Sulfasalazine is a widely prescribed disease-modifying antirheumatic drug (DMARD) used to treat rheumatoid arthritis and inflammatory bowel disease in the UK. Whilst this medication can occasionally affect liver function, there is no established direct link between sulfasalazine and the development of fatty liver disease (hepatic steatosis). Drug-induced liver injury from sulfasalazine typically presents as elevated liver enzymes or hepatitis rather than fatty liver. This article examines the evidence on sulfasalazine's effects on the liver, explains monitoring requirements, and provides guidance on recognising and managing potential liver-related concerns whilst taking this medication.
Summary: Sulfasalazine is not recognised as causing fatty liver disease; hepatotoxicity typically manifests as elevated liver enzymes or hepatitis rather than hepatic steatosis.
- Sulfasalazine is a DMARD used for rheumatoid arthritis and inflammatory bowel disease, working through anti-inflammatory and immunomodulatory mechanisms.
- Drug-induced liver injury from sulfasalazine presents as elevated transaminases or hepatitis, not fatty liver (steatosis).
- Regular liver function monitoring is required: two-weekly initially, then monthly for three months, then at least every 12 weeks.
- Stop sulfasalazine immediately and seek same-day medical advice if you develop jaundice, very dark urine with pale stools, or severe abdominal pain.
- Patients with rheumatoid arthritis or inflammatory bowel disease may have increased background risk of non-alcoholic fatty liver disease due to other factors.
- Liver enzyme elevations more than twice the upper limit of normal typically require withholding sulfasalazine and urgent specialist review.
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What Is Sulfasalazine and How Does It Work?
Sulfasalazine is a disease-modifying antirheumatic drug (DMARD) commonly prescribed in the UK for managing inflammatory conditions, particularly rheumatoid arthritis and inflammatory bowel disease (ulcerative colitis). It is licensed in the UK for these indications and belongs to a class of medications known as aminosalicylates. Sulfasalazine has been used clinically for several decades due to its dual anti-inflammatory and immunomodulatory properties.
Whilst sulfasalazine may occasionally be considered by specialists for selected cases of colonic Crohn's disease, it is not routinely recommended by NICE for Crohn's disease management. Patients with Crohn's disease should discuss treatment options with their gastroenterology team, as other therapies are typically preferred.
The drug works through a unique mechanism of action. After oral administration, sulfasalazine passes largely unchanged through the stomach and small intestine until it reaches the colon. Here, bacterial enzymes cleave the molecule into two active components: 5-aminosalicylic acid (5-ASA) and sulfapyridine. The 5-ASA component exerts local anti-inflammatory effects in the bowel, whilst sulfapyridine is absorbed systemically and contributes to the immunosuppressive effects beneficial in rheumatoid arthritis. The precise mechanisms by which sulfasalazine modulates immune function in rheumatoid arthritis are not fully understood, but include inhibition of prostaglandin synthesis, reduction of pro-inflammatory cytokines, and modulation of immune cell function.
Sulfasalazine is typically initiated at a low dose (500 mg once or twice daily) and gradually increased over several weeks to a maintenance dose of 2–3 grams daily, divided into multiple doses. This gradual titration helps minimise common gastrointestinal side effects such as nausea, dyspepsia, and abdominal discomfort. According to NICE guideline NG100 on rheumatoid arthritis management, sulfasalazine represents a first-line conventional synthetic DMARD option, often used as monotherapy or in combination with other DMARDs such as methotrexate. Patients prescribed sulfasalazine require regular monitoring due to potential effects on various organ systems, including the liver and blood counts, which we shall explore in subsequent sections.
References: MHRA/EMC Summary of Product Characteristics (Salazopyrin EN-Tabs), NICE NG100 (Rheumatoid arthritis in adults: management), NICE NG129 (Crohn's disease: management), BNF sulfasalazine monograph, NHS Medicines A–Z: Sulfasalazine.
Recognising Liver Problems While Taking Sulfasalazine
Whilst sulfasalazine is generally well-tolerated, it can affect liver function in a proportion of patients. Hepatotoxicity associated with sulfasalazine typically manifests as elevated liver enzymes (transaminases) or, less commonly, hepatitis, rather than specific pathological changes such as fatty liver disease (hepatic steatosis). According to the MHRA/EMC Summary of Product Characteristics, hepatic adverse reactions include abnormal liver function tests and hepatitis; fatty liver is not listed as a recognised adverse effect of sulfasalazine. There is no established direct link between sulfasalazine and the development of fatty liver as a primary drug-induced effect.
It is important to note that patients with rheumatoid arthritis and inflammatory bowel disease may have an increased background risk of non-alcoholic fatty liver disease (NAFLD) due to factors such as obesity, metabolic syndrome, and reduced physical activity. If you have concerns about fatty liver, discuss these with your doctor, who can assess your individual risk factors and arrange appropriate investigations if needed.
