Can anesthetic medications and diarrheal viruses cause liver enzyme elevations?

Can Anesthetic Medications and Diarrheal Viruses Cause Liver Enzyme Elevations?

Yes, both anesthetic medications and certain diarrheal viruses can cause liver enzyme elevations, with volatile anesthetics causing hepatotoxicity in approximately 4-12% of exposed patients and COVID-19 (which presents with diarrhea in many cases) causing elevated liver enzymes in a substantial proportion of infected individuals.

Anesthetic Medications and Liver Enzyme Elevations

Volatile Anesthetic Agents

Volatile anesthetics including isoflurane, sevoflurane, and desflurane cause clinically significant drug-induced liver injury in approximately 4.1% of patients, with abnormal liver biochemistry occurring in up to 51% of exposed patients. 1

• Modern volatile anesthetics (sevoflurane, desflurane) cause liver enzyme elevations as frequently as older agents like halothane, with an incidence of drug-induced liver injury around 3-4% 2, 1
• Among patients who develop abnormal liver biochemistry after volatile anesthetics, approximately 26% have peak alanine aminotransferase (ALT) levels greater than 200 U/L, indicating moderate to severe injury 2
• Isoflurane specifically has been documented to cause recurrent transient increases in liver enzymes (GOT: 292-328 IU/L, GPT: 264-341 IU/L) in susceptible patients 3

Severity Spectrum and Clinical Manifestations

The hepatotoxicity from volatile anesthetics ranges from mild asymptomatic enzyme elevations to fatal hepatic necrosis 4:

• Mild cases: Asymptomatic ALT elevations (1-3× upper limit of normal)
• Moderate cases: ALT 3-5× upper limit of normal (occurs in approximately 4 of 15 cases with likely volatile anesthetic-induced liver injury) 1
• Severe cases: ALT >5× upper limit of normal, potentially progressing to hepatic necrosis and failure 4

Contraindications and Risk Factors

Isoflurane and other halogenated anesthetics are contraindicated in patients with 4:

• History of confirmed hepatitis due to halogenated inhalational anesthetics
• History of unexplained moderate to severe hepatic dysfunction (jaundice with fever and/or eosinophilia) after previous halogenated anesthetic exposure
• Known sensitivity to halogenated agents

Repeated anesthetics within a short period may result in increased or additive hepatotoxic effects, particularly in patients with underlying hepatic conditions or those taking hepatotoxic drugs. 4

Mechanism and Prevention

• Volatile anesthetics undergo hepatic metabolism via microsomal enzyme systems, which can be induced by repeated drug administration 5
• Hypoxia increases anaerobic metabolism of halothane and produces free radicals that contribute to hepatic injury 5
• To prevent hepatic dysfunction, avoid hypoxia during anesthesia and minimize repeated administration of enzyme-inducing drugs 5

Ketamine-Specific Considerations

Ketamine infusions can cause substantial liver enzyme elevations within 2 days of initiation 6:

• Liver enzyme elevations can occur even 7 months after the last infusion
• Close monitoring of liver enzymes every 1-2 days during ketamine infusions is recommended 6
• Although enzymes typically normalize within weeks, long-term consequences remain unclear 6

Diarrheal Viruses and Liver Enzyme Elevations

COVID-19 (SARS-CoV-2)

COVID-19, which commonly presents with gastrointestinal symptoms including diarrhea, causes elevated liver enzymes in a significant proportion of patients. 7

The American Gastroenterological Association reports that COVID-19 patients frequently develop hepatotoxicity 7:

• Gastrointestinal symptoms including diarrhea are common manifestations of COVID-19
• Liver enzyme elevations occur as part of the systemic inflammatory response
• The pattern typically shows hepatocellular injury with elevated aminotransferases

Treatment-Related Hepatotoxicity in COVID-19

Medications used to treat COVID-19 and other viral infections causing diarrhea can compound liver injury 7:

Remdesivir:

• 23% of patients (12 of 53) experienced elevated hepatic enzymes in compassionate use studies 7
• 8% discontinued treatment due to elevated aminotransferases 7
• 9% experienced diarrhea as an adverse effect 7

Lopinavir/ritonavir:

• Moderate-to-severe aminotransferase elevations (>5× upper limit of normal) occur in 3-10% of patients 7
• Diarrhea occurs in 10-30% of patients receiving this combination 7
• Hepatotoxicity severity ranges from mild enzyme elevations to acute liver failure 7

Chloroquine/Hydroxychloroquine:

• Rarely linked to aminotransferase elevations or clinically apparent liver injury 7
• Can trigger hypersensitivity attacks with fever and serum aminotransferase elevations in patients with porphyria 7
• Concentrates in the liver, requiring caution in patients with hepatitis or hepatic disease 7

Clinical Monitoring Recommendations

For Anesthetic-Related Hepatotoxicity

Monitor liver function tests (ALT, AST, alkaline phosphatase, bilirubin) in the following scenarios:

• Patients with known hepatic disease or taking hepatotoxic medications 4
• When repeated volatile anesthetic exposure occurs within a short timeframe 4
• Post-operatively in high-risk patients (trauma patients, those with prolonged anesthesia exposure) 2, 1

For Drug-Induced Liver Injury During Treatment

The threshold-based approach for monitoring varies by baseline liver function 7:

Patients with normal baseline liver tests:

• ALT >3× upper limit of normal: Increase monitoring frequency
• ALT >5× upper limit of normal: Consider drug interruption
• ALT >8-10× upper limit of normal: Strong consideration for discontinuation

Patients with abnormal baseline liver tests:

• Use multiples of baseline rather than upper limit of normal 7
• ALP >2× baseline without alternative explanation: Implement accelerated monitoring 8
• ALP >3× baseline: Consider drug interruption unless another etiology confirmed 8

Important Caveats

• The absence of symptoms does not exclude significant liver injury; many cases of volatile anesthetic hepatotoxicity are asymptomatic 2, 3
• No reliable predictors of volatile anesthetic drug-induced liver injury have been identified, making universal screening impractical 2, 1
• Patients who develop liver enzyme elevations after volatile anesthetics may be at risk for severe acute liver injury with subsequent re-exposure 1
• Drug-induced liver injury can progress to acute liver failure despite initial mild presentation 6
• Gilbert's syndrome (affecting 5-10% of the population) can cause indirect hyperbilirubinemia that may be mistaken for drug-induced liver injury 7, 9