Original Article

Correlation of Serum Alpha Feto-Protein (AFP) levels with size of

hepatocellular carcinoma’s tumors.
Names of researchers

Abstract
Objective: The objective of this study is to determine the correlation of high levels of serum Alpha Feto-Protein
(AFP) with larger tumors in hepatocellular carcinoma (HCC).
Methods: Clinical information of 236 patients diagnosed with HCC was taken to perform this study, of which 175
accomplished the required data to perform the correlation. All demographic data and clinical information was
gathered and registered to complete the investigation. The cases were divided into three groups for each variable
to correlate. About the serum alpha-protein levels, they were divided as group 1 (normal level: < 20 UI/ml), group 2
(higher level: 21 to 399 UI/ml) and group 3 (extremely high level: > 400 UI/ml). According to the size of their tumors,
the group A contains patients with less than three cm. tumors, in group B they are three to five cm. and the group
C is formed by patients whose tumors were larger than 6 cm. Other variables such as number of tumors or Child
Plugh and BCLC scores were considered as additional information.
Results: After reviewing all the clinical data of the patients taken for the sample, 175 of them were considered as
the rest had either no size of tumor or no AFP levels recorded. They comprised 121 male and 54 female. The age
range was from 30 to 85 years old. Of them, there were 61 in group 1, 75 in group 2 and 39 in group three. In
addition, according to the size of their tumor, there were 28, 56, 91 for group A, B and C respectively. A clear
correlation between the AFP levels and the size of tumor was noticed, especially for the group 2 with 45% of
correlation with group C.
Conclusion: With the correlation found between the AFT and the size of tumor, there is a significant concordance
with group C and 2 with 55.4%, what points that higher levels of AFP can be a useful key to determine the prognosis
of the tumor and its stage, in order to plan the treatment accurately.
Keywords: Hepatocellular Carcinoma, Serum Alfa Feto-protein, Size of liver tumors.

As an attempt to achieve that goal, the follow up on patients in

Introduction
Hepatocellular Carcinoma, also called malignant hepatoma,
represents 80-90 % of the primary malignant tumors in the liver,
being the third reason of deaths related to cancer, and increasing.
It is closely related to liver cirrhosis, which is considered almost a
direct cause of HCC. Cirrhosis may appear either for a viral
infection like hepatitis C Virus, Delta virus or hepatitis B virus
(though this last one often leads to cancer without developing
cirrhosis), or for non-viral reasons as excessive alcohol drinking,
contaminated water or intoxicated food.
Because HCC is a cancer that does not manifest clear signs until
it is too late, its mortality is much higher than it should be and,
when detected on time, has much more healing opportunities.
This is the main reason why developing detection and diagnostics
tools has to be a priority in order to revert its mortality and
morbidity.
higher risk is the key. The periodic controls includes measures
like the Child Pugh Score (which assesses prognosis in chronic
liver diseases using the levels of Bilirubin, serum Albumin,
Prothrombin time, ascites and Hepatic Encephalopathy); or the
BCLC (a staging system evaluator for liver cancer based on the
number and size of tumors, the patient’s performance status and
liver functions, according to Child Pugh Score). Imaging
technique examinations (like ultrasound or computer
tomography) and serum tumor marker tests are part of the
periodic controls as well.
Tumor markers are cells produced either by the neoplastic cells,
or as a body response for their invasion, which allows determining
the prognosis of a cancer or the efficacy of its treatment. The
tumor marker for the Hepatocellular Carcinoma is the serum
Alpha Feto-Protein (AFP).
AFP is a glycoprotein produced by the foetal yolk sac after the
seventh week of gestation, and later on by the fetus gut and liver.
After birth, its level decreases being usually lower than 20 UI/ml.

