What causes viral elevation of liver (alanine transaminase (ALT) and aspartate transaminase (AST)) levels?

From the Guidelines

Viral elevation of liver levels, also known as viral hepatitis, is a common cause of liver inflammation that can lead to elevated liver enzymes such as ALT and AST, with hepatitis B being a primary cause of chronic liver inflammation, as evidenced by studies showing that antiviral medications like entecavir or tenofovir can reduce HBV viral load and liver inflammation 1.

Causes of Viral Elevation of Liver Levels

The causes of viral elevation of liver levels can be attributed to various factors, including:

• Hepatitis B virus (HBV) infection, which can lead to chronic liver inflammation and elevated liver enzymes 1
• Hepatitis C virus (HCV) infection, which can also cause chronic liver inflammation and elevated liver enzymes
• Other viral infections, such as hepatitis A and E, which can cause acute liver inflammation and elevated liver enzymes

Diagnosis and Treatment

Diagnosis of viral elevation of liver levels involves:

• Liver function tests to monitor ALT and AST levels
• Viral serology tests to detect HBV, HCV, and other viral infections
• Imaging studies, such as ultrasound or CT scans, to evaluate liver damage Treatment of viral elevation of liver levels depends on the underlying cause, but may include:
• Antiviral medications, such as entecavir or tenofovir, for chronic HBV infection 1
• Direct-acting antivirals, such as sofosbuvir/velpatasvir or glecaprevir/pibrentasvir, for HCV infection
• Supportive care, including rest, hydration, and avoidance of hepatotoxic medications, for acute viral hepatitis

Management and Prevention

Management of viral elevation of liver levels involves:

• Regular monitoring of liver function tests to track improvement
• Avoidance of hepatotoxic medications and substances
• Vaccination against HBV and HCV to prevent infection
• Screening for underlying liver disease, such as chronic viral hepatitis or non-alcoholic fatty liver disease (NAFLD), to prevent exacerbation or reactivation of underlying liver disease 1 In summary, viral elevation of liver levels can be caused by various viral infections, and treatment depends on the underlying cause, with antiviral medications and supportive care being primary management strategies, as supported by recent studies 1.

From the FDA Drug Label

The safety and efficacy of entecavir were evaluated in three Phase 3 active-controlled trials [see Clinical Studies (14.1,14. 2)] . These studies included 1633 subjects 16 years of age or older with chronic hepatitis B virus infection (serum HBsAg-positive for at least 6 months) accompanied by evidence of viral replication (detectable serum HBV DNA, as measured by the bDNA hybridization or PCR assay). Subjects had persistently elevated ALT levels at least 1. 3 times ULN and chronic inflammation on liver biopsy compatible with a diagnosis of chronic viral hepatitis.

The cause of viral elevation of liver (alanine transaminase (ALT) and aspartate transaminase (AST)) levels is chronic hepatitis B virus infection. This is evidenced by the fact that subjects in the study had persistently elevated ALT levels and chronic inflammation on liver biopsy compatible with a diagnosis of chronic viral hepatitis 2.

• Key points:
  • Chronic hepatitis B virus infection
  • Viral replication (detectable serum HBV DNA)
  • Persistently elevated ALT levels
  • Chronic inflammation on liver biopsy

From the Research

Viral Elevation of Liver Enzymes

Viral infections are a primary cause of liver diseases worldwide, and can lead to elevated levels of liver enzymes such as alanine transaminase (ALT) and aspartate transaminase (AST) 3, 4, 5, 6, 7.

• Hepatitis viruses, including hepatitis B, C, and E, are the most prevalent contributors to acute and chronic liver disease, and can cause significant elevations in ALT and AST levels 3, 4.
• Other viruses, such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), and hepatitis A virus (HAV), can also cause liver damage and elevate liver enzyme levels 5, 7.
• The elevation of ALT and AST levels can be an indicator of hepatic damage, and can be used as a diagnostic tool to identify viral infections that affect the liver 7.
• Treatment of viral infections that cause liver disease can help to reduce elevated liver enzyme levels, and antiviral agents such as tenofovir and entecavir have been shown to be effective in reducing HBV DNA levels and normalizing ALT levels 6.

Specific Viral Infections

• Hepatitis B virus (HBV) and hepatitis C virus (HCV) can lead to both acute and chronic liver diseases, including liver cirrhosis and hepatocellular carcinoma (HCC), which are principal causes of worldwide morbidity and mortality 3, 4.
• Hepatitis E virus (HEV) primarily causes self-limiting acute hepatitis, but can also cause chronic progression of the disease in immunocompromised patients 4.
• Epstein-Barr virus (EBV) and cytomegalovirus (CMV) can cause liver damage as part of a systemic illness, and can lead to elevated liver enzyme levels 7.

Diagnosis and Treatment

• Diagnosis of viral infections that cause liver disease can be made through serology and liver histology 7.
• Treatment of viral infections that cause liver disease is largely supportive, but antiviral agents such as tenofovir and entecavir have been shown to be effective in reducing HBV DNA levels and normalizing ALT levels 6.
• Host-targeting antivirals (HTAs) have emerged as a promising alternative approach to direct-acting antivirals (DAAs) for the treatment of chronic HBV and HCV infections 4.