RESUMO
BACKGROUND AND AIM OF THE STUDY: There are still patients with hepatitisC in Spain who have yet to be diagnosed, but their clinical profile is unclear. In 2021, 21.93% of patients diagnosed had cirrhosis and were mostly treatment-naïve. METHODS: This sub-analysis describes the clinical profile of the 60Spanish treatment-naïve patients with compensated cirrhosis who were included in the CREST study. MAJOR RESULTS: Sixty percent of patients were male, median age 56years, and 33% had a history of drug use. Almost three-quarters (71.3%) had more than one comorbidity and 78.3% took concomitant medication. At treatment initiation, median platelet count was 139×103/µL and FibroScan® 17kPa. No virological failure was observed and no patient discontinued treatment due to adverse events. No clinically significant changes were noted during or after treatment in the median platelet, albumin, bilirubin, and transaminase levels. CONCLUSIONS: Treatment with glecaprevir/pibrentasvir for 8weeks in this cohort of treatment-naïve patients with compensated cirrhosis in Spain was safe and effective. This information reinforces the use of this short antiviral regimen even when there is compensated cirrhosis, simplifying the approach to hepatitisC among those patients still to be diagnosed and treated in Spain.
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Antivirais , Cirrose Hepática , Humanos , Masculino , Espanha/epidemiologia , Pessoa de Meia-Idade , Feminino , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/complicações , Idoso , Sulfonamidas/uso terapêutico , Benzimidazóis/uso terapêutico , Adulto , Leucina/análogos & derivados , Leucina/uso terapêutico , Pirrolidinas/uso terapêuticoRESUMO
BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality in patients with advanced chronic liver disease (ACLD) caused by chronic hepatitis C who have achieved sustained virologic response (SVR). We developed risk stratification algorithms for de novo HCC development after SVR and validated them in an independent cohort. METHODS: We evaluated the occurrence of de novo HCC in a derivation cohort of 527 patients with pre-treatment ACLD and SVR to interferon-free therapy, in whom alpha-fetoprotein (AFP) and non-invasive surrogates of portal hypertension including liver stiffness measurement (LSM) were assessed pre-/post-treatment. We validated our results in 1,500 patients with compensated ACLD (cACLD) from other European centers. RESULTS: During a median follow-up (FU) of 41 months, 22/475 patients with cACLD (4.6%, 1.45/100 patient-years) vs. 12/52 decompensated patients (23.1%, 7.00/100 patient-years, p <0.001) developed de novo HCC. Since decompensated patients were at substantial HCC risk, we focused on cACLD for all further analyses. In cACLD, post-treatment-values showed a higher discriminative ability for patients with/without de novo HCC development during FU than pre-treatment values or absolute/relative changes. Models based on post-treatment AFP, alcohol consumption (optional), age, LSM, and albumin, accurately predicted de novo HCC development (bootstrapped Harrel's C with/without considering alcohol: 0.893/0.836). Importantly, these parameters also provided independent prognostic information in competing risk analysis and accurately stratified patients into low- (~2/3 of patients) and high-risk (~1/3 of patients) groups in the derivation (algorithm with alcohol consumption; 4-year HCC-risk: 0% vs. 16.5%) and validation (3.3% vs. 17.5%) cohorts. An alternative approach based on alcohol consumption (optional), age, LSM, and albumin (i.e., without AFP) also showed a robust performance. CONCLUSIONS: Simple algorithms based on post-treatment age/albumin/LSM, and optionally, AFP and alcohol consumption, accurately stratified patients with cACLD based on their risk of de novo HCC after SVR. Approximately two-thirds were identified as having an HCC risk <1%/year in both the derivation and validation cohort, thereby clearly falling below the cost-effectiveness threshold for HCC surveillance. LAY SUMMARY: Simple algorithms based on age, alcohol consumption, results of blood tests (albumin and α-fetoprotein), as well as liver stiffness measurement after the end of hepatitis C treatment identify a large proportion (approximately two-thirds) of patients with advanced but still asymptomatic liver disease who are at very low risk (<1%/year) of liver cancer development, and thus, might not need to undergo 6-monthly liver ultrasound.