1
January 2018
 Original Article
People with higher than 20 UI/ml of serum AFP should be closely Table 1 – Demographic and clinical data of patients in
examined as higher levels are usually related to liver cancer. relation with serum AFP levels.
There are other neoplasia than might increase AFP levels as well
Group 2 Group 3
as other liver diseases. That turns the marker not so reliable as Group 1
Features AFP20- AFP>
a diagnostic tool, though correlation of higher AFP levels and AFP<20UI/ml
399UI/ml 400UI/ml
larger tumors shows that it can be a useful method to determine
the stage of the cancer and its prognosis, based on the tumor Number of
61 75 39
size. Patients
Gender
42 / 19 55 / 20 24 / 15
(M/F)
Patients and methods Age
40 / 21 51 / 24 29 / 10
(<65 / >65)
This cross-sectional research study was undertaken from a total Etiology: HCV
of 236 patients diagnosed with HCC who attended to the Military 44 / 9 / 1 / 3 *1 57 / 11 / 3 / 1 34 / 2 / 0 / 2
HBV/Coinf./Neg
Hospital (Rawalpindi, Pakistan) from (**DATE**). Only 175 of Child Pugh
them had substantial data recorded to apply for this research 44 / 12 / 0 51 / 22 / 0 23 / 13 / 1
Score (A/B/C)
(AFP levels and size of tumor registered). Perform Status
Patients included were at all stages of the disease, either with 26 / 28 / 3 / 2 35 / 32 / 2 / 6 13 / 19 / 4 / 2
0/1/2/3
only one, or with multiple tumors, with or without metastases, BCLC System
vascular invasion, lymph nodes involved or coagulopathy. 14 / 16 / 8 / 0 16 / 28 / 12 / 2 4 / 13 / 3 / 1
A/B/C/D
They were examined from demographical data to clinical PT/INR: Y / N
parameters. They all had a record of their serum AFP levels 8 / 57 7 / 65 4 / 32
Coagulopathy
measures, gotten by different laboratory tests, and the sizes of
Vascular
the tumors were taken from imaging technics. All other variables 10 / 51 12 / 63 5 / 34
Invasion Y/N
were obtained by its regular methods. Some of them had some
Lymph Nodes
data missing, though it was not relevant for the correlation proved 3 / 58 7 / 68 2 / 37
Y/N
in this study, so they were incorporated anyway.
Metastases
Taking tumor size as parameter they were divided into three 1 / 60 3 / 72 1 / 38
Y/N
groups (A, B, and C, with less than 3cm, between 3 and 5 cm.
and larger than 5 cm. respectively) and on the Serum AFP levels Renal Profile
0 / 2 / 55 1 / 3 / 67 0 / 2 / 35
basis, they were divided into groups 1 (with serum levels lower Severe/Mild/No
than 20 UI/ml), 2 (serum from 20 to 399 UI/ml) and 3 with serum Size of tumor
11 / 23 / 28 12 / 22 / 41 5 / 12 / 22
levels higher than 400 UI/ml. and the correlation was analyzed <2 / 3-5 / >6 cm
manually, to be able to take all variables in mind for this and future N° of Tumors
31 / 26 / 4 37 / 32 / 6 19 / 19 / 1
researches. 1 / 2-5 / > 5
Results *1 – Two cases of Delta Virus

A sample of 175 patients with hepatocellular carcinoma were Table 2 - Correlation of serum AFP and size of tumors in
taken with all the information needed. They comprised 121 male HCC (no other variable considered)
and 54 female. The age range was from 30 to 85 years old. Of Serum AFP GROUP 1 GROUP 2 GROUP 3
them, there were 61 in the group 1, 75 in the group 2 and 39 in Size (< 20 UI/ml) (21–399 UI/ml) (>400 UI/ml)
the group 3. In addition, according to the size of their tumor, there Total: 62 Total: 74 Total: 39
were 28, 56 and 91 for group A, B and C respectively. Of the 175
of Tumor
patients, 68,5% were under 65 years old, HCV was the etiology GROUP A 11 12 5
of 77,1%; 49,7% had only one tumor and most of them were in (< 3 cm) (A: 39,2% - (A: 42,8% - (A: 17,8% -
level 0 or 1 of performance status. Total: 28 1: 17,7%) 2: 16,2%) 3: 12,82%)
There is a clear correlation between the AFP levels and the size
of tumor, especially for the group 2 with the highest ranges in GROUP B 23 21 12
each of the groups and 45% of correlation with group C, and the (3-5 cm.) (B: 41% - (B: 37,5% - (B: 21,4% -
group 3, with 56,4% of patients with tumors larger than 6 cm.
Total: 56 1: 37%) 2: 28,3%) 3: 30,7%)

GROUP C 28 41 22
(> 6 cm) (C: 30,7% - (C: 45% - (C: 24,1% -
Total: 91 1: 45,1%) 2: 55,4%) 3: 56,4%)

