What does it mean to have continued elevated liver enzymes with leukocytosis (elevated white blood cell count)?

From the Guidelines

Having continued elevated liver enzymes with leukocytosis suggests ongoing inflammation or infection affecting the liver, which requires prompt medical evaluation to determine the underlying cause and prevent potential progression to more serious conditions like fibrosis or cirrhosis. This combination indicates that your body is actively fighting an infection or experiencing inflammation that is causing liver cell damage, resulting in the release of enzymes into the bloodstream. Common causes include viral hepatitis, alcoholic liver disease, medication-induced liver injury, autoimmune hepatitis, or biliary tract infections 1.

Key Considerations

• The elevated white blood cell count specifically points toward an infectious or inflammatory process rather than simple liver injury.
• Treatment depends entirely on the identified cause - viral hepatitis may require antiviral medications, autoimmune hepatitis typically needs immunosuppressants like prednisone or azathioprine, while bacterial infections require appropriate antibiotics.
• Additional tests such as viral hepatitis panels, imaging studies like ultrasound or CT scan, and possibly a liver biopsy in some cases may be ordered to determine the underlying cause.

Potential Causes and Diagnostic Approaches

• Viral hepatitis: Elevated AST and ALT, positive PCR or rapid antigenic tests in respiratory samples 1.
• Alcoholic liver disease: Medical history, elevated AST and ALT, imaging studies.
• Medication-induced liver injury: Medical history of administration of hepatotoxic compounds, ALT >5x ULN, ALP >2x ULN, plus bilirubin >2x ULN 1.
• Autoimmune hepatitis: Elevated levels of AST, ALT, hypergammaglobulinemia and increased IgG; positive (>1/80) ANA, anti-SMA, anti-SLA/− LP in type 1 AIH; anti-LKM 1 and 3, anti-LC-1 in type 2 AIH 1.

Importance of Prompt Evaluation

Without identifying and addressing the underlying cause, continued liver inflammation can potentially progress to more serious conditions including fibrosis or cirrhosis over time. The CLIF-C AD score has been shown to perform better than the MELD, MELD-Na and Child-Pugh scores in predicting 90-day, 180-day and 365-day mortality in patients with acutely decompensated cirrhosis 1.

From the Research

Elevated Liver Enzymes and Leukocytosis

• Continued elevated liver enzymes with leukocytosis (elevated white blood cell count) can indicate a range of conditions, including liver diseases and extrahepatic diseases 2.
• Elevated liver enzymes are a frequent finding in both symptomatic and asymptomatic patients, necessitating further evaluation to clarify the underlying disease 2.
• The pattern of increased liver enzymes can help define the underlying cause, with three different patterns:
  • Predominant increase in transaminase activities, indicating a disturbance of hepatocellular integrity, which can be found in patients with viral hepatitis, genetic liver diseases, or drug-induced liver diseases 2.
  • High serum alkaline phosphatase and γ-glutamyltranspeptidase activities, indicating cholestatic liver diseases, which can be further evaluated with an ultrasound study to discern intra- from extrahepatic cholestasis 2.
  • Predominant rise in γ-glutamyl transpeptidase, observed in alcoholic or non-alcoholic fatty liver disease and infiltrating liver diseases 2.

Diagnostic Approach

• The diagnostic approach to elevated liver enzymes should be guided by both the clinical presentation and the pattern of injury 3.
• Liver biopsy plays an important role in the diagnostic regimen, particularly in the diagnosis of autoimmune hepatitis, where it can help evaluate the severity of portal inflammation and interface hepatitis, and the presence and extent of centrilobular and bridging necrosis 4.
• Serologic markers, such as aminotransferases, IgG, and gamma-globulin levels, can be used to monitor disease activity in autoimmune hepatitis, although liver biopsy remains the gold standard for assessing disease activity and response to treatment 5.

Monitoring and Diagnosis

• Liquid biopsy methods, including cell-free DNA, long non-coding RNA, and proteins in extracellular vesicles, are being researched as potential diagnostic tools and novel therapeutic targets in patients with viral hepatitis, fatty liver steatosis, and alcoholic liver diseases 6.
• These methods may provide a non-invasive means of monitoring chronic liver diseases and detecting liver damage at an early stage.