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Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Albuminas/uso terapêutico , Antivirais/uso terapêutico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/patologia , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Medição de Risco/métodos , Fatores de Risco , Resposta Viral Sustentada , alfa-FetoproteínasRESUMO
BACKGROUND AND AIMS: Patients with hepatitis C virus (HCV) and advanced fibrosis remain at risk of hepatocellular carcinoma (HCC) after sustained viral response (SVR) and need lifelong surveillance. Because HCC risk is not homogenous and may decrease with fibrosis regression, we aimed to identify patients with low HCC risk based on the prediction of noninvasive markers and its changes after SVR. APPROACH AND RESULTS: This is a multicenter cohort study, including patients with HCV and compensated advanced fibrosis that achieved SVR after direct antivirals. Clinical and transient elastography (TE) data were registered at baseline, 1 year, and 3 years after the end of treatment (EOT). All patients underwent liver ultrasound scan every 6 months. Patients with clinical evaluation 1 year after EOT were eligible. Univariate and multivariate Cox regression analysis were performed, and predictive models were constructed. HCC occurrence rates were evaluated by Kaplan-Meier. Nine hundred and ninety-three patients were eligible (56% male; 44% female; median age 62 years), 35 developed HCC (3.9%), and the median follow-up was 45 months (range 13-53). Baseline liver stiffness measurement (LSM) (HR 1.040; 95% CI 1.017-1.064), serum albumin (HR 0.400; 95% CI 0.174-0.923), 1-year DeltaLSM (HR 0.993; 95% CI 0.987-0.998), and 1-year FIB-4 score (HR 1.095; 95% CI 1.046-1.146) were independent factors associated with HCC. The TE-based HCC risk model predicted 0% of HCC occurrence at 3 years in patients with score 0 (baseline LSM ≤ 17.3 kPa, albumin >4.2 g/dL, and 1-year DeltaLSM > 25.5%) versus 5.2% in patients with score 1-3 (Harrell's C 0.779; log-rank 0.002). An alternative model with FIB-4 similarly predicted HCC risk. CONCLUSIONS: A combination of baseline and dynamic changes in noninvasive markers may help to identify patients with a very low risk of HCC development after SVR.
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Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/epidemiologia , Hepatite C Crônica/patologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Progressão da Doença , Técnicas de Imagem por Elasticidade , Feminino , Seguimentos , Hepacivirus/isolamento & purificação , Hepatite C Crônica/sangue , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/sangue , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Resposta Viral SustentadaRESUMO
INTRODUCTION: The aim of this study was to investigate the accuracy of liver and spleen stiffness measurement by transient elastography for the prediction of gastroesophageal varices in patients with HCV-associated cirrhosis treated with new direct-acting antiviral agents. PATIENTS AND METHODS: This cross-sectional observational study included patients with compensated HCV-related cirrhosis and sustained virological response after direct-acting antiviral therapy. Patients underwent liver and spleen stiffness measurement, abdominal ultrasound and oesophago-gastroduodenoscopy. Clinical and laboratory data and non-invasive markers such as the liver stiffness-spleen diameter to platelet ratio score, variceal risk index and platelet count to spleen diameter ratio were analyzed. RESULTS: Ninety-seven consecutive patients were included. Liver stiffness measurement (12.2 vs 16; p=0.02), spleen stiffness measurement (39.4 vs 46.05; p=0.04), liver stiffness-spleen diameter to platelet ratio score (1.21 vs 2.02; p=0.008), platelet count to spleen diameter ratio (1102.19 vs 829.7; p=0.04) and variceal risk index (-3.4 vs -1.02; p=0.01) showed significant differences between patients without/with gastroesophageal varices. The best cut-off value to discard the presence of gastroesophageal varices was 12.3kPa for liver stiffness measurement and 27kPa for spleen stiffness measurement. However, diagnostic accuracy was moderate (AUROC: 0.671 and 0.624 respectively). Combining different non-invasive parameters did not significantly improve the overall performance. DISCUSSION: Liver and spleen stiffness measurement showed suboptimal results for non-invasive assessment of gastroesophageal varices in HCV cirrhotic patients treated with direct-acting antiviral agents. Our results suggest that non-invasive methods cannot substitute standard procedures for predicting gastroesophageal varices in this population.
