Does a patient need to be retested for hepatitis C (Hep C) if their liver enzymes are still elevated 3 years after treatment?

Retesting for Hepatitis C with Persistently Elevated Liver Enzymes 3 Years Post-Treatment

Yes, this patient should be retested for HCV RNA to evaluate for potential reinfection or treatment failure, and the persistently elevated liver enzymes warrant investigation for alternative causes of liver disease.

Initial Assessment of HCV Status

The patient needs HCV RNA testing, not just serology, to definitively assess current infection status. 1

• If HCV RNA was negative at 48 weeks post-treatment (SVR24) and has not been rechecked since, retesting is warranted given the persistently elevated liver enzymes 1
• Anti-HCV antibodies remain positive for life after infection, so only HCV RNA testing can distinguish between past cured infection and current active infection 1
• While late relapse beyond 48 weeks post-treatment is rare (<1%), it can occur, particularly if the patient had risk factors for treatment failure 1

Evaluation for Reinfection

Annual HCV RNA testing is specifically recommended for patients with ongoing risk behaviors. 1

• Reinfection rates range from 1-8% per year in high-risk populations including people who inject drugs (PWID) and men who have sex with men with ongoing risk behavior 1
• If the patient has any ongoing risk factors (injection drug use, high-risk sexual behavior, occupational exposure), reinfection must be ruled out 1
• Even a single HCV RNA test at this 3-year timepoint is justified given the clinical context of persistently abnormal liver enzymes 1

Investigation of Alternative Causes for Elevated Liver Enzymes

Persistently elevated liver enzymes 3 years after achieving SVR strongly suggest an alternative or additional cause of liver disease that requires thorough evaluation. 1, 2

Key cofactors to assess include:

• Alcohol consumption: This is one of the most common causes of persistent liver enzyme elevation post-SVR 1, 2
• Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD/NAFLD): Obesity and type 2 diabetes are major risk factors for ongoing liver disease 1, 2, 3
• Type 2 diabetes: Independently associated with elevated liver enzymes post-SVR 1, 2
• Other hepatotropic viruses: Hepatitis B should be evaluated if not previously done 1
• Medications and hepatotoxins: Review all current medications and supplements 1

Clinical Significance of Persistently Elevated Enzymes

Elevated liver enzymes at 3 years post-SVR are clinically significant predictors of adverse outcomes, even after HCV cure. 2

• Elevated gamma-glutamyltransferase (GGT) at SVR24 is the strongest predictor of hepatic decompensation, hepatocellular carcinoma development, and death, particularly when combined with cirrhosis 2
• Elevated ALT (using AASLD thresholds: >19 U/L in women, >30 U/L in men) also predicts hepatic decompensation 2
• These findings emphasize that liver-related comorbidities (alcohol, obesity, diabetes, cirrhosis) remain clinically relevant even after HCV cure 2

Surveillance Considerations Based on Fibrosis Stage

If the patient had advanced fibrosis (F3) or cirrhosis before treatment:

• Continue HCC surveillance with ultrasound every 6 months indefinitely, regardless of SVR status 1
• Continue endoscopic surveillance for varices if cirrhosis was present 1
• The risk of HCC remains elevated in cirrhotic patients despite SVR, though significantly reduced compared to untreated patients 1

If the patient had minimal fibrosis (F0-F2) before treatment:

• Routine HCC surveillance is not recommended 1
• However, the persistently elevated liver enzymes warrant investigation and may indicate progression of fibrosis from other causes 2, 3

Recommended Testing Algorithm

Order the following tests to comprehensively evaluate this patient:

1. HCV RNA (quantitative) to assess for reinfection or late relapse 1
2. Complete hepatic function panel including ALT, AST, GGT, alkaline phosphatase, bilirubin, albumin, and INR 2
3. Hepatitis B surface antigen and core antibody if not previously tested 1
4. Metabolic panel including fasting glucose or HbA1c, lipid panel 2
5. Detailed alcohol use assessment 1, 2
6. Consider non-invasive fibrosis assessment (FIB-4 score, transient elastography) to evaluate for interval fibrosis progression 1, 2

Common Pitfalls to Avoid

• Do not rely on anti-HCV antibody testing alone – antibodies remain positive after cure and cannot distinguish active from past infection 1
• Do not assume SVR means complete resolution of liver disease – cofactors like obesity, diabetes, and alcohol can cause ongoing liver injury 1, 2
• Do not discontinue HCC surveillance in cirrhotic patients even with SVR and normal liver enzymes 1
• Do not overlook reinfection risk in patients with ongoing risk behaviors 1