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

Abstract

Background & AimWe 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.MethodsWe 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.ResultsThe 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.ConclusionsA 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.

Study of changes in lipid profile and insulin resistance in Egyptian patients with chronic hepatitis C genotype 4 in the era of DAAs

“…Upon treating CHC genotype 1 patients, Hashimoto et al [18] observed a rapid increase in LDLc and TC during the first 28 days of treatment that was stronger in patients who received LDV/SOF than in those who received daclatasvir/sunaprevir (DCV/ASV), while Endo et al [19] reported a significantly greater increase in TC and LDLc in the SOF/LDV group than in the DCV/ASV group during treatment, but at 4 and 12 weeks after therapy, the serum levels of TC and LDL-c were similar in both groups.…”

Impact of interferon-free antivirus therapy on lipid profiles in patients with chronic hepatitis C genotype 1b

“…Meanwhile, the increases in cholesterol levels during treatment were dependent on the treatment regimen[22]. Although the increases in TC and LDL-C levels were features of both DCV + ASV and SOF + LDV treatment, the increase in cholesterol during treatment was much greater in the SOF + LDV-SVR group than in the DCV + ASV-SVR group[22].…”

“…Although the increases in TC and LDL-C levels were features of both DCV + ASV and SOF + LDV treatment, the increase in cholesterol during treatment was much greater in the SOF + LDV-SVR group than in the DCV + ASV-SVR group[22]. The differences in the increase in cholesterol between DCV + ASV-SVR and SOF + LDV-SVR groups may not be simply explained by cancellation of disturbed lipid metabolism caused by HCV.…”

“…Instead, DAAs by themselves may have pharmacological actions on lipid metabolism[22]. This hypothesis that DAAs have pharmacological effects on lipid metabolism was strengthened by the changes in the serum cholesterol in DCV + ASV-nSVR group.…”

“…Hashimoto et al[22] recently examined factors affecting the increase in LDL-C in the early stage of DCV + ASV or SOF + LDV treatment and reported that factors promoting an increase in LDL-C of 25 mg/dL or more at 4 wk of therapy were therapy regimen (SOF + LDV) and change in the quantity of the HCV core antigen. The greater the decrease in the amount of HCV core antigen, the greater the increase in LDL-C.…”