Changes

February 2026 — minor update. Wording of risk factors for gallstones clarified. 

Update

Goals

To support primary healthcare professionals to:

• Make a diagnosis of gallstone disease.
• Refer or admit people, when appropriate, to secondary care.

Outcome measures

Audit criteria

QOF indicators

QIPP - Options for local implementation

No QIPP criteria were found during the review of this topic.

NICE quality standards

Gallstone disease

• Adults with acute cholecystitis have laparoscopic cholecystectomy within 1 week of diagnosis.
• Adults with common bile duct stones causing jaundice have endoscopic retrograde cholangiopancreatography within 72 hours of diagnosis.
• Adults with common bile duct stones who need emergency endoscopic retrograde cholangiopancreatography have it within 24 hours.
• Adults with symptomatic gallstone disease who have not had their gallbladder or gallstones removed are advised to avoid food and drink that trigger their symptoms.

[NICE, 2015]

What are gallstones?

• A gallstone (cholelithiasis) is a solid deposit that forms within the gallbladder. 
  • Most gallstones (over 90%) in developed countries consist of cholesterol. 
• Gallstone disease is a general term that describes the presence of one or more stones in the gallbladder or other parts of the biliary tree, and the symptoms and complications they may cause. 
• In some people, one or more gallstones pass out of the gallbladder into the cystic duct, the common bile duct, or the pancreatic duct.
  • Cholecystolithiasis describes gallstones in the gallbladder. 
  • Choledocholithiasis describes gallstones in the common bile duct. 
• Most people with gallstone disease (80%) are asymptomatic and will never know that they have gallstones.

[NICE, 2014; BMJ Best Practice, 2024]

What causes gallstones?

• Gallstones occur when there is a problem with the chemical composition of bile, which results in precipitation of one or more of the constituents.
  • Cholesterol gallstone formation results from three defects: cholesterol supersaturation, accelerated cholesterol crystal nucleation, and impaired gallbladder motility.
• Gallstones can be classified by the dominant constituent that precipitates.
  • The classification is as follows:
    • Cholesterol stones — by far the most common in developed countries (approximately 90%).
    • Pigmented stones — dark-coloured stones made up of bilirubin and calcium salts.
    • Mixed stones — a combination of cholesterol and pigment stones.
  • The composition of gallstones can only be determined reliably after their removal.
• The reason the chemical constituents of bile may change to favour stone formation is often unclear. The type of stone formed may reflect different underlying mechanisms. However, there are known risk factors that increase the chance of developing gallstones.

 [Sanders, 2007; Gurusamy, 2014; Zdanowicz, 2022; BMJ Best Practice, 2024]

How common is it?

• The prevalence of gallstones is approximately 10–15% of adults in Europe and the US.
  • In the US, gallstone disease prevalence has doubled in the last three decades.
• A review of cohort studies that explored the incidence of screen-detected gallstone disease in unselected general populations found that the incidence in European populations was 0.60–1.39% per year.
  • Long-term follow-up in subgroups with screen-detected gallstone disease found that:
    • The cumulative incidence proportion of symptomatic disease was 18% over 20 years of follow-up.
    • Complicated gallstone disease was reported with low incidences of 8% or less depending on the length of follow-up. 
    • Cholecystectomy rates varied across studies, but the highest cholecystectomy incidence was 25.8% over 10 years.
• In a study that reviewed the records of 40,819 people who had had a cholecystectomy in California in the 1990s, the spectrum of gallstone disease identified from the records included biliary colic (56%), acute cholecystitis (36%), acute pancreatitis (4%), choledocholithiasis (3%), gallbladder cancer (0.3%), and cholangitis (0.2%).

[Glasgow, 2000; Stinton, 2010; Shabanzadeh, 2018; Unalp-Arida, 2023; BMJ Best Practice, 2024]

What are the risk factors?

