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1.
Zhonghua Gan Zang Bing Za Zhi ; 30(4): 395-401, 2022 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-35545564

RESUMO

Objective: To evaluate the real-world efficacy and safety of sofosbuvir and velpatasvir (SOF/VEL) tablets in the treatment of Chinese patients with chronic HCV infection. Methods: An open-label, single-center, prospective clinical study was conducted in a county in northern China. A total of 299 cases were enrolled. Of these, 161 cases with chronic hepatitis C and 73 cases with compensated cirrhosis received SOF/VEL for 12 weeks. 65 cases with decompensated cirrhosis received SOF/VEL combined with ribavirin for 12 weeks (22 cases) or SOF/VEL for 24 weeks (43 cases). Virological indicators, liver and renal function indexes, and liver stiffness measurement were detected at baseline, the fourth week of treatment, the end of treatment, and the 12-weeks of follow-up. Adverse reactions and laboratory abnormalities were observed during the course of treatment . The primary endpoint was undetectable rate of HCV RNA (SVR12) at 12 weeks of follow-up with the use of modified intention-to-treat (mITT) approach. Measurement data between two groups were compared using t-test. One Way ANOVA was used for comparison between multiple groups. Enumeration data were analyzed by chi-square test or Fisher's exact test. Results: 291 cases had completed treatment. HCV RNA was undetectable after 12 weeks of follow-up, and the SVR12 rate was 97.3% (95% confidence interval: 95.4%-99.3%). Among them, 97.4% of genotype 1b, 96.4% of genotype 2a, and 100% of those with undetected genotype achieved SVR12. The SVR12 rates in patients with chronic hepatitis C, compensated and decompensated liver cirrhosis were 98.1%, 98.6% and 93.8%, respectively. An improvement in alanine aminotransferase, aspartate aminotransferase and other liver biochemical indicators accompanied with virological clearance and reduced liver stiffness measurement was observed in patients with compensated cirrhosis, with statistically significant difference. There was no significant abnormality in renal function before and after treatment. The most common adverse reactions were fatigue, headache, epigastric discomfort and mild diarrhea. The overall adverse reactions were mild. One patient died of decompensated liver cirrhosis combined with massive upper gastrointestinal bleeding, which was unrelated to antiviral treatment. Four patients discontinued treatment prematurely due to adverse events. Relapse was occurred in four cases, and drug-resistance related mutations were detected in three cases. Conclusion: Sofosbuvir and velpatasvir tablets in Chinese HCV-infected patients with different genotypes, different clinical stages or previously treated with pegylated interferon combined with ribavirin resulted in higher SVR12, indicating that the treatment safety profile is good.


Assuntos
Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Carbamatos , Quimioterapia Combinada , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis , Humanos , Cirrose Hepática/complicações , Estudos Prospectivos , RNA , Ribavirina/uso terapêutico , Sofosbuvir/efeitos adversos , Resposta Viral Sustentada , Resultado do Tratamento
2.
Can J Gastroenterol Hepatol ; 2022: 7395506, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35531123

RESUMO

Objective: To assess the geographic distribution of HCV genotypes, effectiveness, and safety of DAA treatment for HCV-infected patients in North and Northeast China. Methods: The geographic distribution of HCV genotypes was analyzed in 2162 patients recruited from April 2018 to February 2021. Sustained virologic response rates at 12 (SVR12) or 24 (SVR24) weeks posttreatment and safety were analyzed in 405 patients who completed DAA treatment according to patient baseline characteristics and treatment. Results: Four genotypes and six subtypes were identified as follows: 1b (1187, 54.90%), 2a (790, 36.54%), 3a/b (134, 6.20%), 6a/n (44, 2.04%), mixed genotypes (2a-6a or 2a-3a) (7, 0.32%). Overall, 99.01% patients achieved SVR12, while 98.43% achieved SVR24. All patients treated with elbasvir/grazoprevir (EBR/GZR), sofosbuvir/velpatasvir ± ribavirin (SOF/VEL ± RBV), and SOF/ledipasvir (LDV) achieved SVR12 or SVR24; 92.86% SVR12 and 95.83% SVR24 were observed in patients using SOF + RBV. SVR12 was higher in noncirrhosis versus compensated cirrhosis patients (100% vs. 97.09%, p=0.022). No severe drug-related adverse event was observed. Conclusions: Genotypes 1b and 2a were dominant subtypes in North and Northeast China. The approved drug regimens EBR/GZR and SOF/LDV for subtype 1b and SOF/VEL for nongenotype 1b are the optimal effective and safety profile.


