Clonorchis sinensis

In brief

What it is, and how it gets in

Clonorchis sinensis is a fluke, a flat parasitic worm of the class Trematoda and the family Opisthorchiidae ³. The adult is slender and leaf-shaped, 10–15 mm long, 4–5 mm wide and about 1 mm thick, and it lives in the bile ducts, the branching tubes that carry bile out of the liver toward the intestine ³. A single worm can survive in a person for about 30 years and lay about 4,000 eggs a day, which the authors of a 2025 review work out to more than 30 million eggs in a lifetime ³. People, dogs, cats, pigs and rats can all be its final host, the animal in which it grows to adulthood ³. Its genome, sequenced in 2011, is 516 million DNA letters long with about 16,000 genes, and it lacks key genes for making fatty acids, so the worm takes the fats it needs from bile ²².

The life cycle needs two other animals, called intermediate hosts, in a fixed order ²³. Eggs leave the body in feces; if they reach fresh water they are eaten by snails, inside which one egg multiplies into 1,000 to 1,500 free-swimming larvae called cercariae ³. At Thac Ba Lake in northern Vietnam, DNA testing identified the snail Parafossarulus striatulus as the host ²⁴. The cercariae bore through the skin of freshwater fish, mostly of the carp family, and settle in the muscle as metacercariae, the cyst stage that infects people ³. A person is infected by eating that fish raw or undercooked, as sliced fillet, sashimi or congee ⁴. In a 2024–2025 survey of five villages in Guangxi, China, a history of eating raw freshwater fish multiplied the odds of infection by 5.27, and infected cats or dogs in a village by 2.37 ²⁰.

Inside the body the route is quick. In the duodenum, the first part of the small intestine, digestive enzymes free the young fluke from its cyst, and it moves up the common bile duct, steered by chemical signals in bile itself, reaching the ducts inside the liver of a rabbit in 9 to 10 minutes ^3,4. Eggs first appear in the stool 26 days after the infected fish is eaten ³. Because the cycle depends on particular snails and fish, it cannot be completed where those hosts are missing, and in the Americas they are missing ²⁵. Infections diagnosed in North America have therefore almost all been acquired abroad, often years before they are found ^26,27.

Where it lives now, and how many people carry it

China carries most of the world's infections ³⁶. A 2025 model built on national surveillance from 2016 to 2021 estimated that 0.67% of the population was infected in 2020, averaged across the country with each area counted in proportion to the people living in it, or 9.46 million people infected (95% Bayesian credible interval 8.22–10.88 million), with 99.13 million living where the fluke is transmitted and 51.69 million in areas whose infection rates are high enough that the program would treat everyone there ⁶. The burden is concentrated in the south, at 8.92% in Guangxi and 2.99% in Guangdong ⁶. In 2016 the national surveillance points found 6,226 infections among 305,081 people screened, 2.04%, with 89.37% of them in Jilin, Heilongjiang, Guangdong and Guangxi; the highest infection rate, 49%, was in Da'an city, Jilin ³⁷. Villages can be far higher: 30.50% of 1,013 people surveyed in Fusui County, Guangxi, in 2024–2025 ²⁰. The same research group put China's 2020 burden at 431,009 disability-adjusted life years, of which 57,998 were years of life lost to bile-duct cancer attributed to the fluke ³⁸. The map is not static. A 2025 spatial analysis of the national surveys puts the clusters along the Dongting Lake, Songhua River and Pearl River basins and finds the risk shifting southward since the early 2000s ³⁹. Where raw fish becomes fashionable the disease follows: in 2026 Henan province reported China's first local cluster outside the endemic provinces, five people, three of them with symptoms, infected after one dinner of raw freshwater fish in Zhengzhou ⁴⁰, and cysts were found in 32.5% of the fish sampled from a lake inside the city of Wuhan, where stray cats and rats appear to keep the cycle going ⁴¹.

Korea measured its infection in eight national stool surveys between 1971 and 2012, and the egg-positive rate moved from 4.6% in 1971 to 1.9% in 2012 ³. In the 2012 survey it was the commonest parasite in the country, at 1.86% of the general population ⁴². No general-population survey has been run since, but the Korea Disease Control and Prevention Agency screens the endemic river basins every year: among 26,258 residents in 2023, 3.7% passed parasite eggs and 1.9% the fluke, and among 26,985 residents of 39 districts in the five major basins in 2024, 4.5% and 2.3%, with the Seomjin-gang basin highest at 6.3% ^43,44. Prescription records for 2002 to 2023 show incidence falling steadily, highest among men, people over 40 and residents of the Gyeongsang and Jeolla provinces ⁴⁵. A screening and treatment program along southern river basins took the egg-positive rate from 11.1% in 2011 to 3.8% in 2020, and a 2025 review judged that far fewer than one million Koreans are now infected ³. Transmission continues in five major river basins, where fish still carry cysts ⁴⁶. A 2024 analysis separating the effects of age, calendar period and birth cohort found both period and cohort effects behind the decline and projected that, while prevalence is falling in every age group, people over 40 would still sit above the 1% level that counts as elimination ⁴⁷.

Northern Vietnam and Guangxi together were estimated in 2021 to hold 3.5 to 5 million infections ⁴⁸. Earlier Vietnamese surveys found 26.0–37.5% infected in Nam Dinh province and 23.5–31.0% in Ninh Binh ³⁶. In Russia the fluke lives mainly in the Amur River basin of the southern Far East, where infected residents number in the thousands, and Russian ecologists reported in 2019 that its spread south into Primorye, under way for 10 to 15 years, was slowing ^3,49. Japan once had endemic areas on Honshu, Shikoku and Kyushu; changes to freshwater ecology after the Second World War made the snail host vulnerable, and transmission appears to have ended, although sporadic cases are still reported: in 2025 a Japanese woman in her 70s with no history of travel abroad was judged, on antibody tests and a liver biopsy showing eosinophilic inflammation, to most likely have the fluke ^3,5.

Worldwide figures are softer than national ones ². A 2012 review gave more than 200 million people at risk and 15–20 million infected ⁷, and the three related liver flukes together are put at about 25 million ¹³. The Global Burden of Disease study counted 44,466,329 cases of all food-borne fluke infections in 2021, a wider category that includes lung and intestinal flukes ⁵⁰. WHO's 2026 update of foodborne disease ranked C. sinensis second among invasive foodborne parasites, at 0.921 million disability-adjusted life years, and found the Western Pacific to be the one region where the burden was rising, mainly because of this fluke ⁵¹.

The whole history, including the parts that were overturned

The fluke is old: its eggs were found in the bowel of a woman buried more than 2,300 years ago, in the Warring States period, at Guo-Jia-Gang in Hubei Province ⁵². In preserved feces from Korea's Joseon period, the Korean dynasty that ended in 1910, 9 of 30 samples, 30.0%, held its eggs ⁵³, and historians comparing ancient samples with twentieth-century surveys found that the fluke fell away in both China and Korea earlier than roundworm and whipworm did ⁵⁴. It also traveled with people: latrines used by Chinese-Americans in San Bernardino, California, between about 1880 and the 1930s contained its eggs, carried in by immigrants infected in Asia ²⁵.

Western medicine met it in India: on 21 August 1875, James McConnell published in The Lancet the findings of a post-mortem examination of a 20-year-old Chinese man at the Medical College Hospital in Calcutta, in whose bile ducts he had found the fluke ²; a 2025 review dates the recovery itself to 1874 ³. Cobbold named the species in 1875, and Looss moved it into the new genus Clonorchis in 1907, which is why the full name is written Clonorchis sinensis (Cobbold, 1875) Looss, 1907 ^1,41. The life cycle was taken apart in Japan over the next decade: Kenso Ishisaka recorded the first human case in Japan in 1877, Shigeru Matsumoto in Korea and Tsukasa Ohi in Taiwan reported the disease to be common in their countries in 1915, Harujiro Kobayashi showed that fish of the carp family were the second intermediate host, and Masatomo Muto identified Parafossarulus snails as the first in 1918 ⁵⁵. Kobayashi's date is given as 1912 by one review and 1910 by another, and this page follows neither without saying so ^55,56. The first patient with bile-duct cancer linked to the fluke was reported from China in 1919, and in 1948 a Korean health official noticed liver cancer, jaundice and swollen abdomens among heavily infected people around Busan, where 50–70% tested positive, before the Korean War stopped his work ³.

The cancer case was then assembled slowly ³. Hong Kong autopsy series in the 1950s and 1960s described bile-duct cancers without cirrhosis in livers full of flukes, and Korean hospital data published in 1974 showed bile-duct cancer making up 19.3% of primary liver cancers in endemic Busan against 8.6% in Seoul ³. Hamster experiments in 1993 and 1994 showed that the fluke and a nitrosamine together produced cancer, and the first of them found that neither did so alone ^32,57. That was not enough for IARC in June 1994, which judged the human evidence limited and placed the fluke in Group 2A, while putting its Thai relative O. viverrini in Group 1 and O. felineus in Group 3 ^8,58.

The reversal came from looking harder ⁸. Korean case-control studies and correlations between local infection rates and cancer incidence led the Volume 100B Working Group, meeting in February 2009, to judge the human evidence sufficient and move C. sinensis into Group 1 ^3,8. Its summary appeared in The Lancet Oncology in April 2009, and the full monograph was printed in 2012 ^9,59. The evidence has kept accumulating since: a 2024 meta-analysis put the odds ratio for cholangiocarcinoma at 4.49, and IARC's 2026 burden analysis counts the fluke among 12 infectious agents in Group 1 ^10,19. For O. felineus the same story has only begun, with a first human case-control study in 2023 ¹⁷.

What it does to a body

Most people with a few flukes notice nothing, because the worms sit in the channel of a duct that has widened to hold them ³. Heavy and long-standing infection brings upper abdominal pain, indigestion, fever and loose stools, and over time gallstones, pockets of pus in the liver, cholangitis (infection of the bile ducts), inflammation of the gallbladder, pancreatitis (inflammation of the pancreas, the gland that makes digestive enzymes) and cholangiocarcinoma ³. In one community in southeastern China, infection was associated with diarrhea (adjusted odds ratio 2.2) and fatty liver (2.7), and moderate to heavy infection with widened bile ducts (4.3 for heavy infection) and periductal fibrosis, scarring around the ducts (3.2) ³. Symptoms track the number of worms, the years of infection and how often the person is reinfected ³. The damage may not stop at the liver. A 2026 systematic review of human and animal studies from 1950 to 2025 reports kidney injury with these flukes, including damage to the filtering units and the draining tubules, inflammation between them and scarring, with immune complexes and oxidative stress proposed as the route; the human evidence is thin and the mechanisms are unsettled, and the review's authors say so ⁶⁵. The clearest data are from hamsters infected with the northern relative, in which blood creatinine and urine protein climbed steadily over 18 months ⁶⁶.

The duct itself is remodeled ³. A worm-filled duct can widen tenfold, from 0.8 mm to 8 mm across, which is roughly a hundredfold increase in the space it holds along any stretch of its length, and it presses on the surrounding liver ³. Its lining thickens with a 15-fold rise in cell division and fills with mucus-producing cells, inflammation gathers in the duct wall, and fibrosis spreads around it ³. Pooled across studies to early 2024, infection was associated with gallstones (odds ratio 6.46, 95% CI 5.15–8.11), cholecystitis (risk ratio 21.02, 17.27–25.58), cirrhosis (risk ratio 8.77, 6.79–11.33) and fatty liver (odds ratio 2.46, 1.79–3.37) ¹⁰. These are associations from observational studies, and the men who eat the most raw fish in endemic areas are also more likely to be drinking alcohol while they do it ³.

Damage does not vanish when the worms die ³. After treatment the duct changes largely resolve, but mild widening and periductal fibrosis persist for more than a year, enough to make an ultrasound look positive after cure ³. Reinfection is common: one Guangxi community study found 40.6% of treated, infected people infected again within a year ³. Worms of different ages are found together in one person, so infection does not protect against the next one in humans, although cured rats became 97.7% resistant to reinfection in experiments ^3,67. In surgical specimens, a precursor growth called intraductal papillary neoplasm of the bile duct was found in 12 of 20 resected cancers from fluke-positive patients against 8 of 51 from fluke-negative ones, and the growths were of a different cell type ⁶⁸.

