Can Pre-Exposure Prophylaxis (PrEP) affect liver function?

Can PrEP Affect Liver Function?

Yes, PrEP can affect liver function, particularly causing mild to moderate elevations in liver transaminases (ALT/AST), especially in individuals with hepatitis B virus (HBV) infection or prior HBV exposure. 1

Hepatotoxicity Risk Profile

Transaminase Elevations

• Elevation in liver transaminase levels can occur when taking or after discontinuing antiretrovirals used for PrEP, with this being more common in persons with HBV or hepatitis C virus (HCV) infection. 1
• In clinical trials, the cumulative probability of grade 1+ ALT and AST toxicities was significantly higher among participants in the TDF-FTC arm compared to placebo (p = 0.03 for both). 2
• Women with good adherence to TDF-FTC had higher mean increases in AST levels from baseline to week 4 (2.90 units; p = 0.025) compared to those with less adherence. 2

Hepatitis B Co-infection: Critical Consideration

• For individuals with active HBV infection (detectable HBsAg), discontinuation of TDF/emtricitabine PrEP could lead to acute HBV flares or hepatic decompensation, particularly for patients with hepatic cirrhosis. 1
• Careful monitoring of HBV infection and liver function is recommended after discontinuation of TDF/emtricitabine (evidence rating: AIIa). 1
• The proportions of grade 1+ and grade 2+ ALT or AST toxicities were significantly higher in participants who were HBsAb-positive than in those who were HBsAb-negative, indicating that even prior HBV exposure increases hepatotoxicity risk. 2

Pre-Initiation Screening Requirements

Before starting PrEP, hepatitis B surface antigen (HBsAg) testing is mandatory to identify individuals at risk for hepatic complications. 1

Contraindications and Precautions

• Liver disease with cirrhosis might be a contraindication for certain ARV regimens or might require ARV dosage modifications in persons with Child-Pugh class B or C disease. 1
• Drug-induced liver injury is more common in patients with HCV/HIV co-infection. 1
• For persons with HBV/HCV co-infection or those on direct-acting antiviral (DAA) agents, consultation with clinicians knowledgeable in using ARV medications is encouraged, as DAAs can reactivate HBV. 1

Monitoring Protocol During PrEP

Baseline and Ongoing Monitoring

• HCV serologic testing should be performed at least annually and more frequently in the case of elevated transaminase levels or in high-risk individuals (e.g., people who inject drugs) (evidence rating: BIIa). 1
• For injectable cabotegravir PrEP, liver enzyme tests should be administered every 6 months (evidence rating: BIb). 1, 3
• Additional monitoring is required for exposed persons who have HBV infection, especially when stopping agents that are active in treatment for HBV infection. 1

Frequency Adjustments

• HCV antibody testing should be performed every 3-6 months for people who inject drugs and men who have sex with men who use recreational drugs at the time of sex if liver function test results are abnormal (evidence rating: BIIa). 1

Clinical Significance and Management

Severity and Reversibility

• Adverse events observed in clinical trials include nausea, elevated creatinine and liver enzymes, and decreased bone mineral density, but these can be minimized with clinician-guided monitoring. 4
• Both TDF-FTC and TAF-FTC regimens were well tolerated, with low numbers of participants reporting adverse events that led to discontinuation (1-2% discontinuation rates). 5

Special Population: HBV-Infected Individuals

• PrEP can be safely provided to individuals with HBV infection if there is no evidence of cirrhosis or substantial transaminase elevation. 6
• In a study of 12 participants with chronic HBV on PrEP, liver function tests remained within normal limits at post-stop visits except for a grade 1 elevation in 1 participant, with no evidence of hepatic flares. 6

Common Pitfalls to Avoid

• Do not initiate PrEP without baseline HBsAg testing, as unrecognized HBV infection significantly increases hepatotoxicity risk. 1
• Do not discontinue TDF/emtricitabine abruptly in patients with active HBV infection without close monitoring and transition planning, as this can precipitate hepatic decompensation. 1
• Do not use the "2-1-1" (on-demand) PrEP dosing regimen in patients with active HBV infection because of the risk of hepatitis flare and hepatic decompensation (evidence rating: BIIa). 1