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Original Research (Original Article) 


Ali Al Ahmari et al, 2020;4(2):313–317.

International Journal of Medicine in Developing Countries

Alpha-fetoprotein as a predictor of liver fibrosis: a single center tertiary care study in Saudi Arabia

Ali Al Ahmari1, Ibrahim Masoodi2*, Abdulmalik Mohammed Almalki2, Oqab Muidh Almalki2, Mohammed Mofareh Alsubaie2, Saleh Aedh Alshamrani2

Correspondence to: Ibrahim Masoodi

*College of Medicine, Taif University, Taif, Saudi Arabia.

Email: ibrahimmasoodi [at] yahoo.co.in

Full list of author information is available at the end of the article.

Received: 12 November 2019 | Accepted: 20 December 2019


ABSTRACT

Background:

The quest for noninvasive biomarkers for fibrosis continues, as liver biopsy is invasive. Thereby, this study aimed to correlate fibrosis score with Alpha fetoprotein (AFP) levels in patients with Hepatitis B virus (HBV).


Methodology:

This was an observational prospective study, including 123 patients from Al-Hada Military Hospital, Taif, Saudi Arabia. Patients were enrolled from January 2017 to July 2019. Data were collected related to patients’ demographics, diagnosis, HBV viral load, complete blood count, liver function tests, AFP levels, and alkaline phosphatase levels. Fibro scan was done at the beginning and on follow up. The correlation between AFP levels and severity of liver fibrosis was assessed by fibro scan and viral load levels.


Results:

Of the total 123 participants included in this study with chronic hepatitis B, there was a significant difference in AFP levels and fibrosis score (p-value = 0.009). Additionally, there was a significant difference (p-value = 0.014) detected between median AFP being higher in patients with positive viral load as compared to the patients with negative viral load. It was also observed that there was a significant direct relationship (p-value = 0.016) between the level of AFP and stage detected on the fibro scan.


Conclusion:

AFP could be a useful tool for the staging of liver fibrosis and evaluating response to the treatment. Further studies may confirm the co relation.


Keywords:

Alpha-fetoprotein, liver fibrosis, Hepatitis B virus, fibrosis score, viral load.


Introduction

Hepatitis B virus (HBV) infection is considered as a significant universal health threat with more than 350 million people infected by the virus [1]. Despite the availability of an effective vaccine, many people are still at risk of getting HBV, mainly through either perinatal transmission or through horizontal transmission during childhood [2].

Chronic hepatitis B (CHB) is considered as the leading cause of fibrosis and hepatocellular carcinoma (HCC), with almost a mortality rate of one million per year [3]. In the common progression of CHB, most of the patients develop liver fibrosis after getting chronic hepatitis and then HCC [4]. The degree of liver fibrosis caused by CHB is a significant predictor to decide proper antiviral management in addition to the prognosis for disease progression [5]. Hence, biomarkers to predict CHB non-invasively could affect the overall complication of this dreaded disease. While it has been a long-standing fact that the standard practice to evaluate the level of liver fibrosis is through obtaining a liver biopsy [6]. However, many limitations have been recognized with liver biopsy [7]. These limitations included: being invasive, non-dynamic evaluation, and error during collecting biopsy sample, pain, and inter-observer variability. Sometimes the complications are considered life-threatening [8]; hence, the quest for non-invasive biomarkers continues.

Because of all these limitations and hazards, it was favorable to explore a new non-invasive technique to examine liver fibrosis [9]. These new techniques included biological strategies depending on serum biomarkers evaluating fibrosis in addition to physical strategies depending on the evaluation of liver stiffness utilizing transient elastography [10]. Recently, some of the non-invasive methods that depend on conventional serum biomarkers had been observed to have an increased diagnostic specificity in addition to being cost-effective in detecting significant fibrosis or cirrhosis in patients with CHB [11].

Both the prevalence and risk factors of HCC development for fibrotic CHB patients had been revealed previously [12]. The risk of HCC in fibrotic CHB patients had been estimated to range from 5% to 30%. The broad variation in these calculations might be due to the variability of the level of fibrosis in the recruited patients in these studies [13]. Trials that recruited patients with more severe fibrotic liver patients had a higher incidence of HCC. In spite of that, the cumulative risk estimated for HCC over a follow-up duration beginning from the time of diagnosis to the time of fibrosis occurrence cirrhosis was rarely reported [14].