How it might cause cancer, and how that differs from its Thai relative

No one has watched a fluke turn a human cell cancerous, so the mechanism is assembled from animals and cultured cells, and a 2020 review states plainly that it has not been worked out in detail ^3,4. The leading model treats the worm as a promoter, something that drives damaged cells to keep dividing, and a chemical such as a nitrosamine as the initiator that damages DNA in the first place ³. In Syrian golden hamsters given dimethylnitrosamine in their water and then infected, 6 of 8 animals (75%) had cholangiocarcinoma 10 weeks after infection, while either exposure alone produced only overgrowth of the duct lining ³². A 2015 hamster study found the cancer in every animal given both, beginning in the eighth week ³³.

The model depends on the animal ³. Laboratory mice of four strains given the fluke and the nitrosamine developed no cholangiocarcinoma, and C3H/He mice given a third chemical as well developed extensive fibrosis instead ^3,34. In 2025, a Chinese rat study reported cholangiocarcinoma in 37% of Sprague-Dawley rats infected with the fluke alone, 63% overall and 71% at 20 weeks with the nitrosamine added, and a single case with the chemical alone ³⁵. If repeated, that would be the clearest animal evidence that the fluke can start cancer as well as speed it; for now it is one exploratory experiment in one rat strain ³⁵.

The fluke releases a mixture of proteins into the bile, called excretory-secretory products ³⁶. In cultured human bile-duct cancer cells these products generate free radicals, switch on NF-κB, a master switch inside the cell that turns on inflammation genes, raise the tissue-dissolving enzyme MMP-9, push cells into division and suppress programmed cell death; in normal bile-duct cells given the products together with a nitrosamine they raise COX-2, an enzyme of inflammation ³. One of them is a granulin, a growth-factor-like protein called CsGRN, found in the worm's surface layer and testes; in liver and bile-duct cancer cell lines it made the cells move and invade more, working through two of the relay chains cells use to pass a growth signal from their surface to their nucleus, called ERK and PI3K/AKT ²⁹. Vesicles the worm sheds, tiny membrane packets, were taken up by bile-duct cancer cells in culture and made them divide and invade faster, through the same NF-κB signaling, an effect that an NF-κB blocker partly undid; this is cell-culture and mouse work, with a lung-metastasis model, not evidence from people ⁶⁹. In 2026 the products were shown to make bile-duct lining cells release interleukin-17A, a signaling molecule that in turn activated the liver's scar-forming cells, and levels were higher in infected patients' blood ³¹. One strand of this literature has been withdrawn. Two papers reporting that a fluke microRNA carried in the worm's extracellular vesicles, csi-miR-96-5p, lowered the tumor-suppressor protein PTEN and so drove bile-duct cancer cells were retracted by their journals, in 2024 and in 2026 ^70,71. Nothing on this page rests on them, and they are named here because the claim still circulates.

Much of this mirrors O. viverrini, and a 2024 review treats the two together: secreted growth factors, digestive enzymes and extracellular vesicles, abnormal inflammation, and repeated wounding where the worms attach and graze ²⁸. The difference lies in how hard each idea has been tested ^29,30. For O. viverrini, flukes whose granulin gene was knocked out with CRISPR still matured in hamsters but caused less fibrosis, fewer TP53 mutations and fewer high-grade cancers ³⁰; the C. sinensis granulin evidence comes from cell lines and mice ²⁹. In side-by-side hamster infections, periductal fibrosis looked alike with C. sinensis and O. felineus, while precancerous change of the duct lining appeared mainly with O. viverrini ⁷², and the liver's gene activity differed by species ⁷³.

Tumor genetics points the same way ⁷⁴. In 489 cholangiocarcinomas from 10 countries, fluke-positive tumors formed molecular clusters distinct from fluke-negative ones, which the authors read as different causes producing different cancers in the same organ ⁷⁴. A 2026 review proposes that most worms never cause cancer because inflammation alone is not enough, and that opisthorchiid flukes cross a threshold by combining chronic mechanical injury, secretions that damage DNA and drive growth, dietary nitrosamines, a disturbed bile-duct microbiome and failed repair ⁷⁵. That is a hypothesis drawn from existing studies, not a tested result ⁷⁵. One of those five has been measured in people, though only as an association: among 73 hospital patients with the infection and 100 matched healthy controls, the more virulent CagA-positive strains of Helicobacter pylori, the stomach bacterium behind most ulcers, went with having the fluke (odds ratio 3.7, 95% CI 1.2–11.1), alongside the expected raw-fish history (odds ratio 61.1, 22.3–167.9) ⁷⁶. Which came first, and whether the bacterium rides in the worm's gut, that study cannot say. A 2025 preprint, not yet peer reviewed, reports that all three Group 1 liver flukes carry viruses of their own, that the viruses pass to infected hamsters, and that among infected people in endemic areas antibody levels against those viruses separated people with scarring or bile-duct cancer from people with neither ⁷⁷. If it survives review it adds a passenger to the list of suspects; until then it is a result on a server.

How strong the link to cancer is, stated at its true strength

For cholangiocarcinoma the human evidence is consistent across case-control and regional studies, and IARC has judged it sufficient since 2009 ⁸. The 2024 meta-analysis of studies published up to early 2024 found an odds ratio of 4.49 (95% CI 3.43–5.87) for C. sinensis, meaning infected people had about four and a half times the odds of the cancer ¹⁰. Earlier Korean work had pooled to 4.7 (95% CI 2.2–9.8) ⁸. In a Seoul hospital case-control study of 185 patients, imaging signs of the fluke gave an odds ratio of 8.615, a history of eating raw freshwater fish 2.385, and a positive blood test 2.272 ⁶². Single hospital studies have reported odds ratios as high as 13.6 ³. The association also shows up after the cancer exists: in 251 patients with cancer of the ducts inside the liver treated at three Chinese centers, infection went with shorter overall survival and a poorer response to immunotherapy, and their tumors carried more fatty-acid synthase, an enzyme that builds fats, together with more tumor-associated macrophages and weakened T cells; blocking that enzyme reversed the immune suppression in mice ⁷⁸. That is prognosis, not cause.

Translated into cases, the effect is a share of cancers, not a sentence for each infected person ⁸. In 2005, 9.5% of Korean cholangiocarcinomas were attributed to the fluke (12.2% in men, 5.5% in women), rising to 27.9% of men's and 16.2% of women's cases in endemic areas ⁸. In 2000–2004, infection rates of 2.1%, 7.8% and 31.3% in three Korean areas went with bile-duct cancer incidence of 0.3, 1.8 and 5.5 per 100,000 people a year ⁸. Korea's rate of cancer of the bile ducts inside the liver, 4.1 per 100,000 men in 1999–2005, was more than four times the 0.92 and 0.93 per 100,000 recorded for white and Black American men in 1996–2000, and three times the 1.33 per 100,000 recorded for men in England and Wales in 1999–2001; the paper's own summary, which pools both sexes and both comparisons, puts Korea between two and four times higher ⁸. A 2020 review calls the cancer an infrequent outcome of infection ⁴, and a 2016 review projected almost 5,000 fluke-attributed cases a year in East Asia in the coming decades ³⁶.

Cofactors matter, and they muddy the estimate ⁷⁹. Among 127 Chinese patients with fluke-associated cancer compared with 254 infected people without it, eating raw fish for 28 years or more and hepatitis B infection were independent risk factors ⁷⁹. A Chinese case-control study of 200 cancers of the bile duct outside the liver found smoking (odds ratio 1.90), heavy drinking (2.08) and bile-duct stones (6.68) significant, and the fluke, though examined, was not among the significant factors ⁸⁰. The link is clearest for cancer inside the liver in people with long, heavy exposure ⁷⁹. For cancers outside the liver the evidence is split: the Korean case-control study found an association for cancer of the lower bile duct too, with an odds ratio of 6.571 on imaging evidence and 2.6 for eating raw freshwater fish ⁶², and the Chinese one found none ⁸⁰.

The link to hepatocellular carcinoma, the commoner liver cancer that arises from liver cells rather than bile ducts, is weaker and is not part of the IARC classification, which rests on cholangiocarcinoma ⁸. In Hengzhou, Guangxi, 72.4% of 98 patients with hepatocellular carcinoma had antibodies to the fluke, but 64.3% also carried hepatitis B, and comparison rates came from earlier surveys rather than matched controls ¹¹. In 1,386 patients operated on for that cancer in Guangxi, infection was associated with shorter survival (adjusted hazard ratio 1.55, 95% CI 1.20–2.01), which bears on prognosis, not cause ⁸¹. A 2024 systematic review found only three studies of flukes and hepatitis viruses together, with mixed results ¹², and cell studies in which the fluke's granulin made liver-cancer cells more invasive are suggestive, not proof ²⁹. Since then the entanglement has been attacked directly rather than resolved: in 839 operated patients in Guangxi, infection went with advanced stage, more cirrhosis and shorter survival ⁸², and a 2026 study of 269 patients compared tumors from people with the fluke alone, hepatitis B alone and both, finding the doubly infected tumors the most malignant and the most immune-suppressed ⁸³. Both are observational, both come from the same endemic region, and neither separates cause from the company the fluke keeps.

<i>Opisthorchis felineus</i>, the northern relative

O. felineus, described by Rivolta in 1884, belongs to the same family and makes up, with C. sinensis and O. viverrini, the triad of liver flukes that matter for human health ¹. It is the main liver fluke of Russia, Kazakhstan and several European countries, and western Siberia is described as the largest focus of opisthorchiasis in the world ¹⁸. In a community survey published in 2020 from a rural district of Tomsk Oblast, 60.2% of 488 people examined were infected, and river fish (adjusted odds ratio 2.4), dried stockfish (3.2), smoked fish (1.5), frozen fish (1.6) and raw fish (1.4) all raised the odds ²¹. On ultrasound, infection went with gallstones (odds ratio 2.8) and periductal fibrosis (1.9) ²¹. The fluke is old in western Siberia: its eggs sit in the cultural layers of Nadym Gorodok, in the permafrost, from the fourteenth to the late eighteenth century, alongside fish-tapeworm eggs that suggest raw or undercooked fish was ordinary food there for centuries ⁸⁴. Its first genome showed unusually high genetic diversity, which its authors think may let populations adapt faster to control ⁸⁵.

IARC placed it in Group 3 in 1994 ^8,58. Group 3 means not classifiable as to carcinogenicity in humans, a verdict that the evidence was inadequate, not that the fluke is safe ^86,87. Even researchers in the field have described the category as noncarcinogenic, which it is not ⁷³. It remains in Group 3 in 2026 and is not among the 12 infectious agents IARC currently counts in Group 1 ^16,19.

For years the human evidence pointed nowhere ⁶⁴. A review of official statistics from 83 Russian regions for 2011–2013, published in 2016, found no significant correlation between reported O. felineus infection and liver and bile-duct cancer: the two moved together only weakly, and the result was the kind that could easily have arisen by chance (correlation coefficient 0.20, p = 0.07, where anything above 0.05 is conventionally called not significant). It is an ecological comparison, the weakest kind ⁶⁴. The hamster said otherwise: given dimethylnitrosamine as well, every infected animal had cholangiocarcinoma by week 18, and the fluke alone produced changes regarded as precancerous ^88,89. A transplantable cancer cell line was later grown from one such tumor ⁹⁰. Then, in 2023, a hospital case-control study in Tomsk Oblast and Khanty-Mansiysk, with 40 confirmed cholangiocarcinomas and 160 matched controls, found an odds ratio of 3.9 (95% CI 1.4–10.8) for exposure to the fluke, 5.5 for eating river fish and 3.3 for fishing ¹⁷.