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Antivirais/administração & dosagem , Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas/etiologia , Hepatite C Crônica/complicações , Cirrose Hepática/complicações , Hepatopatias/complicações , Hepatopatias/diagnóstico por imagem , Esplenopatias/complicações , Esplenopatias/diagnóstico por imagem , Administração Oral , Idoso , Estudos Transversais , Varizes Esofágicas e Gástricas/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos TestesRESUMO
BACKGROUND & AIMS: Antiviral therapy for the treatment of hepatitis C (HCV) infection has proved to be safe and efficacious in patients with cirrhosis awaiting liver transplantation (LT). However, the information regarding the clinical impact of viral eradication in patients on the waiting list is still limited. The aim of the study was to investigate the probability of delisting in patients who underwent antiviral therapy, and the clinical outcomes of these delisted patients. METHODS: Observational, multicenter and retrospective analysis was carried out on prospectively collected data from patients positive for HCV, treated with an interferon-free regimen, while awaiting LT in 18 hospitals in Spain. RESULTS: In total, 238 patients were enrolled in the study. The indication for LT was decompensated cirrhosis (with or without hepatocellular carcinoma [HCC]) in 171 (72%) patients, and HCC in 67 (28%) patients. Sustained virologic response (SVR) rate was significantly higher in patients with compensated cirrhosis and HCC (92% vs. 83% in patients with decompensated cirrhosis with or without HCC, p=0.042). Among 122 patients with decompensated cirrhosis without HCC, 29 (24%) were delisted due to improvement. No patient with baseline MELD score >20 was delisted. After delisting (median follow-up of 88weeks), three patients had clinical decompensations and three had de novo HCC. Only two of the patients with HCC had to be re-admitted onto the waiting list. The remaining 23 patients remained stable, with no indication for LT. CONCLUSIONS: Antiviral therapy is safe and efficacious in patients awaiting LT. A quarter of patients with decompensated cirrhosis can be delisted asa result of clinical improvement, which appears to be remain stable in most patients. Thus, delisting is a safe strategy that could spare organs and benefit other patients with a more urgent need. LAY SUMMARY: Antiviral therapy in patients awaiting liver transplantation is safe and efficacious. Viral eradication allows removal from the waiting list of a quarter of treated patients. Delisting because of clinical improvement is a safe strategy that can spare organs for patients in urgent need.
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Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Transplante de Fígado , Antivirais/efeitos adversos , Feminino , Humanos , Cirrose Hepática/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Listas de EsperaRESUMO
BACKGROUND: Form-stable 410 implants have the potential advantage of maintaining their anatomic form thanks to the cohesiveness of the gel. Furthermore, Biocell texturing appears to maximize adhesion and to allow for implant immobility. OBJECTIVES: To compare the rate of reoperations for transaxillary and periareolar approaches for breast augmentation. METHODS: This retrospective study consisted of 373 patients with a 5-year follow up. Patient demographics, self-perception and esteem, surgical technique, and implant characteristics were documented. The reasons for reoperation for both approaches were reviewed. RESULTS: Transaxillary breast augmentation was used in 302 patients (81%) and periareolar breast augmentation in 71 patients (19%). In the axillary group, 210 had subfascial placement (69.5%), and 92 patients had submuscular placement (30.5%). In the nipple-areolar complex group, 50 were subfascial (70.4%), and 21 were submuscular (29.6%). The reoperation rate for the patients operated on during this time and followed for 5 years was 11% (8 patients) for the nipple-areolar complex approach and 8.3% (25 patients) in the axillary group. Capsular contracture grade III or IV were the main causes for reoperation for any technique (4.2% nipple-areolar complex vs 3.3% axillary). Other reasons were implant rupture, seroma, infection, implant malrotation, implant malposition, and rippling. CONCLUSIONS: The rate of reoperations was similar to those described in the literature for this type of implant. There were no statistically significant differences between the various techniques, although the reoperation rate was significantly higher when a periareolar subfascial technique was used. LEVEL OF EVIDENCE: 3 Therapeutic.
