Tamer Elbaz

Hepatic and Intestinal Schistosomiasis: Review

Schistosomiasis is an endemic disease in Egypt caused by the trematode Schistosoma which has different species. Hepatic schistosomiasis represents the best known form of chronic disease with a wide range of clinical manifestations. The pathogenesis of schistosomiasis is related to the host cellular immune response. This leads to granuloma formation and neo angiogenesis with subsequent periportal fibrosis manifested as portal hypertension, splenomegaly and esophageal varices. Intestinal schistosomiasis is another well identified form of chronic schistosomal affection. Egg deposition and granuloma formation eventually leads to acute then chronic schistosomal colitis and is commonly associated with polyp formation. It frequently presents as abdominal pain, diarrhea, tenesmus and anal pain. Definite diagnosis of schistosomiasis disease depends on microscopy and egg identification. Marked progress regarding serologic diagnosis occurred with development of recent PCR techniques that can confirm schistosomal affection at any stage. Many antischistosomal drugs have been described for treatment, praziquantel being the most safe and efficient drug. Still ongoing studies try to develop effective vaccines with identification of many target antigens. Preventive programs are highly needed to control the disease morbidity and to break the cycle of transmission.

Human Schistosomiasis: Clinical Perspective: Review

The clinical manifestations of schistosomiasis pass by acute, sub acute and chronic stages that mirror the immune response to infection. The later includes in succession innate, TH1 and TH2 adaptive stages, with an ultimate establishment of concomitant immunity. Some patients may also develop late complications, or suffer the sequelae of co-infection with other parasites, bacteria or viruses. Acute manifestations are species-independent; occur during the early stages of invasion and migration, where infection-naivety and the host’s racial and genetic setting play a major role. Sub acute manifestations occur after maturity of the parasite and settlement in target organs. They are related to the formation of granulomata around eggs or dead worms, primarily in the lower urinary tract with Schistosoma haematobium, and the colon and rectum with Schistosoma mansoni, Schistosoma japonicum, Schistosoma intercalatum and Schistosoma mekongi infection. Secondary manifestations during this stage may occur in the kidneys, liver, lungs or other ectopic sites. Chronic morbidity is attributed to the healing of granulomata by fibrosis and calcification at the sites of oval entrapment, deposition of schistosomal antigen-antibody complexes in the renal glomeruli or the development of secondary amyloidosis. Malignancy may complicate the chronic lesions in the urinary bladder or colon. Co-infection with salmonella or hepatitis viruses B or C may confound the clinical picture of schistosomiasis, while the latter may have a negative impact on the course of other co-infections as malaria, leishmaniasis and HIV. Prevention of schistosomiasis is basically geared around education and periodic mass treatment, an effective vaccine being still experimental. Praziquantel is the drug of choice in the treatment of active infection by any species, with a cure rate of 80%. Other antischistosomal drugs include metrifonate for S. haematobium, oxamniquine for S. mansoni and Artemether and, possibly, Mirazid for both. Surgical treatment may be needed for fibrotic lesions.

Characteristics, management, and outcomes of patients with hepatocellular carcinoma in Africa: a multicountry observational study from the Africa Liver Cancer Consortium

