What are the causes of hepatic inflammation with liver function test (LFT) derangement?

From the Guidelines

Hepatic inflammation with liver function test (LFT) derangement requires prompt evaluation and management, with initial steps including discontinuing any hepatotoxic medications and conducting comprehensive testing, as recommended by the Asia-Pacific Working Group for Liver Derangement during the COVID-19 Pandemic 1.

Key Considerations

• Discontinuing hepatotoxic medications and avoiding alcohol are crucial initial steps in managing hepatic inflammation with LFT derangement.
• Comprehensive testing, including viral hepatitis panels, autoimmune markers, and imaging studies, is necessary to determine the underlying cause of the liver derangement.
• Treatment depends on the underlying cause, with options including antiviral medications for viral hepatitis, prednisone and azathioprine for autoimmune hepatitis, and complete alcohol cessation with nutritional support for alcoholic hepatitis.
• Supportive care, such as maintaining hydration and monitoring for complications, is essential in managing patients with liver derangement.

Underlying Causes and Treatment

• Viral hepatitis may require antiviral medications like entecavir or tenofovir for hepatitis B, or direct-acting antivirals for hepatitis C.
• Autoimmune hepatitis typically responds to prednisone (starting at 40-60mg daily) with azathioprine (50-150mg daily) added as a steroid-sparing agent.
• Alcoholic hepatitis necessitates complete alcohol cessation with nutritional support.
• Drug-induced liver injury requires immediate cessation of the offending agent.

Monitoring and Supportive Care

• Regular monitoring of liver function tests is necessary in patients with abnormal LFTs, particularly those on potentially hepatotoxic medication or with pre-existing liver disease.
• Supportive care includes maintaining hydration, monitoring for complications like coagulopathy or encephalopathy, and considering ursodeoxycholic acid (10-15mg/kg/day) for cholestatic patterns.
• Severe cases with signs of liver failure require urgent hepatology consultation and possible hospital admission, as recommended by the Asia-Pacific Working Group for Liver Derangement during the COVID-19 Pandemic 1.

Additional Recommendations

• Patients with COVID-19 and liver derangement should have standard investigations for liver diseases, including serological tests for viral hepatitis, as recommended by the Asia-Pacific Working Group for Liver Derangement during the COVID-19 Pandemic 1.
• Off-label treatment for COVID-19 should be used with caution and close monitoring in patients with abnormal liver function, as recommended by the Asia-Pacific Working Group for Liver Derangement during the COVID-19 Pandemic 1.
• Clinicians should test liver function in hospitalized patients with COVID-19, as recommended by the Asia-Pacific Working Group for Liver Derangement during the COVID-19 Pandemic 1.

From the FDA Drug Label

1. 1 Exacerbation of Hepatitis after Discontinuation of Treatment Discontinuation of anti-HBV therapy, including tenofovir disoproxil fumarate, may be associated with severe acute exacerbations of hepatitis Patients infected with HBV who discontinue tenofovir disoproxil fumarate should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment.
2. 3 Lactic Acidosis/Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir DF, alone or in combination with other antiretrovirals

Hepatic Inflammation and LFT Derangement: Tenofovir disoproxil fumarate may be associated with severe acute exacerbations of hepatitis after discontinuation of treatment, and lactic acidosis and severe hepatomegaly with steatosis have been reported with its use 2.

• Patients with hepatitis B should be closely monitored after stopping treatment.
• Lactic acidosis and severe hepatomegaly with steatosis are potential risks associated with tenofovir disoproxil fumarate.

From the Research

Hepatic Inflammation and LFT Derangement

• Hepatic inflammation can lead to derangement of liver function tests (LFTs) 3, 4
• LFT derangement can be categorized into different patterns, including hepatocellular, cholestatic, and mixed 3, 4
• The interpretation of LFT derangement requires consideration of the clinical context, including the patient's medical history, physical examination, and risk factors 3, 4

Causes of LFT Derangement

• LFT derangement can be caused by various factors, including:
  • Hepatic inflammation due to viral hepatitis, autoimmune hepatitis, or other causes 3, 5, 6
  • Biliary obstruction or other structural causes 3
  • Drug-induced liver injury 3, 7
  • Infections, such as opportunistic infections in immunocompromised patients 3
  • Recurrence of primary disease, such as liver cancer 3

Management of LFT Derangement

• The management of LFT derangement depends on the underlying cause and may involve:
  • Medical treatment, such as ursodeoxycholic acid (UDCA) for autoimmune-associated chronic hepatitis C 5, 6
  • Surgical intervention, such as liver transplantation 3
  • Supportive care, such as nutritional support and monitoring of liver function 7
• Liver biopsy may be necessary to confirm the diagnosis and assess the severity of liver disease 3