Impact of direct-acting antiviral regimens on hepatic and extrahepatic manifestations of hepatitis C virus infection

Abstract

Hepatitis C virus (HCV) is a common cause of liver disease and is associated with various extrahepatic manifestations (EHMs). This mini-review outlines the currently available treatments for HCV infection and their prognostic effect on hepatic manifestations and EHMs. Direct-acting antiviral (DAA) regimens are considered pan-genotypic as they achieve a sustained virological response (SVR) > 85% after 12 wk through all the major HCV genotypes, with high percentages of SVR even in advanced fibrosis and cirrhosis. The risk factors for DAA failure include old males, cirrhosis, and the presence of resistance-associated substitutions (RAS) in the region targeted by the received DAAs. The effectiveness of DAA regimens is reduced in HCV genotype 3 with baseline RAS like A30K, Y93H, and P53del. Moreover, the European Association for the Study of the Liver recommended the identification of baseline RAS for HCV genotype 1a. The higher rate of hepatocellular carcinoma (HCC) after DAA therapy may be related to the fact that DAA regimens are offered to patients with advanced liver fibrosis and cirrhosis, where interferon was contraindicated to those patients. The change in the growth of pre-existing subclinical, undetectable HCC upon DAA treatment might be also a cause. Furthermore, after DAA therapy, the T cell-dependent immune response is much weaker upon HCV clearance, and the down-regulation of TNF-α or the elevated neutrophil to lymphocyte ratio might increase the risk of HCC. DAAs can result in reactivation of hepatitis B virus (HBV) in HCV co-infected patients. DAAs are effective in treating HCV-associated mixed cryoglobulinemia, with clinical and immunological responses, and have rapid and high effectiveness in thrombocytopenia. DAAs improve insulin resistance in 90% of patients, increase glomerular filtration rate, and decrease proteinuria, hematuria and articular manifestations. HCV clearance by DAAs allows a significant improvement in atherosclerosis and metabolic and immunological conditions, with a reduction of major cardiovascular events. They also improve physical function, fatigue, cognitive impairment, and quality of life. Early therapeutic approach with DAAs is recommended as it cure many of the EHMs that are still in a reversible stage and can prevent others that can develop due to delayed treatment.

Maximizing Reflexive Hepatitis C Virus (HCV) RNA Testing of HCV Antibody-Reactive Samples Within United States Public Health Laboratories

“…When establishing test menus, laboratories should consider the need to offer not only an HCV antibody with reflex to HCV RNA test, but also a standalone HCV RNA test (particularly quantitative), and potentially an HCV genotyping assay as a reflex or referral test when HCV diagnosis is first established. Although pan-genotypic direct-acting antivirals may obviate the need for genotyping [ 11 ], genotyping may be required by insurance companies prior to initiation of HCV treatment.…”

High-Density Lipoprotein Cholesterol and Systemic Arterial Hypertension Are Associated With Hepatic Necroinflammatory Activity in Patients With Chronic Hepatitis C

“…Blood screening for hepatitis C virus (HCV) and the revolutionary development of direct-acting antivirals (DAAs) have successfully saved millions of lives (1)(2)(3) . Although sustained virological response rates (SVR) linked to DAAs prescription have surpassed 95.0% (4,5) , it is important to bear in mind that there are still various barriers to attain the World Health Organization (WHO) HCV elimination targets by 2030 (6,7) .…”

Efetividade, segurança e dinâmica de seleção de mutações de resistência envolvendo o uso de fármacos de ação direta na infecção crônica pelo genótipo 3 do HCV

“…O HCV se replica nas células β do pâncreas, o que causa redução da reserva destas células. Em adição, por meio de suas proteínas estruturais e não estruturais, afeta vias de sinalização da insulina e inibe a expressão de receptores desse hormônio (MAZZARO et al, 2021;SALAMA et al, 2022).…”

“…A análise dos desfechos em longo prazo, especialmente em populações que apresentam alta prevalência de indivíduos com fibrose hepática avançada é relevante, uma vez que o impacto da RVS na redução do risco para complicações, como, o desenvolvimento de CHC seria menor nesses indivíduos (OKANOUE et al, 1999;SALAMA et al, 2022) do presente estudo ratificam que, embora a RVS tenha um impacto importante para a redução da inflamação do fígado e da incidência de desfechos desfavoráveis, como, o CHC, a manutenção do acompanhamento de pacientes com fibrose hepática avançada em centros especializados, após a cura virológica, é uma conduta fundamental no sentido de oferecer diagnóstico e manejo adequados de eventuais complicações da doença hepática.…”

“…Tais resultados sugerem que a RVS reduz o risco de CHC entre os pacientes com HCC acometidos pelo genótipo 3. A incidência de CHC de cerca de 10% em três anos no grupo que alcançou cura virológica e os resultados que mostraram que todos os pacientes do estudo que evoluíram para CHC, transplante hepático ou óbito após o tratamento apresentavam CH no baseline corroboram dados de estudos que referem que há um risco importante de CHC em cirróticos, mesmo após a RVS(OKANOUE et al, 1999;SALAMA et al, 2022), e a recomendação de manutenção de acompanhamento de pacientes curados, que têm fibrose avançada, em centros especializados no manejo de doenças hepáticas(MINISTÉRIO DA SAÚDE, 2019; EASL, 2020). Ainda sobre os desfechos de longo prazo, somente um paciente, do total de seis que falharam ao tratamento e que permaneceram em acompanhamento no ambulatório de hepatites virais, foi retratado com sucesso, o que evidencia a escassez de opções para retratamento de indivíduos com falha a terapias com DAAs durante a condução do estudo.…”