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Fulltext Levels of PIVKA-II and alpha-fetoprotein in unresectable hepatocellular carcinoma compared to healthy controls and predictive values of both markers with radiological responses after loco-regional interventions

Hamzah N, Kassim NK, Omar J, Abdullah MS, Lee YY

PeerJ, 2023;11:e15988.
PMID: 37780370 DOI: 10.7717/peerj.15988

BACKGROUND: The significance of the current study was to determine normative levels of PIVKA-II and AFP in patients with unresectable HCC and healthy participants. The second goal was to assess the roles of PIVKA-II and AFP in predicting radiological response after loco-regional therapy.
METHODS: This prospective cohort study enrolled consecutive samples of HCC patients and healthy controls. Venous blood samples were obtained at baseline and after interventions to determine serum levels of PIVKA-II and AFP using the chemiluminescent microparticle immunoassay method. Radiologic responses were determined based on the WHO criteria.
RESULTS: Fifty-four HCC patients (mean age 58.9 years, 49 males) and 40 healthy controls (mean age 33.5 years, 26 males) were recruited. The median serum levels of PIVKA-II and AFP in HCC vs. healthy controls were 988.4 vs. 24.2 mAU/ml and 13.6 vs. 1.7 ng/ml, respectively (both p

Matched MeSH terms: alpha-Fetoproteins/analysis
Oesophageal hepatoid carcinoma with liver metastasis, a diagnostic dilemma

Yahaya A, Wa Kammal WS, Abd Shukor N, Osman SS

Malays J Pathol, 2019 Apr;41(1):59-63.
PMID: 31025640

Alpha-fetoprotein (AFP)-producing carcinoma which microscopically mimics hepatocellular carcinoma (HCC) is a rare entity known as hepatoid adenocarcinoma (HC). They usually arise in the stomach, while oesophageal origin is only occasionally encountered. This tumour is highly aggressive and is associated with a poor prognosis. They frequently metastasise to the liver, thus giving rise to diagnostic difficulty, especially in cases where simultaneous oesophageal and liver mass are present. We reported a case of oesophageal hepatoid carcinoma with multiple liver metastasis, that was associated with an increased serum AFP. The distinction between HCC and HC is important because HC is more aggressive and has a poorer prognosis with limited therapeutic options. An extensive diagnostic work-up which include a thorough clinical history, radiological investigations (computed tomography or magnetic resonance imaging) as well as tissue biopsy supported by a panel of immunohistochemical markers are necessary to aid in the diagnosis of HC.

Matched MeSH terms: alpha-Fetoproteins
Fulltext A Rare Manifestation of Cervical Yolk Sac Tumor in an Unfortunate Infant

Saniasiaya J, Hamid SSA, Mohamad H, Wahab WNNWA, Zawawi N

Turk Arch Otorhinolaryngol, 2019 Sep;57(3):157-160.
PMID: 31620699 DOI: 10.5152/tao.2019.3900

Paediatric germ cell tumor is composed of various neoplasms which exhibit capricious clinical presentation and histological features depending on the age and the area of presentation. Yolk sac tumor is an extremely rare malignant tumor of embryonic origin which usually arises from the gonads. Its manifestation in the head and neck region is extremely rare. Here, we report a rare case of the malignant transformation of mature teratoma into yolk sac tumor of the neck in an infant. Diagnosis was confirmed following histopathological examination of the neck mass along with marked increase of the serum alpha-fetoprotein. The child unfortunately succumbed prior to chemotherapy. We highlight the challenge we faced in diagnosing and managing this rare entity. We would also like to recommend serial monitoring of serum alpha-fetoprotein in all patients with mature teratoma to detect malignant transformation early.

Matched MeSH terms: alpha-Fetoproteins
Fulltext Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region

Kim DY, Toan BN, Tan CK, Hasan I, Setiawan L, Yu ML, et al.

