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. 2018 Dec 21;13(12):e0209615.
doi: 10.1371/journal.pone.0209615. eCollection 2018.

Liver Steatosis and Dyslipidemia After HCV Eradication by Direct Acting Antiviral Agents Are Synergistic Risks of Atherosclerosis

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Free PMC article

Liver Steatosis and Dyslipidemia After HCV Eradication by Direct Acting Antiviral Agents Are Synergistic Risks of Atherosclerosis

Naoki Kawagishi et al. PLoS One. .
Free PMC article

Abstract

Aim: We comprehensively analyzed how hepatitis C virus (HCV) eradication by interferon (IFN)-free direct-acting-antiviral-agents (DAAs) affects liver steatosis and atherogenic risk.

Methods: Patients treated with IFN-free-DAAs who underwent transient elastography before and at 24-weeks post-treatment, including controlled attenuation parameter (CAP), and achieved sustained viral response (SVR) were enrolled. The association between changes in liver steatosis, lipid-metabolism, and genetic and clinical factors was analyzed.

Results: A total of 117 patients were included. The mean CAP and low-density lipoprotein cholesterol (LDL-C) levels were significantly elevated at SVR24. However, baseline LDL-C and CAP values were significantly negatively correlated with changes in these values after HCV eradication, indicating that in patients with high baseline values, the values generally decreased after HCV eradication. Mean small-dense LDL-C (sdLDL-C), which has greater atherogenic potential, was significantly elevated only in patients with both dyslipidemia (LDL-C >140 mg/dL) and liver steatosis (CAP >248 dB/m) at SVR24. Those patients had significant higher baseline BMI, LDL-C, and total-cholesterol levels.

Conclusions: Generally, successful HCV eradication by IFN-free-DAAs decreases CAP and LDL-C in patients with high baseline values. However, elevated LDL-C was accompanied with elevated sdLDL-C only in patients with liver steatosis and dyslipidemia at SVR24; therefore, those patients may require closer monitoring.

Conflict of interest statement

Professor Naoya Sakamoto received lecture fees from Bristol Myers Squibb and Pharmaceutical K.K, grants and endowments from MSD K. K and Chugai Pharmaceutical Co., Ltd, and a research grant from Gilead Sciences Inc. Dr. Goki Suda received research grants from Bristol Myers Squibb. The other authors have nothing to disclose. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Changes in lipid profile, body weight, glycoalbumin, LS, and CAP after successful HCV eradication by IFN-free DAAs.
Changes in (1A) total-cholesterol (T-C), (1B) low density lipoprotein-cholesterol (LDL-C), (1C) high density lipoprotein-cholesterol (HDL-C), (1D) glycoalbumin, (1E) liver stiffness (LS), (1F) controlled attenuation parameter (CAP), and (1G) body weight after successful HCV eradication by IFN-Free DAAs. T-C, LDL-C, HDL-C, and CAP were significantly elevated at the SVR24 point compared with baseline. Conversely, glycoalbumin and liver stiffness were improved, and body weight did not significantly change. Statistically significant difference, ** P <0.01. N.S, not significant; LS, liver stiffness; CAP, controlled attenuation parameter; DAAs, direct-acting antiviral agents.
Fig 2
Fig 2
A-B. The correlation between baseline CAP and the change in CAP and after successful HCV eradication by IFN-free DAAs. (2A) The baseline CAP value and ΔCAP values were significantly negatively correlated (r = 0.534, P <0.001). (2B) Receiver operating characteristics (ROC) curve analysis for ΔCAP value. The cut off baseline CAP associated with ΔCAP was 220 dB/m (ROC-AUC = 0.763; P <0.001; sensitivity, 0.7; specificity, 0.7). CAP; controlled attenuation parameter, ΔCAP; the value at SVR24 minus the value at baseline, SVR; sustained viral response, DAAs, direct-acting antiviral agents.
Fig 3
Fig 3
A-B. The correlation between baseline LDL-C and the change in LDL-C after successful HCV eradication by IFN-free DAAs. (3A) The baseline LDL-C level and ΔLDL-C level were significantly negatively correlated (r = 0.406, P <0.001). (3B) ROC curve analysis for ΔLDL-C level. The cut off baseline LDL-C associated with ΔLCL-C is 108 mg/dL (ROC-AUC = 0.615; P <0.001; sensitivity, 0.813; specificity, 0.753). LDL-C; low density lipoprotein-cholesterol, ΔLDL-C; the value at SVR24 minus the value at baseline, SVR; sustained viral response, DAAs, direct-acting antiviral agents.
Fig 4
Fig 4
A-D. The association between liver steatosis and serum cholesterol levels after successful HCV eradication by IFN-free DAAs. (4A) At baseline, there was no significant correlation between CAP and LDL-C (r = 0.137; P = 0.141). However, (4B) at the SVR24 point there was a significant correlation (r = 0.317, P = 0.01). (4C) At baseline (existence of HCV status), there was not significant correlation between CAP value and HDL-C level (r = 0.114, P = 0.221); however, (4D) at SVR24 point, significant correlation between CAP value and HDL-C level (r = 0.328, P <0.001). CAP, controlled attenuation parameter; LDL-C, low density lipoprotein-cholesterol; HDL-C, high density lipoprotein-cholesterol; SVR, sustained viral response; DAAs, direct-acting antiviral agents.
Fig 5
Fig 5
A-B. Changes in LDL-C and sdLDL-C after successful HCV eradication by IFN-free DAAs. The changes in LDL-C (5A) and sdLDL-C (5B) after HCV eradication by IFN-free DAAs were compared among 4 subgroups according to CAP and LDL-C at the SVR24 point (CAP < 248dB/m and LDL-C <140 mg/dL as controls; CAP >248 dB/m and LDL-C <140 mg/dL; CAP < 248dB/m and LDL-C > 140mg/dL; and CAP >248 dB/m and LDL-C >140 mg/dL). The boxplots demonstrate each lipid’s levels at baseline and the SVR24 point. Significant differences from the control group and between baseline and the SVR24 point were observed (*, P <0.05; **, P <0.01). Liver steatosis, CAP >248 dB/m; dyslipidemia, LDL-C > 140 mg/dL; LDL-C, low density lipoprotein-cholesterol; sdLDL-C, small dense LDL-C; CAP, controlled attenuation parameter; SVR, sustained viral response; DAAs, direct-acting antiviral agents.

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Grant support

Goki Suda received the following fundings: The Japan Agency for Medical Research and Development (AMED), Grant Number 16fk0210102h0001, 17fk0210106h0501, URL https://www.amed.go.jp/; and Japan Society for the Promotion of Science (JSPS) KAKENHI, Grant number 16K09334, URL https://www.jsps.go.jp/. Naoya Skamoto received funding from the Japan Agency for Medical Research and Development (AMED). Grant number is 17fk0210102h0001. URL is https://www.amed.go.jp/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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