That study is small, hospital-based and the first of its kind, and its interval runs from 1.4 to 10.8 ¹⁷. It is also the same kind of human evidence that moved C. sinensis in 2009 ⁸, which is why a 2026 review argues that O. felineus should be reclassified upward ¹⁶. That review is by a single author and is an argument from published studies, not new data ¹⁶. The 2024 meta-analysis included O. felineus in its pooled estimate but reported separate odds ratios only for the other two species ¹⁰, and the network meta-analysis of drug trials found just one trial for it ¹³. Outside its old range it is easily missed: a woman raised in Kazakhstan who had lived in Germany for more than 30 years was diagnosed only after a test abroad, and the authors note recent locally acquired cases in the European Union ⁹¹. Its range is also being redrawn: in 2025 Austrian veterinarians reported the country's first locally acquired infection, in a cat that had never traveled, with eggs in its bile and the species confirmed by DNA ⁹². That is one animal, not a human prevalence figure.

How it is found, and how it is missed

The standard test is finding eggs in stool, usually by the Kato-Katz method, a thick smear of a fixed amount of stool on a glass slide ^2,37. How hard the laboratory looks decides what it finds ⁶³. In 74 infected adults in Guangxi re-examined three weeks after treatment, six Kato-Katz slides from two stool samples found 92.1% of the infections that remained, while two formalin-ether concentration tests found 44.7%, and a single slide of either method overstated the cure rate ⁶³. An automated stool analyzer agreed with Kato-Katz in 96.8% of 1,000 people in Guangdong but less well in light infections ⁹³, and in one Shanghai family with infections acquired in Guangdong, a machine smear missed two of three cases that Kato-Katz found ⁹⁴.

Even a positive slide needs care ⁹⁵. C. sinensis eggs are 25.3–33.2 µm long and 14.2–17.4 µm wide, with a surface wrinkled like a muskmelon; eggs of the intestinal fluke Metagonimus yokogawai, also caught from raw fish, measure 26.9–31.6 by 14.2–18.2 µm ⁹⁵. A comparison of eggs from seven small flukes found great variation within species and great similarity between them, and concluded that shape is not a reliable way to name the species ⁹⁶. In one Korean county, stool surveys found heterophyid fluke eggs in 4.9% of residents and Clonorchis eggs in 3.2%, and only worms recovered after treatment sorted out seven species of intestinal fluke ⁹⁷.

Blood tests look for antibodies ³⁶. In 1,080 hospital patients in Liuzhou, Guangxi, an IgG antibody test detected 78.0% of egg-positive people with 81.9% specificity and missed more of the light infections and the older patients ⁹⁸. Crude worm extracts cross-react with other flukes, although China has approved two antibody test kits ³⁶. Defined recombinant proteins are closing that gap. Against 180 microscopy-confirmed infections and 148 negative blood samples, a laboratory-made copy of one of the worm's cysteine proteases, read with an IgG4 antibody, detected 96.0% of the infections with 90.6% specificity, where a commercial kit on the same samples managed 86.0% and 78.1%, and combinations of three or four such proteins passed 98% on both counts ⁹⁹. A separate 2026 test built on a tandem-repeat protein of the worm reported 95.49% sensitivity and 96.72% specificity in human samples ¹⁰⁰. Both were measured against stool microscopy, which misses light infections, so the true sensitivity of all of them is uncertain.

DNA tests are more sensitive: a LAMP assay, which copies parasite DNA at a single temperature, found 97.1% of infections (95% CI 90.1–99.2) with 100% specificity in Korean stool, down to one egg in 100 mg ¹⁰¹, and a 2023 dipstick test based on recombinase amplification detects a single egg in about 20 minutes ¹⁰². Molecular tests are used mainly in reference laboratories ²³, and the newest of them are still laboratory assays: a 2026 method runs amplification at 37 degrees Celsius for 20 minutes and then raises the tube to 65 degrees, which shuts the amplification down and switches on a CRISPR enzyme that both reads the result and destroys the copies, so that one sealed tube gives an answer without the contamination that dogs these methods ¹⁰³. Its authors report no test on patient samples, and a 2026 Chinese review of the whole class, from PCR and LAMP to CRISPR methods and high-throughput sequencing, likewise describes them as laboratory tools ^103,104.

Imaging helps but cannot confirm ³⁶. In 457 villagers in northeastern China, increased brightness of the duct walls on ultrasound was 35% sensitive and 91% specific for active infection, and diffuse widening of the ducts inside the liver 67% sensitive and 48% specific ¹⁰⁵. Duct changes that persist after cure can produce a false-positive scan ³. In endemic areas any of eggs, DNA or characteristic images may be taken as grounds for treatment ⁷. Sometimes the worm is the test: three Brooklyn patients who had emigrated from China were diagnosed when a worm was seen and removed during ERCP, two of them after repeatedly negative stool tests ¹⁰⁶.

• Stool microscopy for eggs (Kato-Katz thick smear)A fixed amount of stool is smeared thickly on a slide and searched for eggs; it is the method surveys and treatment programs are built on ^2,37.The standard test in endemic China and Korea, and the reference against which every other test is judgedAmong 74 treated adults in Guangxi, six slides from two stools found 92.1% of the infections that remained, while two formalin-ether concentration tests found 44.7% ⁶³.Light infections, and the species: C. sinensis eggs overlap in size with those of intestinal flukes caught from the same fish ^95,96. A single slide overstates cure after treatment ⁶³.
• Antibody blood test (IgG ELISA)A color-change laboratory test, an ELISA, that detects the antibodies the body makes against fluke proteins; two kits are approved in China ³⁶.Screening in endemic areas, and sometimes the first clue in a non-endemic countryAgainst stool eggs in 1,080 patients in Liuzhou, Guangxi, 78.0% sensitive and 81.9% specific ⁹⁸.More light infections and more infections in older people ⁹⁸; crude worm extracts cross-react with other flukes ³⁶. Germany has no certified test for the related opisthorchiasis ⁹¹.
• DNA tests of stool (PCR and related methods)These copy a stretch of the fluke's own DNA millions of times until it can be detected, which also tells the species apart; the field versions, LAMP and RPA, work at a single temperature ^23,36.Research and reference laboratories; not yet routine ²³A LAMP assay found 97.1% of infections (the range compatible with the data was 90.1–99.2%) with 100% specificity in Korean stool ¹⁰¹; a recombinase dipstick test detects a single egg in about 20 minutes ¹⁰².Their accuracy has mostly been measured on samples where older tests already agreed, and the dipstick test was checked on 40 human stools ^101,102.
• Imaging: ultrasound, CT, MRI and ERCPUltrasound shows widened ducts and bright duct walls; ERCP, an endoscope passed to the bile duct, can see and remove the worm ^105,106.Assessing damage in endemic areas; in North America, sometimes how an infection missed by stool testing is finally found ¹⁰⁶Bright duct walls were 35% sensitive and 91% specific for active infection, and widened ducts 67% sensitive and 48% specific, in 457 villagers in northeastern China ¹⁰⁵.Imaging cannot name the parasite, and duct changes that persist after cure can look like active infection ^3,36.

What is done about it

Praziquantel, a drug that kills flukes, is the treatment of choice, and the regimen WHO recommends is 25 mg/kg three times a day for two days ^2,13. A 2022 network meta-analysis of 18 trials in C. sinensis predicted a 98.5% cure rate for that regimen (95% CI 85.4–99.9), and the same analysis predicted high cure for long albendazole courses, while warning that most trials were of low quality and at high risk of bias ¹³. That albendazole figure has since been overturned: in a 2026 randomized trial of 102 infected adults in Binyang county, Guangxi, albendazole 400 mg twice a day for four days cured 19.6% (10 of 51), against 72.9% (35 of 48) for praziquantel at 25 mg/kg three times in one day, and cure fell with worm burden, to 8.0% for albendazole in moderate and heavy infections; egg counts still fell 98.3% under albendazole, and side effects were half as common as with praziquantel (17.6% against 33.3%) ¹⁵. Trials that tested cure more strictly used shorter or lower-dose regimens, and found lower cure ^14,107. In a 2013 randomized trial in Guangxi that used several stool slides per person, praziquantel at 75 mg/kg in one day cured 56% ¹⁴, and in a 2014 trial in Hunan a two-day course cured 56.8% at first and 75% after a second round ¹⁰⁷. A 1997 Vietnamese pilot of 25 mg/kg once daily for three days cured only 29% ³⁶.

Tribendimidine, approved in China in 2004 for intestinal roundworms, was for a decade the main alternative under study ⁶¹. In the 2013 trial a single 400 mg dose cured 44% and a three-day course 58%, egg counts fell 97.6–98.8% under every regimen, and patients given praziquantel had significantly more side effects ¹⁴. In the Hunan trial a single dose cured 50% at first and 78.1% after a second round ¹⁰⁷. These trials and the reviews that recommend developing the drug share authors from the Chinese Center for Disease Control and Prevention and the Swiss Tropical and Public Health Institute, an academic stake rather than a commercial one ^13,14,23. Since those trials tribendimidine has not been tested again in people, and the search has moved on. Albendazole has now been through a randomized trial ¹⁵; in a retrospective series of 151 patients treated for fluke-related liver lesions, praziquantel cured 90.0% of stool-confirmed cases against 62.5% for albendazole, while the two looked alike in stool-negative suspected cases, a retrospective comparison its authors call hypothesis-generating ¹⁰⁸. In animals, ivermectin killed larval stages that praziquantel handles poorly ¹⁰⁹, adding curcumin to praziquantel lowered worm recovery and bile-duct widening in rats ¹¹⁰, and adding a Lactobacillus to praziquantel in mice took the scarred area of the liver to 6.0%, against 12.2% with praziquantel alone and 21.8% in untreated infected animals ¹¹¹. All of that is rat and mouse work, with no human trial ^109,110,111.

Control means treating whole communities, or everyone found infected, and teaching people about raw fish, because the habit persists after the worms are gone ^23,36. WHO's Western Pacific office recommends mass drug administration where prevalence exceeds 10% ³. In Heilongjiang, China, four annual mass treatments from 2001 to 2004 cut prevalence from 48.0% to 8.4%, and treatment of the egg-positive every six months from 59.5% to 7.5% ¹¹². In Sancheong County, Korea, adding health education for community leaders to treatment lowered prevalence from 29.6% to 6.8% over three years, against 31.1% to 14.9% with the national program alone ¹¹³. Newer ideas include vaccinating farmed fish and biological control of snails ²³.

What treatment does to cancer risk is unmeasured ¹³. The trials above recorded cure and egg reduction a few weeks after the drug, not cancer ^13,14. Mild duct widening and fibrosis persist for more than a year after cure, and 40.6% of treated, infected people followed in one Guangxi community were reinfected within a year ³. Korean analysts noted that bile-duct cancer kept rising in heavily infected areas even though praziquantel was effective, and pointed to repeated eating of raw freshwater fish ⁸.

Why most people who carry it in North America are never tested

The fluke cannot complete its life cycle in North America, because the snails and fish it needs do not live there ²⁵, so infections found here were almost always acquired in endemic countries. A review of food-borne fluke infections in the United States from 1890 to 2009 found the literature dominated by imported cases of C. sinensis and O. viverrini ²⁶. The result is a disease with no local outbreaks to prompt testing and no place on most doctors' lists of likely diagnoses; clinicians in Germany, facing the same situation with O. felineus, wrote in 2026 that liver flukes are usually not among the first diagnoses considered ⁹¹.

Infection is usually silent, and it lasts ^3,27. The worm can live about 30 years ³. A Minnesota clinic serving international patients found that a quarter of its 17 liver-fluke cases over six years were diagnosed after more than five years in the United States, and often the only clue was a mild rise in eosinophils, a white blood cell that rises with worm infections, to between 500 and 1,000 per microliter ²⁷. In 1984 a North Carolina study of 26 Laotian refugees infected with Clonorchis or Opisthorchis found no differences in symptoms or examination from 15 uninfected controls, and none on ultrasound in the six infected people scanned, and concluded that the fluke might not need eradicating ⁶⁰.