Assuntos
Antivirais , Hepatite C Crônica , Antivirais/efeitos adversos , Quimioterapia Combinada , Genótipo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Humanos , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada , Resultado do Tratamento
3.
World J Gastroenterol ; 28(11): 1172-1183, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35431505

RESUMO

BACKGROUND: Hepatitis C virus (HCV) genotype 6 (HCV-6) infection is prevalent predominantly in Southeast Asia, and the data on the virologic response of HCV-6 to direct-acting antivirals (DAAs) are sparse in people living with human immunodeficiency virus (HIV) (PLWH). AIM: To assess the virologic response of HCV-6 to DAAs in PLWH. METHODS: From September 2016 to July 2019, PLWH coinfected with HCV-6 initiating DAAs were included. Laboratory investigations were performed at baseline, the end of treatment, and 12 wk off-therapy. RESULTS: Of the 349 PLWH included (mean age 48.9 years, 82.5% men), 80.5% comprised people who inject drugs, 18.1% men who have sex with men, and 1.4% heterosexuals. Coexistent hepatitis B virus infection was present in 12.3% of the included PLWH, liver cirrhosis 10.9%, hepatocellular carcinoma 0.9%, and previous HCV treatment experience 10.9%. The mean baseline plasma HCV RNA was 6.2 log10 IU/mL. Treatment with glecaprevir/pibrentasvir was initiated in 51.9%, sofosbuvir/ledipasvir 41.5%, sofosbuvir/velpatasvir 6.3%, and sofosbuvir/daclatasvir 0.3%. At DAA initiation, antiretroviral therapy containing tenofovir alafenamide was given in 26.4%, tenofovir disoproxil fumarate 34.4%, non-tenofovir alafenamide/tenofovir disoproxil fumarate 39.3%, non-nucleoside reverse-transcriptase inhibitors 30.4%, protease inhibitors 4.0%, and integrase strand transfer inhibitors 66.8%; 94.8% of the included patients had CD4 counts ≥ 200 cells/mm3 and 96.0% had plasma HIV RNA < 50 copies/mL. Overall, 96.8% achieved undetectable plasma HCV RNA (< 30 IU/mL) at end of treatment; and 92.3% achieved sustained virologic response 12 wk off-therapy in the intention-to-treat analysis (93.5% in patients receiving sofosbuvir-based DAAs and 91.2% in those receiving glecaprevir/pibrentasvir). CONCLUSION: Similar to the observation made in HIV-negative patients, sustained virologic response 12 wk off-therapy with DAAs is high in PLWH coinfected with HCV-6.


Assuntos
Infecções por HIV , Hepatite C Crônica , Minorias Sexuais e de Gênero , Antivirais/farmacologia , Quimioterapia Combinada , Feminino , Genótipo , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , RNA , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada , Tenofovir/uso terapêutico , Resultado do Tratamento
5.
Turk J Gastroenterol ; 33(3): 240-247, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35410858

