Can tenofovir affect liver function?

Tenofovir's Effects on Liver Function

Tenofovir can affect liver function, primarily through potential hepatotoxicity in patients with pre-existing liver disease, though it is generally considered to have a favorable hepatic safety profile compared to other antivirals. 1

Liver Effects of Tenofovir

Tenofovir is available in two formulations:

• Tenofovir disoproxil fumarate (TDF)
• Tenofovir alafenamide (TAF) - a newer formulation with improved safety profile

Direct Hepatic Effects

• Tenofovir is primarily eliminated by renal excretion and is not significantly metabolized by liver enzymes 2
• No dosage adjustment is necessary in patients with mild hepatic impairment 3
• Drug concentrations are comparable in patients with varying degrees of hepatic impairment 1

Specific Liver-Related Considerations

1. Hepatitis B Treatment:

   • Tenofovir is a first-line treatment for chronic hepatitis B virus (HBV) infection 1
   • It can actually improve liver function in patients with HBV by suppressing viral replication 4
   • In patients with decompensated cirrhosis due to HBV, tenofovir can stabilize and potentially improve liver function 1

2. Severe Acute Exacerbation of Hepatitis B:

   • Discontinuation of tenofovir in HBV-infected patients can lead to severe acute exacerbations of hepatitis B, potentially causing liver decompensation and liver failure 5
   • Close monitoring is required when stopping tenofovir in HBV patients

3. Drug Interactions:

   • Concomitant use of tenofovir with certain medications for hepatitis C treatment may require caution due to potential drug-drug interactions 1
   • Protease inhibitor-containing DAA regimens for hepatitis C virus with lopinavir-ritonavir is contraindicated 1

Monitoring Recommendations

For patients on tenofovir therapy:

• Regular liver function tests should be performed in all hospitalized patients with COVID-19 on tenofovir 1
• Monitoring frequency: Reasonable to monitor liver tests twice weekly in patients on potentially hepatotoxic medication including tenofovir 1
• Dose adjustment: No dose adjustment is required for tenofovir in patients with mild to moderate hepatic impairment 1
• Discontinuation criteria: Consider discontinuing tenofovir in cases of moderate-to-severe liver injury 1

Special Populations

Patients with Cirrhosis

• Tenofovir is preferred (along with entecavir) for treatment of HBV in patients with compensated and decompensated cirrhosis due to its potency and minimal risk of resistance 1
• In decompensated cirrhosis, tenofovir has been shown to be effective and generally safe 1
• Lactic acidosis has been reported in some patients with advanced decompensated cirrhosis (particularly with entecavir), requiring close monitoring 1

Patients with HIV-HBV Coinfection

• In HIV-HBV coinfected patients, tenofovir is often part of the recommended regimen 1
• When used with certain antiretrovirals (ritonavir or cobicistat), tenofovir concentrations may increase, requiring careful monitoring 1

Clinical Pitfalls and Precautions

1. Renal-Hepatic Connection:

   • The primary concern with tenofovir is renal toxicity, which can indirectly affect liver function through altered drug metabolism 6
   • Patients with both liver and kidney dysfunction require especially careful monitoring

2. Switching Considerations:

   • When switching from TDF to TAF in patients with liver disease, monitor for potential increases in lipid levels 1
   • Concomitant use of tenofovir disoproxil fumarate with lopinavir-ritonavir is relatively contraindicated as drug concentration of tenofovir might be increased 1

3. Discontinuation Risk:

   • Never abruptly discontinue tenofovir in HBV patients due to risk of severe hepatitis flares 5
   • If discontinuation is necessary, closely monitor liver function for at least several months 5

In conclusion, while tenofovir is generally well-tolerated from a hepatic perspective and is actually beneficial for liver function in HBV patients, regular monitoring of liver function is recommended, especially in patients with pre-existing liver disease or those taking other potentially hepatotoxic medications.