Clin Mol Hepatol, 2023 Apr;29(2):277-292.
PMID: 36710606 DOI: 10.3350/cmh.2022.0212

Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP has its challenges, including accuracy dependent on its cut-off levels, degree of liver necroinflammation, and etiology of liver disease. Though various studies have demonstrated the utility of protein induced by vitamin K absence II (PIVKA-II) in surveillance, treatment monitoring, and predicting recurrence, it is still not recommended as a routine biomarker test. A panel of 17 experts from Asia-Pacific, gathered to discuss and reach a consensus on the clinical usefulness and value of PIVKA-II for the surveillance and treatment monitoring of HCC, based on six predetermined statements. The experts agreed that PIVKA-II was valuable in the detection of HCC in AFP-negative patients, and could potentially benefit detection of early HCC in combination with AFP. PIVKA-II is clinically useful for monitoring curative and intra-arterial locoregional treatments, outcomes, and recurrence, and could potentially predict microvascular invasion risk and facilitate patient selection for liver transplant. However, combining PIVKA-II with US and AFP for HCC surveillance, including small HCC, still requires more evidence, whilst its role in detecting AFP-negative HCC will potentially increase as more patients are treated for hepatitis-related HCC. PIVKA-II in combination with AFP and US has a clinical role in the Asia-Pacific region for surveillance. However, implementation of PIVKA-II in the region will have some challenges, such as requiring standardization of cut-off values, its cost-effectiveness and improving awareness among healthcare providers.

Matched MeSH terms: alpha-Fetoproteins
Fulltext The role of maternal serum alpha-fetoprotein, human chorionic gonadotrophin and oestriol in the antenatal screening of Down's syndrome

Chang TC, Cheng HH

Med J Malaysia, 1994 Dec;49(4):351-4.
PMID: 7545778

The use of maternal age alone to identify pregnant mothers at risk of a fetus with Down's syndrome has recently been supplemented by maternal serum screening using biochemical markers such as alpha-protein, human chorionic gonadotrophin and oestriol. These tests have been reported to increase the sensitivity of antenatal detection of such fetuses from 35% to 67% with a false positive rate of 5%. However, these maternal serum markers may be affected by maternal weight, the smoking history of mothers and diabetes mellitus. Furthermore, such sensitivities are achieved only when gestational age is assessed accurately by ultrasound. Many further studies need to be carried out before the introduction of maternal serum screening into routine obstetric practice in Singapore. These include studies on the incidence of Down's syndrome in the local population, studies on the distribution of these serum markers in the second trimester of pregnancy, sensitivities and positive predictive values of such a test in the local population as well as the socio-economic implications of implementing such a screening test in the local obstetric population.

Matched MeSH terms: alpha-Fetoproteins/analysis*
Serum CA 125 as a marker of hepatocellular carcinoma

Lopez JB, Balasegaram M, Thambyrajah V

Int. J. Biol. Markers, 1996 Jul-Sep;11(3):178-82.
PMID: 8915714

This study was undertaken to investigate whether serum CA 125 could complement alpha-fetoprotein (AFP) to improve the diagnosis of hepatocellular carcinoma (HCC). CA 125 showed a sensitivity of 92% for HCC against the 58.8% sensitivity of AFP at the cutoff value of 200 ng/ml. However, the former was less specific (48.5% versus 97.4%) in relation to benign liver diseases (BLD). CA 125 had a higher negative predictive value (NPV) of 84.6% compared to 69.2% for AFP; when both markers were combined, however, the NPV rose to 91.7%. Overall, AFP was more efficient than CA 125 for the diagnosis of HCC. While a positive AFP result was highly indicative of HCC, a negative result did not rule out the disease; however, negative AFP and CA 125 meant that the likelihood of the disease was low. In situations of low HCC prevalence, CA 125 could serve as a first-line screening test followed by confirmation of positives by AFP.

