Safiyya Ali

Treatment decisions for hepatocellular carcinoma involve the evaluation of multiple factors including tumor size, location, and morphology; comorbidity and/or extrahepatic disease; health status; patient preferences; and the treating physician's expertise and skill. For patients who are not candidates for transplant or resection, and for whom other therapies (radiofrequency ablation, systemic chemotherapies, transarterial embolization or chemoembolization), may have limited efficacy, an urgent need for bridging procedures, to enable surgery or ablation, or meet transplantation criteria, has led to investigations with radioembolization. A number of recent reports have supported the effectiveness of Yttrium-90 ((90)Y) labeled microspheres to treat intermediate and advanced disease in patients with good overall functional status and liver reserve; patients with portal vein involvement and in a limited role to treat unresectable early-stage disease. This review addresses response rates and survival benefit following radioembolization in different patient populations, in centers throughout Europe, North America, and Asia, and across the spectrum of patients presenting with various prognostic factors. By using stringent selection criteria and conservative models for calculating radiation dosage, radioembolization can be performed safely even in cirrhotic patients, without postembolization syndrome or radiation-induced liver disease, and even with multiple treatments to whole or part of the liver.

Abstract: Organophosphate (OP) poisoning is a progressively worrying phenomenon as worldwide pesticide production and consumption has doubled. On average, WHO estimates that 3% of agricultural workers in developing Asian countries suffer an episode of pesticide poisoning every year. Furthermore, the threat of OP usage in terrorism is existent, as seen by the subway tragedy in Tokyo in 1995 where sarin was used. Despite these alarming facts, there is currently no global system to track poisonings related to pesticide use. Human serum paraoxonase (PON1) is the enzyme that hydrolyses OP compounds. Serum PON1 levels and activity vary widely among different ethnic populations. Two commonly studied polymorphisms of PON1 are PON1Q192R and PON1L55M. PON1R192 hydrolyses paraoxon faster than PON1Q192 but hydrolyses diazoxon, sarin and soman eight times slower, and vice versa. PON1M55 has lower plasma levels of PON1 than PON1L55. As the prevalence of the different alleles and genotypic distrib...

Background/aim: Hepatitis B virus (HBV) and hepatitis delta virus (HDV) coinfection often leads to severe chronic hepatitis and cirrhosis. Data on long term outcome of liver transplantation (LT) for coinfected patients is limited. The aim of this study was to assess the prevalence of HBV and HDV coinfection in our transplant population and to evaluate its long term impact on LT.Methods: Between January 1990 and December 2011 a total of 133(106 males and 27 females) patients were transplanted at our center for HBV related cirrhosis. 32(24%) patients were coinfected with HDV while 70 patients tested negative for HDV. The HDV status was not available for 31 patients. All patients received post transplant combination therapy with nucleos(t)ide analogue and anti-hepatitis B immunoglobulins. Breakthrough infection was de ned as re-emergence of HBV-DNA or HBsAg while on treatment.Results: Patients were followed for an average of 82 months (range 1-274). Post LT survival and HBV recurrence...

To evaluate the indication and outcome of hepatitis B virus (HBV)-related liver transplantation (LT) in the era of newer antiviral agents. We collected data on all patients who underwent transplantation at King Faisal Specialist Hospital and Research Center. These data included demographic, perioperative and long-term postoperative follow-up data including viral serological markers, HBV DNA, and repeated liver imaging. Between January 1990 and January 2012, 133 patients (106 males and 27 females) underwent LT for HBV-related cirrhosis at our center. All patients were followed up frequently during the first year following transplantation, according to our standard protocol; follow-up visits occurred every 3-6 mo thereafter. Breakthrough infection was defined as re-emergence of HBV-DNA or hepatitis B surface antigen (HBsAg) while on treatment. Five patients transplanted prior to 1992 did not receive immediate posttransplant anti-HBV prophylaxis; all other patients were treated with HB...

The estimated prevalence of nonalcoholic fatty liver disease (NAFLD) in Saudi Arabia is 7% to 10%. Despite the high prevalence of risk factors including diabetes, obesity, and hyperlipidemia, no recent epidemiological studies have measured the disease burden. We aimed to determine the characteristics of Saudi NAFLD patients attending a university hospital, and study factors affecting alanine aminotransferase (ALT) levels. A prospective study among patients referred for ultrasonography in King Khalid University Hospital in Riyadh, Saudi Arabia from February to May 2009. NAFLD was defined as an appearance of fatty liver on routine abdominal ultrasound in the absence of coexisting liver disease and alcohol consumption. Patients were classified into normal and high ALT (ALT >60 U/L) level groups for analysis. The prevalence of NAFLD was 16.6% (218/1312). Patients with normal ALT had the mean (SD) age of 45.9 (10.6) years and the mean body mass index of 34.5 (7.9) kg/m2. Forty percent...