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Implante Mamário/instrumentação , Implante Mamário/métodos , Implantes de Mama , Mama/cirurgia , Adolescente , Adulto , Implante Mamário/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Satisfação do Paciente , Fotografação , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Desenho de Prótese , Reoperação , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Transient elastography (TE) is a noninvasive method of assessing hepatic fibrosis in a quick, simple and reproducible manner. FibroScan is the best-known elastography apparatus and can assess a tissue volume 100 times greater than hepatic biopsy. Given that it lacks complications, TE can be repeated in the follow-up visit, thereby providing evolutionary information. One of its limitations, however, is its failure rate (4.5% of examinations), mainly in obese patients. TE has certain characteristics in chronic hepatitis B (HBV) infection. Transaminase levels and necroinflammation increase in reactivations, with hepatic stiffness increasing by 1.2 to 4.4 times. The second characteristic is related to macronodular cirrhosis caused by HBV, with less fibrous tissue compared with that produced by hepatitis C. Therefore, the cutoff values are smaller for hepatitis B than for hepatitis C. FibroScan helps categorize patients with chronic HBV infection into 4 fibrosis groups (approximate mean values and adding 1-2 more points with high transaminase levels): not significant (<6 kPa), grey area (6-9 kPa), significant (>9 kPa) and cirrhosis (>12 kPa). Thus, Fibroscan contributes to the treatment decision, and its repeated use during treatment enables us to verify that fibrosis has not progressed. In cases with no indication for treatment (chronic hepatitis with no criteria, inactive carrier state, immune-tolerant), the periodic reapplication of TE helps determine whether the inactivity continues or not. If the results are compatible with cirrhosis, hepatocarcinoma surveillance should be started.
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Técnicas de Imagem por Elasticidade , Hepatite B Crônica/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/instrumentação , Desenho de Equipamento , Seguimentos , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/virologiaRESUMO
BACKGROUND AND AIMS: The management of acute hepatitis C (AHC) is controversial. We have conducted a retrospective study to determine the epidemiological and biochemical aspects, the genotypes, the spontaneous clearance of HCV (SVC), and the treatment responses in patients with AHC. METHODS: We have retrospectively collected data from 131 patients with AHC from 18 Spanish hospitals. RESULTS: The mean age was 43 ± 16 years (17-83), 69% were symptomatic. The causes of infection were nosocomial in 40% and intravenous drug users in 20%. Eighty two percent had genotype 1. The delay from symptoms-onset to HCV-RNA confirmation was 50 ± 68 days (range, 11-350 days) and to treatment (in 59%) 14±1 3 weeks (range, 2-58 days). In the treated group, 80% achieved sustained virological response (SVR) versus 57% SVC in untreated patients (p = 0.004). Up to 96% of those treated within the first 12 weeks had SVR versus 86% of those treated later (p = 0.04). Patients with HCV-RNA(-) at week 4 resolved with or without treatment more frequently than those HCV-RNA(+) (98% versus 69%, p = 0.005). The treatment was not beneficial if HCV-RNA was undetectable at week 12. No differences in SVR were found in genotype 1 patients treated for 24 or 48 weeks. Patients with low baseline viral load achieved higher SVC and SVR. The SVC in patients with bilirubin > 5 mg/dL was 78 versus 40% in those with lower values (p = 0.004). CONCLUSIONS: The most common transmission route was nosocomial. SVR was higher in patients treated than SVC in non-treated.Early treatment (before week 12) achieved the highest response rate. SVC and SVR were more common in patients with a low baseline viral load. Undetectable HCV-RNA at week 4 was associated with high SVR and SVC rates. Jaundice was related with SVC.
