposed and nonexposed group; multivariable adjustment and balancing using inverse probability of treatment weighting (IPTW). We included 116 patients: 53 treated with DAAs and 63 not treated with DAAs. There was 37.7% and 25.4% recurrence in each group after a median of 16.0 and 23.0 months of follow‐up, respectively. Poisson regression using IPTW demonstrated an association between DAAs and HCC recurrence with an incidence rate ratio of 3.83 (95% CI: 2.02‐7.25), which was similar in the multivariable‐adjusted model and various sensitivity analyses. These results add important evidence towards the possible role of DAAs in HCC recurrence and stress the need for further mechanistic studies and clinical trials to accurately confirm this role and to identify patient characteristics that may be associated with this event.     

Evaluation of serum biomarkers of fibrosis and injury in Egyptian patients with chronic hepatitis C

BACKGROUND/AIMS: We evaluated whether surrogate serum biomarkers for liver injury are comparable to liver biopsy in Egyptian patients with hepatitis C virus (HCV) infection. SUBJECTS: Two hundred and twenty Egyptian patients, 91% infected with genotype-4 HCV, undergoing liver biopsy during evaluation for interferon/ribavirin therapy. METHODS: Liver biopsy scored by the Ishak method was compared to biochemical tests, platelet count and two fibrosis biomarkers: hyaluronic acid (HA) and YKL-40. Univariate and logistic regression analyses determined independent predictors of fibrotic, inflammatory, and fatty changes. Biomarkers were evaluated for ability to differentiate between severe fibrosis/cirrhosis and no/mild fibrosis. RESULTS: Although increasing age, HA, YKL-40, AST, reduced platelet count, and AST and HA/platelet count ratios were associated with fibrosis by univariate analysis, the other variables were not significant after controlling for HA (p=0.0001) and age (p=0.004). Although age and some biomarkers were associated with inflammation, none remained significant after controlling for fibrosis. YKL-40 (p=0.04) and aspartate aminotransferase (p=0.05) remained associated with steatosis after controlling for fibrosis. CONCLUSIONS: In Egyptians with chronic HCV, young patients with low levels of HA are at very low risk of fibrosis. This can limit the number of liver biopsies to those whose clinical findings conflict with the biomarker results.     

Status of intestinal parasitic infections among rural and urban populations,southwestern Iran

Objective: To evaluate the prevalence and risk factors of intestinal parasitic infections in the urban and rural areas of Shushtar County,southwest Iran.Methods: A total of 1 008 fecal samples were analyzed by direct smear examination,formalinether concentration,and Ziehl-Neelsen and trichrome staining; furthermore,PCR was used to distinguish Trichostrongylus and hookworm species based on 28 S rRNA gene.Results: Totally,16.0% cases tested positive,either with a pathogenic or a non-pathogenic parasite. Protozoa were detected in 14.0%,helminths in 1.0%,protozoa and helminth coinfections were detected in 0.3%,and co-infections of two protozoa were detected in 0.7% of cases. The most common protozoa and helminths were Giardia duodenalis(7.7%) and Trichostrongylus spp.(0.5%),respectively. Among five microscopy Trichostrongylus positive cases,Trichostrongylus culbriformis was successfully identified in three isolates by sequencing. In the rural areas,the prevalence of parasitic infection was higher(9.8%) than that in the urban areas(6.2%). A significant association was found between educational level,type of drinking water,animals contact,hand-washing,and clinical symptoms. Conclusions: This study indicates that intestinal parasitic infections remain as a public health priority in Shushtar County. It seems that drinking water and environmental sanitation are the main risk factors of parasitic infections in rural areas.     