Drug-induced liver injury from sulfasalazine can occasionally occur, presenting in various patterns including hepatocellular, cholestatic, or mixed patterns of enzyme elevation. Liver problems related to sulfasalazine usually develop within the first few months of treatment, though they can occur at any time. Most cases are asymptomatic and detected only through routine blood monitoring. When symptoms do occur, patients may experience:
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Fatigue and malaise – generalised tiredness beyond usual levels
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Jaundice – yellowing of the skin or whites of the eyes
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Dark urine – tea-coloured or brown urine
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Pale stools – clay-coloured or unusually light bowel movements
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Right upper quadrant discomfort – pain or tenderness below the right ribcage
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Pruritus – generalised itching without obvious rash
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Nausea and loss of appetite – particularly if new or worsening
If you develop jaundice (yellowing of the skin or eyes), very dark urine with pale stools, severe abdominal pain, marked itching, or confusion, stop taking sulfasalazine immediately and seek same-day medical advice by contacting NHS 111, attending an Urgent Treatment Centre, or going to A&E.
It is important to distinguish between the common gastrointestinal side effects of sulfasalazine (which typically improve with continued use or dose adjustment) and symptoms potentially indicating liver dysfunction. Severe hepatotoxicity is rare but can progress to acute liver failure if the medication is not discontinued promptly. Risk factors for developing liver problems include pre-existing liver disease, concurrent hepatotoxic medications, and alcohol consumption.
Patients are encouraged to report any suspected adverse reactions to sulfasalazine via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk or through the Yellow Card app. This helps the MHRA monitor the safety of medicines.
References: MHRA/EMC Summary of Product Characteristics (Salazopyrin EN-Tabs), NHS Medicines A–Z: Sulfasalazine, NICE NG49 (Non-alcoholic fatty liver disease: assessment and management).
Monitoring Your Liver Function on Sulfasalazine
Regular monitoring of liver function is an essential component of safe sulfasalazine therapy. The British Society for Rheumatology (BSR) DMARD monitoring guidance and NICE guideline NG100 provide clear recommendations on monitoring schedules for patients taking DMARDs, including sulfasalazine. Before starting treatment, baseline blood tests should include a full blood count (FBC), liver function tests (LFTs) (which measure enzymes such as alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and bilirubin), and urea and electrolytes (U&Es).
During the initial phase of treatment, blood tests (FBC, LFTs, and U&Es) should be performed every two weeks until the dose has been stable for six weeks. Monitoring then continues monthly for the first three months of treatment. This frequent early monitoring allows prompt detection of any hepatotoxic effects or blood abnormalities during the period of highest risk. If blood tests remain stable and within normal limits after three months, the monitoring interval can be extended to at least every 12 weeks (three-monthly) thereafter for the duration of treatment. After any dose increase, monitoring should revert to two-weekly checks until the new dose has been stable for six weeks. Some rheumatology departments or local shared-care protocols may adopt slightly different schedules, so follow the advice of your prescribing team.
When interpreting liver function tests, clinicians typically look for:
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Transaminase elevation (ALT/AST) – levels more than twice the upper limit of normal warrant attention and often require the drug to be withheld
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Alkaline phosphatase rise – may indicate cholestatic injury
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Bilirubin elevation – particularly concerning when accompanied by enzyme rises
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Trends over time – progressive increases even within the normal range
If liver enzymes become elevated, your doctor will assess the degree of abnormality. As a general guide, ALT or AST levels more than twice the upper limit of normal typically require sulfasalazine to be withheld and urgent discussion with your rheumatology or gastroenterology team. Mild elevations (less than twice normal) may be monitored closely with more frequent testing, whilst significant elevations usually require drug cessation. Local protocols may vary, so your clinician will follow the guidance applicable to your care. In most cases, liver enzyme abnormalities resolve within weeks to months after stopping sulfasalazine.
Patients should attend all scheduled monitoring appointments and ensure results are reviewed by their prescribing clinician or specialist team. Do not assume that no news is good news; if you have not heard about your blood test results within a reasonable timeframe, contact your GP surgery or hospital clinic to confirm they have been reviewed.
References: BSR DMARD Safety Monitoring Guidelines, NICE NG100 (Rheumatoid arthritis in adults: management), local NHS shared-care protocols for sulfasalazine, MHRA/EMC Summary of Product Characteristics (Salazopyrin EN-Tabs).
What to Do If You Have Concerns About Liver Health
If you develop any symptoms suggestive of liver problems whilst taking sulfasalazine, it is important to seek medical advice promptly. If you experience jaundice (yellowing of the skin or eyes), very dark urine with pale stools, severe abdominal pain, marked itching, or confusion, stop taking sulfasalazine immediately and seek same-day medical assessment by contacting NHS 111, attending an Urgent Treatment Centre, or going to A&E. These symptoms may indicate serious liver injury requiring urgent evaluation.
