Persistent alpha-fetoprotein elevation in patients without viral hepatitis, cirrhosis, hepatocellular carcinoma: A report of six cases and literature review

Table 1 Basic clinical characteristics, follow-up duration, and means and ranges of serum alpha-fetoprotein elevation

Case	Age	Sex	Past medical history	Diagnosis of underlying liver disease	Months of follow-up	Mean AFP elevation (range) ng/mL	AFP initial	AFP EOF
1	69	Female	Pancreatic cyst, stable ovarian cyst	Elevated AFP, liver cyst	54	27.3 (25.2-29.6)	29.6	25.8
2	68	Female	Breast cancer, status post lumpectomy, radiation, chemotherapy, HLD, overweight	Elevated AFP, liver cyst, MASLD	54	16.2 (14.4-18.6)	18.6	14.4
3	61	Female	Right side breast cancer, status post lumpectomy and radiation	Elevated AFP, liver cyst, MASLD	54	12.8 (11.6-14.2)	11.6	14.2
4	74	Male	Macrocytic anemia, alcohol use, hereditary hemochromatosis	Elevated AFP	36	10.7 (9.2-12.9)	9.2	10.6
5	36	Male	Mild elevated LFTs, fatty liver	Elevated AFP, MASLD, liver cyst	36	10.5 (9.7-12.9)	10.4	9.7
6	64	Male	Abnormal LFTs, fatty liver, liver cyst, obesity	Elevated AFP, MASLD	54	9.8 (8.9-11.1)	9.5	10.8

AFP: Alpha-fetoprotein; EOF: End-of-follow-up; MASLD: Metabolic dysfunction-associated steatotic liver disease; HLD: Hyperlipidemia; LFT: Liver function test.

Table 2 The actual alpha-fetoprotein and liver enzyme values during follow-up visits

Case	AFP levels (ng/mL) at different follow-up by months										Liver function test (U/L)
	0	6	12	18	24	30	36	42	48	54	AST	ALT	ALP
1	29.6	26.3	29.6	28.7	26.3	26.8	27.2	27	25.2	25.8	13-20	8-16	57-84
2	18.6	17.3	16.7	17.5	15.3	15.4	15.8	16.3	14.9	14.4	15-31	10-48	39-55
3	11.6	11.9	13.2	11.7	11.8	12.8	12.6	13.9	14	14.2	23-34	16-34	26-43
4	9.2	11.5	12.1	10.6	10.5	10.5	10.6				22-40	17-41	61-80
5	10.4	9.9	10.6	9.9	12.9	10	9.7				15-28	10-27	54-91
6	9.5	9.7	9.4	9	8.9	10.7	9.2	9.4	11.1	10.8	17-25	15-34	37-52

AFP: Alpha-fetoprotein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase.

Table 3 Literature summary on possible underlying causes and mechanisms of serum alpha-fetoprotein elevation

Authors	Summary of findings
Caviglia et al[17]	AFP levels increased significantly from advance fibrosis without HCC to the progression of HCC
Seo et al[18]	An elevated serum AFP level often indicates active liver regeneration
Kuhlmann et al[19]	An increase in AFP expression during hepatocyte regeneration
Nishida et al[20]	Serum AFP level correlated with the accumulation of oxidative DNA damage in hepatocytes
Goldstein et al[21]	Alteration in hepatocellular interactions and loss of the normal structural arrangement led to an elevated serum AFP level

AFP: Alpha-fetoprotein; HCC: Hepatocellular carcinoma.