Liver Flukes and Bile Duct Cancer

Two small flatworms that live in the bile ducts, Opisthorchis viverrini and Clonorchis sinensis, are the clearest example in medicine of a parasite that causes cancer. This page sets one point from a 2026 integrative-oncology presentation — that parasites help drive cancer through inflammation, damage and their own secretions — beside the published research on these liver flukes and bile duct cancer (cholangiocarcinoma). It covers how people become infected through raw fish dishes, what the fluke does to the bile duct, a fluke growth factor called granulin, and the screening and education programmes run in northeast Thailand.


Table of Contents

  1. What the Presentation Said
  2. The Asian Liver Flukes and Where They Live
  3. Raw Fish Dishes and How Infection Happens
  4. Why These Flukes Are Classed as a Cause of Cancer
  5. How a Fluke Can Lead to Bile Duct Cancer
  6. Granulin: A Growth Factor Made by the Fluke
  7. Praziquantel, Clearing the Infection and Reinfection
  8. Ultrasound Screening in Northeast Thailand
  9. Health Education and Community Control
  10. How the Claim Compares With the Research
  11. What Is Not Known
  12. Connections
  13. Key Research Papers
  14. Featured Videos

What the Presentation Said

The presentation, a 2026 webinar given by the medical director of an integrative cancer clinic, did not name liver flukes. It made a general case that parasites help cause cancer, and liver flukes are the best-studied test of that case. The points relevant to this page were:

The speaker did not cite a specific study for the inflammation-to-cancer chain. The sections below report what the research on the two Asian liver flukes shows on each of these points.

The Asian Liver Flukes and Where They Live

A fluke is a flat, leaf-shaped parasitic worm (a trematode). Three closely related flukes live in the bile ducts of people: Clonorchis sinensis in eastern Asia, Opisthorchis viverrini in southeast Asia and Opisthorchis felineus in eastern Europe and Siberia (Qian and colleagues, 2024). The bile ducts are the small tubes that carry bile from the liver to the gut; the adult worms attach to their lining and can live there for many years.

The life cycle

How many people are infected

Most infections cause few or no symptoms for years. Heavy or long-lasting infection is linked to inflammation of the bile ducts, gallstones, cholangitis (infection of the bile ducts), periductal fibrosis (scarring around the ducts) and, in a minority of people, cholangiocarcinoma (Na and colleagues, 2020; Qian and colleagues, 2024).

Raw Fish Dishes and How Infection Happens

All three flukes reach people through freshwater fish, most often small fish of the carp family. The reviews name dishes of raw fish fillet, raw-fish "sashimi" and fish congee in the Clonorchis areas of eastern Asia (Na and colleagues, 2020). The presentation spoke of sushi in general; the published research on these flukes concerns raw or undercooked freshwater fish, and the parasites of sea fish are covered on the page about food sources of parasites.

Koi pla in northeast Thailand

In northeast Thailand the key dish is koi pla, a salad of chopped raw fish. Studies there report how deeply the habit is rooted:

Infection comes from cysts that are still alive in fish dishes that have not been safely prepared (Saengsawang and colleagues, 2016). The reviews describe the control of these flukes as a mix of treatment, education about eating habits and improved sanitation (Qian and colleagues, 2024).

Why These Flukes Are Classed as a Cause of Cancer

The International Agency for Research on Cancer (IARC), the cancer agency of the World Health Organization, classifies infection with Opisthorchis viverrini and infection with Clonorchis sinensis in Group 1, “carcinogenic to humans”. The 2009 International Agency for Research on Cancer review of biological agents confirmed both (Bouvard and colleagues, 2009). Before that review, Clonorchis was rated a probable cause and Opisthorchis viverrini a definite one (Watanapa and Watanapa, 2002). The evidence for Opisthorchis felineus was judged insufficient at that time, although later reviews suggest it may also be carcinogenic (Saltykova and colleagues, 2018).

What the classification rests on

Globally, infections with viruses, bacteria and parasites were estimated to contribute 17.8% of the cancer burden, and only a small share of that comes from worm infections; liver flukes and the bladder fluke Schistosoma haematobium are the three worms in Group 1 (Vennervald and Polman, 2009).

The link is not that infection equals cancer. The reviews describe cholangiocarcinoma as an infrequent outcome that develops in some infected people after decades of infection (Na and colleagues, 2020; Saijuntha and colleagues, 2024). Cholangiocarcinoma also occurs in people without fluke infection (Watanapa and Watanapa, 2002).