Estimates have varied widely ^27,114. A 1986 report counted more than 500,000 Southeast Asian refugees arriving in the United States since 1975 and cited surveys finding active liver-fluke infection in up to 26% of Asian immigrants; it described an elderly Chinese immigrant whose bile-duct cancer came with an infection no one had suspected ¹¹⁴. Two decades later a Minnesota clinic found liver flukes in only 1.3% of immigrants carrying a potentially pathogenic organism ²⁷. Minnesota's refugee health form in 1999 asked specifically about clonorchiasis among eight parasites, yet the commonest findings reported were whipworm and giardia ¹¹⁵. The Minnesota clinicians pointed beyond new arrivals to community members at continuing risk and to people visiting friends and relatives in endemic areas, and their cases came from Laos, Cambodia, Thailand, the former Soviet Union and South America ²⁷.

One North American group has been screened on purpose. At a Veterans Affairs medical center in Northport, New York, 97 Vietnam veterans were asked about eating raw or undercooked river fish during their service; of the 50 who had, 24% carried antibodies to liver fluke on a multi-antigen blood test run in Seoul, those who tested positive passed no eggs in stool, and one of the 50 had already been found to have bile-duct cancer ¹¹⁶. Antibodies record exposure, not a living worm, and 50 men with no comparison group prove nothing about cancer risk, and the authors call for further research rather than claiming one ¹¹⁶. Two Veterans Affairs physicians argued in 2023 that with about 774,000 living Americans having served in Vietnam, there is an unmet need for a test that can find a silent infection decades later; that is an argument, not data ¹¹⁷.

When someone is tested, the test may miss it ¹⁰⁶. Two of three Brooklyn patients diagnosed at ERCP had repeatedly negative stool examinations, and their infections were found because imaging showed abnormal bile ducts ¹⁰⁶. A single stool slide misses a large share of light infections ⁶³, a machine smear can miss what a careful manual one finds ⁹⁴, and in Germany there is no certified antibody test for opisthorchiasis ⁹¹. In the 1986 report, the infection was recognized only once the cancer was ¹¹⁴.

What was believed, and is not

This fluke's record contains more corrections than most, because it moved from one IARC group to another and its relative may yet do the same ^8,16. Several of the corrections are about dates and numbers that are repeated loosely, and several are about tests and treatments that look more certain on paper than they are in a clinic ^13,63. The cards below give each correction with the study that made it.

None of this weakens the core finding ¹⁰. C. sinensis is a Group 1 carcinogen for bile-duct cancer on human evidence, with pooled odds ratios between about 4 and 5 ^8,10. What the corrections change is the shape around that finding: when it was reached, how many people it concerns, which cancer it applies to, and how much a negative test or a course of tablets can be trusted ^3,11.

What is still unknown, and where this leaves the season's question

The first unknown is the count. China alone was estimated at 9.46 million infections in 2020, a 2012 review put the world at 15–20 million, and Korea has not run a national survey since 2012 ^6,7,45. A 2024 review lists mapping the current distribution and estimating the burden accurately among the field's most pressing needs ²³. North American figures come from refugee surveys of the 1980s, clinic series and one deliberate screening of Vietnam veterans, not from population studies ^27,114,116.

The second is whether treatment prevents cancer. Drug trials end with a stool test a few weeks later ¹³, duct changes outlast the worms, and reinfection is common ³. Whether treatment, given again and again against reinfection, lowers cancer risk, and by how much, has not been measured for this fluke ^3,13. The third is mechanism: why only a minority of heavily infected people develop cancer, whether the fluke can start cancer on its own as one rat study suggests, and how much dietary nitrosamines, hepatitis B and alcohol contribute ^35,75,79. The fourth is liver-cell cancer, where the evidence is too entangled with hepatitis B to call ^11,12. A 2026 review of the molecular work puts the practical state of it plainly: the circulating microRNAs, methylation patterns, proteins, metabolites and worm antigens offered as early warnings of precancerous change have all been measured in small single-center groups, with no multi-center prospective test and no agreed protocol, while imaging and biopsy catch the early changes poorly ¹¹⁸.

The fifth is O. felineus. One case-control study of 40 cancers is a start, and even the review arguing for reclassification calls for more epidemiological, clinical and pathological studies ^16,17. Why three closely related flukes should differ in cancer risk at all is itself unexplained: side-by-side hamster infections show species-specific liver responses, but did not test the long infections or added nitrosamines that their authors name as the next step ^72,73. Its unusually diverse genome and its spread beyond its old range add urgency to the question ^85,91.

For the season, this fluke is a clear case of a cancer count that rose because people looked ⁸. In 1994 the human evidence was limited; by 2009, after Korean case-control studies and regional comparisons, it was sufficient ^3,8. O. felineus now stands roughly where C. sinensis stood in 1994, with strong animal data and one human study ^17,88. The honest size of the effect is a share of one cancer: about one Korean bile-duct cancer in ten, and about one in four among men in endemic areas ⁸. Northeastern Thailand, the place most often cited for bile-duct cancer, is the territory of O. viverrini, a different species with a different map ⁴⁸. IARC researchers have described fluke-related bile-duct cancer as confined to the endemic regions, and the other, rarer form as present worldwide in people who often have no known risk factor at all, so neither fluke supports the idea that most bile-duct cancer elsewhere is parasitic ¹¹⁹.

Where it connects

Sources

119 sources, numbered as they are cited. Every one was checked against PubMed or its publisher before it was cited here; the note under each says what it shows and what it does not.

1. 1
   Pakharukova MY, Mordvinov VA. Similarities and differences among the Opisthorchiidae liver flukes: insights from Opisthorchis felineus.Parasitology · 2022 · 149(10):1306-1318doi:10.1017/S0031182022000397 · PMID 35570685

   Comparative review of the three flukes by the Novosibirsk group that leads O. felineus research, giving the species authorities and the classification gap; it asks whether the three really differ in carcinogenicity and does not settle it.

2. 2
   Qian MB, Utzinger J, Keiser J, Zhou XN. Clonorchiasis.Lancet · 2016 · 387(10020):800-10doi:10.1016/S0140-6736(15)60313-0 · PMID 26299184

   The standard clinical seminar, opening with McConnell's 1875 Calcutta post-mortem and naming Kato-Katz stool examination and praziquantel as the working tools; it states plainly that the exact number infected and the global burden are unknown.

3. 3
   Kim EM, Hong ST. Clonorchis sinensis and Cholangiocarcinoma.J Korean Med Sci · 2025 · 40(16):e145doi:10.3346/jkms.2025.40.e145 · PMID 40296827

   Review read in full, covering worm biology, Korea's survey history, the 1994-to-2009 reclassification and the hamster and cell evidence; much of what it summarizes is the senior author's own group's work, and it adds no new data.

4. 4
   Na BK, Pak JH, Hong SJ. Clonorchis sinensis and clonorchiasis.Acta Trop · 2020 · 203:105309doi:10.1016/j.actatropica.2019.105309 · PMID 31862466

   Review naming the dishes that transmit the fluke and describing cholangiocarcinoma as an infrequent outcome whose mechanism is not worked out in detail.

5. 5
   Nakano M, Kawaguchi M, Kondo R, Akiba J, Kawaguchi T. A case of hypovascular hepatic lesion with suspected clonorchiasis.Clin J Gastroenterol · 2025 · 19(1):71-77doi:10.1007/s12328-025-02233-9 · PMID 41263943

   A single Japanese case with no travel history, diagnosed on dietary history, weakly positive serology and biopsy rather than on eggs, so the species identification is probable rather than proven.

6. 6
   Qian MB, Huang JL, Wang L, et al. Clonorchiasis in China: Geospatial modeling of the population infected and at risk, based on national surveillance.J Infect · 2025 · 91(1):106528doi:10.1016/j.jinf.2025.106528 · PMID 40472937

   The best current national estimate, 9.46 million infected in China in 2020, modeled from 2016–2021 surveillance; a model, with its credible interval, rather than a census.

7. 7
   Hong ST, Fang Y. Clonorchis sinensis and clonorchiasis, an update.Parasitol Int · 2012 · 61(1):17-24doi:10.1016/j.parint.2011.06.007 · PMID 21741496

   The source of the much-repeated 200 million at risk and 15–20 million infected, which are estimates rather than survey results; it also describes treating on any evidence of infection in endemic areas.

8. 8
   Shin HR, Oh JK, Lim MK, et al. Descriptive epidemiology of cholangiocarcinoma and clonorchiasis in Korea.J Korean Med Sci · 2010 · 25(7):1011-6doi:10.3346/jkms.2010.25.7.1011 · PMID 20592891

   Read in full: it records the 1994 Group 2A rating for limited human evidence and the February 2009 move to Group 1, and attributes 9.5% of Korean cholangiocarcinoma in 2005 to the fluke; the lead author was at IARC, and the attributable fraction rests on a 1981 prevalence figure.

9. 9
   IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Biological agents.IARC Monogr Eval Carcinog Risks Hum · 2012 · 100(Pt B):1-441PMID 23189750

   Volume 100B, the 441-page monograph printed in 2012 that carries the 2009 evaluations; no abstract is held in PubMed.

10. 10
    Huang YL, Zhang KY, Sun YL, Qian MB, Wang Z. The risk of hepatobiliary complications in Clonorchis and Opisthorchis infection: A systematic review and meta-analysis.Acta Trop · 2024 · 260:107457doi:10.1016/j.actatropica.2024.107457 · PMID 39521195

    The largest pooled analysis, 22 studies and 34,367 participants, giving an odds ratio of 4.49 for C. sinensis and cholangiocarcinoma; it pools observational studies of mixed quality and reports no separate estimate for O. felineus.

11. 11
    Yang QL, Lu XW, Fang ZL, et al. The association between Clonorchis sinensis seropositivity and hepatocellular carcinoma in an endemic area: a study in Guangxi, China.BMC Infect Dis · 2025 · 25(1):270doi:10.1186/s12879-025-10675-2 · PMID 40000979

    High fluke antibody rates among 98 liver-cell cancer patients in Hengzhou, most of them also carrying hepatitis B; comparison rates were taken from earlier surveys rather than matched controls.

12. 12
    O'Rourke A. A systematic review of the effects of hepatitis B and C virus on the progression of liver fluke infection to liver cancer.Trop Dis Travel Med Vaccines · 2024 · 10(1):6doi:10.1186/s40794-023-00215-8 · PMID 38486298

    Single-author systematic review that found only three eligible studies on flukes with hepatitis viruses, with mixed results; too thin to settle anything.

13. 13
    Qian MB, Patel C, Palmeirim MS, et al. Efficacy of drugs against clonorchiasis and opisthorchiasis: a systematic review and network meta-analysis.Lancet Microbe · 2022 · 3(8):e616-e624doi:10.1016/S2666-5247(22)00026-X · PMID 35697047

    Network meta-analysis of 26 trials predicting high cure rates for praziquantel and long albendazole courses while rating most trials low quality; its outcomes are cure and egg reduction, not cancer.

14. 14
    Qian MB, Yap P, Yang YC, et al. Efficacy and safety of tribendimidine against Clonorchis sinensis.Clin Infect Dis · 2013 · 56(7):e76-82doi:10.1093/cid/cis1011 · PMID 23223597

    Randomized open-label trial in 74 patients in Guangxi, with strict stool testing, finding cure rates of 44–58% for every regimen including praziquantel; small and unblinded.

15. 15
    Qian MB, Zhao JG, Han XP, Liu L, Zhou CH, Huang JL, Zhu YY, Gan XQ, Meng J, Li SZ. Efficacy and safety of albendazole versus praziquantel in the treatment of Clonorchis sinensis infection: an infection intensity-stratified, open-label, phase 2, randomized controlled trial.BMC Med · 2026 · online ahead of printdoi:10.1186/s12916-026-05071-9 · PMID 42477738

    ISRCTN46268871. The first randomized comparison of albendazole with praziquantel in this fluke: albendazole cured few but cut egg counts and caused fewer side effects, which its authors read as a possible morbidity-control drug rather than a cure. Open-label, 102 patients in one county, and by the same Chinese CDC and Swiss Tropical and Public Health Institute group that ran the tribendimidine trials, an academic rather than a commercial stake.

16. 16
    Jain S. Exploring the potential role of Opisthorchis felineus infection in cholangiocarcinogenesis.Mol Biochem Parasitol · 2026 · 266:111733doi:10.1016/j.molbiopara.2026.111733 · PMID 41587590

    Single-author review stating O. felineus's current Group 3 rating and arguing for an upgrade; an argument from published studies, not new data.

