Clinical trial NCT04191018: GastrOesophageal Varices After Sustained Virological Response
Official title: Progression of Gastroesophageal Varices After Sustained Virological Response by Interferon-free Regimens in Patients With Advanced Fibrosis / Cirrhosis Due to Chronic Hepatitis C
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Liver Diseases
Hepatitis C
Keywords: sustained virological response
portal hypertension
cirrhosis
gastrointestinal endoscopy
Lead sponsor: Oswaldo Cruz Foundation
Sponsor class: OTHER
First posted: 2019-12-09
Enrollment: 322
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with advanced fibrosis or cirrhosis with sustained virologic response by direct-acting agents for HCV treatment

Brief summary: Chronic hepatitis C remains a public health issue because up to 70 million people are chronically infected by hepatitis C virus (HCV) worldwide. Presence of advanced fibrosis/cirrhosis might be associated with liver-related complications, such as hepatocellular carcinoma and oesophageal varices bleeding. Oesophageal varices (OV) might be present in up to 40% of patients with liver cirrhosis have and the mortality rates from bleeding might be up to 20% per episode. Early diagnosis of advanced fibrosis/cirrhosis associated with hepatitis C treatment are key features for preventive and therapeutic measures to reduce liver-related mortality in HCV-infected patients.

Liver elastography is a high accurate non-invasive test for diagnosis of advanced fibrosis/cirrhosis. Few different methods of liver elastography are currently available: transient elastography by Fibroscan and ultrasound elastography by point-shear wave (p-SWE) and 2D-shear wave (2D-SWE). Gastrointestinal endoscopy (GIE) has been considered the gold standard for screening or surveillance of esophageal varices. More recently, international guidelines have been recommending the use of non-invasive methods to indicate or avoid OV screening: Baveno VI guidelines proposed that compensated cirrhotic patients with a liver stiffness measurement (LSM) by transient elastography \<20kPa and a platelet count \>150,000/μL can avoid screening endoscopy. The use of direct-acting agents (DAAs) has revolutionized the treatment of chronic hepatitis C with high effectiveness shown using all-oral interferon-free regimens. HCV cure, sustained virological response (SVR), has been associated with lower rates of liver-related complications, increase in quality of life and decrease in waiting-list registrations for liver transplantation in patients with chronic hepatitis C. Preliminary studies have been reporting significant regression liver stiffness after SVR. However, it is unclear whether SVR might decrease portal hypertension leading to OV regression and a reduced risk of variceal bleeding. In addition, the use of non-invasive methods to avoid OV screening must be validated in HCV patients after SVR. The aims of this cross-sectional study with prospective inclusion of patients will be: (i) to evaluate the impact of SVR in portal hypertension in HCV patients with advanced fibrosis/liver cirrhosis treated by interferon-free regimens and (ii) to validate non-invasive methods to avoid OV screening by GIE


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Presence of advanced fibrosis or cirrhosis (stage F≥3 METAVIR) based on liver stiffness by transient elastography (≥ 9,5 kPa) or liver biopsy
* Gastrointestinal endoscopy at least 24 months before start of direct-acting agents for HCV treatment
* Liver stiffness measurement at least 18 months after SVR

Exclusion Criteria:

* Autoimmune hepatitis, hepatosplenic schistosomiasis or cholestasis diseases
* Liver transplantation
* Presence of high volume ascites or hepatocellular carcinoma
* Participation in programs of esophageal band ligation for eradication of esophageal varices
* Presence of signs of acute decompensated liver disease

Primary outcomes:
measure: Incidence of esophageal varices (portal hypertension) after SVR
timeFrame: up to 48 months after SVR
measure: Validation of the Baveno's criteria to avoid gastrointestinal endoscopy for screening of esophageal varices after SVR
timeFrame: up to 48 months after SVR
Secondary outcomes:
measure: Incidence of regression of esophageal varices after SVR
timeFrame: up to 48 months after SVR
Other outcomes:
Locations:
city: Rio de Janeiro
country: Brazil
facility: Evandro Chagas National Institute of Infectious Diseases
state: Rio De Janeiro/RJ
city: Rio De Janeiro
country: Brazil
facility: Bonsucesso Federal Hospital
Study officials:
affiliation: Oswaldo Cruz Foundation
name: Hugo Perazzo, PhD
role: PRINCIPAL_INVESTIGATOR
References: