Is elevated Alanine Transaminase (ALT) alone a rating factor for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV)?

From the Guidelines

Elevated alanine transaminase (ALT) levels alone are not a reliable rating factor for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infections. While high ALT levels indicate liver inflammation or damage, specific serological tests are required for accurate diagnosis. For HBV, testing should include hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) 1. For HCV, an initial antibody test (anti-HCV) followed by HCV RNA testing for confirmation is necessary. Many patients with chronic HBV or HCV may have normal or fluctuating ALT levels, potentially leading to missed diagnoses if relying solely on ALT.

Key Considerations

• Elevated ALT can result from numerous other conditions including alcoholic liver disease, nonalcoholic fatty liver disease, medication effects, and other viral infections 1.
• Comprehensive testing is essential for proper diagnosis and management of viral hepatitis, regardless of ALT levels.
• Early detection through appropriate testing allows for timely treatment, which can prevent progression to cirrhosis, liver failure, or hepatocellular carcinoma.
• The most recent guidelines suggest that antiviral therapy is recommended in HBeAg-positive CHB patients with HBV DNA ≥20,000 IU/mL and in HBeAg-negative CHB patients with HBV DNA ≥2,000 IU/mL if serum ALT level is ≥2 times the ULN 1.

Clinical Implications

• ALT levels should not be used in isolation to diagnose or manage HBV or HCV infections.
• A combination of serological tests, liver function tests, and non-invasive fibrosis tests should be used to assess the need for antiviral treatment.
• Close monitoring of ALT levels and liver function is necessary to prevent liver-related complications in patients with HBV or HCV infections 1.

From the Research

Elevated Alanine Transaminase (ALT) as a Rating Factor for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV)

• Elevated ALT levels can be associated with HBV and HCV infections, but the relationship between ALT levels and viral activity is complex 2, 3, 4, 5, 6
• Studies have shown that patients with chronic HBV infection can have elevated ALT levels despite complete viral suppression 2
• In patients with HCV infection, high ALT levels can predict viremia, especially in hemodialysis patients 3
• However, some patients with chronic HCV infection can have normal ALT levels despite the presence of HCV RNA in serum 6
• The use of ALT levels as a rating factor for HBV and HCV infections is limited by the fact that ALT levels can fluctuate over time and may not always reflect the level of viral activity 3, 6

Predictive Value of ALT Levels

• A study found that ALT levels > 27 IU/l had a sensitivity of 50% and specificity of 100% in predicting HCV viremia in hemodialysis patients 3
• Another study found that liver biopsy had greater diagnostic accuracy than ALT levels in determining cirrhosis in patients with chronic HBV infection 4
• The positive predictive value of ALT levels in diagnosing hepatitis C viremia was 100% in one study 3

Management of Patients with Elevated ALT Levels

• Antiviral therapy can improve or regress hepatic fibrosis and cirrhosis in patients with chronic HBV infection and elevated ALT levels 4
• The choice of antiviral agent, such as tenofovir or entecavir, does not appear to affect the efficacy of treatment in patients with chronic HBV infection 5
• Patients with chronic HCV infection and normal ALT levels may not require treatment, as the natural course of the disease is likely to be mild 6