Ankylosing spondylitis and fatty liver disease are two chronic conditions that can coexist in the same patient, creating unique management challenges. Ankylosing spondylitis (AS) is an inflammatory condition affecting the spine and joints, whilst fatty liver disease involves excess fat accumulation in liver cells. Research suggests people with AS may face an increased risk of developing fatty liver due to chronic inflammation, reduced physical activity, metabolic factors, and certain medications. Understanding the connection between these conditions is essential for comprehensive care, as both require ongoing monitoring and lifestyle management to prevent complications and optimise long-term health outcomes.

Understanding Ankylosing Spondylitis and Fatty Liver Disease

Ankylosing spondylitis (AS) is a chronic inflammatory condition primarily affecting the spine and sacroiliac joints. It is part of a group of conditions called axial spondyloarthritis, with AS specifically referring to cases where inflammation has caused visible changes on X-rays (radiographic axial spondyloarthritis). AS typically presents with persistent lower back pain and stiffness, particularly in the morning or after periods of rest. Over time, inflammation can lead to fusion of the spinal vertebrae, reducing flexibility and potentially affecting posture. AS is more common in men and usually begins in early adulthood, though it can affect people of any age.

Fatty liver disease, medically termed hepatic steatosis, occurs when excess fat accumulates in liver cells. There are two main types: non-alcoholic fatty liver disease (NAFLD), which is not related to alcohol consumption, and alcoholic fatty liver disease. NAFLD is increasingly common in the UK and is often associated with metabolic conditions such as obesity, type 2 diabetes, and high cholesterol. In most cases, fatty liver causes no symptoms in its early stages, though it can progress to more serious conditions like non-alcoholic steatohepatitis (NASH), fibrosis, or cirrhosis.

Both conditions are chronic and require ongoing management. Whilst they affect different organ systems—AS primarily impacts the musculoskeletal system and fatty liver affects hepatic function—there are emerging connections between inflammatory conditions and metabolic health. Understanding how these conditions may coexist is important for comprehensive patient care. Patients with AS may be at increased risk of developing fatty liver disease due to several factors, including reduced physical activity from joint pain and stiffness, shared inflammatory pathways, and metabolic comorbidities. Certain medications used to treat AS, particularly systemic corticosteroids (though these are not recommended for axial symptoms) and methotrexate (if used for peripheral joint involvement), may also affect liver health through different mechanisms, including hepatotoxicity and metabolic effects.

The Link Between Ankylosing Spondylitis and Fatty Liver

Observational research suggests that people with ankylosing spondylitis may have a higher prevalence of fatty liver disease compared to the general population, though a direct causal link has not been definitively established. Several mechanisms may explain this association, though the relationship is complex and influenced by multiple confounding factors including obesity, physical inactivity, and treatment exposures.

Chronic systemic inflammation, a hallmark of AS, can contribute to metabolic dysfunction and insulin resistance, both of which are risk factors for developing NAFLD. Inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which are elevated in AS, may also play a role in hepatic fat accumulation.

Reduced physical activity is another important factor. The pain, stiffness, and fatigue associated with AS can limit exercise capacity, leading to a more sedentary lifestyle. Physical inactivity is a well-established risk factor for metabolic syndrome and NAFLD. Additionally, some patients with AS may experience weight gain, further increasing their risk of fatty liver disease.

Certain metabolic comorbidities appear to be more common in people with AS, including hypertension, dyslipidaemia, and type 2 diabetes. These conditions share common pathophysiological mechanisms with NAFLD, including insulin resistance and abnormal lipid metabolism. The presence of metabolic syndrome—characterised by central obesity, raised blood pressure, elevated blood glucose, and abnormal cholesterol levels—significantly increases the risk of both cardiovascular disease and fatty liver disease in patients with inflammatory arthritis.

It is important to note that not all patients with AS will develop fatty liver disease, and the relationship between these conditions is multifactorial. Individual risk factors, genetics, lifestyle, and medication use all contribute to a person's overall risk profile. Regular screening for metabolic risk factors and proactive management of modifiable risks are important aspects of care for people with AS.

How Ankylosing Spondylitis Medications Affect the Liver

Several medications used to manage ankylosing spondylitis can affect liver function, making monitoring essential for patients, particularly those with pre-existing fatty liver disease.

Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, naproxen, and diclofenac, are the first-line treatment for pain and inflammation in AS. Whilst generally well-tolerated, NSAIDs can occasionally cause hepatotoxicity, with elevated liver enzymes (transaminases) occurring in a small percentage of patients. Long-term or high-dose NSAID use requires periodic liver function monitoring.