RESUMO

BACKGROUND: The course of hepatitis C disease has changed with the use of direct-acting antiviral drugs in the treatment of the disease. The aim of this study was to evaluate the real-life efficacy and safety of the sofosbuvir/ledipasvir drug regimen in the treatment of patients with genotype 1b. METHODS: Treatment-naive or -experienced 49 genotypes 1b patients treated with sofosbuvir/ledipasvir participated in the study. Laboratory and hepatitis C virus RNA values were evaluated at baseline, week 12, and week 24 of treatment (36th week for those who received 24 weeks of treatment). RESULTS: The sustained virologic response rate was 100% in patients who completed treatment. At the end of the study, there was a significant decrease in alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, and alpha-fetoprotein levels (P = .000014, P = .000581, P = .000012, and P = .000821), respectively. Renal function tests (creatinine, estimated glomerular filtration rate) worsened (P = .003 and P = .007, respectively). Hepatocellular carcinoma (HCC) was developed in 2 patients during post-treatment follow-up. In Kaplan-Meier analysis, the probability of not developing HCC was 86.5% at 26 months. CONCLUSION: The sofosbuvir/ledipasvir combination is effective in treating genotype 1b chronic hepatitis C with high sustained virologic response rates. Because there are few drug interactions, it may be a suitable option for patients taking multiple medications or who are transplant recipients. Renal function should be monitored closely during and after treatment, as there is a risk of worsening renal function after treatment.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Neoplasias Hepáticas , Antivirais/uso terapêutico , Benzimidazóis , Carcinoma Hepatocelular/tratamento farmacológico , Quimioterapia Combinada , Fluorenos , Genótipo , Hepacivirus/genética , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/etiologia , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada , Resultado do Tratamento
6.
J Acquir Immune Defic Syndr ; 89(5): 546-557, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35485581

RESUMO

BACKGROUND: Perinatally HIV-acquired infants benefit from an early antiretroviral treatment initiation. Thanks to a short viral exposure time, their immune system can be maintained or reconstituted, allowing a "normal" immune development. METHODS: In this study, we mathematically modeled and quantified individual CD4+ T-cell reconstitution of a subset of 276 children who started treatment within 6 months of age and achieved sustained viral suppression. Considering natural age differences in CD4+ T-cell dynamics, we fitted distances to age-matched healthy reference values with a linear model approaching an asymptote. RESULTS: Depleted CD4+ percentages (CD4%) and CD4+ counts (CD4ct) restored healthy levels during treatment. CD4ct recovered with a median rate of 4 cells/µL/d, and individual recovery rates were correlated negatively with their initial CD4ct. CD4 values at onset of treatment decrease with age, whereas recovery times and levels seem to be age-independent. CD4 recovery correlates positively with viral suppression, and the stabilization of CD4 levels usually occurs after viral suppression. CD4 levels stabilize within 3-13 months after treatment initiation. The recovery dynamics of the CD4% is comparable with those of the CD4ct. CONCLUSIONS: In early-treated children with successful viral suppression, the CD4 depletion is typically mild and CD4+ T cells tend to "fully" recover in numbers.


Assuntos
Infecções por HIV , Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Criança , Infecções por HIV/tratamento farmacológico , Humanos , Lactente , Resposta Viral Sustentada
7.
Pharmacotherapy ; 42(5): 397-404, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35396730

RESUMO

STUDY OBJECTIVE: The objective of this study was to determine the clinical relationship between proton pump inhibitor (PPI) use and sustained virologic response (SVR) in patients treated with sofosbuvir/velpatasvir (SOF/VEL) for chronic hepatitis C virus (HCV) infection. DESIGN: This was a multicenter retrospective cohort study. SETTING: Data was collected on patients from 128 Veterans Affairs Medical Centers throughout the United States. PATIENTS: This study included veterans aged 18-89 years with viremic HCV who received a full course of SOF/VEL treatment from June 2016 - July 2017. INTERVENTION: Sustained viral response was compared in patients taking SOF/VEL with or without concurrent PPI prescriptions. MEASUREMENTS AND MAIN RESULTS: Analysis of the primary outcome was completed utilizing logistic regression. The relationship between SVR and PPI use was adjusted for African-American race, presence of cirrhosis, prior treatment, BMI greater than 30 kg/m2, and HCV genotype. The final analysis included 4,008 veterans, 830 with concomitant PPI use and 3,178 without PPI use. After adjustment for other variables in the logistic model, there was no statistically significant association between PPI use and lower SVR (odds ratio 0.67; 95%CI: 0.42, 1.06; p = 0.087). CONCLUSION: Concomitant PPI treatment adjusted for other variables did not significantly impact success or failure of SOF/VEL treatment of chronic HCV. Despite the lack of significant association identified in this study, in efforts to provide the best care possible, it remains prudent to proceed with caution in patients desiring to use PPI therapy while receiving SOF/VEL, and ensure prescribing instructions are closely followed in regard to concomitant PPI use, especially in patients with other risk factors for decreased SVR.


