Is low Alanine Aminotransferase (ALT) activity prognostically significant?

From the Guidelines

Low ALT activity is prognostically significant, as even levels between 20 and 30 IU/mL can increase the risk of mortality from liver complications. This is based on data from cohort studies involving first-time blood donors and healthy volunteers, which suggest that the upper limit of normal (ULN) for ALT should be significantly lower than previously established limits, at 30 IU/mL for men and 19 IU/mL for women 1. The relationship between ALT level and disease progression has been confirmed in a long-term follow-up analysis of 3233 CHB patients from Hong Kong, highlighting the importance of considering ALT levels in the context of liver disease risk.

Some key points to consider when evaluating the prognostic significance of low ALT activity include:

• The lack of strict correlation between the extent of liver cell necrosis and the degree of increase in ALT, which means that ALT alone does not identify patients with necroinflammatory activity or fibrosis with optimal reliability 1
• The potential for ALT activity to be affected by additional factors such as body mass index, gender, abnormal lipid and carbohydrate metabolism, fatty liver, and uremia 1
• The finding that HBV-infected individuals with ALT values <40 to 45 IU/mL are at risk for significant liver disease, and even ALT levels between 20 and 30 IU/mL increase the risk of mortality from liver complications 1

In clinical practice, it is essential to interpret ALT levels in the context of the patient's overall health status, including demographics, comorbidities, and other laboratory results. This will help to identify patients who may be at risk for significant liver disease or other complications, even if their ALT levels are within the normal range. By considering the prognostic significance of low ALT activity, clinicians can provide more accurate risk assessments and develop targeted treatment plans to improve patient outcomes.

From the Research

Prognostic Significance of Low Alanine Aminotransferase (ALT) Activity

• Low ALT activity has been associated with increased long-term mortality in certain populations, including patients with coronary heart disease 2 and the elderly 3.
• A study found that low ALT levels (<17 IU/l) were independently associated with 11% greater long-term (22.8 years) mortality risk in patients with stable coronary heart disease 2.
• Another study discovered that low ALT was associated with loss of independence or death in the elderly, with hazard ratios of 3.02 and 1.55 for ALT <10 and 10-20 U/L groups, respectively 3.
• In contrast, high ALT levels are often used as a marker for liver injury, but low ALT levels may indicate vitamin B6 deficiency or other underlying conditions 3.
• The prognostic utility of ALT levels is complex and may depend on the specific population and context, with some studies suggesting that low ALT levels may be a significant predictor of adverse outcomes 2, 3.

Clinical Implications

• Clinicians should be aware of the potential prognostic significance of low ALT levels, particularly in patients with coronary heart disease or the elderly 2, 3.
• Low ALT levels may indicate underlying conditions such as vitamin B6 deficiency or frailty, which could impact patient outcomes 3.
• Further research is needed to fully understand the clinical implications of low ALT levels and to develop new biomarkers for liver injury that may complement or replace ALT in the future 4.

Study Findings

• A study of patients with Budd-Chiari syndrome found that high ALT levels were associated with more severe liver disease, but the prognostic significance of low ALT levels was not specifically examined 5.
• A study of patients with chronic hepatitis C found that low ALT levels (<20 U/L) could reliably exclude significant liver disease, but the prognostic significance of low ALT levels was not further explored 6.