Investigation of Elevated Aminotransferases

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ACHAIKI IATRIKI | 2025; 44(4):205–212

Review

Stamatia Tsoupra

Department of Internal Medicine, University General Hospital of Patras, Patras, Greece

Received: 07 Mar 2025; Accepted: 12 May 2025

Corresponding author: Stamatia Tsoupra, Resident Doctor of Internal Medicine, PhD Candidate of the Medical School of University of Patras, Patras, 26504 Greece, Tel.: +30 6944943854, E-mail: stamtsoupra@gmail.com

Keywords: Aminotransferases, elevated liver enzymes, hepatocellular injury

 

Abstract

Elevated aminotransferase levels, specifically alanine transaminase (ALT) and aspartate transaminase (AST), are common findings in clinical practice, often indicating hepatocellular injury. These elevations can result from a variety of causes, including metabolic dysfunction-associated steatotic liver disease (MASLD), alcoholic liver disease (ALD), viral hepatitis, medication-induced liver injury (DILI), and metabolic disorders, such as hemochromatosis and Wilson’s disease. The evaluation of elevated aminotransferases should begin with a thorough history and physical examination to identify potential etiologies. Subsequent investigations may include serologic tests for viral hepatitis, assessments for metabolic and genetic liver diseases, and imaging studies to evaluate liver morphology. In cases where initial evaluations are inconclusive, a liver biopsy may be warranted to obtain a definitive diagnosis. Management strategies are directed at the underlying cause of the enzyme elevation. For instance, lifestyle modifications, including weight loss and dietary changes, are recommended for patients with MASLD. Regular monitoring of liver enzymes is essential to assess disease progression and response to therapy. In summary, elevated aminotransferases are frequently encountered and can signify a spectrum of liver disorders and polysystemic diseases. A systematic approach to evaluation and management is crucial for accurate diagnosis and effective treatment.

Introduction

The evaluation of abnormal liver tests is a common concern in clinical practice, given that liver enzymes are frequently included in routine blood panels. As such, elevated liver enzymes, particularly alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are frequently detected even in asymptomatic patients. Although the term “liver function tests” (LFTs) is widely used, it is somewhat misleading. Many of the tests used to assess liver health, including ALT and AST, are not direct measures of liver function. For example, ALT and AST are primarily markers of hepatocyte injury, rather than direct indicators of liver function such as the liver’s ability to synthesize proteins or produce bile. Therefore, an isolated elevation of these enzymes does not necessarily imply liver failure, but instead, liver injury or damage, which can arise from a variety of causes [1]. It is crucial to interpret these markers within the broader context of clinical symptoms, history, and other laboratory findings.

Understanding the underlying causes of elevated aminotransferases is essential for proper patient management. Hepatic causes of elevated aminotransferases are diverse, including viral hepatitis (such as hepatitis A, B, or C), alcoholic liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), and autoimmune conditions like autoimmune hepatitis. Furthermore, genetic disorders such as Wilson’s disease and hemochromatosis can also present with elevated liver enzymes. In addition to these hepatic causes, extrahepatic conditions must also be considered. These include muscle injuries like rhabdomyolysis, hemolysis, thyroid disorders, and metabolic conditions such as celiac disease or adrenal insufficiency. It is important for clinicians to approach these cases with a systematic diagnostic process to distinguish between hepatic and extrahepatic causes, as treatment and management strategies will vary widely depending on the etiology.

The diagnostic approach to elevated aminotransferases involves several steps. A thorough medical history is critical in identifying potential causes, including any exposure to hepatotoxins such as alcohol or medications, as well as risk factors for viral hepatitis. For example, intravenous drug use, blood transfusions, or travel to regions endemic for hepatitis B or C can increase the likelihood of viral hepatitis. A comprehensive physical examination may also reveal clues to the cause of liver dysfunction, such as signs of chronic liver disease like spider nevi, ascites, or hepatomegaly. Laboratory tests, including ALT, AST, bilirubin, and alkaline phosphatase, provide valuable information, and imaging techniques like ultrasound or CT/ MRI scans may be required to assess liver morphology and the extent of fibrosis. In cases where the diagnosis remains unclear, liver biopsy can be a valuable tool, although it is typically reserved for more advanced cases or when non-invasive tests are inconclusive.

