Samar K. Darweesh

Genetic Variability of Antigen B among Echinococcus granulosus Egyptian Isolates

Genetic polymorphisms of encoding antigen B2 gene (AgB2) in Echinococcus granulosus were studied using PCR-RFLP and DNA sequencing among 20 Egyptian isolates. Five isolates from different host origins (humans, camels, pigs, and sheep) were collected and used. All examined isolates of each host group gave very similar patterns of PCR-RFLP after restriction enzyme digestion with AluI, with the gene size of approximately 140 bp and 240 bp for sheep and human isolates, and approximately 150 bp and 250 bp for pig and camel isolates. No digestion pattern was obtained after incubation of all studied isolates with EcoRI. These results reveal high intra-group homogeneity. DNA sequence analysis highlighted that human infecting strain showed 100% identity with respect to sheep infecting isolate, 96% and 99% with pig and camel infecting isolates, respectively.

Clinical Significance of Plasma Osteopontin Level as a Biomarker of Hepatocellular Carcinoma

Background Biomarkers of hepatocellular carcinoma (HCC) are helpful in screening, diagnosis and follow up of cases. Osteopontin (OPN) is a glycoprotein secreted by osteoblasts, osteoclasts, macrophages and T cells, and is over-expressed in a variety of tumors, including carcinomas of liver, stomach, breast, lung, colon, and prostate. So, the aim of this study was to verify the possibility of using the plasma Osteopontin level as a biomarker for diagnosis of HCC. Methods The study included 70 subjects divided into three groups: group I had 30 patients with HCC (proved by histopathology or combined spiral CT and elevated alpha-fetoprotein) on top of HCV, group II had 30 patients with HCV infection and group III had 10 healthy subjects serving as control. Osteopontin level was measured in plasma of the studied subjects by ELISA, serum alpha fetoprotein (AFP) level was also measured by EIA. Results Osteopontin levels were significantly elevated in patients with HCC and in HCV patients in comparison to control group (P: 0.005). There was significant correlation between OPN and AFP levels (P: 0.00). The sensitivity and specificity of OPN for selective detection of HCC group over the non-HCC group (HCV group and healthy control group) were73% and 54%, respectively, at a cut-off value of 128.5 ng/mL. Plasma OPN levels directly correlated with the tumor number but not with the size of the tumor (P: 0.00). Conclusion Plasma OPN level appears to be an additional biomarker for HCC detection.

Losartan may inhibit the progression of liver fibrosis in chronic HCV patients.

BACKGROUND Abundant experimental evidence indicates overproduction of angiotensin II in the injured liver, and a role in stimulation of hepatic stellate cell (HSC) activation and fibrogenesis thereby, representing an attractive antifibrotic target. The aim of this study was to examine the antifibrotic effect of losartan on histopathologic level in chronic HCV patients. METHODS A prospective study on fifty patients with chronic HCV and liver fibrosis proved by liver biopsy was conducted. They included patients who did not respond (n=36) or comply (n=2) or receive therapy due to established cirrhosis (n=10), or refused to receive (n=2) combined interferon and ribavirin therapy. They were divided randomly into 2 groups. The 1(st) group (n=25) was given losartan 50 mg OD for 1 year and the 2(nd) group (25 patients) was given silymarin, 140 mg t.i.d., (silymarin group). Liver biopsy was done at baseline and 1 year from the onset of treatment (end of study). RESULTS In the second liver biopsy after 1 year, the decrease in fibrosis stage was significantly different between losartan group and silymarin group (a decrease of 1.88±0.96 (50.9%) vs. 0.45±0.93 (11.7%), respectively; P<0.01). In patients treated with losartan, regression in fibrosis stage was observed in 14/16 patients vs. 2/11 in silymarin group (P<0.01). No differences were observed in inflammation grades in both groups. A significant increase in albumin and prothrombin levels and a decrease in systolic blood pressure were found in losartan but not in silymarin group (P=0.009, 0.001 & 0.018 respectively and P=0.158, 0.603 & 0.288, respectively). CONCLUSIONS Histopathological scores showed that losartan had an inhibitory effect on progression and even led to regression of fibrosis stage but had no effect on the grade of inflammation.

