Principal Consultant & Unit Head, Liver Transplant, Fortis Hospital, Shalimar Bagh, New Delhi, India
Part 2 of 13 in Management of Primary Liver Cancers
Hepatocellular Carcinoma and Cholangiocarcinoma: Recognising the Two Primary Liver Cancers
August 27, 2026
Before any patient can be staged or treated, the first task is separating hepatocellular carcinoma (HCC) from cholangiocarcinoma, and separating both from the liver metastases that are, in practice, the most common tumours found in the liver. Dr. George's masterclass on the management of primary liver cancers starts here, because the distinction changes every downstream decision, from which tumour marker to check to which surgical approach applies.
Two Cells, Two Cancers
Hepatocytes, the main functional cells of the liver, give rise to hepatocellular carcinoma. Cholangiocytes, the cells lining the bile ducts, give rise to cholangiocarcinoma. HCC accounts for 80 to 85 percent of primary liver cancers and carries a high burden of disease in East Asia and North Africa. Cholangiocarcinoma accounts for the remaining 10 to 15 percent.
Cholangiocarcinoma is further divided by where it originates. Extrahepatic tumours, arising below the hilum, fall outside the scope of this series. Perihilar tumours, also called Klatskin tumours, arise at the confluence of the right and left hepatic ducts. Intrahepatic tumours arise from smaller bile duct cells within the liver parenchyma itself.
Different Patients, Different Presentations
The majority of HCC arises in patients who already have cirrhosis, whatever the underlying cause. Perihilar and, to a lesser extent, intrahepatic cholangiocarcinoma can also arise on a cirrhotic liver, but most cases in Dr. George's experience develop without it. Risk factors for HCC are chronic viral hepatitis B and C, cirrhosis of any cause, older age and family history. Cholangiocarcinoma shares cirrhosis as a risk factor and adds primary sclerosing cholangitis, hepatolithiasis, choledochal cysts and liver flukes.
Location decides how each cholangiocarcinoma announces itself. Perihilar tumours sit across the bile duct highways that carry bile out of the liver, so they cause obstruction and jaundice early, which is exactly why they tend to be diagnosed sooner. Intrahepatic tumours grow peripherally and silently, typically presenting as a mass on imaging, sometimes with weight loss, pain or asthenia, and are usually found later, which contributes to their comparatively poorer prognosis. Some are only picked up incidentally, when a patient is scanned for an unrelated reason.
On a CT scan, an intrahepatic cholangiocarcinoma placed peripherally against the liver capsule can pull the liver's margin inward, a finding Dr. George describes as capsular retraction, a subtle clue that experienced radiologists learn to look for.
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. Ciablo
The majority of HCC patients present late, with very large lesions up to 10 centimetres, and liver transplant isn't available in most of our countries. What criteria should guide resection in that setting?
Dr. Ashish George
The first check is whether the background liver is cirrhotic or, from vertical hepatitis B or C transmission, essentially normal; a normal liver allows extended resection with portal vein embolisation to grow the future remnant. On a cirrhotic background, the priority is ruling out disease outside the liver, then grading any portal vein invasion from VP1 (a segmental branch) to VP4 (the main portal vein). Patients with VP1 or VP2 involvement and no extrahepatic disease can still be offered transplant, upfront or after downstaging with TACE, sometimes combined with SBRT for a portal vein tumour thrombus, aiming for 12 weeks of stable disease.
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Frequently Asked Questions
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.▼
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.
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.
What is capsular retraction and why does it matter on a CT scan?▼
Capsular retraction is when a peripherally placed intrahepatic cholangiocarcinoma pulls the liver's outer margin inward on imaging. It is a subtle sign that experienced radiologists learn to look for, and its presence can help distinguish this tumour type from other liver lesions.
Does cholangiocarcinoma always develop in a cirrhotic liver?▼
No. While cirrhosis is a shared risk factor with hepatocellular carcinoma, most cases of perihilar and intrahepatic cholangiocarcinoma actually arise without cirrhosis being present.
What symptoms suggest an intrahepatic cholangiocarcinoma rather than a perihilar one?▼
Intrahepatic tumours typically present as a liver mass on imaging, sometimes with weight loss, pain or asthenia, and are sometimes found incidentally on a scan ordered for another reason. Perihilar tumours, in contrast, cause early jaundice because they obstruct the main bile duct confluence.
What additional risk factors are linked specifically to cholangiocarcinoma?▼
Beyond the risk factors it shares with HCC, cholangiocarcinoma is also associated with primary sclerosing cholangitis, hepatolithiasis, choledochal cysts and liver flukes.
In This Series: Management of Primary Liver Cancers
- 1.Management of Primary Liver Cancers
- 2.Hepatocellular Carcinoma and Cholangiocarcinoma: Recognising the Two Primary Liver Cancers
- 3.Screening and Tumour Markers for Primary Liver Cancer
- 4.Imaging and Diagnosis of Hepatocellular Carcinoma
- 5.BCLC Staging and Treatment Principles for Hepatocellular Carcinoma
- 6.Curative Options for Early HCC: Resection, Ablation and the Case for Transplant
- 7.Liver Transplant Criteria and Downstaging in Hepatocellular Carcinoma
- 8.Operating on Large and Non-Cirrhotic HCC Without a Transplant Programme
- 9.Intrahepatic and Perihilar Cholangiocarcinoma: Presentation, Staging and the Case for Surgery
- 10.Surgical Management of Perihilar Cholangiocarcinoma: The Bismuth-Corlette Classification in Practice
- 11.Adjuvant and Systemic Therapy, and the R1 Resection Question, in Cholangiocarcinoma
- 12.Building a Liver Transplant Programme in a Resource-Constrained Setting
- 13.Post-Treatment Follow-up and Recurrence Prevention in Primary Liver Cancer