Aiming for the earliest diagnosis of hepatocellular carcinoma
For almost three quarters of hepatocellular carcinoma (HCC) patients in Europe it is too late for curative treatment because the disease is often only diagnosed at a very advanced stage. Interviewed Professor Guido Gerken MD, Director of the Department for Gastroenterology and Hepatology at University Hospital Essen, about improved and timelier diagnostic capabilities that have already been established elsewhere.
Interview: Ralf Mateblowski
Asked about necessary improvements in hepatocellular carcinoma (HCC) diagnoses, gastroenterology expert Professor Guido Gerken explained: ‘Basically we need to identify and diagnose HCC patients earlier and faster and clearly to achieve a better prognosis for treatment and for the course of the disease. HCC is one of the most common primary tumours in humans, ranking among the “top five” for morbidity and amongst the “top three” for mortality. We are looking at a growing problem, as the number of HCC cases is on the increase. We need to intervene to reduce the overall mortality.’
How do AFP-L3 and DCP biomarkers help?
‘Let’s ask ourselves what the current standard for HCC diagnosis is, and what is wishful thinking. In Europe, diagnostic imaging is the gold standard – the only accepted procedure for early diagnosis. Guidelines state that patients with suspected HCC should be monitored, using ultrasound, CT or MRI scans. In Japan, however, there is clear evidence that biomarkers are important, or even decisive, for early detection. China also utilises biomarkers to improve early diagnosis.
‘In any case, clarification of the causes of liver cirrhosis is indispensable, i.e. establishing whether there are viral causes, a non-alcoholic steatohepatitis or genetic factors. Conventional laboratory diagnosis with alpha-fetoproteins (AFP), the biomarkers typical for HCC, has now been enhanced with subtypes such as AFP-L3 (lectin-reactive AFP) and DCP (des-gamma-carboxy prothrombin): The three-way combination of AFP, AFP-L3 and DCP now also allows us to confirm HCC with significantly higher sensitivity and specificity in Europe.’
What is the GALAD-Score?
‘The above-mentioned markers have been known for a decade and a half. They have been established in Japan for years, but have not been accepted in Europe. The GALAD-Score will hopefully initiate a new evaluation of these markers as this new diagnosis algorithm links biological patient data (gender and age) with laboratory data AFP-L3, AFP and DCP.
‘We carried out a prospective study in Essen that was published in December. The data presented clearly speak for the GALAD-Score. Our investigation was carried out over a period of several years and has shown that the individual markers improve the early HCC detection substantially, but the most significant improvement was seen with the combination of all three markers: It achieves a sensitivity of 85% and a specificity of 93%!
‘Improved early detection, as seen with the GALAD-Score, cannot be achieved with dynamic imaging because it has limitations. The significance of ultrasound depends on the patient and examiner and varies according to the standard of equipment used. In turn, cross-sectional imaging procedures have economic aspects, because diagnosis via MRI or contrast enhanced CT has very different financial dimensions compared to biomarkers.
‘The feasibility is also questionable: Can we really carry out diagnostic imaging procedures for a patient every three or six months? For a large country such as ours this is not practicable, and it is also far too expensive for the healthcare system.’
How is GALAD used in Essen?
‘Thanks to the GALAD-Score, we can detect the early stages of HCC earlier and can therefore start the appropriate treatment earlier. The score is established in our central laboratory, CE marked and implemented in the laboratory information system (LIMS). We also offer the determination of AFP-L3 and DCP to other providers nationally, as a service, including Professor Michael Manns in Hannover and Dr Thomas Rasenack in Berlin/Potsdam. We’d like to see the procedure become established so that optimised early detection of HCC, combined with diagnostic imaging, becomes accessible to all.’
As a young internal medicine specialist in the 1980s, and funded with a research grant, Guido Gerken MD carried out research into hepatitis B virus-associated liver disease at the Pasteur Institute in Paris. A recognised expert in gastroenterology, Gerken has been Director of the Department for Gastroenterology and Hepatology for 20 years, and Managing Director of the Centre for Internal Medicine at the University Hospital Essen since 2005. The 64-year-old professor’s treatment focus ranges from acute and chronic liver disease to transplantation. Some of his scientific questions centre around molecular-biological pathomechanisms in acute liver failure and also on the establishment of biomarkers in gastroenterology.