Study of serum ghrelin changes and its correlation with malnutrition in liver cirrhosis in Egypt

Egypt has the highest prevalence of hepatitis C virus (HCV) all over the world, with an estimated 8-10 million among a population of 68 million having been exposed to the virus and 5-7 million active infections (Frank et al., 2000). It is considered the most common aetiology of chronic liver disease (CLD) in Egypt, where prevalence of antibodies to HCV (anti-HCV) is 10-fold greater than in the United States and Europe (Goldstone et al., 2002; Strickland et al., 2002). We have studied the role of plasma ghrelin, an orexigenic hormone that was found to correlate with malnourishment in CLD depending on Child classification. Sixty patients were divided in three groups according to Child classification and were compared to normal healthy controls (20 subjects). There was a highly significant correlation of plasma ghrelin and body mass index (BMI), mid arm circumference (MAC), waist circumference (WC) and tricuspid skin fold thickness (TSF). Also plasma ghrelin was specific and sensitive by the ROC curve analysis to BMI, which would indicate a new marker for malnourishment and possibility of a novel therapeutic approach.     

The role of microbiota in tissue repair and regeneration

A comprehensive understanding of the human body endogenous microbiota is essential for acquiring an insight into the involvement of microbiota in tissue healing and regeneration process in order to enable development of biomaterials with a better integration with human body environment. Biomaterials used for biomedical applications are normally germ‐free, and the human body as the host of the biomaterials is not germ‐free. The complexity and role of the body microbiota in tissue healing/regeneration have been underestimated historically. Traditionally, studies aiming at the development of novel biomaterials had focused on the effects of environment within the target tissue, neglecting the signals generated from the microbiota and their impact on tissue regeneration. The significance of the human body microbiota in relation to metabolism, immune system, and consequently tissue regeneration has been recently realised and is a growing research field. This review summarises recent findings on the role of microbiota and mechanisms involved in tissue healing and regeneration, in particular skin, liver, bone, and nervous system regrowth and regeneration highlighting the potential new roles of microbiota for development of a new generation of biomaterials.     

Therapeutic outcome of 6198 interferon‐naïve Egyptian patients with chronic hepatitis C: a real‐life experience and lessons to be learned in DAAs’ era

Antiviral therapy for HCV infection has been validated in randomized controlled clinical trials, but its value in the real world is less well studied. There is relatively little data on real‐world responses to interferon‐based therapies for patients with genotype 4 infection. We aimed to examine experience with large‐scale access to antiviral therapy in chronic HCV in a real‐life clinical setting in Egypt. Detailed pretreatment data of 6198 IFN‐naïve chronic HCV patients who had received PEG‐IFN/RBV therapy at Cairo‐Fatemic Hospital, Egypt, between 2009 and 2012 were obtained from the HCV database. At week 12, 95.7% of patients had undetectable HCV RNA, and by week 24 and 48, breakthrough was 6% and 4%, respectively. However, 43.7% of patients discontinued treatment prematurely, and intent to treat end of treatment response was 44.6% (79.3% per protocol). Sustai‐ned response data were available from only 1281 patients and was 84.9%. Haematological abnormalities were comparable in patients who did or did not comply with therapy. This is the first real‐world, large‐scale experience of antiviral therapy in chronic HCV in Egypt. Suboptimal response in HCV predominantly genotype 4 was mainly driven by noncompliance as well as gaps in the healthcare system leading to treatment discontinuation. These results need to be considered in the era of all oral antiviral regimes.     

Study of the enhancing effect of sodium chloride injection on radiofrequency ablation of hepatocellular carcinoma

Background and study aimsOne of the potential strategies to increase the efficacy of RFA is to modulate the biologic environment of the treated tissues. Several investigators have studied increasing RFA heating by combining intra-tumoral injections of different concentrations of sodium chloride with RFA. The aim of this study is to assess the enhancing effect of normal saline (NS) on radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) using a cool-tip needle.Patients and methodsThis study included 40 patients with HCC (proved by histopathology or combined spiral CT and elevated alpha-fetoprotein). They were randomly divided into two groups (20 patients in each group). The first group was treated with RFA preceded by intra-tumoral normal saline injection (RFA + S); the second group was treated with RFA only (RFA).ResultsThe procedure was successful in all patients (100%) of the RFA + S group and in 11 (55%) of the RFA group (as proved by spiral CT or pathology). This difference between the two procedures was statistically highly significant (P = <0.01). No major complications occurred in either group.ConclusionsCombined RFA and normal saline is more effective than RFA alone. Considering the reduced cost and wide availability of isotonic saline together with the easy performance of the intra-tumoral injection, the dramatic improvement in therapeutic effect of RFA to 100% could be a breakthrough in future strategies to modernize the RFA technique.     