How a Fluke Can Lead to Bile Duct Cancer

The research describes several processes working together over many years. Much of the detail comes from hamsters (the standard laboratory model for these flukes) and from cells in culture, with supporting findings in human tumour tissue.

Repeated wounding and healing

The adult worms graze on the lining of the bile duct with their suckers. Each feeding site is a wound that heals and is wounded again, for years. The worms also release growth factors, digestive enzymes and extracellular vesicles (tiny packets of proteins and genetic material). Together with the chronic inflammation, these drive biliary hyperplasia (overgrowth of the duct lining), fibrosis and, eventually, malignant change (Smout and colleagues, 2024). One of the authors of that review holds a patent on a wound-healing peptide derived from the fluke, as the paper declares.

Inflammation and DNA damage

Inflamed tissue releases reactive oxygen and nitrogen molecules. In tumour and precancerous tissue from people with Opisthorchis-related cholangiocarcinoma, researchers found two markers of this kind of DNA damage, 8-oxodG and 8-nitroguanine (Murata, 2018). An older review lists chronic irritation, nitric oxide formation, the formation of nitrosamines inside the body, and activation of drug-metabolising enzymes as possible mechanisms (Watanapa and Watanapa, 2002).

A different genetic pattern

Sequencing of fluke-related cholangiocarcinomas found frequent mutations in TP53 (44%), KRAS (16.7%) and SMAD4 (16.7%), plus genes involved in packaging DNA and in cell signalling. The pattern differs from cholangiocarcinoma without a fluke, and the tumours also showed altered DNA methylation (an epigenetic mark) and inflammation-related gene activity (Jusakul and colleagues, 2015).

Effects on the immune setting of the tumour

In 251 patients with intrahepatic cholangiocarcinoma (cancer of the bile ducts inside the liver) in China, Clonorchis infection was associated with shorter overall survival and poorer response to immunotherapy. In the laboratory, tumour cells exposed to the fluke's secretions made more of a fat-building enzyme, and this was linked to immune cells that suppress the attack on the tumour. A drug blocking that enzyme reversed the suppression in mice (Xu and colleagues, 2024). This is the research version of the presentation's point that parasites shape the tumour microenvironment — shown here for one fluke and one cancer.

Bacteria travelling with the fluke

A community of bacteria, including Helicobacter species, lives with the flukes in the bile ducts. In Thailand, Helicobacter infection was more common in people with heavier fluke infections. In hamsters, the fluke changes the bacteria of the gut, and in people Opisthorchis felineus infection changes the bacteria found in bile (Saltykova and colleagues, 2018). A later review reports that more Helicobacter in fluke-infected patients was associated with bile duct inflammation, fibrosis and cell proliferation, while noting that the role of bacteria in this cancer is still unclear (Ketpueak and colleagues, 2020).

Granulin: A Growth Factor Made by the Fluke

One fluke secretion has been studied in detail: a granulin-like growth factor called Ov-GRN-1, released by Opisthorchis viverrini. Granulins are a family of proteins that make cells divide; humans make their own versions.

The same protein is also being studied the other way round: because it speeds wound repair in mice, short laboratory-made versions are being developed as possible wound-healing medicines (Bansal and colleagues, 2017; Haugen and colleagues, 2018). The overlap between wound healing and cancer growth is the central idea in this line of research.

So the presentation's point that parasite secretions distort cell signals has a documented, specific example in this fluke. The evidence is from cells and hamsters; the granulin has not been tested as a cause of cancer in people.

Praziquantel, Clearing the Infection and Reinfection

Praziquantel is the prescription medicine used against these flukes and the mainstay of control programmes (Qian and colleagues, 2024). The research shows that it clears the worms well, but that clearing them does not end the story.

How well it works

Reinfection where raw fish is still eaten

Scarring that persists after the worms are gone

In Khon Kaen, 785 infected people with advanced periductal fibrosis on ultrasound were invited to yearly ultrasound for five years after praziquantel. More than a third (37.5%) still had or relapsed into advanced fibrosis, and five suspected cholangiocarcinomas were seen during follow-up (Mairiang and colleagues, 2021). The authors concluded that the cancer process may continue long after the fluke is cleared. In other words, treatment removes the worm, but damage already done can remain.

