Periodic Reporting for period 4 - RADIcAL (Non-invasive rapid assessment of chronic liver disease using Magnetic Resonance Imaging with LiverMultiScan)
Periodo di rendicontazione: 2019-07-01 al 2020-12-31
Chronic liver diseases are called 'silent killers', as clinical symptoms only surface at late stages of the disease when it is not treatable. Non-alcoholic fatty liver disease (NAFLD), defined by fat accumulation in the liver, is the most prevalent chronic liver disease and, along with its fibroinflammatory sub-type non-alcoholic steatohepatitis (NASH), can lead to cirrhosis and liver failure. This rapidly developing epidemic and associated co-morbidities pose a huge medical and socio-economic burden on society in Europe. In Germany, France, Italy and the UK the annual cost of NAFLD is approximately €35 billion, equating to €354 to €1,163 per patient (Younossi et al, 2016). Furthermore, annual healthcare costs related to liver disease are 86% higher in those with advanced liver disease than without and require additional procedures. For example, liver transplant surgery costs are estimated at €55,677 per patient annually (Petta et al, 2019). Thus, treating NAFLD/NASH patients at an early stage, when the disease is still curable, could benefit these patients and society as a whole.
At present, the gold standard for diagnosing and staging liver disease is liver biopsy, which is costly, invasive, and carries risk for the patient. For these reasons, clinicians are reluctant to use it for people suspected of having NAFLD/NASH or for serial assessment for disease monitoring. Perspectum Ltd has developed LiverMultiScan®, a novel, non-invasive, quantitative Magnetic Resonance Imaging (MRI) post-processing software tool that has demonstrated high diagnostic accuracy for the early assessment of liver disease (Banerjee et al, 2014; Pavlides et al, 2016; Pavlides et al, 2017). This technology has the potential to improve the care pathway for patients with suspected NAFLD, by reducing the number of visits and unnecessary liver biopsies. Perspectum was awarded a Horizon 2020 grant by the European Commission, Executive Agency for Small and Medium-sized Enterprises (EASME) to develop the health economic case for LiverMultiScan as part of the diagnostic pathway in European healthcare settings. This project is known as RADIcAL.
RADIcAL comprises two clinical studies RADIcAL1 (R1) and RADIcAL2 (R2).
The specific objectives are:
•To validate the cost-effectiveness and added value of LiverMultiScan compared to the standard care pathway for assessing chronic liver disease
•To demonstrate the sensitivity and specificity of LiverMultiScan as a medical support tool for stratifying patients that have high risk of liver transplant rejection
•Share and disseminate evidence of benefits of LiverMultiScan as a novel non-invasive, radiation-free, one-step solution that provides fast detection of liver disease at early stage, providing accurate diagnosis for all types of patients (including obese people and those with high iron levels in the liver), and capable of assessing the entire liver volume.
Following the emergence of COVID-19 in 2020, Perspectum launched a new study, COVERSCAN, with the aim to assess the recovery of patients who had contracted the SARS-CoV-2 Virus in the UK. This study is based on the CoverScan Medical Device (MD), which has recently received exceptional use authorisation from the Medicines and Healthcare products Regulatory Agency in the UK and is an extension of LiverMultiScan which can assess multiple visceral organs in addition to the liver. The aim of the COVERSCAN study was to determine the prevalence and degree of organ damage in patients recovering from COVID-19 disease using multi-parametric MRI to assess the lungs, heart, liver, kidneys, pancreas and spleen over a follow up period of 6 months, post infection.
At present, the gold standard for diagnosing and staging liver disease is liver biopsy, which is costly, invasive, and carries risk for the patient. For these reasons, clinicians are reluctant to use it for people suspected of having NAFLD/NASH or for serial assessment for disease monitoring. Perspectum Ltd has developed LiverMultiScan®, a novel, non-invasive, quantitative Magnetic Resonance Imaging (MRI) post-processing software tool that has demonstrated high diagnostic accuracy for the early assessment of liver disease (Banerjee et al, 2014; Pavlides et al, 2016; Pavlides et al, 2017). This technology has the potential to improve the care pathway for patients with suspected NAFLD, by reducing the number of visits and unnecessary liver biopsies. Perspectum was awarded a Horizon 2020 grant by the European Commission, Executive Agency for Small and Medium-sized Enterprises (EASME) to develop the health economic case for LiverMultiScan as part of the diagnostic pathway in European healthcare settings. This project is known as RADIcAL.
RADIcAL comprises two clinical studies RADIcAL1 (R1) and RADIcAL2 (R2).
The specific objectives are:
•To validate the cost-effectiveness and added value of LiverMultiScan compared to the standard care pathway for assessing chronic liver disease
•To demonstrate the sensitivity and specificity of LiverMultiScan as a medical support tool for stratifying patients that have high risk of liver transplant rejection
•Share and disseminate evidence of benefits of LiverMultiScan as a novel non-invasive, radiation-free, one-step solution that provides fast detection of liver disease at early stage, providing accurate diagnosis for all types of patients (including obese people and those with high iron levels in the liver), and capable of assessing the entire liver volume.
Following the emergence of COVID-19 in 2020, Perspectum launched a new study, COVERSCAN, with the aim to assess the recovery of patients who had contracted the SARS-CoV-2 Virus in the UK. This study is based on the CoverScan Medical Device (MD), which has recently received exceptional use authorisation from the Medicines and Healthcare products Regulatory Agency in the UK and is an extension of LiverMultiScan which can assess multiple visceral organs in addition to the liver. The aim of the COVERSCAN study was to determine the prevalence and degree of organ damage in patients recovering from COVID-19 disease using multi-parametric MRI to assess the lungs, heart, liver, kidneys, pancreas and spleen over a follow up period of 6 months, post infection.
