Effects of Empagliflozin on Fibrosis and Cirrhosis in Chronic Hepatitis B
Status:
Not yet recruiting
Trial end date:
2025-12-31
Target enrollment:
Participant gender:
Summary
Chronic hepatitis B (CHB) affects 257million individuals worldwide. In 2017, it caused around
39.7 million cases of cirrhosis and 0.4 million cirrhosis-related deaths in 2017. However,
there is no specific treatment for liver fibrosis/cirrhosis. Although nucleos(t)ide analogues
(NAs) profoundly suppress viral replication, fibrosis/cirrhosis progression can still occur
in NA-treated patients.
Sodium-glucose cotransporter type-2 (SGLT2) inhibitors are antidiabetic drugs that may
prevent fibrosis/cirrhosis progression by reducing hepatic steatosis/inflammation, dampening
renin-angiotensin aldosterone system (RAAS) activation, and reducing fluid retention, effects
of which are independent of glycemic control. Clinical studies in diabetic patients show
SGLT2 inhibitors reduce hepatis steatosis/inflammation, regress ascites (a cirrhotic
complication), and improve liver function parameters and survival prognosis in terms of model
for end-stage liver disease (MELD) score. There are currently no randomized controlled trials
(RCTs) on role of SGLT2 inhibitors in preventing fibrosis/cirrhosis progression in CHB
patients. Magnetic resonance elastography (MRE) and transient elastography (TE) are
non-invasive techniques for liver stiffness measurement (LSM), although MRE is more accurate
than TE.
The investigators propose a double-blind, randomized, placebo-controlled trial to compare
effect of empagliflozin (an SLGT2 inhibitor) with placebo (1:1 ratio) in preventing fibrosis
progression in both diabetic and non-diabetic NA-treated CHB patients with advanced
fibrosis/compensated cirrhosis. 228 patients will be randomly sampled from our pre-existing
TE database. Empagliflozin 10mg daily will be given to treatment arm. Placebo pills will be
manufactured identical in appearance to empagliflozin. Subjects will receive active or
placebo pills for three years, and undergo clinical, anthropometric and laboratory
assessments (at baseline, weeks 8, 16, and every 4 months thereafter). They will undergo LSM
by TE at baseline, end of first, second and third year, and by MRE at baseline and end of
third year. Primary outcome is difference in change to liver stiffness (measured by MRE) from
baseline between the two groups at the end of third year.
The study results will determine whether SGLT2 inhibitors can prevent hepatic
fibrosis/cirrhosis progression in NA-treated CHB patients.