Are IL28B Gene Variations Associated with Outcomes in People with Hepatitis B?
Hepatitis B Treatment Response
In the first study presented at the AASLD meeting, Bart Takkenberg and Hendrik Reesink from the University of Amsterdam investigated whether the rs12979860 SNP linked to hepatitis C outcomes is also associated with outcomes among patients with chronic hepatitis B virus (HBV) infection treated with a combination of pegylated interferon plus adefovir (Hepsera).
The investigators determined IL28B gene patterns for 96 chronic hepatitis B patients -- 45 hepatitis B "e" antigen (HBeAg) positive and 51 HBeAg negative -- with HBV DNA viral load > 20,000 IU/mL at baseline who were treated with pegylated interferon alfa-2a (Pegasys) plus adefovir for 48 weeks, followed by a 24-week post-treatment follow-up period.
The researchers saw no significant association between rs12979860 SNP pattern and viral load or hepatitis B surface antigen (HBsAg) status at baseline. Among patients who completed treatment, there were also no significant differences in overall outcomes between the different rs12979860 groups. There was a trend toward a greater likelihood of sustained virological response (SVR, defined as HBV DNA < 2000 IU/mL) among HBeAg negative patients with the favorable C/C pattern (57%) compared to those with C/T or T/T (36% combined). In contrast, HBeAg seroconversion among initially HBeAg positive patients was somewhat less common in the C/C group (22% vs 54%, respectively). Rates of HBsAg loss were similar.
Finding significant links between IL28B gene patterns and treatment outcomes might require larger studies, the researchers suggested, "as the heterogeneity of HBV patients, viral genotypes, and definitions of outcome make [hepatitis B] more challenging for evaluation of host genetics" than hepatitis C.
HBV Genotype D
In the second study, Pietro Lampertico from Universita degli Studi di Milano in Italy and colleagues looked at the association between the same rs12979860 SNP and outcomes among 101 HBeAg negative chronic hepatitis B patients. Most (92%) had HBV genotype D and about half had liver cirrhosis. Just under half (48) had the C/C pattern, 42 had C/T, and 11 had T/T.
Participants were treated with either conventional or pegylated interferon alfa for 12-24 weeks, and followed for 11 years on average post-treatment. During follow-up 21% experienced HBsAg clearance and 15% achieved HBs antibody response. Here, HBsAg clearance rates differed significantly across IL28B patterns: 36% of T/T patients, 29% of C/C patients, and just 7% of C/T patients.
In a univariate analysis, baseline HBV DNA, ALT level, and IL28B pattern were significantly associated with HBsAg clearance, but not patient age, sex, cirrhosis, or HBV genotype. In a multivariate analysis, baseline HBV DNA 150 IU/mL, and the rs12979860 C/C pattern (odds ratio 3.9; P = 0.025) remained significant predictors.
"IL28B polymorphism may represent an additional pretreatment predictor of interferon response in HBeAg negative, genotype D patients with chronic hepatitis B," the researchers concluded.
i dont think we need these predictors of response after results of nucs+peginterferon sequential treatment, since 90% of patients responded to this treatment and 40% cleared already at 1 year i think we just have to go for this combo treatment.the combo had best results in tdf, etv and adv combos
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