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Abstract Objectives The primary objective was to evaluate Liver-Related Events (LREs), including hepatic decompensation (ascites, hemorrhagic varices and encephalopathy) and Hepatocellular Carcinoma (HCC), as well as changes in liver stiffness during the follow-up period among patients who achieved a Sustained Virological Response (SVR) after treatment for chronic Hepatitis C Virus (HCV) infection. Methods A total of 218 patients with HCV were treated, and those who achieved an SVR were followed up for 3-years. Transient Elastography (TE) using FibroScan® was performed at various time points: before treatment, at the end of treatment, at 6-months post-treatment, at 1-year post-treatment, at 2-years post-treatment, and at 3-years post-treatment. Results At 6-months post-treatment, a Liver Stiffness Measurement (LSM) cutoff of > 19 KPa was identified, leading to a 14.5-fold increase in the hazard of negative outcomes, including decompensation and/or HCC. The analysis of relative changes in liver stiffness between pre-treatment and 6-months posttreatment revealed that a reduction in LSM of -10 % was associated with a -12 % decrease in the hazard of decompensation and/or HCC, with this trend continuing as the LSM reduction reached -40 %, resulting in a -41 % hazard of decompensation and/or HCC. Conversely, an increase in the relative change during this period, such as an LSM increase of +10 %, led to a + 14 % increase in the hazard of decompensation. In cases where this relative change in LSM was +50 %, the hazard of decompensation increased to +92. Conclusion Transient elastography using FibroScan® can be a good tool for monitoring HCV patients with SVR after treatment to predict LREs in the long term.
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ABSTRACT Background: Evaluate the role of liver stiffness measurement (LSM) by transient elastography (TE) as a risk factor for hepatocellular carcinoma (HCC) occurrence in a prospective cohort of Brazilian hepatitis C virus (HCV) patients with cirrhosis. Methods: A cohort of 99 consecutive HCV patients was included between 2011 and 2016 with baseline LSM ≥12 kilopascals (kPa). Baseline variables were evaluated and HCC occurrence was documented. Kaplan-Meier methods with a log-rank test and the use of cox univariate and multivariate analysis assessed the association between variables and clinical results. Results: The mean age was 57.8±10.6 years. In a follow-up over a mean of 3.3 years, 20 (20.2%) patients developed HCC. In univariate logistic regression analysis, variables associated with HCC occurrence were: lower platelet count (P=0.0446), higher serum alpha-fetoprotein (P=0.0041) and bilirubin (P=0.0008) values, higher Model for End-Stage Liver Disease (MELD) score (P=0.0068) and higher LSM (P=0.0354). LSM evaluated by TE was independently associated with HCC development, and the best cut-off value for higher HCC risk was >21.1 kPa (HR: 5.548; 95%CI: 1.244-24.766; P=0.025). Conclusion: A high value of liver stiffness relates substantially to an increased risk for HCC occurrence in Brazilian patients with cirrhosis due to HCV.
RESUMO Contexto: O carcinoma hepatocelular (CHC) é o tumor maligno hepático mais comum, e a cirrose é o principal fator de risco para o seu desenvolvimento. Objetivo: Avaliar o papel da medição da rigidez hepática por elastografia transitória (ET) como fator de risco para ocorrência de CHC em uma coorte prospectiva de pacientes brasileiros com cirrose por vírus da hepatite C (VHC). Métodos: Um total de 99 pacientes com VHC e medida de rigidez hepática ≥12 kilopascals (kPa) foram incluídos consecutivamente, entre 2011 e 2016. As variáveis do baseline foram avaliadas e a ocorrência de CHC foi documentada. Os testes de Kaplan-Meier e log-rank, além das análises uni e multivariadas de Cox avaliaram a associação entre as variáveis e os resultados clínicos. Resultados: A média de idade foi de 57,8±10,6 anos. Vinte (20,2%) pacientes desenvolveram CHC, num período médio de seguimento de 3,3 anos. Na análise de regressão logística univariada, as variáveis associadas à ocorrência de CHC foram: contagem de plaquetas mais baixa (P=0,0446), valores séricos mais elevados de alfa-fetoproteína (P=0,0041) e de bilirrubina (P=0,0008), maior pontuação do escore MELD (P=0,0068) e valores mais altos de rigidez hepática por ET (P=0,0354). A medição da rigidez hepática por ET foi independentemente associada ao desenvolvimento de CHC, e o melhor valor de corte para maior risco de CHC foi >21,1kPa (HR: 5,548; IC95%: 1,244-24,766; P=0,025). Conclusão: Um alto valor de rigidez hepática está relacionado substancialmente a um risco aumentado de ocorrência de CHC em pacientes brasileiros com cirrose por HCV.
