International Journal of Clinical Biochemistry and Research

Print ISSN: 2394-6369

Online ISSN: 2394-6377

CODEN : IJCBK6

International Journal of Clinical Biochemistry and Research (IJCBR) open access, peer-reviewed quarterly journal publishing since 2014 and is published under auspices of the Innovative Education and Scientific Research Foundation (IESRF), aim to uplift researchers, scholars, academicians, and professionals in all academic and scientific disciplines. IESRF is dedicated to the transfer of technology and research by publishing scientific journals, research content, providing professional’s membership, and conducting conferences, seminars, and award more...

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Get Permission Sreedhanya U and Varma: Association between serum alpha-fetoproteinlevel and liver function parameters in hepatocellular carcinoma patients: A case-control study


Introduction

Alpha- fetoprotein, glycoprotein (MW 7000) that is synthesized in yolk sac in early fetal life. The serum level begins to fall before birth and reach a value of less than 10ng/ml within first few weeks of life. Serum AFP can be elevated in some disease state particularly hepatocellular carcinoma (HCC). The aim of the study was to establish any correlation of AFP level and selected test of liver cell function and integrity measured serially in patients with acute viral hepatitis. Each liver function test by itself is neither highly specific nor specific but when interpreted together may provide the clinician with useful information about patient’s liver and may also indicate other health issue such as malnutrition and bone disease. As the liver is involved in excretory, synthetic and metabolic functions. LFT may be ordered by clinicians as a standard order for nonspecific symptoms. LFTs are commonly used in clinical practice to screen for liver disease, monitor the progression of known disease and monitor the effect of potentially hepatotoxic drugs. Alanine transaminase (ALT) and aspartate transaminase (AST) are sensitive indicators of hepatocellular injury, but they lack specificity as they are also present in muscle (cardiac and skeletal).1 In hepatocyte cytoplasm AST is more abundant than ALT. In plasma AST is cleared more rapidly (t1/2 16-18 hours) than ALT (t1/2 42-48 hours). These aminotransferases may be increased in patients presenting with cirrhosis, alcoholic hepatitis, viral hepatitis and cholestasis. Albumin and prothrombin reflect liver synthetic function. The aminotransferases AST and ALT are normally <30-40 units/l. Elevation of amino transferases greater than eight times the upper limit of normal reflect either acute viral hepatitis, ischemic hepatitis or drug or toxin induced liver injury. ALP (alkaline phosphatase) is a hydrolytic enzyme serine protease acting optimally at pH 10. ALT catalyzes reversible transamination between L-alanine and alpha-ketoglutarate to form pyruvate and L-glutamate as such having an important role in gluconeogenesis and amino acid metabolism. The reaction is reversible but equilibrium of ALT reaction favours the formation of L-alanine. ALT enzyme activity is primarily found in liver but its activity although much lower. HCC is the fifth most common cancer worldwide and a leading cause of cancer death2 The incidence of HCC is two to three-fold higher among men than it is among women. The major risk factor for development of HCC is infection with HBV or HCV.1 Clinical features of HCC usually do not occur until late in course of disease, when the tumor is large and resection is impossible.3 Nonspecific signs and symptoms such as fever, malaise, anorexia and anemia are common and jaundice may occur with central tumor that obstruct biliary drainage. Treatment is usually not possible with advanced HCC, there has been much interest in screening high risk individuals. Small tumors detected by screening may be treatable by resection of part of the liver or liver transplantation.4 The most common screening programs use plasma tumor markers or imaging studies. The most widely used tumor marker is AFP. Recently more specific L3 isoform has also been used.5 Use of higher cut off value of AFP than upper reference limit improves clinical specificity of total AFP at expense of clinical sensitivity.6 Tumors often produce one or another tumor marker.

Materialsa and Methods

Direct enzymatic colorimetric method is mainly used in the clinical test.

Collection of blood sample

For biochemistry investigation collect blood sample from venipuncture. Collect 2ml of blood in plain tube for getting serum or collect 2ml of blood in anticoagulant vials like lithium heparin for getting plasma. Majority of the biochemical tests requires serum only because plasma contains fibrinogen which has high protein size.

Preparation of serum or plasma

After collecting the blood sample, centrifuge at 1500-3000 rpm for 10 minutes and separate the clear serum. Take care to avoid hemolysis of serum which may leads to error.

  1. The study was conducted in Tellicherry Co. Operative hospital.

  2. 50 HCC patients with AFP >20 ng/ml and 40 control subjects (normal LFT and AFP value < 10 ng/ml) with an age 40 or more are selected.

