From the Guidelines
Hepatocellular injury pattern is characterized by a predominant elevation in liver enzymes called aminotransferases (ALT and AST), typically with ALT levels higher than AST, and minimal elevation in alkaline phosphatase (ALP), indicating primary damage to the liver cells (hepatocytes) themselves. This pattern is diagnosed through blood tests showing ALT and AST elevations, with an ALT/ALP ratio greater than 5, distinguishing it from cholestatic injury and mixed patterns 1. Common causes of hepatocellular injury include:
- Viral hepatitis (such as hepatitis A, B, and C)
- Drug-induced liver injury (from medications like acetaminophen, statins, and certain antibiotics)
- Alcoholic hepatitis
- Autoimmune hepatitis
- Ischemic injury
- Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) 1
- Immune-mediated liver injury caused by immune checkpoint inhibitors 1 The liver has remarkable regenerative capacity, and with proper management, hepatocellular injury can often be reversed if the cause is identified and addressed promptly. Treatment focuses on removing the underlying cause, such as discontinuing hepatotoxic medications, treating viral infections, or managing autoimmune conditions. In some cases, liver biopsy may be helpful in differentiating between hepatocellular injury and other causes of liver damage, such as idiopathic autoimmune hepatitis 1. Overall, accurate diagnosis and prompt treatment of hepatocellular injury are crucial to prevent long-term liver damage and improve patient outcomes.
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. An exacerbation of hepatitis or ALT flare was defined as ALT greater than 10 times ULN and greater than 2 times the subject’s reference level (minimum of the baseline or last measurement at end of dosing)
The hepatocellular injury pattern is characterized by ALT elevations greater than 10 times the upper limit of normal (ULN) and greater than 2 times baseline, which generally resolve with continued treatment.
- ALT flares are defined as ALT greater than 10 times ULN and greater than 2 times the subject’s reference level. Key points about hepatocellular injury pattern include:
- On-treatment ALT elevations are common
- ALT flares can occur after discontinuation of treatment
- Periodic monitoring of hepatic function is recommended during treatment 2
From the Research
Hepatocellular Injury Pattern
The hepatocellular injury pattern is characterized by a predominant rise in the level of transaminases and results from the demise of hepatocytes by means of either apoptosis or necrosis 3. This pattern of injury is often seen in drug-induced liver injury, where the drug or its metabolite causes direct damage to the hepatocytes.
Characteristics of Hepatocellular Injury
The characteristics of hepatocellular injury include:
- Predominant rise in the level of transaminases, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 3
- Demise of hepatocytes by means of either apoptosis or necrosis 3
- Mitochondrial damage and central (zone 3) necrosis 4
- Fatty change, which can be seen in conditions such as alcoholic liver disease and non-alcoholic steatohepatitis 4
Diagnosis and Differential Diagnosis
The diagnosis of hepatocellular injury can be made by measuring the levels of serum aminotransferases (AST and ALT) and lactate dehydrogenase (LD) 5. The ALT/LD ratio can be used to differentiate between acute viral hepatitis and ischemic hepatitis or acetaminophen injury 5. A ratio of 1.5 or less is suggestive of ischemic hepatitis or acetaminophen injury, while a ratio of greater than 1.5 is suggestive of acute viral hepatitis.
Pathogenesis and Treatment
The pathogenesis of hepatocellular injury involves the activation of various cellular and molecular mechanisms, including the release of damage-associated molecular patterns (DAMPs) and the activation of immune cells such as macrophages and hepatic stellate cells 6, 7. Treatment of hepatocellular injury is often supportive, with the goal of removing the underlying cause of the injury and promoting liver regeneration. In some cases, liver transplantation may be necessary 3.