No trial was found that tested herbal or over-the-counter “parasite cleanses” against liver flukes, and no trial tested whether periodic treatment of people who are not exposed lowers their cancer risk. Decisions about cancer treatment and antiparasitic medicines belong with a clinician.

Ultrasound Screening in Northeast Thailand

Because cholangiocarcinoma is usually found too late for surgery, Thailand began large-scale screening of people at high risk.

The programme's stated aim is earlier diagnosis that allows curative surgery. The papers cited here describe the design and early findings; they do not yet report whether screening has lowered deaths from cholangiocarcinoma. Long-term survival after surgery for fluke-related cholangiocarcinoma was reported to be similar to that for cholangiocarcinoma without a fluke (Watanapa and Watanapa, 2002).

Researchers are also searching for blood, bile and tissue markers that could detect the cancer earlier, but a 2026 review reports that most candidates are still at the laboratory stage, tested in small groups, without large prospective validation (Huang and colleagues, 2026).

Health Education and Community Control

Thailand's control efforts since 1984 have centred on health education (Khuntikeo and colleagues, 2015). The research on how well this works is mixed but encouraging.

The World Health Organization includes the foodborne trematodes, among them these flukes, in its neglected tropical disease targets for 2030 (Kim and Hong, 2025). Research tools include fish vaccines and new drugs such as tribendimidine, a medicine registered in China for other worms that shows activity against both liver flukes (Qian and colleagues, 2024).