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Hepatite C/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/análise , Antivirais/uso terapêutico , Estudos de Coortes , Infecção Hospitalar/complicações , Infecção Hospitalar/terapia , Feminino , Genótipo , Hepacivirus/imunologia , Hepatite C/terapia , Hepatite C/virologia , Humanos , Técnicas Imunoenzimáticas , Imunoglobulina G/análise , Interferon gama/uso terapêutico , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Estudos Retrospectivos , Ribavirina/uso terapêutico , Espanha/epidemiologia , Abuso de Substâncias por Via Intravenosa/epidemiologia , Carga Viral , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: Liver steatosis in chronic hepatitis C (CHC) is related to viral and metabolic factors and likely to genetic factors. The aim of this study was to know if hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR)-C677T polymorphisms are associated with liver steatosis in nonalcoholic patients with CHC. PATIENTS AND METHOD: In 54 consecutive patients with CHC, alcohol consumption less than 40g/week, and no other causes of liver disease, a liver biopsy was performed. All variables were obtained at the time of biopsy. MTHFR-C677T was also performed in 128 healthy subjects, with age and gender similar to the patients. RESULTS: Liver steatosis was found in 33 patients (61%), 30 of them having a mild degree. Hyperhomocysteinemia was more prevalent in patients with steatosis (61% vs 24%; p=0.008) and overweight tended to be more prevalent in the same patients (61% vs 33%; p=0.05). All patients with virus C genotype 3 had steatosis. Viral load, liver inflammatory and fibrosis score were not different in patients with and without steatosis. MTHFR-C677T polymorphism was similar in controls and cases and in cases with and without steatosis. A multiple logistic regression showed that hyperhomocysteinemia was associated with liver steatosis after adjustment for age and sex (OR: 3.94; 95% CI: 1.09-14.29), and adjustment for overweight (OR: 4.43; 95% CI: 1.27-15.51). CONCLUSIONS: In nonalcoholic patients with CHC mild liver steatosis is frequent, and is associated with hyperhomocysteinemia. An association between steatosis and MTHFR-C677T polymorphism was not found.
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Fígado Gorduroso/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/genética , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Mutação , Polimorfismo Genético , Adulto , Fígado Gorduroso/genética , Feminino , Humanos , MasculinoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Vírus da Hepatite B/fisiologia , Hepatite B/virologia , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Ativação Viral/efeitos dos fármacos , Feminino , Hepatite B/complicações , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Pessoa de Meia-Idade , Rituximab/administração & dosagem , Fatores de Tempo , Vidarabina/administração & dosagem , Vidarabina/análogos & derivadosRESUMO
BACKGROUND/AIMS: Alpha-interferon achieves persistent loss of hepatitis B virus (HBV) in about 30-40% of patients with chronic hepatitis B. In non-responder patients, the disease may progress leading to complications such as cirrhosis and hepatocellular carcinoma. The aim of the current study was to evaluate the efficacy of beta-interferon in patients with chronic hepatitis B who did not respond to one course of alpha-interferon. METHODS: Twenty nine alpha-interferon-non-responder patients with chronic hepatitis B (11 hepatitis B e antigen, HBeAg-positive; 18 HBeAg-negative) were treated with 6 million units beta-interferon five times a week for 24 weeks. The post-treatment follow-up lasted for 48 weeks. RESULTS: At the end of treatment, 38% of patients (18% HBeAg-positive; 50% HBeAg-negative) had normal serum aminotransferase levels and negative serum HBV DNA. At the end of follow-up, HBV DNA was no longer detectable in serum in 21% of patients (18% HBeAg-positive; 22% HBeAg-negative). Beta-interferon was well tolerated and safe. CONCLUSIONS: This pilot study suggests that beta-interferon therapy is effective and safe in the retreatment of patients with chronic hepatitis B who had not responded to a previous alpha-interferon cycle.