Matched MeSH terms: alpha-Fetoproteins/analysis
Alpha-fetoprotein in hepatocellular carcinoma: a serological and histochemical study in Malaysian patients

Yap SF, Peh SC

Malays J Pathol, 1991 Dec;13(2):115-8.
PMID: 1726642

Serum alpha-fetoprotein (AFP) levels and its expression in liver tissue was studied in 50 cases of histologically confirmed hepatocellular carcinoma (HCC). Serum AFP levels were elevated (greater than 20iu/ml) in 35/50 (70%) of the cases, 28 of whom had levels greater than 500 iu/ml, which is highly suggestive of HCC. These results indicate that serum AFP, by itself, is a relatively insensitive diagnostic test for HCC. Although elevated levels in high risk patients provide a specific clue, a negative result does not exclude the diagnosis of HCC. Expression of AFP by tumour cells paralleled that of serum in the majority of cases. However, tissue AFP was negative in 7 patients who had markedly elevated serum AFP. This observation may be a reflection of preferential excretion of the tumour antigen or differential expression of the antigen by the tumour cells. None of the patients with normal serum AFP demonstrated a reaction for tissue AFP. There was no correlation between AFP production and tumour differentiation.

Matched MeSH terms: alpha-Fetoproteins/analysis*
Amniocentesis for antenatal diagnosis of chromosomal abnormalities and neural tube defects

Singh P

Med J Malaysia, 1979 Jun;33(4):311-6.
PMID: 93235
Matched MeSH terms: alpha-Fetoproteins/analysis
Fulltext Alpha1-fetoprotein in liver disease in Sarawak

Kothare SN

Singapore Med J, 1978 Dec;19(4):220-4.
PMID: 87015

This is a preliminary report of 46 sera tested for alpha-fetoprotein (AFP) by the Counter immuno-electrophoresis technique in which biopsies for histopathology were also submitted. In 42 cases the needle biopsy of the liver was available. The material was divided into two groups on the basis of AFP positive and AFP negative sera and their histological diagnosis. The overall positivity rate in proven Primary liver cell carcinoma was 64.2 per cent.

Matched MeSH terms: alpha-Fetoproteins/analysis*
Fulltext Selenium and hepatocellular carcinoma

Nasar Alwahaibi, Jamaludin Mohamed

Jurnal Sains Kesihatan Malaysia, 2008;6(2):1-14.
MyJurnal

While cancer is considered to be one of the leading causes of death worldwide, there is a growing scientific and public interests on selenium as a dietary and antioxidant of many diseases, in particular, cancer. Despite advanced technology and significant improvement of surgical, chemical, hormonal and radio therapies, hepatocellular carcinoma (HCC) is still common in Asia and Africa and is increasing in the developed countries. Prognosis of HCC at an early stage is still challenging. At the moment, combination of Alpha feto protein (AFP) and ultrasonography tests offers more accurate and sensitive results for the diagnosis of HCC. Selenium (also known as the moon element) has been recognized for almost 49 years as an antioxidant and anti cancer agent. The weight of evidence supports the position of selenium as an anti cancer agent for HCC but the molecular mechanism of how selenium inhibits HCC is still unknown. Numerous theories have been proposed and selenium induced apoptosis and cell cycle arrest is the predominant one so far.

Matched MeSH terms: alpha-Fetoproteins
Fulltext Effect of protocatechuic acid-layered double hydroxide nanoparticles on diethylnitrosamine/phenobarbital-induced hepatocellular carcinoma in mice

