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National Guideline Centre (UK). Cirrhosis in Over 16s: Assessment and Management. London: National Institute for Health and Care Excellence (NICE); 2016 Jul. (NICE Guideline, No. 50.)
9.1. Introduction
Variceal bleeding occurs in 25–40% of patients with cirrhosis and each bleeding episode is associated with a 10–30% mortality rate.50 Consequently, prevention of variceal bleeding is an important goal in the management of patients with cirrhosis. Therefore, it is important that people with cirrhosis at risk for variceal bleeding should be identified as early as possible.
Clinical signs and symptoms such as ascites, thrombocytopenia, splenomegaly and Child-Pugh class do not adequately predict which patients will develop variceal bleeding.35,147,168 Thus, the American College of Gastroenterology (ACG) and the American Association for the Study of Liver Disease (AASLD) have published guidelines recommending that all people with cirrhosis should be screened for the presence of varices using oesophagogastroduodenoscopy (OGD).89,90
Comparison of endoscopic surveillance versus no surveillance was excluded from the protocol as, due to the high incidence of oesophageal and gastric varices in people with cirrhosis and the subsequent high risk of bleeding and bleeding-related mortality, the GDG considered that all people with cirrhosis should undergo endoscopic surveillance. The question was therefore to find the most clinically and cost-effective frequency of endoscopic surveillance for the detection of the first occurrence of oesophageal or gastric varices in people with cirrhosis. Implicit in the investigation of surveillance frequency is that patients whose varices are detected earlier can be treated earlier with potentially better patient outcomes and a better chance of survival.
9.2. Review question: How frequently should surveillance testing using endoscopy be offered for the detection of oesophageal varices and isolated gastric varices in people with cirrhosis?
For full details see review protocol in Appendix C.
Table 66
PICO characteristics of review question.
9.3. Clinical evidence
Randomised and observational studies comparing different intervals of surveillance testing in detecting varices in people with cirrhosis were searched for. No relevant clinical studies comparing different frequencies of endoscopic surveillance for the detection of varices were identified. For exclusion reasons see Appendix L.
9.4. Economic evidence
9.4.1. Unit costs
See Table 64 in Appendix N.
9.4.2. Published literature
No relevant economic evaluations were identified.
See also the economic article selection flow chart in Appendix F.
9.4.3. New cost-effectiveness analysis
Original cost-effectiveness modelling was undertaken for this question using the NGC liver disease pathway model developed for this guideline. A summary is included here. An evidence statement summarising the results of the analysis can be found below. The full analysis can be found in Appendix N.
9.4.3.1. Aim and structure
The aim of the health economic modelling for this question was to determine the optimal frequency of oesophageal varices surveillance. This was achieved by using the original lifetime diagnostic health state transition (Markov) model (see Section 6.4.3 and Appendix N) which followed the NICE reference case146 and by comparing overall cost and QALYs of the cirrhosis tests of preference in three different scenarios; annual, 2-yearly and 3-yearly varices surveillance.
Patients who had an endoscopy and were identified as having medium to large varices were immediately offered a band ligation procedure. Patients that received this procedure ran a lower risk of variceal bleeding. Therefore, in the economic model, the patient benefit from receiving more frequent endoscopies was the reduced time spent under the increased risk of bleeding from untreated varices.
To determine the most cost-effective surveillance frequency, incremental cost-effectiveness ratios (ICERs) were calculated across the available options. Base case results below were obtained through the probabilistic analysis to take combined parameter uncertainty into account.
9.4.3.2. Results
Table 67
ICERs comparing annual and 2-yearly surveillance against 3-yearly surveillance.
Annual surveillance was not cost-effective compared to 3-yearly surveillance for any of the model cohorts with the ICERs either exceeding £45,000 per QALY gained or showing it being dominated by the 3-year frequency option (more costly and less effective). Two-yearly surveillance was cost-effective compared to 3-yearly surveillance at a cost-effectiveness threshold of £20,000 per QALY in the 2 HCV cohorts.
In the deterministic sensitivity analysis, changes in the surveillance costs or the RR applied on the bleeding probability had considerable effect on the ICERs of the higher frequencies. However with the base case ICERs of the deterministic analysis being far beyond the £20,000 threshold, any reductions in the ICERs made 2-yearly surveillance cost-effective only for the ALD cohort.
9.5. Evidence statements
9.5.1. Clinical
- No relevant clinical studies were identified.