Assuntos
Hepatite C Crônica , Veteranos , Antivirais , Carbamatos , Genótipo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis , Humanos , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos , Sofosbuvir , Resposta Viral Sustentada , Resultado do Tratamento
8.
Eur J Gastroenterol Hepatol ; 34(5): 560-566, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35421021

RESUMO

BACKGROUND AND AIMS: People who use drugs (PWUDs) are the main group at risk for hepatitis C virus (HCV) transmission and a key population for hepatitis C elimination. Multidisciplinary team (MDT) meetings were set up in France in December 2014 within regional reference centers to supervise the prescriptions and delivery of direct-acting antivirals (DAAs) to optimize the management of HCV infection. The aim of this retrospective study was to analyze the changes in the profile and therapeutic care of PWUDs with HCV mono-infection according to the evolution of MDT meetings in a regional tertiary reference center. METHODS: Between 2015 and 2019, overall 1912 HCV-infected patients presented at the MDT meetings, 547 were PWUDs with HCV mono-infection treated with DAAs. Five periods were defined according to the evolution of MDT meetings. The profile and management of PWUDs were compared among these five periods. RESULTS: Over time, the frequency of advanced stage of fibrosis decreased from 90.8 to 36.3% (P < 0.001), whereas the therapeutic care of the patients in primary addictology centers and networks of general practitioners increased from 17.4 to 55% (P < 0.001). The frequency of excessive alcohol consumption varied between 9.1 and 30% (P = 0.003) and that of opioid substitution therapy between 42.5 and 70% (P < 0.001). The Sustained virologic response assessed 12 weeks after the end of treatment rate was above 95% for the five periods. CONCLUSION: Between 2015 and 2019, the changes in the profile and management of PWUDs have followed the evolution of MDT meetings concerning patients with less advanced fibrosis and more therapeutic hepatitis C care made by the primary care centers.


Assuntos
Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Fibrose , Hepacivirus , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Preparações Farmacêuticas , Estudos Retrospectivos , Resposta Viral Sustentada
9.
J Viral Hepat ; 29(5): 395-406, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35266624

RESUMO

Chronic hepatitis C virus (HCV) infection is associated with neuropsychiatric changes. Also, patients with cirrhosis may develop overt or minimal hepatic encephalopathy. Sustained virological response (SVR) with direct-acting antiviral agents (DAAs) may improve the neuropsychiatric manifestations and quality of life (QoL). Consecutive patients (with and without cirrhosis, all genders and aged 18-65 years) with hepatitis C were assessed at enrolment and at 12 weeks after therapy completion for mood (Beck's Depression Inventory [BDI]), anxiety (generalized anxiety disorder [GAD-7]), QoL (SF-36 ver.2) and computer-based tests for number connection (NCT), visual memory, Stroop test and reaction times. We recruited 385 viraemic chronic HCV patients (76.1% male, 21.0% cirrhotic, mean age 39.4 ± 14.2 years, 59.3% genotype 3, mean HCV RNA load 5.8 log). Overall SVR-12 rates were 90.6%, with cure rates 87.6% and 91.4% in patients with and without cirrhosis, respectively. Patients who achieved SVR-12 had mean percentage reduction in BDI (11.3%, p = .000), GAD (8.6%, p = .001) and Stroop test (58.4%, p = .001), with improved NCT (1.7%, p = .001), visual memory (13.7%, p = .001) and digit span (23.8%, p = .002). On multivariate logistic regression, adherence (OR, 17.5 [95% CI 2.80-110.50], p = .000), high ALT (OR 1.02 [95% CI 1.00-1.05]), and BDI score (OR 1.73 [95% CI 1.42-3.26] p = .039) predicted cure. SVR-12 was associated with improved visual memory ≥5.5 (AUC-0.708; sensitivity 62.5%, specificity 63%, p = .000) and % correct Stroop test responses >26.6% (AUC-0.918, sensitivity 94.4% specificity 80.4%, p = .000). In conclusion, given the cumulative evidence of the safety of DAAs and efficacy of improving cognitive and neuropsychological and quality-of-life outcomes irrespective of age and gender, as shown in our study, future recommendations should focus on integrated universal HCV care to enable HCV elimination.


