HCC Biomarkers

AFP-L3 and DCP

HCC Biomarkers News

Latest News

March 1st, 2011
Announcing 510(k) Clearance of a New Microfluidic-based IVD Test System, the μTASWakoTM i30 Immunoanalyzer, and AFP-L3 and DCP Assays for Liver Cancer Risk Assessment.

Contact: Audrey Long at 877-714-1924

News Archive

Oct. 2010
New! Quest Diagnostics now offers HCC panel test. This HCC panel test conveniently allows measurement of AFP-L3% and DCP with a single test code: 16222

Feb. 2010
Quest Diagnostics offers Wako's FDA cleared DCP (Des-gamma-carboxy prothrombin) test for HCC risk assessment

Wako's FDA cleared and CMS reimbursed DCP (Des-gamma-carboxy prothrombin, also known as PIVKA II) test for HCC risk assessment is now available at Quest Diagnostics.

The test became available on February 8, 2010 and is performed by Quest Diagnostics Nichols Institute in San Juan Capistrano, California. Quest Diagnostics reports that Wako's DCP test is "intended for in vitro diagnostic use as an aid in the risk assessment of patients with chronic liver disease for progression to hepatocellular carcinoma (HCC) in conjunction with other laboratory findings and clinical assessment." Quest Diagnostics'test code for Wako's DCP test is 19982.

Sep. 2009
NASH patients are at high risk for hepatocellular carcinoma (HCC)

Researchers at the Cleveland Clinic have found that cirrhotics who suffer from nonalcoholic steatohepatitis (NASH) are at significant risk of developing liver cancer. Dr. Nizar Zein, the Cleveland Clinic's chief of hepatology and medical director of liver transplantation, presented the study results at the 2009 Digestive Disease Week conference in Chicago.

The study followed 510 patients with liver cirrhosis from 2003 to 2006. Cirrhosis was caused by NASH in 195 patients and by hepatitis C viral infection in 315 patients. Over the three-year follow-up period, 20% of the hepatitis C group developed HCC while 13% of the NASH group developed HCC. The researchers also calculated the annual cumulative incidence of HCC since the patient's diagnosis of cirrhosis. In the NASH group, the proportion of patients with HCC detected averaged 2.6% annually. At this rate, more than one-fourth of this patient group would develop HCC in 10 years. The study also showed that NASH patients who consumed even a small amount of alcohol were almost four times more likely to develop HCC (3.6 hazard ratio).

"This study shows for the first time that patients with NASH are at high risk for HCC, especially if they drink, and, as such, would probably benefit from a regular screening strategy," Dr. Zein concluded.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States. NASH is the most serious form of NAFLD. Left untreated, about 20 percent of NASH patients develop cirrhosis. Ultimately, 80 percent of all HCC cases arise from cirrhosis.

The commercially available HCC biomarker DCP (also known as PIVKA II) has been clinically demonstrated to be useful in HCC detection for ALD and NAFLD patients (BMC Cancer. 2008 Jul 18;8:200). Dr. Gary Beale and colleagues measured serum AFP and DCP in patients with HCC arising on a background of ALD (n=31) or NAFLD (n=19). Results were compared and contrasted with a control patient group with biopsy proven steatohepatitis-related cirrhosis (n=41). DCP alone detected 78% of patients with 80% specificity. Combination of AFP and DCP yielded the best diagnostic accuracy: 94% sensitivity and 80% specificity. Dr. Beale therefore recommended using AFP and DCP tests for HCC surveillance in ALD/NAFLD patients.