2
January 2018
 Original Article
Table 3 – Demographic and clinical data of patients in Conclusion
relation with the size of their tumors.
This study shows that although the presence of Serum AFP is not
Group A Group B Group C reliable enough to diagnose a large tumor in the liver, it gets
Features
1 – 2 cm. 3 – 5 cm. > 6 cm. elevated in most of the patients with growing tumors. That
Number of elevation does not have to be too severe; what is more, patients
28 56 91
Patients with largest tumors had around 300 UI/ml AFP.
Gender This is a reason why it is its increment what professionals should
17 / 11 36 / 20 68 / 23
(M/F) be aware of, and look closer to patient of group 2 and 3 according
Age to Serum AFP levels. Also, it correlation to BCLC ranges is an
20 / 8 43 / 13 57 / 34
(<65 / >65) evidence of how aggressively the tumors developed by patients
Etiology: HCV 20 / 3 / 2 / 2 with high AFP levels can behave, and will give us a clue for the
47 / 4 / 1 / 2 68 / 15 / 1 / 3
HBV/Coinf./Neg *1 best treatment strategy for each of them.
Child Pugh Serum AFP levels and its correlation with the sizes of tumors
17 / 10 / 0 34 / 19 / 0 67 / 18 / 1
Score (A/B/C) might also be very useful to evaluate the response to treatment
Perform Status and how it is affecting the tumor itself.
9 / 17 / 0 / 2 28 / 22 / 1 / 2 37 / 40 / 8 / 6
0/1/2/3 To sum up, we concluded that to keep records of the Serum AFP
BCLC System levels is the key to assess the prognosis of a Hepatocellular
15 / 3 / 0 / 0 17 / 16 / 4 / 2 / 38 / 19 / 3
A/B/C/D Carcinoma tumor and to guess what its size will be if not treated
PT/INR: Y / N properly.
7 / 20 7 / 46 5 / 80
Coagulopathy References
Vascular
2 / 26 1 / 55 24 / 67
Invasion Y/N
1. Butt AS, Abbas Z, Jafri W. Hepatocellular Carcinoma in
Lymph Nodes
0 / 28 5 / 51 7 / 84 Pakistan; Where do We Stand?. Hepat Mon. 2012;12(10
Y/N
HCC): e6023. DOI: 10.5812/hepatmon.6023
Metastases 2. Khalil ur Rehman, Samiullah M, Sharif S, Farhat S.
0 / 28 0 / 56 5 / 86
Y/N Hepatocellular carcinoma; correlation of serum alpha
Renal Profile fetoprotein and tumor size. Professional Med J
1 / 0 / 25 0 / 4 / 51 0 / 3 / 81
Severe/Mild/No 2016;23(2):209-212. DOI: 10.17957/TPMJ/16.3178
Serum AFP: <20 3. Pisit Tangkijvanich, M.D., Nopporn Anukulkarnkusol, M.D.,
11 / 12 / 5 23 / 21 / 12 28 / 41 / 22
/ 21-399 / >400 Pongspeera Suwangool, M.D., Somrat Lertmaharit, M.Sc.,
N° of Tumors Orrawadee Hanvivatvong, M.Sc., Pinit Kullavanijaya, M.D.,
16 / 11 / 1 23 / 31 / 2 48 / 35 / 8
1/2–5/>5 and Yong Poovorawan, M.D.. Clinical Characteristics and
*1 – One case of Delta Virus Prognosis of Hepatocellular Carcinoma. J Clin Gastroenterol
2000;31(4):302–308.
Discussions 4. Dr. Javier Gallego Plazas. Cáncer de Hígado
(Hepatocarcinomas). January 2018.
There is an obvious increment in HCV as the etiology of the HCC,
[https://tumortratamiento.blogspot.com.ar/2010/11/cancer-
and it is considered the main reason why its prevalence in man is
de-higado-hepatocarcinomas.html]
getting more and more notorious. The high level of cirrhosis but
5. Dra. Cabrera Carmen M. Utilidad de la alfa-fetoproteina
even more, the high level of HCV patients who develop HCC como marcador. January 2018. [http://www.hgucr.es/wp-
make them two of the most important patients to evaluate
content/uploads/2011/12/utilidad_de_la_alfa-
periodically to detect any tumor as soon as it shows up.
fetoproteina_como_marcador.pdf]
Though it will have to be detected by imaging, taking records of 6. Exámenes de detección del cáncer de hígado
their serum AFP levels may be the key to figure out the prognosis
(hepatocelular) (PDQ®)–Versión para profesionales de
of it. People with normal ranges of AFP than suddenly become
salud
part of the group 2 is more likely to have a more aggressive tumor.
7. S. Sharieff, I. A. Burney, A. Salani, T. Siddiqui ( Department
In the tables, we noticed that from 91 patients of the group C, 41
of Medicine, The Aga Khan University Hospital. Karachi. )
had between 20 to 399 UI/ml of serum AFP. What actually could Lack of Correlation between Aipha-Fetoprotein and Tumor
show that is not only the level of serum but also the increment of
size in Hepatocellular Carcinoma.
it, that we should be aware of, and all patients in risk of developing
8. Amanullah Abbasi, Abdul Rabb Bhutto, Nazish Butt, Syed
HCC whose AFP ranges increases should be monitored even Mohammad Munir. Corelation of serum alpha fetoprotein
closely as that may be a marker of a developing tumor that will
and tumor size in hepatocellular carcinoma. Journal of the
gain size quickly.
Pakistan Medical Association. January 2012
Other researches from all over the world were evaluated to get to
this conclusion with accurate information.

3
January 2018