The management of elevated aminotransferases depends on the underlying cause and ranges from lifestyle changes to pharmacological intervention [2]. For instance, viral hepatitis may require antiviral therapy, while autoimmune conditions could be managed with immunosuppressants. MASLD is increasingly recognized as a significant cause of elevated liver enzymes. These patients often benefit from weight loss and control of metabolic risk factors. In some cases, such as with Wilson’s disease or hemochromatosis, chelation therapy may be necessary. Regardless of the underlying cause, regular monitoring of liver function is recommended, especially for chronic conditions, to prevent progression to more severe liver damage, such as cirrhosis or liver failure. Thus, a structured, stepwise diagnostic and management approach is essential in optimizing patient outcomes, ensuring timely intervention, and preventing irreversible liver damage.

Causes of Elevated Aminotransferases

Hepatic Causes of Elevated Aminotransferases

Viral Hepatitis (HAV, HBV, HCV, HDV, HEV)

Viral hepatitis is one of the most common causes of elevated aminotransferases, with Hepatitis A (HAV), B (HBV), and C (HCV) being the main culprits. These viruses cause inflammation of the liver, leading to hepatocellular injury, which results in the release of ALT and AST into the bloodstream. Hepatitis D virus requires the presence of Hepatitis B virus (HBV) to replicate. It can be transmitted through contact with infected blood, sexual contact, and from mother to child during childbirth. Hepatitis A and E, typically transmitted via the fecal-oral route, often causes acute, self-limiting disease. In contrast, Hepatitis B and especially C can lead to chronic infections that may progress to cirrhosis and hepatocellular carcinoma (HCC) if not properly managed. Chronic hepatitis B and C infections result in persistently elevated aminotransferases and can be detected by measuring viral load and liver function tests [3,4].

Metabolic dysfunction-associated steatotic liver disease (MASLD)

MASLD, once called nonalcoholic fatty liver disease (NAFLD), is closely associated with metabolic syndrome and obesity, and it has emerged as one of the most prevalent causes of liver enzyme elevation worldwide. MASLD refers to the accumulation of fat in liver cells without excessive alcohol intake, and includes conditions ranging from simple fatty liver to metabolic dysfunction-associated steatohepatitis (MASH), which can progress to cirrhosis and HCC. Elevated aminotransferases, especially ALT, are commonly observed in MASLD, with ALT often outpacing AST. The pathogenesis of this condition is thought to involve insulin resistance, oxidative stress, and inflammation, which promote fat accumulation and liver injury. Studies have indicated that the prevalence of MASLD correlates with the rising global incidence of obesity and type 2 diabetes mellitus [5,6]. Non-invasive markers such as the NAFLD fibrosis score can help in assessing disease progression.

Alcoholic Liver Disease (ALD)

Alcoholic liver disease (ALD) is a leading cause of liver dysfunction and elevated aminotransferases, especially in individuals with heavy and prolonged alcohol consumption. The liver’s primary role in alcohol metabolism involves the enzyme alcohol dehydrogenase, which breaks down ethanol to acetaldehyde, a toxic substance that can lead to liver inflammation and damage. In the early stages, ALD may cause elevated ALT and AST levels, with a characteristic AST-to-ALT ratio greater than 2:1. Chronic ALD can lead to fatty liver, alcoholic hepatitis, and eventually cirrhosis, with substantial increases in liver enzymes [7]. Additionally, the development of alcoholic liver disease is influenced by genetic and environmental factors, highlighting the complexity of its pathogenesis.