Gani SA, Muhammad SA, Kura AU, Barahuie F, Hussein MZ, Fakurazi S

PLoS One, 2019;14(5):e0217009.
PMID: 31141523 DOI: 10.1371/journal.pone.0217009

Researchers investigating cancer chemotherapy and management continue to search for agents that selectively kill malignant cells and leave healthy neighboring cells intact. Natural products provide relevant resources for anti-cancer drug discovery. However, the physicochemical properties of these compounds limit their efficient uptake and bioavailability. We introduced a nanocarrier system, namely, zinc-aluminum-layered double hydroxide (ZnAl-LDH) intercalated with protocatechuic acid. In this study, the efficacy and toxicity of protocatechuic acid intercalated in zinc aluminum-layered double hydroxide nanoparticles (PCA-ZnAl) against diethylnitrosamine/phenobarbital (DEN/PB)-induced hepatocellular carcinoma (HCC) in BALB/c mice was evaluated. HCC in male mice was induced by a single-dose intraperitoneal administration of DEN and was promoted by the introduction of PB via drinking water for 12 weeks. HCC induction was confirmed after the DEN/PB introduction period by measurement of the elevated level of serum α-feto protein (AFP). The results showed that the level of α-fetoprotein was significantly reduced in PCA-ZnAl (350±43.90 ng/mL), doxorubicin (DOX) (290±20.52 ng/mL) and ZnAl-LDH (390±19.65 ng/mL) treated animals compared to HCC mice treated with normal saline (580.4± 52.04 ng/mL). Superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were significantly increased, whereas the level of lipid peroxidation was significantly decreased in HCC mice treated with DOX, PCA-ZnAl and ZnAl-LDH compared with those in HCC mice treated with saline. Restoration of hepatocyte morphology was observed following treatment that was comparable to that in the normal control group. Deterioration of hepatic cells and a significant increase of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were observed in the cancer-induced untreated group compared with that in the groups treated with nanoparticles. The histopathological features of the liver obtained from PCA-ZnAl-treated mice showed a uniform size with a similar distribution of the nuclear-cytoplasmic ratio and nucleus centrally located in the cytoplasm, similar to the normal liver cells. The results underscored the potential of PCA-ZnAl for the treatment of hepatocellular carcinoma.

Matched MeSH terms: alpha-Fetoproteins
Hemorrhagic extrahepatic recurrence of hepatocellular carcinoma: A case report

Yeow GPV, Yeow DGE, Sankaran P, Maiyauen T, Sharif MS

Ann Hepatobiliary Pancreat Surg, 2019 Feb;23(1):77-79.
PMID: 30863813 DOI: 10.14701/ahbps.2019.23.1.77

The recurrence of hepatocellular carcinoma (HCC) can mainly be divided into two phases or types: the intrahepatic recurrence (IHR) and the extrahepatic recurrence (EHR). Generally speaking, the EHR is usually referenced as being the less common of the two types or categories. In a post-hemihepatectomy patient with routine surveillance at 6 months, it was noted that the patient appeared to have an elevated alpha-fetoprotein, and also complained of vague lower abdominal pain. The accompanying computed tomography scan revealed a 6 cm-sized heterogeneous mass located at the pelvis region. Next, during a laparotomy for resection, the tumor was found to be bleeding from the omental deposition. In conclusion, a high index of suspicion and early surgical intervention can help in detecting possible bleeding extrahepatic recurrence in the background of a patient with history of HCC.

Matched MeSH terms: alpha-Fetoproteins
Fulltext Remarkable Anticancer Activity of Teucrium polium on Hepatocellular Carcinogenic Rats

Movahedi A, Basir R, Rahmat A, Charaffedine M, Othman F

Evid Based Complement Alternat Med, 2014;2014:726724.
PMID: 25197311 DOI: 10.1155/2014/726724

The term cancer has been concomitant with despair, agony, and dreadful death. Like many other diseases, herbal therapy has been used to prevent or suppress cancer. The present study investigated the capability of the decoction of Teucrium polium L. from Lamiaceae family to protect liver cells against hepatocellular carcinoma in carcinogenesis-induced animal model. After 28 weeks of treatment with decoction of Teucrium polium L., serum biochemical markers including ALT, AST, AFP, GGT, ALP, HCY, TNF-α, α2MG, and CBG have been regulated auspiciously. Total antioxidant status also has been increased intensely. Liver lesion score in treated group was lessened and glucocorticoid activity has been intensified significantly. In conclusion, Teucrium polium L. decoction might inhibit or suppress liver cancer development.