How the Claim Compares With the Research

What the research supports

What it supports only in part

What it does not support or has not tested

What Is Not Known

Connections

Key Research Papers

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  2. Bouvard V, Baan R, Straif K, et al. A review of human carcinogens—Part B: biological agents. The Lancet Oncology. 2009;10(4):321-2. PubMed PMID: 19350698
  3. Vennervald BJ, Polman K. Helminths and malignancy. Parasite immunology. 2009;31(11):686-96. PubMed PMID: 19825108
  4. Watanapa P, Watanapa WB. Liver fluke-associated cholangiocarcinoma. The British journal of surgery. 2002;89(8):962-70. PubMed PMID: 12153620
  5. Smout MJ, Laha T, Chaiyadet S, et al. Mechanistic insights into liver-fluke-induced bile-duct cancer. Trends in parasitology. 2024;40(12):1183-1196. PubMed PMID: 39521672
  6. Kim EM, Hong ST. Clonorchis sinensis and Cholangiocarcinoma. Journal of Korean medical science. 2025;40(16):e145. PubMed PMID: 40296827
  7. Na BK, Pak JH, Hong SJ. Clonorchis sinensis and clonorchiasis. Acta tropica. 2020;203:105309. PubMed PMID: 31862466
  8. Murata M. Inflammation and cancer. Environmental health and preventive medicine. 2018;23(1):50. PubMed PMID: 30340457
  9. Jusakul A, Kongpetch S, Teh BT. Genetics of Opisthorchis viverrini-related cholangiocarcinoma. Current opinion in gastroenterology. 2015;31(3):258-63. PubMed PMID: 25693006
  10. Xu L, Zhang Y, Lin Z, et al. FASN-mediated fatty acid biosynthesis remodels immune environment in Clonorchis sinensis infection-related intrahepatic cholangiocarcinoma. Journal of hepatology. 2024;81(2):265-277. PubMed PMID: 38508240
  11. Saltykova IV, Petrov VA, Brindley PJ. Opisthorchiasis and the Microbiome. Advances in parasitology. 2018;102:1-23. PubMed PMID: 30442306
  12. Ketpueak T, Thiennimitr P, Apaijai N, et al. Association of Chronic Opisthorchis Infestation and Microbiota Alteration on Tumorigenesis in Cholangiocarcinoma. Clinical and translational gastroenterology. 2020;12(1):e00292. PubMed PMID: 33464733
  13. Haugen B, Karinshak SE, Mann VH, et al. Granulin Secreted by the Food-Borne Liver Fluke Opisthorchis viverrini Promotes Angiogenesis in Human Endothelial Cells. Frontiers in medicine. 2018;5:30. PubMed PMID: 29503819
  14. Arunsan P, Ittiprasert W, Smout MJ, et al. Programmed knockout mutation of liver fluke granulin attenuates virulence of infection-induced hepatobiliary morbidity. eLife. 2019;8:e41463. PubMed PMID: 30644359
  15. Saijuntha W, Sithithaworn P, Wangboon C, et al. Liver Flukes: Clonorchis and Opisthorchis. Advances in experimental medicine and biology. 2024;1454:239-284. PubMed PMID: 39008268
  16. Bansal PS, Smout MJ, Wilson D, et al. Development of a Potent Wound Healing Agent Based on the Liver Fluke Granulin Structural Fold. Journal of medicinal chemistry. 2017;60(10):4258-4266. PubMed PMID: 28425707
  17. Ambroise-Thomas P, Goullier A, Peyron F. Therapeutic results in opisthorchiasis with praziquantel in a reinfection-free environment in France. Arzneimittel-Forschung. 1984;34(9B):1177-9. PubMed PMID: 6542388
  18. Saengsawang P, Promthet S, Bradshaw P. Reinfection by Opisthorchis Viverrini after Treatment with Praziquantel. Asian Pacific journal of cancer prevention. 2016;17(2):857-62. PubMed PMID: 26925692
  19. Worasith C, Wangboon C, Kopolrat KY, et al. Application of urine antigen assay to evaluate outcomes of praziquantel treatment and reinfection in opisthorchiasis in northeast Thailand. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2020;114(10):751-761. PubMed PMID: 32735672
  20. Thinkhamrop K, Khuntikeo N, Sithithaworn P, et al. Repeated praziquantel treatment and Opisthorchis viverrini infection: a population-based cross-sectional study in northeast Thailand. Infectious diseases of poverty. 2019;8(1):18. PubMed PMID: 30890188
  21. Saengsawang P, Buakate P. Re- Infection Rate of Opisthorchis Viverrini Five Years After Treatment with Praziquantel in High-Risk Area: A Community-Based Study. Asian Pacific journal of cancer prevention. 2024;25(8):2679-2684. PubMed PMID: 39205565
  22. Mairiang E, Laha T, Kaewkes S, et al. Hepatobiliary morbidities detected by ultrasonography in Opisthorchis viverrini-infected patients before and after praziquantel treatment: a five-year follow up study. Acta tropica. 2021;217:105853. PubMed PMID: 33548204
  23. Khuntikeo N, Chamadol N, Yongvanit P, et al. Cohort profile: cholangiocarcinoma screening and care program (CASCAP). BMC cancer. 2015;15:459. PubMed PMID: 26054405
  24. Chamadol N, Laopaiboon V, Srinakarin J, et al. Teleconsultation ultrasonography: a new weapon to combat cholangiocarcinoma. ESMO open. 2017;2(3):e000231. PubMed PMID: 29209530
  25. Thinkhamrop K, Suwannatrai AT, Chamadol N, et al. Spatial analysis of hepatobiliary abnormalities in a population at high-risk of cholangiocarcinoma in Thailand. Scientific reports. 2020;10(1):16855. PubMed PMID: 33033306
  26. Huang C, Wu Y, Wu A, et al. Clonorchis sinensis and cholangiocarcinoma: molecular mechanisms and biomarker advances. Parasite. 2026;33:16. PubMed PMID: 41919759
  27. Busabong W, Woradet S, Songserm N. Impact of self-efficacy-based health education programs on behavior modification for Opisthorchis viverrini and cholangiocarcinoma prevention in Thailand: A systematic review and meta-analysis. Parasites, hosts and diseases. 2025;63(1):1-11. PubMed PMID: 40045676
  28. Sripa B, Tangkawattana S, Sangnikul M. Integrated opisthorchiasis control through the EcoHealth/one health approach: 15 years of success and experiences with the Lawa model. One Health. 2025;20:101006. PubMed PMID: 40123921
  29. Sornpom J, Suwannatrai AT, Suwannatrai K, et al. Influence of misconceptions and inappropriate eating behaviors on Opisthorchis viverrini infection among at-risk populations undergoing cholangiocarcinoma screening in Northeastern Thailand. Parasitology research. 2023;122(12):3131-3138. PubMed PMID: 37855971

PubMed Topic Searches

  1. Opisthorchis viverrini and cholangiocarcinoma
  2. Clonorchis sinensis and cholangiocarcinoma
  3. Liver fluke granulin
  4. Praziquantel and reinfection in opisthorchiasis
  5. Cholangiocarcinoma ultrasound screening in Thailand