Changes

January to February 2024 — reviewed. A literature search was conducted in January 2024 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last version of this topic. The recommendations have been updated in line with current evidence in the literature. A section on the assessment of a person with suspected cirrhosis has been added. The criteria on when to consider palliative care referral have been expanded. The recommendations on primary care management of a person with cirrhosis have been updated and expanded.

Update

Goals

To support primary healthcare professionals to:

• Identify people at risk of cirrhosis.
• Arrange investigations to assess for cirrhosis and any complications in at-risk people.
• Refer people with suspected cirrhosis for specialist investigation.
• Ensure people with confirmed cirrhosis are under specialist care for treatment of any underlying liver disease and screening and surveillance of complications, if appropriate.
• Offer appropriate self-care and lifestyle advice.
• Arrange appropriate management for complications of cirrhosis including hospital admission or referral, depending on clinical judgement.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

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

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

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

NICE quality standards

The NICE quality standards relevant to this CKS topic are:

• People with non-alcoholic fatty liver disease are given advice on physical activity, diet, and alcohol.
• People with non-alcoholic fatty liver disease are offered regular testing for advanced liver fibrosis.
• Young people and adults with risk factors for cirrhosis are offered non-invasive testing for cirrhosis.
• Adults with cirrhosis are offered 6-monthly surveillance for hepatocellular carcinoma.
• Young people and adults with cirrhosis and upper gastrointestinal bleeding are given prophylactic intravenous antibiotics at presentation.

[NICE quality standard, 2017]

What is it?

• Cirrhosis is a form of liver disease which develops as a result of chronic inflammation of the liver, which can be due to a number of progressive liver conditions, usually over the course of 10–20 years [Gines, 2021; Mansour, 2023a; NICE, 2023].
  • It is defined as the widespread disruption of normal liver structure, which becomes distorted with regenerative nodules surrounded by diffuse fibrosis. This affects the liver's synthetic, metabolic, and excretory actions.
• A transition from compensated to decompensated disease occurs in some people due to the development of portal hypertension (a pathologic increase in portal venous pressure) and/or hepatocellular dysfunction [Muir, 2015; Mansour, 2023b].
  • Compensated cirrhosis — describes the initial largely asymptomatic phase when the liver still functions effectively.
  • Decompensated cirrhosis — describes the symptomatic phase when the liver is damaged affecting its function, with potentially life-threatening complications such as jaundice, ascites, hepatic encephalopathy, and/or variceal bleeding.

How common is it?

It is difficult to assess the true prevalence of cirrhosis because the initial stages are often asymptomatic, and therefore it remains undiagnosed and presents late in many people [OHID, 2022a].

• The prevalence of cirrhosis has risen significantly over recent decades, and is predicted to rise further in the future [Mansour, 2023a].
• The rate of hospital admission for liver disease significantly decreased compared to the previous year from 143.6 per 100,000 population to 124.3 per 100,000 population in England, in the financial year ending 2021 (reflecting the first full year of the COVID-19 pandemic) [OHID, 2022b].
  • Overall rates of liver disease hospital admissions remained highest in the north of England with the North East having the highest rate of 166.8 per 100,000 population.
  • Rates of hospital admission for alcoholic liver disease were the highest (45.5 per 100,000 population).
  • Areas with high levels of deprivation experienced higher rates of hospital admission for liver disease.
• The British Liver Trust web statistics data state there were 12,077 recorded deaths from liver disease in the UK in 2022 [British Liver Trust, 2024].
  • The average age of death from liver disease in 2020 in England was 61 for men and 62 for women [OHID, 2022a].
  • Liver disease deaths are nearly twice as high among men compared to women [BLT stats 2024].
  • Rates of premature death from liver disease are four-fold higher in the most deprived areas of England and Scotland [British Liver Trust, 2024].
• A review of 260 epidemiological studies found that cirrhosis is responsible for about 170,000 deaths in Europe each year, with large variations in death rates between countries [Blachier, 2013].

What are the risk factors?

A variety of factors increase the risk of developing cirrhosis, however, the presence of risk factors does not inevitably lead to its development. The presence of multiple risk factors may lead to a cumulative risk for cirrhosis and its complications. 

