Diclofenac is a widely prescribed non-steroidal anti-inflammatory drug (NSAID) used to manage pain and inflammation in conditions such as osteoarthritis and rheumatoid arthritis. For individuals with fatty liver disease—a condition affecting up to 30% of the UK population—understanding the safety implications of diclofenac use is essential. Whilst diclofenac does not cause fatty liver disease, it undergoes extensive liver metabolism and carries a risk of drug-induced liver injury in susceptible individuals. This article examines the relationship between diclofenac and fatty liver, explores safe prescribing practices, and discusses alternative pain relief options for those with hepatic concerns.

What Is Diclofenac and How Does It Work?

Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) used to manage pain and inflammation associated with various musculoskeletal conditions. In the UK, oral diclofenac (tablets, capsules, suppositories) is available on prescription only, whilst topical formulations (such as Voltarol gel) can be purchased over the counter from pharmacies. Healthcare professionals prescribe diclofenac for conditions including osteoarthritis, rheumatoid arthritis, acute gout, and post-operative pain.

The mechanism of action of diclofenac involves the inhibition of cyclooxygenase (COX) enzymes, specifically COX-1 and COX-2. These enzymes are responsible for converting arachidonic acid into prostaglandins, which are chemical mediators that promote inflammation, pain, and fever. By blocking this conversion, diclofenac effectively reduces inflammatory responses and provides analgesic relief. The drug demonstrates relatively selective COX-2 inhibition compared to some other NSAIDs, though it still affects both enzyme pathways.

Following oral administration, diclofenac is rapidly absorbed from the gastrointestinal tract and undergoes extensive first-pass metabolism in the liver. The hepatic cytochrome P450 enzyme system, particularly CYP2C9, plays a crucial role in metabolising diclofenac into inactive metabolites that are subsequently excreted via the kidneys and bile. This significant hepatic involvement in drug metabolism is particularly relevant for individuals with pre-existing liver conditions.

Common adverse effects associated with diclofenac include:

• Gastrointestinal disturbances (dyspepsia, nausea, abdominal pain)

• Increased risk of cardiovascular events (dose- and duration-dependent)

• Potential for renal impairment

• Hepatotoxicity in susceptible individuals

Important cardiovascular contraindications: The MHRA has issued guidance stating that systemic diclofenac is contraindicated in patients with established ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, or congestive heart failure (NYHA II–IV). Cardiovascular risk is dose- and duration-dependent and may occur early in treatment, particularly at higher doses (e.g., 150 mg daily). It is essential to use the lowest effective dose for the shortest duration necessary to minimise these risks.

Understanding Fatty Liver Disease

Fatty liver disease, medically termed hepatic steatosis, occurs when excessive fat accumulates within liver cells (hepatocytes). This condition has become increasingly prevalent in the UK, affecting an estimated 20–30% of the general population. There are two principal categories: non-alcoholic fatty liver disease (NAFLD) and alcohol-related fatty liver disease (AFLD), with NAFLD representing the more common form in contemporary clinical practice.

NAFLD encompasses a spectrum of liver conditions ranging from simple steatosis (fat accumulation without significant inflammation) to non-alcoholic steatohepatitis (NASH), which involves inflammation and hepatocyte damage. If left unmanaged, NASH can progress to fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. The condition is strongly associated with metabolic syndrome, type 2 diabetes, obesity, and dyslipidaemia.

Key risk factors for developing fatty liver disease include:

• Obesity (particularly central adiposity)

• Type 2 diabetes mellitus

• Insulin resistance and metabolic syndrome

• Hyperlipidaemia (elevated triglycerides and cholesterol)

• Sedentary lifestyle and poor dietary habits

Most individuals with fatty liver disease remain asymptomatic in the early stages, with the condition often detected incidentally through abnormal liver function tests or imaging studies performed for unrelated reasons. It is important to note that liver transaminases (ALT and AST) can be normal in NAFLD, so normal liver function tests do not exclude the diagnosis. When symptoms do manifest, they may include fatigue, right upper quadrant discomfort, and general malaise.

NICE guidance (NG49) recommends a structured approach to NAFLD assessment. Initial risk stratification should use non-invasive fibrosis scores such as the FIB-4 index or NAFLD Fibrosis Score. For patients with indeterminate or high-risk scores, the enhanced liver fibrosis (ELF) blood test should be used to confirm advanced fibrosis. Patients with confirmed advanced fibrosis, or those in whom alternative liver disease is suspected, should be referred to a hepatology specialist. Liver ultrasound may be used to support diagnosis but is not required for risk stratification.

