SEQC Spanish Society of Laboratory Medicine

Figure 1. Fatty liver disease

'The clinical laboratory in chronic liver disease'

Within the framework of the Conference of the Scientific Committee of the Spanish Society of Laboratory Medicine (SEQC^ML), which was held in virtual format from March 28 - 31, the course 'The clinical laboratory in chronic liver disease' was held with the objective of updating attendees about the new diagnostic strategies for the identification of liver tumours and the diagnosis of fatty liver disease associated with metabolic dysfunction.

Chronic liver disease occurs when the liver has been damaged over long periods of time, resulting in scar tissue that limits the liver's ability to function and repair itself. This condition is the fifth leading cause of death in Europe, and at this time advanced chronic liver disease can only be treated with liver transplantation.

Likewise, through this session, according to its coordinators, the member doctors of the Commission for the Biochemical Assessment of Liver Disease of the SEQC^ML, Manuel Morales-Ruiz, from the Biochemistry and Molecular Genetics Service-Hospital Clínic de Barcelona; and Armando R. Guerra-Ruiz, from the Clinical Analysis Service of the Marqués de Valdecilla University Hospital in Santander, hope to stimulate collaboration between hepatologists, clinical laboratory professionals, and scientific societies from both fields. They believe that this is the way for professionals working with liver disease to become familiar with both areas of knowledge, and that this collaboration will translate into an improvement in patient care and management.

Many of the blood tests performed on patients during their clinical care show abnormalities in liver tests. In this context, laboratory professionals require an up-to-date understanding of liver pathophysiology to improve interpretation of results in conjunction with hepatologists. As Dr. Manuel Morales-Ruiz notes, these alterations may indicate the onset of subclinical liver diseases, some of which are highly prevalent.

However, there are a number of factors to take into account. To begin with, Drs. Morales-Ruiz and Guerra-Ruiz noted that currently available liver profile assessment tests, while proven useful, also have drawbacks. Among these are their low sensitivity and lack of specificity, as values ​​may be elevated in non-hepatic pathology. According to Dr. Guerra-Ruiz, these tests, in turn, are subject to intra- and inter-individual, pre-analytical, and analytical variations that could modify their diagnostic value and require additional interpretation according to the experience of the laboratory professional.

Collaboration between hepatologists and clinical laboratory professionals

In the last decade there has been a great advance in the development of new biomarkers of liver injury based on omic study and liquid biopsy strategies. According to both specialists, this rapid progress also requires an effort to update and train professionals who can familiarize themselves with the new methodologies. Thus, all these aspects require close collaboration between hepatologists and clinical laboratory professionals, which should result in an improvement in the diagnosis and prognosis of these patients, among whom there is a high proportion of asymptomatic cases, the specialists specified.

Regarding the types of liver tumours, hepatocellular carcinoma (HCC) represents 90% of the total cases. As stated by Dr. Morales-Ruiz, the diagnosis of HCC is "satisfactory" when the serum levels of alpha-fetoprotein (AFP) are significantly increased and the diagnostic imaging is also clear. The challenge that hepatologists and clinical laboratory specialists face is the early diagnosis and improvement of the diagnosis of AFP-negative HCC, which represents almost half of the cases.

As pointed out, in this type of tumour, diagnostic imaging is not the solution in many cases, despite its high sensitivity of over 90%. Since most of these tumours are small for the sensitivity available, they do not usually present the typical imaging characteristics and their implementation in screening or first-line diagnosis is complex. Beyond HCC, Dr. Morales-Ruiz stressed that cholangiocarcinoma (another type of liver tumour) has a poor prognosis and, as with HCC, early markers are urgently needed.

Fatty liver and metabolic dysfunction

Fatty liver disease, or hepatic steatosis, is characterized by the accumulation of fat in the liver. This condition encompasses a wide spectrum of liver lesions whose common denominator is the accumulation of fat in the liver (steatosis), but which range from simple steatosis without significant necroinflammatory lesions, to a complex, active pattern called steatohepatitis, which includes active lesions of hepatocellular damage, inflammation, and apoptosis.

Various studies have estimated the prevalence in our country at 21-25% of the general population. According to Dr. Guerra-Ruiz, the clinical laboratories of Spanish hospitals have a unique opportunity to contribute to the diagnosis, staging, and control of the most prevalent liver disease today, fatty liver disease associated with metabolic dysfunction.

Early detection of this condition is key, since, as Dr. Guerra-Ruiz asserted, it is a silent disease; that is, it does not show obvious signs or symptoms for a long initial period of time. When fibrosis or cirrhosis have set in, clinical diagnosis is more likely, but by then the patient's prognosis is much more unfavourable, the specialist stressed.

Both experts pointed out that no isolated analytical magnitude is reliable for the diagnosis of this pathology. However, over time, indices or scores have been developed that combine several of these magnitudes with clinical and epidemiological variables of these patients (age, presence of diabetes, etc.) and that are proving to be very useful in detecting steatohepatitis or hepatic fibrosis. According to Dr. Morales-Ruiz and Guerra-Ruiz, these indices, in combination with other non-invasive methods such as ultrasound, elastography, and direct markers of fibrosis, will allow us to detect and evaluate fatty liver disease to act more efficiently in the prevention and treatment of these patients.