Alfa feto protein or AFP

1. Alpha-fetoprotein

2. Alpha-fetoprotein
• — Alpha-fetoprotein is a glycoprotein that is
normally produced during gestation by the fetal
liver and yolk sac, the serum concentration of
which is often elevated in patients with HCC.
Serum levels of AFP do not correlate well with
other clinical features of HCC such as size, stage,
or prognosis. Elevated serum AFP occurs in
pregnancy (figure 1), with tumors of gonadal
origin (both germ cell and non-germ cell [56]) and
in a variety of other malignancies, of which
gastric cancer is the most common [57].

3. • Elevated serum AFP may also be seen in
patients with chronic liver disease without
HCC such as acute or chronic viral hepatitis
[58,59]. AFP may be slightly higher in patients
with cirrhosis due to hepatitis C [60]. In one
report, serum AFP decreased significantly in
patients with cirrhosis from hepatitis C,
treated with peginterferon plus ribavirin [60].

4. • A rise in serum AFP in a patient with cirrhosis
or hepatitis B should raise concern that HCC
has developed. It is generally accepted that
serum levels greater than 500 mcg/L (normal
in most laboratories is between 10 and
20 mcg/L) in a high-risk patient is diagnostic of
HCC [61]. However, HCC is often diagnosed at
a lower AFP level in patients undergoing
screening [58,62].

5. • Not all tumors secrete AFP, and serum
concentrations are normal in up to 40 percent
of small HCCs [63]. Furthermore, an elevated
AFP may be more likely in patients with HCC
due to viral hepatitis compared with alcoholic
liver disease [64].

6. • In a study of 357 patients with hepatitis C and
without HCC, 23 percent had an AFP
>10.0 mcg/L [65]. Elevated levels were
associated with the presence of stage III or IV
fibrosis, an elevated international normalized
ratio, and an elevated serum aspartate
aminotransferase level.

7. • AFP levels are normal in the majority of
patients with fibrolamellar carcinoma, a
variant of HCC (picture 1) [66].
(See "Pathology of malignant liver tumors",
section on 'Fibrolamellar carcinoma'.)

8. • Patients with cirrhosis and persistently
elevated AFP values have an increased risk of
developing HCC compared with those who
have fluctuating or normal levels (29 versus 13
and 2.4 percent, respectively, in one report)
[67].

9. • The sensitivity, specificity, and predictive value for
the serum AFP in the diagnosis of HCC depends
upon the characteristics of the population under
study, the cutoff value chosen for establishing the
diagnosis, and the gold-standard used to confirm
the diagnosis. A number of studies have
described test characteristics in different settings
[68,69]. The following estimates were based
upon a cutoff value of >20 mcg/L in a systematic
review that included five studies [70]:

10. • ●Sensitivity 41 to 65 percent
• ●Specificity 80 to 94 percent
• ●Positive likelihood ratio 3.1 to 6.8
• ●Negative likelihood ratio 0.4 to 0.6
• Three examples (one of which was included in
the above study) illustrate the range of
findings in the individual reports:

11. • One study included 1069 patients who were
chronic carriers of hepatitis B who underwent
regular screening with a serum AFP [68]. Serum
AFP was greater than 20 mcg/L in 9 of 14 patients
with HCC compared with 91 of 964 patients
without the tumor, giving an overall sensitivity
and specificity of 64 and 91 percent, respectively.
However, only 9 of the 100 patients with AFP
values greater than 20 mcg/L had HCC (positive
predictive value 9 percent) even in this
population of patients with a high prevalence of
HCC (table 1).

12. • In a similar study of 1531 patients with hepatitis
B who were receiving entecavir and undergoing
screening, 57 patients developed HCC [71]. An
AFP value ≥20 mcg/L had a sensitivity and
specificity for HCC of 33 and 98 percent,
respectively (positive predictive value of 45
percent, negative predictive value of 98 percent).
If the cutoff was dropped to ≥6 mcg/L, the values
for sensitivity and specificity were 79 and 80
percent, respectively (positive predictive value of
12 percent, negative predictive value of 99
percent).

13. • A case-control study evaluated the diagnostic
characteristics of the serum AFP in screening for HCC in
patients with different types of chronic liver disease. The
following sensitivities and specificities were observed [69]:
• ●AFP cutoff 16 mcg/L (sensitivity 62, specificity 89 percent)
• ●AFP cutoff 20 mcg/L (sensitivity 60, specificity 91 percent)
• ●AFP cutoff 100 mcg/L (sensitivity 31, specificity 99
percent)
• ●AFP cutoff 200 mcg/L (sensitivity 22, specificity 99
percent)

14. • At a prevalence of HCC of 5 percent, a serum AFP
of ≥20 mcg/L (the cutoff value the authors
considered to be best) had a positive and
negative predictive value of 25 and 98 percent,
respectively. At a prevalence of 20 percent, these
numbers were 61 and 90 percent, respectively.
The low positive predictive values observed in
these studies [68,69] (and the test characteristics
described in the systematic review above [70])
underscore the limitation of using the serum AFP
as a screening test for HCC.

15. • Despite the issues inherent in using AFP for
the diagnosis of HCC, it has emerged as an
important prognostic marker, especially in
patients undergoing resection and those being
considered for liver transplantation. Patients
with AFP levels >1000 mcg/L have an
extremely high risk of recurrent disease
following transplantation, irrespective of the
tumor size