Laboratory Tests for Patients with Positive Hepatitis C Test on Buprenorphine
For patients with a positive Hepatitis C (HCV) test who are on buprenorphine therapy, a comprehensive laboratory panel should include HCV RNA testing, liver function tests, complete blood count, fibrosis assessment markers, and hepatitis B/HIV screening to confirm infection status, assess liver damage, and guide treatment decisions.
Confirmation of HCV Infection
- HCV RNA testing should be performed to confirm active infection in all patients with a positive HCV antibody test 1
- A positive HCV antibody test may indicate: 1) current active infection, 2) past resolved infection, or 3) false positivity - only RNA testing can differentiate between these possibilities 1
- For patients on buprenorphine with a positive antibody test, reflex HCV RNA testing is recommended as the standard of care 1
- Quantitative HCV RNA testing is recommended prior to initiating antiviral therapy to document baseline viral load 1
Liver Function Assessment
- Complete liver function tests including ALT, AST, bilirubin (total and direct), albumin, and alkaline phosphatase should be performed to assess liver damage 1
- Patients on buprenorphine require careful liver function monitoring as buprenorphine has been associated with hepatotoxicity in some cases, particularly in those with pre-existing liver disease 2, 3
- Serial monitoring of transaminases is important as some patients with HCV on buprenorphine have shown improvement in liver enzymes during treatment 3
Fibrosis Assessment
- Assessment of liver fibrosis severity is essential prior to antiviral treatment 1
- Non-invasive fibrosis markers should be calculated using:
- APRI (AST-platelet ratio index): calculated as (AST/upper limit of normal for AST) × 100/platelet count; APRI >1.5 predicts significant fibrosis, APRI >2 predicts cirrhosis 1
- FIB-4: calculated as age (yr) × AST (IU/L)/platelet count (109/L × [ALT (IU/L)]1/2); FIB-4 <1.45 has 90% negative predictive value for advanced fibrosis 1
- AST/ALT ratio (AAR): AAR >1.0 has 73.7-100% positive predictive value for advanced fibrosis 1
Complete Blood Count
- Platelet count is essential not only for fibrosis assessment calculations but also to evaluate for thrombocytopenia which may indicate advanced liver disease 1
- Complete blood count helps assess for anemia or leukopenia which may impact treatment decisions 4
HCV Genotyping
- HCV genotyping should be performed prior to antiviral treatment, especially for patients with prior HCV treatment failure 1
- With the advent of pangenotypic direct-acting antiviral regimens, genotyping may not be required for treatment-naive patients without cirrhosis if a pangenotypic regimen is used 1
Additional Testing
- Hepatitis B surface antigen, surface antibody, and core antibody testing to rule out co-infection 1
- HIV testing is recommended as HIV/HCV co-infection requires special consideration 1, 5
- Renal function tests (creatinine, BUN) to assess kidney function which may impact treatment decisions 4
- For patients with advanced fibrosis or cirrhosis, alpha-fetoprotein and liver ultrasound should be considered for hepatocellular carcinoma screening 1
Monitoring During Treatment
- Regular monitoring of liver enzymes is particularly important for patients on buprenorphine with HCV, as some cases of acute cytolytic hepatitis have been reported with buprenorphine use 2
- Despite concerns about hepatotoxicity, studies have shown that patients with acute HCV infection and elevated transaminases can tolerate buprenorphine treatment with improvement in liver enzymes during treatment 3
Common Pitfalls and Caveats
- False negative antibody tests can occur in immunocompromised patients or those with recent exposure (within 6 months); consider direct HCV RNA testing in these cases 1
- Transient elastography (FibroScan) results may be falsely elevated in the setting of acute hepatitis with inflammation 1
- Patients on buprenorphine may have multiple risk factors for liver disease beyond HCV, including alcohol use and other viral hepatitis, which should be assessed 2
- Buprenorphine should not be automatically discontinued in patients with HCV and elevated liver enzymes, as studies have shown it can be safely used with appropriate monitoring 3