## Protocol Section
### Identification Module
**NCT ID:** NCT05956379

**Brief Title:** Chronic Hepatitis B Patients With Concurrent MAFLD: Cohort Study and Exercise Intervention.

**Official Title:** Chronic Hepatitis B Patients With Concurrent MAFLD: Cohort Study and Exercise Intervention.

#### Organization Study ID Info
**ID:** 202212084RINC
#### Organization
**Class:** OTHER
**Full Name:** National Taiwan University Hospital
### Status Module
#### Completion Date
**Date:** 2027-07-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-07-21

**Type:** ACTUAL

**Last Update Submit Date:** 2023-07-13

**Overall Status:** ENROLLING_BY_INVITATION

#### Primary Completion Date
**Date:** 2027-07-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2023-08-01

**Type:** ESTIMATED

**Status Verified Date:** 2023-06

#### Study First Post Date
**Date:** 2023-07-21
**Type:** ACTUAL
**Study First Submit Date:** 2023-06-13
**Study First Submit QC Date:** 2023-07-13
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** National Taiwan University Hospital

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** In Taiwan, HBV infection is endemic in the adult population. With the westernization of eating habit and lifestyle, metabolic syndrome and related non-alcoholic fatty liver diseases (NAFLD, newly proposed as metabolic dysfunction associated fatty liver diseases, MAFLD) has become another important health issue. It is therefore common to encounter subjects with concurrent MAFLD and HBV infection in HBV endemic countries. This project will study the clinical data of patients with concurrent MAFLD and HBV, and aim to explore the impact of exercise intervention on the hepatic fatty infiltration, alteration of gut microbiota and HBV replication status in this group of patients. The research strategies will include (1) improving fatty liver and metabolic syndrome in subjects with concurrent MAFLD and HBV; and (2) exploring the changes of HBV replication and intestinal microflora in patients with concurrent HBV and MAFLD after exercise intervention.

**Detailed Description:** The investigators will first collect and analyze clinical data of patients with concurrent MAFLD and HBV in a retrospective cohort in NTUH. The investigators aim to clarify the interactions of MAFLD and HBV based on different HBV-related liver disease stage and different metabolic derangement.

Second, using the well-established platform for the detection and staging of fatty liver at NTUH, the investigators plan to enroll 100 patients with concurrent HBV and MAFLD. The investigators will collect all basic information including intrahepatic fat and fibrosis severity, and randomize them to the exercise intervention group (n = 50) and the observation group (n = 50) after conditional screening. After 6-month of exercise intervention, the investigators will analyze the effect of exercise on intrahepatic fat (main parameter: 10% reduction in intrahepatic fat; 30% achieved in the exercise intervention group; 5% achieved in the control group) and analyze the influence of co-existing HBV on the change of hepatic steatosis.

Description of the prospective randomized exercise intervention studies

1. Enrolment of 100 patients with concurrent chronic HBV infection and MAFLD
2. Collection of baseline data: Clinical parameters, virologic parameters, metabolic and MAFLD parameters, nutritional and exercise fitness data, and liver steatosis/fibrosis data
3. Randomization: Randomization into exercise (Group I) versus non-exercise group (Group II) will be conducted with the help of random number table.
4. 24-week exercise intervention
5. 12-week post-exercise follow-up period
6. Collection of final data, statistical analyses and paper preparation

II-1: Enrolment of subjects:

Patients from NTUH with the diagnosis of chronic HBV infection will be screened for the presence of MAFLD at the out-patient clinics. Treatment naïve patients found to have co-existing MAFLD and willing to join the active exercise program will be invited to join the study by the clinical physicians after thorough evaluation. Patients with age less than 18 years, concurrent HCV or HIV co-infection will be excluded.

CHB patients fulfilling reimbursement criteria for the treatment of HBAg-positive or -negative CHB, or advanced fibrosis/cirrhosis will not be enrolled since the virologic profiles under NUC therapy would not likely to be affected by the change of hepatic steatosis through exercise intervention.

