国际肝病采访Hans Van Vlierberghe f教授

Hepatology Digest: This past April you published an article entitled “Outcome of Patients with Hepatocellular Carcinoma Listed for Liver Transplantation within the Eurotransplant Allocation System” in Liver Transplantation. You pointed out that allocation rules for HCC should consider not only tumor characteristics, but also the degree of liver impairment. Furthermore, patients older than 50, with a stage above the Milan criteria at transplantation, have a poorer prognosis after transplantation. In a clinical setting, should HCC patients with a good prognosis be given priority for liver transplant rather than those who are sicker and with a poorer prognosis?

Prof. Van Vlierberghe: First of all I would like to thank you for the invitation for this interview. You should consider two things. First, the age is an important thing because the average age of transplant patients in Belgium and Western Europe is 55. This means that the majority of our patients are above the age of 50, which was published in the article, so when we use an age limit we are discarding a lot of patients having access to transplantation. Second, the data were taken out of the explant. So patients outside the Milan criteria sometimes were inside the Milan criteria due to imaging before transplantation. It’s very difficult to make out who in a pathological way will be outside the Milan criteria. Secondly, there are two things. The age limit is very sharp because the majority will not have extra MELD points and so will have a higher priority and also the data were on explant, which means a kind of mismatch could be there between the pathological and radiological images. Secondly, it’s not out of the paper but it is general knowledge and recent literature coming from the United States, that in patients outside the Milan criteria, when you downstage them via different protocols, and UCSF criteria from the United States very well demonstrated that patients outside the Milan but within the UCSF criteria, when they could be downstaged have an excellent prognosis. So I would be very careful to take very clear conclusions from the article because you would discard transplantation for a lot of patients, perhaps on indications that are not valid. The data are very important and the most important thing I conclude from the article is that we need better imaging techniques to have better correlations between radiology and pathology after transplantation.

Hepatology Digest: Clinical Transplantation published your study about split liver transplantation with extended right grafts entitled “Split Liver Transplantation with Extended Right Grafts Under Patient-Oriented Allocation Policy: Single Center Matched-Pair Outcome Analysis” in March of this year. According to this comparative study, split liver transplantation with extended right grafts according to the patient-oriented allocation policy can be performed under emergency or urgent care circumstances with acceptable morbidity and adequate long-term survival. What are the issues requiring special attention in a clinical setting?

Prof. Van Vlierberghe: This is a very straightforward answer because it was already demonstrated by the European transplant group that extended right grafts in conditions where it is not urgent functions very well when the center has experience doing splits. Now we can demonstrate that even in urgent indications this is safe. The message is clear that you can use extended right grafts without any problem in chronic patients as well as in acute patients. You can bring the number of transplants higher by using extended right grafts without having any impact on the outcome of patients in acute and chronic conditions.

Hepatology Digest: At present, the main methods of treatment for solid benign hepatic tumors are laparoscopic liver resection and open liver surgery. In your article published in Surgical Endoscopy in January 2008, “The Value of Laparoscopic Liver Surgery for Solid Benign Hepatic Tumors”, you pointed out that laparoscopic liver resection significantly reduced time to oral intake, hospital stays, and incisional hernias compared to open liver surgery. What are some of the key issues when we use laparoscopic liver resection in a clinical setting?

Prof. Van Vlierberghe: I am a hepatologist and not a surgeon, so considering technical issues; I can not give you any details. Although we published this, we have a very conservative attitude towards resection of benign solid tumors. For example, for focal nodular hyperplasia we seldom resect, and adenomas under 5cm we only observe. In those eligible for resection, our surgeon  Roberto Troisi, who is the first author of the article, clearly demonstrated that in certain conditions a laparoscopic approach could be possible. However, as I mentioned, the tumors that we are resecting are rather big tumors. This can be a problem in doing the resection laparoscopically. I think the bigger the tumor, the more difficult the laparoscopic approach will be, and the smaller the tumor, the easier the laparoscopic approach will be.

Hepatology Digest: Liver biopsy is an invasive test. Therefore, the use of non-invasive serum biomarkers has been developed for diagnosis of liver fibrosis. What are some things we need to be mindful of when we use these biomarkers in a clinical setting?

Prof. Van Vlieberghe: First of all, there are a lot of biomarkers for establishing liver fibrosis, which means the Holy Grail is not there yet. There are a lot of seromarkers so the real one is not there. What those seromarkers are actually doing is distinguishing severe fibrosis and cirrhosis versus the rest. If you use them in these conditions then it is ok. If you want them to distinguish, for example, between an F2 and an F3 on the METAVIR score, then it won’t work very well. So, if you expect this from a biomarker you will lose. I think that biomarkers can be implemented in clinics in a way where we combine two biomarkers. If the two biomarkers are concordant, if they say there is the same degree of fibrosis, if there is less fibrosis then you can wait and not perform a biopsy, if the biomarkers say there is cirrhosis, you don’t need the biopsy and you have to follow-up for HCC and variceal bleeding, and in the gray zone between F0 and F4, then you can decide on what to do. You can perform a liver biopsy regarding if there is an indication for management changes implicated by the biopsy. So, by using two biomarkers, you can avoid a lot of biopsies, but you still can not avoid every biopsy. In my personal point of view, and this is what we do in our hospital, we perform in every patient where we will manage and where we think it is important, for example, patients over 80 where treatment is not available or not necessary of course we do biopsy, but were it is clinically relevant, we perform a biopsy and we perform a one or two biomarkers depending on the situation. If the biopsy and the biomarkers are concordant, and we are not treating the patient for whatever reason, we can follow-up the patient with a biomarker without the need for a repeat liver biopsy after 3-4 years. We know that the concordance between the liver biopsy and the biomarkers is approximately 80%, so we perform a biopsy in everyone but follow-up biopsies can be reduced by 80% using this protocol. There are different ways of working, using two biomarkers, using liver biopsy; with them also the Holy Grail is not there so we need to go on with research regarding these biomarkers. The research is very interesting. It is not only biomarkers, it is also Fibroscan, for example, it is also imaging techniques. So I think the combination of seromarkers together with imaging techniques can be very promising, but again research is necessary to fine-tune the use of these markers and imaging techniques.