Sulfasalazine is recommended by NICE for peripheral arthritis in axial spondyloarthritis. It requires monitoring of liver function tests, as hepatotoxicity can occur, particularly in the first few months of treatment. Baseline liver function tests should be performed, with regular monitoring during the initial treatment period and periodically thereafter.

Methotrexate is not recommended for axial symptoms of AS under NICE guidance (NG65). If considered for peripheral joint involvement in axial spondyloarthritis, this represents off-label use with limited supporting evidence. Methotrexate carries a significant risk of liver toxicity and can cause hepatic fibrosis and cirrhosis with prolonged use, especially in patients with pre-existing liver disease, obesity, or diabetes. Monitoring schedules follow Specialist Pharmacy Service (SPS) and British Society for Rheumatology (BSR) guidance, as well as the Summary of Product Characteristics (SmPC): baseline liver function tests are required, followed by monitoring every 1–2 weeks until therapy is stabilised, then every 2–3 months, adjusted according to local protocols and individual risk. Patients taking methotrexate should also receive folic acid supplementation to reduce toxicity and are advised to avoid alcohol or minimise consumption to reduce hepatotoxic risk.

Biologic therapies, including TNF-α inhibitors (such as adalimumab, etanercept, and infliximab) and interleukin-17 (IL-17) inhibitors (such as secukinumab and ixekizumab), are used for moderate to severe AS when NSAIDs have been inadequate and there is objective evidence of active inflammation. Before starting biologic therapy, screening for tuberculosis (TB) and hepatitis B is mandatory (testing for hepatitis B surface antigen [HBsAg] and hepatitis B core antibody [anti-HBc]); hepatitis C screening is also usually considered. This is because biologics can reactivate latent infections. Mild, transient elevations in liver enzymes may occur but are usually not clinically significant. Baseline liver function tests should be performed, with periodic monitoring as clinically indicated, particularly in the first few months of treatment.

Systemic corticosteroids are not recommended for axial symptoms of AS under NICE guidance. When used in other contexts, they can contribute to metabolic dysfunction, weight gain, and insulin resistance, potentially worsening fatty liver disease.

The choice of medication should be individualised, taking into account liver health, comorbidities, and the need for regular monitoring. Patients should report any suspected side effects via the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk or via the Yellow Card app).

Managing Both Conditions: Treatment Considerations

When a patient has both ankylosing spondylitis and fatty liver disease, a coordinated, multidisciplinary approach to management is essential.

Lifestyle modification forms the cornerstone of treatment for fatty liver disease and can also benefit AS. Weight loss of 7–10% of body weight has been shown to improve liver histology in patients with NAFLD and can reduce inflammation and improve symptoms in AS. A balanced diet rich in vegetables, fruits, whole grains, and lean proteins, whilst limiting processed foods, saturated fats, and added sugars, is recommended.

Regular physical activity is particularly important, though it must be tailored to the individual's capabilities. Exercise helps reduce hepatic fat, improves insulin sensitivity, and maintains spinal mobility in AS. The UK Chief Medical Officers' Physical Activity Guidelines recommend at least 150 minutes of moderate-intensity aerobic activity per week for adults, along with strengthening activities on at least two days per week. For people with AS, physiotherapy and specific exercises focusing on posture, flexibility, and core strength are beneficial. Swimming and hydrotherapy are often well-tolerated options that provide cardiovascular benefits without excessive joint stress.

Medication selection requires careful consideration and should follow NICE guidance (NG65). NSAIDs remain first-line for axial symptoms. For peripheral arthritis in axial spondyloarthritis, sulfasalazine is the recommended conventional disease-modifying drug. Biologic therapies are considered when NSAIDs have been inadequate and there is objective evidence of active inflammation, in line with relevant NICE technology appraisals. In patients with established fatty liver disease or elevated liver enzymes, medications with lower hepatotoxic potential should be preferred. If NSAIDs are necessary, the lowest effective dose should be used, with regular monitoring of liver function.

Referral to hepatology should be considered when non-invasive fibrosis risk scores (such as FIB-4 or NAFLD Fibrosis Score) indicate intermediate or high risk, when the Enhanced Liver Fibrosis (ELF) test shows a score of 10.51 or above (indicating advanced fibrosis risk), or when liver function tests remain abnormal despite optimisation of metabolic risk factors.

Managing comorbidities such as diabetes, hypertension, and dyslipidaemia is crucial, as these conditions contribute to both AS disease activity and fatty liver progression. Optimising glycaemic control, blood pressure, and lipid levels through medication and lifestyle changes can improve outcomes for both conditions. Patients should be advised about UK alcohol limits: no more than 14 units per week, spread over three or more days, with several alcohol-free days each week. Those taking methotrexate should avoid alcohol or minimise consumption further to reduce hepatotoxic risk.