Assessment of HBV replication status and liver disease severity: The clinical phenotype of HBV infection will be determined by liver function test (serum ALT level) and platelet count number, abdominal ultrasonography, FibroScan™, along with serum HBeAg and HBV DNA level. At enrolment, the patients will be categorized into HBeAg positive chronic HBV infection (immune tolerance phase), HBeAg positive chronic hepatitis B (immune clearance phase), HBeAg negative chronic HBV infection (low replication phase), and HBeAg negative chronic hepatitis B (reactivation phase). The stage of liver fibrosis will determined by FIB-4, FibroScan™and MR elastography (MRE).

Diagnosis and assessment of MAFLD: The diagnosis of MAFLD will be made if the patient has evidence of hepatic steatosis by both abdominal ultrasonography and FibroScan™, along with one of the three criteria, namely overweight/obesity, presence of type 2 diabetes mellitus (DM), and at least two metabolic risk abnormalities. Then the degree of hepatic steatosis and fibrosis will be semi-quantitatively assessed by FibroScan™. In this proposal, the investigators will for the first time adopt MR PDFF and MR elastography (MRE) to accurately assess the degree of steatosis and the stage of fibrosis in each enrolled subject before and after the intervention.

### Conditions Module

**Conditions:**

- Chronic Hepatitis B

- Non-alcoholic Fatty Liver Disease

**Keywords:**

- Metabolic syndrome

- Exercise intervention

- Fatty liver

- Chronic Hepatitis B

- Gut microbiota

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 100

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Physical therapists will provide personalized aerobic exercise program prescriptions in the preparatory period based on the results of exercise-related assessments, and the training intensity is based on the results of the maximum exercise test, with moderate intensity for 24 weeks, \>=3 cardio workouts per week.

**Intervention Names:**

- Other: exercise

**Label:** Exercise group

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** No change in exercise habits and maintaining baseline physical activity.

**Label:** Control group

**Type:** NO_INTERVENTION

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Exercise group

**Description:** Physical therapists will provide personalized aerobic exercise program prescriptions in the preparatory period based on the results of exercise-related assessments, and the training intensity is based on the results of the maximum exercise test, with moderate intensity for 24 weeks, \>=3 cardio workouts per week. The form of aerobic exercise can be carried out in the form of treadmill walking, walking, jogging, cycling, aerobic dance, ball games, swimming, rope skipping, stepping exercises, etc. When the exercise reaches the target intensity, we will adjust the training intensity process according to personal ability. The physical therapist will again adjust the content of the aerobic exercise program at week 12 based on the reassessment of the exercise capacity.

**Name:** exercise

**Type:** OTHER

### Outcomes Module

#### Other Outcomes

**Description:** 1. Dynamics of HBV profiles after exercise
2. Impact of diminishing hepatic steatosis on the evolution of liver fibrosis
3. Impact of diminishing hepatic steatosis on the profiles of HBV replication

**Measure:** Exploratory outcomes

**Time Frame:** 24 weeks

#### Primary Outcomes

**Description:** We will measure change of hepatic steatosis at week 24 in comparison to baseline steatosis by MRI-PDFF. Reduction of hepatic steatosis by \>=10% will be defined as responder.

**Measure:** Change of hepatic steatosis after 6-month exercise intervention by MRI-PDFF

**Time Frame:** 24 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Age \>18 years of age
* Either gender
* HBV treatment naïve
* Capable of taking exercise
* HBsAg positivity for \>6 months
* Evidence of fatty liver in both abdominal ultrasonography and Fibroscan™(CAP\>215)

Exclusion Criteria:

* Age \>70 years of age
* Evidence of liver cirrhosis
* Patients fulfilling reimbursement criteria for HBV treatment
* Evidence of severe cardiopulmonary diseases
* Evidence of serious hip or knee problems, incapable of taking exercise
* Evidence of liver decompensation
* Evidence of active HCV (positive for serum HCV RNA) or HIV infection (positive for anti-HCV)
* Clinical diagnosis of Alzheimer's Disease
* Thyroid disease

