Monitoring Liver Disease Progression in Hepatitis C/HIV Co-infected Patients With No-to-moderate Fibrosis, in Phnom Penh, Cambodia (HCV-Monitoring)

Monitoring Liver Disease Progression in Hepatitis C/HIV Co-infected Patients With No-to-moderate Fibrosis, in Phnom Penh, Cambodia (HCV-Monitoring)

Data on the progression of liver fibrosis in patients co-infected with HIV taking effective suppressive antiretroviral therapy with no fibrosis or mild-to-moderate fibrosis at baseline are scarce. This uncertainty is reflected in lack of clear guidance on the need for earlier (than F3-F4) treatment in co-infected patients.

Within our hepatitis C/HIV co-infection project in Cambodia, the investigators have the opportunity to monitor for short-term fibrosis progression in a cohort of co-infected patients with initial no-to-moderate fibrosis being identified during another ongoing study (HCV-Epi) and contribute relevant data to aid the risk/benefit analysis of postponing HCV treatment in HIV/HCV co-infected patients with initial fibrosis stage F0-F2.

The HCV-Monitoring study is a mono-centric prospective cohort study proposing a standardized follow-up (clinical, biological and imaging) to monitor for progression of hepatitis C disease in all patients with HIV infection (on anti-retroviral treatment or not) of Sihanouk Hospital Center of Hope (Phnom Penh, Cambodia) who have chronic HCV infection with GT-1, -2, -3 or -6 but are not considered in immediate need of HCV treatment.

All adult HIV-infected patients of the cohort (on ART or not yet on ART) of Sihanouk hospital Center of Hope who are identified during the HCV-Epi study having chronic HCV infection (all genotypes) and considered not in immediate need of HCV treatment (= Fibrosis stages F0-F2 and no clinical signs of extra-hepatic disease) will be considered for inclusion and invited to participate.

Approximately 70 HCV/HIV co-infected patients with no-to-moderate hepatic fibrosis will be enrolled in this study.

Beyond the baseline visit (HCV-Epi), follow-up visits are planned at 6, 12, 18 and 24 months. These patient visits will comprise of a history taking and physical examination focused on hepatic disease and blood sampling for basic hematologic and hepatic function parameters. Additionally, patients will be referred every year for ultrasound and transient elastography measurements and sampling for some additional liver function tests and measurement of HCV-RNA viral load.

Study Overview

• Status: Terminated
• Conditions: Hepatitis C; HIV
• Intervention / Treatment: Other: Liver fibrosis progression

Detailed Description

Data on the progression of liver fibrosis in patients co-infected with HIV taking effective suppressive antiretroviral therapy with no fibrosis or mild-to-moderate fibrosis at baseline are scarce. This uncertainty is reflected in lack of clear guidance on the need for earlier (than F3-F4) treatment in co-infected patients.

Within our hepatitis C/HIV co-infection project in Cambodia, the investigators have the opportunity to monitor for short-term fibrosis progression in a cohort of co-infected patients with initial no-to-moderate fibrosis being identified during another ongoing study (HCV-Epi) and contribute relevant data to aid the risk/benefit analysis of postponing HCV treatment in HIV/HCV co-infected patients with initial fibrosis stage F0-F2.

The HCV-Monitoring study is a mono-centric prospective cohort study proposing a standardized follow-up (clinical, biological and imaging) to monitor for progression of hepatitis C disease in all patients with HIV infection (on anti-retroviral treatment or not) of Sihanouk Hospital Center of Hope (Phnom Penh, Cambodia) who have chronic HCV infection with GT-1, -2, -3 or -6 but are not considered in immediate need of HCV treatment.

The study will be conducted in Sihanouk Hospital Center of Hope (SHCH) in Phnom Penh (Cambodia), more particularly within the ambulatory HIV clinic setting. SHCH is a non-governmental hospital providing comprehensive HIV care free of charge since March 2003, as part of the national antiretroviral (ARV) program. They dispose of an experienced HIV clinician, counselor and social worker team and several operational research studies were conducted within this setting.

All adult HIV-infected patients of the cohort (on ART or not yet on ART) of Sihanouk hospital Center of Hope who are identified during the HCV-Epi study having chronic HCV infection (all genotypes) and considered not in immediate need of HCV treatment (= Fibrosis stages F0-F2 and no clinical signs of extra-hepatic disease) will be considered for inclusion and invited to participate.