Alpha fetoprotein (AFP) is identified as a fetal protein that is produced in the yolk sac and liver of the fetus in early developmental stages [15]. It has a molecular weight that is on the average between the weight of albumin and weight α1-globulin proteins, this proposes the fact that AFP could be an early stage of albumin formation. Serum AFP was recorded to be a tumor marker for HCC in earlier trials [16]. In spite of being non-specific for HCC diagnosis, increased AFP levels were also observed in chronic liver disease, specifically in viral hepatitis [17]. Measuring the level of AFP is also used to monitor HCC beginning as well as progression. It could also assess the effectiveness management strategy, and expect the outcomes [18]. AFP could be considered as a screening strategy for HCC in some developing countries, especially due to the high incidence of HCC where viral hepatitis is a major risk factor [19]. Levels of AFP >400 ng/ml are considered very high and can be regarded as a strong predictor for HCC. AFP could also be used in an indirect way to identify fibrosis stage in chronic hepatitis C virus infection. Although, data on the AFP levels were still scarce about progressing liver fibrosis as in CHB [20].

Furthermore, there were only a few studies that investigated hepatic fibrosis through measuring the levels of AFP or determining the relation between levels of AFP and the stage of hepatic fibrosis. The data was even fewer in the gulf patient population [21]. Therefore, in the present study, it was aimed to examine the usefulness of AFP as a tool to help in assessing the stage of fibrosis in Saudi Arabian patients with liver fibrosis due to chronic hepatitis B.


Subjects and Methods

This was an observational prospective study that included 123 hepatitis B patients with liver fibrosis from Al-Hada Military Hospital, Taif, Saudi Arabia, from January 2017 to July 2019. All the patients with liver fibrosis due to hepatitis B were included. Patients having liver fibrosis due to any other cause (alcohol, hepatitis C, autoimmune diseases, etc.) were excluded. Chronic HBV patients were enrolled and the data related to demographics, diagnosis, viral load, complete blood count, liver function tests, AFP levels, and alkaline phosphatase levels were observed, including fibro scan of the liver which measured the stiffness from F0, F1, F2, F3, and F4 and data was recorded according to the level of fibrosis affecting the liver.

All the data was recorded in a pre-designed and validated excel sheet. Data was represented in terms of frequencies (number of patients/ cases) and valid percentages for categorical variables. Correlations were done using the chi-square test for categorical variables. The normality test was rejected for all the variables; therefore, non-parametric testing with the Mann–Whitney U test was used. Data was further analyzed using IBM SPSS (Statistical Package for the Social Science; IBM Corp, Armonk, NY), version 21 to perform all statistical calculations.


Results

The study included 123 patients with CHB virus, of which 74 patients (60.2%) were males and 49 (39.8%) were females. Their ages ranged from 22 to 97 years. Age was sub-categorized into four groups including less than 30 years, from 31 to 50 years, from 51 to 70 years, and older than 70 years. The most prevalent age group was between 31 to 50 years (49.6%), while the least number of patients were those less than 30 years with only four patients representing 3.3% of the cohort. Disease state of the recruited subjects was evaluated and classified into either active state, inactive carrier (IC) state, on treatment or other. IC disease state constituted almost half of the patients with 42.3%, while 8.9% of the patients had active disease. A qualitative method was used to detect the presence or absence of Hepatitis B e-antigen. Out of the 123 participants, 108 patients (87.8%) had positive viral load while 15 participants (12.2%) had a negative viral load (Table 1).

Fibro scan investigation was done for all the recruited participants. The result was categorized into nine sub-groups. Patients with the least fibrosis had a score of F0 while those with the most severe fibrosis levels had a score of F4. It was revealed that most of the recruited patients (51 participants) had a mild degree of fibrosis while only 14 participants had severe fibrosis (F4). Only one patient had between F1 and F2 level of fibrosis (Figure 1).

Additionally, an abdominal ultrasound was performed in all patients. The liver condition was described as viewed during the ultrasound as a bright liver, cirrhotic liver, fatty liver, and normal liver (Figure 2).

The levels of AFP in each patient were measured and median AFP was correlated with disease status, viral load, level of fibrosis detected by fibro scan and findings of abdominal ultrasound. It was revealed that there was a significant difference in AFP levels between different disease status (p-value = 0.009). Additionally, there was a significant difference (p-value = 0.014) detected between median AFP, which was higher in patients with positive viral load compared to patients with negative viral load. It was also observed that there was a significant direct relationship (p-value = 0.016) between levels of AFP and stage detected on the fibro scan. However, there was no significant relationship detected between different findings detected by abdominal ultrasound (p-value = 0.440) (Table 2).