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OBJECTIVES: Despite higher rates of sustained virologic response (SVR), important concerns remain when patients with decompensated cirrhosis due to hepatitis C virus (HCV) are treated with direct-acting antiviral agents (DAA). Questions include efficacy, safety, and the magnitude of liver function improvement. Here, we aimed to evaluate HCV treatment data in this specific population in Brazil. METHODS: We included 85 patients with decompensated cirrhosis submitted to HCV therapy with DAA followed at two academic tertiary centers in the southeastern region of Brazil. RESULTS: Seventy-nine patients (92.9%) were Child-Pugh (CP) score B, and six (7.1%) were CP score C. The mean MELD score was 12.86. The most common treatment was sofosbuvir plus daclatasvir±ribavirin for 24 weeks. The overall intention-to-treat (ITT) SVR rate was 87.4% (74/85) and modified-ITT 96.1% (74/77). ITT SVR was associated with lower baseline INR values (p=0.029). Adverse events (AE) occurred in 57.9% (44/76) of patients. Serious AE were reported in 12.8% (10/78), and were related to the presence of hepatic encephalopathy (p=0.027). SVR was associated with improvement in CP (p<0.0001) and MELD scores (p=0.021). Among baseline CP score B patients with SVR, 46% (29/63) regressed to CP score A. Ascites was independently associated with no improvement in liver function in patients who achieved SVR (p=0.001; OR:39.285; 95% CI:4.301-258.832). CONCLUSIONS: Patients with decompensated HCV cirrhosis showed a high SVR rate with interferon-free therapy. Early liver function improvement occurred after successful HCV eradication. However, long-term follow-up of these patients after SVR remains strongly advised.
الموضوعات
Humans , Antiviral Agents/therapeutic use , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Ribavirin/therapeutic use , Treatment Outcome , Hepacivirus , Drug Therapy, Combination , Sustained Virologic Response , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapyالملخص
OBJECTIVES: Co-infection with hepatitis A or B viruses may aggravate liver injury in patients infected with hepatitis C virus (HCV). However, few studies have assessed co-infection with hepatitis E virus (HEV) and HCV. Therefore, this study aimed to assess the prevalence and impact of HEV infection among Brazilian patients with chronic HCV infection. METHODS: This observational study included adult patients with chronic HCV infection who were naive to antiviral therapy from January 2013 to March 2016. A total of 181 patients were enrolled, and HEV serology and PCR were performed for all patients. RESULTS: Seropositivity for anti-HEV IgG was detected in 22 (12.0%) patients and anti-HEV immunoglobulin M in 3 (1.6%). HEV RNA showed inconclusive results in nine (4.9%) patients and was undetectable in the remaining patients. HEV serology positive patients had more severe liver disease, characterized by liver fibrosis ≥3 versus ≤2 (p<0.001), Aspartate Aminotransferase-to-Platelet Ratio Index of ≥1.45 (p=0.003), and Fibrosis-4 score of ≥3.25 (p=0.001). Additionally, the odds of HEV-positive patients developing diabetes mellitus were 3.65 (95% CI 1.40-9.52) times the corresponding odds of HEV-negative patients. A case-control-based histological analysis (n=11 HEV-HCV-positive patients and n=22 HCV-positive patients) showed no significant differences between the groups. CONCLUSIONS: This prevalence is higher than that reported in previous studies of the general population in Brazil. Thus, HEV infection may influence the severity of liver disease and may represent an additional risk of developing diabetes mellitus in patients with HCV infection.
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Humans , Adult , Hepatitis E virus/genetics , Hepatitis E/complications , Hepatitis C , Hepatitis C, Chronic/complications , Diabetes Mellitus/epidemiology , Coinfection , RNA, Viral , Hepatitis Antibodies , Prevalence , Hepatitis E/epidemiology , Hepacivirus/geneticsالملخص
A resistência viral aos inibidores de protease aparece rapidamente, pois essas cepas resistentes já existem naturalmente na população de quasispécies do vírus, emergindo como cepas mais prevalentes em relação às cepas selvagens quando o vírus sofre a pressão da droga. Esta seleção de cepas resistentes (RAVs) tem um papel im¬portante na falha terapêutica dessa classe de droga. Análise por sequenciamento direto em pacientes não tratados têm demonstrado diversas RAVs aos inibidores de protease (substituições nas posi¬ções V36, T54, V55, Q80, R155, D168 e V170). As mutações nas posições R155K e A156T da região NS3 estão associadas à alta resistência aos inibidores de protease. Dessa forma, os antivirais de ação direta (DAA) não podem ser utilizados em monoterapia. Aparentemente, existe uma diferença geográfica na distribuição dessas variantes de resistência. Nas populações europeia e america¬na, por exemplo, a variante de resistência na posição Q80K no ge¬nótipo 1a, que confere resistência ao simeprevir, foi encontrada em 25% a 35%. No entanto, na população brasileira uma frequência em torno de 1,8% de RAVs na posição Q80K, em três estudos, dois em VHC monoinfectados e outro em co-infectados VHC-HIV. O conhecimento da distribuição dos subgenótipos e do perfil de mutações nas diversas populações em todo o mundo vai se tornar importante na confecção de guidelines regionais, que seguramente terão suas particularidades de acordo com o perfil de cada região, no intuito de atingirmos máxima eficácia dos diferentes esquemas terapêuticos
