News

Liver diseases, particularly those associated with alcohol consumption, pose significant challenges to public health worldwide. Identifying these conditions at an early stage can be crucial for effective management and prevention of disease progression. In the pursuit of more accurate diagnostic tools, researchers have studied Keratin 18 (K18), a protein with the potential to change our approach to alcohol-associated liver disease (ALD) diagnosis and prognosis. A recent study led by Dr. Maccioni (2023) and his team sheds light on K18’s role as a promising biomarker for early-stage ALD, offering new insights into disease detection, progression, and potential therapeutic interventions. This is further highlighted by an excellent overview of K18 in ALD in Dr. McClain and his colleagues’ Editorial published in Alcohol: Clinical & Experimental Research.

K18, a critical component of epithelial cells particularly in the liver, plays a pivotal role in keeping the structural integriry and safeguarding hepatocytes from apoptosis (programmed cell death) and necrosis. Extracellular K18 is a marker for epithelial cell death, and serum levels can be significantly elevated following hepatocyte death. K18’s levels increase in response to hepatocyte death, making it a potent indicator of the underlying liver damage. During cell death, loss of cell membrane integrity results in the release of intracellular proteins, including K18, into the extracellular compartment. The caspase cleaved form of K18 (ccK18) is a biomarker for apoptosis which can be detected in serum by the M30 Apoptosense^® ELISA . The M65^® ELISAs detects both caspase-cleaved and uncleaved K18. Thus, measurement of K18 by the M65^® ELISAs can both quantify hepatocyte death and can differentiate necrosis from apoptosis. Several groups have used M65^® as both a diagnostic and prognostic biomarker in severe alcohol-associated hepatitis (AH) (Vatsalya et al., 2020, Bissonnette et al., 2017, Woolbright et al., 2017, Atkinson et al., 2020). Importantly, K18 more accurately measures the magnitude of cell death in alcohol-associated liver disease (ALD) than the regularly used AST and ALT levels.

In this study, Maccioni and his team explored the potential of M65^® as a diagnostic biomarker for early ALD cases. By assessing patients in a rehabilitation program, the study found that “K18-M65 separated minimal liver disease from early ALD (AUROC=0.8704; p<0.0001) with an optimal cut-off at 265.9 U/I”. This discovery would potentially offer a reliable method for identifying ALD at its nascent stages, when intervention is most effective.

Traditional markers like AST and ALT levels, while informative, may fall short in accurately characterizing the extent of liver damage in ALD. Maciconi et al‘s study emphasizes that “K18 more accurately measures the magnitude of cell death in ALD than the regularly used AST and ALT levels”. This heightened accuracy offers a profound advantage in disease assessment and prognostication, enabling medical practitioners to tailor treatment plans more precisely.

The study also touches on an intriguing aspect; patients falling into the “grey zone.” Some individuals with alcohol use disorder (AUD) exhibited K18 levels in the grey zone, indicating possible impending severe AH also shown in earlier trials (Bissonnette et al., 2017). This finding highlights M65^®‘s potential to identify patients who might otherwise be overlooked by conventional markers, ensuring that those at risk receive timely intervention.

The Maccioni et al. study could show that M65® allows detection of early forms of ALD, as well as distinguishing early ALD from the minimal forms of liver disease with a high accuracy (AUROC=0.8704). They also saw that M65® is an independent predictor of more severe forms of ALD, confirming earlier studies that have been done using the biomarker. The authors conclude that the M65® assay can be helpful in in- and out-patient units for:

As research on K18’s diagnostic capabilities deepens, exciting prospects emerge. The study’s robust findings underscore K18’s potential as a diagnostic tool across diverse populations. I would like to end this post by quoting directly from McClain and his colleagues’ Editorial:

“The authors make a strong case for using K18-M65 for detecting early and more aggressive ALD in patients such as those admitted to alcohol treatment programs. Research teams around the world are using terms such as early ALD, mild ALD, “walking ASH”, non-severe ALD, and others to define patient populations with early but clinically relevant ALD. Using tests such as K18, it is becoming clear that there are many of these patients hiding in plain sight. We, as hepatologists, are increasingly teaming up with AUD treatment teams to treat our patients with more severe ALD. In a similar vein, addiction specialists and primary care physicians need to know when to refer patients with AUD to hepatologists. The K18 may be an excellent biomarker for assisting in the decision making. The K18 is not yet FDA approved but the value of this test as an important biomarker across the spectrum of ALD is becoming increasingly clear.” (McClain 2023)

Access the paper here.

