Does ursodeoxycholic acid reduce fatty liver? This question arises frequently as patients and clinicians seek effective treatments for non-alcoholic fatty liver disease (NAFLD). Ursodeoxycholic acid (UDCA), also known as ursodiol, is a bile acid licensed in the UK for primary biliary cholangitis and gallstone dissolution. Despite its hepatoprotective properties, NICE guidance explicitly advises against using UDCA for NAFLD due to insufficient evidence of clinical benefit. This article examines the evidence, explores who truly benefits from UDCA, and outlines proven alternatives for managing fatty liver disease.

What Is Ursodeoxycholic Acid and How Does It Work?

Ursodeoxycholic acid (UDCA), also known as ursodiol, is a naturally occurring bile acid that constitutes a small proportion of the human bile acid pool. In the UK, UDCA is licensed by the Medicines and Healthcare products Regulatory Agency (MHRA) for two specific indications: the treatment of primary biliary cholangitis (PBC) and the dissolution of cholesterol gallstones in selected patients. These licensed uses are detailed in the Summary of Product Characteristics (SmPC) available via the electronic medicines compendium (emc). UDCA is sometimes used off-label for other hepatobiliary conditions, but such use should be under specialist supervision.

The mechanism of action of UDCA is multifaceted. When administered orally, it becomes incorporated into the bile acid pool, where it exerts several beneficial effects on liver cells (hepatocytes). UDCA is hydrophilic and less toxic than endogenous bile acids, helping to protect cell membranes from the damaging effects of more hydrophobic bile acids. It also stimulates bile flow (choleresis), which aids in the elimination of toxic substances from the liver. Additionally, UDCA has demonstrated anti-apoptotic properties, reducing programmed cell death in hepatocytes, and possesses immunomodulatory effects that may reduce liver inflammation in certain conditions.

In the context of non-alcoholic fatty liver disease (NAFLD) and its more severe form, non-alcoholic steatohepatitis (NASH), researchers have investigated whether UDCA's hepatoprotective properties might reduce liver fat accumulation and inflammation. The theoretical rationale is that by improving bile acid composition, reducing oxidative stress, and modulating inflammatory pathways, UDCA could potentially ameliorate the metabolic dysfunction underlying fatty liver disease. However, UDCA is not licensed for the treatment of NAFLD in the UK, and NICE guidance (NG49) explicitly advises not to offer UDCA for treating NAFLD, as there is insufficient evidence of clinical benefit. Any use in this context remains investigational and off-label.

Evidence from Clinical Studies on UDCA and Fatty Liver

The clinical evidence regarding UDCA's efficacy in treating fatty liver disease presents a mixed and largely disappointing picture. Multiple randomised controlled trials and systematic reviews have examined UDCA in patients with NAFLD and NASH, with results that have not established a clear therapeutic benefit.

Early pilot studies suggested potential improvements in liver enzyme levels (particularly alanine aminotransferase, or ALT) in some patients receiving UDCA. However, larger, well-designed trials have generally failed to demonstrate significant improvements in the primary outcomes that matter most: reduction in liver fat content, improvement in liver histology (including fibrosis scores), or prevention of disease progression. A notable study published in Hepatology found that UDCA at standard doses did not significantly improve liver histology compared to placebo in patients with NASH. Systematic reviews and meta-analyses have similarly concluded that UDCA does not produce clinically meaningful benefits in NAFLD or NASH.

Some research has explored higher doses of UDCA (up to 28–35 mg/kg/day), with marginally more promising results in terms of biochemical markers. However, these doses are outside the marketing authorisation, are not recommended in UK practice, and the findings have not been consistently replicated. The European Association for the Study of the Liver (EASL) clinical practice guidelines and NICE guidance (NG49) do not recommend UDCA as a treatment for NAFLD or NASH due to insufficient evidence of clinical benefit.

It is worth noting that combination therapies involving UDCA alongside other agents have been investigated, but again without compelling evidence of superiority over lifestyle modification alone. The current scientific consensus, reflected in UK clinical guidelines, is that UDCA treatment has not been shown to produce clinically meaningful reduction in fatty liver disease. Patients should be aware that while UDCA is generally well-tolerated, its use for fatty liver remains outside licensed indications and is not supported by robust evidence.

Who Might Benefit from Ursodeoxycholic Acid Treatment?

While UDCA has not proven effective for fatty liver disease specifically, there are clearly defined patient groups who do benefit from this medication within its licensed indications. Patients with primary biliary cholangitis (PBC) represent the primary beneficiary group. PBC is a chronic autoimmune liver disease characterised by progressive destruction of small bile ducts, and UDCA is the first-line treatment recommended by NICE and the British Society of Gastroenterology (BSG). In PBC patients, UDCA at a typical dose of 13–15 mg/kg/day improves liver biochemistry, delays histological progression, and may reduce the need for liver transplantation.

