Can Valium Cause Elevated ALT and AST?
Yes, Valium (diazepam) can cause elevated transaminases, though this is uncommon and typically mild. The FDA drug label explicitly lists "elevated transaminases and alkaline phosphatase" as a known adverse reaction, and recommends periodic liver function tests during long-term therapy 1.
Evidence from FDA Labeling and Clinical Studies
The FDA-approved prescribing information for diazepam specifically identifies elevated transaminases as a recognized adverse effect, occurring alongside other laboratory abnormalities 1.
The FDA label recommends periodic blood counts and liver function tests during long-term benzodiazepine therapy due to isolated reports of hepatotoxicity, though these events are rare 1.
A large study of 201 benzodiazepine mono-abusers taking an average of 307 mg diazepam-equivalents daily for 7 years found no significant drug-induced liver injury meeting clinical criteria (ALT or AST >5× upper limit of normal, or combined elevations) 2.
In the same study, none of the subjects showed significant alterations of liver enzymes, and the highest transaminase levels were associated with elevated body mass index rather than benzodiazepine use 2.
Clinical Significance and Monitoring
The risk of clinically significant hepatotoxicity from diazepam is very low, particularly compared to other medications that commonly cause liver injury 2.
When transaminase elevations do occur with benzodiazepines, they are typically mild (<3× upper limit of normal) and do not meet criteria for drug-induced liver injury 2.
Only 10% of chronic high-dose benzodiazepine users showed elevated gamma-glutamyl-transferase (GGT), with no alterations in alkaline phosphatase or bilirubin 2.
Important Differential Diagnoses to Consider
Before attributing elevated transaminases to diazepam, exclude more common causes:
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of elevated liver enzymes, affecting 20-30% of the general population, typically with AST:ALT ratio <1 3.
Alcohol use characteristically shows AST:ALT ratio >2:1, which is highly suggestive of alcoholic liver disease 3.
Muscle injury or recent intensive exercise can significantly elevate AST (and to a lesser extent ALT), confirmed by checking creatine kinase levels 3, 4.
Other medications are a more common cause of drug-induced liver injury than benzodiazepines, accounting for 8-11% of cases with mildly elevated liver enzymes 5.
Recommended Clinical Approach
If a patient on Valium presents with elevated transaminases:
Obtain a complete liver panel including AST, ALT, alkaline phosphatase, GGT, total and direct bilirubin, albumin, and PT/INR 5.
Check creatine kinase to exclude muscle injury as the source, particularly if AST is disproportionately elevated compared to ALT 3, 5.
Review all medications using the LiverTox® database for hepatotoxic potential, as other drugs are more likely culprits 5.
Assess for metabolic syndrome components (obesity, diabetes, hypertension) as NAFLD risk factors 5.
Obtain detailed alcohol consumption history, as this is a more common cause of transaminase elevation than benzodiazepines 3, 5.
Consider abdominal ultrasound if elevations persist, with sensitivity of 84.8% and specificity of 93.6% for detecting moderate to severe hepatic steatosis 5.
Key Clinical Pearls
ALT is more liver-specific than AST, which can be elevated from cardiac muscle, skeletal muscle, kidney, or red blood cell disorders 3, 5.
An AST:ALT ratio <1 suggests NAFLD, viral hepatitis, or medication-induced injury rather than alcoholic liver disease 3.
Normal albumin, bilirubin, and PT/INR indicate preserved liver synthetic function despite transaminase elevation 5.
Diazepam-related transaminase elevations, when they occur, are typically self-limited and do not progress to clinically significant liver injury 2.