Periodic Reporting for period 2 - COCLICAN (COllaborative Consortium for the early detection of LIver CANcer)
Período documentado: 2020-11-01 hasta 2022-10-31
Liver cancer is a significant cause of illness and early death, especially in developing countries where there is difficulty accessing diagnostic technology. In the coming decades, it is likely that this disease will cause a major challenge in global public health, and create a burden to society through illness and death which could be prevented with earlier diagnosis.
Incidence of HCC is closely associated with prevalence of the hepatitis B (HBV) and C (HCV) viruses. Clinically, HCC patients have a very poor prognosis and high 5-year mortality rate, except when detected early. Detecting HCC early is critical in order to prevent the development of tumours. Affordable and accurate diagnostic tools are urgently needed to diagnose liver cancer earlier in developing countries. The COCLICAN project aims to develop effective methods for early diagnosis which can be used at a low cost to medical institutions and patients.
The project brought together a collaborative network of researchers and clinicians in three continents: Europe, South America and Asia. With field sites in Peru and Laos, where liver cancer is an emergent threat to the health of the population, this international team had analysed and compare metabolomic profiles of a consistent cohort of HBV-HBC infected patients to delineate molecules which are predictive of the emergence of liver cancer.
Incidence of HCC is closely associated with prevalence of the hepatitis B (HBV) and C (HCV) viruses. Clinically, HCC patients have a very poor prognosis and high 5-year mortality rate, except when detected early. Detecting HCC early is critical in order to prevent the development of tumours. Affordable and accurate diagnostic tools are urgently needed to diagnose liver cancer earlier in developing countries. The COCLICAN project aims to develop effective methods for early diagnosis which can be used at a low cost to medical institutions and patients.
The project brought together a collaborative network of researchers and clinicians in three continents: Europe, South America and Asia. With field sites in Peru and Laos, where liver cancer is an emergent threat to the health of the population, this international team had analysed and compare metabolomic profiles of a consistent cohort of HBV-HBC infected patients to delineate molecules which are predictive of the emergence of liver cancer.
During the project, work has been undertaken on different aspects of HCC diagnosis, including imaging techniques, metabolomics, plasma extraction and health-seeking behaviour.
In work package 1, staff on secondment and local partners at INEN, Peru, and MoH, Laos, have designed and implemented surveys to learn more about the socio-economic status, therapeutic itineraries, disease perceptions and use of complementary medicines of patients who have been diagnosed with hepatitis or liver cancer. The profile of hepatitis-infected patients at risk of developing liver cancer has been defined in both countries.
In work package 2, European researchers seconded to INEN have provided training on diagnostic methods through a number of workshops and presentations. Together with INEN staff, ULB secondees have implemented a protocol for the acquisition of imaging data that includes the transfer of information between the partners through web servers. The acquisition pipeline is now in place for continuous data acquisition and transfer to ULB server.
In parallel, researchers from INEN and IRD have built a retrospective database of Peruvian HCC patients in order to evaluate the therapeutic outcomes in patients from Peru.
Researchers for the first time have set a contextualized nomogram for the therapeutic decision making. Staff from MOH in Laos have also travelled to ULB in Belgium for training on imaging techniques.
The EchOpen probe has experienced many delays due to the complexity of the design, the impact of the entry into force of the new European regulation on medical devices, the delays of which have been particularly long, and the serious difficulties in supplying electronic components. But the teams are ready to keep working together in the next future when the probe will be ready.
In work package 3, staff from MOH and INEN were seconded to UT3 for the purpose of undertaking metabolomic analysis and training, and staff from Faculty of Pharmacy (MOH) were seconded to KUT for the purpose of developing best extraction methods and training, during the first year of the project. To test extraction methods, plasma from Laos was consecutively extracted by supercritical carbon dioxide, pressurised acetone and pressurized ethanol for step-by-step recovery of the increasing polarity soluble substances from the plasma, and the extracts were collected for chromatographic/spectroscopic analysis. Afterwards they were analysed by UPLC-qTOF. In parallel, a comparative analysis was undertaken in Toulouse. The method allowed to detect some interesting trends regarding control versus HBV samples, mainly related to amino acids compounds, and showed that some lipids were also specifically regulated upon HBV infection. KTU optimized extraction procedures. Although Covid and the political tensions in Europe have greatly affected this workpackage, secondments to UT3 and KTU have highlighted specific patient profiles at risk.
In work package 1, staff on secondment and local partners at INEN, Peru, and MoH, Laos, have designed and implemented surveys to learn more about the socio-economic status, therapeutic itineraries, disease perceptions and use of complementary medicines of patients who have been diagnosed with hepatitis or liver cancer. The profile of hepatitis-infected patients at risk of developing liver cancer has been defined in both countries.
In work package 2, European researchers seconded to INEN have provided training on diagnostic methods through a number of workshops and presentations. Together with INEN staff, ULB secondees have implemented a protocol for the acquisition of imaging data that includes the transfer of information between the partners through web servers. The acquisition pipeline is now in place for continuous data acquisition and transfer to ULB server.
In parallel, researchers from INEN and IRD have built a retrospective database of Peruvian HCC patients in order to evaluate the therapeutic outcomes in patients from Peru.
Researchers for the first time have set a contextualized nomogram for the therapeutic decision making. Staff from MOH in Laos have also travelled to ULB in Belgium for training on imaging techniques.
The EchOpen probe has experienced many delays due to the complexity of the design, the impact of the entry into force of the new European regulation on medical devices, the delays of which have been particularly long, and the serious difficulties in supplying electronic components. But the teams are ready to keep working together in the next future when the probe will be ready.
