IP-10 Levels in Patients Infected with HBV Predicts The Response to Treatment with Entecavir.

Interferon--inducible protein-10 (IP-10), is an inflammatory cytokine produced by different subsets of the immune cells and induces chemotaxis, apoptosis, growth of cells and angiostasis after binding to its receptor CXCR3. Inflammatory disorders, involving infectious diseases, immune dysfunction, and tumour growth have been linked to changes in CXCL10 levels. We aimed to investigate serum levels of IP-10 in chronic HBV infected patients undergoing treatment with entecavir and possible correlation with response to therapy. A total of 53 chronic HBV infected patients and 25 healthy controls were enrolled in this study. Patients included 20 with cirrhosis and 33 non-cirrhotic individuals. All patients received 0.5 mg/day entecavir and serum IP-10 level was determined by ELISA at baseline and at week 24 of treatment. mRNA expression of CXCR3 of PBMC was assessed by real-time polymerase chain reaction (RT-PCR). Response to therapy was achieved in 27/33 (81.8%) non-cirrhotic and 14/20 (70%) cirrhotic patients. Mean serum IP-10 levels was higher in patients than healthy controls, and cirrhotic patients had higher IP-10 than non-cirrhotic patients (520 vs 293.5 pg/ml; P<0.005). Response to treatment was associated with decreased IP-10 levels. Before treatment, the mean level in non-cirrhotic patients was 235±54 pg/ml, which decreased to 95±34 pg/ml (P<0.005) at week 24 of treatment. Similarly, in the cirrhotic group, IP-10 decreased from 458±42 pg/ml to 354±25 pg/ml (P <0.05) after 24 weeks of treatment. On the other hand, no change in IP-10 levels was observed for patients who did not respond to treatment. Interestingly, IP-10 levels correlated with PBMC's expression of CXCR3 mRNA (r= 0.448, P = 0.004), ALT level (r=0.273, P =0.048), liver fibrosis score 4 (FIB-4) (r=0.664, P = 0.01) and HBV DNA level (r=0.762, P =0.0001). In conclusion; IP10 may be used to predict response to therapy in HBV-infected patients.

The role of ITPA and ribavirin transporter genes polymorphisms in prediction of ribavirin-induced anaemia in chronic hepatitis C Egyptian patients.

Few data are available concerning the roles of polymorphisms of inosine triphosphatase (ITPA) gene and ribavirin (RBV) transporter genes in the prediction of RBV-induced anaemia among Egyptians with chronic hepatitis C (CHC). Genotyping of three ITPA gene variants and two variants of RBV transporter genes has been performed in 123 patients under pegylated interferon-α/ribavirin treatment. The baseline haemoglobin and ITPA rs1127354 CA/AA have been found as predictors of anaemia at 4, 8 and 12 weeks of RBV therapy. In addition, ITPA rs7270101 AC/CC and age predicted anaemia after 12 weeks of therapy. In conclusion, the ITPA variant rs1127354C>A significantly predict RBV-induced anaemia during the first 3 months of treatment and it is recommended to be assessed before RBV administration.

Toll Like Receptor 3 Polymorphisms in Hepatitis B Virus Infection.

Hepatitis B virus (HBV) is the one of the major causes of chronic liver disease. Individuals exposed to HBV show wide spectrum outcomes including immunized persons, asymptomatic carrier, chronic active hepatitis, cirrhosis and HCC. The outcome of HBV infection and the severity of associated liver diseases are determined by the nature and strength of host immune responses against the virus. There is accumulating evidence that the innate branch of the host immune system plays an important role in the control of HBV infection. Various components including toll-like receptor (TLR) contribute to this nonspecific innate immune response .TLR3 play an important role in innate immune response against viral pathogens. Single nucleotide polymorphisms (SNPs) in the TLR3 could be considered as factors for the susceptibility to viral pathogens including HBV. This study aimed to investigate the distribution of six SNPs of the TLR3 gene in patients infected with HBV and to determine the relation between these SNPs and the clearance of hepatitis B virus. These SNPs were tested by direct sequencing. Three groups were investigated: chronic HBV carrier (25 patients), chronic active HBV carrier (16 patients) and 13 persons who were previously exposed to HBV and became immunized. These 3 groups were examined for six SNPs (rs5743311, rs5743312, rs5743313, rs5743314, rs5743315, and rs78726532). The analysis showed high frequencies of GCTCCA haplotype and CCA haplotype in the immunized group when compared to chronic hepatitis B groups (P < 0.05). These findings indicate that genetic variations in the TLR3 gene could affect the outcome of HBV infection.

Study of the Urinary Ratio of 6 beta-Hydroxycortisol/Cortisol as a Biomarker of CYP3A4 Activity in Egyptian Patients with Chronic Liver Diseases.

The urinary ratio of 6 beta-hydroxycortisol/cortisol (6 beta-OHC/C) as a biomarker of CYP3A4 metabolizing activity has been studied in Egyptian patients with chronic liver cirrhosis associated with previous hepatic Schistosomiasis infection to determine any possible alteration in enzyme activity. The ratio of 6-beta OHC/C was determined in morning urine samples collected from 8:00 a.m. to 12:00 p.m. in healthy adults (n = 36) and patients with liver cirrhosis (n = 57). The median age for control was 27 years (range: 18-50 years) and 50 years (range: 27-75 years) for patients. 6 beta-OHC was detected in urine by ELIZA kits (Stabiligen, France). Patients with liver cirrhosis were categorized according to Child Pugh Classification into Child B (n = 28) and Child C (n = 29) classes. Cholestasis was observed in 9/28 of Child B class and 8/29 of Child C class of patients. The control subjects showed gender-related difference in the urinary ratio of 6 beta-OHC/C. A significant reduction (P < 0.001) in 6 beta-OHC/C ratio was observed only in Child C patients in comparison with control subjects. Regression analysis showed a significant correlation (P < 0.05) between 6 beta-OHC/C ratio and serum albumin. The influence of cholestasis on the urinary ratio of 6-beta OHC/C was observed on cirrhotic patients of Child B class. In conclusion, patients with chronic liver cirrhosis might have a reduction of metabolizing activity of CYP3A4 enzymes which could be identified by measuring the urinary ratio of 6 beta-OHC/C. This reduction is more apparent in severe liver injury (Child C class). Therefore, it is important to understand the metabolic fate of drugs metabolized by 3A4 enzymes in patients with liver cirrhosis to avoid drug accumulation that might lead to development of drug toxicity.