Matched MeSH terms: alpha-Fetoproteins
Immunohistochemical expression of pi class glutathione S-transferase and alpha-fetoprotein in hepatocellular carcinoma and chronic liver disease

Yusof YA, Yan KL, Hussain SN

Anal. Quant. Cytol. Histol., 2003 Dec;25(6):332-8.
PMID: 14714299

To determine whether tumor marker pi glutathione transferase (GST-pi) is expressed in hepatocellular carcinoma (HCC) and other chronic liver diseases and to compare its expression with that of alpha-fetoprotein (AFP).

Matched MeSH terms: alpha-Fetoproteins/biosynthesis*
Fulltext Radioimmunoassay of serum alpha-fetoprotein in patients with different maliganant tumors

Lie-Injo LE, Caldwell J, Ganesan S, Ganesan J

Cancer, 1976 Jul;38(1):341-5.
PMID: 59626 DOI: 10.1002/1097-0142%28197607%2938%3A1<341%3A%3AAID-C

The level of serum alpha-fetoprotein (AFP) was estimated by radioimmunoassay in 153 normal healthy Malysians of different ethnic groups. The mean level was 7.5 In1/ml (SD 2.28InU/ml). Among 330 patients with malignant tumors, 11 had increased levels of AFP. The only patient who had hepatoma had a very high level of serum AFP. High levels were also found in three of four patients with dysgerminoma of the ovary, in the only two patients with carcinoma of the testis, and in one patient with secondary carcinoma of the humerus of unknown origin. Lower, but significantly increased levels were observed in one patient (of 48) with breast carcinoma, one patient (of 8) with basal cell carcinoma of the nose, one patient (0f 27) with carcinoma of the lung, and one patient (of 59) with nasopharynegeal carcinoma.

Matched MeSH terms: alpha-Fetoproteins/metabolism*
Fulltext Combined assessment of TGF-beta-1 and alpha-fetoprotein values improves specificity in the diagnosis of hepatocellular carcinoma and other chronic liver diseases in Malaysia

Yasmin Anum MY, Looi ML, Nor Aini AH, Merican I, Wahidah A, Mohd Radzi AH, et al.

Med J Malaysia, 2009 Sep;64(3):223-7.
PMID: 20527273 MyJurnal

Transforming growth factor beta-1 (TGF-beta-1) is a multifunctional cytokine involved in the regulation of growth and differentiation of both normal and transformed cells. The main aim of this study was to determine whether TGF-beta-1 or alpha fetoprotein (AFP) or the combination of the two is a better indicator for hepatocellularcarcinoma (HCC). Serum TGF-beta-1 and AFP were measured by ELISA in 40 healthy subjects, 23 patients with hepatocellular carcinoma (HCC), 70 patients with hepatitis B, 26 patients with hepatitis C and 16 patients with liver cirrhosis (LC). Patients with liver diseases showed significantly higher serum TGF-beta-1 values (> 3 fold) compared to control subjects. As for serum AFP, significant elevation was only observed for HCC cases. Serum TGF-beta-1 exhibited higher percent sensitivity compared to serum AFP in all liver diseases. Combination of serum TGF-beta-1 and AFP increased specificities in all cases studied. In conclusion, serum TGF-beta-1 is a more sensitive marker for HCC when compared to serum AFP and its specificity is increased when combined with serum AFP.

Matched MeSH terms: alpha-Fetoproteins/metabolism*
Recombinant human alpha fetoprotein synergistically potentiates the anti-cancer effects of 1'-S-1'-acetoxychavicol acetate when used as a complex against human tumours harbouring AFP-receptors

Arshad NM, In LL, Soh TL, Azmi MN, Ibrahim H, Awang K, et al.