In work package 3, staff from MOH and INEN were seconded to UT3 for the purpose of undertaking metabolomic analysis and training, and staff from Faculty of Pharmacy (MOH) were seconded to KUT for the purpose of developing best extraction methods and training, during the first year of the project. To test extraction methods, plasma from Laos was consecutively extracted by supercritical carbon dioxide, pressurised acetone and pressurized ethanol for step-by-step recovery of the increasing polarity soluble substances from the plasma, and the extracts were collected for chromatographic/spectroscopic analysis. Afterwards they were analysed by UPLC-qTOF. In parallel, a comparative analysis was undertaken in Toulouse. The method allowed to detect some interesting trends regarding control versus HBV samples, mainly related to amino acids compounds, and showed that some lipids were also specifically regulated upon HBV infection. KTU optimized extraction procedures. Although Covid and the political tensions in Europe have greatly affected this workpackage, secondments to UT3 and KTU have highlighted specific patient profiles at risk.
Management of hepatitis:
Each year (2019 to 2022) secondees organised Mekong Hepatitis Symposium in Vientiane, Laos, on the implementation of guidelines for the management of hepatitis infected patients. A workshop on hepatitis genotyping took place at CILM. It brought together students, supervised by specialists from the Institut Pasteur of Paris.
Imaging:
Although the EchOpen device was not ready in the frame of the Coclican project, we know that the device will have an important socio-economic impact, giving access to diagnosis in remote regions with poor access to medical care. It has the potential to radically transform the diagnostic orientation of liver carcinogenesis in medically underserved areas (representing about two-thirds of the world population).
Potential impacts:
Diagnostic:
We set up a dedicated nomogram, determining whether a patient with large HCC might truly benefit from liver resection, which is paramount in low- and middle-income countries where HCC is often diagnosed at advanced stages.
The search for the cause of the emergence of HCC in Peru:
The Central Andes of Peru are a region of great concern regarding pesticide risk to the health of local communities. We conducted the first comprehensive investigation of pesticide-related compounds detected in people living in these areas. Our findings pinpoint an alarming environmental situation that threatens human health and provide a rationale for improving public policies to protect local communities.
Application of the Extraction process:
Chemists who went to Lithuania developed extraction techniques to analyse protein and other high added value compounds to boost the Rocket Project, aiming to the empowerment of women in extreme poverty through sustainable, low-cost, high-tech production of edible crickets.
https://en.ird.fr/no-skipping-meals-crickets
https://en.ird.fr/project-rocket-training-continues-despite-bad-weather
Thanks to Coclican, the Foundation Pierre Fabre has funded a Supercritical CO2 extractor for the faculty of Pharmacy of Vientiane to perform eco-friendly extractions.
Epidemiological study:
Thanks to Coclican, the Merieux Foundation has donated 120.000 rapid tests for the detection of Hepatitis B. This donation is a unique opportunity to find out the reality of the infection in the country. Our estimates suggest that Laos may no longer be a country highly endemic for chronic infection with HBV but rather a country with intermediate endemicity.
This exceptional work suggests that developing countries with predominantly rural populations can emerge from high endemicity for chronic hepatitis B virus infection within a single generation. The improving situation in Laos appears to have resulted from the determined application of public health measures benefitting populations whose many children are now protected from infection. It is, therefore, a message of hope for many other countries facing similar circumstances.
Each year (2019 to 2022) secondees organised Mekong Hepatitis Symposium in Vientiane, Laos, on the implementation of guidelines for the management of hepatitis infected patients. A workshop on hepatitis genotyping took place at CILM. It brought together students, supervised by specialists from the Institut Pasteur of Paris.
Imaging:
Although the EchOpen device was not ready in the frame of the Coclican project, we know that the device will have an important socio-economic impact, giving access to diagnosis in remote regions with poor access to medical care. It has the potential to radically transform the diagnostic orientation of liver carcinogenesis in medically underserved areas (representing about two-thirds of the world population).
Potential impacts:
Diagnostic:
We set up a dedicated nomogram, determining whether a patient with large HCC might truly benefit from liver resection, which is paramount in low- and middle-income countries where HCC is often diagnosed at advanced stages.
The search for the cause of the emergence of HCC in Peru:
The Central Andes of Peru are a region of great concern regarding pesticide risk to the health of local communities. We conducted the first comprehensive investigation of pesticide-related compounds detected in people living in these areas. Our findings pinpoint an alarming environmental situation that threatens human health and provide a rationale for improving public policies to protect local communities.
Application of the Extraction process:
Chemists who went to Lithuania developed extraction techniques to analyse protein and other high added value compounds to boost the Rocket Project, aiming to the empowerment of women in extreme poverty through sustainable, low-cost, high-tech production of edible crickets.
https://en.ird.fr/no-skipping-meals-crickets
https://en.ird.fr/project-rocket-training-continues-despite-bad-weather
Thanks to Coclican, the Foundation Pierre Fabre has funded a Supercritical CO2 extractor for the faculty of Pharmacy of Vientiane to perform eco-friendly extractions.
Epidemiological study:
Thanks to Coclican, the Merieux Foundation has donated 120.000 rapid tests for the detection of Hepatitis B. This donation is a unique opportunity to find out the reality of the infection in the country. Our estimates suggest that Laos may no longer be a country highly endemic for chronic infection with HBV but rather a country with intermediate endemicity.
This exceptional work suggests that developing countries with predominantly rural populations can emerge from high endemicity for chronic hepatitis B virus infection within a single generation. The improving situation in Laos appears to have resulted from the determined application of public health measures benefitting populations whose many children are now protected from infection. It is, therefore, a message of hope for many other countries facing similar circumstances.