Chronic Hepatitis B, Safety Issues, Transplant Recipient
Conditions
Keywords
renal function, hepatitis, patient adherence
Brief summary
tenofovir alafenamide (TAF) has been approved to be highly effective and safe in patients with chronic hepatitis B (CHB), therefore TAF may be a good option in kidney or liver transplant patients with chronic HBV infection. The aim of this prospective cohort study is to assess the safety, efficacy, and drug adherence improvement of TAF switching therapy in kidney or liver transplant patients with HBV infection.
Detailed description
Life-long nucleos(t)ide analogue (NA) therapy has been recommended in patients with chronic HBV infection after organ transplantation, therefore the safety of long-term NA therapy is particularly important in transplant patients. Entecavir, tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are recommended drugs for CHB patients in current guidelines because of their high potency in antiviral efficacy and low rate in virological resistance. However, the data of TAF therapy in transplant patients remain limited. The potential nephrotoxicity and a decrease in bone mineral density (BMD) of TDF therapy have been reported in previous studies. TAF is a novel prodrug of tenofovir and is formulated to deliver the active metabolite to target cells more efficiently than TDF at a much lower dose, thereby reducing systemic exposure to tenofovir. In the randomized controlled trials of TDF versus TAF showed that virological and serological results were similar in both arms. However, patients in TAF arm had improved renal effects and BMD as compared to TDF. Improvement in renal function and BMD were also found in chronic hepatitis B patients who switched from TDF to TAF. Furthermore, in some retrospective studies, switching from entecavir to TAF may present a superior efficacy in HBV DNA suppression and HBsAg level reduction, and renal safety was comparable between the TAF switch group and the entecavir continuation group. Interestingly, switching from entecavir to TAF is associated with improvement of the medication adherence, which may be particularly important to patients under long-term NA therapy. The clinical data of TAF therapy in transplant patients remain very limited, particularly in kidney transplant patients. With a high virological response rate and a low adverse effect (AE) rate in patients with CHB, TAF may be a good option for patients underwent liver or kidney transplantation.The aim of this study is to assess the safety, drug adherence, and efficacy of TAF switching therapy in kidney or liver or transplant patients with chronic HBV infection.
Interventions
To assess the safety, efficacy, and drug adherence improvement of TAF switching therapy in kidney or liver transplant patients with HBV infection.
Sponsors
Taichung Veterans General Hospital
Institute of Adherence to Medication
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. At least 20 years of age 2. Chronic HBV infection under NA therapy other than TAF 3. Underwent kidney and/ or liver transplantation 4. Without clinical or pathologic evidence of moderate or severe rejection 5. Patients who are indicated for TAF switching therapy, such as concerns in virological response, biochemical response, drug compliance, or safety issues to other NAs.
Exclusion criteria
1. End stage renal disease (eGFR \< 15 mL/min/1.73m2) 2. Co-infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV) 3. Any active malignancies 4. Pregnant or breast-feeding women 5. Known allergy to tenofovir-contained regimens
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Estimated glomerular filtration rate | week 48 | 0-120 ml/min/1.73m2 (higher scores mean a better outcome) |
| HBV viral load | week 48 | 0-8 log10 IU/mL; blood HBV DNA level (higher scores mean a worse outcome) |
| Drug adherence score | week 48 (higher scores mean a better outcome) | Score 1-8; Morisky Medication Adherence Scale-8 questionnaire |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimated glomerular filtration rate | week 144 | 0-120 ml/min/1.73m2 (higher scores mean a better outcome) |
| HBV viral load | week 144 | 0-8 log10 IU/mL; blood HBV DNA level (higher scores mean a worse outcome) |
| Drug adherence score | week 144 (higher scores mean a better outcome) | Score 1-8; Morisky Medication Adherence Scale-8 questionnaire |
| Bone mineral density | week 144 | 0-5 g/cm2; dual-energy X-ray absorptiometry (higher scores mean a better outcome) |
| Alanine aminotransferase | week 144 | 0-150000 IU/mL; blood ALT level (higher scores mean a worse outcome) |
| Quantitative HBsAg | week 144 | 0-10000 IU/mL; blood qHBsAg level (higher scores mean a worse outcome) |
| Liver fibrosis elastography | week 144 | 0-30 kPa; ultrasound elastography (higher scores mean a worse outcome) |
Countries
Taiwan
Contacts
PRINCIPAL_INVESTIGATORTeng-Yu Lee, MD, PhD
Taichung Veterans General Hospital
Outcome results
None listed