Worsening of serum lipid profile after direct acting antiviral treatment

Abstract

Host lipid metabolism influences viral replication and lifecycle of hepatitis C virus. Our aim was to evaluate changes in glucose and lipid metabolism of patients with chronic hepatitis C after therapy with direct acting antivirals (DAA). Material and Material and Material and Material and Material and methods. methods. methods. methods. methods. We considered patients consecutively treated between January and November 2015 recording clinical data at baseline and week 24 of follow-up. Frozen serum samples were used for apolipoprotein A1 (apoA1), apolipoprotein B (apoB) and lipoprotein (a) [Lp(a)]. Wilcoxon test was utilized to estimate trends and Logistic Regression for predictors of lipid changes. Results. Results. Results. Results. Results. We enrolled 100 patients, mostly cirrhotic (81%) and with genotype 1b (59%). Ninety-three patients achieved sustained virological response (SVR), while 7 relapsed. Homeostasis model assessment of insulin resistance declined (from 3 to 2.7, p < 0.001); non-high density lipoprotein (HDL) cholesterol increased from 102 ± 29 to 116 ± 35 (p < 0.001), and Lp(a) from 5.6 ± 6.5 to 9.8 ± 11.5 mg/dL (p < 0.001). Rise of low-density lipoprotein/HDL and apoB/apoA1 ratio were registered (from 1.79 ± 1.10 to 2.08 ± 1.05 and from 0.48 ± 0.18 to 0.53 ± 0.18 mg/dL, p < 0.001). We conducted a subanalysis on patients with relapse. In this subgroup, no change of lipid profile was recorded. At multivariate analysis emerged that the addition of ribavirin to DAA, represented an independent predictor of increased Lp(a) (OR 3.982, 95% CI 1.206-13.144, p = 0.023). Conclusion. Conclusion. Conclusion. Conclusion. Conclusion. DAA therapy led to reduction of insulin resistance. In contrast, pro-atherogenic lipid changes were observed in patients with SVR. Further studies will be necessary to evaluate the cardiovascular balance between amelioration of glucose metabolism and negative changes of lipid profile.

Anthropometric parameters and liver histology influence lipid metabolic changes in HCV chronic hepatitis on direct-acting antiviral treatment

“…In this study, we analyzed the dynamics of circulating lipid profile in patients treated with DAA for CHC. In line with previous reports (10,12,13,31), total and LDL cholesterol levels increased in parallel to HCV RNA clearance. These changes persisted during the subsequent follow-up, indicating that a different, more 'atherogenic' lipid pattern establishes after CHC cure.…”

“…Also, HCV clearance was shown to be associated with a reduction of atherosclerosis lesions in the short term (38). These data are apparently in contrast with the establishment of a more atherogenic lipid pattern emerging from this and prior studies (10,12,13 risk showed that, at least in the short term, cardiovascular risk after DAA treatment does not change despite of the increase in total and LDL cholesterol levels. Time of observation is probably too short to detect important modifications of these parameters, but it is probable that overweight and particular visceral obesity play a role in the lipid pattern changes during and soon after DAA treatment.…”

“…The availability of direct-acting antivirals (DAA) for HCV treatment made possible to better assess the effects of antiviral therapy on host lipid metabolism (10,11). HCV RNA clearance associated with increased cholesterol levels, particularly LDL, without major effects on triglycerides (10,12,13), confirming the direct role of HCV on ApoBrelated lipid metabolic changes. The resulting lipid pattern, however, turns to a more atherogenic one, thereby possibly increasing cardiovascular risk long term.…”

“…In the next future, patients with SVR to DAA may need specific cardiovascular risk stratification (13) and easily validated predictors, as VAI and Tr/HDL, should enter clinical practice in those with long term SVR. Early detection of an increased cardiovascular risk would favor indication to specific treatments, as statins, in a population previously considered at low risk for hypercholesterolemia and lacking a stringent need for lipid treatment.…”

“…This is an important issue in DAA-treated HCV patients as viral clearance is often associated with favorable behavioral changes and a psychological wellbeing that may increase food intake. Notwithstanding, the role of anthropometric parameters in relation to changes of lipid profile during DAA treatment has not been fully assessed (10,12,13).…”