HCC Diagnosis and Prognosis

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Minsig Choi, MD: Hepatocellular cancer [HCC] diagnosis is mainly done with different imaging modalities. I have mentioned previously that ultrasound is used as a screening methodology, but in the diagnosis of liver cancer we use either contrast-enhanced CT [computed tomography] scan or cheaper-phase CT scan, or MRI [magnetic resonance imaging] in diagnosing those patients. Usually in the background of patients who have underlying liver disease or cirrhosis, when you have a liver mass that’s arterially enhanced and washes out, this is a typical diagnostic for liver cancer.

In light of underlying liver disease, we usually mention alpha-fetoprotein as a prognostic marker in patients with liver cancer. Usually I assess for serum albumin levels, serum PT [prothrombin time] or INR [internalized normalized ratio] levels, as well as bilirubin. By assessing those things, I’ll be able to calculate the Child-Pugh score, which shows you the severity of liver cirrhosis. With those 3 levels of findings as well as 2 clinical parameters, which are presence and absence of ascites and hepatic encephalopathy, you would be able to calculate the Child-Pugh score. This is important because in liver cancer, you’re dealing with not just liver cancer itself but underlying liver disease. You’re fighting 2 fronts, the cancer as well as the liver disease. This is important in managing hepatocellular cancer.

Moving on to the second question, alpha-fetoprotein is a glycoprotein that is usually excreted during the gestational period between the yolk sac and the liver. Usually this is an area where there’s a lot of inflammation going on and alpha-fetoprotein is generated. It is also a tumor marker for hepatocellular cancer as well as in some yolk sac cancer or teratoma and other things. Usually, about 400 ng/mL of alpha-fetoprotein is diagnostic in the background of our liver lesion for patients with hepatocellular cancer, and increased levels of alpha-fetoprotein have been correlated with increased risk of angiogenesis and metastases and tumor burden, so high alpha-fetoprotein is usually correlated with poor prognosis.

Basically, we use both MELD [model for end-stage liver disease] score and Child-Pugh score in assessing liver disease. The MELD score is model for end-stage liver disease, and usually a patient’s MELD score is calculated based on serum bilirubin, creatinine, and PT [prothrombin time] and INR [international normalized ratio]. The reason the MELD score is used is that the 3-month overall survival on mortality associated with liver disease is strictly correlated with the MELD score. Because of this, United Network for Organ Sharing has adapted using the MELD score to prioritize who can get liver transplant.

I personally use the Child-Pugh score because I’m not a transplant physician, so I use the Child-Pugh score A, B, and C in guiding my management for systemic therapies. For patients who are young, who have good performance status, and who meet the Milan criteria—which is a single lesion less than 5 cm and 3 lesions less than 3 cm—we have to consider liver transplant because this is a way of procuring those patients.

Peter Galle, MD: The standard assessment is either CT or MRI assessment. You are checking hypervascular lesions, and you’re asking for the late washout of hypervascularization. If you see these hallmark pictures, the diagnosis is safe. CT is not considered to be evidence based; therefore, the guideline recommendations do not include PET [positron emission tomography] or CT in the diagnostic armamentarium.

Minsig Choi, MD: When do we do liver biopsy? Because people with liver cancers have underlying liver disease, they have coagulopathy. In the past, we wanted to avoid doing the liver biopsy because you don’t want to do a liver biopsy and cause either peritoneal spread or bleeding problems associated with liver biopsy. Usually most oncologists want to treat when there are biopsy results. The only exception is the liver cancer, where we can diagnose patients with underlying liver disease. Hepatic lesions enhance arterially and wash out on a delayed phase, and we have more than 95% chance of diagnosing liver cancer without a biopsy. However, because we are not doing a lot of liver biopsies, we don’t have the tissue to do genetic studies and clinical trials that can correlate with these genomic findings.

Over the last few years, most of the medical oncologists and hepatologists have been thinking maybe we should do more liver biopsies so we have more samples, so we can study this genomic alteration in liver cancer, and so we can come up with better treatments in the future. In general, we might not need it. But for the improvement in the future of science as well as improving scientific knowledge, we actually should be doing more liver biopsies. Nowadays, interventional radiologists do the liver biopsies without many other complications. So it’s pretty safe to do liver biopsies.

Masatoshi Kudo, MD, PhD: In Asia, it’s not much different from in the United States. The surveillance too is ultrasound and AP [arterial perfusion]. Then if there is a suspicious lesion of HCC in an Asian country, most patients receive CT scans, which will confirm HCC. The difference between Japan and United States may be the frequency of EOB [ethoxybenzyl] MRI use—gadoxetic acid MRI. That is a very sensitive and specific tool for detecting smaller lesions less than 1 cm, and the accuracy is much better. As I said before, The Japan Society of Hepatology guidelines recommend EOB MRI should be used as a diagnostic tool. That’s a big difference between Japan and United States.

Peter Galle, MD: The standards are pretty similar. Again, CT and MRI are the standard diagnostic procedures. In Europe, this is influenced by the fact that the ultrasound is typically in the hands of hepatologists and not radiologists. Also playing a role, particularly in dedicated centers, is CEUS, contrast-enhanced ultrasound. It is indeed used by some centers and can be helpful in individual patients; for example, in those patients who, because of a close personality, cannot use MRI assessment, and ultrasound might be more appropriate. It’s quite clear that CT and MRT [magnetic resonance tomography] are typically giving a more panoramic picture, and this is the standard in most cases. Ultrasound in Europe, however, plays a little more prominent role than it does in the United States. Particularly contrast-enhanced ultrasound, which virtually does not exist in the United States.

Transcript Edited for Clarity

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