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Elastografia hepática transitória em doentes com hepatite c crónica : influência da terapêutica na regressão da fibrose
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Introdução: A resposta virológica sustentada tem sido associada a um prognóstico favorável nos doentes com infecção crónica pelo VHC. Os métodos de avaliação da fibrose hepática como a biópsia hepática têm como principal desvantagem serem invasivos. Novos métodos não-invasivos como a elastografia hepática transitória são compatíveis com uma avaliação sequenciada da fibrose hepática e apresentam-se como uma ferramenta valiosa no seguimento destes doentes.
Objectivo: Avaliar retrospectivamente a regressão de fibrose hepática e factores associados em doentes com infecção crónica pelo vírus hepatite C, com e sem tratamento antivírico e utilizando elastografia hepática transitória (EHT).
Métodos: Foram estudados retrospectivamente doentes com infecção crónica pelo VHC e com pelo menos 2 EHT válidas (Taxa de Sucesso ≥ 60% e IQR/M ≤ 0,3). Os pontos de corte foram definidos através de 110 doentes submetidos a biópsia hepática: 5.43kPa para F≥2 (VPP 0.98; VPN 0.25); 8.18kPa para F≥3 (VPP 0.87 VPN 0.97); 10,08kPa para F=4 (VPP 0.82; VPN 0.98). Os critérios de estratificação utilizados foram os seguintes: sem tratamento (ST) / com tratamento (CT) e com resposta virológica sustentada (RVS) / sem resposta virológica sustentada (SRVS). A regressão de fibrose hepática foi avaliada em todos os doentes com EHT inicial > F2 (>5.43kPa) e definida como a passagem para um estádio inferior de fibrose segundo a classificação de Peter Scheuer. Foi utilizado o Modelo de Regressão de Cox para avaliação dos factores do hospedeiro. Foi considerado como estatisticamente significativo p-value<0.05.
Resultados: Foram incluídos 149 doentes, 87 do sexo feminino, idade média 52.5 ± 9.3, distribuída por genótipos (65.7% genótipo 1; 51% 1a) e dividida em dois grupos: ST=57 (38.3%) e CT=92 (61.7%). A RVS foi atingida em 62.9% dos doentes. A mediana dos valores de EHT inicial não foi significativamente diferente entre os grupos CT vs ST (6,45 vs 5,90kPa, p-value 0,236) ou os grupos RVS vs SRVS (6,55 vs 6,35kPa, p-value 0,480). O número médio de EHT foi de 3,3 e o tempo mediano entre a EHT inicial e final foi de 51 meses. O grupo RVS apresentou idade inferior (p-value 0,010), genótipo não 1 mais frequente (p-value 0,001), RNA-VHC inferior (p-value 0,017), γ-GT inferior (p-value<0,001) e contagem de plaquetas superior (p-value 0,049) quando comparado com o grupo SRVS. A regressão foi significativamente superior no grupo RVS: aumento do número de doentes com estádio < F2 (+35,6% p-value 0,001), diminuição do valor médio de EHT (7,1±3,4kPa para 5,0±1,1kPa p-value<0,001), diminuição do valor mediano de EHT (6,55kPa para 5,55kPa p-value<0,001). O grupo RVS apresentou 71% de doentes com regressão vs 26,7% do grupo SRVS (p-value 0,002) e menor tempo mediano até à regressão quando comparado com o da população (38 meses vs 51 meses, p-value 0,045). Foram associados à regressão os seguintes factores: genótipo não 1 (HR 2,478 p-value 0,030), fosfatase alcalina (HR 0,978 p-value 0,040), valor de EHT inicial (HR 0,932 p-value 0,041) e RVS (HR 3,913 p-value 0,010).
Conclusões: A regressão de fibrose hepática é um processo lento. A regressão foi mais prevalente e mais rápida no grupo com RVS. A resposta virológica foi o factor que mais influenciou a regressão da fibrose. A EHT permite um follow-up contínuo e fiável ao longo do tempo, característica relevante para avaliar um fenómeno lento como a regressão de fibrose.
