What to do with a patient with positive hepatitis C antibody, negative hepatitis C RNA, and elevated liver enzymes?

From the Guidelines

For a patient with positive hepatitis C antibody, negative hepatitis C RNA, and elevated liver enzymes, the recommended approach is to first confirm that the patient has truly cleared the hepatitis C virus by repeating the HCV RNA test, as this pattern typically indicates either spontaneous clearance of a past HCV infection or a false-positive antibody test, and then investigate alternative causes of liver disease promptly. This is based on the most recent and highest quality study available, which emphasizes the importance of appropriate medical care for patients with hepatitis C, including education on preventing further liver damage and referral to a practitioner with expertise in liver disease severity and HCV treatment 1.

Since the liver enzymes are elevated, alternative causes of liver disease should be investigated promptly, including:

• Alcoholic liver disease
• Non-alcoholic fatty liver disease
• Autoimmune hepatitis
• Drug-induced liver injury
• Hemochromatosis
• Wilson's disease
• Other viral hepatitis infections such as hepatitis B or A

A comprehensive workup should include:

• A detailed history of alcohol use, medications, and supplements
• Laboratory tests including liver function tests, hepatitis B serology, autoimmune markers, iron studies, ceruloplasmin levels
• Imaging studies such as an ultrasound of the liver

If the etiology remains unclear after initial evaluation, referral to a hepatologist for possible liver biopsy may be necessary, as emphasized by the importance of continuous management and surveillance for development of cirrhosis and HCC in chronic hepatitis C patients 1. It's also important to note that once a person has been infected with hepatitis C, they will typically remain antibody-positive for life, even after successful clearance of the virus, but they are not considered to have active infection if HCV RNA is negative.

In terms of management, patients with chronic HCV infection without antibodies against HAV and HBV should be vaccinated for HAV and HBV, and abstinence from alcohol or moderation in drinking, and maintaining suitable body weight through physical exercise and dietary control, is recommended since disease progression is related to alcohol, obesity, or insulin resistance 1. However, in this case, since the patient has a negative HCV RNA, the focus should be on investigating alternative causes of liver disease and managing the patient accordingly.

From the Research

Patient with Positive Hepatitis C Antibody and Negative Hepatitis C RNA

• The patient has a positive hepatitis C antibody test, which indicates that they have been exposed to the hepatitis C virus (HCV) at some point in their lives 2.
• However, the negative hepatitis C RNA test suggests that the patient does not have an active HCV infection 3.
• Elevated liver enzymes (transaminases) can be caused by a variety of factors, including hepatitis C, but also other liver diseases or conditions such as alcoholic liver disease 4.

Interpretation of Test Results

• The presence of hepatitis C antibody without detectable HCV RNA may indicate that the patient has cleared the virus or is in a state of latent infection 5.
• Alternatively, it is possible that the patient has a false-negative HCV RNA test result, which can occur if the test is not sensitive enough or if the patient has a low viral load 3.
• The elevated liver enzymes may be related to the patient's hepatitis C infection, but further testing and evaluation are needed to determine the cause of the elevated enzymes 2.

Clinical Implications

• The patient should undergo further evaluation to determine the cause of the elevated liver enzymes, which may include additional liver function tests, imaging studies, and liver biopsy 2.
• The patient should also be counseled about the risks and benefits of treatment for hepatitis C, even if they do not have an active infection 3.
• It is also important to note that persistent hepatitis C viraemia without liver disease is possible, and the patient should be monitored regularly to assess for any changes in their liver function or viral status 6.