Liver Status and Presence of MASLD/MASH in Patients With Chronic Hepatitis B (Faraday)

The Value of Fibroscan® in Assessing the Liver Status and Presence of MASLD/MASH in Patients With Chronic Hepatitis B and Monitoring Changes by Antiviral Therapy: Faraday Study

The aim of the study was to evaluate the consistency between liver biopsy and Liver Stiffness Measurement (LSM) for fibrosis and controlled attenuation parameter (CAP) for steatosis in FibroScan® in patients with chronic hepatitis B. The secondary aim of the study was to demonstrate the efficacy of FibroScan® for following the CHB patients at 12th month of antiviral therapy.

The study was prospectively planned in four different centers. Patients with HBsAg positivity for more than six months and HBV-DNA>2,000 IU/mL, underwent liver biopsy and FibroScan® together within two week. FibroScan® was performed twice, before the antiviral therapy and one year later.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B; Hepatic Steatosis
• Intervention / Treatment: Diagnostic test: Transient elastography; Drug: Tenofovir Disoproxil Fumarate

Detailed Description

Patients aged 18 years and older with HBsAg positivity for more than six months and HBV-DNA level >2,000 IU/ml were included in the study. The exclusion criteria were established as presence of cirrhosis, alcohol consumption >140 g/week for women and 210 g/week for men, hepatitis C, hepatitis D and/or HIV coinfections.

The baseline characteristics including patient demographics, BMI, comorbidities, LSM and CAP via transient elastography (FibroScan®), liver ultrasound, HBV serology, platelet count, ALT, HBV viral load.

All patients underwent liver biopsy before initiating antiviral therapy, with a maximum interval of two week between liver biopsy and the FibroScan®.

Transient elastography was performed by a certified operator, using the M probe for patients with skin to capsule distance < 2.5 cm or an XL probe for patients with skin to capsule distance > 2.5 cm. Patients were fasted for > 2 h before FibroScan®. At least 10 successful measurements were performed and recorded.

Fibrosis stage by Liver Stiffness Measurement (LSM) and steatosis by Controlled Attenuation Parameter (CAP) were investigated on FibroScan® for MASLD and MASH. Obese or diabetic patients with a CAP value >240 dB/m were considered MASLD. Patients with normal BMI and nondiabetic patients had at least two risk factors for metabolic dysfunction were also considered to have MASLD. Patients with MASLD and concomitant necroinflammation in the liver were considered as MASH. Necroinflammation was considered as LSM ≥7.2 kPa in patients with MASLD or LSM >5.5 kPa in patients with liver injury (histologic and/or ALT>NSU).

The study protocol was approved by the Ethics Committee of Dicle University (Protocol number: 2022/261) The IBM SPSS 21.0 statistical software for Windows was used for the statistical evaluation of the research data. The measurable variables were presented as the mean ± standard deviation (SD), while the categorical variables were presented as the number and percentage (%). Spearman's rho correlation analysis was performed to determine the relationship between the variables. The hypotheses were bidirectional, and p ≤0.05 was considered statistically significant.

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

Contacts and Locations

Study Locations

• Turkey
  • Ankara, Turkey, TR-06540
    • Güven Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients aged 18 years and older with HBsAg positivity for more than six months and HBV-DNA level >2,000 IU/ml were included in the study. The exclusion criteria were established as presence of cirrhosis, alcohol consumption >140 g/week for women and 210 g/week for men, hepatitis C, hepatitis D and/or HIV coinfections.

Description

Inclusion Criteria:

• Patients aged 18 years and older with HBsAg positivity for more than six months
• Patients have HBV-DNA level >2,000 IU/ml for more than six months

Exclusion Criteria:

• Presence of cirrhosis
• Alcohol consumption >140 g/week in women and 210 g/week in men
• Hepatitis C coinfection
• Hepatitis D and/or HIV coinfections

