Liver Tumors and Transplantation: Liver Tumors and Transplantation: Liver Cancer

0:00Welcome to Board Pearls. This is episode two of four of the Liver Tumors and Transplantation chapter, in the Liver Disease module. This episode is hepatocellular carcinoma, from surveillance to treatment. A man whose hepatitis C was cured shows who needs surveillance and why a cure doesn't end it, why it's done every six months with ultrasound and alpha-fetoprotein, AFP, and what to do when ultrasound can't see the liver. A man with hepatitis B and no cirrhosis, and a woman with fatty liver disease and advanced fibrosis, show who needs surveillance without cirrhosis and who doesn't. A woman with a new nodule shows how the Liver Imaging Reporting and Data System, LI-RADS, reads it, which features make the diagnosis without a biopsy, and what happens to the nodules that fall short. Two more patients show the malignant lesions that aren't hepatocellular carcinoma and the tumor that grows into a vein. Then her treatment, and the patients after her, show how the Barcelona Clinic Liver Cancer, BCLC, stage chooses between resection, ablation, transplant, chemoembolization, and the systemic drugs, and the safety check one of those drugs requires.

1:07Here's the first patient. A fifty-six-year-old man had hepatitis C cured with a sustained virologic response four years ago. He has compensated cirrhosis, Child-Pugh A. His body mass index, BMI, is forty-one. He hasn't had imaging since his cure, because he was told the virus was gone. His last ultrasound, years ago, was limited by his body habitus.

1:29He was told wrong. The cure removed the virus but left the compensated cirrhosis behind, and cirrhosis puts him at risk of hepatocellular carcinoma, so he needs surveillance. The twenty twenty-three American Association for the Study of Liver Diseases, AASLD, guidance recommends surveillance in every patient with Child-Pugh A or B cirrhosis whatever the cause, explicitly including hepatitis C cured by sustained virologic response, because the cirrhosis, not the virus, is what grows the cancer. Child-Pugh C cirrhosis is surveyed only when the patient is listed or being evaluated for transplant, because liver function that poor rules out every cancer treatment short of transplant, so finding a tumor would change nothing.

2:12His surveillance has a set interval and a set test. The interval is every six months, calibrated to how fast the tumor doubles in volume, so that a cancer is caught while it's still small enough to cure. The test is a right upper quadrant ultrasound with an AFP. Adding AFP to the ultrasound raises its sensitivity to about eighty-five percent, which is why the twenty twenty-three guidance moved AFP from optional to recommended. AFP alone is poor in both directions. A low value doesn't exclude cancer, and hepatitis flares and regeneration can raise it modestly. But an AFP over two hundred nanograms per milliliter with arterial enhancement strongly supports cancer even when the imaging is otherwise equivocal, because values that high are uncommon in benign disease.

2:58His body habitus is the specific problem. Severe obesity or marked steatosis attenuates the ultrasound beam and makes the study non-diagnostic, and an inadequate ultrasound isn't surveillance. Those patients get magnetic resonance imaging, MRI, or computed tomography, CT, every six months instead. He has a multiphase MRI now with an AFP, and both are repeated every six months.

3:25The second patient shows that hepatitis B can need surveillance without cirrhosis. A forty-four-year-old man born in China has hepatitis B, normal liver tests, no cirrhosis, and a low viral load. Chronic hepatitis B carries a cancer risk even without cirrhosis, and surveillance is recommended for an Asian man over forty, an Asian woman over fifty, a person of African ancestry at an earlier age, anyone with a family history of liver cancer, a viral load over two hundred thousand international units per milliliter, positive hepatitis B e antigen, HBeAg, a prior liver cancer, or a PAGE-B score of ten or higher on long-term entecavir or tenofovir. He qualifies on his age and ancestry alone, so he's surveyed every six months. At thirty-five, without another trigger, the benefit would be uncertain. Hepatitis D coinfection is surveyed in any phase of hepatitis B, because the two viruses are synergistically carcinogenic.

