Chang-Wen Huang

IL28B SNP rs12979860 is a critical predictor for on-treatment and sustained virologic response in patients with hepatitis C virus genotype-1 infection.

Background Single nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) have received considerable interest for their association with sustained virological response (SVR) when treating patients of genotype-1 hepatitis C virus (GT1-HCV) chronic infection with pegylated interferon and ribavirin (PegIFN/RBV). This study was to investigate the predictive power of IL28B SNPs for on-treatment responses and SVR in treatment-naïve patients with GT1-HCV chronic infection. Methodology/Principal Findings We analyzed ten SNPs of IL28B in 191 treatment-naïve patients with GT1-HCV chronic infection who received PegIFN/RBV. In these patients, rapid virological response (RVR), early virological response (EVR) and SVR were achieved in 69.6%, 95.8% and 68.6% of the patients, respectively. Multivariate analysis (odds ratio; 95% confidence interval; P value) indicated age (0.96; 0.93–0.99; 0.012), low baseline viral load (4.65; 2.23–9.66; <0.001) and CC genotype of rs12979860 (7.74; 2.55–23.53; <0.001) but no other SNPs were independent predictors for SVR. In addition, none of the ten SNPs examined were associated with baseline viral load and stages of liver fibrosis. Regarding RVR, low baseline viral load (2.83; 1.40–5.73; 0.004) and CC genotype of rs12979860 (10.52; 3.45–32.04; <0.001) were two critical predictors. As for EVR, only CC genotype of rs12979860 (36.21; 6.68–196.38; <0.001) was the predictor. Similarly, for end of treatment response (ETR), CC genotype of rs12979860 (15.42; 4.62–51.18; <0.001) was the only predictor. For patients with RVR, only low baseline viral load (3.90; 1.57–9.68; 0.003) could predict the SVR. For patients without RVR, only rs12979860 (4.60; 1.13–18.65; 0.033) was the predictor for SVR. Conclusions/Significance rs12979860 is the critical predictor for RVR, EVR, ETR and SVR in treatment-naïve patients of GT1-HCV chronic infection. Furthermore, this SNP is the only predictor for SVR in patients without RVR. These results have provided evidence that rs12979860 is the ideal IL28B SNP for genetic testing in treating patients of GT1-HCV chronic infection.

MELD score can predict early mortality in patients with rebleeding after band ligation for variceal bleeding

AIM To investigate the outcomes, as well as risk factors for 6-wk mortality, in patients with early rebleeding after endoscopic variceal band ligation (EVL) for esophageal variceal hemorrhage (EVH). METHODS Among 817 EVL procedures performed for EVH between January 2007 and December 2008, 128 patients with early rebleeding, defined as rebleeding within 6 wk after EVL, were enrolled for analysis. RESULT The rate of early rebleeding after EVL for acute EVH was 15.6% (128/817). The 5-d, 6-wk, 3-mo, and 6-mo mortality rates were 7.8%, 38.3%, 55.5%, and 58.6%, respectively, in these early rebleeding patients. The use of beta-blockers, occurrence of hypovolemic shock, and higher model for end-stage liver disease (MELD) score at the time of rebleeding were independent predictors for 6-wk mortality. A cut-off value of 21.5 for the MELD score was found with an area under ROC curve of 0.862 (P < 0.001). The sensitivity, specificity, positive predictive value, and negative predictive value were 77.6%, 81%, 71.7%, and 85.3%, respectively. As for the 6-mo survival rate, patients with a MELD score ≥ 21.5 had a significantly lower survival rate than patients with a MELD score < 21.5 (P < 0.001). CONCLUSION This study demonstrated that the MELD score is an easy and powerful predictor for 6-wk mortality and outcomes of patients with early rebleeding after EVL for EVH.

None of the six SNPs of IL28B could predict treatment responses in genotype 2 chronic HCV infected patients by propensity score matching analysis.

Background & Aims A combination of pegylated interferon-alpha and ribavirin (PR) is the standard therapy for patients with chronic hepatitis C. The impact of polymorphism of interleukin-28B (IL28B) on sustained virological response (SVR) to PR has been well documented in patients with CHC genotype-1 (GT1), but it is controversial in genotype-2 (GT2) CHC patients. This study investigated the predictability of six single nucleotide polymorphisms (SNP) of IL28B on the treatment responses of PR in patients with CHC GT2. Method 197 CHC GT2 consecutive patients who received PR treatment in our prospective cohort were enrolled. Hepatitis C virus (HCV) genotyping, quantification of HCV-RNA and genotyping of the ten SNPs of IL28B were performed. Six SNPs of IL28B were chosen for analysis. The propensity score matching (PSM) analysis was applied using patients with CHC GT1 in another prospective cohort as a positive comparison to avoid covariate bias. Results The distribution of the six SNPs was similar in GT1 and GT2 patients. Five of these SNPs had strong association with treatment responses in GT1 but not in GT2 patients. After PSM analysis, these five SNPs still showed strong association with rapid virological response (RVR), cEVR and SVR in GT1 and had no influence in GT2 patients. Furthermore, rs12979860 and baseline viral load were the predictors for both RVR and SVR in GT1 patients. However, only baseline viral load could predict RVR and SVR in GT2 patients. In addition, in patients without RVR, rs12979860 was the only predictor for SVR in GT1 but no predictor for SVR was found in GT2. Conclusions The genetic polymorphisms of IL28B had no impact on treatment responses in GT2 patients.

Various predictors of sustained virologic response in different age groups of patients with genotype-1 chronic hepatitis C.

Background: Age is one of the sustained virologic response (SVR) predictors for genotype-1 chronic hepatitis C patients treated with pegylated interferon-&agr;/ribavirin. However, variation of SVR predictors in different age groups was not explored before. We therefore conducted this study for investigating this issue. Methods: We retrospectively analyzed 265 genotype-1 chronic hepatitis C patients who received pegylated interferon-&agr;/ribavirin treatment. These patients were divided into 3 age groups. Clinical parameters including the genotype of rs12979860 were analyzed. Results: SVR rate was highest in patients younger than 45 years and lowest in patients older than 65 years even through propensity score matching analysis. As for rapid virologic response (RVR) predictors, genotype of rs12979860 was the predictor for the patients younger than 45 years and patients aged between 45 and 65 years, but no RVR predictor was found for patients older than 65 years. As for the SVR predictors, HbA1c, baseline viral load, and RVR but not genotype of rs12979860 were the predictors in patients younger than 45 years. For patients between 45 and 65 years, the predictors for SVR were liver fibrosis, genotype of rs12979860, and RVR. For patients older than 65 years, RVR was the only predictor for SVR. Conclusions: SVR predictors are various in different age groups. RVR is the SVR predictor for all age groups, but the genotype of rs12979860 is the SVR predictor only for patients with age between 45 and 65 years but not younger or older patients.

IL28B polymorphism and early anemia predict the rapid null response in genotype-1 chronic hepatitis C with dual therapy

Rapid null response (rNR), defined as less than one log decline of Hepatitis C virus (HCV‐RNA) at Week 4 of treatment with pegylated interferon‐α and ribavirin (PegIFN/RBV), is highly correlated with treatment failure in patients with chronic hepatitis C (CHC), genotype‐1 (GT‐1). In this study, we investigate the possible predictors of rNR.