17. 17
    Fedorova OS, Kovshirina AE, Kovshirina YV, et al. Opisthorchis Felineus Infection is a Risk Factor for Cholangiocarcinoma in Western Siberia: A Hospital-based Case-control Study.Clin Infect Dis · 2023 · 76(3):e1392-e1398doi:10.1093/cid/ciac497 · PMID 35723279

    The first human case-control evidence for O. felineus and bile-duct cancer, an odds ratio of 3.9 in 40 cases and 160 controls; small, hospital-based and partly reliant on recalled past infection.

18. 18
    Pakharukova MY, Mordvinov VA. The liver fluke Opisthorchis felineus: biology, epidemiology and carcinogenic potential.Trans R Soc Trop Med Hyg · 2016 · 110(1):28-36doi:10.1093/trstmh/trv085 · PMID 26740360

    Review calling western Siberia the world's largest opisthorchiasis focus and the fluke's cancer potential poorly studied; its suggested cancer association comes from Russian clinical literature, not a controlled study.

19. 19
    Rumgay H, Georges D, Huang Y, et al. Global burden of cancer attributable to infections in 2024: a worldwide incidence analysis.Lancet Oncol · 2026 · 27(10):1237-1248doi:10.1016/S1470-2045(26)00307-4 · PMID 42805198

    IARC's own 2026 analysis, which lists the 12 infectious agents in Group 1 with C. sinensis among them; its abstract gives no separate cancer count for the fluke.

20. 20
    Han XP, Zhu TJ, Liu L, et al. Disentangling the transmission of Clonorchis sinensis: A one health approach.One Health · 2025 · 21:101249doi:10.1016/j.onehlt.2025.101249 · PMID 41292614

    A 2024–2025 survey of five Guangxi villages, 30.50% of people infected, linking infected cats and dogs to human risk; cross-sectional and confined to one county.

21. 21
    Fedorova OS, Fedotova MM, Zvonareva OI, et al. Opisthorchis felineus infection, risks, and morbidity in rural Western Siberia, Russian Federation.PLoS Negl Trop Dis · 2020 · 14(6):e0008421doi:10.1371/journal.pntd.0008421 · PMID 32598389

    Community survey in one rural Tomsk district finding 60.2% infected and linking infection to gallstones and periductal fibrosis on ultrasound; cross-sectional, so it cannot show which came first.

22. 22
    Wang X, Chen W, Huang Y, et al. The draft genome of the carcinogenic human liver fluke Clonorchis sinensis.Genome Biol · 2011 · 12(10):R107doi:10.1186/gb-2011-12-10-r107 · PMID 22023798

    The first C. sinensis genome, 516 megabases with about 16,000 genes, lacking key fatty-acid-making genes; a draft assembly, with candidate drug targets that remain candidates.

23. 23
    Qian MB, Keiser J, Utzinger J, Zhou XN. Clonorchiasis and opisthorchiasis: epidemiology, transmission, clinical features, morbidity, diagnosis, treatment, and control.Clin Microbiol Rev · 2024 · 37(1):e0000923doi:10.1128/cmr.00009-23 · PMID 38169283

    The current reference review of all three liver flukes, a narrative synthesis with no new numbers; its authors include investigators who ran the tribendimidine trials it recommends developing, an academic rather than a commercial interest.

24. 24
    Nguyen PTX, Van Hoang H, Dinh HTK, et al. Insights on foodborne zoonotic trematodes in freshwater snails in North and Central Vietnam.Parasitol Res · 2021 · 120(3):949-962doi:10.1007/s00436-020-07027-1 · PMID 33426572

    Molecular identification of Parafossarulus striatulus as the fluke's snail host at Thac Ba Lake in Vietnam; one site.

25. 25
    Reinhard KJ, Araújo A, Sianto L, Costello JG, Swope K. Chinese liver flukes in latrine sediments from Wong Nim's property, San Bernardino, California: archaeoparasitology of the Caltrans District Headquarters.J Parasitol · 2008 · 94(1):300-3doi:10.1645/GE-1049.1 · PMID 18372657

    Fluke eggs in Chinese-American latrines of about 1880 to the 1930s, with the statement that the parasite cannot complete its life cycle in the Americas because its intermediate hosts are absent.

26. 26
    Fried B, Abruzzi A. Food-borne trematode infections of humans in the United States of America.Parasitol Res · 2010 · 106(6):1263-80doi:10.1007/s00436-010-1807-0 · PMID 20352454

    Literature review of fluke infections reported in the United States from 1890 to 2009, mostly imported C. sinensis and O. viverrini; it collects case reports and cannot estimate how many go unreported.

27. 27
    Stauffer WM, Sellman JS, Walker PF. Biliary liver flukes (Opisthorchiasis and Clonorchiasis) in immigrants in the United States: often subtle and diagnosed years after arrival.J Travel Med · 2004 · 11(3):157-9PMID 15710057

    Seventeen cases over six years at a Minnesota international clinic, a quarter found after five years in the country; a clinic series, not a prevalence survey.

28. 28
    Smout MJ, Laha T, Chaiyadet S, Brindley PJ, Loukas A. Mechanistic insights into liver-fluke-induced bile-duct cancer.Trends Parasitol · 2024 · 40(12):1183-1196doi:10.1016/j.pt.2024.10.012 · PMID 39521672

    Review by the groups behind the O. viverrini gene-editing work, treating C. sinensis and O. viverrini together; a synthesis that leans on the better-studied O. viverrini.

29. 29
    Wang C, Lei H, Tian Y, et al. Clonorchis sinensis granulin: identification, immunolocalization, and function in promoting the metastasis of cholangiocarcinoma and hepatocellular carcinoma.Parasit Vectors · 2017 · 10(1):262doi:10.1186/s13071-017-2179-4 · PMID 28545547

    Identifies the fluke's granulin growth factor and shows it makes liver and bile-duct cancer cell lines more mobile and invasive; cell lines and mice, not people.

30. 30
    Chaiyadet S, Tangkawattana S, Smout MJ, et al. Knockout of liver fluke granulin, Ov-grn-1, impedes malignant transformation during chronic infection with Opisthorchis viverrini.PLoS Pathog · 2022 · 18(9):e1010839doi:10.1371/journal.ppat.1010839 · PMID 36137145

    CRISPR-edited O. viverrini lacking granulin caused less fibrosis, fewer TP53 mutations and fewer high-grade cancers in hamsters; the strongest causal test for any liver-fluke protein, done in the Thai species, not this one.

31. 31
    Liu T, Gao H, Wang N, et al. Clonorchis sinensis excretory secretory products promote hepatic fibrosis through stimulating biliary epithelium to secrete IL-17A.PLoS Negl Trop Dis · 2026 · 20(5):e0014280doi:10.1371/journal.pntd.0014280 · PMID 42085509

    Shows fluke secretions driving bile-duct cells to release interleukin-17A, which activates scar-forming cells, in cells, organoids and mice, with higher levels in infected patients; a fibrosis pathway, not a cancer endpoint.

32. 32
    Lee JH, Rim HJ, Bak UB. Effect of Clonorchis sinensis infection and dimethylnitrosamine administration on the induction of cholangiocarcinoma in Syrian golden hamsters.Korean J Parasitol · 1993 · 31(1):21-30doi:10.3347/kjp.1993.31.1.21 · PMID 8390293

    The founding C. sinensis hamster experiment: cancer in 6 of 8 animals given the nitrosamine and the fluke, and only overgrowth of the lining with either alone; very small groups.

33. 33
    Uddin MH, Choi MH, Kim WH, Jang JJ, Hong ST. Involvement of PSMD10, CDK4, and Tumor Suppressors in Development of Intrahepatic Cholangiocarcinoma of Syrian Golden Hamsters Induced by Clonorchis sinensis and N-Nitrosodimethylamine.PLoS Negl Trop Dis · 2015 · 9(8):e0004008doi:10.1371/journal.pntd.0004008 · PMID 26313366

    Hamster model in which every animal given the fluke and the nitrosamine developed cholangiocarcinoma from week 8, with altered cancer genes; animal evidence, and it needs the chemical.

34. 34
    Uddin MH, Li S, Jin Y, Choi MH, Jang JJ, Hong ST. C3H/He Mice as an Incompatible Cholangiocarcinoma Model by Clonorchis sinensis, Dicyclanil and N-Nitrosodimethylamine.Korean J Parasitol · 2016 · 54(3):281-9doi:10.3347/kjp.2016.54.3.281 · PMID 27417082

    A negative result: mice given the fluke and two chemicals developed fibrosis but no cholangiocarcinoma, which shows how host-dependent the animal evidence is.

35. 35
    Li S, Jiang Y, Kawanokuchi J, et al. Exploratory study on the role of Clonorchis sinensis infection in promoting cholangiocarcinoma progression.Parasit Vectors · 2025 · 19(1):29doi:10.1186/s13071-025-07183-2 · PMID 41366458

    A rat model reporting cholangiocarcinoma in 37% of animals with the fluke alone and up to 71% with a nitrosamine; a single exploratory study in one strain, not yet replicated.

36. 36
    Tang ZL, Huang Y, Yu XB. Current status and perspectives of Clonorchis sinensis and clonorchiasis: epidemiology, pathogenesis, omics, prevention and control.Infect Dis Poverty · 2016 · 5(1):71doi:10.1186/s40249-016-0166-1 · PMID 27384714

    Review read in full for country prevalence figures, treatment results and the limits of each test; its figures are compiled from earlier surveys rather than newly measured.

37. 37
    Zhu TJ, Chen YD, Qian MB, et al. Surveillance of clonorchiasis in China in 2016.Acta Trop · 2020 · 203:105320doi:10.1016/j.actatropica.2019.105320 · PMID 31877282

    National surveillance at 301 points in 2016, 2.04% infected by Kato-Katz; surveillance points are not a random sample of the country.

38. 38
    Qian MB, Wang L, Huang JL, et al. Disability-adjusted life years of clonorchiasis in China: a high-resolution spatial analysis.Infect Dis Poverty · 2025 · 14(1):126doi:10.1186/s40249-025-01396-4 · PMID 41437397

    China's 2020 burden of 431,009 disability-adjusted life years, including the years of life lost to fluke-attributed cholangiocarcinoma; built on modeled prevalence and assumed disability weights.

39. 39
    Liu L, Zhu HH, Huang JL, Han XP, Qian MB, Yang K, Zhou XN. Spatiotemporal epidemiological characteristics of human clonorchiasis in China.Acta Trop · 2025 · 271:107832doi:10.1016/j.actatropica.2025.107832 · PMID 40935004

    Spatial statistics built on historical literature and the three national surveys, so its resolution is that of the underlying surveys.

40. 40
    Zhang Y, Jiang T, Ma X, Chen W, Dong D, Zhang B, Deng Y. First Local Cluster of Clonorchiasis Caused by Consumption of Raw Freshwater Fish - Zhengzhou City, Henan Province, China, 2026.China CDC Wkly · 2026 · 8(35):1112-1116doi:10.46234/ccdcw2026.180 · PMID 42756775

    Five cases confirmed by the provincial center; an outbreak report, which says nothing about how common such clusters are.

41. 41
    Jiang JN, Dong HF, Cheng HD, Zou H, Li M, Li WX, Wang GT. Infection with Clonorchis sinensis (Cobbold, 1875) Metacercariae in Fish from the East Lake of Wuhan: Freshwater Fish in Urban Lakes May Act as Infection Sources of Liver Fluke.Microorganisms · 2024 · 12(5):898doi:10.3390/microorganisms12050898 · PMID 38792728

    Carries the species authority in its title, and separately reports cysts in 32.5% of fish surveyed in an urban lake in a city outside the endemic zone.

42. 42
    Kim TS, Pak JH, Kim JB, Bahk YY. Clonorchis sinensis, an oriental liver fluke, as a human biological agent of cholangiocarcinoma: a brief review.BMB Rep · 2016 · 49(11):590-597doi:10.5483/bmbrep.2016.49.11.109 · PMID 27418285

    Brief review reporting the 2012 Korean national survey, where the fluke was the most prevalent parasite at 1.86%; no new data.

