How to manage a patient with elevated liver enzymes and abnormal protein levels in general practice?

From the Guidelines

Management of a patient with elevated liver enzymes and abnormal protein levels in general practice requires a systematic approach focusing on diagnosis, monitoring, and appropriate intervention, with the primary goal of preventing progression to cirrhosis and liver failure, as outlined in the 2023 guidelines on the role of noninvasive biomarkers in the evaluation and management of nonalcoholic fatty liver disease 1.

Initial Assessment

Begin with a thorough history and physical examination, looking for risk factors such as alcohol use, medications, obesity, and family history of liver disease. Order comprehensive liver function tests including ALT, AST, ALP, GGT, bilirubin, albumin, and prothrombin time. Additional testing should include viral hepatitis serology (HBV, HCV), autoimmune markers (ANA, ASMA, immunoglobulins), iron studies, and abdominal ultrasound.

Risk Stratification

Use the Fibrosis 4 Index (FIB-4) as a first-line point-of-care test to assess the risk of advanced hepatic fibrosis, as recommended by the 2023 guidelines 1. For patients with a FIB-4 <1.3, advanced hepatic fibrosis can be excluded with a high negative predictive value, and these patients can be reassessed every 2 years. For patients with a FIB-4 ≥1.3, a secondary assessment (enhanced liver fibrosis [ELF], vibration-controlled elastography [VCTE] or magnetic resonance elastography [MRE]) can be performed.

Lifestyle Modifications

Recommend lifestyle modifications, including weight loss of 7-10% through a Mediterranean diet and regular exercise, for patients with metabolic-associated fatty liver disease, as suggested by the 2023 guidelines on the role of noninvasive biomarkers in the evaluation and management of nonalcoholic fatty liver disease 1.

Referral to Specialist

Patients with signs of advanced liver disease (ascites, encephalopathy, coagulopathy) or persistent significant elevations (greater than 3 times normal for over 6 months) should be referred to a hepatologist for further evaluation and management, as recommended by the 2018 guidelines on the management of abnormal liver blood tests 1.

Key Considerations

• The 2023 guidelines on the role of noninvasive biomarkers in the evaluation and management of nonalcoholic fatty liver disease provide a framework for the evaluation and management of patients with NAFLD 1.
• The 2018 guidelines on the management of abnormal liver blood tests emphasize the importance of a systematic approach to the evaluation and management of patients with abnormal liver function tests 1.
• The ACR Appropriateness Criteria for abnormal liver function tests provide guidance on the use of imaging modalities in the evaluation of patients with abnormal liver function tests 1.

From the Research

Patient Management

To manage a patient with elevated liver enzymes and abnormal protein levels in general practice, the following steps can be taken:

• Evaluate the patient's medical history and perform a physical examination to identify potential causes of elevated liver enzymes 2, 3, 4
• Order initial investigations, such as a fasting lipid profile, measurement of glucose, serum iron, and ferritin, total iron-binding capacity, and hepatitis B surface antigen and hepatitis C virus antibody testing 5
• Consider the patterns of liver enzyme elevation, including hepatocellular, cholestatic, and isolated hyperbilirubinemia, to narrow down the differential diagnosis 3, 4
• If the patient has a predominant increase in transaminase activities, consider viral hepatitis, genetic liver diseases, and drug-induced liver diseases as potential causes 3
• If the patient has high serum alkaline phosphatase and γ-glutamyltranspeptidase activities, consider cholestatic liver diseases, such as primary and secondary sclerosing cholangitis, and extrahepatic cholestasis, such as obstruction of the large bile ducts by gall stones or tumors 3

Further Evaluation

If the initial investigations do not reveal a cause for the elevated liver enzymes, further evaluation may be necessary, including:

• Ultrasonography to discern intra- from extrahepatic cholestasis 3
• Measurement of α(1)-antitrypsin and ceruloplasmin to evaluate for α(1)-antitrypsin deficiency and Wilson disease 5
• Serum protein electrophoresis to evaluate for hemochromatosis and other genetic liver diseases 5
• Antinuclear antibody, smooth muscle antibody, and liver/kidney microsomal antibody type 1 testing to evaluate for autoimmune hepatitis 5

Referral and Follow-up

If the patient's transaminase levels remain elevated for six months or more, referral for further evaluation and possible liver biopsy is recommended 5 Regular follow-up appointments should be scheduled to monitor the patient's liver enzyme levels and adjust the management plan as necessary 2, 6