Recommendations for research

The guideline committee has made the following recommendations for research.

Key recommendations for research

1 Effectiveness of endoscopic variceal band ligation plus a non-selective beta-blocker for preventing variceal bleeding in people with medium or large oesophageal varices

What is the effectiveness and cost effectiveness of endoscopic variceal band ligation plus a non-selective beta-blocker compared with either of these interventions alone for preventing variceal bleeding in adults with cirrhosis and medium or large oesophageal varices? [2023]

2 Antibiotic prophylaxis to prevent spontaneous bacterial peritonitis

What is the clinical and cost effectiveness of antibiotic prophylaxis to prevent spontaneous bacterial peritonitis (SBP) in people with cirrhosis and ascites? [2023]

For a short explanation of why the committee made this recommendation for research, see the rationale section on preventing SBP.

Full details of the evidence and the committee's discussion are in evidence review B: use of antibiotics to prevent SBP.

3 Primary prevention of decompensation using non-selective beta-blockers

What is the clinical and cost effectiveness of non-selective beta-blockers for the primary prevention of decompensation in people with compensated cirrhosis and signs of clinically significant portal hypertension from non-invasive tests (such as tests to measure liver stiffness, or biomarkers)? [2023]

For a short explanation of why the committee made this recommendation for research, see the rationale section on primary prevention of decompensation.

Full details of the evidence and the committee's discussion are in evidence review C: clinical and cost effectiveness of non-selective beta-blockers for the primary prevention of decompensation in people with compensated cirrhosis.

Other recommendations for research

4 Assessing the risk of cirrhosis

How can the development of a risk tool help identify people at risk of cirrhosis? [2016]

Why this is important

For much of the time, until presentation with jaundice or decompensation, liver disease may remain asymptomatic and silent. The earlier that liver disease and even cirrhosis is diagnosed, the better the opportunity to treat, limiting disease progression and, in many cases, offering a cure. The prevention of progression to end-stage liver disease, avoiding complications, and reducing the need for investigation, hospitalisation and intervention would have the potential for very large savings for the NHS. The earlier the diagnosis, the greater the potential patient and financial benefit. This is why GPs need a guide or 'toolkit' to identify people who are at high risk of having, or developing, advanced liver fibrosis or cirrhosis.

One approach would be to identify a retrospective cohort of people with cirrhosis, and to look at their cirrhosis risk factors. The proposed study should use a multivariate analysis to find the risk factors associated with the outcome of cirrhosis. By weighting the risk factors according to their association with the outcome, a risk tool should be developed to predict a person's risk of developing cirrhosis.

5 Treating small oesophageal varices

Do non-selective beta-blockers improve survival and prevent first variceal bleeds in people with cirrhosis that is associated with small oesophageal varices? [2016]

Why this is important

Bleeding from oesophageal varices is a major complication of cirrhosis. Approximately half of patients with cirrhosis have oesophageal varices, and one‑third of all patients with varices will experience bleeding at some point. Despite improvements in the management of acute haemorrhage in recent decades, the 6‑week mortality associated with variceal bleeding remains at 10% to 20%. The risk of variceal bleeding increases with variceal size. Whether non-selective beta-blockers are of benefit as primary prophylaxis in people with cirrhosis and small oesophageal varices has not been adequately studied.

6 Antibiotic resistance in treating spontaneous bacterial peritonitis

How frequently does antibiotic resistance occur, and how significant are antibiotic treatment-related complications when antibiotics are used for the primary prevention of SBP in people at high risk of having, or developing, cirrhosis? [2016]

Why this is important

SBP is the most common serious infection in people with cirrhosis, occurring in 25% of those who develop ascites. It is associated with significant morbidity and mortality rates of 20% to 40%. It occurs most commonly in people with advancing liver disease; approximately 70% of cases occur in people with Child–Pugh class C cirrhosis.

Several oral antibiotics that have been investigated for the prophylaxis of SBP have shown benefits and a significant reduction in the incidence of SBP in people at high risk of having, or developing, cirrhosis. However, they are associated with antibiotic resistance, adverse reactions and drug interactions. There is a lack of good quality, recent evidence regarding the prevalence and consequences of antibacterial resistance that may occur during long-term oral antibiotic therapy when used to prevent SBP.

7 Transjugular intrahepatic portosystemic stent

What is the quality of life in people who have had a transjugular intrahepatic portosystemic stent (TIPS)? [2016]

Why this is important

Before TIPS, people may have had several problems resulting from portal hypertension, including variceal bleeding from veins in the stomach, oesophagus or intestines, ascites or hydrothorax – all of which will have had a detrimental effect on their quality of life. TIPS should alleviate these problems, but little is known about the consequential effect on quality of life and any effects that potential problems following TIPS (for example, hepatic encephalopathy, stent blockages, infection and cardiac problems) have on each person. It is therefore important to assess what benefits TIPS has to the quality of life of people with advanced liver disease.

8 Acute hepatic encephalopathy

In people with cirrhosis and an acute episode of hepatic encephalopathy secondary to a clearly identified, potentially reversible precipitating factor, does management of the precipitating event alone improve the hepatic encephalopathy without specific treatment? [2016]

Why this is important

Hepatic encephalopathy is a major complication of cirrhosis. Approximately 50% of people with cirrhosis will develop clinically apparent hepatic encephalopathy at some stage after diagnosis – the risk being around 5% to 25% within 5 years. Hospital admissions are common and inpatient stays often prolonged. The presence of hepatic encephalopathy is associated with a significant increase in mortality; survival after the first episode is 42% at 1 year and 23% at 3 years.

At present, treatment of hepatic encephalopathy is directed primarily at reducing the production and absorption of gut-derived neurotoxins, particularly ammonia, mainly through bowel cleansing, and the use of non-absorbable disaccharides, such as lactulose, although several other agents such as non-absorbable antibiotics are also used. However, in approximately 50% of people admitted with episodic hepatic encephalopathy, there is a clearly defined precipitating factor (for example, infections, gastrointestinal bleeding or overuse of diuretics). Treatment is often challenging and some people may need to be cared for in an intensive care setting, at least initially. The identification and correction of any precipitating events is important as there is evidence that this alone may improve hepatic encephalopathy without recourse to specific therapies. However, this has not been rigorously tested in a randomised clinical trial.

  • National Institute for Health and Care Excellence (NICE)