Viral resistance to protease inhibitors appear quickly because these resistant strains occur naturally in the virus quasispecies population, emerging as the most prevalent strains compared to wild type strains when the virus is under drug pressure. This selection of resistant strains (RAVs) has an important role in therapeutic failure of this class of drug. Analyses by direct sequencing in untreated patients have shown various RAVs to protease inhibitors (substitutions at positions V36, T54, V55, Q80, R155, A156, D168 and V170). Mutations at positions R155K and A156T on NS3 region are associated with high resistance to protease inhibitors. Thus, the direct action antivirals (DAA) may not be used as monotherapy. Apparently, there is a geographical difference in the distribution of these variants of resistance worldwide. In European and American HCV population for example, resistance variants in the position Q80K genotype 1a, which confers resistance to simeprevir was found in 25% to 35% of patients. However, in the Brazilian population the Q80K mutation was found at a frequency of around 1.8%, in three studies, two in HCV monoinfected and another in coinfected HIV-HCV patients. The distribution of this mutation profile in different populations around the world will become important in the preparation of regional guidelines, which surely will have their particularities according to the HCV subtyping distribution and mutation profile of each region in order to achieve maximum effectiveness of different treatment regimens
الموضوعات
Hepacivirus , Hepatitis C , Hepatitis C, Chronic , Drug Resistance, Viral , Genotype , Protease Inhibitorsالملخص
CONTEXTO: A prevalência e significado patológico dos reflexos primitivos (RP) no adulto, bem como sua relação com a idade e a cognição, são questões controversas. OBJETIVO: Estudar a relação entre RP e cognição em 30 pacientes com doença de Alzheimer (DA) e 154 sujeitos controles normais. MÉTODO: O diagnóstico de DA baseou-se nos critérios DSM-IV, NINCDS-ADRDA e CAMDEX. Os RP foram quantificados de 0 (ausente) a 1 (leve) ou 2 (acentuado). CASI-S (Cognitive Abilities Screening Instrument -Short Form) foi usado para avaliar o registro, orientação temporal, fluência verbal e evocação. Um teste de cópia de pentágonos foi acrescentado. RESULTADOS: Os RP mais frequentes nos pacientes e controles foram o de sucção (77% e 62%, respectivamente) e "snout" (60% e 27%), seguidos do glabelar (30% e 19%), paratonia (37% e 5%) e palmomentoniano (23% e 5%). Nenhum sujeito controle teve mais que três RP. A frequência dos RP tendeu a aumentar com a idade e a deterioração cognitiva. O reflexo de preensão e o sinal de Babinski foram encontrados apenas nos pacientes com DA. Os RP não se correlacionaram uns com os outros, exceto o reflexo "snout" com o de sucção e com o glabelar.CONCLUSÃO: O achado de reflexo de preensão e sinal de Babinski, ou a presença de mais de três sinais primitivos, particularmente a combinação de paratonia e reflexos "snout", sucção e palmomentoniano, são sugestivos de disfunção cerebral, especialmente quando esses sinais são acentuados e acompanhados de déficits de orientação, evocação, fluência verbal e praxia construcional.
الموضوعات
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Alzheimer Disease/complications , Cognition Disorders/etiology , Reflex, Abnormal/physiology , Alzheimer Disease/physiopathology , Case-Control Studies , Cognition Disorders/diagnosis , Neuropsychological Tests , Prevalence , Psychiatric Status Rating Scales , Severity of Illness Indexالملخص
OBJETIVO: Determinar a acurácia do CASI-S no diagnóstico de demência. MÉTODO: O CASI-S (Cognitive Abilities Screening Instrument - Short Form) foi aplicado em 43 pacientes com doença de Alzheimer (DA) e 74 controles normais. O diagnóstico de DA baseou-se no DSM-IV, NINCDS-ADRDA e CAMDEX. O CASI-S inclui: registro, orientação temporal, fluência verbal (animais quadrúpedes em 30s), e evocação (3 palavras). O escore máximo é 33 pontos. Foi adicionado um teste de cópia de 2 pentágonos. RESULTADOS: A curva ROC mostrou acurácia de 0,87, com erro padrão de 0,032, e intervalo de confiança de 95% entre 0,795 e 0,925. O ponto de corte para déficit cognitivo foi 23 pontos, com sensibilidade de 76,7%, especificidade de 86,5%, valor preditivo (VP) positivo de 5,68, e VP negativo de 0,27. Para sujeitos com 70 anos ou mais, o ponto de corte foi 20, com sensibilidade de 71,4% e especificidade de 97,1%. CONCLUSION: O CASI-S é um teste prático, com alta especificidade, particularmente em indivíduos com idade acima de 70 anos. O teste de cópia dos pentágonos não melhorou sua acurácia.