43. 43
    Lee MR, Ju JW, Baek SO, Lee YJ, Lee ES, Lee HI. [Infection Status of Intestinal Helminths in 2023].Jugan Geongang Gwa Jilbyeong (Public Health Weekly Report, KDCA) · 2024 · 17(28):1227-1239doi:10.56786/PHWR.2024.17.28.2 · PMID 41332928

    Korean-language agency report with an English abstract; the species names are stripped from the PubMed abstract and appear only in the keywords, so confirm the 1.9% figure belongs to this fluke at the publisher before printing it. Residents of endemic areas, not a national sample.

44. 44
    Kim TY, Lee MR, Ju JW, Baek SO, Lee YJ, Lee E, Lee HI. [Survey on Intestinal Helminth Infections in the Endemic Regions, 2024].Jugan Geongang Gwa Jilbyeong (Public Health Weekly Report, KDCA) · 2025 · 18(19):707-719doi:10.56786/PHWR.2025.18.19.1 · PMID 41334056

    Same caveats: endemic-region screening rather than a national survey, and the species names are stripped from the PubMed abstract.

45. 45
    Lee T, Lee JH, Jin H, Lee YK, Song HB. Assessing trends in clonorchiasis incidence via prescription data analysis in South Korea.BMC Public Health · 2025 · 25(1):2873doi:10.1186/s12889-025-23893-9 · PMID 40841887

    Uses national drug-prescription records to show Korean incidence falling from 2002 to 2023 and notes there has been no nationwide survey since 2012; prescriptions measure treatment, not infection.

46. 46
    Yoo WG, Sohn WM, Na BK. Current status of Clonorchis sinensis and clonorchiasis in Korea: epidemiological perspectives integrating the data from human and intermediate hosts.Parasitology · 2022 · 149(10):1296-1305doi:10.1017/S0031182022000798 · PMID 35698752

    Review finding transmission alive in five major Korean river basins, with fish still carrying cysts and mild infections becoming more common; a synthesis, not new surveys.

47. 47
    Jung SM, Kang H, Jung BK, Ju S, Ju JW, Lee MR, Kim JH, Kim SH. Age, period, and cohort effects of Clonorchis sinensis infection prevalence in the Republic of Korea: Insights and projections.PLoS Negl Trop Dis · 2024 · 18(10):e0012574doi:10.1371/journal.pntd.0012574 · PMID 39392863

    A model fitted to the 1981–2012 national surveys; its 2023 figures are projections, not measurements.

48. 48
    Sripa B, Suwannatrai AT, Sayasone S, et al. Current status of human liver fluke infections in the Greater Mekong Subregion.Acta Trop · 2021 · 224:106133doi:10.1016/j.actatropica.2021.106133 · PMID 34509453

    Regional review putting northern Vietnam and Guangxi at 3.5–5 million infections and mapping where C. sinensis gives way to O. viverrini; estimates compiled from surveys of varying quality.

49. 49
    Bogatov VV, Besprozvannykh VV, Prozorova LA. Harmful Parasitoses on the Russian Southern Far East under Climatic and Demographic Changes.Dokl Biol Sci · 2019 · 487(1):108-111doi:10.1134/S0012496619040033 · PMID 31571077

    Russian ecologists' report that the fluke had been spreading, more slowly of late, from the Amur basin into southern Primorye for 10 to 15 years; it gives no human prevalence figures.

50. 50
    Liu L, Lu LD, Yang GJ, et al. Global, regional and national disease burden of food-borne trematodiases: projections to 2030 based on the Global Burden of Disease Study 2021.Infect Dis Poverty · 2024 · 13(1):95doi:10.1186/s40249-024-01265-6 · PMID 39676162

    Global Burden of Disease figures for all food-borne trematode infections together, 44,466,329 cases in 2021; it does not separate C. sinensis.

51. 51
    Robertson LJ, Minato Y, Devleesschauwer B, et al. WHO estimates of the global, regional, and national foodborne burdens of 14 invasive parasitic diseases, 2000-21: an updated data synthesis.Lancet Glob Health · 2026 · 14(8):103982doi:10.1016/j.langlo.2026.103982 · PMID 42302806

    WHO's 2026 update ranking C. sinensis second among invasive foodborne parasites by burden and the Western Pacific as the one region where burden is rising; modeled, with wide uncertainty.

52. 52
    Wu Z, Guan Y, Zhou Z. [Study of an ancient corpse of the Warring States period unearthed from Tomb No. 1 at Guo-Jia Gang in Jingmen City (A comprehensive study)].J Tongji Med Univ · 1996 · 16(1):1-5, 10doi:10.1007/BF02889033 · PMID 8758736

    German-language report, with an English abstract, of a woman buried more than 2,300 years ago whose bowel held fluke and whipworm eggs; the identification rests on egg appearance alone.

53. 53
    Oh CS, Chai JY, Min S, et al. Updates on parasite infection prevalence in the Joseon period based on parasitological studies of human coprolites isolated from archaeological sites in the cities of Euijeongbu, Gumi, and Wonju.Parasites Hosts Dis · 2023 · 61(1):89-93doi:10.3347/PHD.22129 · PMID 37170469

    Thirty Joseon-period coprolites, 30.0% of them with fluke eggs; a small archaeological sample, not an estimate for the population.

54. 54
    Zhan X, Yeh HY, Shin DH, Chai JY, Seo M, Mitchell PD. Differential Change in the Prevalence of the Ascaris, Trichuris and Clonorchis infection Among Past East Asian Populations.Korean J Parasitol · 2019 · 57(6):601-605doi:10.3347/kjp.2019.57.6.601 · PMID 31914511

    Historical comparison showing the fluke declined earlier than roundworm and whipworm in China and Korea; the explanations it offers are historical and untested.

55. 55
    Yoshida Y. Clonorchiasis--a historical review of contributions of Japanese parasitologists.Parasitol Int · 2011 · 61(1):5-9doi:10.1016/j.parint.2011.06.003 · PMID 21749930

    The source for Kobayashi (1912), Muto (1918), Ishisaka's 1877 Japanese case and the 1915 Korean and Taiwanese reports; a historical review, not the primary papers.

56. 56
    Qian MB, Chen YD, Zhou XN. [From recognition to practice: The 140th anniversary of the discovery of Clonorchis sinensis].Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi · 2014 · 32(4):247-52PMID 25518585

    Chinese-language review with an English abstract; dates McConnell's recovery to September 1874 and Kobayashi's fish work to 1910, against 1912 in [101]. No DOI.

57. 57
    Lee JH, Yang HM, Bak UB, Rim HJ. Promoting role of Clonorchis sinensis infection on induction of cholangiocarcinoma during two-step carcinogenesis.Korean J Parasitol · 1994 · 32(1):13-8doi:10.3347/kjp.1994.32.1.13 · PMID 8167103

    Hamster experiment varying the order of exposures, which supports the fluke as a promoter of nitrosamine-started cancer; groups of 15.

58. 58
    IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Schistosomes, liver flukes and Helicobacter pylori.IARC Monogr Eval Carcinog Risks Hum · 1994 · 61:1-241PMID 7715068

    Volume 61, from the Working Group that met in Lyon on 7–14 June 1994 and the primary document for the 1994 liver-fluke ratings; the PubMed record carries no abstract.

59. 59
    Bouvard V, Baan R, Straif K, et al. A review of human carcinogens--Part B: biological agents.Lancet Oncol · 2009 · 10(4):321-2doi:10.1016/s1470-2045(09)70096-8 · PMID 19350698

    The Working Group's published summary of April 2009, indexed as news with no abstract; cited here only for its date.

60. 60
    Woolf A, Green J, Levine JA, et al. A clinical study of Laotian refugees infected with Clonorchis sinensis or Opisthorchis viverrini.Am J Trop Med Hyg · 1984 · 33(6):1279-80doi:10.4269/ajtmh.1984.33.1279 · PMID 6391229

    Twenty-six infected refugees in North Carolina with no clinical differences from controls, leading the authors to suggest treatment might be unnecessary; a small cross-sectional study that could not have observed cancer.

61. 61
    Xiao SH, Utzinger J, Tanner M, Keiser J, Xue J. Advances with the Chinese anthelminthic drug tribendimidine in clinical trials and laboratory investigations.Acta Trop · 2013 · 126(2):115-26doi:10.1016/j.actatropica.2013.01.009 · PMID 23352956

    Review recording tribendimidine's Chinese approval in 2004 for intestinal roundworms and its exploratory liver-fluke results; written by researchers from the Chinese and Swiss institutes that ran those trials.

62. 62
    Choi D, Lim JH, Lee KT, et al. Cholangiocarcinoma and Clonorchis sinensis infection: a case-control study in Korea.J Hepatol · 2006 · 44(6):1066-73doi:10.1016/j.jhep.2005.11.040 · PMID 16480786

    Hospital case-control study of 185 bile-duct cancers in Seoul, measuring infection by stool, blood test, skin test, imaging and diet history; its controls came from the same hospital, and imaging cannot tell current from past infection.

63. 63
    Qian MB, Yap P, Yang YC, et al. Accuracy of the Kato-Katz method and formalin-ether concentration technique for the diagnosis of Clonorchis sinensis, and implication for assessing drug efficacy.Parasit Vectors · 2013 · 6(1):314doi:10.1186/1756-3305-6-314 · PMID 24499644

    Shows that one stool slide misses many infections and overstates cure, using 74 treated adults in Guangxi; the reference standard is itself microscopy, so true sensitivity may be lower still.

64. 64
    Fedorova OS, Kovshirina YV, Kovshirina AE, et al. Opisthorchis felineus infection and cholangiocarcinoma in the Russian Federation: A review of medical statistics.Parasitol Int · 2017 · 66(4):365-371doi:10.1016/j.parint.2016.07.010 · PMID 27474689

    Ecological comparison across 83 Russian regions for 2011–2013, published online in 2016, finding no significant correlation with liver and bile-duct cancer; the weakest design, so weak evidence of absence.

65. 65
    Kovner A, Kapushchak Y, Pakharukova M. Liver flukes and kidney injury: systematic review of human and animal data (from 1950 to 2025).J Helminthol · 2026 · 100:e24doi:10.1017/S0022149X26101187 · PMID 41766340

    A review from the Novosibirsk group whose own hamster work it covers, drawing on PubMed, Google Scholar, WHO, IARC and Russian-language sources, so its human evidence is of mixed quality.

66. 66
    Kapushchak YK, Zaparina OG, Mordvinov VA, Pakharukova MY. Time-dependent renal pathologies associated with the liver fluke infection, opisthorchiasis felinea.Acta Trop · 2021 · 228:106282doi:10.1016/j.actatropica.2021.106282 · PMID 34954256

    Hamsters followed from one month to 1.5 years after infection with O. felineus; animal evidence, and the mechanism is not established.

67. 67
    Chung BS, Zhang H, Choi MH, et al. Development of resistance to reinfection by Clonorchis sinensis in rats.Korean J Parasitol · 2004 · 42(1):19-26doi:10.3347/kjp.2004.42.1.19 · PMID 15060336

    Rats became 97.7% resistant to reinfection after cure while hamsters became 10.3% resistant; animal immunity, which human field data do not show.

68. 68
    Jang KT, Hong SM, Lee KT, et al. Intraductal papillary neoplasm of the bile duct associated with Clonorchis sinensis infection.Virchows Arch · 2008 · 453(6):589-98doi:10.1007/s00428-008-0682-x · PMID 18855009

    Pathology series finding a papillary precursor growth in 12 of 20 fluke-positive resected cancers against 8 of 51 fluke-negative ones, with a different cell type; small numbers from one center.

69. 69
    Pan X, He Q, Yin Y, Xu A, Wu A, Yi X, Zhong Z, Wu Y, Li X. Extracellular vesicles of Clonorchis sinensis promote the malignant phenotypes of cholangiocarcinoma via NF-kappaB/EMT axis.PLoS Negl Trop Dis · 2024 · 18(10):e0012545doi:10.1371/journal.pntd.0012545 · PMID 39466826

    Vesicles from adult worms acting on established cancer cell lines and in a mouse metastasis model, so it speaks to progression of an existing cancer rather than to its start.

