What is the management approach for a patient with elevated Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and alkaline phosphatase (alk phos)?

From the Guidelines

The management of a patient with elevated AST, ALT, and alkaline phosphatase should begin with a thorough diagnostic evaluation to determine the underlying cause before initiating specific treatment. Initial steps include obtaining a detailed medical history focusing on medication use, alcohol consumption, and risk factors for viral hepatitis, followed by comprehensive laboratory testing including hepatitis serologies, autoimmune markers, iron studies, and ceruloplasmin levels 1. Imaging studies such as ultrasound or CT scan of the liver should be performed to assess for structural abnormalities, biliary obstruction, or masses. While investigating the cause, patients should discontinue potentially hepatotoxic medications and alcohol consumption.

Management is then tailored to the specific etiology:

• viral hepatitis may require antiviral medications (entecavir or tenofovir for hepatitis B; sofosbuvir/ledipasvir or glecaprevir/pibrentasvir for hepatitis C)
• autoimmune hepatitis typically responds to prednisone (starting at 40-60mg daily) with or without azathioprine (50-150mg daily)
• primary biliary cholangitis is treated with ursodeoxycholic acid (13-15mg/kg/day)
• and alcoholic liver disease requires complete alcohol cessation with nutritional support. For drug-induced liver injury, the offending agent should be discontinued 1. Throughout treatment, liver enzymes should be monitored regularly, typically every 2-4 weeks initially, then less frequently as they normalize. Patients with signs of liver failure (encephalopathy, coagulopathy, ascites) require immediate hospitalization and possible referral for liver transplantation evaluation.

Key considerations in the diagnostic workup include:

• Monitoring patient for abnormal liver blood tests: AST, ALT, and bilirubin before each infusion and/or consider weekly if grade 1 LFT elevations 1
• Reviewing medications and supplements that may cause hepatotoxicity and ruling out abnormal liver enzymes from development or progression of liver metastases
• Considering liver biopsy if the patient is steroid-refractory or if concern for other differential diagnoses that would alter medical management 1. Given the complexity of interpreting ALP in patients, those meeting certain ALT and TBIL criteria, regardless of ALP, should be assessed for DILI 1. A thorough accounting of concomitant medications, herbals, and dietary supplements should also be obtained.

In patients without TBIL elevations, a tiered approach towards investigating liver test abnormalities is recommended, evaluating the most likely alternative causes of liver injury first, before moving onto investigations for rarer causes of liver injury 1. Liver biopsy may be useful in patients where liver biochemical tests fail to resolve, or worsen, despite removal of study drug, and where other testing is unremarkable. This can identify unexpected causes of liver injury such as occult hepatic metastases, opportunistic infections, or other disorders.

From the Research

Management Approach for Elevated AST, ALT, and Alkaline Phosphatase

The management approach for a patient with elevated Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and alkaline phosphatase (alk phos) involves a series of steps to determine the underlying cause of the elevation.

• The first step is to evaluate the patient's medical history, perform a physical examination, and apply non-invasive diagnostic tests such as serology, iron levels, autoimmunity, or abdominal ultrasound 2.
• The evaluation of liver function tests, including biochemical parameters (AST, ALT, GGT or Alkaline phosphatase), bilirubin, and albumin levels, as well as coagulation tests, is crucial in determining the cause of the elevation 2.
• In cases of cytolytic elevation in serum aminotransferases, pharmacological toxicity, viral hepatitis, alcoholic and non-alcoholic fatty liver disease, and hemochromatosis should be excluded 2.
• For cholestatic elevation of serum enzymes, the origin of the alkaline phosphatase elevation should be established, and the evaluation of GGT levels can confirm the hepatic origin 2.
• The next step is to distinguish between extrahepatic (biliary obstruction) or intrahepatic (PBC, PSC, drugs, etc.) cholestasis, and abdominal ultrasound can be used to evaluate the biliary system 2.

Diagnostic Considerations

• The ratio of AST to ALT can help differentiate between alcoholic and non-alcoholic liver disease, with a higher ratio often indicating alcoholic liver disease 3.
• The presence of autoimmune antibodies, such as antinuclear antibody, can indicate autoimmune hepatitis or cholangitis 4.
• Liver biopsy can be used to confirm the diagnosis and evaluate the extent of liver damage 5, 6, 4.

Treatment Options

• Treatment for elevated AST, ALT, and alkaline phosphatase depends on the underlying cause, and may include pharmacological therapy, such as ursodeoxycholic acid, immunosuppressive agents, or vitamin E 6, 4.
• Lifestyle modifications, such as weight reduction, alcohol abstinence, and avoidance of hepatotoxic drugs, may also be recommended 3.
• In cases of non-alcoholic steatohepatitis (NASH), treatment with pioglitazone and vitamin E may be effective in normalizing liver enzymes and improving lipid profiles 6.