Scientific Calendar May 2026

Chronic liver disease (CLD)

Chronic liver disease (CLD) is a long-term condition in which the liver is progressively damaged over more than six months, leading to inflammation, scarring (fibrosis), and, in some cases, cirrhosis. It can impair the liver’s ability to perform vital functions such as detoxification, protein production, and bile excretion.¹ CLD exists on a continuum that typically progresses from persistent liver injury and inflammation to fibrosis, advanced fibrosis, and cirrhosis, with increasing risk of portal hypertension, liver failure, and hepatocellular carcinoma. Although this progression is often stepwise, the rate and pattern vary according to the underlying cause, and some patients may develop hepatocellular carcinoma even 

in the absence of established cirrhosis.² In addition, disease progression shows great variability depending on the patient and the specific aetiology. Especially in the initial stages, CLD often progresses silently without major symptoms, and progression to cirrhosis can take up to 50 years.³

The most common drivers of CLD are metabolic dysfunction-associated steatotic liver disease (previously termed NAFLD), alcohol-related liver disease, chronic viral hepatitis (particularly hepatitis B and C), and less commonly autoimmune, cholestatic, genetic, or drug-induced liver disorders. These conditions differ in pathogenesis, but all can promote persistent hepatic injury and fibrogenesis, making early identification of the underlying aetiology essential for risk stratification and management. Among these drivers, metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognised as a leading cause of CLD in many high-income settings and is strongly associated with obesity, insulin resistance, type 2 diabetes, dyslipidaemia, and the broader metabolic syndrome. Alcohol-related liver disease remains a major contributor worldwide and spans a spectrum from steatosis and steatohepatitis to advanced fibrosis and cirrhosis. Chronic hepatitis B and C continue to be important causes of CLD globally, particularly where viral prevalence remains high, while autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, haemochromatosis, Wilson disease, and selected hepatotoxic drugs represent less common but clinically important drivers that should be considered in the differential diagnosis.⁴

Chronic liver disease represents a substantial and growing global health burden. Each year it is responsible for around two million deaths worldwide, principally due to cirrhosis, viral hepatitis and liver cancer, making it the 11th leading cause of death globally. Importantly, the impact is not confined to one demographic group: approximately one in three liver-related deaths occurs among females, highlighting its broad population reach. Beyond mortality, the disease contributes significantly to long-term disability, with cirrhosis ranking as the 15th leading cause of disability‑adjusted life years (DALYs) worldwide, reflecting years of life lost and lived with ill health. The economic consequences are also considerable; in the United States alone, liver disease is estimated to cost US$32.5 billion, underscoring the substantial strain placed on healthcare systems and society. Together, these figures demonstrate that chronic liver disease is not only a clinical challenge but also a major public-health and economic concern.⁵

Liver fibrosis

Liver fibrosis is the pathological accumulation of extracellular matrix (particularly fibrillar collagen) in response to chronic liver injury, representing a potentially reversible wound-healing process that distorts normal hepatic architecture to varying degrees. Cirrhosis is the advanced stage of chronic liver disease in which extensive fibrosis is accompanied by regenerative nodules and marked architectural remodelling, resulting in increased risks of portal hypertension, hepatic decompensation, and hepatocellular carcinoma. In short, fibrosis is the process of scar formation, whereas cirrhosis is the structurally and clinically advanced end-stage consequence of severe, widespread fibrosis.^6,7,8

The stage of liver fibrosis is a key determinant of patient prognosis, as higher fibrosis stages are strongly associated with increased risks of cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver-related mortality. Accurate fibrosis staging enables risk stratification, guides treatment decisions and helps monitor disease progression or regression in response to therapy.⁹

Assessment of chronic liver disease increasingly combines non-invasive methods to evaluate fibrosis and guide management. Traditional tools include liver biopsy, serum biomarkers (e.g., APRI, FIB-4), and imaging-based elastography, each with limitations such as invasiveness, intermediate-stage inaccuracy, or influence by comorbid conditions. Biomarker-driven approaches, such as measurement of Mac-2 binding protein glycosylation isomer (M2BPGi), offer a simple blood-based test reflecting fibrogenesis, enabling early detection, risk stratification, and monitoring of disease progression or regression with greater patient convenience.¹⁰

M2BPGi – Mac-2 binding protein glycosylation isomer

M2BP is widely expressed across many tissues, with predominant cellular expression in immune cells, epithelial cells, fibroblasts and tumour cells. In the liver, M2BP is produced by both hepatocytes and non‑parenchymal cells, including Kupffer cells, hepatic stellate cells and cholangiocytes. From a glycobiological perspective, M2BP is a heavily glycosylated secreted protein, bearing multiple N‑linked glycans that are modified by glycosyltransferases within the Golgi apparatus. Under physiological conditions, M2BP displays a stable and well‑regulated glycosylation pattern.¹¹

During liver fibrosis, inflammation‑driven increases in glycosyltransferase activity lead to pathological changes in M2BP glycosylation. These include the addition and branching of O‑linked glycans, enhanced fucosylation (both core and outer‑arm) and altered sialylation. Together, these fibrosis‑associated modifications shift M2BP from its normal glycosylation state and enable its binding to Wisteria floribunda agglutinin (WFA).¹²

During liver fibrosis, hepatic stellate cells (HSCs) become a major source of M2BPGi, with expression levels correlating with fibrosis severity. M2BPGi activates Kupffer cells, stimulating the upregulation and release of Mac‑2 (galectin‑3), a key profibrotic lectin. Mac‑2 in turn further activates HSCs, promoting profibrotic cytokine expression, extracellular-matrix deposition and sustained fibrogenic signalling. This creates an amplifying feedback loop that drives the progression of liver fibrosis.¹³

Detection of M2BPGi

M2BPGi is detected using the HISCL™ M2BPGi™-Qt Assay Kit (RUO*) on the HISCL™ platform through a lectin–glycoprotein assay that specifically recognises fibrosis‑associated glycosylation changes in M2BP. In this method, the M2BP glycosylation isomer in serum is captured by a monoclonal anti‑M2BP antibody bound to lectin‑linked magnetic particles, followed by detection with an alkaline phosphatase‑labelled anti‑M2BP antibody. The lectin Wisteria floribunda agglutinin (WFA) plays a key role by selectively binding to the altered O‑glycan structures of M2BPGi, which are characterised by increased fucosylation and sialylation. This highly specific binding enables quantitative chemiluminescent measurement of M2BPGi and reflects the extent of liver fibrogenesis.¹⁴