Is it safe to use Glucagon-like peptide-1 (GLP-1) receptor agonists, such as liraglutide (Victoza) or semaglutide (Ozempic), in a patient with chronic Hepatitis B (HBV) and fatty liver disease?

GLP-1 Receptor Agonists in Patients with Fatty Liver Disease and Chronic Hepatitis B

GLP-1 receptor agonists are safe and beneficial for patients with chronic Hepatitis B and fatty liver disease, with no specific contraindications related to HBV infection and demonstrated efficacy in improving hepatic steatosis and fibrosis markers. 1, 2, 3

Safety Profile in Hepatic Impairment

GLP-1 receptor agonists demonstrate a favorable safety profile even in patients with liver disease:

• Liraglutide exposure is not increased by hepatic impairment—in fact, exposure tends to decrease with worsening liver function, eliminating concerns about drug accumulation in patients with compromised hepatic function 4
• No dose adjustment is required for patients with hepatic impairment, including those with mild, moderate, or severe liver dysfunction 5, 4
• The FDA label for liraglutide states it should be used with caution in patients with hepatic impairment due to limited clinical experience, but no specific contraindications exist for chronic viral hepatitis 5

Therapeutic Benefits for Fatty Liver Disease

GLP-1 receptor agonists provide multiple hepatic benefits that are particularly relevant for patients with concurrent fatty liver disease:

• Semaglutide achieved resolution of steatohepatitis in 59% of patients versus 17% with placebo (P < 0.001) in biopsy-proven NASH, and significantly slowed progression of liver fibrosis over 72 weeks 1
• Liraglutide improved liver histology and delayed progression of fibrosis in patients with biopsy-proven NASH, with more frequent resolution of NASH (9/23 versus 2/22; P=0.019) and less progression of fibrosis (2/23 versus 8/22; P=0.04) 1
• GLP-1 receptor agonists reduce hepatic steatosis, improve liver enzymes (AST, ALT), and decrease oxidative stress while improving hepatic de novo lipogenesis 1, 2, 3

Real-World Evidence in Patients with Liver Disease

Recent clinical data support the use of GLP-1 receptor agonists in patients with steatotic liver disease:

• Patients treated with GLP-1 receptor agonists had less evidence of liver fibrosis progression compared to no treatment, with FIB-4 scores decreasing to 1.77 in the GLP-1 RA group while increasing to 2.71 in controls (P = 0.045) 6
• A 48-week study suggested that GLP-1 receptor agonists may be safe in patients with NASH and compensated cirrhosis 1

Specific Considerations for Hepatitis B Patients

There are no specific contraindications or warnings against using GLP-1 receptor agonists in patients with chronic Hepatitis B infection. The key considerations are:

• Chronic HBV infection does not appear on any contraindication list for liraglutide, semaglutide, or other GLP-1 receptor agonists 7, 5
• The absolute contraindications remain limited to personal or family history of medullary thyroid carcinoma and multiple endocrine neoplasia syndrome type 2 (MEN2) 7, 8
• Patients with active gallbladder disease should use these medications with caution due to increased risk of cholecystitis 7

Practical Implementation

For a patient with chronic Hepatitis B and fatty liver disease:

• Start with standard dosing (liraglutide 0.6 mg daily or semaglutide 0.25 mg weekly) and titrate gradually to minimize gastrointestinal side effects 7, 8
• Monitor liver enzymes at baseline and periodically during treatment, though improvements in transaminases are expected rather than worsening 1, 2
• Prioritize semaglutide 2.4 mg weekly or tirzepatide 15 mg weekly if maximum weight loss and hepatic benefit are primary goals, as these achieve superior outcomes (14.9% and 20.9% weight loss respectively) 1, 8
• Use pioglitazone as an alternative if GLP-1 receptor agonists are not tolerated, as it also improves steatohepatitis and may improve fibrosis, though it causes weight gain 1

Important Caveats

• Rare cases of drug-induced liver injury (IDILI) have been reported with liraglutide, though causality is difficult to establish and such cases are extremely uncommon 9
• Insulin is the preferred glucose-lowering agent for patients with decompensated cirrhosis, given lack of robust evidence about safety of GLP-1 receptor agonists in this specific population 1
• Ensure adequate hydration as dehydration from gastrointestinal side effects could theoretically worsen renal function, which is already a concern in patients with chronic liver disease 5