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

From the Guidelines

For a patient with reactive Hepatitis C Virus (HCV) and negative Hepatitis A IgM, negative Hepatitis B surface antigen (HBsAg), and negative Hepatitis B core IgM, the next step should be HCV RNA testing to confirm active infection, as recommended by the American Association for the Study of Liver Diseases-Infectious Diseases Society of America 1. This quantitative PCR test will determine if there is ongoing viral replication, as a positive antibody test alone could indicate either current infection or past, resolved infection.

Key Considerations

• If HCV RNA is detected, the patient should undergo HCV genotyping to guide treatment selection, as different genotypes may respond better to specific treatments 1.
• Additional baseline testing should include complete blood count, liver function tests, assessment of liver fibrosis (through noninvasive markers or liver biopsy, if required), and screening for HIV and hepatitis B, as these coinfections can affect treatment outcomes and prognosis 1.
• For confirmed active HCV infection, direct-acting antiviral (DAA) therapy is recommended, with specific regimens depending on genotype, liver status, and comorbidities, and the patient should be counseled on avoiding alcohol, maintaining a healthy diet, and preventing transmission to others while undergoing evaluation and treatment 1.

Treatment and Prevention

• The patient should receive education and interventions aimed at reducing liver disease progression and preventing HCV transmission, including abstinence from alcohol and interventions to facilitate cessation of alcohol consumption, if necessary 1.
• Vaccination against hepatitis A and hepatitis B is recommended for all susceptible persons with HCV infection, as well as pneumococcal vaccination for those with cirrhosis 1.
• Ongoing imaging surveillance for hepatocellular carcinoma and gastroesophageal varices is recommended for patients with cirrhosis, and the patient should be advised to avoid hepatotoxic and nephrotoxic drugs 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)]. The patient has already been tested for HBsAg and Hepatitis B core IgM, and the results are negative. However, the label recommends testing for hepatitis B core antibody (anti-HBc) as well.

• The patient's Hepatitis B core antibody (anti-HBc) status is unknown.
• The patient's HCV genotype is also unknown. Given the unknowns, the next steps would be to:
• Test for Hepatitis B core antibody (anti-HBc).
• Determine the HCV genotype. Then, treatment can be considered based on the patient's HCV genotype and other factors, such as the presence of cirrhosis and treatment history 2.

From the Research

Next Steps for Patient with Reactive HCV and Negative Hepatitis A IgM, HBsAg, and HB core IgM

• The patient's reactive Hepatitis C Virus (HCV) result indicates potential HCV infection, and further testing is necessary to confirm current infection 3, 4.
• Given the negative results for Hepatitis A IgM, HBsAg, and HB core IgM, the focus should be on HCV diagnosis and management.
• The next steps would involve:
  • Confirming current HCV infection with a qualitative HCV RNA test, as anti-HCV positivity may indicate past infection, current infection, or non-specific reactivity 5.
  • If the qualitative HCV RNA test is positive, quantitative HCV RNA testing and HCV genotype testing should be performed to guide treatment decisions 3.
  • Assessing the degree of liver fibrosis through liver biopsy or noninvasive testing to determine the urgency of treatment 3.
  • Considering treatment options based on genotype, extent of fibrosis or cirrhosis, prior treatment, comorbidities, and potential adverse effects, with the goal of reducing all-cause mortality and liver-associated complications 3.
• Automatic reflexive HCV RNA testing of HCV antibody-reactive specimens is recommended to facilitate diagnosis and ensure patients are not lost to follow-up 4.
• Analyzing signal-to-cutoff ratios of the HCV antibody assay may help determine the need for supplementary testing, such as recombinant immunoblot assay (RIBA) or reverse transcription (RT)-PCR 6.