What is cholestatic liver disease?

From the Guidelines

Cholestatic liver disease is a condition where bile flow from the liver is reduced or blocked, causing bile to accumulate in the liver, and it can occur due to problems within the liver itself (intrahepatic) or in the bile ducts outside the liver (extrahepatic) 1.

Definition and Causes

Cholestatic liver disease comprises many conditions of dysfunctional bile flow and/or formation, which can lead to progressive hepatobiliary damage and its complications 1. The primary pathogenic mechanisms are yet to be fully elucidated, but improved knowledge of the molecular and cellular pathophysiology and immunopathogenesis of cholestatic liver diseases has led to a resurgence of interest in developing new therapies 1. Common causes include primary biliary cholangitis, primary sclerosing cholangitis, drug-induced liver injury, alcoholic liver disease, and bile duct obstructions from gallstones or tumors.

Diagnosis and Treatment

Diagnosis involves blood tests to check liver function and bilirubin levels, imaging studies like ultrasound or MRI, and sometimes liver biopsy 1. Treatment depends on the underlying cause but may include ursodeoxycholic acid for certain conditions, medications to relieve itching like cholestyramine, addressing the underlying cause (such as removing obstructing gallstones), and in severe cases, liver transplantation 1. Patients with chronic cholestatic liver disease do not appear to have an increased susceptibility for drug-induced liver injury (DILI) compared with those patients without chronic liver disease, but should DILI occur, they have an increased incidence of morbidity and mortality compared with those with healthy livers 1.

Management and Prevention

The condition is serious because prolonged cholestasis can lead to liver damage, cirrhosis, and liver failure if not properly managed 1. Patients should avoid alcohol and certain medications that can worsen liver function, and follow a low-fat diet to help reduce the burden on bile production. The European Association for the Study of the Liver (EASL) Clinical Practice Guidelines provide recommendations for the management of cholestatic liver diseases, including diagnostic approaches, treatment of primary biliary cirrhosis, primary sclerosing cholangitis, and other conditions 1.

Key Considerations

• Patients with chronic cholestatic liver disease require careful monitoring and management to prevent complications and improve outcomes 1.
• A thorough patient history and physical examination are essential in the diagnostic process, and may provide valuable information to predict the nature of cholestasis 1.
• Abdominal ultrasonography is usually the first step to exclude dilated intra- and extrahepatic ducts and other causes of cholestasis 1.

From the FDA Drug Label

Lithocholic acid causes cholestatic liver injury and can cause death from liver failure in certain species unable to form sulfate conjugates.

Cholestatic liver disease is a condition where the flow of bile from the liver is blocked or reduced, causing a buildup of bile in the liver. This can lead to liver injury and potentially death from liver failure, as seen with lithocholic acid in certain species.

• Key points about cholestatic liver disease include:
  • Blockage or reduction of bile flow from the liver
  • Buildup of bile in the liver
  • Potential for liver injury and death from liver failure 2

From the Research

Definition of Cholestatic Liver Disease

• Cholestatic liver disease is a condition that causes liver damage and fibrosis due to bile stasis 3.
• It is characterized by the slowing or stopping of bile flow, which can lead to liver injury, cirrhosis, and death 4.

Types of Cholestatic Liver Disease

• Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are two types of cholestatic liver disease, with different pathophysiological pathways causing bile stasis 3.
• Other conditions, such as intrahepatic cholestasis of pregnancy, liver disease of cystic fibrosis, and chronic graft-versus-host disease, can also cause cholestasis 5.

Symptoms and Diagnosis

• Jaundice is a common symptom of cholestasis, but it may be absent in adults with chronic cholestatic liver disease 6.
• A detailed history, physical examination, and non-invasive radiologic tests (e.g., ultrasound, CT scan, and MRI) can aid in diagnosis 6.
• Liver biopsy can evaluate damage to the small bile ducts, but only if sufficient portal tracts are present 6.

Treatment and Management

• Ursodeoxycholic acid (UDCA) is a widely used treatment for cholestatic liver disease, which can improve serum liver chemistries and delay disease progression 3, 4, 5, 7.
• UDCA has been shown to protect the liver from injury by harmful bile acids and improve symptoms in patients with PBC and PSC 4, 5, 7.
• Liver transplantation is the only potentially curative treatment for cholestatic liver disease 6.