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Chronic hepatitis B patients; Patients aged 18 years and older with HBsAg positivity for more than six months and HBV-DNA level >2,000 IU/ml	Diagnostic test: Transient elastography; Liver Stiffness Measurement, Controlled Attenuation Parameter; Other Names: Fibroscan; Drug: Tenofovir Disoproxil Fumarate; Guided Therapy; Other Names: TDF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Histological activity index (HAI) evaluatin by liver biopsy in patients with chronic hepatitis B before initiating antiviral therapy.	All patients underwent liver biopsy before initiating antiviral therapy, for evaluating histological activity index (HAI). According to modified HAI system (Ishak), HAI scores ranging from 0 to 18 were used.	23.01.2023-25.04.2023
Fibrosis score evaluation by liver biopsy in patients with chronic hepatitis B before initiating antiviral therapy.	All patients underwent liver biopsy before initiating antiviral therapy, for evaluating fibrosis score. According to modified HAI system (Ishak), seven point scale ranging from 0 to 6 for fibrosis stage.	23.01.2023-25.04.2023
Hepatic steatosis evaluation by Controlled Attenuation Parameter (CAP) on FibroScan® in patients with chronic hepatitis B before initiating antiviral therapy.	FibroScan® measurements were perfomred at most two weeks apart from biopsy. Hepatic steatosis by Controlled Attenuation Parameter (CAP) were investigated on FibroScan® for MASLD and MASH. Obese or diabetic patients with a CAP value >240 dB/m were considered MASLD. Patients with normal BMI and nondiabetic patients had at least two risk factors for metabolic dysfunction were also considered to have MASLD.	23.01.2023-25.04.2023
Fibrosis stage by Liver Stiffness Measurement (LSM) on FibroScan® in patients with chronic hepatitis B before initiating antiviral therapy.	FibroScan® measurements were perfomred at most two weeks apart from biopsy. Fibrosis stage by Liver Stiffness Measurement (LSM) was investigated on FibroScan®. Necroinflammation was considered as LSM ≥7.2 kPa in patients with MASLD. Patients with MASLD and concomitant necroinflammation in the liver were considered as MASH.	23.01.2023-25.04.2023

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatic steatosis evaluation by Controlled Attenuation Parameter (CAP) on FibroScan® in patients with chronic hepatitis B at 12th month of antiviral therapy.	Hepatic steatosis by Controlled Attenuation Parameter (CAP) were investigated on FibroScan® for MASLD and MASH. Obese or diabetic patients with a CAP value >240 dB/m were considered MASLD. Patients with normal BMI and nondiabetic patients had at least two risk factors for metabolic dysfunction were also considered to have MASLD.	23.01.2024-25.04.2024
Fibrosis stage by Liver Stiffness Measurement (LSM) on FibroScan® in patients with chronic hepatitis B.	FibroScan® measurements were performed at most two weeks apart from biopsy. Fibrosis stage by Liver Stiffness Measurement (LSM) was investigated on FibroScan®. Necroinflammation was considered as LSM ≥7.2 kPa in patients with MASLD. Patients with MASLD and concomitant necroinflammation in the liver were considered as MASH.	23.01.2024-25.04.2024

Collaborators and Investigators

• Sponsor: Yaşar Bayındır, MD
• Collaborators: Nobel Pharmaceuticals
• Investigators: Principal Investigator: Mustafa Kemal Çelen, MD, Dicle University, Medical Faculty, Department of Infectious Diseases

Publications and helpful links

General Publications

• European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370-398. doi: 10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18.
• Vittal A, Ghany MG. WHO Guidelines for Prevention, Care and Treatment of Individuals Infected with HBV: A US Perspective. Clin Liver Dis. 2019 Aug;23(3):417-432. doi: 10.1016/j.cld.2019.04.008.
• Wang L, Wang Y, Liu S, Zhai X, Zhou G, Lu F, Zhao J. Nonalcoholic fatty liver disease is associated with lower hepatitis B viral load and antiviral response in pediatric population. J Gastroenterol. 2019 Dec;54(12):1096-1105. doi: 10.1007/s00535-019-01594-6. Epub 2019 May 27.
• Jiang K, Zhang L, Li J, Hu H, Huang Q, Qiu T, Mo X, Ren J, Guo W, Tao Y, Cui H, Zuo Y, Chen X, Xie Y, Li Y, Liang H, Liu Z, Xie L, Mao R, Jiang Q, Huang K. Diagnostic efficacy of FibroScan for liver inflammation in patients with chronic hepatitis B: a single-center study with 1185 liver biopsies as controls. BMC Gastroenterol. 2022 Jan 29;22(1):37. doi: 10.1186/s12876-022-02108-0.

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2023
• Primary Completion (Actual): April 25, 2023
• Study Completion (Actual): May 15, 2024

Study Registration Dates

• First Submitted: August 7, 2024
• First Submitted That Met QC Criteria: August 25, 2024
• First Posted (Actual): August 27, 2024

Study Record Updates

• Last Update Posted (Actual): August 27, 2024
• Last Update Submitted That Met QC Criteria: August 25, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Metabolic syndrome; Hepatic fibrosis; Chronic hepatitis B; Hepatic steatosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Fatty Liver; Hepatitis B, Chronic; Hepatitis, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: Guven Health Group Faraday

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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