Assuntos
Hepatite C Crônica , Hepatite C , Adulto , Antivirais/uso terapêutico , Ansiedade , Transtornos de Ansiedade/induzido quimicamente , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/tratamento farmacológico , Estudos de Coortes , Depressão , Feminino , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Resposta Viral Sustentada , Resultado do Tratamento
11.
J Viral Hepat ; 29(6): 474-486, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35278339

RESUMO

Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12 weeks post-treatment (SVR12). We assembled a global data set of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique) and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th, 95th, 97th and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as <1000 IU/mL). There were 5973 cases of detectable viraemia at SVR12 from the combined data set. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95th percentile was 227 IU/mL (95% CI 170-276). Females and those with minimal fibrosis were more likely to experience low-level viraemia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30-1.97 and those with cirrhosis (AOR = 1.49 95% CI 1.15-1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low-level treatment failure.


Assuntos
Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Feminino , Genótipo , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Humanos , Limite de Detecção , Masculino , RNA Viral , Resposta Viral Sustentada , Resultado do Tratamento , Carga Viral , Viremia/diagnóstico , Viremia/tratamento farmacológico
12.
JAMA Intern Med ; 182(5): 494-502, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35285851

RESUMO

Importance: To achieve hepatitis C elimination, treatment programs need to engage, treat, and cure people who inject drugs. Objective: To compare a low-threshold, nonstigmatizing hepatitis C treatment program that was colocated at a syringe service program (accessible care) with facilitated referral to local clinicians through a patient navigation program (usual care). Design, Setting, and Participants: This single-site randomized clinical trial was conducted at the Lower East Side Harm Reduction Center, a syringe service program in New York, New York, and included 167 participants who were hepatitis C virus RNA-positive and had injected drugs during the prior 90 days. Participants enrolled between July 2017 and March 2020. Data were analyzed after all patients completed 1 year of follow-up (after March 2021). Interventions: Participants were randomized 1:1 to the accessible care or usual care arm. Main Outcomes and Measures: The primary end point was achieving sustained virologic response within 12 months of enrollment. Results: Among the 572 participants screened, 167 (mean [SD] age, 42.0 [10.6] years; 128 (77.6%) male, 36 (21.8%) female, and 1 (0.6) transgender individuals; 8 (4.8%) Black, 97 (58.5%) Hispanic, and 53 (32.1%) White individuals) met eligibility criteria and were enrolled, with 2 excluded postrandomization (n = 165). Baseline characteristics were similar between the 2 arms. In the intention-to-treat analysis, 55 of 82 participants (67.1%) in the accessible care arm and 19 of 83 participants (22.9%) in the usual care arm achieved a sustained virologic response (P < .001). Loss to follow-up (12.2% [accessible care] and 16.9% [usual care]; P = .51) was similar in the 2 arms. Of the participants who received therapy, 55 of 64 (85.9%) and 19 of 22 (86.3%) achieved a sustained virologic response in the accessible care and usual care arms, respectively (P = .96). Significantly more participants in the accessible care arm achieved all steps in the care cascade, with the greatest attrition in the usual care arm seen in referral to hepatitis C virus clinician and attending clinical visit. Conclusions and Relevance: In this randomized clinical trial, among people who inject drugs with hepatitis C infection, significantly higher rates of cure were achieved using the accessible care model that focused on low-threshold, colocated, destigmatized, and flexible hepatitis C care compared with facilitated referral. To achieve hepatitis C elimination, expansion of treatment programs that are specifically geared toward engaging people who inject drugs is paramount. Trial Registration: ClinicalTrials.gov Identifier: NCT03214679.