Patients with cholesterol gallstones who are not suitable candidates for surgery may also benefit from UDCA therapy, typically at a dose of approximately 10 mg/kg/day. Treatment is appropriate only for carefully selected patients: stones must be small (typically less than 15 mm), radiolucent (non-calcified) on imaging, and the gallbladder must remain functional. Treatment typically requires 6–24 months, and periodic imaging is needed to assess response. Patients should be aware that gallstones may recur after successful dissolution.

For individuals with fatty liver disease, the question of who might benefit from UDCA remains largely unanswered by current evidence. Some hepatologists may consider a trial of UDCA in patients with NAFLD who have concurrent conditions that might respond to the medication, such as those with overlapping features of cholestatic liver disease. However, this represents off-label use and should only be undertaken by specialists after thorough discussion of the limited evidence base and shared decision-making with the patient.

Patient safety considerations are important. Common adverse effects of UDCA include diarrhoea, nausea, and abdominal discomfort, though these are generally mild. Patients should be advised to contact their GP if they experience:

• Severe or persistent diarrhoea

• Right upper quadrant pain

• Jaundice (yellowing of skin or eyes)

• Unexplained fatigue or malaise

Monitoring for patients on UDCA therapy for PBC should follow the UK SmPC recommendations: liver function tests should be checked monthly for the first three months, then every three months thereafter (and as clinically indicated). Once stable, monitoring may be less frequent. If you experience any side effects, including those not listed in the patient information leaflet, you should report them via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk or search for MHRA Yellow Card in the Google Play or Apple App Store.

Alternatives and Lifestyle Changes for Fatty Liver Management

Given the lack of proven pharmacological treatments for NAFLD, lifestyle modification remains the cornerstone of management, as emphasised in NICE guidance (NG49). Weight loss is the most effective intervention for reducing liver fat and improving liver histology in patients with NAFLD and NASH. Evidence demonstrates that a sustained weight loss of 7–10% of body weight can lead to significant improvements in liver inflammation and even regression of fibrosis in some patients.

Dietary modifications should focus on reducing overall calorie intake and improving diet quality. The Mediterranean diet pattern, rich in vegetables, fruits, whole grains, legumes, nuts, and olive oil, with moderate fish consumption and limited red meat, has shown particular promise in clinical studies. Patients should be advised to:

• Reduce intake of refined carbohydrates and added sugars, particularly sugar-sweetened beverages

• Limit saturated fat consumption

• Avoid excessive fructose intake

• Follow UK Chief Medical Officers' low-risk drinking guidelines (no more than 14 units per week, spread over three or more days, with several drink-free days). Patients with advanced fibrosis or cirrhosis should be advised to abstain from alcohol entirely, as should those for whom specialists have recommended abstinence

Physical activity is equally important, with NICE recommending at least 150 minutes of moderate-intensity aerobic activity per week. Both aerobic exercise and resistance training have demonstrated benefits for reducing liver fat, even independent of weight loss. Patients should be encouraged to find sustainable forms of activity they enjoy.

Pharmacological alternatives are limited. NICE NG49 advises that vitamin E may be considered for non-diabetic adults with biopsy-proven NASH, and pioglitazone may be considered for adults with biopsy-proven NASH, both as off-label use in secondary care after discussion of potential risks and benefits. Neither is licensed specifically for NAFLD in the UK. Management of associated metabolic conditions—including type 2 diabetes, hypertension, and dyslipidaemia—is essential and should follow standard NICE guidance.

Patients with NAFLD should be referred to hepatology services if they have:

• Advanced fibrosis suggested by non-invasive markers. For adults under 65 years, a FIB-4 score greater than 3.25 suggests high risk of advanced fibrosis; for those aged 65 and over, a threshold of greater than 2.0 may be more appropriate. A FIB-4 score less than 1.3 (under 65 years) or less than 2.0 (65 years and over) suggests low risk. The Enhanced Liver Fibrosis (ELF) test (NICE DG34) may be used, with a score of 10.51 or above suggesting advanced fibrosis and warranting referral

• Persistently abnormal liver function tests despite lifestyle modification

• Uncertainty about the diagnosis

• Concurrent liver diseases

Regular monitoring through primary care, including assessment of cardiovascular risk factors and liver fibrosis scores (such as FIB-4 or NAFLD fibrosis score), helps identify those requiring specialist input and ensures appropriate ongoing management.

Frequently Asked Questions