What is the next step for a patient with chronic HBV, elevated ALT and AST, and high HBV DNA, but undetectable HCV RNA and unremarkable liver ultrasound?

From the Guidelines

I would strongly recommend option D, HDV RNA testing for this 45-year-old gentleman with chronic hepatitis B. The patient has significantly elevated liver enzymes (ALT 250, AST 200) despite a relatively low HBV DNA level of 700, which creates a discrepancy that needs explanation. This pattern of high liver enzymes with low viral load is characteristic of hepatitis delta virus (HDV) superinfection in patients with chronic hepatitis B, as suggested by the EASL clinical practice guidelines for the management of chronic hepatitis B virus infection 1. HDV is a defective RNA virus that requires the presence of HBV to replicate and can cause more severe liver disease when it coinfects or superinfects HBV patients. HCV has already been ruled out with negative antibody and undetectable RNA. HBV genotyping (option B) would not explain the elevated enzymes, and repeating HCV RNA (option C) is unnecessary given the already negative results. HEV RNA (option A) is less likely given the chronic nature of this patient's condition, as HEV typically causes acute hepatitis. Testing for HDV is essential as its presence would significantly impact management decisions and prognosis for this patient with chronic hepatitis B. According to the treatment algorithm for the management of chronic hepatitis B virus infection in the United States, other causes of chronic liver disease, including co-infections with HDV, should be systematically looked for 2.

Some key points to consider in this case include:

• The patient's elevated liver enzymes (ALT 250, AST 200) despite a relatively low HBV DNA level of 700
• The importance of testing for HDV in patients with chronic hepatitis B and elevated liver enzymes
• The potential for HDV superinfection to cause more severe liver disease in patients with chronic hepatitis B
• The need to rule out other causes of chronic liver disease, including co-infections with HCV and HIV, as well as other liver diseases such as autoimmune hepatitis and metabolic liver disease.

Given the potential for HDV superinfection to cause significant morbidity and mortality in patients with chronic hepatitis B, testing for HDV RNA is the most appropriate next step in the management of this patient. This is in line with the EASL clinical practice guidelines, which recommend testing for HDV in patients with chronic hepatitis B and elevated liver enzymes 1.

From the Research

Patient Diagnosis and Recommendations

The patient in question has chronic hepatitis B with elevated liver enzymes (ALT 250, AST 200) and is HCV negative with undetectable HCV RNA. Given the clinical presentation, the following options are considered for further diagnosis:

• A. HEV RNA: This option is not directly relevant to the patient's current diagnosis of chronic hepatitis B.
• B. HBV genotype: While knowing the HBV genotype can be useful for understanding the potential severity and treatment options for HBV, it does not directly address the elevated liver enzymes.
• C. Repeat HCV RNA: The patient is already HCV negative with undetectable HCV RNA, making this option unnecessary.
• D. HDV RNA: Given the patient's chronic hepatitis B status and elevated liver enzymes, testing for HDV RNA is crucial. HDV infection can only occur in individuals with HBV infection, either as a coinfection or superinfection, and can lead to more severe liver disease than HBV monoinfection 3, 4, 5.

Rationale for HDV RNA Testing

HDV infection is known to cause more severe liver disease, including accelerated fibrosis progression, increased risk of hepatocellular carcinoma, and early decompensation in cirrhosis 3. The diagnosis and monitoring of HDV infection rely on the detection and quantification of HDV RNA 4. A study on universal HDV testing among veterans with chronic hepatitis B found that implementing such testing can identify patients with viremic HDV, allowing for timely diagnosis and potential treatment 6.

Clinical Utility and Challenges

The clinical utility of HDV RNA assays is significant for diagnosing and monitoring HDV infection, especially with the development of new treatments 4. However, challenges exist due to viral heterogeneity, intrahost viral diversity, and the lack of standardization across testing laboratories 4. Despite these challenges, testing for HDV RNA is a critical step in managing patients with chronic hepatitis B and elevated liver enzymes, as it can identify those who may benefit from specific treatments for HDV infection 3, 5.