Liver flukes

What we are reading

Gathered for the investigation and not yet written up. Each note says what the paper does and does not show.

1. Sivanand A, Talati D, Kalariya Y, Patel P, Gandhi SK. Associations of liver fluke infection and cholangiocarcinoma: a scoping review.Cureus · 2023 · 15(10):e4640010.7759/cureus.46400 · PMID 37927641

   Scoping review. Mechanism is specific and worth the airtime: mechanical injury from the fluke feeding in the bile duct, plus a secreted protein (OvGRN-1) taken up by human cholangiocytes that shifts gene expression toward wound-healing and cancer pathways. Note the journal — Cureus has light peer review, so verify the primary OvGRN-1 work before quoting it.

2. 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):590–59710.5483/bmbrep.2016.49.11.109 · PMID 27418285

   Names the three organisms IARC lists as Group 1 human carcinogens: Clonorchis sinensis, Opisthorchis viverrini and Schistosoma haematobium. Also the scale nobody in the West registers — C. sinensis was the most prevalent parasite in the 2012 Korean national survey at 1.86% of the general population, and it is still actively transmitted.

3. Buisson Y. [Control of Opisthorchis viverrini infection for cholangiocarcinoma prevention].Bull Soc Pathol Exot · 2017 · 110(1):61–6710.1007/s13149-017-0544-8 · PMID 28105582

   The clearest account of the mechanism, and it is three mechanisms braided: mechanical damage from adult flukes feeding on bile-duct lining for TEN TO THIRTY YEARS; chronic inflammation and oxidative stress; and mitogenic, anti-apoptotic proteins the fluke itself secretes. Plus a dietary co-factor — nitrosamines in the fermented raw fish that carries the parasite. Khon Kaen province in Thailand has the highest cholangiocarcinoma incidence on earth. Five-year survival under 5%. The detail that should end the episode's optimism: mass deworming FAILED, because people are reinfected, and repeated cure-and-reinfection cycles may themselves promote carcinogenesis.

4. Arunsan P, Ittiprasert W, Smout MJ, Cochran CJ, Mann VH, Chaiyadet S, Karinshak SE, Sripa B, Young ND, Sotillo J, Loukas A, Brindley PJ, Laha T. Programmed knockout mutation of liver fluke granulin attenuates virulence of infection-induced hepatobiliary morbidity.eLife · 2019 · 8:e4146310.7554/eLife.41463 · PMID 30644359

   The experiment that turns the association into causation. The team CRISPR-edited the granulin gene out of Opisthorchis viverrini itself — the first programmed gene knockout in a parasitic flatworm — then let the edited flukes infect hamsters. The flukes colonised the bile ducts and grew to adults normally, but the bile-duct overgrowth and fibrosis that precede cholangiocarcinoma were markedly reduced. Delete one parasite growth factor, and the pre-cancer largely does not happen. This is as close to proof of a parasite-driven cancer mechanism as the field has.

5. Feng M, Cheng X. Parasite-Associated Cancers (Blood Flukes/Liver Flukes).Adv Exp Med Biol · 2017 · 1018:193–20510.1007/978-981-10-5765-6_12 · PMID 29052139

   The compact summary of all three Group 1 organisms in one place, and blunt about the hole: the cellular and molecular mechanisms linking fluke infection to cancer 'have yet to be defined'. Also the epidemiological point that makes this a diagnosis problem as much as a biology problem — infection is frequently ASYMPTOMATIC and therefore rarely diagnosed early.

6. Maksimova GA, Zhukova NA, Kashina EV, Lvova MN, Katokhin AV, Tolstikova TG, Mordvinov VA. [Role of opisthorchis felineus on induction of bile duct cancer].Parazitologiia · 2015 · 49(1):3–11PMID 26016330

   The fourth fluke, and the one that is not on the IARC list. Opisthorchis felineus is endemic across Siberia and parts of Europe, with up to 80% infestation in endemic areas. In hamsters, infection alone produced hyperplastic and dysplastic bile-duct change; infection plus dimethylnitrosamine produced cholangiocarcinoma in EVERY animal by week 18. The authors argue their data should be used to assign it an IARC category. It still has none. That is not evidence of safety; it is evidence that nobody has run the human study.