Does elevated Alanine Transaminase (ALT) alone indicate Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection?

From the Guidelines

Elevated ALT alone is not sufficient to indicate Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection, and a comprehensive evaluation including viral hepatitis serologies is necessary for accurate diagnosis. While high ALT levels suggest liver inflammation or damage, they are non-specific and can result from many conditions including alcoholic liver disease, non-alcoholic fatty liver disease, drug-induced liver injury, autoimmune hepatitis, and other viral infections 1. To diagnose HBV infection, specific serological tests are required, including hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) 1. For HCV, initial screening involves testing for HCV antibodies, followed by HCV RNA testing to confirm active infection.

Key Considerations

• The degree of ALT elevation does not reliably correlate with the severity of viral hepatitis 1
• Patients with unexplained elevated ALT should undergo comprehensive evaluation including viral hepatitis serologies rather than assuming a diagnosis based on ALT alone 1
• A liver biopsy may be required to assess the need for antiviral treatment in certain cases, such as HBeAg-positive CHB patients with an HBV DNA level of ≥ 20,000 IU/mL and an ALT level of 1-2× ULN 1
• Antiviral therapy is indicated if a moderate-to-severe degree of inflammation or periportal fibrosis is present, regardless of the ALT level 1

Diagnostic Approach

• Specific serological tests for HBV and HCV are essential for accurate diagnosis
• Comprehensive evaluation including viral hepatitis serologies is necessary for patients with unexplained elevated ALT
• Liver biopsy may be required in certain cases to assess the need for antiviral treatment

Treatment Considerations

• Antiviral therapy is indicated if a moderate-to-severe degree of inflammation or periportal fibrosis is present, regardless of the ALT level 1
• Patients with compensated cirrhosis are indicated for antiviral therapy if the HBV DNA level is ≥ 2,000 IU/mL, regardless of the ALT level 1
• Patients with decompensated cirrhosis are indicated for antiviral therapy if HBV DNA is detectable, and liver transplantation should be considered 1

From the Research

Elevated Alanine Transaminase (ALT) and Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Infection

• Elevated ALT levels can be associated with viral hepatitis, but they do not exclusively indicate HBV or HCV infection 2, 3, 4.
• A study found that in primary care patients with an ALT level of 50-100 IU/l, HCV prevalence is tenfold the population prevalence, whereas HBV prevalence is not elevated 2.
• Another study discovered that fluctuations in serum ALT levels may change the prognosis of a HBV inactive carrier state, and elevation of ALT levels, even in the absence of HBV replication, increased the risk for the development of chronic HBV e antigen (HBeAg)-negative hepatitis B (CHB) up to 8-fold in prospective follow-ups 3.
• Elevated ALT levels can also be found in HIV-infected persons without HBV or HCV coinfection, and are associated with high HIV viral load, mean body mass index, and diabetes mellitus 5.
• Monitoring of ALT is of value in assessing hepatocellular damage in patients with chronic hepatitis B virus infection, and HBeAg-negative patients with elevated ALT levels and some with normal ALT levels should be considered highly infectious in the course of chronic HBV infection 4.
• Even in patients with complete viral suppression, persistently elevated ALT levels can occur, and circulating metabolites such as Ser-Phe-Ala, Lys-Ala-Leu-Glu, 3-methylhippuric acid, 3-methylxanthine, and 7-methylxanthine have been identified as critical differential metabolites between patients with persistently elevated ALT and those with persistently normal ALT 6.

Association between ALT and HBV or HCV Infection

• The presence of elevated ALT levels does not necessarily indicate HBV or HCV infection, as other factors such as HIV infection, high body mass index, and diabetes mellitus can also contribute to elevated ALT levels 2, 3, 5, 4, 6.
• However, in patients with chronic HBV infection, elevated ALT levels can be associated with increased risk of developing CHB, and monitoring of ALT is important in assessing hepatocellular damage 3, 4.
• In patients with complete viral suppression, changes in circulating metabolites may contribute to persistently elevated ALT levels, and further research is needed to understand the mechanisms underlying this association 6.

Clinical Implications

• Elevated ALT levels should be further investigated to determine the underlying cause, as they can be associated with various conditions including viral hepatitis, HIV infection, and other liver diseases 2, 3, 5, 4, 6.
• Patients with chronic HBV infection and elevated ALT levels should be closely monitored for signs of liver disease progression, and antiviral treatment should be considered if necessary 3, 4.
• Further research is needed to understand the relationship between ALT levels, circulating metabolites, and liver disease progression in patients with chronic HBV infection, particularly in those with complete viral suppression 6.