Chronic Kidney Disease Progression in Chronic Hepatitis B Patients on Tenofovir Alafenamide (TAF) Versus Entecavir

Study Overview
=================
Brief Summary
-----------------
Tenofovir alafenamide (TAF), a novel prodrug of tenofovir (TFV), has been approved for the treatment of chronic hepatitis B virus (HBV) infection. TAF has been shown to be a potent inhibitor of HBV replication at a low dose, with high intracellular concentration and more than 90% lower systemic TFV concentration than tenofovir disoproxil fumarate (TDF). TAF has been approved in the clinical practice guidelines in the west. Since its availability in Asia in 2017, there have been evolving data concerning its positive impact on renal safety as shown in registration trials. The primary objective of this study is to compare the risk of chronic kidney disease (CKD) progression in chronic hepatitis B patients on TAF versus ETV in a territory-wide cohort in Hong Kong.

Detailed Description
-----------------
Antiviral therapy with nucleos(t)ide analogues (NAs) has revolutionized the management of chronic hepatitis B (CHB) in the last two decades.1 Entecavir (ETV), a nucleoside analogue, is one of the first-line NAs recommended by all international treatment guidelines.2-4 As hepatitis B surface antigen (HBsAg) seroclearance rarely occurs, most patients require long-term, if not life-long, NA therapy. Hence, the safety of NAs requires careful scrutiny. In clinical trials, nephrotoxicity may occur in a small proportion of patients receiving nucleotide analogues. We previously demonstrated that tenofovir disoproxil fumarate (TDF) was associated with mild renal impairment in a minority of patients; those treated with entecavir (ETV) had a similar risk compared to untreated patients.5 Tenofovir alafenamide (TAF), a novel prodrug of tenofovir (TFV), has been approved for the treatment of chronic hepatitis B virus (HBV) infection. TAF has been shown to be a potent inhibitor of HBV replication at a low dose, with high intracellular concentration and more than 90% lower systemic TFV concentration than tenofovir disoproxil fumarate (TDF). TAF has been approved in the clinical practice guidelines in the west. Since its availability in Asia in 2017, there have been evolving data concerning its positive impact on renal safety as shown in registration trials.

Official Title
-----------------
Chronic Kidney Disease Progression in Chronic Hepatitis B Patients on Tenofovir Alafenamide (TAF) Versus Entecavir

Conditions
-----------------
Chronic Hepatitis B

Intervention / Treatment
-----------------
* Drug: Tenofovir alafenamide
* Drug: Entecavir


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Positive hepatitis B surface antigen (HBsAg) or documented history of CHB for 6 months or more; AND On TAF 25 mg daily as antiviral treatment for CHB (cases); OR On ETV 0.5 to 1.0 mg daily as antiviral treatment for CHB (controls) Exclusion Criteria: Previous NA treatment prior to TAF or ETV Positive antibody against hepatitis C, D, or human immunodeficiency virus (anti-HCV, anti-HDV, or anti-HIV) Evidence of other autoimmune or metabolic liver diseases (except non-alcoholic fatty liver disease). Moribund state including advanced/pre-terminal liver cancer or other non-hepatic cancers Non-hepatic cancer undergoing chemotherapy within last 6 months

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| TAF-treated Chronic hepatitis B patients<br>Chronic hepatitis B patients that treated with Tenofovir alafenamide | Drug: Tenofovir alafenamide<br>* Chronic hepatitis B patients who are receiving TAF as antiviral therapy for CHB, who were previously treatment naïve.<br>|
| ETV-treated Chronic hepatitis B patients<br>Chronic hepatitis B patients that treated with Entecavir | Drug: Entecavir<br>* Chronic hepatitis B patients who are receiving ETV as antiviral therapy for CHB, who were previously treatment naïve.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CKD at 12 months | To evaluate chronic kidney disease (CKD) progression at 12 months. The CKD progression is defined as an increase in CKD stage for at least 1 stage for at least 3 consecutive months during follow-up. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in eGFR | calculated using the CKD Epidemiology Collaboration (CKD-EPI) equation expressed as a single equation: GFR (in mL/min/1.73 m2) = 141 × min (Scr /κ, 1)α × max(Scr /κ, 1)-1.209 × 0.993Age × 1.018 [for the cases of females] × 1.159 [for the cases of ethnic Africans ]; where: Scr is the serum creatinine in mg/dL (equals to serum creatinine in micromole/L /88.4) , κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr /κ or 1, and max indicates the maximum of Scr /κ or 1.11 CKD stages 1, 2, 3A, 3B, 4 and 5 were defined based on eGFR | 12 months |