What are the next steps for a patient with reactive Hepatitis C Virus (HCV) antibody, negative Immunoglobulin M (IgM) for Hepatitis A, negative Hepatitis B surface antigen (HBsAg), and negative Immunoglobulin M (IgM) for Hepatitis B core antibody?

From the Guidelines

For a patient with reactive hepatitis C virus (HCV) antibody and negative hepatitis A IgM and negative hepatitis B markers (HBsAg and core IgM), the next step should be an HCV RNA test to confirm active infection, as recommended by the 2016 guidelines from the Clinical and Molecular Hepatology journal 1. This quantitative PCR test will determine if there is ongoing viral replication, as a positive antibody test alone only indicates past exposure but doesn't confirm current infection.

Key Considerations

• The patient's negative hepatitis A and B markers indicate no current infection with these viruses, but vaccination would prevent future co-infection which could worsen liver damage.
• According to the 2016 guidelines, HCV RNA testing is required to confirm the diagnosis in patients with a positive anti-HCV test 1.
• The 2001 guidelines from the Gut journal also recommend PCR testing of serum in patients with positive antibody tests to confirm current viraemia 1.

Next Steps

• If the HCV RNA test is positive, the patient should be referred to a gastroenterologist or hepatologist for further evaluation, including HCV genotyping and assessment of liver fibrosis (through FibroScan or other non-invasive methods) 1.
• Direct-acting antiviral (DAA) therapy is highly effective for HCV, with cure rates exceeding 95%, and common regimens include Mavyret (glecaprevir/pibrentasvir) for 8-12 weeks or Epclusa (sofosbuvir/velpatasvir) for 12 weeks, depending on genotype and liver status.
• During this process, the patient should avoid alcohol, limit acetaminophen use, and be vaccinated against hepatitis A and B if not already immune.

Important Recommendations

• Assessment of liver disease severity is essential prior to antiviral treatment, and liver biopsy and/or noninvasive tests for assessment of hepatic fibrosis can be performed to make treatment decisions and predict prognosis 1.
• HCV RNA quantitative assay and genotyping/subgenotyping should be performed prior to antiviral treatment to determine the duration of treatment and predict treatment outcomes 1.

From the FDA Drug Label

Test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment with ledipasvir and sofosbuvir [see Warnings and Precautions (5.1)]. Test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment with SOVALDI [see Warnings and Precautions (5.1)].

The patient has already been tested for HBV infection, with negative HBsAg and negative IgM for Hepatitis B core antibody.

• The patient is HCV antibody reactive.
• The patient has negative IgM for Hepatitis A, indicating no current Hepatitis A infection.
• The patient has negative HBsAg, indicating no current HBV infection.
• The patient has negative IgM for Hepatitis B core antibody, indicating no current or recent HBV infection.

Since the patient has a reactive HCV antibody and no evidence of current HBV infection, the next steps would be to:

• Confirm the HCV diagnosis with further testing, such as HCV RNA testing.
• Assess the patient's liver disease status, including liver function tests and possibly liver biopsy or imaging studies.
• Determine the HCV genotype, as this will guide treatment decisions.
• Consider treatment options for HCV, such as ledipasvir and sofosbuvir, based on the patient's genotype, liver disease status, and other factors 2, 3.

From the Research

Next Steps for Patient with Reactive HCV Antibody

The patient has a reactive Hepatitis C Virus (HCV) antibody, negative Immunoglobulin M (IgM) for Hepatitis A, negative Hepatitis B surface antigen (HBsAg), and negative Immunoglobulin M (IgM) for Hepatitis B core antibody. The following steps can be considered:

• Confirm the diagnosis of HCV infection using a more specific test, such as HCV RNA testing by polymerase chain reaction (PCR) 4, 5
• Evaluate the patient's liver disease status and assess for any signs of liver damage 6, 7
• Consider testing for other liver diseases, such as hepatitis B and hepatitis A, to rule out other causes of liver damage 8
• If the patient is confirmed to have HCV infection, consider referral to a specialist for further evaluation and treatment 5

Interpretation of HCV Antibody Results

The interpretation of HCV antibody results can be complex, and a positive result does not always indicate active infection 5. The signal to cutoff (S/CO) ratio can be used to classify positive antibody results into different levels, including very low, low, and high 5.

• A very low level of Anti-HCV may indicate a false-positive result, and further diagnostic testing may not be necessary 5
• A low antibody level may be related to false-positive results, and testing with Immunoblot is recommended 5
• A high Anti-HCV level is an accurate serological marker for predicting viremia and denotes the need for routine HCV RNA testing to confirm hepatitis C 5

HCV RNA Testing

HCV RNA testing by PCR can be used to confirm the diagnosis of HCV infection and to assess the patient's viral load 4, 5.

• HCV RNA testing can detect the presence of HCV RNA in the blood, which indicates active infection 4
• The results of HCV RNA testing can be used to guide treatment decisions and to monitor the patient's response to treatment 6, 7