Hepatitis C Workup in Primary Care: Screening, Diagnosis, and Pre-Treatment Assessment

Infectious Disease Labs
Written By Victoria Sanderson

Hepatitis C diagnosis requires a two-step testing approach: an initial hepatitis C antibody test followed by confirmatory HCV RNA testing to identify active infection. Once infection is confirmed, clinicians should assess for cirrhosis using non-invasive fibrosis scores such as APRI or FIB-4 and complete baseline laboratory investigations before initiating antiviral therapy. With modern direct-acting antivirals achieving cure rates above 95%, many patients can be successfully evaluated and treated in primary care.

Hepatitis C is often asymptomatic for years, yet untreated infection can progress to cirrhosis, liver failure, and hepatocellular carcinoma. Because many cases are identified incidentally through screening or routine bloodwork, primary care clinicians play a key role in diagnosing hepatitis C infection and initiating treatment.

With modern direct-acting antiviral therapies achieving cure rates above 95%, early diagnosis can significantly reduce the long-term burden of liver disease. Increasingly, hepatitis C assessment and treatment are being managed in primary care settings, particularly when cirrhosis is not present.

In this post, we review hepatitis C testing, diagnostic interpretation, fibrosis assessment, and pre-treatment laboratory evaluation, with practical guidance for clinicians.

Who Should Be Screened for Hepatitis C?

Current guidelines recommend screening in the following groups:

  • All adults ≥18 years at least once (1)

  • All pregnant patients during each pregnancy (2,3)

  • Additional high-risk populations, including:

    • Current or past injection drug use

    • History of incarceration

    • HIV infection

    • Exposure to contaminated blood products

    • Sexual partners of individuals with hepatitis C

    • Immigration or travel from regions with higher hepatitis C prevalence (1)

Hepatitis C Diagnostic Testing

Step 1: Hepatitis C Antibody Test

The hepatitis C antibody test is the initial screening test and detects past exposure to the virus.

Key points:

  • Hepatitis C antibodies persist for life

  • A positive antibody result does not confirm active infection

  • False negatives can occur during the 5–10 week window period

  • If exposure is suspected during this period, repeat testing later (1)

Step 2: HCV RNA Test

If the antibody test is positive, the HCV RNA test confirms whether active infection is present.

Key points:

  • Detects viral RNA within 1–2 weeks of exposure

  • Quantifies the viral load

  • In many laboratories, genotyping may be performed automatically

HCV RNA testing is required:

  • Before initiating treatment

  • After treatment to confirm cure

  • Whenever reinfection is suspected

Interpretation:

  • Positive → active infection

  • Negative → prior infection that has cleared or was successfully treated

Reflex Testing

Many laboratories perform reflex RNA testing automatically after a positive antibody result.

In some testing centres, genotyping may also be performed automatically if:

  • Viral load is >125 IU/mL

  • Adequate sample volume is available.

If reflex testing is not performed, clinicians must order the HCV RNA test separately, along with genotyping if needed (1)

Point-of-Care Hepatitis C Testing

Rapid testing options are increasingly available. Examples include:

  • OraQuick HCV Antibody Test (Canada & US): provides results in 20–40 minutes and detects antibodies only (4)

  • INSTI HCV Antibody Test (Canada): provides results in approximately 1 minute with similar performance characteristics

  • Xpert HCV Viral Load Fingerstick Test (Canada & US): detects active infection in under 60 minutes and demonstrates high sensitivity and specificity (5)

💡 Clinical Tip: Always obtain informed consent prior to hepatitis C testing.

Baseline Evaluation Before Hepatitis C Treatment

Once active hepatitis C infection is confirmed, the primary goal before initiating treatment is to determine whether cirrhosis is present or suspected, as this significantly affects treatment planning.

Management differs for:

  • Treatment-naïve patients without cirrhosis

  • Treatment-naïve patients with compensated cirrhosis

  • Patients with decompensated cirrhosis, who require specialist referral

Non-Invasive Fibrosis Assessment: APRI, FIB-4, FibroScan

Liver biopsy is no longer recommended for routine fibrosis staging prior to hepatitis C treatment.

Instead, clinicians typically use non-invasive fibrosis assessments, including:

  • APRI score

  • FIB-4 score

  • Liver elastography (FibroScan) (6,7)

1. APRI Score

The AST to Platelet Ratio Index (APRI) uses AST and platelet count.

Interpretation:

  • <1.0 → minimal fibrosis

  • 1.0–2.0 → calculate FIB-4

  • >2.0 → suggests significant fibrosis

2. FIB-4 Score

The FIB-4 score uses:

  • Age

  • AST

  • ALT

  • Platelet count

Interpretation:

  • <1.45 → minimal fibrosis

  • 1.45–3.25 → indeterminate fibrosis

  • >3.25 → advanced fibrosis or cirrhosis

Clinical considerations

FIB-4 is validated for patients aged 35–65 years.

