Pretreatment prediction of the outcome of response-guided peginterferon-α and ribavirin therapy for chronic hepatitis C.
Bottom Line: Our in vitro study revealed that the numbers of (TA) dinucleotide repeats [(TA)n] of rs72258881, which is located in the promoter region of IL28B gene, might regulate IL28B transcription.We aimed to evaluate the usefulness of these host factors for predicting virological outcomes of this therapy in response-guided clinical settings.Multivariate logistic regression analysis revealed that rs8099917 non-TT genotype (P < 0.001), shorter (TA)n (P = 0.011), mutation of amino acid 70 in the virus core region (P = 0.029), and lower levels of serum albumin (P = 0.036) were independently associated with non-virological response.
Affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.Show MeSH
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Mentions: After excluding 13 patients who were lost to follow-up, we attempted to identify the variables that were associated with final virological outcome. As shown in Table 2, univariate analysis indicated that nine variables were significantly different or tended to be different between VR and NVR. NVR was associated with higher levels of serum AST, γ-GTP, and FIB-4, but with lower levels of T.Chol. Whereas the core 70-mino acid mutation was a viral factor related to NVR, the rs8099917 non-TT genotype and shorter (TA)n were host factors related to NVR. For nine variables for which univariate analysis indicated that the P value less than 0.15, multivariate logistic regression analysis identified four variables for the prediction of NVR: HCV core 70 amino acid mutation, rs8099917 non-TT genotype, shorter (TA)n, and the lower levels of serum albumin. Finally, a decision tree temporarily modeled 22 pretreatment factors (see the legend to Fig. 4) to predict NVR. For this purpose, 13 patients who were lost to follow-up were excluded from the analysis, in order to avoid their influence on final decision. As shown in Figure 4, if the rs8099917 genotype was primarily selected as the predictive factor (P < 0.001, χ2 = 57.647), then the shorter (TA)n attributed to the NVR in patients with the TT genotype (P = 0.023, χ2 = 5.166). In cases with the shorter (TA)n (n = 11 or 12), the presence of the core 70 amino acid mutation in HCV might significantly increase the incidences of NVR (P = 0.008, χ2 = 9.115). On the other hand, in the patients with non-TT genotype, higher viral load was the second most powerful determinant of NVR (P = 0.001, χ2 = 15.645).
Affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.