COMMENTARY

New AASLD Guidelines for Hepatocellular Carcinoma: The Big Questions Tackled

David A. Johnson, MD

Disclosures

February 21, 2018

Screening for Hepatocellular Carcinoma

Hello. I'm Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia.

When we see patients with cirrhosis in the clinic, we are concerned about screening for hepatocellular carcinoma (HCC). I'm not a transplant hepatologist, but I deal with these patients all the time, as you do.

HCC is an incredibly common disease. It's the fifth most common tumor in the world and the second leading cause of cancer-related death.[1] In the United States, there are an estimated 39,000 new cases per year and over 27,000 related deaths[2,3]; the incidence is likely to rise at least until 2030.[4] This problem is not going away.

Why is that? It's about cirrhosis. The majority of HCCs, 85%-95%, occur in patients with cirrhosis[5,6]—the exception to the rule being hepatitis B, where patients do not need to be cirrhotic. The incidence of HCC in patients with cirrhosis that I quote to my patients is 2%-4% per year.[7] Thus, it is recommended that we screen these patients because early screening may lead to earlier diagnosis and appropriate interventions.

It's very pragmatic, at this point, to review new guidelines issued by the American Association for the Study of Liver Diseases (AASLD)[2] in the January 2018 issue of Hepatology. They used a graded system for their recommendations and provide strength of evidence and support of the recommendation. Let's focus on the 10 questions and answers from this evidence-based analysis and recommendation.

AASLD Guidelines: Questions and Answers

Should Patients With Cirrhosis Undergo Surveillance for HCC?

Should adults with cirrhosis undergo surveillance for HCC? The answer is yes. But which surveillance test is best? Ultrasound is still the best. It's relatively cheap and [may be used] with or without alpha-fetoprotein (AFP). According to the recommendation, [surveillance should occur] every 4-8 months; we use 6 months [in my clinic]. You can choose to couple that with AFP, but that is not a strong recommendation.

Multiphasic CT or Multiphasic MRI for Diagnostic Evaluation?

Should adults with suspected HCC and cirrhosis undergo multiphasic CT or multiphasic MRI for diagnostic evaluation? The data are fairly mixed. There may be a little marginal data bias toward MRI on smaller lesions, but the available evidence suggests that both are equivocal. There are some variable differences. CT is more available and may result in repetitive radiation exposure, and MRI is a lot more expensive. There may be issues of claustrophobia, and patients with large-volume ascites may have movement issues during their positioning in the MRI. These are potential reasons to choose one versus the other. The evidence suggests that we could use either at this point.

Which Diagnostic Evaluation Should Patients With Cirrhosis and an Indeterminate Nodule Undergo?

Should adults with cirrhosis and an indeterminate nodule undergo biopsy, repeat imaging, or alternative imaging? According to the current guideline, all three are acceptable. This is a difference from the previous AASLD guideline. Now they say to consider these things but not biopsy every individual indeterminate nodule because the majority of them are likely benign and potentially subject to sampling bias. Repeat imaging by another alternative may be the best course of action. Consider all three as viable options under these new evidence-based recommendations.

How Should Patients With Child-Pugh Class A Cirrhosis and Early-Stage HCC Be Managed?

Is resection or locoregional therapy recommended for a patient with Child-Pugh class A cirrhosis and early-stage HCC (T1 or T2)? If you want to do an intervention that is not a transplant, resection in the viable candidate is recommended. A good surgeon is really the course of action.

The diagnosis now for these lesions begins at ≥ 10 mm by radiologic CT or MRI diagnostic criteria. T1-stage HCC is potentially referred to the transplant center and T2-stage HCC is now the threshold for transplant evaluation. T2-stage HCC, by radiologic imaging, is a single lesion ≥ 2 cm, or two to three lesions that are 1-3 cm.

Is Adjuvant Therapy Recommended for Resected or Ablated HCC?

Should patients with cirrhosis and successfully resected or ablated HCC undergo adjuvant therapy? Probably not. The weak recommendation is conditional and based on histology and radiologic imaging. The broad recommendation is that these patients need not receive adjuvant therapy.

Should Patients With T1 HCC and Cirrhosis Be Treated or Undergo Observation?

Should adults with T1 HCC and cirrhosis be treated or undergo observation? If you treat these patients, you may take them out of the transplant window, so observation is really the best course of action. Stay in close concert with a transplant center and be ready to transplant these patients when they hit that threshold. Waiting and watching may be somewhat disconcerting to a lot of people, but that is how they get into the transplant window.

Transplantation Alone or Transplantation With Bridging?

Should patients with cirrhosis awaiting liver transplant undergo transplant alone or transplant with bridging therapy? Bridging therapy is adjuvant locoregional therapy. Provided that the patient is a good candidate and you have expertise, bridging therapy is recommended because you do not want them to progress and migrate out of the transplant window. The transplant window may be an extended period of time, depending on where the transplant center is. Bridging therapy should be considered.

Is Transplant After Downstaging Recommended?

Should patients with cirrhosis and HCC beyond Milan criteria (T3) be transplanted following downstaging? The answer is yes. They should be considered for transplant once they have been downstaged. It's a weak recommendation and conditional. This is something that needs to be driven by the transplant center, but it's important that you understand this when conversing with your patients.

Is Embolization/External Radiation Recommended for Advanced HCC?

Should patients with cirrhosis and HCC (T2 or T3, but no vascular involvement) who are not candidates for a resection or transplantation undergo treatment with transarterial chemoembolization, transarterial radioembolization, or external radiation? The answer is yes. If those options are available, they are reasonable things to offer. The recommendation did not pick one over the other; that is something that is substantive to your local expertise.

Therapy or No Therapy for Patients With Advanced HCC?

Should a patient with Child-Pugh class A/B cirrhosis and advanced HCC with evidence of macrovascular involvement and/or metastatic disease be treated with systemic, locoregional, or no therapy? The answer is: Treat them if they are good candidates. This needs to be considered on an individual, case-by-case basis.

Takeaway Message

These are AASLD's 10 evidence-based-focused questions. Most of these recommendations are based on weak evidence and are conditional; nonetheless, this is where we are. We need to understand this as we communicate with our patients and transplant centers, but even more so as we screen patients and manage them once a diagnosis of HCC is made.

This evidence-based guideline has been extremely helpful for me. As a gastroenterologist and not a transplant hepatologist, I've tried to give my perspective on what I do in my clinical practice. Hopefully this will be helpful for your practice.

I'm Dr David Johnson. Thanks again for listening. I'll see you next time.

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