9.5.2. Economic
- One original cost-utility analysis that compared annual, 2-yearly and 3-yearly surveillance for the detection of varices in people with cirrhosis at a cost-effectiveness threshold of £20,000 per QALY gained found that:
- Annual surveillance was not cost-effective compared to 3-yearly surveillance (ICERs: £48,430–122,413 per QALY gained or dominated).
- 2-yearly surveillance was cost-effective compared to 3-yearly surveillance in people with hepatitis C (ICERs: £75per QALY gained or dominant).
- 2-yearly surveillance was not cost-effective compared to 3-yearly surveillance in people with NAFLD and advanced fibrosis, ALD or hepatitis B (ICERs: £36,552–63,167 per QALY gained or dominated).
This analysis was assessed as directly applicable with minor limitations.
9.6. Recommendations and link to evidence
| Recommendations |
|
|---|---|
| Relative values of different outcomes | For comparison of surveillance frequency the GDG assessed the critical outcomes of all-cause mortality, freedom from variceal bleeding and health-related quality of life. The other important outcomes for decision-making were freedom from varices, the development of moderate or large varices, the size of varices and the number of patients receiving prophylactic treatment (beta-blockers or endoscopic variceal band ligation). |
| Trade-off between clinical benefits and harms | The GDG considered that all people with cirrhosis should be offered endoscopic surveillance, due to the high incidence of oesophageal and gastric varices in people with cirrhosis, and the subsequent high risk of bleeding and bleeding-related mortality. Therefore, the comparison of endoscopic surveillance versus no surveillance was excluded from the protocol. The question was therefore to find the most clinically and cost-effective frequency of endoscopic surveillance for the detection of the first occurrence of varices in people with cirrhosis. No clinical evidence was identified from RCTs or observational studies comparing different frequency of surveillance and the effect on patient outcomes. The GDG discussed the potential harms of monitoring for varices too infrequently, including not identifying people with varices soon enough to give prophylactic treatment for the prevention of variceal bleeding. There is also a high incidence of bleeding-related mortality in this population. As the GDG has also made a recommendation that people with medium or large oesophageal varices should be given prophylactic band ligation to prevent bleeding (see recommendation 22), it was agreed that people with cirrhosis should undergo endoscopy at the time of diagnosis and that those with no evident varices initially should undergo regular surveillance. The GDG also discussed the potential harms of undergoing endoscopy, including discomfort, aspiration, broken teeth and in rare instances perforation of the oesophagus and rupture of varices and, very rarely, death. The GDG agreed that the benefits of endoscopic surveillance outweighed the harms. A recommendation was made that people newly diagnosed with cirrhosis should undergo surveillance and that, in those with no evident varices, surveillance should be continued at 3-yearly intervals until detection of varices of any size. It was highlighted that if signs and symptoms indicating the presence of varices developed (for example, clinical or laboratory evidence suggestive of portal hypertension, such as ascites, splenomegaly or thrombocytopaenia), then endoscopy should be performed earlier. |
| Trade-off between net clinical effects and costs | No published economic evidence was identified. In the original economic modelling conducted for this guideline (see Appendix N), the impact of varying the frequency of testing people with cirrhosis but without varices from every 3 years to every 2 years or every year was investigated. This showed that the increased frequency had small health benefits with significant additional costs. Two-yearly testing was found to be cost-effective in the HCV cohorts at a cost-effectiveness threshold of £20,000 per QALY, but not for the other cohorts. Annual surveillance was not cost-effective for any of the populations. The GDG acknowledged that there was significant variation in the cost-effectiveness of more frequent testing between the population groups, with associated uncertainty, and that a consistent strategy for all groups would be beneficial. It therefore agreed not to recommend testing more frequently than every 3 years for any group. |
| Quality of evidence | No clinical evidence was identified from RCTs or observational studies for this review question. |
| Other considerations | The GDG noted that both the EASL and AASLD guidelines used consensus to make recommendations on surveillance for varices in people with cirrhosis. The GDG agreed that endoscopic surveillance should be performed by a person experienced in interventional endoscopy. Therefore, if medium or large varices are detected, the band ligation procedure can be performed at the same time to avoid the need for a second procedure. The GDG also discussed that there is a certain degree of inter-observer variability associated with the procedure17,26,48, highlighting the need for endoscopists to be appropriately trained and experienced. |
- Surveillance for the detection of varices - Cirrhosis in Over 16sSurveillance for the detection of varices - Cirrhosis in Over 16s
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