From the Guidelines
Chloroquine-induced liver dysfunction is a rare but serious adverse effect that requires careful monitoring and management, and patients taking chloroquine should have baseline liver function tests performed before starting therapy and monitored periodically during treatment, especially in the first few months when most hepatotoxicity occurs, as recommended by the Asia-Pacific position statement 1.
Risks of Chloroquine-Induced Liver Dysfunction
The risk factors for chloroquine-induced liver dysfunction include pre-existing liver disease, alcohol use, concomitant hepatotoxic medications, and higher cumulative doses. Chloroquine hepatotoxicity typically presents as asymptomatic transaminase elevations but can progress to acute hepatitis with symptoms like fatigue, nausea, abdominal pain, jaundice, or even fulminant liver failure in severe cases.
Management of Chloroquine-Induced Liver Dysfunction
Management involves immediate discontinuation of chloroquine upon detection of significant liver dysfunction (typically ALT/AST >3 times upper limit of normal with symptoms or >5 times without symptoms) 1. No specific antidote exists, so treatment is supportive with close monitoring of liver function until normalization. Most cases resolve within weeks to months after drug discontinuation. For patients requiring antimalarial therapy after experiencing chloroquine-induced liver injury, alternative medications with different metabolic pathways should be considered, though cross-reactivity with hydroxychloroquine may occur.
Monitoring and Prevention
Patients with abnormal liver function should be closely monitored when using off-label lopinavir–ritonavir, chloroquine, hydroxychloroquine, and tocilizumab, preferably monitored in the setting of clinical trials 1. The optimal interval for liver tests is uncertain; however, it would be reasonable to monitor liver tests twice weekly in patients on potentially hepatotoxic medication, patients with pre-existing liver disease, and more frequently in any patients with abnormal liver function 1.
Key Recommendations
- Patients with COVID-19 and persistent liver derangement should have standard investigations for liver diseases 1.
- Off-label treatment for COVID-19 should be withheld in the case of moderate-to-severe liver injury 1.
- Clinicians should test liver function in hospitalized patients with COVID-19 1.
- The concomitant use of tenofovir disoproxil fumarate or tenofovir alafenamide with lopinavir–ritonavir is relatively contraindicated 1.
From the FDA Drug Label
Hepatotoxicity Associated with Porphyria Cutanea Tarda Cases of hepatotoxicity have been reported when chloroquine was used in patients with porphyria cutanea tarda (PCT). Patients received dosages up to 500 mg per day Most of the PCT-related cases presented with marked elevations in transaminases (> 20 times the upper limit of the reference range) within days to a month of chloroquine initiation. Measure liver tests promptly in patients who report symptoms that may indicate liver injury, such as fatigue, rash, nausea, dark urine, or jaundice In this clinical context, if the patient is found to have abnormal serum liver tests, interrupt chloroquine treatment and investigate further to establish the probable cause. Gastrointestinal disorders: Hepatitis, increased liver enzymes, anorexia, nausea, vomiting, diarrhea, abdominal cramps
The risks of chloroquine-induced liver dysfunction include:
- Hepatotoxicity
- Increased liver enzymes
- Hepatitis The management of chloroquine-induced liver dysfunction includes:
- Measuring liver tests promptly in patients who report symptoms that may indicate liver injury
- Interrupting chloroquine treatment if the patient is found to have abnormal serum liver tests
- Investigating further to establish the probable cause of liver injury 2 2 also reports hepatitis and increased liver enzymes as potential adverse reactions.
From the Research
Risks of Chloroquine-Induced Liver Dysfunction
- Chloroquine has been associated with hepatotoxicity, as reported in a case study where a fixed combination of chloroquine and proguanil caused liver injury 3.
- The pathophysiological mechanism of chloroquine-induced liver dysfunction is unclear, but it may be related to an allergic reaction 3.
- Elevated liver enzymes are a major concern in patients taking chloroquine, and should be well investigated 4.
- Chloroquine has been shown to cause toxic hepatitis in some patients, which can rapidly return to normal after cessation of the medication 4.
Management of Chloroquine-Induced Liver Dysfunction
- Cessation of chloroquine is recommended in cases of suspected liver injury 4.
- Alternative medications, such as mycophenolate mofetil, may be administered after cessation of chloroquine 4.
- Coenzyme Q10 (CoQ10) has been shown to protect against liver injury induced by other drugs, such as acetaminophen, by enhancing mitophagy 5.
- However, the use of CoQ10 in the management of chloroquine-induced liver dysfunction has not been specifically studied.
- Ursodeoxycholic acid (UDCA) has been shown to reduce liver injury associated with complete biliary obstruction, but its use in chloroquine-induced liver dysfunction is not established 6.