Both R1 and R2 studies have completed recruitment and primary analyses have been performed. A total of 802 subjects were recruited to R1 and a further 131 subjects (25 paediatric and 106 adults) were recruited to R2.
The long-term (over 15 years) cost-effectiveness analysis for R1 identified that using LiverMultiScan following ultrasound elastography in the instances that elastography fails or is unsuitable (for example in patients with high steatosis) is most cost-effective in terms of incremental cost per quality adjusted life year gained.
The R2 study demonstrated that non-invasive MRI derived metrics showed superior diagnostic utility to discriminate those who had a transplant rejection (both complication and histological rejection) compared to traditional blood markers. Moreover, by combining imaging and blood markers, excellent diagnostic utility was obtained.
R1 abstracts have been presented at The Liver Meeting (AASLD 2017 & 2019) as well as at Digestive Disease Week (DDW 2020), all of which are widely attended by scientists and clinicians in the hepatology field. The R1 study protocol was published in JMIR Research Protocols in October 2020. We will further promote our final results on clinical validation from both R1 and R2 studies in high impact Open Access journals for optimal knowledge distribution.
In COVERSCAN, 445 subjects with confirmed COVID-19 and 50 healthy controls have been imaged; over two thirds of individuals who were at low risk of COVID-19 mortality with ongoing Long COVID symptoms showed impairment in one or more organs four months after contracting the virus. This poses a substantial under-recognised health economic burden on the public health system, as previously it was assumed that in the community, low risk, young individuals without comorbidities have no long-term outcomes post infection. Results from the first 201 patients were made publicly available on the preprint service for health sciences medRxiv, and the full manuscript is currently under review with the British Medical Journal.
The long-term (over 15 years) cost-effectiveness analysis for R1 identified that using LiverMultiScan following ultrasound elastography in the instances that elastography fails or is unsuitable (for example in patients with high steatosis) is most cost-effective in terms of incremental cost per quality adjusted life year gained.
The R2 study demonstrated that non-invasive MRI derived metrics showed superior diagnostic utility to discriminate those who had a transplant rejection (both complication and histological rejection) compared to traditional blood markers. Moreover, by combining imaging and blood markers, excellent diagnostic utility was obtained.
R1 abstracts have been presented at The Liver Meeting (AASLD 2017 & 2019) as well as at Digestive Disease Week (DDW 2020), all of which are widely attended by scientists and clinicians in the hepatology field. The R1 study protocol was published in JMIR Research Protocols in October 2020. We will further promote our final results on clinical validation from both R1 and R2 studies in high impact Open Access journals for optimal knowledge distribution.
In COVERSCAN, 445 subjects with confirmed COVID-19 and 50 healthy controls have been imaged; over two thirds of individuals who were at low risk of COVID-19 mortality with ongoing Long COVID symptoms showed impairment in one or more organs four months after contracting the virus. This poses a substantial under-recognised health economic burden on the public health system, as previously it was assumed that in the community, low risk, young individuals without comorbidities have no long-term outcomes post infection. Results from the first 201 patients were made publicly available on the preprint service for health sciences medRxiv, and the full manuscript is currently under review with the British Medical Journal.
Final results from the R1 study demonstrate that LiverMultiScan has the potential to optimise the clinical care pathway by ruling out progressive disease and enabling identification of patients at low risk of NASH. Dedicating secondary care resources only to those patients presenting as high risk for NASH would reduce unnecessary invasive procedures, increase efficiency in the health care system and reduce unnecessary patient anxiety.
Our findings show that LiverMultiScan should be used in patients where elastography is unsuitable, with considerable impact on improving the course of illness and treatment management. LiverMultiScan would reduce healthcare costs, estimated at £2,537 saved per quality adjusted life year gained over a 15-year time horizon.
The MRI derived metrics of R2 could noninvasively identify those who have histological rejection, as well as those who have liver related complications, to better monitor the post-transplant population. Positioning LiverMultiScan to identify early rejection could positively impact transplant patient management by replacing invasive alternatives.
Finally, COVERSCAN has demonstrated the large burden of comorbidities found in post-COVID-19 syndrome. This large imaging study allowed the establishment of a medical device that measures multiple organs in one scan, and can report on those metrics outside of normal ranges. CoverScan MD can be used to monitor subjects suffering from Long COVID non-invasively. This medical device has been cleared for sale in the UK, with USA clearance pending, and is on track for CE-marking for the EU. Perspectum is now working with NHS England to deliver this service to the NHS.
Our findings show that LiverMultiScan should be used in patients where elastography is unsuitable, with considerable impact on improving the course of illness and treatment management. LiverMultiScan would reduce healthcare costs, estimated at £2,537 saved per quality adjusted life year gained over a 15-year time horizon.
The MRI derived metrics of R2 could noninvasively identify those who have histological rejection, as well as those who have liver related complications, to better monitor the post-transplant population. Positioning LiverMultiScan to identify early rejection could positively impact transplant patient management by replacing invasive alternatives.
Finally, COVERSCAN has demonstrated the large burden of comorbidities found in post-COVID-19 syndrome. This large imaging study allowed the establishment of a medical device that measures multiple organs in one scan, and can report on those metrics outside of normal ranges. CoverScan MD can be used to monitor subjects suffering from Long COVID non-invasively. This medical device has been cleared for sale in the UK, with USA clearance pending, and is on track for CE-marking for the EU. Perspectum is now working with NHS England to deliver this service to the NHS.