Assuntos
Usuários de Drogas , Hepatite C , Adulto , Feminino , Hepacivirus , Hepatite C/tratamento farmacológico , Humanos , Masculino , Resposta Viral Sustentada
13.
Zhonghua Gan Zang Bing Za Zhi ; 30(1): 103-106, 2022 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-35152679

RESUMO

Hepatitis C virus (HCV) RNA can be cleared from the blood circulation by direct antiviral treatment to achieve sustained virologic response (SVR). Studies have shown that SVR after direct antiviral therapy can reduce the incidence of hepatocellular carcinoma; however, monitoring for hepatocellular carcinoma is still needed. This review briefly summarizes and discusses the existing studies on the possible causes of hepatitis C secondary to HCC after antiviral therapy, which is mainly divided into epigenetic alterations and abnormal DNA methylation, HCV-related cirrhosis and abnormal DNA amplification, HBV reactivation, several aspects of occult HCV infection, and the effect of direct antiviral treatment on hepatocellular carcinoma recurrence. In few cases, direct antiviral treatment cannot completely prevent the occurrence and recurrence of hepatitis C-related hepatocellular carcinoma. Therefore, its mechanism needs to be studied and explored, and clinicians should also approach it with caution.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/etiologia , Resposta Viral Sustentada
15.
Eur J Gastroenterol Hepatol ; 34(6): 693-697, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35170532

RESUMO

OBJECTIVE: Patients with chronic hepatitis C virus (HCV) infection who achieve sustained virologic response (SVR) to anti-HCV therapy, that is the eradication of HCV, are recommended to continue regular hospital visits for the surveillance of hepatocellular carcinoma (HCC) that can develop after SVR. However, it is unclear how well patients with SVR adhere to post-SVR follow-up over the long term. We investigated this adherence and the factors associated with it. METHODS: Medical record data on regular hospital visits were reviewed in 1329 patients with no history of HCC who achieved SVR by anti-HCV therapy. At the time of SVR confirmation, all patients were advised to continue regular visits, and the risk of post-SVR HCC was explained. The adherence rate of post-SVR follow-up and associated factors were analyzed. RESULTS: Adherence rates decreased continuously over time, as follows: 76.6% at 5 years, 62.4% at 10 years, 48.8% at 15 years, and 35.3% at 20 years after SVR. Adherence rates did not differ based on the degree of baseline liver fibrosis and were significantly lower in patients who achieved SVR by interferon (IFN)-free therapy and those with HCV genotype 2b. CONCLUSION: Adherence to post-SVR follow-up decreased over the long term, and rates differed by patient background. Adherence was especially poor in patients who achieved SVR by IFN-free therapy, and therefore, strategies are necessary to encourage these patients to maintain their regular schedule of hospital visits.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Resposta Viral Sustentada
16.
World J Gastroenterol ; 28(1): 96-107, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35125821

RESUMO

Hepatitis C virus (HCV) is a significant cause of hepatocellular carcinoma (HCC). The direct-acting antivirals marked a new era of HCV therapy and are associated with greater than 95% cure rate. Successful treatment of chronic hepatitis C greatly reduces the risk of HCC. A proportion of patients, especially those with pre-existing cirrhosis, remain at risk for HCC despite sustained virologic response (SVR). Diabetes mellitus, hepatic steatosis, alcohol consumption and lack of fibrosis regression are associated with risks of HCC after HCV cure. Noninvasive modalities such as aspartate aminotransferase to platelet ratio index and fibrosis-4 index and transient elastography have been used to monitor hepatic fibrosis. More recently, various fibrosis scores have been combined with clinical parameters and other novel biomarkers to predict risks of HCC for patients who achieved SVR. These models still need to be validated and standardized prior to applying to routine clinical care.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Resposta Viral Sustentada
17.
Front Immunol ; 13: 803417, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35154118

