ALT Elevation in Hemochromatosis
Yes, ALT can be elevated in patients with hemochromatosis, and elevated ALT levels are recognized as an important indicator of significant liver disease and iron overload. 1
Clinical Significance of ALT Elevation
Elevated ALT (and AST) levels serve as key indicators for determining the need for liver biopsy in hemochromatosis patients. According to the American Association for the Study of Liver Diseases, C282Y homozygotes with elevated ferritin (<1000 μg/L) but without ALT or AST elevation can proceed directly to phlebotomy without liver biopsy. 1 However, when liver enzymes are elevated, liver biopsy is recommended to stage the degree of liver disease. 1
Predictive Value for Iron Overload
The presence of elevated ALT has strong predictive value for substantial iron overload:
A serum ferritin level >1000 μg/L combined with elevated aminotransferase levels (ALT or AST) and platelet count <200 predicted the presence of cirrhosis in 80% of C282Y homozygotes. 1
Elevated ALT levels are associated with a 10.1-fold increased risk (95% CI 4.8-21.2) for serum ferritin levels ≥1000 μg/ml in hemochromatosis patients. 2
Elevated ALT levels remained independently associated with elevated ferritin levels even after adjustment for possible confounders. 2
Screening and Detection
ALT elevation can serve as an initial screening trigger for hemochromatosis:
In screening studies, the association of raised ALT activity and transferrin saturation >60% provides a simple, cost-effective method for detecting individuals with clinical hemochromatosis. 3
A common initial presentation is an asymptomatic patient with mildly elevated liver enzymes who is subsequently found to have elevated serum ferritin and transferrin saturation. 4
Among participants with increased transferrin saturation and ferritin levels, ALT increases were found in 8.4% of Caucasians, 11% of Asian and Pacific Islanders, 18% of Hispanics, and 33% of African Americans. 5
Clinical Context and Caveats
It is critical to recognize that not all hemochromatosis patients will have elevated ALT, and the absence of ALT elevation does not exclude the diagnosis. 1 The guidelines specifically distinguish between patients with and without liver enzyme elevation when determining the diagnostic pathway. 1
Even heterozygous carriers can present with elevated ALT when iron overload is present. A case report documented a C282Y heterozygote with significantly elevated transferrin saturation, serum ferritin, and elevated ALT and AST levels requiring phlebotomy treatment. 6
Practical Algorithm
When evaluating a patient with suspected hemochromatosis:
If ferritin is elevated but <1000 μg/L AND ALT/AST are normal: Proceed directly to phlebotomy without liver biopsy 1, 7
If ferritin is >1000 μg/L OR ALT/AST are elevated: Liver biopsy is recommended to stage liver disease 1
If ALT is elevated with high transferrin saturation (>60%): This combination strongly suggests clinically significant hemochromatosis requiring further evaluation 3
The elevation of ALT in hemochromatosis reflects hepatocellular injury from iron deposition and serves as both a diagnostic clue and a prognostic indicator for advanced disease. 1, 2