Approximately 70 HCV/HIV co-infected patients with no-to-moderate hepatic fibrosis will be enrolled in this study. No formal sample size is being calculated. The final sample will comprise all patients fulfilling the inclusion criteria.

The data collected from the HCV-Epi study will be considered as the baseline visit for the HCV-Monitoring study. Thereafter, visits are planned at 6, 12, 18 and 24 months follow-up. These patient visits will, beyond the habitual HIV follow-up, integrate a history taking and physical examination focused on hepatic disease and blood sampling for basic hematologic and hepatic function parameters. Additionally, patients will be referred every year for ultrasound and transient elastography measurements and sampling for some additional liver function tests and measurement of HCV-RNA viral load.

• Study Type: Observational
• Enrollment (Anticipated): 70

Contacts and Locations

Study Locations

• Cambodia
  • Phnom Penh, Cambodia
    • Sihanouk Hospital Center of HOPE (SHCH), Cambodia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult HIV-infected patients of the SHCH cohort who have chronic HCV infection (all genotypes) with no-to-moderate hepatic fibrosis and not considered in immediate need of HCV treatment.

Description

Inclusion Criteria:

• Male and females
• ≥18 years
• Documented HIV infection
• Evidence of infection with hepatitis C virus (all genotypes): Positive anti-HCV antibody and HCV RNA

• Absence of advanced liver disease or clinical signs of extra-hepatic disease:

  • F0-F2 (< 9,5 kPa) established by transient elastography, and
  • No clinical signs of extra-hepatic disease
• Not on HCV antiviral treatment

Exclusion Criteria:

• Currently on/or history of hepatitis C treatment
• Patients with initial fibrosis stage ≥ F3 (≥ 9,5 kPA on transient elastography)
• Patients not able/willing to adhere to the consultation, laboratory and liver stiffness measurement testing schedule as proposed in this study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HCV coinfection with no-to-moderate fibrosis	Other: Liver fibrosis progression; A history taking and physical examination focused on hepatic disease and blood sampling for basic hematologic and hepatic function parameters will be performed. Patients will also be referred every year for ultrasound and transient elastography measurements and sampling for some additional liver function tests and measurement of HCV-RNA viral load.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Short-term progression to advanced liver fibrosis	Proportion of patients who progress to advanced liver fibrosis (F≥3; LSM ≥9.5 kPa).	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Demographic characteristics	Demographic baseline characteristics of the study participants	Baseline
Clinical characteristics	Clinical baseline characteristics of the study participants	Baseline
Laboratory characteristics	Laboratory baseline characteristics of the study participants	Baseline
Progression to cirrhosis	Proportion of patients who progress to cirrhosis ((F=4, > 14 kPa)	30 months
Liver stiffness measurement	Median Liver stiffness measurement increase per year	30 months
Changes in fibrosis stage scores	Change in Metavir score (regression/progression, number of stages difference)	30 months
Diagnostic accuracy of non-invasive serum bio-markers: APRI	Predictive value of APRI to identify a shift from (≤F2) to advanced fibrosis (≥3)	30 months
Diagnostic accuracy of non-invasive serum bio-markers: FIB-4	Predictive value of FIB-4 to identify a shift from (≤F2) to advanced fibrosis (≥3)	30 months
Predictive factors for liver fibrosis progression	Factors associated with rapid fibrosis progression in HCV/HIV coinfected patients with initial mild to moderate fibrosis: age, gender, alcohol use, smoking, coffee consumption, comorbidities, liver enzymes, HCV viral load, HIV viral load, and ART exposure	30 months

Collaborators and Investigators

• Sponsor: Institute of Tropical Medicine, Belgium
• Collaborators: University Hospital, Antwerp; Sihanouk Hospital Center of HOPE
• Investigators: Study Director: Anja De Weggheleire, MD, Institute of Tropical Medicine, Antwerp, Belgium; Principal Investigator: An Sokkab, MD, Sihanouk Hospital Center of HOPE (SHCH), Cambodia

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2015
• Primary Completion (Actual): July 12, 2017
• Study Completion (Actual): July 12, 2017

Study Registration Dates

• First Submitted: November 25, 2015
• First Submitted That Met QC Criteria: December 9, 2015
• First Posted (Estimate): December 11, 2015

Study Record Updates

• Last Update Posted (Actual): August 23, 2017
• Last Update Submitted That Met QC Criteria: August 22, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Liver Diseases; Disease Progression; Hepatitis; Hepatitis A; Hepatitis C
• Other Study ID Numbers: HCV-Monitoring

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No