Page Top

Mar. 2009
AFP, AFP-L3 and DCP are a useful marker combination to assess response to Sorafenib treatment

Clinicians from University of Mainz announced that AFP, AFP-L3 and DCP serve as "a readily available marker combination to assess the response to sorafenib treatment in patients with advanced hepatocellular carcinoma (HCC)". Results from their study, which measured serum HCC biomarkers AFP, AFP-L3 and DCP in patients receiving sorafenib treatment, were presented at the 2009 annual congress of the German Association for the Study of the Liver in Heidelberg, Germany. Before the treatment, all three HCC biomarkers were elevated in 14 of 32 patients (44%). DCP was elevated in 29 of 32 patients (91%). AFP was elevated in 22 of 32 (69%) patients. Of the patients with elevated AFP (> 10 ng/mL), 16 of 22 showed an elevated AFP-L3. The calculated Disease Control Rate (DCR) for the total cohort was 35% after 3-4 months of therapy. The DCR for patients with no AFP increase was 38%. Patients without DCP or AFP-L3 increase had a DCR of 67%. DCR was 100% in patients with no increase of AFP-L3 and DCP. Patients with increased DCP during therapy had shorter survival time compared to those with constant or decreased DCP.

Summary

Calculated Disease Control Rate (DCR)
Patients with no increase in AFP 38%
Patients with no increase in DCP or AFP-L3 67%
Patients with no increase in DCP and AFP-L3 100%

AFP, AFP-L3%, and DCP levels in patients with advanced hepatocellular carcinoma treated with sorafenib
Henning Schulze-Bergkamen, Arndt Weinmann, Marcus A. Wö rns, Pia R. Spies, Andreas Teufel, Christoph Dü ber, Gerd Otto, Annette Shresta, Binje Vick, Robert Kü per, Josef Schurek, Peter R. Galle, Marcus Schuchmann, Martin Volkmann

Poster was presented at the 2009 annual congress of the German Association for the Study of the Liver in Heidelberg, Germany

Page Top

Jan. 2009
Wako's DCP test receives a unique CPT code and a $94.04 CMS reimbursement

The Centers for Medicare & Medicaid Services has released the new Clinical Laboratory Fee Schedule test code and final payment for the testing of DCP (Des-gamma-carboxy prothrombin) also known as PIVKA-II. The new code number, unique to DCP, is CPT 83951. The new National Limitation Amount (NLA) for this code is $94.04, effective January 1, 2009. This follows the FDA 510(k) clearance of the DCP test in January 2007. Wako's test is the only FDA-cleared DCP assay. Hepatologists and gastroenterologists use DCP as a risk assessment and rule-out test for hepatocellular carcinoma (HCC)

Page Top

Oct. 2008
AFP, PIVKA II, GP3, SCCA-I and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease

Clinicians at Newcastle University, UK and University of Bari, Italy measured several HCC biomarkers (AFP, PIVKA II, GP3, and SCCA-I) in 50 patients with HCC arising on a background of ALD (n=31) or NAFLD (n=19). Results were compared and contrasted with a control patient group with biopsy proven steatohepatitis-related cirrhosis (n=41). PIVKA II alone had diagnostic sensitivity of 78% and 80.5% specificity. However, combination of AFP and PIVKA II yielded the best diagnostic accuracy. The authors note that the combination of serum AFP and PIVKA II in these patients is better than either alone, with a combined sensitivity of 94% and a specificity of 80.5%.

While the patient number for this study is relatively small, it is noteworthy since the diagnostic performance of PIVKA II has not been evaluated for this etiology. Fifteen percent of US population is estimated to have a non-alcoholic fatty liver. In addition, approximately 38 million US patients suffer from NAFLD. Therefore, it is especially important to consider using additional tools such as DCP (PIVKA II), and AFP-L3 for HCC surveillance in ALD and NAFLD patients. Wako's AFP-L3 and DCP tests have the FDA clearance as HCC risk assessment tests. In addition, both tests have unique CPT codes and are CMS reimbursed. Several reference labs offer Wako's AFP-L3 and DCP tests.

Gary Beale, Dipankar Chattopadhyay, Joe Gray, Stephen Stewart, Mark Hudson, Christopher Day, Paolo Trerotoli, Gianluigi Giannelli, Derek Manas and Helen Reeves, BMC Cancer 2008, 8:200, 18 July 2008.

