RESUMO
Objectives: To assess the impact of all-oral direct-acting antiviral agent (DAA) regimens on the risk of hepatocellular carcinoma (HCC) in HIV/HCV-coinfected patients with cirrhosis. Methods: This was a multicentre prospective cohort study recruiting HIV/HCV-coinfected patients with a new diagnosis of compensated cirrhosis. Patients were followed up until HCC, death or the censoring date (March 2017). The primary endpoint was the emergence of HCC. The incidence rate (IR) (95% CI) of HCC in different groups was computed. Time-to-event analyses were performed to identify predictors of HCC emergence. Results: The study included 495 HIV/HCV-coinfected patients with cirrhosis. After a median (IQR) follow-up of 59 (27-84) months, 22 (4.4%; 95% CI 2.6-6.3) patients developed an HCC. The IR (95% CI) of HCC was 0.93 (0.06-1.42) per 100 person-years (PY). Three hundred and three (61%) patients achieved sustained virological response (SVR) during follow-up, 79 after interferon (IFN)-based regimens and 224 after an all-oral DAA regimen. The IR (95% CI) of HCC after all-oral DAA was 0.35 (0.14-0.85) per 100 PY whereas it was 1.79 (1.11-2.88) per 100 PY in the remaining cohort (P = 0.0005). When only patients with SVR were considered, the IR (95% CI) of HCC after all-oral DAA was 0.32 (0.12-0.86) whereas it was 0 per 100 PY among those with SVR after IFN-based therapies (P = 0.27). Achieving SVR with an all-oral DAA regimen during follow-up was independently associated with a lower risk of HCC emergence (subhazard ratio 0.264; 95% CI 0.070-0.991; P = 0.049). Conclusions: SVR with all-oral DAA regimens reduces the risk of HCC in HIV/HCV-coinfected patients with compensated cirrhosis.
Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/prevenção & controle , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Adulto , Coinfecção/complicações , Coinfecção/tratamento farmacológico , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Resposta Viral SustentadaRESUMO
OBJECTIVE: To assess the possible association between the use of direct antiviral agents (DAA) and the risk of hepatocellular carcinoma (HCC) in HIV/hepatitis C virus (HCV)-coinfected patients. METHODS: The GEHEP-002 cohort recruits HCC cases in HIV-infected patients from 32 centers from Spain. Three analyses were performed: the proportion of HCC cases after sustained virological response (SVR) and the evolution of this proportion over time, the frequency of HCC after SVR in HIV/HCV-coinfected patients with cirrhosis, and the probability of HCC recurrence after curative therapies among those undergoing HCV therapy. RESULTS: Forty-two (13%) out of 322 HCC cases in HIV/HCV-coinfected patients occurred after SVR. Twenty-eight (10%) out of 279 HCC cases diagnosed during the years of use of IFN-based regimens occurred after SVR whereas this occurred in 14 (32.6%) out of the 43 HCC cases diagnosed in the all-oral DAA period (Pâ<â0.0001). One thousand, three hundred and thirty-seven HIV/HCV-coinfected patients with cirrhosis achieved SVR in the cohort. The frequency of HCC after SVR declined from 15% among those cured with pegylated-IFN with ribavirin to 1.62 and 0.87% among those cured with DAA with and without IFN, respectively. In patients with previous HCC treated with curative therapies, HCC recurrence occurred in two (25%) out of eight patients treated with IFN-based regimens and four (21%) out of 19 treated with DAA-IFN-free regimens (Pâ=â1.0). CONCLUSION: The frequency of HCC emergence after SVR has not increased after widespread use of DAA in HIV/HCV-coinfected patients. DAA do not seem to impact on HCC recurrence in the short-term among those with previously treated HCC.
