Renoprotective Effects of Telbivudine in Chronic Hepatitis B

Background

Both CHB and chronic kidney disease are major health issue affecting millions of persons worldwide. Based on a large European multicenter database, the Virgil-database, it is estimated that 15% and 4% of the CHB patients in Europe had mild (GFR 50-80ml/min) and moderate (GFR <50ml/min) renal impairment respectively . These group of patients require special attention as the nucleos(t)ides agents (NA) used in the treatment of CHB are cleared by kidneys and may worsen the kidney function. Recently, a subgroup analysis of the GLOBE study and 4 small prospective studies provide circumstantial evidence on the use of telbivudine (LDT) that can improve renal function in CHB patients. However, there are no prospective, controlled trials to date to evaluate the relationship between LDT and renal function.

Research plan and methodology

This is a prospective study in CHB patients treated with NA and pre-existing mild to moderate renal impairment defined as estimated GFR (eGFR) 30-90ml/min.

Aims

To compare the renal function of patients before and after switching lamivudine to telbivudine.

To determine any adverse events from switching other NA to telbivudine To determine any biochemical and virological change from switching other NA to telbivudine by checking ALT, HBV DNA at baseline, and at weeks 12, 24, 36, 48, 60, 72, 84, 96 and 108 weeks To determine any change in 24 hour urinary protein and urinary glucose level To determine the in vitro effects of telbivudine on renal tubular cells

• Telbivudine (Drug), also known as lamivudine is switched to telbivudine: CHB patients who are receiving adefovir or tenofovir disoproxil fumarate are recruited. At the time of recruitment (0 month, baseline), lamivudine is switched to telbivudine while adefovir or tenofovir disoproxil fumarate was continued. The patients are followed-up for 24 months.

Primary outcomes

• Renal function change [108 weeks]: Describe the change in renal function after 108 weeks of telbivudine switch

Secondary outcomes

• Virologic suppression [108 weeks]: Rate of virologic suppression
• Adverse events [108 weeks]: Rate of adverse events

Sex: All, ages: 18 Years to 70 Years

Inclusion Criteria:

1. Age 18 - 70 years
2. Documented HBsAg positivity for at least 6 months. Patients can be either HBeAg positive AND HBV DNA < 9 log10 copies/mL or HBeAg negative AND HBV DNA < 7 log10 copies/mL
3. On combination therapy (lamivudine and tenofovir or lamivudine and adefovir) for at least 1 year
4. Documented serum creatinine at least in 2 separate occasions in the last 1 year before recruitment
5. MDRD eGFR 30-89ml/min at baseline

Exclusion Criteria:

1. Concomitant liver disease including chronic hepatitis C and/or D infection, Wilson's disease, autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis
2. Significant alcohol intake or drug abuse
3. Pregnant subjects
4. Patients with co-existing significant chronic kidney disease (e.g.post renal transplantation etc.)
5. Allergic to any of the medications involved in the study

• Results publication: Mak LY, Liu SH, Yap DY, Seto WK, Wong DK, Fung J, Chan TM, Lai CL, Yuen MF. In Vitro and In Vivo Renoprotective Effects of Telbivudine in Chronic Hepatitis B Patients Receiving Nucleotide Analogue. Dig Dis Sci. 2019 Dec;64(12):3630-3641. doi: 10.1007/s10620-019-05717-0. Epub 2019 Jul 6. PMID 31280390

• Man-Fung Yuen, DSc, MD, PhD, Principal investigator, The University of Hong Kong