Apinya Leerapun

Genetic variation in the vitamin D pathway CYP2R1 gene predicts sustained HBeAg seroconversion in chronic hepatitis B patients treated with pegylated interferon: A multicenter study

Evidence of a role of vitamin D in the immune system is increasing. Low serum vitamin D is associated with increased hepatitis B virus replication. Genome-wide association study (GWAS) data has revealed a number of the single nucleotide polymorphisms (SNPs) within the vitamin D synthetic pathway that affect vitamin D functions. We aimed to determine the association between SNPs in the vitamin D gene cascade and response to pegylated interferon (PegIFN) therapy in hepatitis B e-antigen (HBeAg)-positive patients. One hundred and eleven patients treated for 48 weeks with PegIFN-alfa 2a at 13 hospitals were retrospectively evaluated. Thirteen SNPs derived from vitamin D cascade-related genes, including DHCR7 (rs12785878), CYP27B1 (rs10877012), CYP2R1 (rs2060793, rs12794714), GC (rs4588, rs7041, rs222020, rs2282679), and VDR (FokI, BsmI, Tru9I, ApaI, TaqI), were genotyped. Thirty-one patients (27.9%) seroconverted to HBeAg after 24 weeks of treatment. Multivariate analysis found pretreatment qHBsAg <10,000 IU/mL (OR = 7.73, 95% CI: 2.36–25.31, P = 0.001), CYP2R1 rs12794714 TT genotype (OR = 4.16, 95% CI: 1.07–16.25, P = 0.04), and baseline ALT >2 times the upper limit of normal (OR = 3.83, 95% CI: 1.31–11.22, P = 0.014) predicted sustained HBeAg seroconversion after completion of PegIFN treatment. HBV DNA during study period tended to be lower with the rs12794714 CYP2R1 TT than the non-TT genotype. The rs12794714 CYP2R1 polymorphism may be a useful pretreatment factor predictive of sustained HBeAg seroconversion after PegIFN therapy. This study provides evidence that not only vitamin D level but also genetic variation of CYP2R1 in the vitamin D cascade influences host immune response in chronic HBV infection.

Three‐day versus five‐day somatostatin infusion combination with endoscopic variceal ligation in the prevention of early rebleeding following acute variceal hemorrhage: A randomized controlled trial

Combined pharmacological and endoscopic therapy is recommended for initial treatment of acute variceal bleeding (AVB). The optimal duration of therapy with a vasoactive agent is not well established. The aim of this study was to compare the efficacy and safety of 3‐day and 5‐day somatostatin treatment in the prevention of early rebleeding after endoscopic variceal ligation (EVL).

Mo1023 The Single Nucleotide Polymorphism in the Vitamin D Pathway DHCR7 Gene and Pre-Treatment HBV-DNA Strongly Predict HBeAg Loss in HBeAg-Positive Chronic Hepatitis B Patients Treated With Pegylated Interferon: Multicenter Study

Aim: Clinical outcome after hepatitis B virus (HBV) exposure vary extremely from spontaneous clearance to chronic hepatitis B and often progresses to liver cirrhosis and hepatocellular carcinoma. Host genetic factor plays an important role in the regulation of immune response. The study was designed to investigate whether (HLA) class II DQA1 and DQB1 gene polymorphism are associated with chronic hepatitis B infection and whether it leads to the development of HBV related liver cirrhosis (LC) and hepatocellular carcinoma (HCC) in north Indian population. Methods: We have assessed the DQA1 and DQB1 allele polymorphism in 187 HBV related liver diseases which included (73 chronic hepatitis B, 84 LC, and 30 HCC patients) and 109 controls who had spontaneously recovered from HBV infection by using polymerase chain reaction amplification with sequence specific primers (PCR-SSP). Results: The data suggest that DQA1*0101/2/4 (OR=2.78; P=0.003), DQA1*0103 (OR= 2.64; P=0.0007) and DQB1*0302/3 (OR=2.15; P=0.01) were associated with protection from chronic HBV infection, while DQB1*0402 (OR=0.25; P=0.001) conferred susceptibility to chronic HBV infection, respectively. It was also observed that DQB1*0601 (OR=3.73; P=0.006) conferred protective effect from developing Liver Cirrhosis, similarly DQB1*0302/ 3 (OR=5.53; P=0.05) and DQB1*0402 (OR=0.00; P=0.0001) conferred protective effect from progressing to HCC. Though, DQA1*0601 and DQB1*0503 showed some susceptible effect on chronic HBV infection, these association were no longer significant after Bonferroni correction (P=0.23, P=0.59). Conclusion: The results suggest that various subtypes of HLA-DQA1 and DQB1 does influence the HBV clearance and development of chronic HBV infections in north Indian population.