• Common risk factors [Newsome, 2018] [Gines, 2021] [Mansour, 2023a] [NICE, 2023] 
  • Increased alcohol intake — over 50 units of alcohol per week for men, and over 35 units of alcohol per week for women, for at least several months, which increases the risk of developing alcohol-related liver disease. See the CKS topic on Alcohol - problem drinking for more information.
  • Hepatitis B and C virus infection. See the CKS topics on Hepatitis B and Hepatitis C for more information.
  • Obesity and/or type 2 diabetes — increased risk of cirrhosis if concomitant non-alcoholic fatty liver disease (NAFLD) and increased risk of advanced liver fibrosis. See the CKS topics on Diabetes - type 2, Non-alcoholic fatty liver disease (NAFLD), and Obesity for more information.
    • Obesity also increases the risks of alcohol-related liver disease [OHID, 2022a].
• Other risk factors [Newsome, 2018] [Smith, 2019] [Gines, 2021]
  • Autoimmune liver disease (such as autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis).
  • Genetic conditions (such as haemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, and cystic fibrosis).
  • Drug-induced liver injury — for example, due to long-term amiodarone, methotrexate, or methyldopa use.
  • Budd-Chiari syndrome; veno-occlusive disease; and hereditary haemorrhagic telangiectasia.
  • Sarcoidosis and type IV glycogen storage disease.

What are the complications?

General risks and complications

• Malnutrition and frailty
  • Malnutrition can be present in up to 20% of people with compensated cirrhosis [Mansour, 2023a]. It is due to multiple factors including reduced oral intake (due to hepatic encephalopathy, ascites, or reduced appetite), malabsorption (due to portal enteropathy, jaundice, or pancreatic insufficiency), and protein loss into ascites. It leads to an increased risk of sarcopenia (reduced muscle mass, strength, and function) and frailty [Mansour, 2023b]. See the CKS topics on Adult Malnutrition and Multimorbidity for more information.
• Osteoporosis
  • There is an increased risk of osteoporosis and associated fracture risk [Mansour, 2023a]. See the CKS topic on Osteoporosis - prevention of fragility fractures for more information.
• Infection and sepsis
  • People with cirrhosis are immunosuppressed and are at higher risk of complications and serious morbidity and mortality from infection, such as spontaneous bacterial peritonitis (bacterial infection of ascitic fluid), urinary tract infection, pneumonia, skin and soft tissue infection, and/or sepsis [Gines, 2021; Mansour, 2023a]. See the CKS topics on Cellulitis - acute, Chest infections - adult, Sepsis, and Urinary tract infection (lower) - men, and Urinary tract infection (lower) - women for more information.
    • Spontaneous bacterial peritonitis occurs in 25% of people with cirrhosis and ascites, particularly in people with advanced liver disease [NICE, 2023]. It may present with an increased volume of ascites, abdominal pain, and fever [Mansour, 2023b].
    • Bacterial infection increases the risk of progression of liver disease and the development of other complications including gastrointestinal bleeding, acute kidney injury (AKI), and shock [Gines, 2021]. See the CKS topic on Acute kidney injury for more information.

The transition from compensated to decompensated disease may present with:

