Randomized Open-label and Non-inferiority Clinical Trial to Evaluate the Safety, Adherence, and Cost-effectiveness of Simplified and Decentralized Hepatitis C Treatment in Primary Health Care Compared to Standard-of-care in the Brazilian Public Health System

In Brazil, liver cirrhosis was the cause of death for over 265,000 people between 2000 and 2012. The mortality rate from cirrhosis in 2012 was 12 deaths per 100,000 inhabitants, and the number of deaths from liver cirrhosis increased by about 22% in the last decade.

Recently, hepatitis C treatment has been revolutionized by the use of direct-acting antivirals (DAAs), which are safe and highly effective oral medications. Cure rates for hepatitis C, known as sustained virological response (SVR), in studies conducted in Brazil and Latin America were higher than 90%. Hepatitis C cure (SVR) is associated with a reduction in the incidence of HCC, the need for liver transplantation, improvement in quality of life, and a decrease in HCV transmission. These new medications have been available for hepatitis C treatment through the Brazilian Public Health System, known as Sistema Único de Saúde (SUS) since 2015.

The Ministry of Health of Brazil signed an agreement with the WHO in 2016 and with the goal of defining public health strategies to eliminate viral hepatitis by 2030, reducing new infections by 90% and global hepatitis-related mortality by 65%.

Identifying individuals with HCV infection is crucial for the (micro) elimination of hepatitis C. The majority of chronically infected HCV patients are asymptomatic until the development of liver cirrhosis and/or its complications. Therefore, screening for HCV infection should be performed in individuals, even when asymptomatic, through HCV antibody (HCVab) test. Currently, HCV rapid tests (HCVRT) in fingerstick blood with results in 15-20 minutes are available in Brazil.

Historically, HCV screening was recommended for individuals over 40 years of age and high-risk populations for HCV infection, such as people who inject drugs (PWID), prisoners, and men who have sex with men (MSM). However, recent international guidelines recommend screening for all individuals aged 18-79. Active HCV infection should be confirmed by detecting HCV viral load using molecular tests by polymerase chain reaction (PCR). Currently, the identification of HCV-RNA by PCR as a point-of-care tests (PoCT), GeneXpert® System, is also possible. The Xpert HCV VL Fingerstick test has excellent accuracy for detecting HCV-RNA in fingerstick blood, providing results in up to 105 minutes.. Liver elastography is a rapid imaging method (< 5 minutes), similar to abdominal ultrasound, painless, and free of complications, that can be performed at the bedside and provides real-time results for fibrosis stage/liver cirrhosis diagnosis. The technical principle of this method is based on measuring the propagation of ultrasound waves, called shear waves, through the liver parenchyma, estimating the organ's fibrosis degree through liver stiffness measurement (LSM). Currently, portable/semi-portable hepatic elastography devices are available, allowing for the staging of liver fibrosis in regions with difficult access to healthcare.