Drug-Induced Liver Injury (DILI)

Drug-induced liver injury (DILI) is a well-known cause of elevated aminotransferases, and it can result from a wide variety of substances, pharmaceutical agents, both over the counter and prescription medications. Drugs such as acetaminophen, statins, and antibiotics are frequently associated with liver toxicity, leading to hepatocellular damage and enzyme elevation. DILI can present as acute or chronic liver injury, with elevated ALT and AST levels being one of the first signs. Acetaminophen overdose is particularly notorious for causing acute liver failure and dramatically raising aminotransferase levels. The mechanism of drug-induced hepatotoxicity is complex, involving both dose-dependent and immune-mediated pathways. Genetic factors, including polymorphisms in drug-metabolizing enzymes, also play a critical role in susceptibility to DILI [8]. The management of DILI typically requires discontinuing the offending drug and providing supportive care, though in severe cases, liver transplantation may be necessary.

Extrahepatic Causes of Elevated Aminotransferases

Muscle Injury (Myositis, Rhabdomyolysis)

Muscle injury, particularly conditions like myositis and rhabdomyolysis, can lead to elevated aminotransferase levels, especially AST, due to the release of these enzymes from damaged muscle cells. Rhabdomyolysis, in which skeletal muscle tissue breaks down and releases intracellular contents into the bloodstream, can cause a dramatic increase in aminotransferases. This condition is often triggered by trauma, prolonged immobilization, strenuous physical activity, or the use of certain medications, including statins. Elevated AST in this context may be disproportionate to ALT levels, as AST is also present in muscle tissue. Myositis, an inflammatory condition of the muscles, can also elevate aminotransferases but typically in lower concentrations compared to rhabdomyolysis. The increased release of enzymes, such as AST and creatine kinase (CK), can indicate the severity of muscle damage and aid in diagnosing these conditions [9,10]. Prompt recognition and management of the underlying cause, including hydration and cessation of any contributing medications, are key to preventing complications such as renal failure, which can occur in severe cases of rhabdomyolysis.

Hemolysis

Hemolysis, the destruction of red blood cells, can also result in elevated aminotransferases, particularly in cases of severe hemolytic anemia. While the primary markers of hemolysis are elevated levels of indirect bilirubin and lactate dehydrogenase (LDH), aminotransferases can be mildly elevated as a secondary effect. The release of AST from red blood cells during hemolysis can contribute to elevated liver enzymes, although the increase is often mild compared to other causes like viral hepatitis or liver disease. Hemolysis may be caused by autoimmune disorders, infections, or certain drugs that target red blood cells. In the setting of hemolytic disease, the liver’s role in processing the breakdown products of red blood cells, such as heme, can further complicate enzyme elevation. Monitoring the pattern of aminotransferase elevation in conjunction with other hemolysis markers is essential in distinguishing hemolysis-related increases from liver-specific causes [11]. Treatment includes addressing the underlying cause that caused the hemolysis, such as blood transfusions for the anemia or immunosuppressive therapy in autoimmune conditions.

Thyroid Disorders and Adrenal Insufficiency

Thyroid disorders, including both hypothyroidism and hyperthyroidism, can influence liver enzyme levels and lead to the elevation of aminotransferases. In hypothyroidism, the slowdown of metabolic processes may lead to a reduction in liver blood flow, which can result in mild hepatocellular damage and consequently elevated aminotransferase levels. The enzyme ALT is typically more affected than AST in hypothyroidism. On the other hand, hyperthyroidism, characterized by overproduction of thyroid hormones, can result in increased hepatic metabolism and, in some cases, hepatocellular injury. Both thyroid conditions may also affect lipid metabolism, leading to MASLD and further enzyme elevations. Monitoring thyroid function in patients with unexplained liver enzyme abnormalities is crucial, as proper management of thyroid disorders often leads to normalization of aminotransferase levels [12,13]. Treatment strategies include hormone replacement for hypothyroidism and anti-thyroid medications or radioactive iodine for hyperthyroidism. Similarly, adrenal insufficiency, which results from inadequate cortisol production due to primary adrenal failure or secondary pituitary dysfunction, can also cause elevated aminotransferases. The pathophysiology behind this elevation is not entirely understood, but it may involve impaired metabolic function in the liver due to insufficient cortisol, which plays a role in glucose and fat metabolism. In both conditions, diagnosing the underlying disease and addressing the root cause is crucial for normalizing liver enzyme levels and preventing further complications [14,15].

