From the Guidelines
Deranged liver function tests (LFTs) are most commonly caused by non-alcoholic fatty liver disease (NAFLD) and alcohol-induced liver disease, with the former being the most prevalent liver disease in first-world countries, affecting 20-30% of the general population. The causes of deranged LFTs can be broadly categorized into hepatocellular and cholestatic patterns. Hepatocellular injury, characterized by elevated aminotransferases (AST and ALT), can result from various factors, including fatty liver disease, viral hepatitis, autoimmune hepatitis, and medications/toxins 1. On the other hand, cholestatic patterns, marked by elevated alkaline phosphatase and bilirubin, are often associated with bile flow problems.
Some of the key causes of deranged LFTs include:
- Non-alcoholic fatty liver disease (NAFLD)
- Alcohol-induced liver disease
- Viral hepatitis (hepatitis A, B, C, D, and E)
- Drug-induced liver injury
- Autoimmune hepatitis
- Biliary obstruction
- Metabolic conditions such as hemochromatosis, Wilson's disease, and alpha-1 antitrypsin deficiency
The pattern of LFT abnormalities can provide valuable clues to the underlying cause. For instance, a hepatocellular pattern with elevated AST/ALT suggests direct liver cell damage, while a cholestatic pattern with elevated alkaline phosphatase and bilirubin points to bile flow problems 1. When evaluating abnormal LFTs, it is essential to consider the patient's complete medical history, medication use, alcohol consumption, and risk factors for viral hepatitis to determine the appropriate diagnostic workup and management.
The diagnosis and management of liver disease have evolved significantly, with the development of new diagnostic tools and treatment options. The FIB-4 and NAFLD fibrosis scores are useful in assessing the likelihood of liver fibrosis in patients with NAFLD or liver disease of unknown etiology 1. Additionally, imaging modalities such as ARFI elastography/FibroScan can help identify patients with advanced fibrosis.
In clinical practice, it is crucial to prioritize the most common and significant causes of deranged LFTs, such as NAFLD and alcohol-induced liver disease, and to consider the patient's individual risk factors and medical history when determining the appropriate diagnostic and management approach.
From the FDA Drug Label
Among entecavir-treated subjects in these studies, on-treatment ALT elevations greater than 10 times the upper limit of normal (ULN) and greater than 2 times baseline generally resolved with continued treatment. A majority of these exacerbations were associated with a ≥2 log 10/mL reduction in viral load that preceded or coincided with the ALT elevation ALT >10 x ULN and >2 x baseline 2% 4% 2% 11% ALT >5 x ULN 11% 16% 12% 24%
The causes of deranged LFT's include:
- ALT elevations: on-treatment ALT elevations greater than 10 times the upper limit of normal (ULN) and greater than 2 times baseline
- Viral load reduction: a ≥2 log 10/mL reduction in viral load that preceded or coincided with the ALT elevation
- Hepatitis exacerbation: severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including entecavir 2
- Lactic acidosis and hepatomegaly: lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogue inhibitors 2
From the Research
Causes of Deranged Liver Function Tests (LFTs)
Deranged LFTs can be caused by various factors, including:
- Hepatocellular damage, which can be due to non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol use, chronic viral hepatitis, liver cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, celiac disease, medication-induced liver injury, and ischemic hepatitis 3
- Cholestatic disorders, which can be caused by biliary pathology, such as obstruction or autoimmune diseases, as well as other conditions that lead to hyperbilirubinemia (conjugated and unconjugated) 3
- Alcoholic liver disease (ALD), which can cause deranged LFTs due to excessive alcohol intake, leading to hepatic mitochondrial injury and pyridoxine deficiency 4
- Non-alcoholic steatohepatitis (NASH) and acute viral hepatitis, which can also cause deranged LFTs, although the patterns of liver enzyme elevation may differ from those seen in ALD 4
Patterns of LFT Derangement
The patterns of LFT derangement can provide clues to the underlying cause, including:
- Hepatocellular pattern, characterized by elevated aminotransferases, which can be further sub-classified based on the magnitude of elevation 3
- Cholestatic pattern, characterized by elevated alkaline phosphatase and gamma-glutamyl transferase, which can be caused by biliary pathology or other conditions leading to hyperbilirubinemia 3
- Mixed pattern, which can be seen in cases of ALD, NASH, and acute viral hepatitis 4
Diagnostic Approaches
The diagnosis of deranged LFTs involves a combination of clinical evaluation, laboratory tests, and imaging studies, including:
- Liver biochemical tests, such as aminotransferases, alkaline phosphatase, gamma-glutamyl transferase, bilirubin, albumin, prothrombin time, and international normalized ratio (INR) 3
- Non-invasive tests, such as ultrasound, computed tomography (CT) scan, and magnetic resonance imaging (MRI), which can help identify liver damage and fibrosis 5
- Liver biopsy, which can provide a definitive diagnosis of liver disease, although it is an invasive procedure 6