• Jaundice
  • See the CKS topic on Jaundice in adults for more information [Mansour, 2023a; Mansour, 2023b].
• Ascites 
  • Ascites develops due to renal dysfunction caused by portal hypertension leading to sodium and water retention, causing fluid accumulation in the peritoneal cavity [Muir, 2015; Mansour, 2023b]. It may present with abdominal swelling, bloating, and pain, and may be the first sign of decompensation [D'Amico, 2006; Gines, 2021].
    • Severe hepatic impairment is suggested by large-volume or refractory ascites [Gines, 2021].
    • People with cirrhosis and ascites are at high risk of further complications such as spontaneous bacterial peritonitis, hyponatraemia, hepatorenal syndrome, and umbilical hernia [Smith, 2019; Mansour, 2023c].
• Hepatic encephalopathy
  • Hepatic encephalopathy describes potentially reversible neuropsychiatric changes related to the reduced clearance of gut-derived neurotoxins (such as ammonia) due to portosystemic shunting and/or hepatic dysfunction [Muir, 2015; Gines, 2021; NICE, 2023]. It is associated with a poor prognosis and significantly increased mortality rates [Shawcross, 2016; NICE, 2023].
    • It may present as irritability and agitation, disinhibition, disorientation, short-term memory loss and confusion, loss of concentration, lethargy, ataxia, slurred speech, behaviour or personality change, sleep-wake cycle reversal, and eventual coma [Vilstrup, 2014; Ellul, 2015; Shawcross, 2016; Mansour, 2023b].
    • It affects about 50% of people with cirrhosis at some point after diagnosis (5–25% within five years and around 1 in 5 people with cirrhosis each year), and is more common in people with other evidence of decompensated liver disease [Ellul, 2015; NICE, 2023].
    • Potential precipitating factors include constipation, dehydration, electrolyte disturbance, infection, gastrointestinal bleeding, surgery, or drugs (such as opiates, benzodiazepines, or diuretics) [Muir, 2015; Shawcross, 2016].
• Variceal bleeding
  • An increase in portal pressure may cause portosystemic collaterals and the development of varices in the oesophagus (more common) or stomach, which may cause life-threatening bleeding [Muir, 2015]. Risk factors for rupture include increased size of varices, increased severity of liver disease, sepsis, and hepatocellular carcinoma (HCC) [Keane, 2016; NICE, 2023].
  • The American Association for the Study of Liver Diseases (AASLD) practice guidance states that gastro-oesophageal varices occur in about 50% of people with cirrhosis, but this is dependent on clinical stage [Garcia-Tsao, 2017]. A prospective database analysis cohort study of prognostic stages of cirrhosis (n = 494) found a 10- and 20-year cumulative incidence of new varices of 44% and 53% respectively [D'Amico, 2014].
  • The British Society of Gastroenterology (BSG) best practice guideline cites evidence that the risk of rebleeding from variceal haemorrhage can be as high as 60% at one year, with 20% mortality for each rebleeding episode [Mansour, 2023b].

Other complications

• Acute kidney injury (AKI) and hepatorenal syndrome  
  • There is an increased risk of AKI due to hypovolaemia secondary to diuretics or other nephrotoxic drugs, gastrointestinal bleeding, or infection [Gines, 2021; Mansour, 2023b].
  • Hepatorenal syndrome refers to end-stage kidney disease in people with cirrhosis and ascites in the absence of any other identifiable cause [Mansour, 2023b]. It results from progressive systemic arterial vasodilatation, sodium and water retention, and intrarenal arterial vasoconstriction, leading to a rapid deterioration in kidney function [Muir, 2015]. See the CKS topic on Acute kidney injury for more information.
• Hepatocellular carcinoma (HCC)
  • Analysis of cancer registration data in England between 2010–2016 found an increase in the age-standardised incidence rate of HCC in both men and women nationally, with significant regional variations [Burton, 2022].
  • The development of most HCC is linked to cirrhosis, mainly due to alcohol consumption or hepatitis B or C virus infection [OHID, 2022a].
  • HCC accounts for 70–90% of primary liver cancers, and its management is complicated by the presence of cirrhosis in more than 80% of affected people [Blachier, 2013]. It develops at a fairly constant rate of 3% per year in people with cirrhosis, and is associated with a worse outcome at whatever stage it develops [D'Amico, 2006].
• Portal vein thrombosis
  • This may be asymptomatic, may be diagnosed on routine HCC screening, or during liver decompensation. It is independently associated with an increased risk of worsening decompensation and variceal bleeding [Mansour, 2023c].

What is the prognosis?

The natural history of cirrhosis typically follows a course of largely asymptomatic compensated disease which may progress to symptomatic decompensated disease in some people over years [Mansour, 2023b]. Progressive portal hypertension, systemic inflammation, and liver failure drive poor outcomes in decompensated disease [Gines, 2021].