4:25The third patient shows the other side. A fifty-two-year-old woman has metabolic dysfunction-associated steatotic liver disease, MASLD, with stage three fibrosis and no cirrhosis. She isn't surveyed. Surveillance isn't recommended in men with hepatitis B under forty or women under fifty without an endemic-country or family-history trigger, in hepatitis C with stage three fibrosis but no cirrhosis, or in metabolic dysfunction-associated steatohepatitis, MASH, or MASLD without cirrhosis, because the absolute incidence of cancer in those groups is too low to justify the cost and the harm of false positives. Her fibrosis is worse than the man with hepatitis B, but hepatitis B causes cancer without cirrhosis, and MASLD rarely does at a rate worth screening for. Her care targets her fibrosis, and surveillance starts if she reaches cirrhosis.

5:15Every other cause of cirrhosis follows the same six-month schedule. In hemochromatosis with cirrhosis, about thirty percent develop liver cancer, and the risk persists after the iron is removed. In primary sclerosing cholangitis, cholangiocarcinoma has its own surveillance, and liver cancer surveillance is added once there's cirrhosis.

5:36Surveillance exists to find a new nodule, and that finding has a fixed meaning. A new lesion in cirrhosis or chronic hepatitis B is hepatocellular carcinoma until proven otherwise. That overrides features that would suggest a benign lesion in a normal liver, because in cirrhosis the pretest probability of cancer is too high to ignore. So the nodule is characterized with multiphase imaging and read with LI-RADS.

6:01Here's the fourth patient. A sixty-one-year-old woman has compensated hepatitis B cirrhosis on entecavir. Her surveillance ultrasound shows a new nodule, and multiphase MRI shows a two-point-two-centimeter lesion that enhances brightly in the arterial phase, washes out in the portal venous phase, and has an enhancing rim on delayed images. Her AFP is thirty-eight. Her surgeon has asked for a biopsy.

6:28Her lesion is read with LI-RADS, which may make the biopsy unnecessary. LR-1 is definitely benign, LR-2 probably benign, LR-3 indeterminate, LR-4 probably hepatocellular carcinoma, and LR-5 definitely hepatocellular carcinoma. Two more categories sit outside that scale: LR-M is malignant but not specific for hepatocellular carcinoma, and LR-TIV is tumor in vein. LR-5 requires a size of one centimeter or more, arterial-phase hyperenhancement, and at least one major feature: washout, an enhancing capsule, or threshold growth of fifty percent or more within six months. An LR-5 lesion in cirrhosis is diagnostic without a biopsy, because the combination is essentially pathognomonic there.

7:16Each feature comes from the tumor's blood supply. Hepatocellular carcinoma is fed by new, unpaired branches of the hepatic artery, while normal hepatocytes get a dual supply that comes mostly from the portal vein, so the tumor lights up in the arterial phase. Washout reflects contrast clearing quickly through abnormal tumor capillaries while the surrounding liver brightens as portal blood arrives. The enhancing capsule is the fibrous pseudocapsule around an expanding tumor.

7:45Her two-point-two-centimeter lesion with arterial hyperenhancement, washout, and a capsule is LR-5, so she has hepatocellular carcinoma without a biopsy. Skipping an unneeded biopsy also avoids the small but real risk of seeding tumor along the needle tract. Her AFP of thirty-eight doesn't change the diagnosis. She stays on entecavir, and she'll need lifelong imaging.

8:08Less typical nodules fall into the other categories. Arterial hyperenhancement without a major feature is LR-4, managed with short-interval imaging or biopsy, depending on the patient's risk and whether she's a candidate for treatment. LR-3 is followed with imaging at three to six months, because these lesions can regress or slowly evolve, and threshold growth on follow-up can upgrade a lesion to LR-5. A typical-looking lesion under one centimeter can't be LR-5 and is followed until it reaches a centimeter. An LR-4 nodule with an AFP that has climbed over two hundred calls for prompt biopsy or short-interval imaging.

8:44The fifth patient shows a malignant lesion that isn't hepatocellular carcinoma. A fifty-eight-year-old man with alcohol-related cirrhosis has a three-centimeter lesion with rim arterial enhancement, peripheral washout, and a targetoid appearance. That's LR-M. These features favor intrahepatic cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma, so he needs a biopsy, because the management diverges: intrahepatic cholangiocarcinoma larger than two centimeters isn't transplanted, and the systemic treatments differ. His biopsy shows adenocarcinoma consistent with intrahepatic cholangiocarcinoma, and at three centimeters he isn't a transplant candidate. Episode three follows him.

