Renal impairment in patients with chronic hepatitis C treated with first generation protease inhibitors

<div><p><b><i>Background</i></b>: The incidence, course and risk factors associated with renal impairment (RI) in patients treated with triple therapy (TT) with pegylated interferon, ribavirin and telaprevir/boceprevir (PR/TVR/BOC) vs. dual therapy (DT) with PR were analyzed in this study. The association between RI and the decline of hemoglobin (Hb) was also examined.</p><p><b><i>Methods</i></b>: Retrospective analysis included 110 patients with genotype 1b chronic HCV infection, aged 18 – 80 years, who underwent TT (48TVR/14BOC) or DT (48 patients). The estimated glomerular filtration rate (eGFR), serum creatinine concentration (SCr) and Hb were measured at baseline, at weeks 4, 12, 24, 48 of treatment, and post-treatment week 24.</p><p><b><i>Results</i></b>: RI occurred in 9/62 (14.5%) patients who underwent TT, eight of whom were treated with TVR, one with BOC, and none treated with DT. The risk factors associated with RI were the following: TT (p = 0.0078), usage of nephrotoxic drugs (p = 0.0288), and older age (p < 0.0001). RI was reversible. A drop of Hb was associated with RI, older age and TT.</p><p><b><i>Conclusions</i></b>: RI is not a rare but a reversible complication of TT. It is necessary to monitor SCr and eGFR, especially in patients with a potential risk factor of RI occurrence. The Hb drop is more severe in patients with RI than in those without it.</p></div

Association between the hepatic expression of IP10, IFI27, ISG15, and MX1 with F0-1 and F2-4 fibrosis.

<p>The y-axis shows the relative unit of a given gene, normalized to GAPDH in log scale, as a box plot displaying the 10th, 25th, 50th, 75th, and 90th percentiles of expression levels. Fibrosis stages are defined according to the modified Scheuer classification.</p

Relationship between hepatic expression of ISGs and treatment outcome, stratified by IL28B genotype.

<p>Expression of IP10, IFI27, ISG15, and MX1 in CC (A) and CT-TT (B) IL28B genotype subgroups, stratified by SVR response (for CC subgroup SVR, n = 12, non-SVR [nSVR], n = 6; for CT-TT subgroup SVR, n = 7, nSVR, n = 22). The y-axis shows the relative unit of a given gene, normalized to GAPDH in log scale, as an aligned dot plot displaying the median gene expression level. Each dot represents one sample.</p

Impact of IP10 expression on SVR response.

<p>SVR rate (%) in CHC patients was stratified according to pretreatment hepatic expression of IP10 (above versus below 0.035); IL28B rs12979860 genotype is shown. The threshold value of 0.035 demonstrated the relative unit of IP10 gene expression, normalized to GAPDH. Number of patients is shown as n, and SVR/n is the total subgroup. The <i>P</i> values were obtained by Fisher’s exact test.</p

Association between IP10 expression and the progression of liver fibrosis.

<p>The y-axis shows the relative unit of a given gene, normalized to GAPDH in log scale, as a box plot displaying the 10th, 25th, 50th, 75th, and 90th percentiles of expression levels. The <i>P</i> value was obtained by the Kruskal-Wallis test. F0, F1, F2, and F3 (fibrosis stages) are defined according to the modified Scheuer classification.</p

Impact of fibrosis stage and IL28B genotype on hepatic IP10 expression.

<p>Levels of IP10 expression were determined by rs12979860 (A) and rs8099917 (B) IL28B genotypes in patients, stratified by fibrosis F0-1 and F2-4 groups. Conversely, levels of IP10 expression were also determined according to the F0-1 and F2-4 fibrosis grouping in patients stratified by rs12979860 (C) and rs8099917 (D) IL28B genotypes. The y-axis shows the relative unit of a given gene, normalized to GAPDH in log scale, as a box plot displaying the 10th, 25th, 50th, 75th, and 90th percentiles of gene expression levels. n = number of patients in each group.</p

Relationship between hepatic expression of IP10, IFI27, ISG15, and MX1 and treatment outcome in individual cases.

<p>Empty circles, rectangles, and filled diamonds represent TT, CT, and CC rs12979860 genotypes, respectively. The y-axis shows the relative unit of a given gene, normalized to GAPDH in log scale, as a box plot displaying the 10th, 25th, 50th, 75th, and 90th percentiles of gene expression levels. Each dot represents one sample. The <i>P</i> values were obtained by the Mann-Whitney test (for SVR, n = 19; non-SVR [nSVR], n = 28).</p