Practical adjustments:

  • If <35 years, use age 35 in the calculator to avoid underestimating fibrosis risk

  • If >65 years, consider using APRI instead

3. Liver Elastography (FibroScan)

FibroScan measures liver stiffness, which correlates with liver fibrosis.

Important considerations:

  • Not widely available in all regions

  • Often not publicly funded

  • Not required prior to initiating treatment

It may be useful when:

  • APRI or FIB-4 results are indeterminate

  • Results are discordant

  • Fibrosis risk remains uncertain (6,7)

How to Stage Cirrhosis: Child-Pugh and MELD

Once the non-invasive fibrosis assessment has been completed, if cirrhosis is suspected, staging helps guide treatment decisions.

Child-Pugh Score

The Child-Pugh score uses:

  • Bilirubin

  • Albumin

  • INR

  • Presence of ascites

  • Presence of hepatic encephalopathy

Classification:

  • Class A – compensated cirrhosis (treatment can proceed)

  • Class B or C – referral to specialist recommended

MELD Score

The Model for End-Stage Liver Disease (MELD) score uses:

  • Creatinine

  • Total bilirubin

  • INR

  • Sodium

Higher scores indicate more severe liver dysfunction.

MELD >10 should prompt referral to a liver transplant centre.

Baseline Laboratory Tests Before Hepatitis C Treatment

The following investigations should typically be completed within 6 months prior to treatment initiation:

  • Quantitative HCV RNA

  • Hepatitis B screening (HBsAg, anti-HBc, anti-HBs): if there is an active Hep B infection, it is recommended to treat first prior to Hep C treatment

  • Hepatitis A immunity (HAV IgG)

  • HIV antigen/antibody

  • CBC (including platelet count)

  • Liver panel (ALT, AST, total and direct bilirubin, albumin): to assess for liver dysfunction and cirrhosis

  • eGFR and urine ACR: to assess for secondary kidney dysfunction, and to ensure direct-acting antivirals are safe to take

  • Pregnancy test: for females of childbearing age

Additional labs if cirrhosis is suspected:

  • INR + Sodium: for MELD score calculation

Clinicians should also consider screening for:

  • Syphilis

  • Chlamydia

  • Gonorrhea

Drug resistance testing is rarely required, but may be considered in patients with genotype 3 infection and cirrhosis (6,7).

💡 Clinical Pearl: Normal ALT does not exclude chronic hepatitis C. Approximately 25% of individuals with chronic infection have normal ALT levels.

💡 Practical Tip: Some clinicians choose to order a complete baseline panel for all patients being assessed, allowing early identification of abnormalities such as thrombocytopenia, elevated INR, low albumin, or elevated bilirubin without requiring additional testing.

Hepatitis C Testing Algorithm

A simplified diagnostic approach in primary care:

  1. Screen with hepatitis C antibody test

  2. If positive → order HCV RNA test (some labs perform automatic reflex testing)

  3. If RNA positive → active infection

  4. Assess fibrosis using APRI or FIB-4 (liver elastography can be completed, but is not necessary for all cases)

  5. Complete baseline labs prior to treatment

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  1. CATIE. Hepatitis C testing and diagnosis [Internet]. Toronto (ON): CATIE; 2026 [cited 2026 Mar 9]. Available from: https://www.catie.ca/testing-diagnosis/hepatitis-c-testing-and-diagnosis
  2. Atkinson A, Bjurman N, Yudin M, Elwood C, et al. Clinical consensus statement No. 458: hepatitis C virus in pregnancy. J Obstet Gynaecol Can. 2025;47(2):102780.
  3. Centers for Disease Control and Prevention. Testing for hepatitis C [Internet]. Atlanta (GA): CDC; 2025 [cited 2026 Mar 9]. Available from: https://www.cdc.gov/hepatitis-c/testing/index.html
  4. D’Angelo RG, Klepser M, Woodfield R, Patel H. Hepatitis C virus screening: a review of the OraQuick hepatitis C virus rapid antibody test. J Pharm Technol. 2015;31(1):13-19.
  5. Lamoury FMJ, Bajis S, Hajarizadeh B, et al. Evaluation of the Xpert HCV viral load finger-stick point-of-care assay. J Infect Dis. 2018;217:1889-1896.
  6. Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C [Internet]. 2025 [cited 2026 Mar 9]. Available from: https://www.hcvguidelines.org/
  7. American Association for the Study of Liver Diseases; Infectious Diseases Society of America. Test, evaluate, monitor [Internet]. 2025 [cited 2026 Mar 9]. Available from: https://www.hcvguidelines.org/test-evaluate-monitor/
Victoria Sanderson
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