9:25The sixth patient shows tumor growing into a vein. A sixty-six-year-old woman with cirrhosis and a known liver mass has a new portal vein thrombus that enhances in the arterial phase. That's LR-TIV, tumor in vein, which is almost always hepatocellular carcinoma invading the portal vein. A bland thrombus doesn't enhance, because it has no new vessels. A tumor thrombus isn't anticoagulated, and it counts as metastatic disease, which excludes transplant. Taken together, biopsy is essential for LR-M, for imaging that's truly ambiguous, and when systemic therapy is planned and tissue is needed for molecular testing.

10:05With the diagnosis made, the stage decides the treatment, and the fourth patient shows how. The sixty-one-year-old woman with the LR-5 lesion is Child-Pugh A with a normal bilirubin, feels well, and has an Eastern Cooperative Oncology Group, ECOG, performance status of zero. Her platelets are ninety thousand and her liver stiffness is twenty-seven kilopascals. Her surgeon would like to resect.

10:31The BCLC system combines tumor burden, Child-Pugh class, and performance status. BCLC zero, very early, is a single lesion under two centimeters with Child-Pugh A and ECOG zero. BCLC A, early, is a single lesion or up to three lesions each three centimeters or less, with Child-Pugh A or B and ECOG zero. Both are treated with curative intent. BCLC B, intermediate, is multifocal disease beyond those limits without macrovascular invasion or spread, with Child-Pugh A or B and ECOG zero. BCLC C, advanced, is macrovascular invasion or metastases with preserved liver function and ECOG one to two. BCLC D, terminal, is ECOG over two, or Child-Pugh C without a transplant option. Her single two-point-two-centimeter lesion makes her BCLC A.

11:29Her surgeon's plan runs into her portal pressure. Resection suits patients without cirrhosis, especially those with hepatitis B cancers, which are often resectable even when large. In cirrhosis, it's for highly selected patients with a normal bilirubin and a hepatic venous pressure gradient under ten, because liver failure after resection tracks portal pressure. Her stiffness over twenty-five kilopascals rules in clinically significant portal hypertension, as do her low platelets, so she doesn't meet the criteria despite her small tumor.

12:00Two other treatments can still cure her. Radiofrequency or microwave ablation substitutes for resection, typically for tumors under three centimeters. Thermal ablation kills reliably only within a defined zone, so larger tumors risk incomplete ablation, and tumors next to large vessels lose heat to the flowing blood, the heat-sink effect. Liver transplant is the treatment of choice for early cancer in cirrhosis, because it removes both the tumor and the cirrhotic liver that would grow the next one.

12:28The Milan criteria define who can be transplanted: a single lesion of five centimeters or less, or up to three lesions each three centimeters or less, with no spread outside the liver and no macrovascular invasion. Within Milan, survival five years after transplant approaches seventy percent. The University of California, San Francisco, UCSF, criteria extend eligibility to a single lesion up to six and a half centimeters, or two to three lesions with the largest up to four and a half centimeters and a total diameter up to eight. Downstaging is accepted too. A patient beyond Milan who's brought within it by locoregional treatment, with three to six months of stable imaging, can be listed. She's within Milan, so she's referred for transplant evaluation and is a candidate for exception points, covered in episode four, with ablation reasonable while she waits.

13:18The seventh patient has more tumors, and that changes his stage. A sixty-three-year-old man with alcohol-related cirrhosis has five cancers, the largest four centimeters, without vascular invasion or spread, with Child-Pugh A and ECOG zero. He's BCLC B and outside Milan. His treatment is transarterial chemoembolization, TACE, with doxorubicin and lipiodol or drug-eluting beads, or selective transarterial radioembolization, TARE, with yttrium-ninety microspheres. Both use the tumor's arterial supply to deliver a high dose of drug or radiation to the tumor while sparing the surrounding liver, which is fed mainly by the portal vein, and both are repeated as needed.

14:03His response is graded by modified Response Evaluation Criteria in Solid Tumors, mRECIST, which measures the viable enhancing tumor rather than total size, because a successfully treated tumor becomes necrotic before it shrinks. If treatment brings him within Milan, with three to six months of stability, he can be listed.

