The technology

LiMAx (Humedics GmbH) is a point-of-care diagnostic test for the quantitative measurement of the ratio of breath levels of 13CO2 to 12CO2. This can be used as a measure of functional liver capacity in people with primary and secondary liver tumours, as well as in people having liver surgery or liver transplant. The test is designed to be used with other investigations to help predict and monitor post-operative outcome in liver resection and transplant. The technology helps in selecting patients who are likely to benefit from liver resection. It has the potential to improve patient outcomes by allowing individualised treatment strategies, mainly by informing the surgeon on the extent of resectability.

The technology comprises of an injectable diagnostic drug (13C-methacetin, 'LiMAxetin'); a LiMAx FLIP medical device and LiMAx breathing masks. To do a test, 13C-methacetin (which is labelled with a stable isotope and is not radioactive) is given by intravenous injection. The drug is metabolised by the liver-specific CYP1A2 enzyme into 13CO2 and a small sub-therapeutic amount of paracetamol. Using continuous breath analysis, the LiMAx FLIP medical device measures the change in the ratio of 13CO2 compared with 12CO2. The change in ratio is combined with the patient's body weight to provide a measure of CYP1A2 activity, expressed as a LiMAx value as micrograms per kilogram per hour. The LiMAx value can be determined within 60 minutes and is used to stratify the patient's functional liver capacity into 3 levels of impairment: normal liver function (more than 315 micrograms per kilogram per hour), limited impairment (140 to 314 micrograms per kilogram per hour) and significant impairment (0 to 139 micrograms per kilogram per hour).

An algorithm has been developed for using the test in evaluating patients before liver surgery (Stockmann et al. 2010). It represents a clinical decision tree, based on preoperative LiMAx test results, to support surgical planning in people with a risk of pre-existing liver injury or a planned resection of 2 or more segments. If preoperative LiMAx values indicate normal function, resections of up to 4 segments can be done. In patients with limited impairment or in whom major resection (more than 4 segments) is planned, clinical decisions should also be guided by preoperative liver or tumour volume analysis (for example by computed tomography volumetry). Depending on future remnant liver function (FRLF), resections are classed as either regular (FRLF more than 150 micrograms per kilogram per hour), feasible (FRLF 100 to150 micrograms per kilogram per hour) or critical (80 to 100 micrograms per kilogram per hour), or should not be considered (FRLF less than 80 micrograms per kilogram per hour). For this last group, alternative preoperative options could be considered to improve remnant liver volume (such as portal vein embolisation). Patients with significant impairment should not be considered for surgery and alternative management options should be considered.

LiMAx should not be used in people who are allergic to paracetamol because a small amount is produced during the test. People with an allergy to silicone should also not use LiMAx, because it is present in the LiMAx breathing mask.


The LiMAx system uses a novel marker of liver function capacity, which is measured at point-of-care. It is claimed that current tests are not reliable enough to predict or monitor post-operative complications and mortality after liver surgery or liver transplant.

Current care pathway

The European Association for the Study of the Liver (EASL) clinical practice guidelines on hepatocellular carcinoma (HCC) recommend tailored treatment based on tumour stage, location and how well the patient's liver function is preserved. Although surgical approaches (liver resection or liver transplant) are the main treatments for people with liver cancer, non-surgical options can include thermal ablation, chemoembolisation, systemic chemotherapy and best supportive care (terminal stage).

Liver resection is recommended first-line treatment in people with liver cancer with a non-cirrhotic liver. In cirrhosis, only patients with well-preserved liver function are eligible for resection because of the high risk of post-operative decompensation. Suitability for surgery will depend on a multiparametric evaluation including the Child classification and Model for End-Stage Liver Disease (MELD) score, among other parameters, which together aim to assess liver function reserve and estimate perioperative mortality. The type of surgical technique used for resection will depend on the size and location of the tumour. NICE has published interventional procedures guidance on laparoscopic and radiofrequency-assisted liver resection surgery, as well as ex-vivo hepatic resection and reimplantation. Transplant is recommended in people with liver cancer for whom resection is not suitable, but who stay within Milan criteria for liver transplant (a solitary tumour measuring 5 cm or less and up to 3 nodules measuring 3 cm or less).

According to policies set out by NHS England and the Liver Advisory Group (LAG) of NHS Blood and Transplant (NHSBT), the conditions considered for transplant in adults include acute liver failure, chronic liver failure, liver cancer, and variant syndromes. People needing a transplant are classed as 'super-urgent' (those who have sudden liver failure and are likely to die unless transplanted) or 'elective'. The criteria for an elective transplant, which are set out by the Liver Advisory Group, include people with chronic liver disease who are likely to die within 1 year unless they have a transplant and people with liver cancer for whom a resection is not suitable, as stated above. Prognostic models, such as MELD and United Kingdom Model for End-Stage Liver Disease (UKELD), can help predict survival on the waiting list. Both of these scores are used nationally to list patients (minimal listing criteria is a UKELD score of at least 49) and prioritise those on transplant waiting lists. Like MELD, UKELD is also derived from the patient's serum creatinine and bilirubin and International Normalised Ratio (INR) of the prothrombin time, but it also incorporates information about the patient's serum sodium level. The decision to recommend a transplant is agreed by a multidisciplinary team involving a transplant hepatologist and surgeon. Long-term transplant care should be given by consultant hepatologists in specialist wards and outpatient clinics.

Population, setting and intended user

The LiMAx test would be used as well as current standard tests for the quantitative assessment of liver capacity in adults under evaluation for liver surgery or transplant. The test would be done by any healthcare professional who is authorised to administer intravenous drugs, and results would be interpreted by a medical specialist. The test can be done in an outpatient clinic, intensive care unit, recovery room or standard hospital ward setting. Adoption of the LiMAx system would not need substantial changes to the current care pathway, but operators will need a limited amount of product-specific training. Free on-site training is provided by the company when the device is purchased.


Technology costs

The LiMAx test consists of the LiMAx test kit (single use breathing mask and LiMAxetin diagnostic drug) and LiMAx FLIP reusable breath analysis device. The cost of each LiMAx test is £341 (excluding VAT) based on a minimum annual order of 50 test kits per year. The purchase cost is expressed as an annual charge of £17,050 and includes 1 LiMAx FLIP breath analysis device and 2 LiMAx test training sessions but excludes shipment costs. Since 2 tests are done per patient (before and after surgery), a LiMAx test has a per-patient cost of £682. All technology costs were converted from Euro at a rate of 0.88 pound sterling to 1 Euro.

Costs of standard care

The company identified no currently available comparable real-time technology. Indocyanine green plasma disappearance rate (ICG-PDR) was identified by specialist commentators as an alternative method of evaluating overall liver function, but it is not widely used across the NHS.

Resource consequences

The LiMAx test would be an additional cost to standard investigations of liver function such as biochemical tests or imaging techniques. These costs may be offset if the test allows less expensive management on the basis of predicting post-operative management, for example through a reduced length of stay in hospital.

If adopted, no substantial changes to the current care pathway or to facilities or infrastructure would be needed.