BACKGROUND Hepatocellular carcinoma is a leading cause of cancer-related death in Africa, but there is still no comprehensive description of the current status of its epidemiology in Africa. We therefore initiated an African hepatocellular carcinoma consortium aiming to describe the clinical presentation, management, and outcomes of patients with hepatocellular carcinoma in Africa. METHODS We did a multicentre, multicountry, retrospective observational cohort study, inviting investigators from the African Network for Gastrointestinal and Liver Diseases to participate in the consortium to develop hepatocellular carcinoma research databases and biospecimen repositories. Participating institutions were from Cameroon, Egypt, Ethiopia, Ghana, Ivory Coast, Nigeria, Sudan, Tanzania, and Uganda. Clinical information-demographic characteristics, cause of disease, liver-related blood tests, tumour characteristics, treatments, last follow-up date, and survival status-for patients diagnosed with hepatocellular carcinoma between Aug 1, 2006, and April 1, 2016, were extracted from medical records by participating investigators. Because patients from Egypt showed differences in characteristics compared with patients from the other countries, we divided patients into two groups for analysis; Egypt versus other African countries. We undertook a multifactorial analysis using the Cox proportional hazards model to identify factors affecting survival (assessed from the time of diagnosis to last known follow-up or death). FINDINGS We obtained information for 2566 patients at 21 tertiary referral centres (two in Egypt, nine in Nigeria, four in Ghana, and one each in the Ivory Coast, Cameroon, Sudan, Ethiopia, Tanzania, and Uganda). 1251 patients were from Egypt and 1315 were from the other African countries (491 from Ghana, 363 from Nigeria, 277 from Ivory Coast, 59 from Cameroon, 51 from Sudan, 33 from Ethiopia, 21 from Tanzania, and 20 from Uganda). The median age at which hepatocellular carcinoma was diagnosed significantly later in Egypt than the other African countries (58 years [IQR 53-63] vs 46 years [36-58]; p<0·0001). Hepatitis C virus was the leading cause of hepatocellular carcinoma in Egypt (1054 [84%] of 1251 patients), and hepatitis B virus was the leading cause in the other African countries (597 [55%] of 1082 patients). Substantially fewer patients received treatment specifically for hepatocellular carcinoma in the other African countries than in Egypt (43 [3%] of 1315 vs 956 [76%] of 1251; p<0·0001). Among patients with survival information (605 [48%] of 1251 in Egypt and 583 [44%] of 1315 in other African countries), median survival was shorter in the other African countries than in Egypt (2·5 months [95% CI 2·0-3·1] vs 10·9 months [9·6-12·0]; p<0·0001). Factors independently associated with poor survival were: being from an African countries other than Egypt (hazard ratio [HR] 1·59 [95% CI 1·13-2·20]; p=0·01), hepatic encephalopathy (2·81 [1·72-4·42]; p=0·0004), diameter of the largest tumour (1·07 per cm increase [1·04-1·11]; p<0·0001), log α-fetoprotein (1·10 per unit increase [1·02-1·20]; p=0·0188), Eastern Cooperative Oncology Group performance status 3-4 (2·92 [2·13-3·93]; p<0·0001) and no treatment (1·79 [1·44-2·22]; p<0·0001). INTERPRETATION Characteristics of hepatocellular carcinoma differ between Egypt and other African countries. The proportion of patients receiving specific treatment in other African countries was low and their outcomes were extremely poor. Urgent efforts are needed to develop health policy strategies to decrease the burden of hepatocellular carcinoma in Africa. FUNDING None.

New era for management of chronic hepatitis C virus using direct antiviral agents: A review.

Graphical abstract

Survival and Prognostic Factors for Hepatocellular Carcinoma: an Egyptian Multidisciplinary Clinic Experience

BACKGROUND Hepatocellular carcinoma (HCC) is a dismal tumor with a high incidence, prevalence and poor prognosis and survival. Management of HCC necessitates multidisciplinary clinics due to the wide heterogeneity in its presentation, different therapeutic options, variable biologic behavior and background presence of chronic liver disease. We studied the different prognostic factors that affected survival of our patients to improve future HCC management and patient survival. MATERIALS AND METHODS This study is performed in a specialized multidisciplinary clinic for HCC in Kasr El Eini Hospital, Cairo University, Egypt. We retrospectively analyzed the different patient and tumor characteristics and the primary mode of management applied to our patients. Further analysis was performed using univariate and multivariate statistics. RESULTS During the period February 2009 till February 2013, 290 HCC patients presented to our multidisciplinary clinic. They were predominantly males and the mean age was 56.5 ± 7.7 years. All cases developed HCC on top of cirrhosis that was mainly due to HCV (71%). Most of our patients were Child-Pugh A (50%) or B (36.9%) and commonly presented with small single lesions. Transarterial chemoembolization was the most common line of treatment used (32.4%). The overall survival was 79.9% at 6 months, 54.5% at 1 year and 22.4% at 2 years. Serum bilirubin, site of the tumor and type of treatment were the significant independent prognostic factors for survival. CONCLUSIONS Our main prognostic variables are the bilirubin level, the bilobar hepatic affection and the application of specific treatment (either curative or palliative). Multidisciplinary clinics enhance better HCC management.

Microwave ablation versus transarterial chemoembolization in large hepatocellular carcinoma: prospective analysis.

Abstract Objective. Limited therapies are offered for large hepatocellular carcinoma (HCC). It carries dismal prognosis and efforts tried changing its management from a palliative to a curative mode. Transarterial chemoembolization (TACE) is a palliative procedure that may have survival benefit if compared to non-management of large lesions. Microwave ablation (MWA) has emerged as a relatively new technique with promise of larger and faster ablation. We aim to evaluate the efficacy and safety of percutaneous MWA versus TACE for large tumors (5–7 cm) and to assess their effects on local tumor progression and survival. Patients and methods. Sixty-four patients with large lesions are managed in our multidisciplinary HCC clinic and were divided into two groups treated either by MWA or TACE. Complete response rate, local recurrence, de novo lesions, and overall survival analysis are compared between both procedures. Results. Both groups were comparable as regards the demographic and ultrasonographic features. MWA showed higher rates of complete ablation (75%) with fewer sessions, lower incidence of tumor recurrence (p = 0.02), development of de novo lesions (p = 0.03), occurrence of post-treatment ascites (p = 0.003), and higher survival rates (p = 0.04). The mean survival of the microwave group was 21.7 months with actuarial probability of survival at 12 and 18 months 78.2% and 68.4%, respectively. The mean survival of the TACE group was 13.7 months with actuarial probability of survival at 12 and 18 months being 52.4% and 28.6%, respectively. Conclusion. MWA showed better results than TACE in the management of large HCC lesions.

