What labs should be monitored and how often for a patient with chronic hepatitis B infection on Tenofovir (Tenofovir disoproxil fumarate)?

Laboratory Monitoring for Chronic Hepatitis B on Tenofovir

For patients with chronic hepatitis B on tenofovir disoproxil fumarate, monitor HBV DNA and liver function tests (ALT, AST) every 3-6 months during treatment, along with baseline and periodic renal function monitoring (serum creatinine, estimated creatinine clearance, serum phosphorus, urine protein) every 6 months due to tenofovir's nephrotoxic potential. 1, 2, 3

Initial Baseline Assessment Before Starting Tenofovir

Before initiating tenofovir therapy, obtain the following baseline labs:

• Renal function panel: Serum creatinine, estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein 3
• Complete liver panel: ALT, AST, bilirubin, albumin, alkaline phosphatase 2
• Viral markers: HBV DNA (quantitative PCR), HBeAg, anti-HBe 1, 2, 4
• Complete blood count to assess for cytopenias 2
• Alpha-fetoprotein (AFP) for hepatocellular carcinoma surveillance in high-risk patients 2
• Coinfection screening: HIV, hepatitis C, hepatitis D antibodies 2, 4

The FDA label specifically emphasizes renal monitoring before treatment initiation, particularly in patients at risk for renal dysfunction 3.

During Treatment Monitoring Schedule

Virologic and Hepatic Monitoring

• HBV DNA (quantitative PCR): Every 3-6 months initially, then every 3-6 months after achieving virologic response 1, 2
• Liver function tests (ALT, AST): Every 3-6 months 1, 2
• HBeAg and anti-HBe: Every 3-6 months in HBeAg-positive patients 1, 2

The 2007 AASLD guidelines recommend testing serum HBV DNA every 3-6 months during treatment to monitor virologic response and detect breakthrough 1. More recent consensus from resource-constrained settings suggests ALT monitoring every 6 months for tenofovir therapy 1.

Renal and Bone Safety Monitoring

This is a critical distinction for tenofovir compared to other hepatitis B antivirals:

• Serum creatinine and estimated creatinine clearance: Every 6 months 1, 3
• Serum phosphorus: Every 6 months (baseline and periodic) 3
• Spot urine protein/creatinine ratio: Every 6 months if possible 1

The FDA label warns that tenofovir can cause new onset or worsening renal impairment, including acute renal failure and Fanconi syndrome 3. Patients with abnormal renal tests require more cautious monitoring and potentially dose reduction 1.

Hepatocellular Carcinoma Surveillance

• Ultrasound examination: Every 6-12 months for high-risk patients (Asian men >40 years, Asian women >50 years, cirrhosis, family history of HCC, Africans >20 years, any carrier >40 years with persistent ALT elevation or high HBV DNA >2,000 IU/ml) 1
• AFP: Can be used in conjunction with ultrasound or alone when ultrasound is unavailable 1

Monitoring for Treatment Response and Resistance

Check for medication compliance in patients with virologic breakthrough (defined as >1 log increase in HBV DNA from nadir after initial response) 1. Confirm antiviral resistance with genotypic testing if breakthrough occurs 1.

The primary endpoint for successful treatment is achieving serum HBV DNA <20 IU/ml, which occurs in approximately 77% of patients by week 144 of tenofovir monotherapy 5.

Post-Treatment Monitoring (If Therapy Discontinued)

This is critically important: The FDA black box warning states that severe acute exacerbations of hepatitis have been reported after discontinuation of anti-hepatitis B therapy 3.

• Hepatic function monitoring: Both clinical and laboratory follow-up for at least several months after discontinuation 3
• ALT levels: Monitor at least monthly for the first 3 months after cessation, then every 3 months thereafter 1
• HBsAg and HBV DNA: Monitor for reactivation 1

Special Monitoring Considerations

Patients with Comorbidities

Manage diabetes and hypertension aggressively to reduce nephrotoxicity risk 1. Avoid concurrent or recent use of other nephrotoxic drugs 3.

Resource-Constrained Settings

When HBV DNA testing is unavailable, the 2011 expert panel consensus recommends monitoring compliance and measuring ALT and serum creatinine every 6 months as a minimum standard 1.

Comparison to Entecavir Monitoring

Unlike tenofovir, entecavir requires only ALT monitoring every 6 months without the intensive renal monitoring 1. This makes tenofovir's monitoring requirements more burdensome but necessary given its renal toxicity profile.

Common Pitfalls to Avoid

• Do not skip renal monitoring: Tenofovir's nephrotoxicity distinguishes it from entecavir and requires vigilant creatinine, phosphorus, and urine protein monitoring 3
• Do not delay treatment for virologic breakthrough: Confirm compliance first, then perform genotypic testing and switch therapy promptly 1
• Do not stop monitoring after achieving undetectable HBV DNA: Continue every 3-6 month monitoring indefinitely as optimal treatment duration is unknown 3
• Do not forget post-treatment monitoring: Hepatitis flares after discontinuation can be severe and require at least several months of close follow-up 3