RESUMO

T and natural killer (NK) cells are effector cells with key roles in anti-HIV immunity, including in lymphoid tissues, the major site of HIV persistence. However, little is known about the features of these effector cells from people living with HIV (PLWH), particularly from those who initiated antiretroviral therapy (ART) during acute infection. Our study design was to use 42-parameter CyTOF to conduct deep phenotyping of paired blood- and lymph node (LN)-derived T and NK cells from three groups of HIV+ aviremic individuals: elite controllers (N = 5), and ART-suppressed individuals who had started therapy during chronic (N = 6) vs. acute infection (N = 8), the latter of which is associated with better outcomes. We found that acute-treated individuals are enriched for specific subsets of T and NK cells, including blood-derived CD56-CD16+ NK cells previously associated with HIV control, and LN-derived CD4+ T follicular helper cells with heightened expansion potential. An in-depth comparison of the features of the cells from blood vs. LNs of individuals from our cohort revealed that T cells from blood were more activated than those from LNs. By contrast, LNs were enriched for follicle-homing CXCR5+ CD8+ T cells, which expressed increased levels of inhibitory receptors and markers of survival and proliferation as compared to their CXCR5- counterparts. In addition, a subset of memory-like CD56brightTCF1+ NK cells was enriched in LNs relative to blood. These results together suggest unique T and NK cell features in acute-treated individuals, and highlight the importance of examining effector cells not only in blood but also the lymphoid tissue compartment, where the reservoir mostly persists, and where these cells take on distinct phenotypic features.


Assuntos
Infecções por HIV/imunologia , Leucócitos/classificação , Linfócitos/imunologia , Fenótipo , Resposta Viral Sustentada , Adulto , Idoso , Antirretrovirais/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Infecções por HIV/tratamento farmacológico , HIV-1/imunologia , Humanos , Células Matadoras Naturais/imunologia , Leucócitos/imunologia , Linfócitos/classificação , Masculino , Pessoa de Meia-Idade
18.
World J Gastroenterol ; 28(1): 140-153, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35125824

RESUMO

BACKGROUND: Chronic hepatitis C virus (HCV) infection induces profound alterations in the cytokine and chemokine signatures in peripheral blood. Clearance of HCV by antivirals results in host immune modification, which may interfere with immune-mediated cancer surveillance. Identifying HCV patients who remain at risk of hepatocellular carcinoma (HCC) following HCV eradication remains an unmet need. We hypothesized that antiviral therapy-induced immune reconstruction may be relevant to HCC development. AIM: To investigate the impact of differential dynamics of cytokine expression on the development of HCC following successful antiviral therapy. METHODS: One hundred treatment-naïve HCV patients with advanced fibrosis (F3/4) treated with direct-acting antivirals (DAAs) or peginterferon/ribavirin who achieved sustained virologic response [SVR, defined as undetectable HCV RNA throughout 12 wk (SVR12) for the DAA group or 24 wk (SVR24) for the interferon group after completion of antiviral therapy] were enrolled since 2003. The primary endpoint was the development of new-onset HCC. Standard HCC surveillance (abdominal ultrasound and α-fetoprotein) was performed every six months during the follow-up. Overall, 64 serum cytokines were detected by the multiplex immunoassay at baseline and 24 wk after end-of-treatment. RESULTS: HCC developed in 12 of the 97 patients over 459 person-years after HCV eradication. In univariate analysis, the Fibrosis-4 index (FIB-4), hemoglobin A1c (HbA1c), the dynamics of tumor necrosis factor-α (TNF-α), and TNF-like weak inducer of apoptosis (TWEAK) after antiviral therapy were significant HCC predictors. The multivariate Cox regression model showed that ΔTNF-α (≤ -5.7 pg/mL) was the most important risk factor for HCC (HR = 11.54, 95%CI: 2.27-58.72, P = 0.003 in overall cases; HR = 9.98, 95%CI: 1.88-52.87, P = 0.007 in the interferon group). An HCC predictive model comprising FIB-4, HbA1c, ΔTNF-α, and ΔTWEAK had excellent performance, with 3-, 5-, 10-, and 13-year areas under the curve of 0.882, 0.864, 0.903, and 1.000, respectively. The 5-year accumulative risks of HCC were 0%, 16.9%, and 40.0% in the low-, intermediate-, and high-risk groups, respectively. CONCLUSION: Downregulation of serum TNF-α significantly increases the risk of HCC after HCV eradication. A predictive model consisting of cytokine kinetics could ameliorate personalized HCC surveillance strategies for post-SVR HCV patients.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Citocinas , Hepacivirus , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Fatores de Risco , Resposta Viral Sustentada , Fator de Necrose Tumoral alfa
19.
Viruses ; 14(2)2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-35215901

