We fully agree with Dr. Sonneveld et al.'s interpretation of our study1 suggesting an interplay between response to interferon and rs12979860 polymorphisms in hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B in Italy. The reason we omitted presenting data on an association between interleukin (IL)28B polymorphisms and HBV genotype was that more than 90% of the patients of Italian descent enrolled in the study carry the genotype D of HBV. Owing to the small sample size of the study, we thought it was impossible to evaluate predictors of response to interferon in relation to HBV genotype, yet to comply with Dr. Sonneveld et al.'s,2 we reanalyzed our results according to HBV genotype. IL28B stratification was 48% for CC, 41% for CT, and 11% for TT, the rates of end-of-treatment response, sustained response, and HBsAg clearance among the 93 genotype D patients being still significantly higher in CC than in non-CC carriers, i.e., 69% versus 44% (P = 0.014), 31% versus 12% (P = 0.028), and 29% versus 12% (P = 0.048).

To obtain further insights into the association between interferon response and IL28B polymorphisms in our population, we expanded our investigation to the rs8099917 polymorphism of IL28B that was recently shown to refine the prediction of a response to interferon and ribavirin therapy among chronic hepatitis C patients carrying the CT genotype of rs12979860.3 In our study, the favorable rs8099917 TT genotype was found in 100% of the rs12979860 CC patients compared to 31% of CT and 10% of TT patients only. Among the 42 rs12979860 CT patients, off-therapy responses were significantly higher in the 13 rs8099917 TT than in the 29 rs8099917 TG patients, with a rate of sustained virological response of 23% versus 3%, P = 0.045 and of HBsAg loss of 23% versus 0%, P = 0.007. Taken together, our findings not only confirm the association between IL28B polymorphism of rs12979860 and response to interferon in genotype D patients with HBeAg-negative chronic hepatitis B, but, for the first time, provide evidence that the copresence of the rs8099917 SNP near IL28B may improve pretreatment prediction of response to interferon.


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  • 1
    Lampertico P, Vigano M, Cheroni C, Facchetti F, Invernizzi F, Valveri V, et al. IL28B polymorphisms predict interferon-related HBsAg seroclearance in genotype D HBeAg-negative patients with chronic hepatitis B. HEPATOLOGY 2013;57:xx–xx.
  • 2
    Sonneveld MJ, Wong VW, Woltman AM, Wong GL, Cakaloglu Y, Zeuzem S, et al. Polymorphisms near IL28B and serological response to peginterferon in HBeAg-positive patients with chronic hepatitis B. Gastroenterology 2012; 142: 513520.
  • 3
    Fischer J, Bohm S, Scholz M, Muller T, Witt H, George J, et al. Combined effects of different interleukin-28B gene variants on the outcome of dual combination therapy in chronic hepatitis C virus type 1 Infection. HEPATOLOGY 2012 [Epub ahead of print].

Pietro Lampertico M.D., Ph.D.*, Enrico Galmozzi Ph.D.*, Massimo Colombo M.D.*, * “A.M. e A. Migliavacca” Center for the Study of Liver Disease, 1st Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy.