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HomeHealth articlesliver disordersWhat Are the Biomarkers of Liver Damage?

Liver Disease Biomarkers - An Overview

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The utilization of biomarkers is integral in screening, assessing, monitoring, and forecasting illness prognosis associated with liver disease.

Medically reviewed by

Dr. Vishal Patidar

Published At February 12, 2024
Reviewed AtFebruary 28, 2024


Due to the rising prevalence of liver disease worldwide, the delayed onset of symptoms that can last decades, the need for an invasive reference test (liver biopsy) to assess disease severity, and the lack of reliable tools to evaluate therapeutic interventions, biomarker research in hepatology is progressing.

Pathological damage such as fatty deposits in liver cells, necroinflammation, cell death, and fibrosis expand the range of possible damage in liver disease. The growing need to correlate damage markers with clinical outcomes to improve diagnosis, prognosis, and therapy has addressed the difficulty. Current findings and evaluations cover biomarker identification, hepatic injury, and repercussions biomarkers.

What Is a Biomarker?

A biomarker, also called a biological marker, is a broad category of measurements describing how a cell or organism currently functions. In contrast to the patient's subjectively stated symptoms, biomarkers are medically objective signs used to evaluate the presence or progression of a disease or the effectiveness of a treatment. Molecular, histologic, radiographic, or physiological properties are only a few biomarkers' characteristics. The term "biomarker" refers to a broad category of indicators, including physiological measurements like blood pressure and heart rate, basic metabolic studies, X-ray observations, and complex histological and genetic investigations of blood and diverse tissues. Biomarkers are measures that exclude an individual's subjective sensations or functional skills.

  • Numerous biomarkers, such as heart rate, urinalysis, and blood lead levels, are commonly used and intensively researched in academic studies.

  • Genomics and other advancements in molecular biology have ushered in a bright era for biomarker research, promising early sickness identification and customized treatment techniques.

  • Biomarkers have the potential to serve as surrogate markers in clinical trials, allowing for the evaluation of the efficacy of a certain therapeutic intervention in the treatment of a disease.

What Is Liver Disease?

The term "liver disease" encompasses a range of pathological diseases that have the potential to impact and impair the functioning of the liver adversely. Over a prolonged period, liver disease has the potential to induce the development of cirrhosis, characterized by the formation of scar tissue. The progressive replacement of good liver tissue by scar tissue ultimately impairs the liver's ability to operate optimally. If liver disease is not treated, it has the potential to progress to liver failure and liver cancer.

What Are the Different Types of Biomarkers?

  • Biochemical Biomarkers: These include serum phosphorus, fibrinogen, alpha-fetoprotein, and other markers of differentiation or genetic biomarkers like miRNAs that indicate liver damage. Some biomarkers demonstrate liver cell injury directly, whereas others are indirect byproducts of cellular-intracellular processes.

  • Cytokeratin-18: It is a biomarker that is determined by antibodies M30 and M65. Damage to a hepatocyte cell causes the release of toxins. Other signs of mitochondrial damage in hepatocytes are GDM, mtDNA, and glycodeoxycholate.

  • Lect 2: The liver is responsible for secreting leukocyte-derived chemokine2 (also known as Lect 2) into the serum, which is essential for liver regeneration. The prognosis is improved only when the serum level of Lect 2 is lower. The enzymes SGPT and SGOT, as well as serum Lect 2, would be adversely affected by acute liver failure.

  • NLR: The peripheral neutrophil-lymphocyte ratio, also known as the NLR, is yet another biomarker determined by the complete blood count.

How Are Liver Damage Biomarkers Determined?

Steatosis, necroinflammation, oxidative stress, apoptosis(programmed cell death), and fibrosis are shared by numerous liver diseases. Identifying these distinct elements makes assessing the biomarker-based effectiveness of suggested treatment approaches easier. Since pathological processes are typically interdependent or correlative, identifying biomarkers specific to a single mechanism of injury is difficult. More AFP (alpha-fetoprotein) is produced by hepatic-originating cells due to injury-induced regeneration.

  • Numerous natural history studies have provided evidence indicating that the identification and advancement of fibrosis can be predicted based on the presence and stage of fibrosis observed in liver biopsy samples.

  • Determining biomarkers based on pathological fibrosis has been the focus of the previous decade.

  • Diverse hepatic injuries result in liver fibrosis, a generic wound-healing response with a common pathway.

  • Due to its structure and physical and biochemical features, the hepatic scar inhibits remodeling and architectural alterations, making administering antifibrotic medication challenging. The ability to act in the process of decline may result in the invention of additional medications that have enhanced targeting and pharmacological profiles.

What Are the Biomarkers of Liver Damage?

  • Liver Fibrosis- After a long-term liver injury, liver fibrosis progresses to cirrhosis, which is associated with architectural disruption, angiogenesis (the process of new blood vessel formation from pre-existing vessels), and hemodynamic changes (intra- and extrahepatic), resulting in portal hypertension and genetic alterations. Some will suffer liver failure, bleeding, and hepatocellular carcinoma, which can lead to death if not eliminated. Biomarkers that directly predict these events may improve prognosis and provide a meaningful clinical efficacy assessment (unlike therapeutic success indicators such as fibrosis reduction). Due to the scarcity of liver biopsies and pathological grading systems in hepatology, biomarkers have been extrapolated from pathological to clinical end goals.

  • Alcoholic Hepatitis- Accuracy of scoring methods in determining the long-term prognosis of alcoholic hepatitis. These grading techniques provided an unreliable prediction of death after one year. However, abstinence from alcohol within three to six months of diagnosis was positively correlated with survival. This not only encourages abstinence but also indicates how dynamic measurement can affect the prognosis of liver disease.

  • Portal Hypertension- It causes vascular bleeding, accumulation of fluid, and renal failure. Cirrhosis treatments reduce portal hypertension in the hepatic venous pressure gradient. With abundant evidence supporting its prognostic relevance and management utility, this test is invasive and only available at specialty centers. Credible biomarkers that offer a noninvasive alternative are necessary to assess portal hypertension in clinical practice.

  • Hepatocellular Carcinoma (HCC)- The leading cause of cancer death and the fastest-growing cancer in the world. The majority of patients present at an advanced stage with limited treatment options, and HCC has an uncertain future. Although ultrasound-based testing approaches are widely used, they have limited diagnostic accuracy, with sensitivity values ranging from 25 to 65 percent. Better diagnostic tools are required to detect it earlier and with greater accuracy.

Noninvasive approaches to profile liver disease patients based on liver injury, history of disease, and clinical outcomes are needed to determine care. Although unthinkable, a patient's treatment decision is frequently an empirical activity needing "trial and error." These barriers to care individualization should be solved by biomarker research and dissemination.


Further validation is necessary for biomarkers in liver disease. They differ depending on the state of inflammation, angiogenesis, or fibrosis. The grading and staging of liver injury must be connected to the biomarker's expression. An early-grade biomarker may not accurately predict end-stage liver disease. According to necrotic, cholestasis, drug-induced, or apoptotic liver injury patterns, inflammatory indicators frequently prevail. End-stage liver disease fibrotic biomarkers are represented differently. Studies with sound methodology are needed. The next step in the research is to explore therapeutic approaches that target a certain level of reaction or harm indicative of a biomarker.

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Dr. Vishal Patidar
Dr. Vishal Patidar

General Medicine


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