Accurate Prediction of Advanced Liver Fibrosis Using the Decision Tree Learning Algorithm in Chronic Hepatitis C Egyptian Patients

Background/Aim. Respectively with the prevalence of chronic hepatitis C in the world, using noninvasive methods as an alternative method in staging chronic liver diseases for avoiding the drawbacks of biopsy is significantly increasing. The aim of this study is to combine the serum biomarkers and clinical information to develop a classification model that can predict advanced liver fibrosis. Methods. 39,567 patients with chronic hepatitis C were included and randomly divided into two separate sets. Liver fibrosis was assessed via METAVIR score; patients were categorized as mild to moderate (F0–F2) or advanced (F3-F4) fibrosis stages. Two models were developed using alternating decision tree algorithm. Model 1 uses six parameters, while model 2 uses four, which are similar to FIB-4 features except alpha-fetoprotein instead of alanine aminotransferase. Sensitivity and receiver operating characteristic curve were performed to evaluate the performance of the proposed models. Results. The best model achieved 86.2% negative predictive value and 0.78 ROC with 84.8% accuracy which is better than FIB-4. Conclusions. The risk of advanced liver fibrosis, due to chronic hepatitis C, could be predicted with high accuracy using decision tree learning algorithm that could be used to reduce the need to assess the liver biopsy.

Hypertonic saline-enhanced radiofrequency versus chemoembolization sequential radiofrequency in the treatment of large hepatocellular carcinoma.

Background and study aim Large hepatocellular carcinoma (HCC) appears to be a major obstacle for radiofrequency ablation (RFA); therefore, attempts to increase the volume of coagulation by injecting hypertonic saline before and/or during RFA have been made. Transarterial chemoembolization (TACE) combines the effect of targeted chemotherapy with ischemic necrosis and eliminates heat loss if combined with RFA. Our aim was to compare the efficacy of hypertonic saline-enhanced RFA versus TACE sequential RFA in the treatment of medium and large nodular HCC. Patients and methods This prospective study was carried out on 40 patients with 40 HCCs between 2008 and 2010 in the Tropical Medicine and Hepatology Department, Faculty of Medicine, Cairo University. They were divided into two groups (20 patients each): the first group received hypertonic saline-enhanced RFA (RFA+HS) and the second group underwent transarterial chemoembolization, followed by RFA (TACE+RFA). Results Triphasic computed tomography 1 month after the procedure showed that 17 (85%) patients in each group achieved complete ablation, whereas three (15%) in each group achieved partial ablation. In the RFA+HS group, 12/13 (92%) of medium HCC and 5/7 (71%) of large HCC were successfully ablated. In the TACE+RFA group, 8/8 (100%) medium HCC and 9/12 (75%) of large lesions were successfully ablated. The relation between success rate and lesion diameter was statistically significant only in RFA+HS group. After 6 months, 73.7% of patients in the RFA+HS group and 83.3% of patients in the TACE+RFA group showed maintained ablation (P=0.86). Conclusion RFA+HS and TACE+RFA are safe and equally effective treatments for medium to large HCC.

Ophthalmological side effects of interferon therapy of chronic hepatitis C

BACKGROUND Egypt has one of the highest prevalence of hepatitis C virus (HCV) worldwide. Ophthalmological side effects are recognized complications of interferon (IFN) therapy. This study aimed to evaluate IFN-induced ophthalmological manifestations in patients receiving PEGylated interferon (PEG IFN) and ribavirin (RBV) and to assess the effect of IFN duration, response and systemic risk factors on the severity. METHODS We retrospectively analyzed 100 patients with chronic HCV who were candidates for PEG-IFN and RBV therapy. All patients were subjected to clinical and ophthalmological examination, laboratory investigations, abdominal ultrasound, colored fundus photography and fundus fluorescein angiography, follow up was made at weeks 12, 24, and 48 of treatment. RESULTS IFN-induced retinopathy had been found in (9/100; 9%), 5 (5/9; 55.5%) of them had bilateral lesions, (3/9; 33.3%) were treatment responders and (6/9; 66.6%) non responders. The time of retinopathy appearance was mainly at W12. Retinopathy was asymptomatic in most of the affected patients (7/9; 77.77%) and reversible, cotton wool spots was the major associated sign. Patients with older age, DM and or HTN, and non-responders to antiviral therapy were associated with more severe retinopathy. CONCLUSIONS Retinopathy is not a rare complication of IFN therapy for chronic HCV infection, but fortunately its asymptomatic and reversible. Ophthalmological assessment at base-line and at follow up during IFN treatment is very important.