Celiac Disease

Celiac disease, an autoimmune disorder triggered by the ingestion of gluten in genetically predisposed individuals, is another extrahepatic cause of elevated aminotransferases. Although the primary manifestations of celiac disease are gastrointestinal, liver involvement can occur in up to 50% of patients, often presenting with elevated ALT and AST levels. Liver damage in celiac disease is believed to be immune-mediated, with inflammation and fibrosis contributing to enzyme elevation [15]. Once a gluten-free diet is implemented, liver enzymes often normalize, though some patients may experience persistent mild elevations.

Diagnostic Approach to Elevated Aminotransferases

History & Clinical Examination

The diagnostic approach to elevated aminotransferases begins with a detailed history and clinical examination. A thorough patient history is crucial, as it can provide insights into potential causes of liver enzyme abnormalities. Key factors to explore include medication use, alcohol intake, metabolic risk factors, and family history. Medications, both prescription and over the counter, as well as herbal supplements, are known contributors to DILI, which can cause significant elevations in aminotransferases. Alcohol consumption is a major risk factor for hepatic conditions such as alcoholic liver disease, which typically presents with elevated AST to ALT ratios. Metabolic risk factors, including obesity, diabetes, and hyperlipidemia, are strongly associated with MASLD and MASH. Family history might provide information regarding inherited conditions like hemochromatosis or Wilson’s disease, which can lead to chronic liver damage and elevated liver enzymes. Clinicians should look for signs of liver disease such as jaundice, hepatomegaly, and ascites, and physical findings of systemic conditions like thyroid disease or muscle tenderness, which may point to extrahepatic causes of elevated aminotransferases [17,18].

Laboratory Tests

Laboratory testing is essential for further evaluating elevated aminotransferases and identifying the underlying cause. The initial blood tests typically include ALT and AST, bilirubin, alkaline phosphatase, and viral hepatitis serologies. ALT and AST levels are the primary markers of hepatocellular injury, with ALT being more liver-specific and AST being present in other tissues such as muscle. An elevated ALT-to-AST ratio is often seen in liver diseases like MASLD, while a higher AST-to-ALT ratio may suggest alcoholic liver disease or cirrhosis. Bilirubin levels, both total and direct, help assess the liver’s ability to excrete waste products and can indicate jaundice. Alkaline phosphatase (ALP) is useful for identifying cholestatic liver diseases, such as primary biliary cirrhosis or gallstone disease. Viral hepatitis serologies, including tests for hepatitis A, B, C, D, E, are necessary to rule out viral infections that are common causes of liver enzyme elevation. Autoimmune markers (e.g., antinuclear antibody [ANA], anti-smooth muscle antibody [SMA]) are essential when autoimmune conditions of the liver, such as autoimmune hepatitis, are suspected. Iron studies, including ferritin and transferrin saturation, can help diagnose conditions like hemochromatosis, a genetic disorder leading to iron overload and liver damage [19,20].

Imaging

Imaging studies play a significant role in the diagnostic evaluation of liver diseases, particularly in assessing hepatic morphology and fibrosis. Ultrasound is the first-line imaging modality due to its non-invasive nature and ability to detect signs of liver disease, such as hepatomegaly, steatosis (fatty liver), and cirrhosis. It can also be used to rule out biliary obstructions, such as gallstones or tumors that might cause secondary liver enzyme elevation. In cases where ultrasound findings are inconclusive or further assessment is needed, more advanced imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) are employed. CT scans provide detailed images of liver structure and are useful in detecting liver masses, cysts, or tumors. MRI, especially with the addition of elastography, offers superior visualization of liver tissue and can help assess the degree of liver fibrosis, a critical determinant of liver disease prognosis. These imaging modalities are invaluable for evaluating chronic liver conditions and can help guide decisions about biopsy or other interventions [21,22].