• Risk factors for developing gallstones include:
  • Crohn's disease.
  • Diabetes mellitus.
  • Diet — diets which promote hypertriglyceridaemia (high in refined carbohydrates/sugars), and are low in fibre, are associated with gallstones.
  • Female sex — women have a 2–3 times higher incidence of gallstones compared to men. 
  • Genetic and ethnic factors.
    • In the US, people of Hispanic and Native-American ethnicity have the highest prevalence of gallstones, reaching rates of 50% among men and 70% among women aged over 50 years.
  • Increasing age — incidence rises noticeably in people aged over 40 years, and is 4–10 times more likely in older people, peaking at 70–79 years.
  • Medication: 
    • Somatostatin analogue octreotide impairs gallbladder and small intestinal motility. 
    • Glucagon-like peptide-1 analogues are associated with an increased risk of bile duct and gallbladder disease.
    • Ceftriaxone has been associated with pigment stone development due to precipitation in bile.
  • Non-alcoholic fatty liver disease.
  • Haemolytic anaemia, cystic fibrosis, cirrhosis and ileal disease  — are associated with an increased risk of black pigment stones.
  • Bacterial infection and partial biliary obstruction (such as from primary biliary cirrhosis or malignancy) — are associated with an increased risk of brown pigment stones.
    • In Southeast Asia, the major risk factor is chronic infectious cholangitis caused by infection with biliary parasites (including Clonorchis sinensis, Opisthorchis species, and Fasciola hepatica) 
  • Obesity — people with a Body Mass Index (BMI) over 30 are at greater risk of gallstone formation. 
  • Prolonged fasting/weight loss — this causes gallbladder hypomotility and increases cholesterol excretion in bile.
    • Weight loss exceeding 1.5 kg a week — for example, people who have had bariatric surgery are at increased risk due to cholesterol supersaturation of bile from enhanced cholesterol mobilisation accompanied by decreased bile acid secretion.
  • Use of hormone replacement therapy (HRT).

[EASL, 2016; Shabanzadeh, 2018; BMJ Best Practice, 2024]

What are the complications?

• Complications of gallstones can include:
  • Biliary colic — this is pain caused by the gallbladder, cystic duct, or common bile duct contracting around a gallstone. It is, by far, the most common complication of gallstones. Repeated bouts of biliary colic may develop and it often precedes other complications.
    • The rate of gallstone-related complications is higher in people with a history of uncomplicated biliary colic. 
  • Acute cholecystitis (0.3-0.4% annually in asymptomatic gallstone carriers) — this occurs when obstruction of the cystic duct leads to gallbladder inflammation. It is the second most common complication of gallstones. Acute infective cholecystitis may progress to more severe infection, perforation, or fistula formation. 
  • Acute pancreatitis (0.04-1.5% annually in asymptomatic gallstone carriers) — this occurs when a stone that has migrated along the common bile duct becomes stuck in the biliopancreatic duct causing pancreatic outflow obstruction, and can be life threatening. 
  • Obstructive jaundice (0.1-0.4% annually in asymptomatic gallstone carriers) — a partially or completely blocked common bile duct causes an accumulation of bile pigments in the bloodstream. The obstruction is caused, most commonly, by a stone that has passed from the gallbladder into the bile duct. Rarely, it is due to compression of the common bile duct or the common hepatic duct by a stone in the neck of the gallbladder or cystic duct (Mirizzi syndrome).
  • Other uncommon or rare complications include:
    • Acute cholangitis (also called ascending cholangitis) — this occurs when there is complete obstruction of the bile duct resulting in cholestasis and infected bile, which can be life-threatening. 
    • Fistula formation — if a gallstone erodes through the gallbladder, a fistula can develop causing a duodenal obstruction (Bouveret's syndrome). Erosion of a stone into the common bile duct produces a biliary fistula (a form of Mirizzi syndrome), and if it occurs in the ileum it is known as gallstone ileus. 
    • Biliary peritonitis. 
    • Gallbladder mucocele. 
    • Gallbladder cancer — there is an association between gallstones and cancer of the biliary tract, however, no causative link has been established.

