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Managing Risk Reduction in the Changing Face of Liver Cancer
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This month’s cover story gives us a glimpse into the changing face of hepatocellular carcinoma from causes to diagnosis to treatments, including newly approved antibodies.
This is an area with a lot of evolution and we can anticipate the guidelines for all of that to change in due time. But guidelines lag by the diagnostic information that goes into them. They will change but it might be that our practice patterns change concomitantly.
Hepatitis C in HCC
Although the face of liver disease is changing and hepatitis C virus is certainly shrinking as a driver for decompensated liver disease, the one place it’s going to continue to persist is liver cancer.
When I talk about HCV in liver cancer, my most important message to providers is you should not withhold treating a patient with cirrhosis for fear of accelerating their risk for cancer. There’s still misinformation coming out about the role of all-oral, direct-acting HCV therapy and the risk for de novo cancer as well as recurrent cancer. Providers should know that — hands down — large cohorts of patients have shown that if you eliminate HCV in a group of individuals with advanced liver disease, you decrease the risk for liver cancer.
Still, you don’t eliminate that risk. If you reassess that person after achieving sustained virologic response and you believe they no longer have cirrhosis, they still have a risk for liver cancer and you need to continue to screen them.
We see patients come back to us 5 to 10 years after cure where they’ve fallen out of monitoring and they return with late-stage HCC.
Changing the Risk Profile
When we look at our patients, we need to remember that obesity and fatty liver disease do increase the risk for liver cancer and so the patient that you expect to have cancer is changing.
As discussed in the cover story, liver cancer does not have a very obvious set of warning signs. Most of the time when you present with symptoms, you present with very late stage disease.
But we have yet to definitively pinpoint whom to screen in our population of patients with obesity and fatty liver disease.
Anyone with cirrhosis obviously dictates screening, but a lot of our patients with fatty liver disease who have cirrhosis are not being diagnosed as cirrhotic. We must understand the importance of staging a person so that you can risk reduce. It is imperative, especially in fatty liver disease because if you don’t think to stage the patient, you will miss those with advanced disease and miss the opportunity to screen them for HCC.
Cumulative Factors
You also must remember the other components of a patient’s life when considering their risk level. Alcohol certainly drives risks for liver cancer as does hemochromatosis. These things are still very prevalent in our patient populations and they have a cumulative impact. If you cure someone of their HCV but they continue to drink or they are still obese or they have iron overload, you have not fully risk reduced and you will need to screen them more closely.
Some of the best databases coming out of the VA show that those patients who develop HCC after SVR tend to have more advanced liver disease, tend to be male, tend to be older, tend to have concomitant alcohol use and tend to have concomitant diabetes. These data show you the risk factors do accumulate. You can’t cure a person of a disease like HCV and assume the risk just decreases every year with time. It’s not true.
Screening Tools
In cirrhosis, especially in diagnosis in fatty liver, noninvasive assessment is an evolving field and one that practitioners may not yet fully understand.
What we do know is that in many radiology units, whether it’s at a community center or a tertiary care center, the ultrasound or MRI technology have the ability to do elastography by ultrasound or ultrasound by MR. Though they may not advertise these abilities, a hepatologist or gastroenterologist can request the diagnostics be performed with technology already within the institution or practice. Sometimes it’s about just beginning to understand what is accessible to you.
Also, find out what your friends have. I work at a community center where one of the local offices has a Fibroscan (Echosens) so I send my patients there. If you don’t have it, find out if there’s one close. Most providers who own a scanner will allow screening of patients who aren’t within their care.
The biomarkers, whether you use Fib4 or APRI or a more specific set of markers, can help to identify a group that is low or high risk. They aren’t as accurate in the grey area between but they can help you flag patients who are at higher risk for advanced fibrosis.
Use the tools that are available to you, but if you don’t have any of these tools, biopsy still remains an option. Every local center can do a biopsy. You just have to figure out how to get it done and use it judiciously. If you have a noninvasive marker that confirms a patient is low risk, you wouldn’t confirm low risk with a biopsy, but accurately staging the person might help you risk reduce them.
On the Horizon
While we can look back on the peak of HCV therapies and look ahead to anticipated milestones in fatty liver, the horizon for liver cancer is right in front of us.
Management for HCC may change in that we might start doing biopsies for biomarkers or genetic information so we can better choose our therapeutics. When you look at the chemotherapies that are already being used for lung cancer, renal cell, etc., this is what’s trickling down to liver cancer.
Most of these more tailored approaches are going to require a tailored approach for the liver. You might find that where we have traditionally based a diagnosis on noninvasive alpha fetoprotein, we might start turning to histology to more accurately direct us to appropriate therapeutics.
Liver transplant as an alternative for liver cancer might start to decrease. As the prevalence of liver cancer increases, we’re not going to have the organs available for these patients. If fatty liver is driving the epidemic or patients are becoming older, these are situations where transplant is a harder match. If you don’t want the morbidity and mortality associated with transplant, if you can find a locally acting chemotherapeutic that would give them a similar outcome, this may be the direction in which we move.
If I’m putting my crystal ball in front of me, I think we are going to start carving out a portion of the liver cancer population that we deprioritize for transplant, and start more accurately identifying patients for appropriate therapeutics.
Moving On
Sadly, I have stepped down as your Co-Chief Medical Editor of Healio Gastroenterology and Liver Disease as I embark on my new role with AASLD’s Clinical Liver Disease. It has been a fantastic year with this publication and I will still participate as part of the Peer Perspective Board.
Thank you for helping us improve our coverage of liver disease and I hope to see the continued growth in this area for this publication. Continue to give us your thoughts and join the conversation with @HealioGastro.
Disclosure: Reau reports receiving research support from AbbVie and serving on medical advisory boards for AbbVie, Gilead and Merck in the last 12 months.