Access the Editorial here.

Reda Elkhatib

Hello dear friends and supporters,

As the warmth of the Swedish summer slowly gives way to the soon coming colorful embrace of autumn, we find ourselves reenergized and ready to continue our mission. We are delighted to be back and to share with you the passion that fuels our purpose.

After a well-deserved break, we’re excited to return to our work, more determined than ever to raise awareness about chronic liver conditions and make strides towards our vision of a world with no undiagnosed liver diseases. The sunshine and relaxation (and quite a lot of rain!) of the summer months have provided us with the inspiration needed to push forward and make a lasting impact on the lives of those affected by these silent ailments.

The Swedish summer has always been a time of reflection, growth, and rejuvenation for us. We’ve taken this opportunity to recharge our energies, connect with our loved ones, and find fresh perspectives to bring back to our mission.

We extend our heartfelt gratitude to all of our partners and friends for this half of the year. Together, we shall continue our work toward making a difference in the lives of countless liver disease patients, with raised awareness, early detection, and well established treatment and follow-up.

As we dive back into our work, we invite you to join us on this journey towards our vision. Keep an eye out for our upcoming events, publications, and educational initiatives during the fall and winter.

Thank you for being a part of our community, for your trust, and for your commitment. Together, we can make a significant impact and work towards a world where no one has to suffer from undetected liver conditions. Here’s to a season of renewed purpose and the promise of a healthier, brighter future for all. Please enjoy some lovely pictures from a typical summer here in Stockholm, Sweden.

With gratitude and determination,

The VLVbio Team

We are heading to Vienna for the EASL Congress together with the European Association for the Study of the Liver!

We’re happy to yet again be exhibiting at the face-to-face #EASLcongress with EASL | The Home of Hepatology! We are happy to yet again be an industry partner for the biggest liver event in Europe!

The latest in hepatology is happening 📅 21–24 June.
🤝 Join us at the highlight of the year! Register today, and lets meet and discuss liver biomarkers at our booth.

Learn how to combine the use of FIB-4 together with the M30 Apoptosense® ELISA to asses hepatic fibrosis in NAFLD already at primary care!

As NAFLD global prevalence is at a record high, and continuing to increase, there is a great need to non-invasively assess patients at risk of developing NASH and fibrosis already at primary care.

By using Non-Invasive Tests to evaluate risk group patients already at primary care, only the patients at highest risk of disease progression and liver related complications  will proceed to a specialist in secondary care for further investigation. 

FIB-4 has shown to be a valuable tool to exclude advanced fibrosis, and is widely recommended  in clinical guidelines to be used. The combination of the M30 Apoptosense® ELISA with FIB-4 could enable a more reliable identification of patients with increased risk of progressed NAFLD and might be helpful for deciding which patient should be referred to a specialist and considered for liver biopsy.

Hence, in accordance with the German Society of Gastroenterology, Digestive and Metabolic Diseases Guidelines, a diagnostic tree incorporating FIB-4 and M30® is recommended for the use in NAFLD suspect patients at primary care.

Click here to access the Diagnostic Tree!

NASH and all its complications are especially prevalent in patients with severe obesity and type 2 diabetes. Yet few study data exist on biomarker performance within this patient group, in order to move away from the necessity of liver biopsy in clinical practice.

Sami Qadri, MD & Hannele Yki-Järvinen, MD et al. performed a study to evaluate the use of the M30 Apoptosense ELISA® to diagnose NASH or fibrotic NASH in an obese cohort.

They found that plasma levels of M30® associated with the full histological spectrum of NASH and also had a good ability to identify both NASH and fibrotic NASH with high sensitivity and specificity!

Click here to access the full White Paper!

🚌 We’re aboard the bus to London for a face-to-face ILC2022 with EASL | The Home of Hepatology! We are happy to yet again be an industry partner for the biggest liver event in Europe!

The latest in hepatology is happening 📅 22–26 June.
🤝 Join us at the highlight of the year! Register today, and lets meet and discuss liver biomarkers at our booth.