• The British Society of Gastroenterology (BSG) best practice guidance notes that decompensation is potentially reversible and the liver may recompensate, particularly if the underlying cause for cirrhosis is removed (such as abstinence from alcohol or antiviral treatment of untreated chronic viral hepatitis) [Mansour, 2023b].
  • The variability of disease progression is influenced by the underlying cause and the presence or absence of treatment and ongoing liver injury [Smith, 2019].
  • If the underlying cause for cirrhosis persists, progression to end-stage liver failure is likely [OHID, 2022a].
• Mortality rates for liver disease in people aged under 75 years have increased by almost 35% between 2001 and 2020 [OHID, 2022a].
  • People in geographical areas with higher levels of deprivation are more likely to die from liver disease and cirrhosis [Mansour, 2023a]. 
• A systematic review of 118 prognostic studies (n = 23,797) states that [D'Amico, 2006]:
  • The transition from compensated to decompensated cirrhosis occurs at a rate of approximately 5–7% per year.
  • Median survival in the compensated stage is more than 12 years, compared with about 2 years in the decompensated stage.
  • There was a wide range of reported survival rates, reflecting the heterogeneity of the studies included.
• A UK population-based cohort study (n = 4537 with cirrhosis) using General Practice Research Database statistics found that [Fleming, 2012]:
  • People with compensated cirrhosis had a nearly five-fold increased risk of death compared with the general population.
  • People with decompensated cirrhosis had a nearly 10-fold increased risk of death compared with the general population.
  • Alcohol-related liver disease had a worse prognosis than non-alcohol-related liver disease.
• A UK population-based cohort study of people with cirrhosis (n = 5118) found [Ratib, 2014]:
  • Average survival probabilities at 1 and 5 years were better for people in the general practice data group (0.88 and 0.74) compared with people in the hospital episode statistics data group after hospital admission (0.56 and 0.30).
  • A hospital admission at diagnosis or during subsequent care for liver disease resulted in a poorer prognosis, independent of the stage of cirrhosis.
  • In general, survival decreased with age and was better for women across the groups studied.

When should I suspect a diagnosis of cirrhosis?

Be aware that 40% of people with cirrhosis have no symptoms of liver disease. Suspect a diagnosis of cirrhosis, particularly if a person has risk factors, and:

• There are non-specific symptoms, such as:
  • Malaise, fatigue, anorexia, nausea, unexplained weight loss, muscle wasting, or abdominal pain.
• There are symptoms suggestive of chronic liver disease, such as:
  • Abnormal bruising, bleeding, or itch.
• There are suggestive clinical features on examination, such as:
  • Signs of chronic liver disease, including hepatosplenomegaly, clubbing, abnormal bruising, spider naevi, palmar erythema, nail changes (proximal nail-bed pallor), muscle wasting, or gynaecomastia and/or testicular atrophy in men.
  • Signs of severe hepatic impairment and decompensated liver disease, such as:
    • Jaundice (yellowing of mucous membranes; examine the sclera under natural light). See the CKS topic on Jaundice in adults for more information.
    • Peripheral oedema and/or abdominal swelling due to ascites (suggested by flank dullness and shifting dullness).
    • Variceal bleeding (a medical emergency).
    • Hepatic encephalopathy (suggested by asterixis [hand tremor with wrist extension], ataxia, slurred speech, and loss of concentration).
• There is known chronic liver disease and abnormal liver blood test results, such as:
  • A low platelet count, elevated aspartate aminotransferase (AST): alanine transaminase (ALT) ratio, high bilirubin, low albumin, or increased prothrombin time or international normalized ratio (INR).
• There are abnormal liver blood test results in a person not known to have liver disease.
  • Be aware that liver blood tests may be normal in a person with cirrhosis, so assess on the basis of all clinical features, not just blood test results. Consider a diagnosis of liver disease if other symptoms or signs are present.
  • Be aware that liver blood tests may be abnormal due to conditions other than liver disease, such as acute intercurrent illness, bone marrow disease, or haemolysis.

How should I assess a person with suspected cirrhosis?

If a person has a suspected diagnosis of cirrhosis, assess the person to guide the urgency of referral and onward management.

