The study, known as COMIT-ANZ, was led by researchers at the University of Melbourne’s Austin Health Precinct together with the Prometheus Transplant Collaborative, spanning hospitals from Queensland to Western Australia and Auckland City Hospital in New Zealand. The team set out to measure clinical outcomes for patients who had undergone liver transplantation either knowingly for cholangiocarcinoma or unknowingly, when the tumour was discovered only after the diseased liver had been removed and examined under the microscope. Their findings carry real weight for a subspecialty that is expanding faster than its evidence base.

Cholangiocarcinoma is a malignancy that arises from the epithelial cells lining the bile ducts, the narrow channels that drain bile from the liver into the intestine. It carries a notoriously poor prognosis, and its behaviour depends heavily on where it sits. Intrahepatic cholangiocarcinoma develops within the liver substance itself, while the majority of extrahepatic tumours are perihilar, clustering at the liver hilum where the bile ducts converge. That anatomical distinction is not merely academic; it determines which transplant pathway a patient can access, because the evidence supporting transplantation differs profoundly between the two sites.

For perihilar tumours that cannot be surgically resected, transplantation is only offered when centres have an established neoadjuvant chemoradiotherapy protocol in place, a strategy pioneered at the Mayo Clinic in which patients receive external beam radiotherapy followed by chemotherapy before the transplant itself. International series report five-year overall survival of roughly 53 to 71 percent for these patients. For very early intrahepatic cholangiocarcinoma, defined as a single tumour smaller than two centimetres in a cirrhotic liver, a growing body of retrospective data has convinced the International Liver Transplant Society to endorse transplantation. The catch, as the COMIT-ANZ authors point out, is that nearly all of the data informing that guidance came from North American, Asian and European centres, leaving the applicability to Australia and New Zealand genuinely unknown.

To close that gap, the researchers mined the Australia and New Zealand Liver and Intestinal Transplant Registry, the national registry that has captured transplant activity since the region’s programmes began in 1986. Local transplant unit leads re-identified eligible recipients and entered de-identified clinical data into a REDCap database, capturing demographics, transplant details, explant histology, patient and graft survival, recurrence status and cause of death. The primary outcome was five-year overall survival, with recurrence-free survival as a secondary measure. In total, 64 adult patients were identified who had been transplanted for either known or incidentally detected cholangiocarcinoma or a mixed hepatocellular-cholangiocarcinoma, a rare biphenotypic tumour carrying histological features of both parent cancers.

The demographic profile of these patients was telling. Three-quarters were male, the median age at transplant was 55 years, and the median MELD score, the laboratory measure of liver disease severity used to prioritise waiting-list patients, was 14. Perhaps the most consequential finding was the timing of diagnosis: 75 percent of these tumours were detected incidentally on explant histology, meaning neither the patient nor the surgical team knew the cancer was there before the transplant. Only 16 patients, one quarter of the cohort, were knowingly transplanted for cholangiocarcinoma, and most of those had underlying primary sclerosing cholangitis, an inflammatory condition of the bile ducts that predisposes patients to perihilar tumours.

The survival figures tell a nuanced story. Across all 64 patients, the five-year overall survival was 47 percent, with recurrence-free survival of 60 percent, figures that sit well below the 83 percent five-year survival for liver transplantation in the region overall and the 79 percent for hepatocellular carcinoma. But the all-comer number conceals the real signal. When the researchers stratified by tumour size, patients with intrahepatic cholangiocarcinomas smaller than two centimetres achieved five-year overall and recurrence-free survival of 80 percent, squarely in line with the international data underpinning the current ILTS guidance. By contrast, patients with perihilar tumours fared far worse, with five-year overall survival of just 31 percent and recurrence-free survival of 40 percent, significantly inferior to the intrahepatic group.

The statistical analysis sharpened these contrasts further. Univariate Cox regression identified age, known pre-transplant tumours, mixed histological type and poorly differentiated tumours as factors associated with poorer overall survival. When variables with p values below 0.20 were carried into a multivariate model, only one factor remained independently significant: poorly differentiated tumours, which carried a hazard ratio of 4.78 for death compared with better-differentiated cancers. The authors suggest this finding could eventually inform pre-transplant decision making, since a biopsy demonstrating poorly differentiated cholangiocarcinoma might steer a patient toward a different treatment path, though they caution that the role of pre-operative biopsies in risk stratification requires further study.

The mixed hepatocellular-cholangiocarcinomas deserve particular attention, because clinical outcomes after transplantation for these tumours have never been clearly established. All 17 mixed tumours in this cohort were detected incidentally on explant histology, and none were knowingly transplanted, a reflection of how difficult these cancers are to diagnose before surgery. Radiologically, mixed tumours cannot be reliably distinguished from pure hepatocellular carcinoma, and neither biopsies nor tumour markers such as alpha-fetoprotein and CA19-9 carry sufficient sensitivity, since elevated levels of both may reflect the biphenotypic nature of the neoplasm. Yet the survival data was unexpectedly reassuring: five-year overall survival for the mixed group was 68 percent, significantly better than the 51 percent for pure cholangiocarcinomas, and comparable to the 70 percent reported in a multi-centre American study of 67 patients transplanted for mixed tumours within Milan criteria.

The authors are candid about the limitations of their work. The study is retrospective, spanning an era in which clinical practice has changed enormously, and not every data point was available for every patient, which affected the completeness of the statistical analysis. Significant heterogeneity also exists within the cohort, mixing knowingly transplanted perihilar and intrahepatic tumours with incidental discoveries and the mixed histological subtype. Still, the central conclusion stands: the international guidance on very early intrahepatic cholangiocarcinoma does apply to Australia and New Zealand, and patients transplanted with cirrhosis and tumours under two centimetres can expect excellent five-year survival. As transplant oncology expands and demand for donor organs grows, audits like this one provide the regional evidence needed to decide, ethically and practically, who should receive a scarce and precious liver.

Subject of Research: Liver transplantation outcomes for cholangiocarcinoma and mixed hepatocellular-cholangiocarcinoma in Australia and New Zealand

Article Title: COMIT-ANZ: an audit of cholangiocarcinoma and mixed hepatocellular carcinoma-cholangiocarcinoma outcomes for patients undergoing liver transplantation in Australia and New Zealand

Article References: Riddiough, G. E., Hall, K., Byrne, M., Brown, K., Kilburn, D., Goh, S. K., Marshall-Webb, M., Pulitano, C., Chan, K., Philipoff, A., Nazaar, A., & Lee, E. (2026). COMIT-ANZ: an audit of cholangiocarcinoma and mixed hepatocellular carcinoma-cholangiocarcinoma outcomes for patients undergoing liver transplantation in Australia and New Zealand. Frontiers in Transplantation, 5, Article 1856922. https://doi.org/10.3389/frtra.2026.1856922

Image Credits: AI Generated

DOI: 10.3389/frtra.2026.1856922

Keywords: liver transplantation, cholangiocarcinoma, transplant oncology, mixed hepatocellular-cholangiocarcinoma, intrahepatic cholangiocarcinoma, survival outcomes, Australia New Zealand, ILTS guidance, COMIT-ANZ, audit, mixed, hepatocellular