Recommendations for research
The guideline committee has made the following recommendations for research. The guideline committee's full set of research recommendations is detailed in the full guideline.
Development of a risk tool to identify people at risk of cirrhosis.
For much of the time, until presentation with jaundice or decompensation, liver disease may remain asymptomatic and silent. The earlier 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.
Do non‑selective beta-blockers improve survival and prevent first variceal bleeds in people with cirrhosis that is associated with small oesophageal varices?
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 10–20%. 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.
How frequently does antibiotic resistance occur, and how significant are antibiotic treatment-related complications when antibiotics are used for the primary prevention of spontaneous bacterial peritonitis in people at high risk of having, or developing, cirrhosis?
Spontaneous bacterial peritonitis is the most common serious infection in people with cirrhosis, occurring in 25% of people who develop ascites. It is associated with significant morbidity and mortality rates of 20–40%. 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 spontaneous bacterial peritonitis have shown benefits and a significant reduction in the incidence of spontaneous bacterial peritonitis 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 spontaneous bacterial peritonitis.
What is the quality of life in people who have had a transjugular intrahepatic portosystemic shunt (TIPS)?
Prior to 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, shunt 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.
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?
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 5–25% 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.