• Ask about:
  • Any symptoms suggestive of liver disease, their timescale, and severity.
  • Any symptoms suggestive of liver decompensation or serious complications of cirrhosis.
  • Any risk factors for cirrhosis including lifestyle (obesity, current and past alcohol intake, travel history, and occupational exposure) and any comorbidities.
  • Any medications (prescribed, over-the-counter, herbal, or illicit) that may cause liver injury or increase the risk of complications, such as hepatic encephalopathy.
  • Any family history of liver disease or risk factors for cirrhosis including autoimmune disease and genetic conditions.
  • Any impact on daily functioning, social support including family, or any dependents.
• Examine the person:
  • Check pulse, blood pressure, body mass index (BMI), and the risk of malnutrition. See the CKS topic on Adult Malnutrition for more information.
  • For signs of liver disease, including chronic liver disease and signs of decompensation.
• Arrange blood tests in primary care, if not already performed, such as:
  • Liver blood tests. See the section on Diagnosis for more information on possible abnormal liver blood test results that may suggest a diagnosis of cirrhosis.
    • Be aware that routine liver blood tests should not be used to rule out a diagnosis of cirrhosis.
  • Consider arranging additional blood tests to assess for any underlying cause and/or the severity of liver disease, depending on clinical judgement, such as:
    • Full blood count, albumin, clotting screen, international normalized ratio (INR), Fibrosis-4 (FIB-4) score, Hepatitis B and C viral serology, autoantibodies and serum immunoglobulins, and ferritin and transferrin saturation. See the CKS topics on Hepatitis B, Hepatitis C, and Non-alcoholic fatty liver disease (NAFLD) for more information.
    • HbA1c and lipids if there are risk factors for non-alcoholic fatty liver disease (NAFLD). See the CKS topic on Non-alcoholic fatty liver disease (NAFLD) for more information.
• Arrange referral for additional investigations such as transient elastography to confirm the diagnosis, depending on clinical judgement and local availability and referral pathways. See the section on Investigations for more information.

When should I refer for further investigations?

If a person has risk factors for, or a suspected diagnosis of, cirrhosis, consider referral for additional investigations to confirm the diagnosis, depending on local availability and referral pathways.

• Offer referral for transient elastography (or referral to a hepatologist or gastroenterologist with an interest in hepatology if this is not available or unsuitable), if a person is at risk of cirrhosis with:
  • Hepatitis C virus infection. See the CKS topic on Hepatitis C for more information.
  • Increased alcohol intake. See the CKS topic on Alcohol - problem drinking for more information.
  • Known alcohol-related liver disease.
• If a person has hepatitis B virus infection, refer to their gastroenterologist for specialist assessment for cirrhosis. See the CKS topic on Hepatitis B for more information.
• If a person has non-alcoholic fatty liver disease (NAFLD) and advanced liver fibrosis on the basis of an elevated non-invasive advanced liver fibrosis risk score, offer referral for either transient elastography or acoustic radiation force impulse elastography to diagnose cirrhosis.
  • See the CKS topic on Non-alcoholic fatty liver disease (NAFLD) for more information on non-invasive scoring systems for advanced liver fibrosis and monitoring of a person with NAFLD.
• If a person has obesity and/or type 2 diabetes, do not offer tests to diagnose cirrhosis unless they have NAFLD and advanced liver fibrosis on the basis of an elevated advanced liver fibrosis risk score.
  • See the CKS topic on Non-alcoholic fatty liver disease (NAFLD) for more information on non-invasive scoring systems for advanced liver fibrosis and monitoring of a person with NAFLD.
• If a person has an additional liver disorder (such as primary biliary cholangitis, primary sclerosing cholangitis, haemochromatosis, or Wilson's disease) and a diagnosis of cirrhosis is suspected, liaise with the person's specialist or refer to a hepatologist or gastroenterologist with an interest in hepatology for further assessment.
• If cirrhosis is not diagnosed on initial testing, ensure retesting for cirrhosis is offered every 2 years for:
  • A person with alcohol-related liver disease.
  • A person with hepatitis C virus infection who has not shown a sustained virological response to antiviral therapy — this would usually be a specialist decision.
  • A person with NAFLD and advanced liver fibrosis.

Scenario: Management of cirrhosis

From age 16 years onwards.

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of cirrhosis.

Search dates

April 2018 - January 2024

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

• (MH "Liver Cirrhosis+")
• AB ((liver or hepat*) N3 (cirrho* or fibrosis))  OR TI ((liver or hepat*) N3 (cirrho* or fibrosis))  

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
• Institute for Clinical Systems Improvement
• 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

• Bandolier
• 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)
• LactMed
• 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.

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• 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.
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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.