Assuntos
Antivirais/administração & dosagem , Carcinoma Hepatocelular/epidemiologia , Coinfecção/complicações , Coinfecção/tratamento farmacológico , Infecções por HIV/complicações , Hepatite C Crônica/tratamento farmacológico , Resposta Viral Sustentada , Feminino , Hepatite C Crônica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Medição de Risco , Espanha/epidemiologiaRESUMO
BACKGROUND: Antiretroviral drugs with a lower potential to induce hepatic steatosis in human immunodeficiency virus (HIV) infection need to be identified. We compared the effect of switching efavirenz (EFV) to raltegravir (RAL) on hepatic steatosis among HIV-infected patients with nonalcoholic fatty liver disease (NAFLD) receiving EFV plus 2 nucleoside analogues. METHODS: HIV-infected patients on EFV plus tenofovir/emtricitabine or abacavir/lamivudine with NAFLD were randomized 1:1 to switch from EFV to RAL (400 mg twice daily), maintaining nucleoside analogues unchanged, or to continue with EFV plus 2 nucleoside analogues. At baseline, eligible patients should show controlled attenuation parameter (CAP) values ≥238 dB/m. Changes in hepatic steatosis at 48 weeks of follow-up over baseline levels were measured by CAP. RESULTS: Overall, 39 patients were included, and 19 of them were randomized to switch to RAL. At week 48, median CAP for the RAL group was 250 (Q1-Q3, 221-277) dB/m and 286 (Q1-Q3, 269-314) dB/m for the EFV group (P = .035). The median decrease in CAP values was -20 (Q1-Q3, -67 to 15) dB/m for the RAL arm and 30 (Q1-Q3, -17 to 49) dB/m for the EFV group (P = .011). CAP values <238 dB/m at week 48 were observed in 9 (47%) patients on RAL and 3 (15%) individuals on EFV (P = .029). CONCLUSIONS: After 48 weeks, HIV-infected individuals switching EFV to RAL showed decreases in the degree of hepatic steatosis, as measured by CAP, compared with those continuing with EFV. In addition, the proportion of patients without significant hepatic steatosis after 48 weeks was greater for those who switched to RAL. CLINICAL TRIALS REGISTRATION: NCT01900015.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Benzoxazinas/efeitos adversos , Infecções por HIV/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Raltegravir Potássico/efeitos adversos , Alcinos , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/uso terapêutico , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Ciclopropanos , Didesoxinucleosídeos/uso terapêutico , Substituição de Medicamentos , Quimioterapia Combinada , Técnicas de Imagem por Elasticidade , Emtricitabina/uso terapêutico , Feminino , Humanos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Raltegravir Potássico/uso terapêutico , Tenofovir/uso terapêutico , Triglicerídeos/sangue , Relação Cintura-QuadrilRESUMO
UNLABELLED: Liver fibrosis is used to make decisions about the timing of therapy against hepatitis C virus (HCV) in routine clinical practice, which should be based on the short-term likelihood of liver decompensations. Thus, we aimed at evaluating the risk of decompensations and death among human immunodeficiency virus (HIV)/HCV-coinfected individuals according to their baseline fibrosis classified by either liver biopsy or liver stiffness measurement (LSM). Patients coinfected with HIV/HCV, naive or without sustained virological response to HCV therapy, were included in this cohort. Fibrosis was classified by biopsy in 683 patients and by LSM in 1046 individuals. Reference categories were fibrosis stage 0 and LSM <6 kPa. For patients with biopsy, the adjusted subhazard ratio for decompensations and 95% confidence interval (95% CI) by fibrosis stage were as follows: stage 1, 2.3 (0.27-20.3), P = 0.443; stage 2, 2.8 (0.33-24), P = 0.345; stage 3, 4.91 (0.60-41), P = 0.137; stage 4, 9.89 (1.25-79.5), P = 0.030. For patients with LSM, the adjusted subhazard ratio and 95% CI by LSM category were as follows: 6-9.4 kPa, 1.89 (0.18-20.3), P = 0.599; 9.5-14.5 kPa, 6.59 (0.73-59.2), P = 0.092; ≥14.6 kPa, 59.5 (8.3-427), P < 0.0001. Regarding the risk of death, the adjusted hazard ratio and 95% CI for death by fibrosis stage were as follows: stage 1, 1.3 (0.4-4.11), P = 0.677; stage 2, 2.68 (0.86-8.36), P = 0.090; stage 3, 2.58 (0.82-8.15), P = 0.106; stage 4, 4.35 (1.43-13.3), P = 0.010. For patients with LSM, the adjusted hazard ratio and 95% CI for death by LSM were as follows: 6-9.4 kPa, 1.7 (0.63-4.79), P = 0.288; 9.5-14.5 kPa, 3.38 (1.2-9.5), P = 0.021; ≥14.6 kPa, 12.7 (4.9-33.6), P < 0.0001. CONCLUSION: Patients coinfected with HIV/HCV without advanced fibrosis are at very low risk of decompensations in the short term; deferral of HCV therapy for a few years and monitoring fibrosis progression is a safe option until cheaper, more effective, and more convenient HCV treatment becomes widely available.