Page Top

July 2008
Surveillance for Hepatocellular Carcinoma in Cirrhotic patients saves lives

"The quality of surveillance has a direct impact on hepatocellular carcinoma stage at diagnosis, access to liver transplantation, and survival", says Dr. Richard Stravitz in the February 2008 issue of The American Journal of Medicine. Dr. Stravitz and his colleagues at Virginia Commonwealth University and VA medical center in Richmond, Virginia conducted a study in which 269 patients with cirrhosis and hepatocellular carcinoma were retrospectively categorized into three groups according to quality of surveillance: standard-of-care (n = 172) (group 1); substandard surveillance (n = 48) (group 2); and absence of surveillance in patients not recognized to be cirrhotic (n = 59) (group 3). HCC was diagnosed at stages 1 and 2 in 70% of patients in group 1, 37% of patients in group 2, and only 18% of patients in group 3. Liver transplantation was performed in 32% of patients in group 1, 13% of patients in group 2, and only 7% of patients in group 3. The three-year survival in patients who underwent liver transplant was 81% versus 12% who did not undergo transplantation. Three-year survival from HCC diagnosis for patients who were not under surveillance (group 3) was only 13%. On the other hand, groups 1 and 2 had three-year survival of 39%, and 27%, respectively. Dr. Stravitz and his colleagues conclude that the application of even a modest surveillance program for HCC in cirrhotic patients identifies patients with early-stage disease who are candidates for liver transplantation. In turn, HCC surveillance improves long-term, tumor-free survival of HCC patients.

Surveillance for Hepatocellular Carcinoma in Patients with Cirrhosis Improves Outcome. Stravitz RT, Heuman DM, Chand N, et al., Am J Med. 2008 Feb;121(2):119-126.

Page Top

May. 2008
UCLA clinicians recommend using DCP as a main serum test for HCC surveillance and AFP-L3 for HCC prognosis

"DCP appears to be the most accurate tumor marker and should be used for HCC surveillance", says Dr. Francisco Durazo in the May 2008 issue of Journal of Gastroenterology and Hepatology. Dr. Durazo and his colleagues at UCLA Medical Center compared three HCC serum biomarkers (AFP, AFP-L3, DCP) in two groups of patients: HCC patients with chronic HCV or HBV infection, and non-HCC patients with chronic viral hepatitis or cirrhosis. Two hundred and forty patients with HBV or HCV infection were studied. These include 144 patients with HCC, 47 with chronic hepatitis and 49 cirrhotic patients. The authors note that the serum levels of all three HCC biomarkers were significantly elevated in patients with HCC compared to non-HCC patients (P < 0.0001). In addition, all three markers were significantly elevated in the presence of metastatic HCC. Cutoff for DCP, AFP, and AFP-L3 were 84 mAU/mL, 25 ng/mL, and 10%, respectively. DCP performed the best with 87%, 85%, and 86.8% for sensitivity, specificity, and PPV, respectively. AFP-L3's performance showed the best specificity (90%), with 56% sensitivity and 56.1% PPV. AFP had the second best sensitivity with 69%, 87%, and 69.8% for sensitivity, specificity, and PPV, respectively. DCP was correlated with tumor size, and was not elevated in any patients without HCC. Authors recommend DCP for HCC surveillance and diagnosis. The authors recommend using AFP-L3 for prognosis since it has been related to rapid tumor growth, larger size, PVI and metastasis.

Des-γ-carboxyprothrombin, α-fetoprotein and AFP-L3 in patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma. Durazo FA, Blatt LM, Corey WG, et al., J Gastroenterol Hepatol.(May 2008)

Page Top

Feb. 2008
Using HCC biomarkers AFP-L3% and DCP in the HCC surveillance strategy is most cost-effective and improves patient care