A major concern of cancer chemotherapy is the side effects caused by the non-specific targeting of both normal and cancerous cells by therapeutic drugs. Much emphasis has been placed on discovering new compounds that target tumour cells more efficiently and selectively with minimal toxic effects on normal cells. The cytotoxic effect of thymoquinone, a component derived from the plant Nigella sativa, was tested on human glioblastoma and normal cells. Our findings demonstrated that glioblastoma cells were more sensitive to thymoquinone-induced antiproliferative effects. Thymoquinone induced DNA damage, cell cycle arrest and apoptosis in the glioblastoma cells. It was also observed that thymoquinone facilitated telomere attrition by inhibiting the activity of telomerase. In addition to these, we investigated the role of DNA-PKcs on thymoquinone mediated changes in telomere length. Telomeres in glioblastoma cells with DNA-PKcs were more sensitive to thymoquinone mediated effects as comp...

Organophosphate (OP)-containing pesticides are widely used worldwide for domestic and industrial purposes. Studies on acute and chronic exposure to OPs have revealed numerous health effects attributed mainly to acetylcholinesterase (AChE) inhibition. The enzyme human serum paraoxonase (PON1) is involved in the detoxification of OP compounds. PON1 polymorphisms have been shown to affect susceptibility to OP exposure. We studied the effect of OP exposure on pest control workers and assessed the distribution of two common PON1 polymorphisms in our local population. The exposed group consisted of 103 workers from various pest control companies under the Singapore Pest Management Association while the 91 unexposed workers were from a lead stabilizer factory. For all workers, the mean age was 36.9 (20-70) years and the ethnic distribution was 38.1% Chinese, 44.3% Malay and 17.5% Indian. The mean+/-S.D. exposure duration among the pesticide workers was 10.4+/-8.4 years. The mean+/-S.D. RBC cholinesterase level was 18436.2+/-2078U/L and 18079.6+/-1576U/L for the exposed and unexposed groups, respectively (p=0.216). The mean+/-S.D. serum pseudocholinesterase was 11028.4+/-2867.4U/L and 9433.6+/-2022.6U/L in the exposed and unexposed groups, respectively…

Hepatitis C virus (HCV) genotype 4 (G4) infection is common in the Middle East. Post-treatment long-term outcomes have not been reported in these patients. This study evaluates these outcomes in patients after interferon-based therapy. A total of 157 patients were followed from June 2001 to February 2012. Descriptive and analytical statistics, cumulative outcomes and the independent predictors of disease progression were calculated. The overall age was 48.0 ± 11.8 years, 75 (47.8%) were males and 53 (70.7%) of 75 who were genotyped had G4. The follow-up period was 63.8 ± 32.8 months. Sustained virological response (SVR) was achieved in 62 (39.5%) and 24 (45.3%) patients in the whole group and the G4 subgroup respectively. Among the whole cohort and the G4 subgroup, disease progressed in 59 (37.6%) and 21 (39.6%), respectively, with less progression in the SVR groups; 15/62 (24.2%) and 3/24 (12.5%) compared with non-responders; 44 (46.3%) and 18 (62.1%) with P = 0.01 and 0.001 respectively. Multivariate logistic regression analysis showed that having diabetes mellitus (P = 0.03), higher baseline APRI score (P = 0.00) and non-SVR (P = 0.00) were independent predictors of disease progression. G4 patients showed similar results, but 'non-SVR' (P = 0.00) was the only independent predictor of progression. Eight patients died and four developed HCC all among the non-SVR group only. This study describes, for the first time, the natural history and demonstrates the beneficial long-term effects of interferon-based therapy in HCV G4 patients.

Hepatic steatosis in hepatitis C virus (HCV)-infected patients has been shown to enhance the progression of liver fibrosis and decrease the response to antiviral therapy. We aimed to determine the role of HCV genotype 4 (HCV-G4) in the prevalence of hepatic steatosis, its impact on antiviral therapy, and its associations and predictive factors in comparison to HCV-G1-infected patients. Treatment-naïve HCV patients who were started on pegylated interferon a-2b plus ribavirin therapy in two centers in Saudi Arabia were included. The severity of steatosis was assessed using the METAVIR and NAS (non-alcoholic fatty liver disease [NAFLD] activity score) scoring systems. Sustained virological response (SVR) was studied in relation to the degree of steatosis. Associations between steatosis and multiple demographic, laboratory, and virological factors were examined. HCV-G1 and HCV-G4 patients were compared. A total of 116 patients (HCV-G4 85 [73.3%]; HCV-G1 31 [26.7%]) were included. The mean age was 50.4±10.7 years and 56.9% were males. In terms of steatosis grading using the NAS scoring system, 50% had steatosis grade 0, 26.7% grade 1, 14.7% grade 2, and 8.6% grade 3, while the overall staging of steatosis revealed that 43.1% had mild steatosis, 42.2% moderate, and 14.7% severe. Gamma-glutamyl transpeptidase (GGT), platelet count, body mass index (BMI), cholesterol level, presence of hyperlipidemia, liver histology stage, and grade were significantly correlated with hepatic steatosis in one or more of the statistical analyses. Twenty-two out of 55 patients (40.0%) had an SVR in the mild steatosis group, compared to 52.7% in the moderate group and 7.3% in the severe group (P=0.03). The HCV genotype did not correlate with steatosis or SVR. Our study confirms the high prevalence of steatosis in HCV-G4 and HCV-G1 patients, but with no difference in the grade or score of steatosis between the two genotypes. The grade of steatosis correlates with GGT, platelet count, and BMI, while the NAS score of steatosis correlates with response to antiviral therapy.