Response and seroconversion rates among HBeAg-positive chronic HBV Egyptian patients treated with peginterferon alpha 2a (Pegasys), a single-centre experience

Background and study aimsWe aimed to evaluate the therapeutic efficacy of pegylated interferon alpha-2a 180 μg as a treatment for hepatitis B ‘e’ antigen (HBeAg)-positive genotype D chronic hepatitis B patients.Patients and methodsThirty patients attending the outpatient clinic at the National Hepatology and Tropical Medicine Research Institute were treated with peg.interferon alpha-2a (180 μg) weekly for a period of 48 weeks. Pre-enrolment assessment was performed through biochemical, serological and quantitative HBV DNA testing. Liver biopsy was performed in all patients. Evaluation was done at weeks 12, 24 and 48 of treatment by liver enzymes, complete blood count (CBC), HBeAg/HBeAb and quantitative HBV DNA testing.ResultsAt the end of 48 weeks of treatment only three cases (10%) of the study population showed HBeAg seroconversion and an undetectable HBV DNA level. None of responders exhibited hepatitis B surface antigen (HbsAg) loss. There were five (16.7%) primary non-responders, four (13.3%) relapsers, four (13.3%) cases flared at week 12, and 14 (46.6%) cases who were non-responders. No specific predictors of response could be identified among patients.ConclusionOne year of peg. interferon alpha-2a 180 μg weekly led to HBeAg seroconversion and an undetectable HBV DNA level in 10% of cases. Considering the privilege of a finite duration of treatment, tailoring of treatment and proper patient selection is of great importance in considering this therapy as a first line of treatment among HBeAg-positive chronic HBV Egyptian patients.     

Tamoxifen alleviates hepatitis C virus‐induced inhibition of both toll‐like receptor 7 and JAK‐STAT signalling pathways in PBMCs of infected Egyptian females

Summary. Hepatitis C virus (HCV) is a major health concern in Egypt being highly prevalent among Egyptians. The two genders experience different responses to HCV infection and show variations in response to interferon (IFN)‐based therapy that may be attributed to sex hormones. We previously demonstrated the suppressive effect of 17β‐estradiol (E2) on the expression of the IFN‐stimulated gene MxA in HCV‐infected peripheral blood mononuclear cells (PBMCs). The selective oestrogen receptor (ER) modulator Tamoxifen has been shown to have an antiviral effect against HCV, but its effect on the host immune response is unknown. We investigated the effect of Tamoxifen on the IFN signalling pathways in PBMCs of HCV‐infected Egyptian females. We pooled PBMCs and treated then with exogenous interferon alpha (IFNα) or the TLR7 ligand, Imiquimod, and quantified the relative expressions of MxA using RTqPCR. Studies were performed with and without Tamoxifen pretreatment. Pretreatment with Tamoxifen reversed the suppressive effect of E2 on the JAK‐STAT pathway in IFNα‐treated PBMCs as indicated by a significant increase in MxA expression (P = 0.05*). Tamoxifen pretreatment also significantly upregulated MxA expression in Imiquimod‐treated PBMCs (P = 0.0011**), an effect not ascribed to ER blocking nor to an upregulation in TLR7 expression because Tamoxifen showed no potentiating effect on the expression of the receptor. In conclusion, our findings reveal that Tamoxifen has immunomodulatory effects whereby it enhances the host IFN signalling pathways during HCV infection.