A recent study shows that including the HCC biomarkers AFP-L3% and DCP in the HCC screening strategy both reduces the cost of screening and improves patient care. Dr. Mark Russo from Carolinas Medical Center and Dr. Richard Sterling from Medical College of Virginia, presented their cost-effectiveness analysis of 9 HCC screening strategies at AASLD's 2007 Liver Meeting. The authors state that current screening program using only ultrasound (US) is expensive. This is because a positive US is frequently followed by CT or MRI. Given the low diagnostic specificity of US, the follow-up CT or MRI is often unwarranted. The addition of HCC biomarkers AFP-L3% and DCP, offer an opportunity to reduce the cost of screening. The authors state that these markers, which have "better test characteristics than total AFP", help identify which patients should proceed directly to CT or MRI. The study compared all other strategies including the method set forth in the 2005 AASLD guidelines for using annual or semiannual US. The authors conclude that a semi-annual screening strategy, which alternates US with AFP-L3% plus DCP, "saves more lives" and is most cost-effective compared to US only strategy. For an annual screening strategy, using AFP-L3% plus DCP instead of US saves more lives and is most cost-effective because fewer patients would undergo frequent and repeated CT. Both AFP-L3 and DCP have the FDA 510(k) clearance as risk assessment tests for development of HCC. Most major reference labs now offer both tests. Please contact Wako Diagnostics (liver@wakousa.com) or your local reference lab representative to order these tests.

Page Top

Nov. 2007
DCP test is now available at major reference labs!

DCP complements AFP-L3% measurement for HCC risk assessment. Simultaneous measurement of AFP-L3% and DCP has been demonstrated to increase the sensitivity for HCC detection while maintaining high specificity. DCP test is 510(k) FDA cleared.
To find more information, download this document.

Page Top

Oct. 2007
New report: AFP, AFP-L3, and DCP are useful in assessment of tumor progression and HCC patient outcome prediction

Toyoda et al. report in the September 2007 issue of Hepatology Research (2007 Sep;37 Suppl 2:S166-71) that HCC markers AFP, AFP-L3 and DCP tests are "objective, simple to perform, and easy to repeat,..., for the evaluation of tumor progression and prediction of patient outcome." The study shows that the rate of survival in patients with elevated HCC markers is significantly (p<0.0001) lower than that of patients without elevated level. The percentage of patients with elevated level gradually increased in parallel with the progression of tumor stage for all three markers. In addition, the number of elevated tumor markers increased with recurrence of HCC and tumor progression. Although HCC markers cannot replace the results of imaging or pathology studies, the markers are advantageous in terms of objectivity and simplicity. In conclusion, authors state, "Although most currently available standards to evaluate tumor progression do not contain tumor markers, measurement of levels of those markers will provide additional important information for the management of patients with HCC."

Role of tumor markers in assessment of tumor progression and prediction of outcomes in patients with hepatocellular carcinoma. Toyoda H. et al., Hepatology Research 2007; 37(suppl. 2):S166-S171.

Page Top

Aug. 2007
A new North American multicenter study for clinical utility of AFP-L3% for detection of HCC in patients with chronic hepatitis (CH) C virus-related cirrhosis

Dr. Richard K. Sterling at Virginia Commonwealth University Health Systems reports in the October, 2007 issue (Epub ahead of print) of American Journal of Gastroenterology (2007 Oct:102(10):2196-2205), a 7 clinical site prospective study to compare the clinical utility of AFP-L3% with that of AFP alone in North American patients with chronic hepatitis C virus-related cirrhosis. The patients were prospectively followed every 3-6 months for 2 years. The study evaluated 372 patients with chronic hepatitis C virus-related cirrhosis, of which 40 patients had hepatitis C virus-related HCC at entry. Of 332 patients without HCC at entry, 34 developed HCC, yielding an annual incidence of 4.3 %. The remaining 298 patients remained free of HCC. In patients with elevated total AFP (20-199.9 ng/mL), AFP-L3% (cutoff at 10%) exhibited a specificity of 86.6% and negative predictive value (NPV) of 80.7% The distribution of AFP-L3% differed significantly between the groups of patients with and without HCC. Authors note, "Multivariate analysis identified positive AFP-L3% as an independent predictor of the presence of HCC (p<0.0001, odds ratio: 7.2)." Furthermore, AFP-L3%-positive patients were significantly more likely to have HCC than the overall group (p=0.0001) and the AFP-positive group (p=0.01541). Authors conclude, "The clinical utility of AFP-L3% is in the increased specificity, especially in those with increased AFP, in reducing the relative high false positive rate of total AFP indicating a low likelihood of HCC."