RESUMO

A hepatitis C virus (HCV) screening and treatment program was conducted in Hungarian prisons on a voluntary basis. After HCV-RNA testing and genotyping for anti-HCV positives, treatments with direct-acting antiviral agents were commenced by hepatologists who visited the institutions monthly. Patients were supervised by the prisons' medical staff. Data were retrospectively collected from the Hungarian Hepatitis Treatment Registry, from the Health Registry of Prisons, and from participating hepatologists. Eighty-four percent of Hungarian prisons participated, meaning a total of 5779 individuals (28% of the inmate population) underwent screening. HCV-RNA positivity was confirmed in 317/5779 cases (5.49%); 261/317 (82.3%) started treatment. Ninety-nine percent of them admitted previous intravenous drug use. So far, 220 patients received full treatment and 41 patients are still on treatment. Based on the available end of treatment (EOT) + 24 weeks timepoint data, per protocol sustained virologic response rate was 96.8%. In conclusion, the Hungarian prison screening and treatment program, with the active participation of hepatologists and the prisons' medical staff, is a well-functioning model. Through the Hungarian experience, we emphasize that the "test-and-treat" principle is feasible and effective at micro-eliminating HCV in prisons, where infection rate, as well as history of intravenous drug usage, are high.


Assuntos
Antivirais/administração & dosagem , Hepacivirus/isolamento & purificação , Hepatite C/tratamento farmacológico , Adolescente , Adulto , Feminino , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C/sangue , Hepatite C/diagnóstico , Hepatite C/virologia , Humanos , Hungria , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Prisões/estatística & dados numéricos , Estudos Retrospectivos , Resposta Viral Sustentada , Adulto Jovem
20.
Curr Gastroenterol Rep ; 24(1): 1-9, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35142988

RESUMO

PURPOSE OF REVIEW: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in the United States (U.S.).1 The purpose of this review is to highlight published models that predict development of HCC and estimate risk of HCC recurrence after treatments. RECENT FINDINGS: There have been several models created for both de novo HCC and HCC recurrence, with the more recent models using a combination of age, sex, decompensation, and laboratory values (platelet count, albumin, bilirubin), and liver disease etiology to predict both 5 and 10-year HCC incidence. For chronic hepatitis C, sustained virologic response has been a useful component of understanding HCC risk reduction. BMI and diabetes have been utilized in non-alcoholic fatty liver disease (NAFLD) models to predict HCC risk. For HCC recurrence after treatment (for both surgical resection and liver transplant), tumor size and number, vascular invasion, alpha-fetoprotein (AFP) and neutrophil to lymphocyte ratio (NLR) are all components of HCC recurrence risk models. Although numerous HCC risk prediction models have been established over the last several years, challenges remain including how to best incorporate these models into clinical practice, improve surveillance for NAFLD-HCC development, and determine timing and duration of post-resection recurrence surveillance.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Neoplasias Hepáticas , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/terapia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/terapia , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Resposta Viral Sustentada
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