Lifestyle modification is the cornerstone of NAFLD management, including weight loss (target 7–10% body weight if overweight), optimisation of cardiometabolic risk factors (diabetes control, lipid management), regular physical activity, and alcohol intake within recommended limits. The liver's capacity to metabolise medications may be compromised in fatty liver disease, particularly when inflammation and fibrosis are present. This altered hepatic function can affect drug clearance and increase the risk of medication-related adverse effects, making careful consideration essential when prescribing hepatically metabolised drugs such as diclofenac.

Using Diclofenac Safely with Fatty Liver Disease

The relationship between diclofenac use and fatty liver disease requires careful clinical consideration, as both the underlying liver condition and the medication itself can influence hepatic function. Whilst there is no evidence establishing that diclofenac causes fatty liver disease, NSAIDs including diclofenac are recognised as potential hepatotoxins that can cause drug-induced liver injury in susceptible individuals.

Diclofenac-associated hepatotoxicity, though uncommon, typically manifests as elevated liver transaminases (ALT and AST) and can occasionally progress to more severe hepatocellular or cholestatic injury. The risk appears higher in certain populations, including elderly patients, those with pre-existing liver disease, and individuals taking multiple hepatotoxic medications concurrently. For patients with established fatty liver disease, the compromised hepatic reserve may increase vulnerability to drug-induced liver injury.

Safety considerations for diclofenac use in fatty liver disease:

• Consider baseline liver function tests in patients with hepatic risk factors before starting treatment

• If diclofenac is continued beyond short-term use, check liver function tests within 2–4 weeks and monitor periodically thereafter

• Discontinue diclofenac if liver function tests become persistently abnormal or worsen, or if symptoms of liver dysfunction develop

• Use the lowest effective dose for the shortest duration

• Avoid concurrent use of other hepatotoxic medications where possible

• Consider topical formulations (available over the counter) as alternatives to systemic administration, which significantly reduce hepatic exposure

The British National Formulary (BNF) advises caution when prescribing diclofenac to patients with hepatic impairment, recommending dose reduction or avoidance in severe liver disease. For individuals with mild to moderate fatty liver disease without significant inflammation or fibrosis, short-term diclofenac use under medical supervision may be appropriate, provided liver function is monitored. However, systemic NSAIDs should generally be avoided in patients with cirrhosis (including NASH-related cirrhosis) due to increased risks of hepatotoxicity, gastrointestinal bleeding, renal impairment, and sodium retention; paracetamol is usually the preferred analgesic in this population, with appropriate dose caution.

In addition to hepatic considerations, prescribers must take account of the MHRA cardiovascular contraindications for systemic diclofenac (established cardiovascular disease, heart failure) when assessing suitability. Where systemic NSAIDs are unavoidable in patients at higher gastrointestinal risk, consider co-prescribing gastroprotection (e.g., a proton pump inhibitor) in line with BNF and NICE guidance.

Patients should be advised to report any symptoms suggestive of liver dysfunction, including jaundice (yellowing of skin or eyes), dark urine, pale stools, persistent nausea, or unexplained fatigue, and to discontinue diclofenac pending urgent medical review.

Alternative Pain Relief Options for Liver Conditions

For individuals with fatty liver disease requiring analgesia, several alternative options exist that may present more favourable safety profiles compared to systemic NSAIDs. The selection of appropriate pain relief should be individualised based on the severity of liver disease, the nature and intensity of pain, and other patient-specific factors including comorbidities and concurrent medications.

Paracetamol is often an appropriate first-line analgesic for mild to moderate pain in patients with stable chronic liver disease. Contrary to common misconceptions, paracetamol can be used safely in stable chronic liver disease when taken at recommended doses (up to 4 g daily in divided doses for adults) for short-term use. However, in severe hepatic impairment, low body weight, malnutrition, or chronic harmful alcohol use, reduced maximum doses (for example 2–3 g daily) and extended dosing intervals should be used under clinician oversight. Paracetamol should be avoided in acute liver failure. Patients with liver disease should seek medical advice before using paracetamol regularly.