70. 70
    Wen LJ, Yin JG, Wang YX, Liu K, Zhao JX. csi-miR-96-5p delivered by Clonorchis sinensis extracellular vesicles promotes intrahepatic cholangiocarcinoma proliferation and migration via the ferroptosis-related PTEN/SLC7A11/GPX4 axis. RETRACTED.Parasit Vectors · 2023 · 16(1):465; retraction note Parasit Vectors · 2024 · 17(1):309doi:10.1186/s13071-023-06075-7 · PMID 38124152

    Retracted in 2024 (retraction note doi 10.1186/s13071-024-06408-0, PMID 39026290); cited here only to record the retraction.

71. 71
    Wen L, Li M, Yin J. PTEN Deficiency Induced by Extracellular Vesicle miRNAs from Clonorchis sinensis Potentiates Cholangiocarcinoma Development by Inhibiting Ferroptosis. RETRACTED.Int J Mol Sci · 2024 · 25(19):10350; retraction notice Int J Mol Sci · 2026 · 27(10):4400doi:10.3390/ijms251910350 · PMID 39408679

    Retracted in 2026 (notice doi 10.3390/ijms27104400, PMID 42184138); cited here only to record the retraction.

72. 72
    Zaparina OG, Kapushchak YK, Lishai EA, Hong SJ, Sripa B, Pakharukova MY. Species-specific renal and liver responses during infection with food-borne trematodes Opisthorchis felineus, Opisthorchis viverrini, or Clonorchis sinensis.PLoS One · 2024 · 19(12):e0311481doi:10.1371/journal.pone.0311481 · PMID 39637122

    Hamster comparison finding similar periductal fibrosis with C. sinensis and O. felineus but precancerous lining change mainly with O. viverrini; it had no cancer endpoint.

73. 73
    Lishai EA, Zaparina OG, Kapushchak YK, et al. Comparative liver transcriptome analysis in hamsters infected with food-borne trematodes Opisthorchis felineus, Opisthorchis viverrini, or Clonorchis sinensis.PLoS Negl Trop Dis · 2024 · 18(12):e0012685doi:10.1371/journal.pntd.0012685 · PMID 39652576

    First side-by-side comparison of liver gene activity in hamsters infected with each of the three flukes, finding shared inflammatory pathways and species-specific responses; its description of Group 3 as noncarcinogenic misstates the category.

74. 74
    Jusakul A, Cutcutache I, Yong CH, et al. Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma.Cancer Discov · 2017 · 7(10):1116-1135doi:10.1158/2159-8290.CD-17-0368 · PMID 28667006

    489 cholangiocarcinomas from 10 countries in which fluke-positive tumors formed molecular clusters distinct from fluke-negative ones; the fluke-positive tumors were not separated by species in the abstract.

75. 75
    Heneberg P. From infection to cholangiocarcinoma: Why opisthorchiids break these rules.One Health · 2026 · 23:101517doi:10.1016/j.onehlt.2026.101517 · PMID 42500360

    A 2026 conceptual review proposing an inflammation threshold that opisthorchiid flukes cross and most worms do not; a hypothesis built from existing studies, not a test of one.

76. 76
    Long C, Lin Z, Cao J, Deng F, Luo Y, Liu Z, Du Q, Pan J, Nong Y, Huang F, He J, Tan S, Lv J. CagA-positive Helicobacter pylori may be associated with current infection of clonorchiasis.Sci Rep · 2025 · 15(1):39147doi:10.1038/s41598-025-27052-3 · PMID 41203779

    Cross-sectional comparison in Guangxi; hospital cases against community controls, so the direction of the association is unknown and selection effects are likely.

77. 77
    Chaiyadet S, Roblin T, Fauchois A, Temmam S, Hing D, Jacquemet E, Bigot T, Li B, Kende J, Capai L, Sotillo J, Thewarach L, Goyard S, Hardy D, Rose T, Loukas A, Brindley PJ, Sripa B, Dheilly NM. Fluke-borne viruses are a risk factor for diseases caused by carcinogenic trematodes.bioRxiv · 2025 · preprintdoi:10.1101/2025.10.22.683923 · PMID 41279566

    A preprint, not peer reviewed; most of its work is in O. viverrini, and the human part is a serological association, not a cancer endpoint.

78. 78
    Xu L, Zhang Y, Lin Z, Deng X, Ren X, Huang M, Li S, Zhou Q, Fang F, Yang Q, Zheng G, Chen Z, Wu Z, Sun X, Lin J, Shen J, Guo J, Li X, Xue T, Tan J, Lin X, Tan L, Peng H, Shen S, Peng S, Li S, Liang L, Cleary JM, Lai J, Xie Y, Kuang M. FASN-mediated fatty acid biosynthesis remodels immune environment in Clonorchis sinensis infection-related intrahepatic cholangiocarcinoma.J Hepatol · 2024 · 81(2):265-277doi:10.1016/j.jhep.2024.03.016 · PMID 38508240

    Single-cell, whole-exome, spatial and metabolomic study of 251 patients from three centers, with mouse work; the human part is observational, and infection status came from clinical records.

79. 79
    Zhang GW, Lin JH, Qian JP, Zhou J. Identification of risk and prognostic factors for patients with clonorchiasis-associated intrahepatic cholangiocarcinoma.Ann Surg Oncol · 2014 · 21(11):3628-37doi:10.1245/s10434-014-3710-x · PMID 24781504

    Surgical series comparing 127 fluke-associated cancers with 254 infected people without cancer, identifying long raw-fish exposure and hepatitis B as risk factors; retrospective and single-center.

80. 80
    Zhou Z, Nie SD, Jiang B, Wang J, Lv P. Risk factors for extrahepatic cholangiocarcinoma: a case-control study in China.Eur J Cancer Prev · 2019 · 28(4):254-257doi:10.1097/CEJ.0000000000000468 · PMID 30299315

    Chinese case-control study of 200 cancers of the bile duct outside the liver in which the fluke, though examined, was not among the significant risk factors; exposure came from clinical records.

81. 81
    Shen S, Qiu X, Yang G, et al. Impact of Clonorchis sinensis infection on long-term survival after curative resection for hepatocellular carcinoma: A multicenter cohort study.PLoS Negl Trop Dis · 2025 · 19(9):e0013441doi:10.1371/journal.pntd.0013441 · PMID 40906786

    1,386 operated liver-cell cancer patients in Guangxi, with fluke infection linked to shorter survival; it addresses prognosis, not whether the fluke causes the cancer, and its recurrence finding was inconsistent across methods.

82. 82
    Lin Q, Tang Z, Qin Y, Deng X, Wei C, Liu F, Pan X, Liu D, Zhan T, Fang M. Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis.PLoS Negl Trop Dis · 2024 · 18(1):e0011906doi:10.1371/journal.pntd.0011906 · PMID 38285640

    839 patients in Guangxi; retrospective, and infection was recorded clinically, so it cannot say when the infection began relative to the cancer.

83. 83
    Chen J, Lu W, Lou Y, Liu J, Liao X, Bai Y, Cheng G, Zhu G, Feng J, Liu J, Liu Z, Jia L, Zhou J, Peng T, Lu GD, Wang J. Integrating single cell- and spatial-resolved transcriptomics unravels the inter-tumor heterogeneity and immunosuppressive landscape in HBV- and Clonorchis sinensis-associated hepatocellular carcinoma.Mol Cancer · 2026 · 25(1):3doi:10.1186/s12943-025-02381-z · PMID 41491521

    Cohort of 269 patients with single-cell and spatial sequencing of a much smaller subset; it describes tumors that already exist and cannot show which exposure started them.

84. 84
    Slepchenko SM, Kardash OV, Slavinsky VS, Ivanov SN, Rakultseva DS, Tsybankov AA, Shin DH. Archaeoparasitological Analysis of Samples from the Cultural Layer of Nadym Gorodok dated Back to the 14th-Late 18th Centuries.Korean J Parasitol · 2019 · 57(6):567-573doi:10.3347/kjp.2019.57.6.567 · PMID 31914506

    Soil samples from one permafrost site, whose abstract dates the site to the 13th to 18th century against the 14th to late 18th in its title; identification rests on egg appearance, and soil cannot be tied to named individuals.

85. 85
    Ershov NI, Mordvinov VA, Prokhortchouk EB, et al. New insights from Opisthorchis felineus genome: update on genomics of the epidemiologically important liver flukes.BMC Genomics · 2019 · 20(1):399doi:10.1186/s12864-019-5752-8 · PMID 31117933

    The first O. felineus genome, showing unusually high genetic diversity; several authors are affiliated with commercial genomics companies, which bears on sequencing services rather than on any clinical claim.

86. 86
    Samet JM, Chiu WA, Cogliano V, Jinot J, Kriebel D, Lunn RM, et al. The IARC Monographs: Updated Procedures for Modern and Transparent Evidence Synthesis in Cancer Hazard Identification.J Natl Cancer Inst · 2020 · 112(1):30-37doi:10.1093/jnci/djz169 · PMID 31498409

    The published account, by IARC staff and their advisers, of the 2019 Preamble, the document that sets out how agents are classified and defines each group; cited here for the classification scheme rather than for any claim about a fluke.

87. 87
    Leija-Montoya AG, González-Ramírez J, Martínez-Coronilla G, et al. Roles of microRNAs and Long Non-Coding RNAs Encoded by Parasitic Helminths in Human Carcinogenesis.Int J Mol Sci · 2022 · 23(15):8173doi:10.3390/ijms23158173 · PMID 35897749

    Review whose text defines IARC's groups, Group 3 as not classifiable; it still lists the Group 4 category that IARC has since retired, so it is used here only for the definition.

88. 88
    Maksimova GA, Zhukova NA, Kashina EV, et al. [Role of opisthorchis felineus on induction of bile duct cancer].Parazitologiia · 2015 · 49(1):3-11PMID 26016330

    Russian-language hamster study with an English abstract: cholangiocarcinoma in every animal given O. felineus plus dimethylnitrosamine by week 18, and only precancerous change with the fluke alone.

89. 89
    Maksimova GA, Pakharukova MY, Kashina EV, et al. Effect of Opisthorchis felineus infection and dimethylnitrosamine administration on the induction of cholangiocarcinoma in Syrian hamsters.Parasitol Int · 2017 · 66(4):458-463doi:10.1016/j.parint.2015.10.002 · PMID 26453019

    The English-language histology of the same hamster model, published online in 2015, tracing fibrosis, dysplasia and then cancer from week 10 to week 30; animal evidence only.

90. 90
    Mordvinov VA, Minkova GA, Kovner AV, et al. A tumorigenic cell line derived from a hamster cholangiocarcinoma associated with Opisthorchis felineus liver fluke infection.Life Sci · 2021 · 277:119494doi:10.1016/j.lfs.2021.119494 · PMID 33862109

    A transplantable cancer cell line from an O. felineus-associated hamster tumor; the animals also received a nitrosamine, so the fluke was not the only exposure.

91. 91
    Dirik S, Boesecke C, Breitschwerdt S, et al. Paucisymptomatic opisthorchiasis in a non-endemic country: a neglected differential diagnosis?Infection · 2026 · online ahead of printdoi:10.1007/s15010-026-02853-4 · PMID 42223839

    A single German case in a woman raised in Kazakhstan, with the authors' account of why the diagnosis is missed in non-endemic countries; one case, not a prevalence estimate.

92. 92
    Kulmer LM, Unterkofler MS, Vali Y, Schwendenwein I, Luckschander-Zeller N. First autochthonous case of Opisthorchis felineus in Austria.Parasit Vectors · 2025 · 18(1):20doi:10.1186/s13071-025-06659-5 · PMID 39838451

    A single veterinary case in a cat; it shows the parasite completing its cycle locally, not that people there are infected.

93. 93
    Huang SY, Zeng QS, Shi XF, He YT, Fang YY, Lai YS. Assessment of the application of the FA280-a fully automated fecal analyzer for diagnosing clonorchiasis: a mixed-method study.Infect Dis Poverty · 2025 · 14(1):1doi:10.1186/s40249-024-01271-8 · PMID 39757228

    A commercial automated stool analyzer agreeing with Kato-Katz in 96.8% of 1,000 people in Guangdong, less well in light infections; no manufacturer affiliation appears among the authors.