Introduction: Sustained virological response has been associated with better prognosis. Former tools to address liver fibrosis were invasive. New non-invasive tools, such as liver stiffness measurements (LSM), are easier to perform sequentially and more valuable in the follow up of chronic hepatitis C patients. Objective: To assess retrospectively fibrosis regression in patients with chronic hepatitis C virus infection with and without antiviral treatment, and its associated factors using LSM. Methods: Patients with chronic HCV infection were retrospectively studied with a minimum of two valid LSM (success rate ≥ 60% and IQR/M ≤ 0.3). The cutoff values were defined by our department in 110 patients submitted to liver biopsy: 5.43kPa for F≥2 (PPV 0.98; NPV 0.25); 8.18kPa for F≥3 (PPV 0.87 NPV 0.97); 10,08kPa for F=4 (PPV 0.82; NPV 0.98). Criteria for stratification were: non treated (NT) / treated (T) and with sustained virological response (SVR) and without (N-SVR) according to the international guidelines definition. Regression of liver fibrosis was defined as transition from higher to a lower stage (Peter Scheuer classification) and was evaluated in all the patients with initial LSM ≥ F2 (5.43 kPa). A Cox Regression Model was used to analyse the regression independent associated factors. Statistical significance p-value <0.05. Results: This study included 149 patients, 87 female, mean age 52.5 ± 9.3, distributed by genotypes (GT) (65.7% GT1; 51% 1a) and divided in two groups: NT=57 (38.3%) and T= 92 (61.7%) patients. The SVR was achieved in 62.9% of the patients. The median pre-treatment LSM were not significantly different between T vs NT (6,45 vs 5,90kPa, p-value 0,236) or SVR vs N-SVR (6,55 vs 6,35kPa, p-value 0,480). The average number of LSM was 3,3 and the median time between first and last LSM was 51 months. The SVR group were younger (p-value 0,010), non 1 genotype was more prevalent (p-value 0,001), had lower viral load (p-value 0,017), lower γ-GT values (p-value<0,001) and higher platelet count (p-value 0,049), when compared against non-SVR. Fibrosis regression was significantly more observed in the SVR group: increase in the number of patients with stage <F2 (+35,6%, p-value 0,001), decreased average LSM (7,1±3,4kPa to 5,0±1,1kPa p-value<0,001), decreased median LSM (6,55kPa to 5,55kPa p-value<0,001). SVR group achieved fibrosis regression in 71% vs 26.7% of N-SVR (p-value 0,002) and had a lower median time (38 months) to achieve regression, when compared to all the population (51 months), p-value 0,045. In the Cox Regression Model only non 1 genotype (HR 2,478 p-value 0,030), alkaline phosphatase (HR 0,978 p-value 0,040), initial LSM value (HR 0,932 p-value 0,041) and SVR (HR 3,913 p-value 0,010) were associated with fibrosis regression. Conclusion: Fibrosis regression is a slow process. It was predominantly observed and faster in the SVR group. More than the antiviral treatment, the sustained virologic response was the most important parameter associated with fibrosis regression. LSM is a reliable noninvasive method to assess liver disease following in time, which makes it suitable to better evaluate a slow process like fibrosis regression.
Introduction: Sustained virological response has been associated with better prognosis. Former tools to address liver fibrosis were invasive. New non-invasive tools, such as liver stiffness measurements (LSM), are easier to perform sequentially and more valuable in the follow up of chronic hepatitis C patients. Objective: To assess retrospectively fibrosis regression in patients with chronic hepatitis C virus infection with and without antiviral treatment, and its associated factors using LSM. Methods: Patients with chronic HCV infection were retrospectively studied with a minimum of two valid LSM (success rate ≥ 60% and IQR/M ≤ 0.3). The cutoff values were defined by our department in 110 patients submitted to liver biopsy: 5.43kPa for F≥2 (PPV 0.98; NPV 0.25); 8.18kPa for F≥3 (PPV 0.87 NPV 0.97); 10,08kPa for F=4 (PPV 0.82; NPV 0.98). Criteria for stratification were: non treated (NT) / treated (T) and with sustained virological response (SVR) and without (N-SVR) according to the international guidelines definition. Regression of liver fibrosis was defined as transition from higher to a lower stage (Peter Scheuer classification) and was evaluated in all the patients with initial LSM ≥ F2 (5.43 kPa). A Cox Regression Model was used to analyse the regression independent associated factors. Statistical significance p-value <0.05. Results: This study included 149 patients, 87 female, mean age 52.5 ± 9.3, distributed by genotypes (GT) (65.7% GT1; 51% 1a) and divided in two groups: NT=57 (38.3%) and T= 92 (61.7%) patients. The SVR was achieved in 62.9% of the patients. The median pre-treatment LSM were not significantly different between T vs NT (6,45 vs 5,90kPa, p-value 0,236) or SVR vs N-SVR (6,55 vs 6,35kPa, p-value 0,480). The average number of LSM was 3,3 and the median time between first and last LSM was 51 months. The SVR group were younger (p-value 0,010), non 1 genotype was more prevalent (p-value 0,001), had lower viral load (p-value 0,017), lower γ-GT values (p-value<0,001) and higher platelet count (p-value 0,049), when compared against non-SVR. Fibrosis regression was significantly more observed in the SVR group: increase in the number of patients with stage <F2 (+35,6%, p-value 0,001), decreased average LSM (7,1±3,4kPa to 5,0±1,1kPa p-value<0,001), decreased median LSM (6,55kPa to 5,55kPa p-value<0,001). SVR group achieved fibrosis regression in 71% vs 26.7% of N-SVR (p-value 0,002) and had a lower median time (38 months) to achieve regression, when compared to all the population (51 months), p-value 0,045. In the Cox Regression Model only non 1 genotype (HR 2,478 p-value 0,030), alkaline phosphatase (HR 0,978 p-value 0,040), initial LSM value (HR 0,932 p-value 0,041) and SVR (HR 3,913 p-value 0,010) were associated with fibrosis regression. Conclusion: Fibrosis regression is a slow process. It was predominantly observed and faster in the SVR group. More than the antiviral treatment, the sustained virologic response was the most important parameter associated with fibrosis regression. LSM is a reliable noninvasive method to assess liver disease following in time, which makes it suitable to better evaluate a slow process like fibrosis regression.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2015
Palavras-chave
Elastografia Hepatite C Hepatite crónica Cirrose hepática Gastroenterologia