Elevated alpha-fetoprotein = liver cancer? What is the connection between the two?

AFP

Alpha-fetoprotein (AFP) is the most widely used serum marker for the auxiliary diagnosis of liver cancer in clinical practice. The 2017 Guidelines for the Diagnosis and Treatment of Primary Liver Cancer points out that serum AFP and liver ultrasound examination are the main means of early screening, and it is recommended that high-risk groups undergo at least one examination every 6 months.

The 2015 edition of my country's "Guidelines for the Prevention and Treatment of Chronic Hepatitis B" states: "Serum alpha-fetoprotein (AFP) and its isomers are important indicators for diagnosing hepatocellular carcinoma." Does elevated alpha-fetoprotein mean liver cancer? Be careful of missed or misdiagnosis!

Alpha-fetoprotein and its detection value

Alpha-fetoprotein (AFP) is a single-chain glycoprotein synthesized by fetal liver cells and is a special protein that normally exists in fetal serum. AFP disappears from the blood about two weeks after the birth of the fetus, and the content of AFP in normal human serum is less than 20 ng/ml. In adults, elevated AFP can be seen in primary liver cancer, active liver disease, reproductive system tumors, pregnant women, pancreatic cancer, and lung cancer.

The 2017 Guidelines for the Diagnosis and Treatment of Primary Liver Cancer recommends that the criteria for diagnosing liver cancer with elevated alpha-fetoprotein levels are:

AFP ≥ 400 μg/L excludes chronic or active hepatitis, cirrhosis, testicular or ovarian embryonic tumors, and pregnancy. Patients with low-level elevations in AFP should be dynamically observed and compared with changes in liver function to help with diagnosis. About 30% of liver cancer patients have normal AFP levels, and the detection of alpha-fetoprotein isomers can help improve the diagnosis rate.

In addition to liver cancer, AFP will also increase in these situations

About 80% of patients with primary liver cancer have elevated alpha-fetoprotein in their serum. Liver cancer is one of the common causes of elevated alpha-fetoprotein. When liver cells become cancerous, they regain the ability to produce alpha-fetoprotein, and as the disease worsens, its content in the serum increases dramatically. Alpha-fetoprotein has become an effective indicator for auxiliary diagnosis, efficacy assessment, and prognosis of primary liver cancer.

1

Pregnant women

Women with normal pregnancies will also experience a temporary increase in alpha-fetoprotein, but the increase is not as high as that of liver cancer. Alpha-fetoprotein in the fetal period is produced by the yolk sac and liver of pregnant women. Alpha-fetoprotein is a normal plasma protein component of the fetus and the main protein in the early embryo. The alpha-fetoprotein level of pregnant women will increase significantly. Generally, alpha-fetoprotein will increase significantly in the third month of pregnancy. The amount of AFP in the blood of pregnant women reaches its peak and is relatively stable in July and August, but it is still below 400 ng/ml. It gradually returns to normal levels about 3 weeks after delivery.

2

Acute/chronic hepatitis, cirrhosis

In the recovery period of acute/chronic hepatitis, severe hepatitis or cirrhosis, the patient's serum alpha-fetoprotein may increase, but the increase is usually small and lasts for a short time. For example, the serum alpha-fetoprotein concentration of patients with cirrhosis is mostly between 25 and 200 ng/ml, and generally decreases within 2 months as the condition improves, and most of them will not exceed 2 months; at the same time, it is accompanied by an increase in transaminase. When the transaminase decreases, the alpha-fetoprotein also decreases. The serum alpha-fetoprotein concentration is often parallel to the transaminase. If the alpha-fetoprotein concentration is at a high level for a long time (above 500 ng/ml), or increases progressively, you should be alert to the occurrence of liver cancer.

3

Neonatal hepatitis

AFP can be detected in 30% of neonatal hepatitis, and the incidence increases with the severity of the disease, and most cases are significantly higher. It should be differentiated from congenital biliary atresia, in which AFP is mostly normal.

4

Other causes

Patients with liver damage, congestive hepatomegaly, telangiectasia, congenital tyrosinosis, testicular or ovarian embryonal tumors, some other digestive tract tumors, pancreatic cancer, etc. may also have varying degrees of elevated alpha-fetoprotein.

Elevated alpha-fetoprotein does not mean liver cancer

AFP can be considered a tumor signal, which means that liver cancer may have occurred. However, there is no absolute relationship between the level of AFP and the size of liver cancer. There are two points to note about the relationship between AFP and liver cancer:

First, about one-third of small liver cancers will not have elevated AFP, so normal AFP does not mean that there is no liver cancer.

Second, elevated alpha-fetoprotein levels do not necessarily indicate liver cancer. Since alpha-fetoprotein is a special protein produced during liver cell development, it can also be produced and secreted during acute and chronic hepatitis and cirrhosis, along with liver repair and liver cell regeneration, causing an increase in serum AFP. AFP levels may also increase after the use of some drugs that stimulate liver cell regeneration (such as hepatocyte growth hormone). Therefore, attention should be paid to the magnitude of AFP increase, its dynamic changes, and its relationship with ALT and AST, and a comprehensive analysis should be conducted in combination with clinical manifestations and liver imaging examination results.

If the alpha-fetoprotein level is greater than 500 ng/ml and persists for 4 weeks, or if the alpha-fetoprotein level is between 200 and 500 ng/ml and persists for 8 weeks, after excluding other factors that cause increased alpha-fetoprotein level (such as acute or chronic hepatitis, cirrhosis, etc.), a diagnosis can be made by combining positioning examinations such as B-ultrasound, CT, magnetic resonance imaging (MRI) and hepatic angiography.

【References】

[1] Liang Kuohuan et al. Hepatology. 2nd edition[M]. People's Medical Publishing House. 2003:252-253.

[2] Cai Haodong. Understanding the 2015 edition of the “Guidelines for the Prevention and Treatment of Chronic Hepatitis B”[M]. China Medical Science and Technology Press. 2015: 64-65.