for Health Care Providers
1: When is it necessary to perform a biopsy on a liver lesion to confirm hepatocellular carcinoma?
The patient is a 55-year-old Latino male with a history of chronic hepatitis C cirrhosis and a new development of ascites. He drinks alcohol on a regular basis. His provider was screening him for hepatocellular carcinoma (HCC) and found an alpha-fetoprotein (AFP) level of 33 ng/mL. The screening was repeated a month later, and the AFP level had risen to 89 ng/mL. A computed tomography (CT) scan for surveillance revealed a 3 x 3.3 cm contrast-enhanced lesion at the left lobe of the liver, as well as a significance degree of ascites.
The patient has a past medical history of chronic hepatitis C virus (HCV) with decompensated cirrhosis, ascites, encephalopathy with elevated ammonia and mild changes in mental state, thrombocytopenia, mild hyperlipidemia, and depression. He drinks alcohol (2-4 beers daily) but denies smoking tobacco or using drugs.
Medications: potassium chloride (40 mEq daily); Lasix (40 mg daily); Aldactone (100 mg daily); Prozac (20 mg daily); lactulose (10 cc twice daily)
Pertinent findings on the physical examination: weight = 220 lb; gynecomastia bilaterally; ascites; caput medusae; no organomegaly; no edema; muscle wasting of the temporal muscles, upper extremities, and torso
Laboratory findings: platelet count = 19,000 cells/µL
Because of the thrombocytopenia, it was determined that the patient was not a candidate for percutaneous or transjugular biopsy of the hepatic lesion. Interventional radiologists were consulted, and they stated that he was not a candidate for chemoembolization, but possibly for radiofrequency ablation (RFA). A magnetic resonance imaging (MRI) procedure was recommended to help make a better assessment of the lesion.
MRI of the abdomen, without and with gadolinium: There is a lesion in the lateral segment of the left lobe of the liver that measures approximately 35.2 mm anteroposterior, 37.5 mm transverse, and 33 mm craniocaudal. The lesion is hyperintense relative to the liver on precontrast T1-weighted images. There are areas in the lesion that are hypointense on T1 and hyperintense on T2, which are suspicious as areas of necrosis. The lesion shows intense enhancement on the arterial phase (except for the presumed necrotic areas) and shows relative washout on the interstitial phase of contrast. There is suggestion of a low-signal capsule around the lesion. There is no invasion of the portal or hepatic veins at this time. Overall, the findings raise concerns regarding the possibility of neoplasm, including hepatocellular cancer, in a patient with known hepatitis and suspected cirrhosis.
Question 1: In this patient's case, is it necessary to pursue a biopsy of the lesion to have histological confirmation of HCC? Or, can a diagnosis be made on the basis of his history of HCV, cirrhosis, alcohol use, elevated alkaline phosphatase and bilirubin, a near-tripling of the AFP level, and an enhancing mass detected on imaging scan?
Question 2: Is there anything else that should be done for this patient as part of a workup? He has not had an esophagogastroduodenoscopy (EGD) performed because of transportation and social issues.
Speaker 1: This case involves a 55-year-old Latino man with a history of chronic hepatitis C cirrhosis, newly decompensated, who continues to drink and has a rising AFP level. His bilirubin level is 2.8 mg/dL, and his international normalized ratio (INR) measure is 1.7 seconds. The patient's creatinine measures are OK, but his platelet count is 19,000 cells/µL. He had a CT scan for surveillance, and it showed a 3 x 3.3 cm lesion in the left lobe. Thereafter, the MRI revealed a 3.5 x 3.75 cm lesion in the same place as the one revealed by CT, and it was consistent with hepatocellular carcinoma. There was no invasion of the portal vein--which is fortunate--and then there were some additional small lesions.
Thus, the main question is whether the provider needs histologic confirmation of metastatic carcinoma based on the clinical scenario. And what else should be done for the patient as part of a workup for his many conditions?
Who feels that this patient needs a liver biopsy or a biopsy of the lesion to prove that he has hepatocellular carcinoma?