Table 1. Demographic data of the participants and diagnostic baseline investigations.

Frequency Percentage (%)
Gender
Male 74 60.2
Female 49 39.8
Age
<30 4 3.3
31–50 61 49.6
51–70 44 35.8
>70 14 11.4
Disease state
Active 11 8.9
IC 52 42.3
On treatment 25 20.3
Other 35 28.5
HbeAg result
Negative 15 12.2
Positive 108 87.8

Figure 1. The number of participants in each degree of fibrosis.


Discussion

Liver fibrosis is highly prevelent in patients with hepatits B which is not detected by routine ultrasound.While Fibroscan detects fibrosis in a noninvasive manner, it is not available at all centers. The present study investigated the correlation between measured levels of AFP and stages of liver fibrosis in terms of fibro scan, viral load, and the disease state at time of diagnosis. The study revealed that the AFP level was directly related to the status of the disease with a statistically significant difference (p-value = 0.009).

Additionally, there was a significant difference (p-value = 0.014) detected between median AFP and viral load. Also, a significant direct relationship (p-value = 0.016) between the level of AFP and stage detected on a fibro scan was observed.

Previous studies have also evaluated the relation between AFP and liver fibrosis in different patient populations. Liu et al. study [10] was one of these examples that examined liver fibrosis in the Chinese population. A total of 619 patients retrospectively with CHB virus were recruited to detect the link between the AFP level and the pathological state of the liver through obtaining a biopsy. The study revealed that AFP levels were directly related to the pathological condition of the liver biopsy. In the present work, patients were prospectively evaluated in contrast to Liu et al. [10]. Similar to Liu et al. [10], there was a significant direct correlation between AFP levels and stage liver fibrosis in terms of fibro scan, viral load, and disease state at the time of diagnosis.

Furthermore, some studies like Feng et al. [9] proposed a mathematical model based on AFP and other biomarkers to predict liver fibrosis in patients with hepatitis B. A non-invasive index to predict liver fibrosis in patients with CHB was developed from records of 506 patients retrospectively. The index included levels of AFP and activated prothrombin time. It was proposed that the new index was a promising tool for predicting fibrosis without the need for invasive liver biopsy. The results of the present work are in cognizance with Feng et al., nevertheless , it did not develop a calculation for prediction of liver fibrosis.

Figure 2. Frequency of different disorders appearing on abdominal ultrasounds.

Table 2. Correlation between AFP levels (in medians and IQR) and liver fibrosis diagnostic tools.

Median (IQR) p-value
Status Active 2.05(4) 0.009*
IC 2.40(1)
On treatment 2.70(2)
Other 3.40(2)
HbeAg Negative 2.70(2) 0.014*
positive 4 (3)
Fibro scan F0 2.27(2) 0.016*
F0–F1 2.44(1)
F2–F3 2.86(1)
F3–F4 4.16(2)
Ultrasound Bright Liver 2.60(3) 0.440
Cirrhotic 3.34(2)
Fatty Liver 2.73(2)
Normal 2.80(2)

*Level of significance at p ≤ 0.05.

In another study, Chien et al. [8] examined patients with cirrhosis due to hepatitis B to detect risk factors for HCC. 4155 participants were followed up for 6 to 12 months and showed that old age, positive HbeAg, increased levels of AFP were all risk predictors for HCC. Although HCC was not targeted in the present study, the current results were in agreement with the previous study where AFP level was directly related to the degree of fibrosis. Additionally, Yao et al. [6] also evaluated the value of measuring AFP in patients with hepatitis B in the Chinese population. The study examined records of 318 cases of hepatitis retrospectively and concluded that elevated levels of AFP could be used to diagnose and predict HCC in hepatitis B patients. These findings comply with the results of the present study.


Conclusion

From the discussed results it may be concluded that serial AFP levels during the management of chronic hepatitis B may help to predict significant fibrosis in a given case and thus help in the detection of early hepato cellular carcinoma.However, further studies are required to confirm the correlation.


List of Abbreviations

AFP Alpha-fetoprotein
HBV Hepatitis B virus
CHB Chronic hepatitis B
HCC Hepatocellular carcinoma
IC Inactive carrier

Conflict of interest

The authors declared that there is no conflict of interest regarding the publication of this article.


Funding

None.