Topical NSAIDs, including diclofenac gel (available over the counter), offer localised anti-inflammatory effects with significantly reduced systemic absorption compared to oral formulations. For localised musculoskeletal pain affecting accessible joints or soft tissues, topical preparations provide effective analgesia whilst minimising hepatic exposure and associated risks. Studies demonstrate that topical NSAIDs achieve therapeutic concentrations at the application site whilst maintaining plasma levels approximately 5–15% of those seen with oral administration, though this varies by product and application site. For osteoarthritis, NICE guidance (NG226) recommends considering topical NSAIDs as first-line pharmacological treatment.

Opioid analgesics may be considered for moderate to severe acute pain unresponsive to other measures, though they require careful dose adjustment in liver disease. Medications such as oxycodone and morphine undergo hepatic metabolism and may accumulate in hepatic impairment, necessitating dose reduction and extended dosing intervals. Tramadol should be used with particular caution due to its complex metabolism. NICE guidance (NG193) advises against initiating opioids for chronic primary pain; if opioids are used for short-term or severe pain, use the lowest dose for the shortest duration and review regularly.

Non-pharmacological approaches should be emphasised as integral components of pain management:

• Physiotherapy and structured exercise programmes

• Weight management for obesity-related musculoskeletal pain

• Heat or cold therapy for localised pain

• Psychological therapies such as cognitive behavioural therapy for chronic pain

For specific conditions, follow NICE guidance: for osteoarthritis (NG226), consider topical NSAIDs and exercise; for low back pain (NG59), do not offer paracetamol alone and consider exercise and manual therapy. For chronic primary pain (NG193), focus on supervised exercise programmes and psychological therapies rather than routine pharmacological treatment.

For inflammatory arthritis, disease-modifying treatments prescribed by rheumatology specialists may reduce the underlying need for analgesics. Patients should discuss their liver condition with all prescribers to ensure coordinated, safe medication management.

When to Seek Medical Advice About Diclofenac Use

Patients taking diclofenac, particularly those with known fatty liver disease or risk factors for liver conditions, should be aware of important warning signs that warrant prompt medical attention. Early recognition of potential complications can prevent serious adverse outcomes and allow timely intervention.

Seek urgent medical advice or attend A&E if you experience:

• Jaundice (yellowing of the skin or whites of the eyes)

• Dark urine resembling tea or cola

• Pale or clay-coloured stools

• Severe abdominal pain, particularly in the right upper quadrant

• Persistent vomiting or inability to tolerate oral intake

• Signs of gastrointestinal bleeding (black tarry stools, vomiting blood)

Call 999 immediately if you experience signs of a severe allergic reaction:

• Difficulty breathing or swallowing

• Swelling of the face, lips, tongue, or throat

• Widespread rash or skin peeling

• Collapse or loss of consciousness

Contact your GP or pharmacist for routine advice if you notice:

• Persistent indigestion, heartburn, or abdominal discomfort

• Unexplained fatigue or general malaise

• New or worsening ankle swelling

• Unexplained bruising or bleeding tendency

• Any concerns about medication interactions

Patients with diagnosed fatty liver disease should inform their GP before starting diclofenac or any new medication. Your healthcare provider may wish to check baseline liver function tests and establish a monitoring plan if diclofenac is deemed necessary. Regular medication reviews are essential, particularly for individuals taking diclofenac long-term, to assess ongoing need, efficacy, and safety.

If you have been prescribed diclofenac and subsequently receive a diagnosis of fatty liver disease, do not stop the medication abruptly without medical guidance, but arrange a prompt appointment with your GP to discuss alternative options. If you are considering purchasing topical diclofenac over the counter (oral diclofenac is prescription-only in the UK), consult a pharmacist about your liver condition before use.

Pregnancy and breastfeeding: Diclofenac is contraindicated in the third trimester of pregnancy and should be avoided earlier in pregnancy unless the benefits clearly outweigh the risks. If you are pregnant, planning pregnancy, or breastfeeding, seek medical advice before using diclofenac.

Pregnant women, individuals with cardiovascular disease, those with kidney problems, and patients taking anticoagulants or multiple medications should exercise particular caution with diclofenac and ensure close medical supervision. The principle of using the lowest effective dose for the shortest duration remains paramount in minimising risks whilst achieving adequate symptom control.

Reporting side effects: If you experience any side effects from diclofenac, including those not listed in the patient information leaflet, you can report them via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk or by downloading the Yellow Card app. Reporting helps improve the safety of medicines for everyone.

Open communication with your healthcare team about all aspects of your health enables informed, safe prescribing decisions tailored to your individual circumstances.

Frequently Asked Questions