Should aged patients with chronic hepatitis C be treated with interferon and ribavirin combination therapy?

The aim of this study was to investigate the efficacy and safety of combination therapy of interferon and ribavirin for aged patients with chronic hepatitis C. METHODS: This study was conducted at Osaka University Hospital and institutions participating in the Osaka Liver Disease Study Group on 329 patients with chronic hepatitis C receiving interferon and ribavirin combination therapy (group A, under 60 year old, n=199; group B, 60-64 year old, n=64; group C, over 65 year old (mean age, 67.8+/-2.2 year old, n=66)). Of the 293 patients who were tested for HCV serotype and HCV viral loads, 215 had HCV-RNA with serotype 1 and high viral loads (1H) and the other 78 had HCV-RNA with serotype 2 or low viral loads (non-1H). RESULTS: In per-protocol analysis, the overall SVR rate of 1H patients was 28% (51/184). Among the 1H patients, the SVR rate was significantly lower in group C (16%) and group B (17%) than in group A (34%) (p<0.05). The overall SVR rate of non-1H patients was 85% (57/67). No significant difference was found in the SVR rate among group C (79%), group B (100%), and group A (84%). On the other hand, the discontinuance of both drugs due to side effects was 29% (19/66) in group C, 20% (13/64) in group B, and 11% (21/199) in group A, with the discontinuance rates being higher in the older group (p=0.002). CONCLUSIONS: In aged chronic hepatitis C patients, interferon and ribavirin combination therapy can be recommended for the non-1H patients who showed a high SVR rate of approximately 65%, but not for the 1H patients.     

DNA methylation in peripheral blood: a potential biomarker for cancer molecular epidemiology

Aberrant DNA methylation is associated with cancer development and progression. There are several types of specimens from which DNA methylation pattern can be measured and evaluated as an indicator of disease status (from normal biological process to pathologic condition) and even of pharmacologic response to therapy. Blood-based specimens such as cell-free circulating nucleic acid and DNA extracted from leukocytes in peripheral blood may be a potential source of noninvasive cancer biomarkers. In this article, we describe the characteristics of blood-based DNA methylation from different biological sources, detection methods, and the factors affecting DNA methylation. We provide a comprehensive literature review of blood-based DNA methylation as a cancer biomarker and focus on the study of DNA methylation using peripheral blood leukocytes. Although DNA methylation patterns measured in peripheral blood have great potential to be useful and informative biomarkers of cancer risk and prognosis, large systematic and unbiased prospective studies that consider biological plausibility and data analysis issues will be needed in order to develop a clinically feasible blood-based assay.     

Body mass index and colorectal cancer risk: A Mendelian randomization study

Traditional observational studies have reported a positive association between higher body mass index (BMI) and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between BMI and CRC is sparse. A two-sample Mendelian randomization (MR) study was undertaken using 68 single nucleotide polymorphisms (SNPs) from the Japanese genome-wide association study (GWAS) and 654 SNPs from the GWAS catalogue for BMI as sets of instrumental variables. For the analysis of SNP-BMI associations, we undertook a meta-analysis with 36 303 participants in the Japanese Consortium of Genetic Epidemiology studies (J-CGE), comprising normal populations. For the analysis of SNP-CRC associations, we utilized 7636 CRC cases and 37 141 controls from five studies in Japan, and undertook a meta-analysis. Mendelian randomization analysis of inverse-variance weighted method indicated that a one-unit (kg/m²) increase in genetically predicted BMI was associated with an odds ratio of 1.13 (95% confidence interval, 1.06-1.20; P value <.001) for CRC using the set of 68 SNPs, and an odds ratio of 1.07 (1.03-1.11, 0.001) for CRC using the set of 654 SNPs. Sensitivity analyses robustly showed increased odds ratios for CRC for every one-unit increase in genetically predicted BMI. Our MR analyses strongly support the evidence that higher BMI influences the risk of CRC. Although Asians are generally leaner than Europeans and North Americans, avoiding higher BMI seems to be important for the prevention of CRC in Asian populations.     

Efficacy of re-treatment with pegylated interferon plus ribavirin combination therapy for patients with chronic hepatitis C in Japan

Background

It is still not known which patients with chronic hepatitis C who failed to respond to previous pegylated interferon (Peg-IFN) plus ribavirin therapy can benefit from re-treatment.

Methods

Seventy-four patients (HCV genotype 1, n?=?56, genotype 2, n?=?18) were re-treated with Peg-IFN plus ribavirin.

Results

On re-treatment, the sustained virologic response (SVR) rate was 41% for genotype 1 and 56% for genotype 2. With genotype 1, the factors associated with an SVR were previous treatment response and the serum hepatitis C virus (HCV) RNA level at the start of re-treatment. Patients with a ???2-log decrease in HCV RNA at week 12 (partial early virologic response, p-EVR) in previous treatment had significantly higher SVR rates than those without these decreases (p?10 IU/ml of HCV RNA at the start of re-treatment attained an SVR (6/6), while only 33% (15/45) of those patients with ??5 log₁₀ IU/ml of HCV RNA attained an SVR (p?p?=?0.01).

Conclusions

Re-treatment of genotype 1 patients should be limited to patients with a p-EVR in the previous treatment and a low HCV RNA level at the start of re-treatment. In re-treatment with Peg-IFN plus ribavirin, longer treatment duration can contribute to increasing the anti-viral effect.