Hepatobiliary & Liver Transplant SurgeryDr. Ashish GeorgePrimary Liver Cancers

Principal Consultant & Unit Head, Liver Transplant, Fortis Hospital, Shalimar Bagh, New Delhi, India

Part 3 of 13 in Management of Primary Liver Cancers

Screening and Tumour Markers for Primary Liver Cancer

August 27, 2026

Screening exists for one of the two primary liver cancers, not both. Hepatocellular carcinoma (HCC) has an established protocol built around cirrhotic patients. Cholangiocarcinoma has no equivalent population screening programme.

The Six-Month Rule for Cirrhotic Patients

Patients with known cirrhosis are followed with an ultrasound and an alpha-fetoprotein (AFP) test every six months. Dr. George describes this as a fair screening strategy that has been shown to improve survival, and it remains the standard of care for this population.

Three Markers, Three Roles

AFP is the primary tumour marker for HCC, but it is elevated in only about 40 percent of patients who have the disease; the remaining 60 percent have a normal level. PIVKA-II is used alongside AFP to increase sensitivity, though it too can be normal in confirmed HCC. Both markers can be entirely unremarkable in a patient who unquestionably has the disease, which is why Dr. George is emphatic that diagnosis should never rest on tumour markers alone.

CA19-9 is the primary marker associated with cholangiocarcinoma and other biliary tumours. It can also rise in HCC patients who have advanced underlying liver disease, so while it is sensitive in that setting, it is not especially specific, and a raised CA19-9 in a cirrhotic patient does not, by itself, point away from HCC.

Imaging Carries the Diagnosis

Because none of the three markers is reliable enough to stand alone, radiology does the real diagnostic work. Ultrasound remains a screening tool rather than a diagnostic one; the imaging pathway that actually confirms HCC or cholangiocarcinoma is covered in the next article in this series.

This guide is based on a live Jivo Masterclass — Dr. Ashish George taught doctors across Africa on March 22, 2026.

FROM THE LIVE Q&A

DR

Dr. Ciablo

We see a lot of non-cirrhotic HCC, mainly hepatitis B, often resectable at 2 centimetres, but we struggle to get these patients optimised for surgery.

AG

Dr. Ashish George

Non-cirrhotic HCC is uncommon in Dr. George's own caseload, around 5 patients in every 100 he sees, but for exactly this group his unit is far more aggressive: extended resections, portal vein embolisation, and even ALPPS, a staged hepatectomy, are all options, because a normal liver can lose as much as 80 percent of its volume and still regenerate enough function from what remains.

See all 11 questions from this masterclass →

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Frequently Asked Questions

How do you make a diagnosis of HCC, and is liver biopsy common?

HCC has a characteristic imaging signature, so biopsy is reserved for genuine diagnostic dilemmas. An arterially enhancing lesion with venous washout on a properly phased triphasic CT is treated as diagnostic in around 95 percent of cases; MRI is used when the CT is inconclusive. Around 40 percent of HCC patients have an elevated AFP, meaning 60 percent do not, so diagnosis relies on radiology rather than tumour markers.

In cholangiocarcinoma, is there a bilirubin cut-off above which you would not operate?

No. Dr. George has operated on perihilar cholangiocarcinoma patients with bilirubin as high as 30 to 35. Surgical practice has also evolved: where extended resections once left only the left lateral section or right posterior sector achievable, his unit now more often does a left- or right-with-caudate resection with extended bile duct resection, preserving more liver parenchyma. Preoperative biliary drainage, usually percutaneous (PTBD) rather than endoscopic nasobiliary drainage, is reserved for patients with cholangitis or those planned for portal vein embolisation.

Between CA19-9 and alpha-fetoprotein, which is more specific?

Alpha-fetoprotein is the marker primarily elevated in hepatocellular carcinoma. CA19-9 comes primarily from the biliary system and can rise somewhat in cirrhotic patients, but not to a high degree, so it remains the more specific marker for cholangiocarcinoma.

After surgery, does the patient take any anti-cancer drugs, and if so, which ones?

After HCC resection on a normal liver, patients are generally placed on lenvatinib long-term. After transplant, there is no separate adjuvant chemotherapy; instead, immunosuppression is adjusted to tacrolimus plus everolimus rather than the standard tacrolimus and mycophenolate, since everolimus is associated with a lower recurrence risk. For cholangiocarcinoma with nodal or vascular invasion, patients are referred to medical oncology for cisplatin or gemcitabine-based adjuvant therapy, usually once they have recovered, six to twelve weeks later, from preoperative jaundice and cholangitis.

A patient developed deranged bilirubin and liver enzymes following a Pringle manoeuvre during hepatectomy, later requiring ERCP stenting. Is this a common complication of the Pringle manoeuvre?

No, this is not typical of the Pringle manoeuvre itself. Needing a stent afterwards points to bile duct involvement: a narrowed biliary confluence after a right hepatectomy, a bile leak that progressed to a stricture after a hepaticojejunostomy, or compromised duct vascularity following preoperative radiotherapy. The Pringle manoeuvre alone may raise liver enzymes, but it should not cause obstructive jaundice.

How often should cirrhotic patients be screened for hepatocellular carcinoma?

Patients with known cirrhosis should have an ultrasound and an alpha-fetoprotein (AFP) test every six months. This six-month protocol has been shown to improve survival and remains the standard of care for this population.

Is there a screening programme for cholangiocarcinoma?

No. Unlike hepatocellular carcinoma, cholangiocarcinoma has no established population screening programme.

Can alpha-fetoprotein be normal in a patient who has hepatocellular carcinoma?

Yes. AFP is elevated in only about 40 percent of HCC patients, meaning 60 percent have a normal level. PIVKA-II is used alongside AFP to raise sensitivity, but it too can be normal in confirmed disease, which is why diagnosis should never rest on tumour markers alone.

Is ultrasound sufficient to diagnose hepatocellular carcinoma?

No. Ultrasound remains a screening tool rather than a diagnostic one. Because none of the three tumour markers is reliable enough to stand alone, radiology, specifically phased CT or MRI, carries the actual diagnostic work.

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