Impact of ITPA gene polymorphism for predicting anemia and treatment outcome in HCV infected patients taking Sofosbuvir Ribavirin therapy.

BACKGROUND: Globally, 80 million people are suffering from chronic Hepatitis C virus (HCV) infection. Sofosbuvir ribavirin-based anti-HCV therapy is associated with anemia and other adverse effects. Polymorphisms of Inosine triphosphatase (ITPA) gene may cause functional impairment in the Inosine triphosphate pyrophosphatase enzyme, resulting in enhanced sustained viral response (SVR) and protection from ribavirin-associated anemia in patients on therapy. The study objective was to investigate the effect of Inosine triphosphatase gene polymorphism on SVR achievement, hemoglobin decline and ribavirin dose reduction in patients on therapy. METHODS: This prospective cohort study was of 170 hepatitis C infected patients received 6-month sofosbuvir ribavirin therapy. Patient viral load, reduction in ribavirin amount, liver function test, and complete blood count were noted monthly. Inosine triphosphatase variants rs1127354 and rs7270101 were assessed through the restriction fragment length polymorphism and confirmed using Sanger sequencing. The impact of polymorphism on cumulative reduction of ribavirin, and anti-HCV therapy outcome were studied. RESULTS: A total of 74.3% of patients had ITPA rs1127354 CC genotype, 25.7% were CA and AA 0%. The frequency of ITPA genotype rs7270101-AA was 95%, AC 5%, and CC was 0%. ITPA rs1127354-CA had a notably positive impact on SVR achievement with a zero-relapse rate. ITPA rs1127354-CA genotype was significantly (P ˂0.05) protective against ≥ 2 g/dl Hb reduction from baseline to 1st, 2nd and 6th months of therapy. During treatment, Hb reduction ≥ 10 g/dl was frequently observed in rs1127354-CC genotype and rs7270101-AA genotype patients. Ribavirin dose reduction was significantly (P ˂0.05) high in rs1127354-CC genotype as compared to genotype CA whereas no significant difference was observed in ribavirin dose reduction in rs7270101 AA and non-AA genotype. Patient baseline characteristics such as age, body mass index, rs1127354-CC genotype, and baseline Hb were significantly associated with significant Hb reduction. CONCLUSION: Pretreatment evaluation of ITPA polymorphism can be a diagnostic tool to find out patients at risk of anemia and improve treatment adherence. ITPA genotype rs1127354-CA contributes to improved compliance with ribavirin dose and protects against hemoglobin decline in HCV patients while taking ribavirin-based therapy. However, ITPA rs1127354, rs7270101 polymorphism have no significant impact on SVR achievement.

Hypovitaminosis D in Hepatitis C patients and its relation with demographic and laboratory data.

OBJECTIVE: To determine the frequency of vitamin-D deficiency in hepatitis C patients and its relation with demographic and baseline laboratory data. METHODS: The cross-sectional study was conducted at the University Institute of Medical Laboratory Technology, Faculty of Allied Health Sciences, The University of Lahore, Pakistan, from April 3 to July 24, 2017, and comprised diagnosed hepatitis C genotype 3 patients aged 18-60 years. Demographic data was collected on a predesigned proforma. Tests included complete blood counts, liver function test, hepatitis C viral load and 25-hydroxy Vitamin-D level. Data was analysed using SPSS 24. RESULTS: Of the 115 patients, 54(47%) were male and 61(53%) were females. Mean vitamin-D level was 22.3±11.3. Total 25(21.7%) patients showed normal level of vitamin-D while the level was low in 90(78.3%) patients; 41(35.6%) showed vitamin-D insufficiency and 49(42.6%) vitamin-D deficiency. Significant effect of sun exposure was recorded on patient's vitamin-D level (p=0.00). Significantly low hepatitis C viral load was seen in patients with normal vitamin-D (p= 0. 02 6 ). CONCLUSIONS: Patients with hepatitis C virus infection had high incidence of hypo-vitaminosis D.

Efficacy of standard triple therapy versus Levofloxacin based alternate therapy against Helicobacter pylori infection.

OBJECTIVE: To assess the effectiveness of clarithromycin based standard triple therapy verses levofloxacin based first line therapy against Helicobacter pylori infection. METHODS: This prospective observational study was performed at Akhter Saeed Trust Teaching Hospital, Lahore, from May 2016 to 31st May 2017 and comprised of all patients with positive H. pylori, confirmed by gastroscopic biopsy; fulfill the inclusion criteria of this study. Patients were divided into two groups (Group A and Group B). Group A received clarithromycin 500mg, amoxicillin 1g and omeprazole 20mg twice a day for two weeks. In group B levofloxacin 250mg was replaced by clarithromycin whereas rests of medicines remain the same. Patients were followed up at end of first week, second week and at end of treatment to record any adverse effects and cure rate. Data was analyzed by using SPSS version 24.0 and MINITAB V.16.. RESULTS: Out of 300 enrolled patients (150 patients in each group), 123 (87.85%) patients cured in group A whereas 134 (92.4%) patients cured in group B. Both treatment regimens were almost equally effective in our population with no statistically significant difference in outcome. Significantly less adverse effects were observed in patients having levofloxacin as compared to standard triple therapy. CONCLUSIONS: Effectiveness of both standard triple therapy and alternate triple therapy were found satisfactory to be used for treatment in our region. Levofloxacin based alternate therapy is safer to the patients. It can be used in conditions where adverse effects caused by standard therapy are unbearable.

Detection of antibacterial activities of Miswak, Kalonji and Aloe vera against oral pathogens & anti-proliferative activity against cancer cell line.

BACKGROUND: Emerging drug resistance and hindrance of treatment is provoking scientists to search new, less expensive medicinally active compounds. Dental diseases caused by oral pathogens are very frequent chronic infections around the world. The medical potentials of a lot of Pakistani local herbs and herbal combinations is relatively unknown, hence attempted to explore. A study was designed to investigate potential role of local medicinal herbs for example Miswak, Kalonji & Aloe vera as antimicrobial, antioxidant and anti-proliferative agents against oral pathogens and cancer cell line. METHODS: Medicinal extracts were prepared in solvents of different polarities. Their antimicrobial activity was determined alone and in combination against oral pathogens. Antioxidant activity was evaluated through Catalase and Superoxide dismutase assay and anti-proliferative activity was evaluated through 3-(4, 5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide) assay. RESULTS: Plant extracts alone and in combinations were found significantly effective as antimicrobial agent against standard ATCC strains of C. albicans and S. aureus (P ˂0.001). Especially Miwak extract was found highly significant against fungus. Extracts of Kalonji were found significant in inhibiting growth of HeLa cell lines. Miswak and Kalonji showed significant levels of antioxidant activity. CONCLUSION: Medicinal herbs Miswak and Kalonji have potential to be used for therapeutic purposes. Results suggested that herbal medicinal composition can be prepared using these extracts after applying scientific standardization methods.