Consent of publication

Informed consent was obtained from all participants.


Ethical approval

Ethical approval was obtained from Institutional research and ethics board. Ethical approval from Medical services General Directorate M.S.D Research & Ethics committee Western region Saudi Arabia. Reg.No = H-02-T-078 Dated 15-10-2019


Author details

Ali Al Ahmari1, Ibrahim Masoodi2, Abdulmalik Almalki2, Oqab Muidh Almalki2, Mohammed Mofareh Alsubaie2, Saleh Aedh Alshamrani2

  1. Al-Hada Military Hospital, Taif, Saudi Arabia
  2. College of Medicine, Taif University, Taif, Saudi Arabia

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How to Cite this Article
Pubmed Style

Ahmari AA, Masoodi I, Almalki A, Almalki OM, Alsubaie MM, Alshamrani SA. Alpha-fetoprotein as a predictor of liver fibrosis: a single center tertiary care study in Saudi Arabia. IJMDC. 2020; 4(2): 313-317. doi:10.24911/IJMDC.51-1573570950


Web Style

Ahmari AA, Masoodi I, Almalki A, Almalki OM, Alsubaie MM, Alshamrani SA. Alpha-fetoprotein as a predictor of liver fibrosis: a single center tertiary care study in Saudi Arabia. https://www.ijmdc.com/?mno=73548 [Access: October 15, 2021]. doi:10.24911/IJMDC.51-1573570950


AMA (American Medical Association) Style

Ahmari AA, Masoodi I, Almalki A, Almalki OM, Alsubaie MM, Alshamrani SA. Alpha-fetoprotein as a predictor of liver fibrosis: a single center tertiary care study in Saudi Arabia. IJMDC. 2020; 4(2): 313-317. doi:10.24911/IJMDC.51-1573570950



Vancouver/ICMJE Style

Ahmari AA, Masoodi I, Almalki A, Almalki OM, Alsubaie MM, Alshamrani SA. Alpha-fetoprotein as a predictor of liver fibrosis: a single center tertiary care study in Saudi Arabia. IJMDC. (2020), [cited October 15, 2021]; 4(2): 313-317. doi:10.24911/IJMDC.51-1573570950



Harvard Style

Ahmari, A. A., Masoodi, . I., Almalki, . A., Almalki, . O. M., Alsubaie, . M. M. & Alshamrani, . S. A. (2020) Alpha-fetoprotein as a predictor of liver fibrosis: a single center tertiary care study in Saudi Arabia. IJMDC, 4 (2), 313-317. doi:10.24911/IJMDC.51-1573570950



Turabian Style

Ahmari, Ali Al, Ibrahim Masoodi, Abdulmalik Almalki, Oqab Muidh Almalki, Mohammed Mofareh Alsubaie, and Saleh Aedh Alshamrani. 2020. Alpha-fetoprotein as a predictor of liver fibrosis: a single center tertiary care study in Saudi Arabia. International Journal of Medicine in Developing Countries, 4 (2), 313-317. doi:10.24911/IJMDC.51-1573570950



Chicago Style

Ahmari, Ali Al, Ibrahim Masoodi, Abdulmalik Almalki, Oqab Muidh Almalki, Mohammed Mofareh Alsubaie, and Saleh Aedh Alshamrani. "Alpha-fetoprotein as a predictor of liver fibrosis: a single center tertiary care study in Saudi Arabia." International Journal of Medicine in Developing Countries 4 (2020), 313-317. doi:10.24911/IJMDC.51-1573570950



MLA (The Modern Language Association) Style

Ahmari, Ali Al, Ibrahim Masoodi, Abdulmalik Almalki, Oqab Muidh Almalki, Mohammed Mofareh Alsubaie, and Saleh Aedh Alshamrani. "Alpha-fetoprotein as a predictor of liver fibrosis: a single center tertiary care study in Saudi Arabia." International Journal of Medicine in Developing Countries 4.2 (2020), 313-317. Print. doi:10.24911/IJMDC.51-1573570950



APA (American Psychological Association) Style

Ahmari, A. A., Masoodi, . I., Almalki, . A., Almalki, . O. M., Alsubaie, . M. M. & Alshamrani, . S. A. (2020) Alpha-fetoprotein as a predictor of liver fibrosis: a single center tertiary care study in Saudi Arabia. International Journal of Medicine in Developing Countries, 4 (2), 313-317. doi:10.24911/IJMDC.51-1573570950