RESUMO
INTRODUCTION: 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 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: 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: 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.
Assuntos
Antivirais/efeitos adversos , Dislipidemias/induzido quimicamente , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Lipídeos/sangue , Idoso , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Distribuição de Qui-Quadrado , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/metabolismo , Hepatite C Crônica/sangue , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/virologia , Interações Hospedeiro-Patógeno , Humanos , Resistência à Insulina , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Recidiva , Estudos Retrospectivos , Fatores de Risco , Resposta Viral Sustentada , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND AND AIM: In patients with chronic hepatitis C receiving Peg interferon/ribavirin (PEG-IFN/RBV) who do not achieve ≥ 2 log-reduction in HCV-RNA at week 12 (null responders, NR) and in those with ≥ 2 log-decrease but detectable at week 24 (partial responders, PR) the probability to achieve the sustained virological response (SVR) is almost null. The aim of this study was to investigate the efficacy of individualized schedule of progressively increased RBV doses in the setting of PEG-IFN/RBV treatment. MATERIAL AND METHODS: PR or NR to PEG-IFN/RBV instead of discontinuing treatment were enrolled to receive increasing doses of RBV until a target theoretical concentration ([tRBV]) of ≥ 15 µmol/L (by pharmacokinetic formula based on glomerular filtration rate). HCV-RNA was assessed every 4 weeks and, if detectable, RBV dose was gradually increased until negativization. Twelve weeks later, patients with detectable HCV-RNA discontinued therapy while those with undetectable HCV-RNA continued for further 48 weeks. RESULTS: Twenty genotype-1 patients (8 NR and 12 PR) were enrolled. After 12 weeks 9 (45%) were still HCV-RNA positive and were discontinued, while remaining 11 had undetectable HCV-RNA. One stopped treatment for side effects. Ten completed treatment. Five (all PR) achieved SVR. Side effects incidence was similar to that observed during PEG-IFN/RBV. CONCLUSIONS: In conclusion, RBV high doses, according to individualized schedule, increase SVR in PR on a similar extent to that of triple therapy but without increase of side effects. Such treatment should be considered in PR with no access or intolerant to protease inhibitors (PI).