  3. Both male and female subjects are selected in the study.

  4. Sample: serum

  5. Analyzer: Erba XL 640, Maglumi1000 biochemistry analyzer

  6. Principle: Chemiluminescence immunoassay, spectrophotometry

  7. Statistical analysis: unpaired t test (IBM SPSS 22.0).

Result & Discussion

Table 1

Mean of serum level of AFP, SGOT, SGPT, ALP in the HCC and control subjects

S No

Parameter

Test (N=50)

Control (N=40)

t Vaiue

P Value

1

AFP (ng/ml)

98.96±203.3

2.46±1.52

2.997

0.004

2

SGOT (IU/L)

86.82±36.03

27.5±5.76

10.295

0.000

3

SGPT (IU/L)

64.88±24.11

24.47±7.81

10.167

0.000

4

ALP (IU/L)

116.30±49.3

65.92±13.14

6.274

0.000

Figure 1

The graph marked with ** indicate they are statistically significant to the study (p value<0.05 for AFP and p value<0.001 for other parameters

https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/e67c5b89-0d9e-49ca-8dff-11480ec6d5fcimage1.png

HCC is the fifth most common cancer worldwide and a leading cause of cancer death. Treatment is usually not possible with advanced HCC occurs due to failure of not doing proper screening at appropriate time. Small tumors detected by screening may be treatable by resection of part of liver or liver transplantation.7 The most common screening programme use plasma tumor markers or imaging studies.8 The most widely used tumor marker is AFP. Use of higher cutoff value of AFP than upper reference limit improves clinical specificity of total AFP at expense of clinical sensitivity. In the case control study of serum AFP level on liver function parameters where elevated level of AFP (p value <0.05), SGOT (p value <0.001), SGPT (p value <0.001), ALP (p value <0.001) in liver disease patients.

AFP as a biomarker in early diagnosis of HCC concluded that HCC is characterized by more in male incidence than female.

From the graph it is clear that there is marked elevation in the mean of ALP, SGPT, SGOT and ALP in HCC patients than control patients.

Our results also indicated a risk of developing HCC with respect to AFP level in liver disease patients with elevated liver function parameters.

In early findings also reported that AFP is useful not only for diagnosis but also a prognostic indicator in patients with HCC.2

Clinical utility of AFP –L3 where incidence of HCC was significantly higher in patients with elevated AFP-L3% than in those with elevated AFP.9

Conclusion

50 hepatocellular carcinoma patients and 40 control subjects were studied. From the study it is concluded that LFT and AFP are comparatively elevated in HCC.10 Treatment is usually not possible with advanced HCC due to failure of not doing proper screening at appropriate time which is rectified by early diagnosis and monitoring of HCC are possible with the help of tumor marker AFP.11

Source of Funding

None.

Conflict of Interest

None.

References

1 

PJ Johnson SJ Pirrie TF Cox S Berhane S Berhane M Teng Determinants of alpha-fetoprotein levels in patients with hepatocellular carcinoma: implications for its clinical useCancer20141201421507

2 

P Tangkijvanich N Anukulkarnkusol P Suwangool S Lertmaharit O Hanvivatvong P Kullavanijaya Clinical characteristics and prognosis of hepatocellular carcinoma: analysis based on serum alpha-fetoprotein levelsJ Clin Gastroenterol20003143028

3 

R Saffroy P Pham M Reffas M Takka A Lemoine B Debuire New perspectives and strategy research biomarkers for hepatocellular carcinomaClin Chem Lab Med2007459116979

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OV Makarova-Rusher SF Altekruse TS Mcneel S Ulahannan AG Duffy BI Graubard Population attributable fractions of risk factors for hepatocellular carcinoma in the United StatesCancer201612211175765

5 

H Toyoda T Kumada Y Kaneoka Y Osaki T Kimura A Arimoto Prognostic value of pretreatment levels of tumor markers for hepatocellular carcinoma on survival after curative treatment of patients with HCCJ Hepatol200849222332

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JH Shim MJ Jun S Han YJ Lee SG Lee KM Kim Prognostic nomograms for prediction of recurrence and survival after curative liver resection for hepatocellular carcinoma Ann Surg2015261593946

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I Parisi E Tsochatzis H Wijewantha M Rodríguez-Perálvarez LD Luca P Manousou Inflammation-based scores do not predict post-transplant recurrence of hepatocellular carcinoma in patients within Milan criteriaLiver Transpl20142011132735

8 

F Piscaglia G Svegliati-Baroni A Barchetti A Pecorelli S Marinelli C Tiribelli Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective studyHepatology201663382738

9 

RK Sterling L Jeffers F Gordon M Sherman AP Venook KR Reddy Clinical utility of AFP-L3% measurement in North American patients with HCV-related cirrhosisAm J Gastroenterol2007102102196205

10 

X Liu J Meng H Xu J Niu Alpha-fetoprotein to transaminase ratio is related to higher diagnostic efficacy for hepatocellular carcinomaMedicine (Baltimore)20199817e1541410.1097/MD.0000000000015414MD, PhD∗

11 

EJ Park JH Lee GY Yu G He SR Ali RG Holzer Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expressionCell20101402197208



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Article type

Original Article


Article page

176-178


Authors Details

Sreedhanya U, Poornima R Varma*


Article History

Received : 10-06-2023

Accepted : 24-06-2023


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