Comparison of serum HCV dynamics of patients after starting IFN-free treatment stratified by ΔLDL-C level.

<p>(a) The decrease of HCV core antigen was more rapid in the patients with higher ΔLDL-C values than in those with low ΔLDL-C. (b) There was no difference in the decline of HCV-RNA regardless of the value of ΔLDL-C. Open circles: the LDV/SOF patients. Closed circles: the DCV/ASV patients.</p

Correlation between ΔLDL-C (D0-D28) and ΔHCV core antigen (D0-D1).

<p>Scatterplots with fitting line show positive correlation between ΔLDL-C and ΔHCV core antigen. Pearson’s correlation provides coefficient (r) and p-value. Open circles: the LDV/SOF patients. Closed circles: the DCV/ASV patients.</p

Rapid Increase in Serum Low-Density Lipoprotein Cholesterol Concentration during Hepatitis C Interferon-Free Treatment

<div><p>Background & Aim</p><p>We performed lipid analyses at the early period of therapy in patients with chronic hepatitis C who underwent interferon (IFN)-free direct-acting antiviral (DAA) treatment, and we attempted to identify the factors that contributed to a rapid increase in the patients’ serum low-density lipoprotein cholesterol (LDL-C) concentration.</p><p>Methods</p><p>We retrospectively analyzed the cases of 100 consecutive patients with HCV infection treated at the National Hospital Organization Nagasaki Medical Center: 24 patients underwent daclatasvir (DCV) and asunaprevir (ASV) combination therapy (DCV/ASV) for 24 weeks, and the other 76 patients underwent ledipasvir and sofosbuvir combination therapy (LDV/SOF) for 12 weeks. ΔLDL-C was defined as the changed in LDL-C level at 28 days from the start of therapy. To determine whether ΔLDL-C was associated with several kinds of factors including viral kinetics, we performed a stepwise multiple linear regression analysis.</p><p>Results</p><p>The LDL-C levels in patients treated with LDV/SOF were markedly and significantly elevated (87.45 to 122.5 mg/dl; p<10⁻¹⁰) compared to those in the DCV/ASV-treated patients (80.15 to 87.8 mg/dl; p = 0.0056). The median levels of ΔLDL-C in the LDV/SOF and DCV/ASV groups were 33.2 and 13.1, respectively. LDV/SOF combination therapy as an IFN-free regimen (p<0.001) and ΔHCV core antigen (0–1 day drop) (p<0.044) were identified as independent factors that were closely related to the ΔLDL-C.</p><p>Conclusions</p><p>A rapid increase in the serum LDL-C concentration during the IFN-free treatment of hepatitis C was associated with the type of HCV therapy and a decline of HCV core protein.</p></div

Factors Associated with ΔLDL-C value with HCV administered IFN-free regimen, Analyzed by Linear Regression Analysis.

<p>Factors Associated with ΔLDL-C value with HCV administered IFN-free regimen, Analyzed by Linear Regression Analysis.</p

Scatterplots and boxplots of ΔTC or ΔLDL-C levels after the administration of the IFN-free regimen.

<p>(a) Median changes of TC in each therapy. (b,c) Scatterplots and boxplots of ΔTC in the LDV/SOV patient group (b) and in the DCV/ASV group (c). (d) Median changes of LDL-C in each therapy. (e,f) Scatterplots and boxplots of ΔLDL-C in the LDV/SOF (e) and DCV/ASV (f) −groups. *p<0.001.</p

LIPS for gAChR in the sera from AIH patients with or without HLA-DRB1 *0403 allele.

<p>We tested the sera from AIH patients with or without HLA-DRB1 *0403 allele. The mean anti-gAChR α3 antibody level in patient with *0403 allele was 1.06 antibody index (AI), which was significantly higher than in those without *0403 allele with a mean level of 0.59 A.I. (<i>p</i> = 0.043). The mean anti-gAChR β4 antibody level in patients with *0403 allele was 0.76A.I, which was significantly higher than in the mean level of 0.50A.I. in those without *0403 allele (<i>p</i> = 0.010).</p

Factors Associated with ΔLDL-C value with HCV administered IFN-free regimen, Analyzed by Multiple Logistic-regression Analysis.

<p>Factors Associated with ΔLDL-C value with HCV administered IFN-free regimen, Analyzed by Multiple Logistic-regression Analysis.</p

Baseline Demographics and Clinical Characteristics of Patients.

<p>Baseline Demographics and Clinical Characteristics of Patients.</p

Relationship between anti-gAChR α3 and anti- gAChR β4 antibody levels.

<p>Calculation of the correlation between anti-gAChR α3 and anti-gAChR β4 antibody levels in AIH patients with both autoantibodies (n = 17). Correlation was calculated using Spearman’s Rank Correlation test. There is no correlation at all (r = -0.04, <i>p</i> = 0.58).</p

Relationship between post-treatment WFA⁺-M2BP values and HCC development.

<p>The distribution of WFA⁺-M2BP values was plotted. The dashed line indicates the 2.0 COI for WFA⁺-M2BP. The 16 patients who developed HCC were stratified according to the duration from SVR to HCC development in 5-year increments. Each time point is designated by a distinct symbol as indicated. 222 patients did not develop HCC, and 209 of these 222 patients (94.1%) were in the post-treatment WFA⁺-M2BP ≤ 2.0 COI group (white circles). During the follow-up period, 5 of 18 patients (27.8%) developed HCC in the post-treatment WFA⁺-M2BP > 2.0 COI group, which was significantly higher than the rate in the post-treatment WFA⁺-M2BP ≤ 2.0 COI group (5.0%, <i>P</i> < 0.001). In the post-treatment WFA⁺-M2BP > 2.0 COI group, 4 of 5 cases developed HCC within 5 years after IFN treatment (black circles).</p