Liver Biopsy

In cases where the diagnosis remains uncertain despite history, clinical examination, laboratory tests, and imaging studies, a liver biopsy is often considered to obtain a definitive diagnosis. Liver biopsy is the gold standard for assessing the degree of liver damage and fibrosis in conditions like MASLD and autoimmune hepatitis. It involves obtaining a small sample of liver tissue for histopathological examination, which allows for the identification of inflammatory activity, fibrosis, or cirrhosis. Biopsy is particularly valuable in situations where the diagnosis is unclear or when there is a need to assess the stage of liver disease, such as in patients with MASH, where liver damage can range from simple steatosis to advanced cirrhosis. However, because liver biopsy is an invasive procedure with potential risks, it is reserved for cases where the benefits outweigh the risks. Non-invasive methods, such as elastography and serum biomarkers, are increasingly being used as alternatives to biopsy in the evaluation of liver fibrosis [23,24].

Management and Treatment of Elevated Aminotransferases

Management Guided by Underlying Etiology

The management of elevated aminotransferases hinges on identifying and addressing the underlying etiology of the liver injury. Since elevated aminotransferases can arise from a broad spectrum of liver and extrahepatic conditions, treatment strategies vary significantly depending on the cause. For viral hepatitis, antiviral therapy is the cornerstone of management. In contrast, for autoimmune hepatitis, immunosuppressive therapy, including corticosteroids and azathioprine, is used to reduce hepatic inflammation and prevent progression to cirrhosis [25]. For conditions like hemochromatosis and Wilson’s disease, treatment involves chelation therapy to remove excess iron or copper from the body, respectively, preventing further liver damage and systemic complications. Understanding the precise cause of liver enzyme elevation allows for tailored interventions aimed at mitigating damage, improving liver function, and reducing the risk of long-term complications.

Antiviral Therapy and Immunosuppressants

For viral causes of elevated aminotransferases, antiviral therapy plays a critical role in preventing liver damage and improving long-term outcomes. In chronic hepatitis B, antiviral agents like tenofovir and entecavir help suppress viral replication, thereby reducing the risk of liver cirrhosis, HCC, and the need for liver transplantation [26]. HCV has a more favorable prognosis with the advent of direct-acting antivirals (DAAs), which target specific steps in the viral lifecycle, offering cure rates exceeding 95% in most patients [27,28]. For patients with autoimmune hepatitis, immunosuppressive therapy is often necessary to prevent further liver damage. Corticosteroids, such as prednisone, and immunosuppressive drugs like azathioprine are commonly used to reduce inflammation and halt the progression to cirrhosis [25]. In some cases, patients who are refractory to conventional immunosuppressive therapy may require alternative treatments such as mycophenolate mofetil or tacrolimus. The choice of therapy in autoimmune hepatitis depends on the severity of liver damage and the response to initial treatment. For patients with Wilson’s disease, chelation therapy with agents like penicillamine or trientine is used to remove excess copper from the body, while for hemochromatosis, therapeutic phlebotomy is employed to reduce iron levels and prevent further liver damage [29].

Lifestyle Interventions in Chronic Liver Diseases

For many non-viral and non-autoimmune causes of elevated aminotransferases, lifestyle modifications form the foundation of management. MASLD and its more severe form, MASH, are strongly associated with metabolic syndrome, including obesity, diabetes, and hyperlipidemia. In these cases, weight loss through a combination of diet and physical activity is the primary intervention. Studies have demonstrated that even modest weight loss (5-10% of body weight) can significantly reduce liver fat and inflammation, leading to improved aminotransferase levels and reduced risk of progression to cirrhosis [30]. Patients with MASLD are also encouraged to adopt a Mediterranean-style diet, which is rich in antioxidants and healthy fats and has been shown to improve liver function. In addition to dietary changes, the management of associated metabolic risk factors, such as controlling blood sugar levels in diabetic patients and using statins to manage hyperlipidemia, is crucial to prevent further liver injury and reduce the burden of cardiovascular disease, which is a common comorbidity in these patients [31]. Lifestyle changes, such as smoking cessation and limiting alcohol intake, are also essential in protecting liver health [32].