Monitoring Liver Health with Ankylosing Spondylitis

Regular monitoring of liver health is essential for patients with ankylosing spondylitis, particularly those taking medications that may affect hepatic function or those with risk factors for fatty liver disease.

Liver function tests (LFTs) are the primary screening tool and typically include measurements of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, and albumin. Elevated transaminases may indicate liver inflammation or damage, though mild elevations can occur in fatty liver disease without significant harm. Prothrombin time or INR may also be checked when there is concern about liver synthetic function.

The frequency of monitoring depends on the medications being used. For patients on methotrexate, monitoring follows SPS, BSR, and SmPC guidance: liver function tests should be checked at baseline, then every 1–2 weeks until therapy is stabilised, followed by monitoring every 2–3 months, adjusted according to local protocols and individual risk factors. For those on NSAIDs long-term, periodic monitoring (e.g., every 6–12 months) is prudent. Patients on sulfasalazine require baseline LFTs and regular monitoring, particularly in the first few months. Those on biologic therapies should have baseline LFTs and periodic monitoring as clinically indicated, particularly in the first few months of treatment.

Assessment for fatty liver disease and fibrosis risk should include non-invasive fibrosis risk scores as a first-line approach. The FIB-4 score and NAFLD Fibrosis Score can be calculated from routine blood tests and help stratify patients into low, intermediate, or high risk of advanced fibrosis. For those at intermediate or high risk, the Enhanced Liver Fibrosis (ELF) test may be used; a score of 10.51 or above indicates a high likelihood of advanced fibrosis and warrants specialist referral, in line with NICE guidance (DG34).

Imaging investigations may be warranted if fatty liver disease is suspected or confirmed. Ultrasound scanning is a non-invasive method to detect moderate to severe hepatic steatosis, though it has limited sensitivity for mild steatosis. Transient elastography (FibroScan) can measure liver stiffness, which correlates with fibrosis severity, and is useful for assessing disease progression. Blood tests including a full lipid profile, fasting glucose or HbA1c, and assessment of metabolic syndrome components are important for evaluating overall metabolic health.

Patient education about the importance of monitoring is crucial. Patients should be encouraged to attend scheduled blood tests and report any symptoms that might suggest liver problems, such as unusual fatigue, jaundice (yellowing of skin or eyes), dark urine, pale stools, or abdominal discomfort. Maintaining a record of test results can help patients and healthcare professionals track trends over time and make informed treatment decisions.

When to Seek Medical Advice

Patients with ankylosing spondylitis should be aware of situations that warrant prompt medical attention, particularly concerning liver health.

New or worsening symptoms such as persistent nausea, vomiting, loss of appetite, unexplained weight loss, or abdominal pain—especially in the upper right quadrant—should be reported to a GP promptly. These symptoms could indicate liver inflammation or other hepatic complications.

Jaundice, characterised by yellowing of the skin or whites of the eyes, dark urine, or pale stools, is a red flag symptom requiring urgent medical assessment. Whilst jaundice is uncommon in simple fatty liver disease, it may indicate more advanced liver disease, bile duct obstruction, or drug-induced liver injury. Patients should seek same-day medical advice if jaundice develops.

Unusual fatigue or malaise that is disproportionate to AS disease activity, particularly if accompanied by other symptoms, should be discussed with a healthcare professional. Whilst fatigue is common in AS, significant changes in energy levels or general wellbeing may warrant investigation, including liver function assessment.

Patients should also contact their GP or rheumatology team if they experience unexpected bruising or bleeding, as this can indicate impaired liver synthetic function affecting clotting factors. Emergency symptoms such as confusion or drowsiness, vomiting blood, black tarry stools, or severe abdominal swelling warrant immediate assessment via 999 or attendance at an emergency department.

Any new medications or supplements should be discussed with a healthcare professional before starting, as some over-the-counter products and herbal remedies can affect liver function or interact with AS medications.

If routine blood tests show abnormal liver function, patients should ensure appropriate follow-up is arranged. Action thresholds for abnormal LFTs vary by medication, pattern of derangement, and local protocols (for example, some drugs require interruption at three times the upper limit of normal). Persistent or significantly elevated liver enzymes require further investigation and may necessitate medication adjustment or specialist referral. Regular communication with the healthcare team, adherence to monitoring schedules, and prompt reporting of concerning symptoms are essential for maintaining both musculoskeletal and liver health in patients managing ankylosing spondylitis.

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