Regulatory and activated effector T cells in chronic hepatitis C virus: Relation to autoimmunity

AIM To investigate how Tregs are regulated in chronic hepatitis C virus (HCV) patients via assessment of Tregs markers (granzyme 2, CD69 and FoxP3), Teffs markers [TNFRSF4 (OX40), INFG] and CD4, CD25 genes. METHODS A prospective study was conducted on 120 subjects divided into 4 groups: Group I (n = 30) treatment naïve chronic HCV patients; Group II (n = 30) chronic HCV treated with Peg/Riba; Group III (n = 30) chronic HCV associated with non-organ specific autoantibody and Group IV (n = 30) healthy persons as a control group. Tregs and Teffs markers were assessed in peripheral blood mononuclear cells by quantitative real time reverse transcriptase-polymerase chain reaction. RESULTS Chronic HCV patients exhibited significant higher levels of both Teffs and Tregs in comparison to healthy control group. Tregs markers were significantly decreased in Peg/Riba treated HCV patients in comparison to treatment naïve HCV group. In HCV patients with antinuclear antibody (ANA) +ve, Tregs markers were significantly decreased in comparison to all other studied groups. Teffs markers were significantly elevated in all HCV groups in comparison to control and in HCV group with ANA +ve in comparison to treatment naïve HCV group. CONCLUSION Elevated Tregs cells in chronic HCV patients dampen both CD4+ and CD8+ autologous T cell immune response. Interferon-α and ribavirin therapy suppress proliferation of Tregs. More significant suppression of Tregs was observed in HCV patients with autoantibodies favoring pathological autoimmune response.

Etiology and prevalence of fatigue in chronic liver disease: clinical view

Introduction and aim Fatigue is one of the most common and prominent symptoms in liver cirrhosis and was reported in 60–80% of these patients. The study outcome was to prospectively evaluate the etiology and the degree of fatigue and how to improve it in chronic liver disease patients. Patients and methods A prospective cross-sectional study on fatigue in chronic liver diseases was conducted on 500 patients: 475 patients had hepatitis C virus (HCV) and 25 had combined HCV and hepatitis B virus. They were divided into five groups: group 1 included 100 patients with chronic hepatitis, group 2 included 100 patients with Child class A cirrhosis, group 3 included 100 patients with Child class B cirrhosis, group 4 included 100 patients with Child class C cirrhosis, and group 5 included 100 patients with hepatocellular carcinoma (HCC). They were administered the Fatigue Impact Scale and the Fatigue Severity Scale questionnaires (translated into Arabic) as well as subjected to laboratory investigations, abdominal ultrasonography, and upper endoscopy. Results All (100%) patients complained of longstanding fatigue. HCC had the highest prevalence of high fatigue (65%) and Child class C cirrhosis had the longest fatigue duration. Female sex and anemia were significantly related to both the Fatigue Impact Scale and the Fatigue Severity Scale in each group separately and all patients collectively. Age had a significant relation with all patients collectively but not separately. Fatigue scores were related to Child score but not related to liver profile, α-fetoprotein, varices, ascites, and HCV load. Conclusion Correction of anemia, not liver profile, helps in alleviating fatigue in cirrhotic patients. Female patients suffered from fatigue more frequently compared with male patients. HCC patients had highest fatigue and patients with Child class C cirrhosis had longest fatigue indices.

Colonic mucosal changes in Egyptian patients with liver cirrhosis and portal hypertension

Background and aims In patients with liver cirrhosis and portal hypertension (PHT), portal hypertensive colopathy (PHC) is thought to be an important cause of lower gastrointestinal bleeding. This study aimed at evaluating the prevalence and clinical significance of colonic mucosal changes in Egyptian patients with liver cirrhosis and PHT. Patients and methods A prospective study was conducted on 35 patients with liver cirrhosis and PHT (proved by upper endoscopy and/or abdominal ultrasonography). They were evaluated using full colonoscopy to detect changes in colonic mucosa and using gastroscopy to detect the presence of both gastroesophageal varices and portal hypertensive gastropathy. Results Colonic lesions were found in 27 patients (77.1%), including haemorrhoids in 20 patients (57.1%), diffuse hyperaemic mucosa in 16 patients (45.7%), angiodysplastic lesions in 12 patients (34.3%) and rectal varices in five patients (14.3%). Bleeding per rectum was detected in seven patients (20%), and it significantly correlated with the presence of haemorrhoids ( P = 0.02). The prevalence of PHC and the presence of haemorrhoids increased with the worsening Child-Pugh class ( P = 0.01 and 0.02, respectively). Conclusion The prevalence of PHC and haemorrhoids increases with the progression of liver disease and worsening of the Child-Pugh grading in cirrhotic patients. However, haemorrhoids, rectal varices, hyperaemia and colonic angiodysplasia are not affected by the presence of portal hypertensive gastropathy.