Regular Monitoring and Follow-up in Chronic Liver Diseases

For patients with chronic liver diseases, regular monitoring and follow-up are essential to assess liver function, track the progression of the disease, and detect complications early. Monitoring aminotransferase levels, bilirubin, and alkaline phosphatase is crucial in evaluating the response to treatment and detecting any signs of disease progression, such as fibrosis or cirrhosis. Liver function tests should be repeated periodically to assess the effectiveness of lifestyle interventions, antiviral therapy, or immunosuppressive treatment. In addition to laboratory tests, imaging studies such as ultrasound, elastography, or MRI can help monitor the degree of liver fibrosis and assess the risk of cirrhosis or liver cancer. For patients with chronic hepatitis or MASLD, regular screenings for HCC are also recommended, especially for those with advanced liver disease. In patients with cirrhosis, surveillance for esophageal varices and other complications of portal hypertension should be carried out to prevent life-threatening bleeding. The overall goal of regular monitoring is to optimize treatment, prevent complications, and improve the quality of life for patients with chronic liver conditions [33].

Discussion on Elevated Aminotransferases and Liver Disease

Rising Prevalence of MASLD and Metabolic Syndrome

MASLD has become one of the most common causes of elevated aminotransferases, largely due to the rising global prevalence of metabolic syndrome. Metabolic syndrome, a cluster of risk factors that include obesity, hypertension, dyslipidemia, and insulin resistance, is strongly associated with MASLD [34]. In fact, MASLD has now emerged as a major cause of chronic liver disease, affecting a significant portion of the adult population worldwide. The global prevalence of MASLD is estimated to be around 25-30%, and this number is expected to rise due to the increasing incidence of obesity and type 2 diabetes [35]. Elevated aminotransferases, particularly ALT, are often the first indicators of liver dysfunction in patients with metabolic syndrome, as the liver is directly affected by factors such as insulin resistance and the accumulation of fat within hepatocytes. This trend underscores the importance of monitoring liver enzymes in individuals with metabolic risk factors to identify liver abnormalities early, potentially preventing the progression to more severe liver conditions such as MASH or cirrhosis.

Impact of Early Identification on Liver Disease Progression

Early identification of liver disease, especially in patients with metabolic syndrome and MASLD, is crucial to preventing the progression of liver damage to cirrhosis and hepatic failure. Without intervention, MASLD can progress to more severe forms of liver disease, including MASH, cirrhosis, and eventually liver failure or HCC [31]. However, the progression from simple hepatic steatosis (fat accumulation in the liver) to MASH, which is characterized by inflammation and fibrosis, is not inevitable. In many cases, lifestyle modifications such as weight loss, a healthy diet, and exercise can reverse liver damage, especially in the early stages of the disease. Studies have demonstrated that even a modest weight loss of 5-10% can improve liver histology and reduce the risk of fibrosis progression [35]. Moreover, managing associated metabolic conditions such as obesity and diabetes is essential to reducing the burden of liver disease. For patients with metabolic syndrome, managing risk factors through medications and lifestyle changes can lead to substantial improvements in aminotransferase levels and overall liver health. This highlights the importance of early screening and monitoring of liver enzymes, as timely interventions can prevent irreversible liver damage.

Non-invasive Biomarkers for Liver Health Assessment

One of the key challenges in the management of liver diseases is the lack of reliable, non-invasive biomarkers to assess liver health, particularly for the early stages of the disease. Currently, liver biopsy remains the gold standard for diagnosing the severity of liver damage, such as fibrosis or cirrhosis. However, this procedure is invasive, expensive, and carries risks such as abdominal pain and hemorrhage, which has prompted a growing interest in non-invasive diagnostic methods. Several non-invasive biomarkers have been proposed, including serum markers, imaging techniques such as elastography, and novel biomarkers like the Fibrosis-4 (FIB-4) index or the NAFLD fibrosis score (NFS) [33]. These tests have been shown to correlate well with liver fibrosis and can be used to monitor disease progression and response to treatment. Additionally, imaging techniques like ultrasound and magnetic resonance elastography (MRE) provide valuable insights into liver stiffness, which is indicative of fibrosis [34]. However, despite the progress in developing non-invasive biomarkers, there is still a need for further research to refine these tools and validate their use in clinical practice. The development of highly sensitive and specific biomarkers that can reliably assess liver health and predict disease progression would significantly aid early diagnosis, reduce reliance on invasive procedures, and help tailor individualized treatments.