Are we certain enough of the diagnosis in this case without a biopsy? And, once we have a diagnosis, what are we going to do with the information? Unless we plan to intervene based on the results of the biopsy, maybe we do not need to put the patient at risk just to prove the diagnosis. Or, instead of using biopsy results, can we establish the diagnosis with noninvasive information, such as the imaging study showing typical enhancement characteristics or a growth over time?
Speaker 2: The information we have already meets the European Association for the Study of the Liver (EASL) criteria for the diagnosis of HCC: having a mass lesion greater than 2 cm in diameter seen on at least 2 imaging modalities. So, I agree that you really do not need a biopsy of the lesion to prove that the patient has HCC.
Speaker 1: In fact, according to the HCC criteria of the American Association for the Study of Liver Diseases (AASLD), which differ somewhat from those of the EASL, if you have a cirrhotic patient and the typical arterial enhancement and venous washout pattern in a lesion larger than 2 cm in diameter, then you need only 1 imaging study to have a diagnosis of HCC.
Still, it seems that most oncologists will not treat HCC unless there has been confirmation of the diagnosis with a biopsy. Therefore, we have to try to create a multidisciplinary team that includes an oncologist, a radiologist, and a surgeon, so that each case of HCC is discussed among all team members with reference to the relevant guidelines for each area of specialty, and we approach these cases on a one-by-one basis.
My own question to the audience is this: If a patient clearly is not a transplant candidate--for example, a patient such as this one, who continues to drink--should we be screening that patient for HCC in the first place?
Speaker 3: We have a patient with a lesion that measures 3.5 x 3.5 cm. You could approach the patient and say, "OK, you have to make a decision. You can continue to drink and let this take its natural course. Or, you can get into an alcohol treatment program to stop drinking, because you do have time since the lesion isn't too big yet. If you can stop drinking, we will get you at least some palliative therapy and we'll try to work you up for transplant." So I think the best thing you can say to this patient is, "You have cancer but you still have time to choose between one thing and another."
Speaker 2: That is a very important point, because we still see treatment potential for this patient. He's not transplantable now because he is drinking. If this is an aggressive tumor, we probably are not going to be able to cure it, even if he were a transplant candidate right now. But if this is a relatively indolent hepatoma--and there are indolent hepatomas with doubling times of 6 months (that is a doubling of volume and an increase in diameter by about 20%)--after 6 months without drinking, he may be ready for a transplant. I think you will find out whether he can quit drinking. Actually, the moment this diagnosis is made is his last opportunity to decide whether he is going to stop drinking; it's the one thing you have that really offers some prospect for cure to this fellow.
The other point I would make is that this patient may die of liver disease instead of cancer, unless he quits drinking and the liver disease gets a lot better. He has a Model for End-Stage Liver Disease (MELD) score of about 16, with persistent ascites, and there are a lot of prognostic factors that suggest he may die within a year even if he didn't have the tumor. In other words, this is a person who would be referred for transplant based on his liver disease, even without any tumor, if he weren't drinking.
Participant: I think we have determined basically that the patient in this case does not need a biopsy to confirm the HCC.
In our VA facility, we do not have an interventional radiology department. So, in regard to a possible RFA or chemotherapy, we always contact Pittsburgh. We have had patients who met the EASL criteria for HCC without a biopsy, but Pittsburgh has asked for biopsies anyway. We never asked why it would still be necessary to perform a biopsy on a patient who has typical enhancing characteristics with a lesion that measures more than 2 cm and is visible on 2 modalities.
Speaker 1: Despite the existence of guidelines, there may be differences in practice among various centers. It is difficult when another center wants a biopsy. It may be best to ask for a discussion to review the guidelines together.
Participant: In this particular patient, if he does stop drinking, you have to wait 6 months at least. What would you do about his HCC in the meantime?
Speaker 3: You certainly should perform another CT scan in 3 months to monitor any growth in the lesion. Another benefit of having an interventional radiologist is that it gives you the ability to conduct an angiogram with attendant chemoembolization. One thing I do not understand about this case is why the patient was not a candidate for chemoembolization. At our institution, we mostly do chemoembolization and we would have given the patient in this case platelets and conducted that process. Does anybody have an idea?