**Maximum Age:** 70 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Taipei

**Country:** Taiwan

**Facility:** National Taiwan University Hospital

**State:** Zhongzheng Dist.

**Zip:** 100229

#### Overall Officials

**Official 1:**

**Affiliation:** National Taiwan University Hospital

**Name:** Chun-Jen Liu, Professor

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000006525

- Term: Hepatitis, Viral, Human

- ID: D000014777

- Term: Virus Diseases

- ID: D000007239

- Term: Infections

- ID: D000004769

- Term: Enterovirus Infections

- ID: D000010850

- Term: Picornaviridae Infections

- ID: D000012327

- Term: RNA Virus Infections

- ID: D000086982

- Term: Blood-Borne Infections

- ID: D000003141

- Term: Communicable Diseases

- ID: D000018347

- Term: Hepadnaviridae Infections

- ID: D000004266

- Term: DNA Virus Infections

- ID: D000002908

- Term: Chronic Disease

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC01

- Name: Infections

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M9592

- Name: Hepatitis A

- Relevance: HIGH

- As Found: Hepatitis

- ID: M9595

- Name: Hepatitis B

- Relevance: HIGH

- As Found: Hepatitis B

- ID: M21609

- Name: Hepatitis B, Chronic

- Relevance: HIGH

- As Found: Chronic Hepatitis B

- ID: M9591

- Name: Hepatitis

- Relevance: HIGH

- As Found: Hepatitis

- ID: M9607

- Name: Hepatitis, Chronic

- Relevance: HIGH

- As Found: Chronic Hepatitis

- ID: M11107

- Name: Liver Diseases

- Relevance: HIGH

- As Found: Liver Disease

- ID: M23005

- Name: Metabolic Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M8375

- Name: Fatty Liver

- Relevance: HIGH

- As Found: Fatty Liver

- ID: M30540

- Name: Non-alcoholic Fatty Liver Disease

- Relevance: HIGH

- As Found: Non-alcoholic Fatty Liver Disease

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9610

- Name: Hepatitis, Viral, Human

- Relevance: LOW

- As Found: Unknown

- ID: M17522

- Name: Virus Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10283

- Name: Infections

- Relevance: LOW

- As Found: Unknown

- ID: M6368

- Name: Communicable Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7930

- Name: Enterovirus Infections

- Relevance: LOW

- As Found: Unknown

- ID: M13745

- Name: Picornaviridae Infections

- Relevance: LOW

- As Found: Unknown

- ID: M15149

- Name: RNA Virus Infections

- Relevance: LOW

- As Found: Unknown

- ID: M2593

- Name: Blood-Borne Infections

- Relevance: LOW

- As Found: Unknown

- ID: M20487

- Name: Hepadnaviridae Infections

- Relevance: LOW

- As Found: Unknown

- ID: M7442

- Name: DNA Virus Infections

- Relevance: LOW

- As Found: Unknown

- ID: M6147

- Name: Chronic Disease

- Relevance: LOW

- As Found: Unknown

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

- ID: T1303

- Name: Chronic Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

- ID: T5868

- Name: Visceral Steatosis

- Relevance: HIGH

- As Found: Fatty Liver

### Condition Browse Module - Meshes

- ID: D000006506

- Term: Hepatitis A

- ID: D000006509

- Term: Hepatitis B

- ID: D000019694

- Term: Hepatitis B, Chronic

- ID: D000006505

- Term: Hepatitis

- ID: D000006521

- Term: Hepatitis, Chronic

- ID: D000008107

- Term: Liver Diseases

- ID: D000005234

- Term: Fatty Liver

- ID: D000065626

- Term: Non-alcoholic Fatty Liver Disease

### Intervention Browse Module - Browse Branches

- Abbrev: Hemat

- Name: Hematinics

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M11110

- Name: Liver Extracts

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