14:23The woman with tumor in her portal vein shows advanced disease. She has preserved liver function and an ECOG of one, so she's BCLC C, and transplant and surgery are off the table. The preferred first-line regimen is atezolizumab plus bevacizumab, a programmed death-ligand one, PD-L1, inhibitor with an antibody against vascular endothelial growth factor, VEGF, which improved overall survival over sorafenib. Bevacizumab blocks angiogenesis and impairs vascular healing, so it's contraindicated with uncontrolled varices, recent significant bleeding, or recent surgery. An upper endoscopy within six months before starting it, with treatment of any high-risk varices, is mandatory. Her endoscopy shows large varices, which are banded before she starts.

15:15When bevacizumab is unsafe, durvalumab plus tremelimumab, which pairs PD-L1 blockade with blockade of cytotoxic T-lymphocyte antigen four, CTLA-4, is the alternative checkpoint combination. Nivolumab plus ipilimumab received Food and Drug Administration approval as another first-line combination in April twenty twenty-five. When checkpoint inhibitors are contraindicated, lenvatinib or sorafenib are the alternatives. In the second line, cabozantinib is the multikinase inhibitor, and ramucirumab is approved when the AFP is over four hundred. BCLC D receives best supportive care.

15:55Here are the traps the boards set in these patients. A cure of hepatitis C doesn't end surveillance in cirrhosis. Child-Pugh C patients who aren't transplant candidates aren't surveyed. AFP alone isn't surveillance, and neither is an inadequate ultrasound in severe obesity. The interval is six months, not a year. Non-cirrhotic hepatitis B patients who meet the criteria need surveillance, and so does hepatitis D in any phase. Stage three fibrosis without cirrhosis, and MASLD without cirrhosis, don't. And a new nodule in cirrhosis isn't benign because of how it looks.

16:33The diagnostic traps follow from LI-RADS. An LR-5 lesion doesn't need a biopsy to confirm it. A lesion under one centimeter, or arterial enhancement without a major feature, isn't LR-5. An LR-3 lesion needs repeat imaging, not neglect. An LR-M lesion needs a biopsy and shouldn't be called hepatocellular carcinoma and listed for transplant. An enhancing portal vein thrombus is tumor and isn't anticoagulated. And imaging, not AFP, makes the diagnosis.

17:03The treatment traps come last. Resection with clinically significant portal hypertension invites liver failure. Ablation of a tumor larger than three centimeters risks leaving tumor behind. Transplant treats the cirrhosis as well as the cancer. A patient with macrovascular invasion isn't listed, while a downstaged patient can be. Chemoembolization is judged by mRECIST, not size. And bevacizumab isn't started without an endoscopy and variceal treatment, with other combinations available when it's unsafe.

17:37So, start to finish. Survey with ultrasound and AFP every six months in all Child-Pugh A and B cirrhosis, including cured hepatitis C, in Child-Pugh C only on the transplant path, in non-cirrhotic hepatitis B by risk, and in hepatitis D in any phase. Switch to MRI or CT when ultrasound is inadequate. Don't survey stage three fibrosis without cirrhosis or non-cirrhotic MASLD. Treat any new nodule in cirrhosis as cancer until proven otherwise.

18:08An LR-5 lesion, one centimeter or more with arterial hyperenhancement plus washout, a capsule, or threshold growth, is hepatocellular carcinoma without a biopsy. Follow LR-3 at three to six months, manage LR-4 with short-interval imaging or biopsy, and biopsy LR-M. An enhancing thrombus is tumor in vein: metastatic, excluding transplant, and not anticoagulated.

18:33Treat by BCLC stage. Early disease is curable: ablate tumors under three centimeters, resect only with a normal bilirubin and a gradient under ten, and transplant within Milan, including after downstaging. Intermediate disease gets TACE or TARE, judged by mRECIST. Advanced disease gets atezolizumab and bevacizumab after an endoscopy and variceal treatment, or durvalumab and tremelimumab, or nivolumab and ipilimumab, with lenvatinib or sorafenib as alternatives and cabozantinib or ramucirumab second line. Terminal disease gets supportive care.

19:12Episode three is cholangiocarcinoma: why location decides everything, the imaging that separates it from liver cancer, the transplant protocol, and the targeted drugs.

19:24For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode two of four of chapter twenty-four, and I'll see you in the next one.