Oncotarget, 2015 Jun 30;6(18):16151-67.
PMID: 26158863

Previous in vitro and in vivo studies have reported that 1'-S-1'-acetoxychavicol acetate (ACA) isolated from rhizomes of the Malaysian ethno-medicinal plant Alpinia conchigera Griff (Zingiberaceae) induces apoptosis-mediated cell death in tumour cells via dysregulation of the NF-κB pathway. However there were some clinical development drawbacks such as poor in vivo solubility, depreciation of biological activity upon exposure to an aqueous environment and non-specific targeting of tumour cells. In the present study, all the problems above were addressed using the novel drug complex formulation involving recombinant human alpha fetoprotein (rhAFP) and ACA.

Matched MeSH terms: alpha-Fetoproteins/pharmacology*
Management of primary liver cell carcinoma

Balasegaram M

Am J Surg, 1975 Jul;130(1):33-7.
PMID: 50750

A review of 352 patients with primary liver cell carcinoma treated by the author is presented. The poor rate of resectability (7 per cent) has necessitated various forms of treatment over the years. These are described in detail. Based on this experience, the current form of treatment for nonresectable carcinoma is summarized. Although it is too early to assess this form of treatment, initial results appear to be promising. A second report in the near future is planned.

Matched MeSH terms: alpha-Fetoproteins/analysis
Alpha-Fetoprotein levels in normal males from seven ethnic groups with different hepatocellular carcinoma risks

Sizaret P, Tuyns A, Martel N, Jouvenceaux A, Levin A, Ong YW, et al.

Ann N Y Acad Sci, 1975 Aug 22;259:136-55.
PMID: 54017

Alpha-Fetoprotein (AFP) levels of 1,335 males (15 years and older) of seven ethnic groups (Chinese, Indians, and Malays from Singapore, Caucasians from Lyon, and Blacks from Nairobi, forest, and the savanna region of the Ivory Coast) were determined by radioimmunoassay. A few elevated levels (up to 30 nanounits/ml) were detected in some normal individuals, especially in the older age-groups. In addition, there was a systematic age-dependency of AFP levels particularly evident in the groups from Singapore-Lyon, in which there was a 50% AFP increase between the ages of 20 and 40. Comparison between Africans on the one hand and people from Singapore-Lyon on the other hand revealed highly significant differences (p less than 0.001), especially in the younger groups, whereas Chinese, Malays, and Indians from Singapore had very similar AFP pattern; this suggests an important role for environmental factors in the regulation of AFP levels. The age dependency of the presumed effect of environmental factors is in keeping with experimental data showing that young animals respond more vigorously to AFP-stimulating factors. Although the incidence of hepatocellular carcinoma (HCC) differs in the three Singapore groups (the highest in Chinese and the lowest in Indians), no relationship was observed in this study between mean AFP level and HCC incidence in Singapore.

Matched MeSH terms: alpha-Fetoproteins/metabolism*
Hepatitis markers in Malaysians with hepatocellular carcinoma

Lopez JB, Thambyrajah V, Balasegaram M, Satgunasingam N

Br J Biomed Sci, 1994 Jun;51(2):177-80.
PMID: 7519505

Sera from 80 Malaysians with confirmed hepatocellular carcinoma were tested for five markers of the hepatitis B virus, anti-HCV and anti-HDV by enzyme immunoassay, and alpha fetoprotein (AFP) was measured by radioimmunoassay. Of the patients, 98.8% had evidence of HBV infection and 75% were positive for HBsAg--which latter correlated with AFP raised above cut-off values of 500 ng/ml (P = 0.0001) and 200 ng/ml (P = 0.005). Males correlated significantly with the presence of HBsAg (P = 0.002). Thirty-one per cent of HBsAg positive patients were also positive for HBeAg and 74% for anti-HBe. Twenty per cent of the cases were concurrently positive for both HBsAg and anti-HBs. Six of 70 (8.6%) patients were positive for anti-HCV, of whom four were also positive for HBsAg. None of 67 patients tested for anti-HDV were positive. The results strongly indicate an important aetiological role for hepatitis B virus in causation of hepatocellular carcinoma among Malaysians.

Matched MeSH terms: alpha-Fetoproteins/analysis

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