[Sanders, 2007; Gurusamy, 2014; Unalp-Arida, 2023; BMJ Best Practice, 2024]

What is the prognosis?

• Most people with gallstone disease (approximately 80%) are asymptomatic and remain asymptomatic. 
  • For people with asymptomatic gallstone disease there is no reliable pre-morbid indicator to predict who might develop symptoms or complications.
  • People with symptomatic disease are at a persistent high risk for symptom recurrence and need for cholecystectomy. 
• About 20% of people with gallstone disease will develop symptoms during long-term follow-up. 
  • Each year approximately 2-4% of people with previously asymptomatic gallstones develop symptoms — biliary colic is the most common presentation.
• Should a complication develop, the prognosis varies for each type of complication. For example:
  • Although uncomplicated biliary colic is unpleasant, it is not normally life-threatening.
  • Acute pancreatitis and cholangitis are life-threatening complications, with reported figures of 3–20% mortality after a first attack of acute pancreatitis, and 24% mortality after acute cholangitis.
  • Other serious complications (such as gallbladder empyema, perforation, and fistula formation) may result from untreated acute cholecystitis. The prognosis may depend on how quickly and appropriately treatment is given for symptomatic gallstone disease.

[Yadav, 2006; Salek, 2009; Gurusamy, 2014; NICE, 2014; Shabanzadeh, 2018; BMJ Best Practice, 2024]

When should I suspect gallstone disease?

• Suspect gallstone disease in people who present with the classical symptoms and signs of symptomatic gallstone disease or complications of gallstone disease.
  • Biliary colic — this is the most common presentation. Steady non-paroxysmal biliary pain occurs in the epigastrium or right upper quadrant and typically lasts for more than 30 minutes, but less than 8 hours. It is often severe and may be associated with nausea and vomiting, but is not associated with fever or abdominal tenderness.
    • Pain of shorter duration (less than 30 minutes) is less likely to be biliary colic.
  • Acute cholecystitis — this is the second most common presentation. Classical symptoms and signs are similar to biliary colic, but in addition other classical features are fever and tenderness in the right upper quadrant. 
  • Obstructive jaundice — yellowish discolouration of the skin, dark urine, and pale stools. 
  • Cholangitis — typical features, referred to as Charcot's triad, are diagnostic: fever (often with rigors), jaundice, and upper quadrant abdominal pain. 
  • Gallstone pancreatitis — constant epigastric pain radiating through to the back and profuse vomiting. 
  • Various other complications can cause a variety of symptoms.
    • Features that suggest the presence of complications include fever, rigors, hypotension, epigastric pain radiating to the back, dark urine, jaundice, Murphy’s sign (tenderness in the right upper quadrant below the costal margin on deep inspiration), diffuse abdominal tenderness, or a positive result for urine bile pigments on urinalysis.
• Some people with gallstone disease do not have classical symptoms or signs and present with mild and varied symptoms such as indigestion, intolerance to fried or fatty food, or epigastric pain.
  • Consider gallstone disease in any person with any abdominal symptom that is not confirmed to be due to another cause.
• Gallstones may be detected as an incidental finding on abdominal ultrasound or X-ray examination.

What diagnostic tests should I arrange for a person with suspected gallstone disease?

• If gallstone disease is suspected in primary care, or people with abdominal or gastrointestinal symptoms have been unresponsive to previous management, offer: 
  • An abdominal ultrasound examination — this may confirm the presence of one or more gallstones.
    • The absence of stones on an ultrasound scan does not exclude their existence. 
  • Liver function tests (LFTs) — gallstones in the common bile duct may result in abnormal LFTs.
• Consider referral for further investigation if results are normal but clinical suspicion remains high. This may include: 
  • Magnetic resonance cholangiopancreatography (MRCP), if ultrasound has not detected common bile duct stones, but the:
    • Bile duct is dilated and/or
    • Liver function test results are abnormal.
  • Endoscopic ultrasound (EUS) if MRCP does not allow a diagnosis to be made.
• Refer people for further investigations if conditions other than gallstone disease are suspected.

