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Pretreatment prediction of the outcome of response-guided peginterferon-α and ribavirin therapy for chronic hepatitis C.

Masaki N, Sugiyama M, Shimada N, Tanaka Y, Nakamuta M, Izumi N, Watanabe S, Tsubota A, Komatsu M, Masaki T, Enomoto N, Yoneda M, Murata K, Ito K, Koike K, Mizokami M - J. Gastroenterol. Hepatol. (2014)

Bottom Line: The accuracy for predicting virological outcomes of peginterferon-α and ribavirin therapy in patients with chronic hepatitis C is limited to approximately 80%, even with IL28B genotyping.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.

View Article: PubMed Central - PubMed

Affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.

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Decision tree analysis for the virological outcomes. Boxes indicate the factors used for splitting and the cut-off value for the split. Pie charts indicate the rate of non-virological response for each group of patients after splitting. A total of 202 patients were included in this analysis, after excluding 13 patients who were lost to follow-up, in order to avoid the influence on final decision. Among 22 pretreatment factors (gender, prior history of interferon, pegylated interferon regimen, age, body weight; serum albumin, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, γ-glutamyl transpeptidase, total cholesterol; white blood cell, hemoglobin, platelets; FIB-4; serum levels of hepatitis C virus (HCV) RNA (reverse transcription–polymerase chain reaction), core 70/91 amino acid mutation, interferon-sensitivity determining region mutation; rs8099917 genotype, TA repeat length) tested for their abilities to predict non-virological responses, determinations of (TA)n of rs72258881 and/or the HCV core 70 amino acid substitution were useful, especially for patients with the TT genotype. In the patients with a non-TT genotype, HCV viral load was the second most important determinant of virological response. MA, major-homo; HE, hetero; mi, minor-homo; aa, amino acid. The units used to measure levels of albumin and HCV RNA were g/dL and Log IU/mL, respectively.
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fig04: Decision tree analysis for the virological outcomes. Boxes indicate the factors used for splitting and the cut-off value for the split. Pie charts indicate the rate of non-virological response for each group of patients after splitting. A total of 202 patients were included in this analysis, after excluding 13 patients who were lost to follow-up, in order to avoid the influence on final decision. Among 22 pretreatment factors (gender, prior history of interferon, pegylated interferon regimen, age, body weight; serum albumin, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, γ-glutamyl transpeptidase, total cholesterol; white blood cell, hemoglobin, platelets; FIB-4; serum levels of hepatitis C virus (HCV) RNA (reverse transcription–polymerase chain reaction), core 70/91 amino acid mutation, interferon-sensitivity determining region mutation; rs8099917 genotype, TA repeat length) tested for their abilities to predict non-virological responses, determinations of (TA)n of rs72258881 and/or the HCV core 70 amino acid substitution were useful, especially for patients with the TT genotype. In the patients with a non-TT genotype, HCV viral load was the second most important determinant of virological response. MA, major-homo; HE, hetero; mi, minor-homo; aa, amino acid. The units used to measure levels of albumin and HCV RNA were g/dL and Log IU/mL, respectively.

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).


Pretreatment prediction of the outcome of response-guided peginterferon-α and ribavirin therapy for chronic hepatitis C.

Masaki N, Sugiyama M, Shimada N, Tanaka Y, Nakamuta M, Izumi N, Watanabe S, Tsubota A, Komatsu M, Masaki T, Enomoto N, Yoneda M, Murata K, Ito K, Koike K, Mizokami M - J. Gastroenterol. Hepatol. (2014)

Decision tree analysis for the virological outcomes. Boxes indicate the factors used for splitting and the cut-off value for the split. Pie charts indicate the rate of non-virological response for each group of patients after splitting. A total of 202 patients were included in this analysis, after excluding 13 patients who were lost to follow-up, in order to avoid the influence on final decision. Among 22 pretreatment factors (gender, prior history of interferon, pegylated interferon regimen, age, body weight; serum albumin, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, γ-glutamyl transpeptidase, total cholesterol; white blood cell, hemoglobin, platelets; FIB-4; serum levels of hepatitis C virus (HCV) RNA (reverse transcription–polymerase chain reaction), core 70/91 amino acid mutation, interferon-sensitivity determining region mutation; rs8099917 genotype, TA repeat length) tested for their abilities to predict non-virological responses, determinations of (TA)n of rs72258881 and/or the HCV core 70 amino acid substitution were useful, especially for patients with the TT genotype. In the patients with a non-TT genotype, HCV viral load was the second most important determinant of virological response. MA, major-homo; HE, hetero; mi, minor-homo; aa, amino acid. The units used to measure levels of albumin and HCV RNA were g/dL and Log IU/mL, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263356&req=5

fig04: Decision tree analysis for the virological outcomes. Boxes indicate the factors used for splitting and the cut-off value for the split. Pie charts indicate the rate of non-virological response for each group of patients after splitting. A total of 202 patients were included in this analysis, after excluding 13 patients who were lost to follow-up, in order to avoid the influence on final decision. Among 22 pretreatment factors (gender, prior history of interferon, pegylated interferon regimen, age, body weight; serum albumin, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, γ-glutamyl transpeptidase, total cholesterol; white blood cell, hemoglobin, platelets; FIB-4; serum levels of hepatitis C virus (HCV) RNA (reverse transcription–polymerase chain reaction), core 70/91 amino acid mutation, interferon-sensitivity determining region mutation; rs8099917 genotype, TA repeat length) tested for their abilities to predict non-virological responses, determinations of (TA)n of rs72258881 and/or the HCV core 70 amino acid substitution were useful, especially for patients with the TT genotype. In the patients with a non-TT genotype, HCV viral load was the second most important determinant of virological response. MA, major-homo; HE, hetero; mi, minor-homo; aa, amino acid. The units used to measure levels of albumin and HCV RNA were g/dL and Log IU/mL, respectively.
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).

Bottom Line: The accuracy for predicting virological outcomes of peginterferon-α and ribavirin therapy in patients with chronic hepatitis C is limited to approximately 80%, even with IL28B genotyping.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.

View Article: PubMed Central - PubMed

Affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.

Show MeSH
Related in: MedlinePlus