PrEP-Associated Liver Function Alterations

Hepatotoxicity Risk Profile

The American College of Physicians and other guideline societies recommend careful monitoring of liver function in individuals with hepatitis B virus (HBV) infection or prior HBV exposure, as PrEP can cause mild to moderate elevations in liver transaminases (ALT/AST) 1, 2
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

The Centers for Disease Control and Prevention (CDC) recommends that hepatitis B surface antigen (HBsAg) testing is mandatory before starting PrEP to identify individuals at risk for hepatic complications 5, 2, 4

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, according to the CDC 1
Drug-induced liver injury is more common in patients with HCV/HIV co-infection, as reported by the CDC 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

The American Association for the Study of Liver Diseases (AASLD) recommends that 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) 5, 2, 4
For injectable cabotegravir PrEP, liver enzyme tests should be administered every 6 months (evidence rating: BIb), as recommended by the World Health Organization (WHO) 6
Additional monitoring is required for exposed persons who have HBV infection, especially when stopping agents that are active in treatment for HBV infection, according to the CDC 1

The CDC advises against initiating PrEP without baseline HBsAg testing, as unrecognized HBV infection significantly increases hepatotoxicity risk 5, 2
The American College of Physicians recommends against discontinuing TDF/emtricitabine abruptly in patients with active HBV infection without close monitoring and transition planning, as this can precipitate hepatic decompensation 2, 3
The WHO advises against using 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) 2, 3, 4