What else might it be?

• The differential diagnoses of gallstone disease include:
  • Acute hepatitis — for more information, see the CKS topics on Hepatitis A, Hepatitis B, and Hepatitis C.
  • Bile duct stricture.
  • Gallbladder polyps. 
  • Gastritis — for more information, see the CKS topic on Dyspepsia - unidentified cause.
  • Gastro-oesophageal reflux disease — for more information, see the CKS topic on Dyspepsia - proven GORD.
  • Inflammatory bowel disease — for more information, see the CKS topics on Crohn's disease and Ulcerative colitis.
  • Irritable bowel syndrome — for more information, see the CKS topic on Irritable bowel syndrome.
  • Non-biliary acute pancreatitis — for more information, see the CKS topic on Pancreatitis - acute.
  • Peptic ulcer disease — for more information, see the CKS topic on Dyspepsia - proven peptic ulcer.
  • Tumours of the gallbladder, liver, stomach, gut, and pancreas — for more information on stomach cancer, see the CKS topic on Gastrointestinal tract (upper) cancers - recognition and referral.
• One or more of these conditions may occur simultaneously with gallstone disease, making the diagnosis more challenging.

Scenario: Management of people with asymptomatic gallstones

From age 18 years onwards.

Scenario: Management of people with symptomatic gallstones

From age 18 years onwards.

Search strategy

Scope of search

A literature search was conducted for guidelines and systematic reviews on primary care management of gallstones.

Search dates

April 2019 - April 2024

Key search terms

The terms listed below are the core search terms that were used for EBSCOhost MEDLINE (searched 23rd April 2019). The were combined with filters to identify guidelines, systematic reviews and primary care relevant literature in EBSCOhost MEDLINE. The strategy was adapted for The Cochrane Library databases. 

S3    S1 OR S2 
S2    AB ( ((gall stone*) or (gallstone*) or cholelithias* or cholecystolithias* or choledocholithias* or bile duct stone*) ) OR TI ( ((gall stone*) or (gallstone*) or cholelithias* or cholecystolithias* or choledocholithias* or bile duct stone*) ) 
S1    (MH "Cholelithiasis+") 

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• World Health Organization
• Guidelines International Network
• TRIP database
• Agency for Healthcare Research and Quality
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Drug and Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalk
• BMJ - Patient Journeys

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• Medicines and Healthcare products Regulatory Agency (MHRA)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
• Consistency with other providers of clinical knowledge for primary care.
• Accuracy of implementation of national guidance (in particular NICE guidelines).
• Usability.

Principles of the consultation process

• The process is inclusive and any individual may participate.
• To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
• Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
• Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
• External reviewers are not paid for commenting on the draft topics.
• Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
• All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
• All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

• Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
• Stakeholders identified from the following groups are invited to review draft topics:
  • Experts in the topic area.
  • Professional organizations and societies (for example, Royal Colleges).
  • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
  • Guideline development groups where the topic is an implementation of a guideline.
  • The British National Formulary team.
  • The editorial team that develop MeReC Publications.
• Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

• Topic selection
• Scoping of topic
• Selection of clinical scenarios
• First draft internal review
• Second draft internal review
• External review
• Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
• Outcomes have no clear evidence of clinical effectiveness
• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
  • Eligible population
  • Current interventions
  • Likely uptake of new intervention or recommendation
  • Cost of the current or new intervention mix
  • Impact on other costs
  • Condition-related costs
  • In-direct costs and service impacts
  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

• Personal financial interests
• Personal family interest
• Personal non-financial interest
• Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.