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, 11 (9), e0163644

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


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

Satoru Hashimoto et al. PLoS One.


Background & aim: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Conflict of interest statement

HY received financial support from Chugai Pharmaceutical Co., Ltd.There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials


Fig 1
Fig 1. Scatterplots and boxplots of ΔTC or ΔLDL-C levels after the administration of the IFN-free regimen.
(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.
Fig 2
Fig 2. Comparison of serum HCV dynamics of patients after starting IFN-free treatment stratified by ΔLDL-C level.
(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.
Fig 3
Fig 3. Correlation between ΔLDL-C (D0-D28) and ΔHCV core antigen (D0-D1).
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.

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Grant support

HY received grants and endowments from Chugai Pharmaceutical Co., Ltd. The other authors have nothing to disclose. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.