Is an elevated alpha-fetoprotein (AFP) scary?

  I often sit in the clinic, patients are especially afraid of methemoglobin, especially worried about the occurrence of cancer. Once it rises a little, they often look it up on the Internet and can’t sleep at night. Is this really the case? Here I will explain the basic situation of AFP to all patients.  Alpha-fetoprotein is a glycoprotein that is normally found in small amounts in the body, and the reference value varies greatly from one test manufacturer to another. This protein is mainly derived from developing liver cells or tumor primitive cells. It can also be seen in pregnant women, and alpha-fetoprotein disappears from the blood about two weeks after the birth of the fetus. Methemoglobin is mainly synthesized in the fetal liver and gradually rises after 13 weeks of gestation, and is also an important marker for the gradual development of the fetal liver in pregnant women. It maintains its peak after 30 weeks of gestation, and the concentration in plasma at birth is about 1% of the peak and approaches adult levels (below 30 μg/L) at the age of one week.  AFP in maternal amniotic fluid or maternal plasma can be used for prenatal monitoring of the fetus. For example, in neural tube defects, spina bifida, anencephaly, 85% of mothers with spina bifida and anencephaly; also intrauterine fetal death, teratoma and other congenital defects can have increased AFP in amniotic fluid. However, these cases are relatively rare; especially in Chinese hepatitis B pregnant women, try to avoid amniocentesis to reduce the chances of intrauterine infection, most of which can be detected by ultrasound. Therefore it must be combined with clinical experience to avoid false positives.  In adults, AFP can be elevated in the serum of about 80% of patients with liver cancer (a great innovation of our scientific and technical workers), and in germ cell tumors the rate of positive AFP is 50%. In other gastrointestinal tumors such as pancreatic cancer or lung cancer and cirrhosis of the liver, patients may also show varying degrees of elevation. However, when hepatocellular carcinoma occurs, that is to say, hepatocytes repolarize under certain conditions and transform into primitive cells (that is to say, the process of carcinoma), but the function of producing this protein is restored, and as the cells become more primitive, its level becomes higher, therefore, in advanced hepatocellular carcinoma, its level in the serum increases dramatically, and AFP becomes a specific clinical indicator for diagnosing primary hepatocellular carcinoma. The level of fetoprotein in serum increases dramatically in advanced hepatocellular carcinoma. From here, we can analyze that as long as the cells are primitive, the biochemical reactions have the possibility of producing AFP. Therefore, AFP is a marker of primary cellular rejuvenation, and liver cancer is only a special case of primary cellular rejuvenation. There are many phenomena of cell primordial regeneration in human body, including hepatocyte regeneration after cirrhosis, cell regeneration after cell injury, fetal liver development, etc. All of them are the process of hepatocytes gradually developing from primordial to mature hepatocytes, and all of them will be accompanied by different degrees of AFP increase. The molecular mechanism in the former is gene-induced orderly expression of orderly driven genes, while the latter (HCC) is disorderly or stalled expression of genes. Therefore, it has been considered as a specific tumor marker for the diagnosis of primary liver cancer in the past, with the role of establishing diagnosis, early diagnosis and differential diagnosis. Later, a large number of clinical findings showed that some patients with cirrhosis would have long-term AFP reaching thousands, but no signs of liver cancer for many years; meanwhile, it was found that about 20% of patients with advanced liver cancer (disordered expression of AFP, negative) still had AFP of no more than 10 umol until their death. AFP is secreted by newborn infantile hepatocytes, and fetal hepatocytes are not fully developed (differentiated) and secrete a The amount of AFP secreted by the fetal liver cells is not fully developed (differentiated), so the pregnant woman will have a positive AFP. The fetoprotein level in pregnant women will return to normal after 1 year of delivery. The value of alpha fetoprotein in twin pregnancy is higher than that in single pregnancy. 350ng/ml measured is within the normal range and more than three times the normal value is clinically significant. There is a reference value for singleton pregnancy: the average value of 82.3 at 21 weeks of gestation, and the twin pregnancy should be greater than 493 or more to be meaningful.  Clinical significance of the test: 1. If AFP is greater than 500 micrograms/liter and lasts for 4 weeks, or if AFP is between 200 and 500 micrograms/liter and lasts for 8 weeks, after excluding other factors causing increased AFP such as acute or chronic hepatitis, post-hepatitis cirrhosis, embryonal tumor, gastrointestinal cancer, combined with CT, magnetic resonance imaging (MRI) and liver angiography to find a clear occupancy, the diagnosis can be clear. Of course AFP negative, if there is clear occupancy by imaging test, it needs to be combined with other tests, such as PIVKA-II, etc.  2, normal pregnant women, a few cases of hepatitis and cirrhosis, malignant tumors of the gonads, etc. AFP may also be elevated, but the magnitude of elevation is not as high as that of hepatocellular carcinoma; at the same time, PIVKA-II test is generally negative, which is conducive to differential diagnosis; or combined with AFP heteroplasm can also be differential diagnosis.  3, serum fetoprotein concentration in cirrhotic patients is mostly between 25 and 200 micrograms/liter, and generally decreases within 2 months with the improvement of the disease, most will not exceed 2 months; accompanied by elevated transaminase, when transaminase decreases, fetoprotein also decreases, serum fetoprotein concentration is often in parallel with transaminase. If the concentration of alpha-fetoprotein is above 500 micrograms/liter, although transaminase is elevated, the possibility of hepatocellular carcinoma is high.  4.AFP is elevated 8 months before the appearance of symptoms of hepatocellular carcinoma, when most patients with hepatocellular carcinoma still have no obvious symptoms and the tumor is small, the prognosis of these patients can be significantly improved after surgical treatment; if AFP decreases after treatment, it is also a marker of good prognosis.  Suggestions: 1. If there is a history of hepatitis or family history of HCC, it is recommended to review AFP regularly, 3-4 times a year.  2.If there is cirrhosis with normal liver function (ALT, AST) and AFP is found to be elevated, it is more important to follow up closely and combine with liver imaging tests; if liver imaging is not suggestive, promptly review the germline imaging tests.  3, if the ALT is high accompanied by elevated AFP, it is mostly a marker of good regeneration of hepatocytes or a marker of better prognosis, only regular observation is needed; 4, pregnant patients, if there is elevated AFP, pay attention to regular perinatal work and timely communication with obstetrics and gynecology.  This article is authorized by Dr. Yu Zujiang.