Long-Term Follow-Up of Advanced Liver Disease after Sustained Virological Response to Treatment of Hepatitis C with Direct-Acting Antivirals: Outcomes from a Real-World Portuguese Cohort

Abstract

Background: Direct-acting antivirals (DAA) have revolutionized hepatitis C treatment, with high sustained virological response (SVR) rates reported, even in historically difficultto-treat groups. SVR is associated with a decreased risk of hepatocellular carcinoma (HCC), need for transplantation, and overall and liver-related mortality. Data from real-life cohorts on the medium-to long-term outcomes of patients with advanced liver disease and DAA-induced SVR are still missing. Objectives: To report and analyze the long-term Seguimento a longo prazo da doença hepática avançada após cura do vírus C com antivíricos de ação direta: dados de uma coorte Portuguesa Palavras ChaveAgentes antivirais · Carcinoma hepatocelular · Cirrose hepática · Hepatite C · Resposta virológica sustentada Resumo Introdução: Os antivíricos de ação direta (AAD) revolucionaram o tratamento da hepatite C ao atingirem elevadas taxas de resposta virológica sustentada (RVS), mesmo em grupos historicamente difíceis de tratar. A RVS associa-se a uma diminuição do risco de carcinoma hepatocelular (CHC), necessidade de transplantação e mortalidade, global e de causa hepática. São ainda insuficientes de coortes reais na literatura dados que permitam avaliar a extensão dos benefícios clínicos a médio-longo prazo do atingimento de uma RVS com os AAD. Objetivos: Reportar e analisar o impacto a longo prazo da RVS numa coorte real de doentes com doença hepática avançada, tratados com AAD. Métodos: Estudo unicêntrico, retrospetivo, longitudinal com inclusão de doentes com hepatite C crónica com cirrose ou fibrose avançada, que iniciaram tratamento com AAD de fevereiro de 2015 a janeiro de 2017. Resultados: Foram incluídos 237 doentes. Verificou-se uma taxa de retenção no tratamento de 98.7% com uma taxa de RVS de 97.8% (intention to treat: 96.6%). Dos 229 doentes curados, 67.2% eram cirróticos (64.2% Child-Pugh A, 3.1% Child-Pugh B) e 32.8% F3, com um seguimento médio de 28 meses. A taxa de mortalidade global foi de 19/1,000 pessoas-ano e de mortalidade associada à doença hepática de 9.5/1,000 pessoasano. A incidência de eventos de descompensação hepática foi de 25/1,000 pessoas-ano e a de CHC foi de 11.6/1,000 pessoas-ano. Verificou-se um aumento sustentado dos valores séricos de plaquetas até 2 anos de seguimento. A história de eventos de descompensação hepática, concentração de plaquetas e albumina prétratamento encontrou-se significativamente associada a eventos adversos hepáticos durante o seguimento. Conclusões: A cura virológica após tratamento com AAD é sustentada no tempo, encontrando-se associada a um excelente prognóstico clínico em doentes com doença hepática avançada compensada, e a uma melhoria ou estabilização da doença em doentes descompensados. O atingimento de RVS associa-se a um baixo risco de CHC, não o eliminando, e de progressão da doença, sobretudo perante a presença de outros cofatores de agressão hepática, recomendando-se a manutenção do seguimento destes doentes.

Five-Year Follow-Up of Cured HCV Patients under Real-World Interferon-Free Therapy

“…Our observations on the reduced risk of liver cancer in cirrhotic patients following HCV clearance are consistent with results coming from numerous RWE cohorts and meta-analysis of earlier studies, but we were able to demonstrate this DAA effect during the longest follow-up period [21,[38][39][40][41][42]. It should be emphasized that despite the dominance of SOF-based regimens in most studies available in large patient populations, the reduction in the risk of HCC after DAA therapy was observed regardless of the therapeutic regimen used [18,40,43,44].…”

“…Our analysis confirmed the durability of the virologic response following the DAA therapy across all liver fibrosis stages. Long-term persistence of viral clearance was documented in patients with advanced liver disease in Austrian and Portuguese RWE cohorts treated with DAA, but the observation period was much shorter than ours [17,18]. Both studies analyzed patients predominantly treated with IFN-free, SOF-based regimens, 87% and 95%, and reported durability of viral eradication over a follow-up period of 65.6 weeks and 28 months, respectively.…”

Effect of Baseline Resistance-Associated Substitutions on Thalassemia Patients with Chronic HCV Infection: A Two-Year Follow-Up

“…Follow-up studies are recommended for patients surveillance. 16 The present study was an attempt to investigate the treatment outcome of the patients with RASs as a surveillance study, finding that DAA therapy had a satisfactory result on both patients with and without cirrhosis; this is while we followed up patients with different genotypes, subtypes, and RASs frequencies.…”

The Patient Bomb: Sustained Viral Response after Hepatitis C in Cirrhosis

“…The paper by Pereira Guedes et al [1], analyzing data from a real-world Portuguese cohort with advanced liver disease, provides us with some interesting ideas, with translation into our clinical and real practice. The study, albeit retrospective, has evaluated data from 237 patients in a tertiary university hospital; 99% completed treatment, and the sustained viral response (SVR) was 98%, similar to the best trial results [2].…”

“…In the paper by Pereira Guedes et al [1], elastography, liver biopsy and clinical evaluation was used before therapy. After DAA treatment, there is a reduction of the value of elastography.…”