For non-urgent concerns such as mild fatigue, nausea, or general unease, do not stop taking sulfasalazine without medical guidance, as this could lead to flare-ups of your underlying inflammatory condition. Instead, arrange an appointment with your GP or rheumatology/gastroenterology team. They can arrange blood tests to check your liver function and assess whether any abnormalities are present. Be prepared to discuss:
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When symptoms started and their progression
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All medications you are taking, including over-the-counter medicines, herbal remedies, and supplements
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Alcohol consumption – even moderate intake can compound liver stress
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Other health conditions that might affect the liver
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Recent infections or illnesses
If liver function tests reveal abnormalities, your doctor will determine the appropriate course of action. This may include temporary cessation of sulfasalazine, dose reduction, or switching to an alternative DMARD. In cases where sulfasalazine-induced hepatotoxicity is confirmed, the drug should not be restarted. Alternative DMARDs such as hydroxychloroquine, methotrexate, or leflunomide may be considered, each with their own monitoring requirements and safety profiles.
To support liver health whilst taking sulfasalazine, patients should:
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Limit alcohol consumption – the UK Chief Medical Officers advise that if you drink regularly, you should consume no more than 14 units per week, spread over three or more days, with several alcohol-free days each week. If you are taking medicines that can affect the liver, it is advisable to minimise alcohol intake further or avoid it altogether.
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Maintain a healthy weight – obesity independently increases the risk of non-alcoholic fatty liver disease (NAFLD)
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Avoid unnecessary medications – particularly those known to affect the liver; always check with your pharmacist or doctor before taking new medicines, including over-the-counter products
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Attend all monitoring appointments – even when feeling well
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Report new medications – inform all healthcare providers about your sulfasalazine use
The NHS Medicines A–Z provides patient-facing resources on sulfasalazine, including advice on side effects and when to seek help. If you have pre-existing liver conditions such as non-alcoholic fatty liver disease (NAFLD), hepatitis, or cirrhosis, these should be discussed with your rheumatologist or gastroenterologist before starting sulfasalazine, as alternative treatments may be more appropriate. With appropriate monitoring and patient vigilance, the vast majority of people taking sulfasalazine do so safely without significant liver complications.
References: NHS Medicines A–Z: Sulfasalazine, UK Chief Medical Officers' low-risk drinking guidelines, NICE NG49 (Non-alcoholic fatty liver disease: assessment and management), MHRA/EMC Summary of Product Characteristics (Salazopyrin EN-Tabs).
Frequently Asked Questions
Does sulfasalazine damage your liver or cause fatty liver?
Sulfasalazine can occasionally cause liver injury, but this typically presents as elevated liver enzymes or hepatitis rather than fatty liver disease (hepatic steatosis). There is no established direct link between sulfasalazine and the development of fatty liver as a primary drug-induced effect, according to MHRA guidance and the Summary of Product Characteristics.
What are the warning signs of liver problems when taking sulfasalazine?
Warning signs include jaundice (yellowing of skin or eyes), very dark urine with pale stools, severe abdominal pain, marked itching, confusion, or persistent fatigue. If you develop jaundice, very dark urine with pale stools, or severe abdominal pain, stop sulfasalazine immediately and seek same-day medical advice via NHS 111, an Urgent Treatment Centre, or A&E.
How often do I need blood tests to check my liver on sulfasalazine?
Blood tests including liver function tests should be performed every two weeks until your dose has been stable for six weeks, then monthly for the first three months. After three months of stable treatment, monitoring continues at least every 12 weeks (three-monthly) for as long as you take sulfasalazine, according to British Society for Rheumatology guidance.
Can I drink alcohol whilst taking sulfasalazine for rheumatoid arthritis?
It is advisable to minimise alcohol intake or avoid it altogether whilst taking sulfasalazine, as alcohol can compound liver stress. If you do drink, follow UK Chief Medical Officers' guidance of no more than 14 units per week spread over three or more days, but discuss your individual circumstances with your doctor or rheumatology team.
What's the difference between sulfasalazine liver damage and fatty liver disease?
Sulfasalazine-induced liver injury typically causes elevated liver enzymes (transaminases) or hepatitis, whilst fatty liver disease (NAFLD) involves fat accumulation in liver cells and is usually related to obesity, metabolic syndrome, or diabetes. Patients with rheumatoid arthritis or inflammatory bowel disease may have increased background risk of NAFLD due to factors unrelated to sulfasalazine itself.
What happens if my liver function tests are abnormal on sulfasalazine?
If liver enzymes (ALT or AST) rise to more than twice the upper limit of normal, sulfasalazine is typically withheld and your rheumatology or gastroenterology team will be contacted urgently. Mild elevations may be monitored closely with more frequent testing, and in most cases, liver enzyme abnormalities resolve within weeks to months after stopping the medication.
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