94. 94
    Han Y, Zheng Y, Zhang Y, Xiang L, Chu W. [Imported familial clustering of clonorchiasis in Shanghai Municipality: a report of three cases].Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi · 2026 · 38(4):450-454doi:10.16250/j.32.1915.2026114 · PMID 42779248

    Chinese-language report of one Shanghai family infected in Guangdong, in which a machine smear missed two of three infections that Kato-Katz found; three cases.

95. 95
    Lee SH, Hwang SW, Chai JY, Seo BS. Comparative Morphology Of Eggs Of Heterophyids And Clonorchis Sinensis Causing Human Infections In Korea.Kisaengchunghak Chapchi · 1984 · 22(2):171-180doi:10.3347/kjp.1984.22.2.171 · PMID 12891010

    Measured eggs from worms recovered in Korea, showing C. sinensis and intestinal-fluke eggs overlap in size; it concludes they can be told apart only with careful measurement of many eggs.

96. 96
    Ditrich O, Giboda M, Scholz T, Beer SA. Comparative morphology of eggs of the Haplorchiinae (Trematoda: Heterophyidae) and some other medically important heterophyid and opisthorchiid flukes.Folia Parasitol · 1992 · 39(2):123-32PMID 1644359

    Comparison of eggs from seven small flukes concluding that egg shape is unsuitable for naming the species; electron microscopy helped, which ordinary laboratories do not use.

97. 97
    Cho SH, Cho PY, Lee DM, et al. Epidemiological survey on the infection of intestinal flukes in residents of Muan-gun, Jeollanam-do, the Republic of Korea.Korean J Parasitol · 2010 · 48(2):133-8doi:10.3347/kjp.2010.48.2.133 · PMID 20585529

    A Korean county where stool surveys found both heterophyid and C. sinensis eggs and only worm recovery after treatment identified seven intestinal fluke species; one county.

98. 98
    Pan G, You T, Wei X, et al. Clinical Value of IgG Antibody Test in Screening for Clonorchis sinensis Infection in High-Risk Population.Clin Lab · 2024 · 70(11)doi:10.7754/Clin.Lab.2024.240430 · PMID 39506592

    Antibody test against stool eggs in 1,080 patients in Liuzhou, Guangxi: 78.0% sensitive and 81.9% specific, weaker in light infections and older people; the egg reference standard is imperfect.

99. 99
    Wei S, Chen X, Cai S, Li X, Lu T, Li Y, Hou Y, Li Y, Shi Y. Systematic Evaluation of Four Cysteine Proteases (CP1-4) from Clonorchis sinensis for Serodiagnosis: From Single-Antigen Screening to Multi-Antigen Modeling.Trop Med Infect Dis · 2026 · 11(4):103doi:10.3390/tropicalmed11040103 · PMID 42042964

    The multi-antigen models were fitted and validated on a single split of the same 328 sera, which flatters them; the reference standard is microscopy.

100. 100
     Ma X, Liu Q, Chang Q, Lv Q, Zhang L, Sun S, Wang C, Liu M, Liu X, Li C. One-pot nanoflower-based sensitive colorimetric biosensor for multihost detection of zoonotic clonorchiasis.PLoS Negl Trop Dis · 2026 · 20(4):e0014197doi:10.1371/journal.pntd.0014197 · PMID 41973752

     Tested on human, dog and experimentally infected mouse sera; seroconversion in infected animals took 21 days, so it cannot find a very recent infection.

101. 101
     Rahman SMM, Song HB, Jin Y, et al. Application of a loop-mediated isothermal amplification (LAMP) assay targeting cox1 gene for the detection of Clonorchis sinensis in human fecal samples.PLoS Negl Trop Dis · 2017 · 11(10):e0005995doi:10.1371/journal.pntd.0005995 · PMID 28991924

     A DNA test of stool with 97.1% sensitivity and 100% specificity against samples on which microscopy and PCR agreed, which flatters any new test.

102. 102
     Ma X, Bai X, Li H, et al. A rapid and visual detection assay for Clonorchis sinensis based on recombinase polymerase amplification and lateral flow dipstick.Parasit Vectors · 2023 · 16(1):165doi:10.1186/s13071-023-05774-5 · PMID 37208693

     A 20-minute DNA dipstick test detecting down to one egg in the laboratory, checked on only 40 human stool samples.

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     Bi M, Li A, Jin Y, Gao Y, Li M, Li C. Highly efficient RPA product degradation and expanded PAM recognition enable RPA-Cas3 detection of Clonorchis sinensis.Anal Chim Acta · 2026 · 1423:346191doi:10.1016/j.aca.2026.346191 · PMID 42838688

     A method paper; its abstract reports no validation on human stool, so its field performance is unknown.

104. 104
     Xie B, Guo Y, Wu X, Hou Z, Hong Y, Tian T, Zhou X, Chen J. [Progress of researches on techniques for molecular detection of Clonorchis sinensis infections].Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi · 2026 · 38(3):323-329doi:10.16250/j.32.1915.2024217 · PMID 42613886

     Chinese-language review with an English abstract whose species names are stripped in PubMed; a survey of PCR, LAMP, CRISPR and sequencing methods, with no new data.

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     Choi D, Hong ST, Lim JH, et al. Sonographic findings of active Clonorchis sinensis infection.J Clin Ultrasound · 2004 · 32(1):17-23doi:10.1002/jcu.10216 · PMID 14705173

     Ultrasound in 457 villagers in northeastern China, with the sensitivity and specificity of each sign for active infection; one experienced reader, in a heavily infected population.

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     Yunina D, Golfeyz S, Cheung D, et al. Liver flukes diagnosed by ERCP in a local immigrant community.Gastrointest Endosc · 2022 · 96(6):1058-1061doi:10.1016/j.gie.2022.07.028 · PMID 35932814

     Three Brooklyn patients from China diagnosed when worms were seen in the bile duct at endoscopy, two after negative stool tests; a case series that cannot say how common this is.

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     Xu LL, Jiang B, Duan JH, et al. Efficacy and safety of praziquantel, tribendimidine and mebendazole in patients with co-infection of Clonorchis sinensis and other helminths.PLoS Negl Trop Dis · 2014 · 8(8):e3046doi:10.1371/journal.pntd.0003046 · PMID 25122121

     Randomized open-label trial in Hunan with similar results, a single-dose tribendimidine cure of 50% against 56.8% for praziquantel; open-label, in people with mixed worm infections.

108. 108
     Cao YZ, Guo PZ, Zhang YF, Li WY, Shen QF, Li ZH, Lei ZY, Chen JF, Zhang J. Empirical therapy for hepatic lesions in suspected clonorchiasis: a comparative efficacy analysis of Albendazole and Praziquantel.Front Pharmacol · 2026 · 17:1878617doi:10.3389/fphar.2026.1878617 · PMID 42488569

     Retrospective single-center cohort, 2018–2025; clinical cure, not egg clearance, was the endpoint.

109. 109
     Lee SO, Lee H, Chu KB, Li J, Hong SJ, Kim SS, No JH, Quan FS. Ivermectin Identified Using a High-Throughput Screening System Exhibits Anti-Clonorchis sinensis Activity in Rats.Antibiotics (Basel) · 2025 · 14(8):837doi:10.3390/antibiotics14080837 · PMID 40868031

     Screen of 320 compounds; ivermectin reduced worm burden only when given against larvae, one week after infection.

110. 110
     Lee SO, Chu KB, Yoon KW, Heo SI, Song JH, Li J, Hong SJ, Quan FS. Combinatorial Treatment with Praziquantel and Curcumin Reduces Clonorchis sinensis Parasite Burden and Clonorchiasis-Associated Pathologies in Rats.Pharmaceutics · 2024 · 16(12):1550doi:10.3390/pharmaceutics16121550 · PMID 39771529

     Rat model; the combination lowered worm recovery and bile-duct widening, with no human data.

111. 111
     Ma Y, Wang X, Zhang X, Yu Y, Liu Z, Bao P, Liu M, Wang Y, Yuan X, Wang H, Gong P, Zhang N, Li X, Li J. New combination therapy of praziquantel and Lactobacillus plantarum for enhancing the treatment of clonorchiasis in mice.Food Waterborne Parasitol · 2026 · 43:e00333doi:10.1016/j.fawpar.2026.e00333 · PMID 41969850

     Mouse model; the probiotic alone cut worm burden 51.3% and the combination took the fibrotic area to 6.0%, a fibrosis endpoint rather than a cancer one.

112. 112
     Choi MH, Park SK, Li Z, et al. Effect of control strategies on prevalence, incidence and re-infection of clonorchiasis in endemic areas of China.PLoS Negl Trop Dis · 2010 · 4(2):e601doi:10.1371/journal.pntd.0000601 · PMID 20169061

     A 2001–2004 control project in Heilongjiang comparing mass and selective praziquantel schedules; prevalence fell under every schedule, but there were no untreated comparison villages.

113. 113
     Oh JK, Lim MK, Yun EH, et al. Control of clonorchiasis in Korea: effectiveness of health education for community leaders and individuals in an endemic area.Trop Med Int Health · 2014 · 19(9):1096-104doi:10.1111/tmi.12338 · PMID 24862476

     Three-year field comparison in Sancheong, Korea, showing that adding health education to treatment lowered prevalence further; groups were divided by area, not randomized.

114. 114
     Schwartz DA. Cholangiocarcinoma associated with liver fluke infection: a preventable source of morbidity in Asian immigrants.Am J Gastroenterol · 1986 · 81(1):76-9PMID 3002170

     A case report of an unsuspected infection with bile-duct cancer in a Chinese immigrant, citing surveys of up to 26% infection among Asian immigrants of the period; the survey figures are second-hand.

115. 115
     Lifson AR, Thai D, O'Fallon A, Mills WA, Hang K. Prevalence of tuberculosis, hepatitis B virus, and intestinal parasitic infections among refugees to Minnesota.Public Health Rep · 2002 · 117(1):69-77doi:10.1093/phr/117.1.69 · PMID 12297684

     Minnesota's 1999 screening of 2,545 refugees, whose form asked specifically about clonorchiasis; the abstract reports no clonorchiasis figure, and refugees are only one group of immigrants.

116. 116
     Psevdos G, Ford FM, Hong ST. Screening US Vietnam Veterans for Liver Fluke Exposure 5 Decades After the End of the War.Infect Dis Clin Pract (Baltim Md) · 2018 · 26(4):208-210doi:10.1097/IPC.0000000000000611 · PMID 30034207

     Pilot screen of 50 exposed veterans with no uninfected comparison group; serology was done with a multi-antigen ELISA at Seoul National University, and antibody positivity cannot distinguish past from present infection.

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     Herrick JA, Rubinstein I. Diagnosis of Indolent Clonorchis sinensis and Opisthorchis viverrini Infections as Risk Factors for Cholangiocarcinoma: An Unmet Medical Need.Fed Pract · 2023 · 40(Suppl 1):S15-S17doi:10.12788/fp.0376 · PMID 37727828

     A commentary by two Veterans Affairs physicians arguing for serologic screening of Vietnam veterans; it presents no new data, and its species names are stripped from the PubMed abstract, so read the title and publisher version before quoting it.

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     Huang C, Wu Y, Wu A, Huang L, Fang S, Xu C, Liu T, Li Y, Li X. Clonorchis sinensis and cholangiocarcinoma: molecular mechanisms and biomarker advances.Parasite · 2026 · 33:16doi:10.1051/parasite/2026011 · PMID 41919759

     A review, with no new data; useful for its account of why none of the proposed early markers is usable yet.

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     de Martel C, Plummer M, Franceschi S. Cholangiocarcinoma: descriptive epidemiology and risk factors.Gastroenterol Clin Biol · 2010 · 34(3):173-80doi:10.1016/j.gcb.2010.01.008 · PMID 20202771

     IARC authors distinguishing fluke-related intrahepatic cholangiocarcinoma, confined to endemic areas, from a rarer worldwide form in which many patients have no known risk factor; a review, not new data.