Generic daclatasvir plus sofosbuvir, with or without ribavirin, in treatment of chronic hepatitis C: real-world results from 18 378 patients in Egypt

Treatment of chronic hepatitis C using combination of sofosbuvir (SOF) and daclatasvir (DCV) was used in several clinical trials and multicentre studies, which were somewhat limited to genotypes 1‐3. The national program in Egypt is using SOF‐DCV combination for large scale treatment.

Nitazoxanide plus pegylated interferon and ribavirin in the treatment of genotype 4 chronic hepatitis C, a randomized controlled trial

Nitazoxanide has been proposed as a novel therapeutic agent for chronic hepatitis C virus (HCV) potentiating the effect of interferon and improving sustained virological response rates to up to 80% in genotype 4. This is an independent randomized trial to confirm the efficacy of nitazoxanide in the treatment of chronic hepatitis C genotype 4.

Safety of direct antiviral agents in the management of hepatitis C

ABSTRACT Introduction: Hepatitis C virus is a hepatotropic virus that generally leads to chronic hepatitis and various harmful sequelae. The lone standard of treatment has been pegylated interferon and ribavirin, which produces a modest response and many side effects. However, a new era of management was declared with the introduction of various directly acting antiviral agents. Areas covered: Recent direct antiviral agents (DAAs) primarily target the non-structural proteins of the virus and affect its replication. These agents successfully achieve a sustained virologic response. However, some serious side effects were reported, which may or may not be drug-related effects. Important drug-drug interactions were also reported. The treating physician should be reasonably familiar with these effects. We review the safety profile of these agents in the management of HCV. Expert opinion: Cautious concomitant drug intake is necessary for the new HCV therapies. Future HCV management will depend on interferon-free and likely ribavirin-free regimens. The co-administration of direct antiviral agents of different classes increases the probability of side effects and drug-drug interactions.

Circulating Levels of Adipocytokines as Potential Biomarkers for Early Detection of Colorectal Carcinoma in Egyptian Patients

BACKGROUND Early detection of various kinds of cancers nowadays is needed including colorectal cancer due to the highly significant effects in improving cancer treatment. The aim of this study was to evaluate the potential value of adiponectin, visfatin and resistin as early biomarkers for colorectal cancer patients. MATERIALS AND METHODS Serum levels of adiponectin, visfatin and resistin were measured by a sandwich-enzyme-linked (ELISA) assay technique in 114 serum samples comprising 34 patients with colorectal cancer (CRC), 27 with colonic polyps (CP), 24 with inflammatory bowel disease (IBD) and 29 healthy controls .The diagnostic accuracy of each serum marker was evaluated using receiver-operating characteristic (ROC) curve analysis. RESULTS The mean concentration of adiponectin was significantly higher in CRC and CP groups than IBD and control groups (P-value <0.05). Also the mean concentration of serum resistin was significantly elevated in the IBD and control groups compared to CRC and CP groups (P-value = 0.014). However, no significant difference was noted in patients of the CRC and CP groups. On the other hand, the mean concentration of visfatin was significantly elevated in CRC and control groups compared to CP and IBD groups (P-value = 0.03). ROC analysis curves for the studied markers revealed that between CRC and IBD groups serum level of adiponectin had a sensitivity of 76.7% and a specificity of 76% at a cut off value of 3940, +LR being 3.2 and -LR 0.31 with AUC 0.852, while serum level of adiponectin between CP and IBD had a sensitivity of 77.8% and a specificity of 75% at a cut off value of 3300, with +LR=3.11 and -LR = 0.3 with AUC 0.852. On the other hand the serum level of visfatin between CRC and CP groups had a sensitivity of 65.5% and a specificity of 66.7 at a cut off value of 2.4, +LR being 1.67 and -LR 0.52 with AUC 0.698. Also the serum level of resistin had a sensitivity of 62.5% and a specificity of 70.3% at a cut off value of 24500, with +LR=2.1 and -LR = 0.53 with AUC 0.685 between control and other groups. On the other hand by comparing control vs CP groups resistin had a sensitivity of 81.8% and a specificity of 70.8% at a cut off value of 17700, with +LR=2.8 and -LR = 0.26 with AUC 0.763 while visfatin had a sensitivity of 68.2% and a specificity of 70.8% at a cut off value of 2.7, with +LR=2.34 and -LR = 0.0.45 with AUC 0.812. CONCLUSIONS These findings support potential roles of adiponectin, visfatin and resistin in early detection of CRC and discrimination of different groups of CRC, CP or IBD patients from normal healthy individuals.