The Need for Continued Research and Advances in Diagnostics

Although there have been significant strides in understanding the pathophysiology of MASLD and other liver diseases, continued research is essential to improve diagnostics and treatment options. As the prevalence of metabolic syndrome and MASLD continues to rise globally, it is increasingly important to focus on refining non-invasive methods for liver health assessment. For example, while liver function tests like aminotransferases are useful for detecting liver injury, they lack specificity for detecting early stages of liver disease. Novel biomarkers that can detect fatty liver, liver inflammation, and early fibrosis without the need for a biopsy could significantly improve patient outcomes by enabling earlier intervention. Moreover, research into the molecular mechanisms underlying MASLD and its progression to MASH and cirrhosis could lead to the development of targeted therapies that can halt or even reverse liver damage. Such advancements would complement lifestyle interventions and existing treatments, offering patients a broader range of options to manage their liver health [35]. Thus, while current diagnostic approaches offer useful tools for managing liver disease, the future lies in the development of more precise, accessible, and cost-effective diagnostics that can accurately predict disease progression and guide personalized treatment strategies.

Conclusion on Elevated Aminotransferases and Diagnostic Approaches

Elevated aminotransferases are a common clinical finding, and their presence demands a thorough and structured evaluation to accurately distinguish between hepatic and extrahepatic causes. While aminotransferases, particularly ALT and AST, serve as vital markers of liver injury, their elevation can be due to a variety of underlying conditions, ranging from liver-specific diseases such as viral hepatitis, alcoholic liver disease, and MASLD, to extrahepatic causes like muscle injury, hemolysis, and thyroid disorders. Therefore, it is crucial to approach the diagnosis in a systematic, stepwise manner. This process typically begins with a detailed patient history and clinical examination, including assessment of lifestyle factors, medication use, and family history. Following this, appropriate laboratory tests, imaging, and, when necessary, liver biopsy, help to narrow down the potential causes of the elevated aminotransferases.

The adoption of a stepwise diagnostic approach, involving both non-invasive markers and more specific tests, plays a pivotal role in ensuring timely diagnosis and appropriate management. Early detection of the underlying cause of elevated aminotransferases, particularly in conditions like MASLD, can significantly influence treatment strategies. For instance, lifestyle interventions such as dietary changes and weight loss can be effective in the early stages of liver disease, preventing its progression to more severe forms like cirrhosis. Furthermore, the timely management of extrahepatic causes such as hypothyroidism or rhabdomyolysis can help alleviate symptoms and prevent complications. By integrating clinical history, laboratory results, and imaging, healthcare providers can make informed decisions that tailor treatments to the individual needs of the patient, improving both short-term outcomes and long-term prognosis.

Importantly, while significant advances have been made in the diagnosis of liver diseases, further research into non-invasive biomarkers for liver function and fibrosis assessment is essential. Non-invasive tools, such as imaging technologies and blood tests, are increasingly being refined to offer a more accurate, cost-effective, and accessible means of diagnosing liver conditions. These innovations could help reduce the reliance on invasive procedures, such as liver biopsies, and provide patients with a more comprehensive understanding of their liver health. However, despite these advancements, early detection remains the cornerstone of effective management, as it allows for timely intervention and the possibility of reversing or slowing the progression of liver disease, particularly in patients with metabolic syndrome or MASLD.

In conclusion, the evaluation of elevated aminotransferases is an essential clinical task that requires a methodical approach to differentiate between various potential causes. The importance of early diagnosis and appropriate management cannot be overstated, as it is crucial in preventing the progression to more severe liver diseases and improving patient outcomes. Continuing advancements in diagnostic tools and treatment strategies hold promise for enhancing the care of patients with elevated aminotransferases, and ultimately, for reducing the global burden of liver disease.

Conflict of Interest

None to declare.

Declaration of Funding Sources

None to declare.

Author Contributions

Stamatia Tsoupra is the sole author.

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