Speaker 1: Our radiologists hesitated on this issue because, if the patient has evidence of liver dysfunction, chemoembolization can also destroy his few working hepatocytes and bring on decompensation. So that's why they're concerned when the liver synthetic function is not good, which is the situation with this patient.
Speaker 2: There are some patients who really cannot be treated. We have seen people decompensate after embolization, and we have seen them decompensate after RFA of tumors. There is a risk to interventions, and I think it's perfectly reasonable to follow this up in 3 months and see what is happening in this patient. There is certainly a chance he is going to die of liver disease instead of cancer, and we do not want to worsen things by trying to treat the tumor.
Participant: I have one other remark. Would anybody do a biopsy in order to be sure that this is a straight HCC rather than a mixed tumor? Occasionally, patients have a mixed cholangiocarcinoma and HCC, which could be amenable to chemotherapy. I think it is something to consider in this case, as the AFP is not that convincing. On the other hand, if you had an AFP measurement of 500 to 1,000, it would be pretty clear that the tumor is probably an HCC.
Speaker 3: You raise the interesting point that the mixed tumors are uncommon, and they appear to behave more aggressively than run-of-the-mill HCC. I still think that if you have a relatively slow-growing solitary lesion, whether or not it has a mixed component, you have a chance at being able to perform a transplant. But again, you will see over the course of 3-6 months how the natural history of this lesion will evolve. If it is a relatively indolent natural history, we may be able to do something. If not, perhaps we won't. But, I think it is not necessary that we intervene at this point with the patient. Our interventions may not have any beneficial effect on a patient this sick and are likely to have an adverse effect.
Speaker 2: I think we have all seen the indolent, slow-growing tumors with doubling times of 6 months, but we also have seen tumors that are treated with chemoembolization yet appear 3 times as large upon the 3-month follow-up and have a very aggressive biology. We used to be taught that the pathology of the tumor really did not predict prognosis, that is, the well-differentiated ones and the poorly differentiated ones were pretty similar. But now that we're getting much more experience with HCC, I think there is definitely a difference.
- A diagnosis of HCC does not always require confirmation with a biopsy of tissue.
- Guidelines from the EASL and the AASLD include noninvasive criteria for making an HCC diagnosis without a biopsy. There are some differences between the criteria set forth by the two organizations. This case demonstrates a patient who meets the criteria for an HCC diagnosis without a biopsy by both the EASL and the AASLD guidelines.
- A biopsy may still be needed for confirmation in some cases, depending on the size of the lesion, imaging characteristics of the lesion, and AFP level.
- Before a biopsy is performed, the risks of the biopsy should be weighed against the potential benefits to the patient of subsequent interventions if the procedure is performed.
- Each case of HCC should be carefully evaluated for HCC treatment consideration, including the possibility of chemoembolization, transplant, or RFA. Factors to consider include not only the characteristics of the tumor but also the risk of the treatment to the patient's underlying liver function.
- Patients who are actively drinking with a diagnosis of HCC should be counseled to immediately stop drinking. In some cases, the possibility of definitive treatment with a transplant could still be considered if drinking is stopped and the tumor is slow growing.
- Ann Busch, Liver Transplant Clinical Nurse Specialist, Portland VAMC
- Sue Currie, Associate Director, HCRC, San Francisco VAMC
- Guadalupe Garcia-Tsao, Director, HCRC, Connecticut VAMC
- Douglas Heuman, Liver Transplant Program Director, Richmond VAMC
- Alexander Monto, Director, HCRC, San Francisco VAMC
- Roberta Ruimy, Manager, Liver/Kidney Transplant Programs, Portland VAMC
- Brenda Salvas, Health System Specialist, Manager, Liver and Kidney Transplant Program, VA Transplant Program, VA Central Office, Washington, DC
- Anna Sasaki, Staff Physician, Portland VAMC
- Kristine Stick, Nurse Practitioner for Hepatology, San Francisco VAMC
- Suchat Wongcharatrawee, Associate Director HCRC, Connecticut VAMC
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