Clinical Utility of AFP-L3% Measurement in North American Patients with HCV-Related Cirrhosis. Richard K. Sterling, Lennox Jeffers, Frederic Gordon, Morris Sherman, Alan P. Venook, K. Rajender Reddy, Shinji Satomura, Myron Schwartz, American Journal of Gastroenterology 2007 Oct;102(10):2196-2205. Epub 2007 Jul 7.

To request a reprint of this article, please email to liver@wakousa.com with your mailing address.

Page Top

July 2007
New report on enhanced serum marker combination tests from University of Pittsburgh

Dr. Brian Carr at the Liver Cancer Center of the University of Pittsburgh Medical Center reported the results of a prospective study of several HCC biomarkers on 99 United States HCC patients in the January 2007 issue of Digestive Diseases and Sciences (52:776-782). Serum concentrations of AFP-L3%, DCP and AFP were measured in 99 patients histologically diagnosed with unresectable HCC. The sensitivity of AFP-L3%, DCP, and AFP was 61.6%, 72.7%, and 67.7%, respectively. The highest sensitivity of 85.9% was achieved when all three markers were used in concert. In addition, AFP-L3% level was significantly associated with portal vein invasion (p = 0.0059) and presented a strong statistical relationship to patient outcome. The authors stated that "the combination of AFP-L3% and DCP might be the best panel to detect HCC", and that AFP-L3% "appears to be a useful prognostic marker for HCC". Metastasis of HCC was significantly associated with DCP levels (p = 0.0368) but DCP alone was not associated with the cumulative survival rate (p = 0.9581). These results are different from previous reports. The authors attributed these discrepancies to ethnic differences or differences in HCC populations since the prior results came only from Japanese HCC patients. The authors concluded that "the combination of AFP-L3%, DCP, and AFP was demonstrated to be superior in the detection of HCC compared with each marker alone".

Clinical Evaluation of Lens culinaris Agglutinin-Reactive a-Fetoprotein and Des-Gamma-Carboxy Prothrombin in Histologically Proven Hepatocellular Carcinoma in the United States. Brain I. Carr, Futoshi Kanke, Margaret Wise, Shinji Satomura, Dig Dis Sci (2007) 52:776-782.

Page Top

June 2007
Mayo Clinic Study evaluates the diagnostic use of the HCC marker, AFP-L3%

Apinya Leerapun and Mayo Clinic colleagues report in the March 2007 issue of Clinical Gastroenterology and Hepatology (5:394-402) their retrospective study of the biomarker AFP-L3 of 272 patients with HCC (n=166) or benign liver disease (n=106). Leerapun et al. note that patients at risk for HCC but with indeterminate total AFP values "present a diagnostic dilemma." In patients with total AFP in the 10-200 ng/mL range, an AFP-L3% greater than 10% had sensitivity of 71% and specificity of 63% for the diagnosis of HCC. Using the higher cut-off of 35% AFP-L3%, the authors found that the AFP-L3% test had a diagnostic specificity of 100%. The authors conclude that "AFP-L3%, used in combination with AFP, may be a clinically useful adjunct marker for the diagnosis of HCC."

Page Top

Press release

Feb. 1, 2007
WakoUSA Reports the 510(k) Clearance of Des-Gamma Carboxyprothrombin (DCP) Test for HCC Risk Assessment

Nov. 15, 2006
Wako Diagnostics Reports the Release of a New CPT Code for AFP-L3%

Page Top

Other publications

AFP-L3% on CAP Today

AFP-L3% is highlighted in CAP Today July 06 article, "For tumor markers, hope springs eternal."